Paprosky classification systems for femoral defects.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
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Total hip arthroplasty (THA) is one of the most successful surgical procedures with well documented survivorship at up to 25 years. With ageing of the population and higher arthritis prevalence in older adults, the demand for the procedure increases worldwide [89]. In addition, over the last two decades the age range has been broadened to include younger patients. Over 270 000 hip replacements are performed annually in the US alone, and the annual volume of hip joint replacement is projected to double by the year 2030 [89]. Although very successful procedure, significant percentage of patients undergoing total hip arthroplasty require revision within 10 to 15 years after the surgery. Aseptic loosening and the associated osteolysis have been recognized as the main reason for implant failure in 71% of cases [66]. Other indications for revision include periprosthetic fracture, dislocation, and infection. New technologies in implant design and advances in surgical technique have improved the outcomes after primary total hip arthroplasty and decreased the rate of complications. However, as a consequence of increased rate of primary THA\'s the prevalence of revision hip surgery is increasing proportionally. The increased rate and costs of revision procedures impose high demands on both surgeon and healthcare system. Moreover, the cost of hip replacement is exponentially increasing [82].
Bone loss is the major challenge in revision setting. In 2009, Bozic et al. reviewed the most common causes for revision hip arthroplasty [8]. Aseptic loosening, instability, and infection were reported as the main reasons for revision surgery. This study underlined the need for a complex approach to evaluation and management of patients with implant failure after hip replacement. Such approach will guarantee precise diagnosis, proper selection of revision implant and surgical approach, uncomplicated surgery, and optimal clinical result.
This chapter provides an overview of aseptic loosening of revision hip arthroplasty and outlines the management strategies in the clinical scenario of a failed hip prosthesis.
Various signs and symptoms can occur in the clinical setting of a failed hip prosthesis. Painful hip arthroplasty is the most common complication after total hip arthroplasty reaching 18% of patients in some series [6]. Most of these painful hips will require revision. Groin pain can be referred to implant failure easily whereas occasional hip pain, pain in the buttock, knee pain or migrating pain can have different etiology. Other diseases and conditions such as disk disease, radiculopathy, inguinal or femoral hernia, pelvic infections, tumors, and trauma may have manifestations similar to that of a failed prosthesis.
The differential diagnosis of hip pain requires a careful history and examination. In simple cases, the reason could be identified with clinical examinations and standard radiographs only. Thorough examination elicits the underlying cause of hip complains such as infection, neurological injury, referred pain, wear, aseptic loosening or instability. In many cases, the diagnosis is a challenge to the surgeon. In addition to clinical history and physical examination, radiographic examination and advanced imaging techniques could help establish exact localization of pain, and its possible connection with the implant. Additional radiographic examinations as well as an algorithmic approach with special diagnostic imaging and tests help establishing precise diagnosis. Computed tomography and 3-D computed tomography is often helpful in establishing periprosthetic osteolysis and its severity. In addition to plain radiographs arthrography with contrast medium could be considered in certain cases.
Once extrinsic and periarticular diseases have been excluded as a reason for the hip pain, septic loosening should be excluded. Laboratory investigations are the initial tests that help differentiate septic from aseptic loosening. A standard set includes WBC, Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete chemistries and urinalysis. In addition to plain radiographs and laboratory tests joint aspiration is considered the most important diagnostic tool in ruling out periprosthetic infection. The aspirate should be sent for cell count and anaerobic and aerobic cultures. Recently, local markers such as interleukin-6 (IL-6) and other cytokines [34], synovial CRP, and leukocyte esterase (LE) [118] from joint aspirate have been proposed. All of these local markers have shown accuracy of more than 90% in predicting periprosthetic infection. Nuclear medicine scans with technetium-99m-HDP, gallium citrate, and labeled WBC have been used to diagnose the presence of infection. However, because of poor sensitivity, specificity, and accuracy, it is cost-prohibitive and remains a tertiary tool. Nuclear medicine is used only if infection could not be proven otherwise. Intraoperatively, diagnostic evaluations such as Gram stains and frozen sections have been proposed.
Guidelines and algorithms for evaluation of painful hip arthroplasty have been published in the literature and implemented in practice [119]. Such approach helps eliminate infection of the failed hip that would change treatment approach and could exclude one-stage revision.
It is important to have a practical, relatively simple classification system for assessment of bone defects associated with loose hip implants. The use of a radiographic classification system helps to establish the severity and localization of bone defects, and to guide treatment decisions. It should allow the surgeon to be prepared for the possible intraoperative findings and to plan adequate treatment approach. Numerous classification systems have been described in the literature [17,23,25,32,40,58,60,99,116,137,158].
The American Academy of Orthopedic Surgeons (AAOS) classification system of bone defects, described by D’Antonio et al. identifies the pattern and localization of osteolysis but does not quantify the bone loss [23-25]. It is one of the most widely used classification system in the literature.
Perhaps the most widely used classification system, the Paprosky Classification [32,116,158] (Tables 1, 2) was developed to establish bone defect type, size, and localization in order to allow selection of appropriate cementless reconstructive option for a given bone loss pattern. We base our clinical decisions on this classification system.
The key advantage of this classification is the assessment of the host bone ability to provide initial stability of a cementless implant until bone ingrowth occurs. The bone defects are usually classified on the basis of plain radiographs. However, final assessment is made intraoperatively, after removal of the failed implant and thorough debridement of the host bone. Intraoperative assessment of implant stability is made with help of trial components. The remaining host bone determines the stability of the implant and the type of the defect.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
1 | \n\t\t\tMinimal metaphyseal bone loss | \n\t\t
2 | \n\t\t\tExtensive metaphyseal bone loss and an intact diaphysis | \n\t\t
3A | \n\t\t\tExtensive metadiaphyseal bone loss and a minimum of 4 cm of intact cortical bone in the diaphysis | \n\t\t
3B | \n\t\t\tExtensive metadiaphyseal bone loss and <4 cm of intact cortical bone in the diaphysis | \n\t\t
4 | \n\t\t\tExtensive metadiaphyseal bone loss and a nonsupportive diaphysis | \n\t\t
Paprosky classification systems for femoral defects.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
1 | \n\t\t\tAcetabular rim, anterior-posterior column intact | \n\t\t
2 | \n\t\t\tLess than 3 cm superior migration Distorted acetabular rim. Intact anterior and posterior columns Adequate stability with Trial. Greater than 50% contact surface | \n\t\t
2A | \n\t\t\tSuperior and medial cavitation defect. Intact rim | \n\t\t
2B | \n\t\t\tSegmental supero-lateral defect (less than 1/3 of circumference) | \n\t\t
2C | \n\t\t\tMedial defect with cup medial to Kohler’s line (Protrusio) | \n\t\t
3 | \n\t\t\tGreater than 3 cm superior migration Non-supportive acetabular rim for biological fixation | \n\t\t
3A | \n\t\t\tLateral to Kohler’s line. Intact medial support Moderate ischial lysis (<15 mm below superior obturator line) Medial limb of teardrop is intact Superior and lateral migration “up and out” Contact of trial with bone over 40-60% | \n\t\t
3B | \n\t\t\tBroken Kohler’s line. No medial or superior support Extensive ischial osteolysis (>15 mm below superior obturator line) Complete destruction of tear drop Superior and medial migration “up and in” Under 40% contact surface. High risk of occult pelvic discontinuity | \n
Paprosky classification system for acetabular defects.
Careful preoperative planning is a prerequisite for successful revision surgery. The principle aims in revision hip arthroplasty are to achieve supportive host bone, secure implant fixation and to restore hip center and joint kinematics. The type and severity of host bone loss determine the method of reconstruction. Careful preoperative planning improves effectiveness during surgery, and helps distinguish more complex alternatives for reconstruction if needed.
Thorough clinical and radiographic examination is essential for determining the extent and severity of bone loss, quality of the host bone, exclusion of infection, additional deformities, and potentially confounding factors. Computed tomography may be needed in the presence of massive bone loss. In case of medial migration of the failed components angiography with contrast medium should be considered. Manual or digital templating helps for adequate selection (size, diameter, length) of revision implant and reduce the operative room inventory. Templating also helps determine whether stable initial fixation could be obtained and the need for additional procedures. Preoperative planning is critical for the assessment of the need of graft, tools for implant removal, and selection of proper components available at the time of surgery. Appropriate surgical exposure should be planned with an extensile approach often necessary. Classification system of bone defects based on radiographs that assesses the severity of bone loss according to the type of fixation for a given bone loss pattern is beneficial. In our practice, we find the Paprosky classification system a useful tool for guidance of clinical decisions. Any attempt should be made to identify the failed implant. The implant manufacturer should be contacted for implant-specific extraction devices if available. In case of isolated partial revision, it is advisable to have an option for partial (liner or head) exchange.
The aims of revision surgery are to extract the failed prosthesis with minimal soft tissue and bone damage, to restore bone loss, and to implant prosthesis with stable and durable fixation. Ultimate goals are long-lasting and painless joint function. To obtain these goals arthroplasty surgeons may require a variety of approaches for adequate exposure of the femur and acetabulum in different revision settings. Usually arthroplasty surgeons are familiar and most comfortable with a certain approach and use it in most surgeries. However, in order to obtain reproducible results after revision of most difficult cases, surgeons should be familiar with all approaches to the hip joint. Next to standard approaches used in primary total hip arthroplasty, extensile approaches were developed in order to minimize damage to the host bone, safely remove the loose implant and provide good visualization for correct insertion of the revision components. Contained defects can be reconstructed through any conventional approach. For uncontained defects, we prefer to have wide access and, therefore, we use transtrochanteric approach or trochanteric slide osteotomy with preserved insertion of vastus lateralis. If greater exposure is needed extended trochanteric osteotomy is advisable.
The extended trochanteric osteotomy (ETO) is one of the significant achievements in revision surgery [9] (Figure 1).
It is safe and straightforward, saving time and minimizing risk of fracture during cement and failed implant removal. However, it limits femoral component options to those that rely on distal fixation. Advantages of the technique are: predictable healing of the osteotomy, decrease in intraoperative fractures and femoral perforations, direct access to the distal canal for cement removal and neutral reaming, and decreased surgical time [9,104]. Favorable clinical results after use of ETO have been published in the literature [9,104].
(A) The Extended trochanteric osteotomy is performed by cutting from the greater trochanter distally along the long axis of the femur. (B) The bone is cut with a saw. (C) The flap with the attached muscles is elevated. (D) Exposed femoral bone bed.
Majority of hip revisions could be performed using cementing technique. However, patients with severe bone loss and poor bone quality require complex alternatives for revision.
Various studies publish the outcomes after cemented femoral revision [2,13,122]. Use of the early cementing technique produced disappointing results [2,69]. Gaining more extensive experience resulted in acceptable short- to mid-term results [13,81,122]. Re-revision rates ranging from 4.3% to 6.0% and radiographic loosening ranging from 12% to 44% after mid-term follow-up of 3.4 to 4.5 years were reported (Table 3). However, long-term studies showed suboptimal outcomes after revision with an early cementing technique. At 8.1-year follow-up of the initial group of cemented revisions, Pellicci et al. found more than doubled incidence of re-revision and radiographic loosening ranging from 5.4% to 19% and from 13.6% to 29%, respectively [121]. Similar results were published by Kavanagh et al. in a 10-year follow-up study [79]. Sixty-four per cent of the stems had been revised or were radiographically loose. The incidence of revision had more than doubled from 18% at 3 years to 39% at final follow-up.
\n\t\t | \n\t\t | \n\t\t | \n\t\t | \n\t | |
Amstutz et al. [2] | \n\t\t1982 | \n\t\t66 | \n\t\t2.1 | \n\t\t9.0 | \n\t\t29.9 | \n\t
Pellicci et al. [122] | \n\t\t1982 | \n\t\t110 | \n\t\t3.4 | \n\t\t5.4 | \n\t\t13.6 | \n\t
Pellicci et al. [121] | \n\t\t1985 | \n\t\t99 | \n\t\t8.1 | \n\t\t19.0 | \n\t\t29.0 | \n\t
Kavanagh et al. [81] | \n\t\t1985 | \n\t\t166 | \n\t\t4.5 | \n\t\t6.0 | \n\t\t44.0 | \n\t
Engelbrecht et al. [39] | \n\t\t1990 | \n\t\t138 | \n\t\t7.4 | \n\t\t8.8 | \n\t\t38.0 | \n\t
\n\t\t | \n\t\t | \n\t\t | \n\t\t | \n\t | |
Rubash and Harris [134] | \n\t\t1988 | \n\t\t43 | \n\t\t6.2 | \n\t\t2.0 | \n\t\t11.0 | \n\t
Katz et al. [78] | \n\t\t1997 | \n\t\t79 | \n\t\t11.9 | \n\t\t5.4 | \n\t\t16.0 | \n\t
Callaghan et al. [13] | \n\t\t1985 | \n\t\t139 | \n\t\t3.6 | \n\t\t4.3 | \n\t\t12.0 | \n\t
Estok and Harris [43] | \n\t\t1994 | \n\t\t38 | \n\t\t11.7 | \n\t\t10.5 | \n\t\t10.5 | \n\t
Mulroy and Harris [109] | \n\t\t1996 | \n\t\t43 | \n\t\t15.1 | \n\t\t20.0 | \n\t\t6.0 | \n\t
Results of cemented femoral revision.
The main reason for suboptimal results with early cemented revisions was difficulty in obtaining stable and long-lasting fixation in compromised host bone stock where the rate of re-revision was very high [83]. In early studies, the reactive sclerotic bone between the fibrous membrane and the native cancellous bone was not removed [12]. Poor fixation of the revision femoral component compared to that in the primary setting may be due to inadequate excision of residual fibrous membrane, incomplete drying of bone, suboptimal cement filling technique, or insufficient cement-bone interlock on the smooth sclerotic bone surface. In such setting, even long cemented stems, are generally difficult to be inserted with adequate primary and long lasting stability. Femoral revision using so-called modern cementing techniques may yield promising results (Figure 2).
Modern cementing technique. (A) Distal cement plug. (B) Cement injector. (C) Delivery and pressurization of cement using cement injector.
Different studies have demonstrated that modern cementing techniques have improved implant survival and clinical outcome compared with the mid-term results after revision with use of so-called first-generation technique [71,85,109,128,134] (Figure 3).
(A) Preoperative radiograph of a failed cemented prosthesis. (B) Grade A cemented fixation achieved with modern cementing technique.
Cemented femoral revision has several advantages in elderly patients. It allows early mobilization, a shorter operating time, and possibly less risk of a peroperative fracture. Use of modern cementing techniques seems to improve fixation of the femoral components and clinical outcomes and justifies its use. Whenever possible the failed arthroplasty should be revised before occurrence of severe bone loss and femoral enlargement.
Removal of the well-fixed cement mantle around the stem can be extremely difficult, time consuming, and risky procedure. A solution to the problem, cement-within-cement revision was first proposed by Eftekhar who advised on preserving the existing well cemented mantle and re-cementing the new stem into it [36]. In a biomechanical study, Greenwald et al. demonstrated that the separation strength was 94% that of a single block when the existing cement mantle was adequately prepared [56]. The technique requires that the old cement surface be dried and roughened in order to provide contact area for fixation of the new cement. The cement should be injected in the early liquid phase in order to prevent lamination and to promote polymerization within the existing cement mantle.
This technique has been questioned by other authors [96], but subsequent biomechanical and clinical studies have favored its use in properly selected cases [35,67,97]. In a cadaver study, Rosenstein et al. demonstrated that cut strength at the cement-cement interface was greater than the strength at the cement bone interface [133]. However, the cut strength of the cement bone interface was 30% weaker when cement was placed against a revised bone surface.
Femoral impaction grafting with a cemented stem was first performed in Exeter in 1987 [67] (Figure 4). The rationale behind this simple concept is to rebuild femoral bone stock and to provide secure fixation to the femoral stem. The biologic approach of bone restoration during revision hip arthroplasty is a highly appealing solution for restoring host bone stock a difficult procedure with usually deficient femurs.
Following the initial report of Gie and coworkers of highly successful results after 56 revisions with follow-up of 18-49 months [53] the technique received wide attention and spread rapidly [64,114,141,161]. Further studies confirmed the favorable outcomes, and it became evident that the technique resulted in restoration of femoral bone loss as the impacted allograft was incorporated and remodeled [67,161].
The technique of impaction grafting appeared to be reliable, reproducible, can be learned rapidly, and produced predictably favorable outcomes. In a series of 226 revisions, Halliday et al. reported the Exeter initial experience with femoral impaction grafting [64]. The overall rate of mechanical failure was 7% (16/221) at a minimum follow-up of five years. Ten to 11-year survivorship with removal of the stem for any reason as the end point was 90.5% and survivorship with revision for aseptic loosening as the end point was 99.1% [64]. In 2006, Schreurs et al. published their results with the technique using a cemented polished tapered stem at an average 10.4-year follow-up [140]. The average subsidence of the stem within the cement mantle was 3 mm, and seven stems migrated 5 mm. [140]. No stem was revised for aseptic loosening. Three periprosthetic fractures at the sults of 1305 femoral revisions with impaction grafting from the Swedish arthroplasty registry [114]. Survivorship at 15 years for aseptic loosening was 99.1%, for infection 98.6%, for subsidence 99.0%, and for fracture 98.7%.
Femoral impaction grafting. (A) Preoperative radiograph. B) Immediate postoperative and, (C) at 8 years after revision.
However, other authors reported higher percentage of intraoperative complications, mainly femoral fractures and suboptimal cementing technique [84,86,101,123]. A high incidence of up to 12% intraoperative femoral fractures have been reported [64,140,103]. Stem subsidence of greater than 5 mm is a typical complication with this technique with a prevalence of up to 38% in some series [38,49,86,101]. Impaction grafting has certain disadvantages: it is prone to femoral fractures [103]; has a steep learning curve; and shows highly variable outcomes, probably related to the surgical technique. The causes of early subsidence of the stem might be insufficient impaction of the allograft, suboptimal cement penetration and interdigitation, use of synthetic graft substitutes, or other graft additives, loss of primary fixation of the allograft-cement composite due to soft-tissue infiltration and substitution of the allograft in the process of remodeling and revascularization, unrecognized femoral fracture, or fracture of the cement-allograft composite. However, in a study on saw femurs, Flannery et al. and Cummins et al. were unable to find a correlation between threshold force needed to achieve stable construct in impaction bone grafting without fracture and bone mineral density, canal-cortex ratio, or cortical thickness [22,48]. According to Gokhale et al. four variables (age, intramedullary canal diameter, stem design, and density of the graft at the tip of the stem) affected the subsidence of the stem [54].
The original technique of impaction grafting utilized the Exeter stem [53]. The impacted graft is subjected to continuous loading and deformation. Thus, the use of double-tapered polished stem appears suitable option as the stem could achieve secondary stability after subsidence. Arguing that the technique is more important than the type of prosthesis other authors have used different implant designs from those of Exeter wedge shaped prosthesis [49,77, 124]. Uncemented technique was also used with an equally good outcome at mid-term follow-up [100].
Femoral impaction bone grafting is a suitable indication for cases with severe bone deficiency. The technique is expensive, prone to complications, hast steep learning curve, and results depend on surgical skills. It may be a viable revision option for young patients with severe bone loss.
Severe bone loss in femoral revision is increasing problem as the number of patients with multiple previous revision increases. These complex cases are further increasing as the age of patients undergoing hip replacement is diminishing.
A stable initial fixation is hardly obtainable in complex cases with circumferential proximal bone loss >5 cm in length. Severe bone loss makes femoral revision using conventional techniques difficult. Alternatives include distal fixation of the stem or use of a proximal femoral allograft. Distal fixation requires the use of a proximally femoral replacement prosthesis or megaprosthesis. This has some disadvantages such as: instability due to poor soft-tissue attachment [62,120], early loosening of the distally fixed stem [47], stress shielding [10,46,110], intraoperative fractures [110] or difficulty with fixation in an ectatic femur. Various studies of revisions using megaprosthesis reported survival rate within the range 58% to 84% at five to ten year follow-up [98,120,164].
The viable revision technique using proximal femoral allograft consists of a long-stem prosthesis cemented to the allograft but not to the host bone [59] (Figure 5). Uncemented fixation of the allograft prosthesis construct would not result in long lasting stability of the prosthesis as neither in-growth nor on-growth could be expected at the allograft-implant interface. The importance of the allograft-host bone contact is a key factor for achieving stability of the construct and ensuring long-term stability of the implant [136].
Individual studies published encouraging results after use of proximal femoral allograft-prosthesis construct in large segmental defects of the proximal femur. In a series of 44 revisions with a mean follow-up of 7.2 years Vastel et al. observed two deep infections, two aseptic loosening and two fractures bellow the tip of the prosthesis [155]. The final prosthesis survivorship rate with revision as the end point was 82.4% at 14 years of follow-up. The nonunion of the greater trochanter was considered major complication and was observed in 25 cases. In another series of 30 hips who underwent revision total hip replacement with an allograft prosthetic composite Sternheim et al. observed favorable long-term outcome [149]. The survivorship at 10, 15 and 20 years was 93%, 75.5% and 75.5%, respectively. Encouraging results were published by Blackley et al. with 78% successful results for an average of eleven-year follow-up [7]. The allograft-prosthesis construct survivorship at five years was 90% and at 10 years was 86%. A recent systematic review of 498 hips with a mean follow-up of 8.1 years reported survival rate of 82% [131]. The major complications were aseptic loosening observed in 13.7% of patients followed by dislocation in 12.8%.
The technique of bone reconstruction with use of a proximal femoral allograft-prosthesis construct as described by Gross et al. [
The use of a proximal femoral allograft-prosthesis construct has some inherited disadvantages characteristic for complex surgery. Allograft resorption eventually leading to failure of the revision is of major concern with longer follow-up [61]. Usually, it was observed after several years of follow-up but did not progress [7,155]. Authors that utilize uncemented distal fixation support the concept of direct loading of the host-allograft junction and argue that it minimizes allograft resorption [7,59]. On the other hand, cementing the prosthesis to the distal femur and thus stress shielding the allograft may explain the high rate of allograft resorption [61]. Nonunion of the allograft-host junction [7] or the greater trochanter [61,155] are of major concern with this technique. A step-cut osteotomy may provide rotational stability while an oblique osteotomy may provide greater surface area for bone healing compared to a transverse osteotomy. Dislocation is a frequent complication after revision with proximal femoral allograft with incidence ranging from to 7.3% to 16.7% [15, 61,131,155]. As with other cases, the high risk of dislocation may be lowered by optimal reconstruction of length, adequate version and high offset of the prosthesis-allograft construct and by maintaining the soft tissue tension and its attachment to the host femur [131]. The infection rates after revision with allograft-prosthesis construct are higher than that reported after primary hip arthroplasty. Rates of infection ranging from 0 to 10.9% were reported [15,94,132,136,155]. However, considering the high complexity of the technique these levels of infection are not unacceptable.
Femoral revision using proximal femoral allograft cemented to a long-stem prosthesis is appealing option for revision. The current data from the literature support the use of the technique as a durable solution, with available evidence reporting a long-term survivorship up to 86%. It is of a particular interest in the young patients because of its potential to improve bone stock and provide a substrate for subsequent revision. The development and refinement of this technique should be encouraged.
Obtaining stable and long lasting fixation in femoral revision in patients with severe bone deficiency is a difficult task. Long-term results after cemented revision have not been optimal [81,83,121]. High failure rates ranging between 12% to 44% at mid-term follow-up have been reported [2,81,83,121]. The main reason was difficulty in obtaining stable and long-lasting fixation in severe bone loss. Cementless fixation proved a promising alternative and was soon introduced in practice. However, for fears of stress shielding the ingrowth surface of first-generation designs was confined to the proximal part of the stem. Although highly successful in primary arthroplasty, the limited amount of porous coating with proximal fixation led to less favorable results in revision surgery (Table 4). Failure rates of 4% to 10% were reported at short- to mid-term follow-up. These results were slightly better than those obtained with an early cementing technique. The technique yielded acceptable results in less severe deformities [71]. Retrieval studies have demonstrated that less bone ingrowth occurs in revision stems compared to primary stems [21]. Porous surface extending to the diaphysis is needed to ensure stable primary fixation. In support of this, various authors have reported promising long-term results after revision with use of extensively coated uncemented stems [1,41,88,115].
Proximal femoral deficiency results from osteolysis, infection, fracture or bone damage during implant extraction. In such cases with severe bone loss, distal fixation with cylindrical, tapered or fluted stem designs is a viable option [4,14,41]. The technique requires accurate preparation of 4 cm to 7 cm of diaphyseal bone [41,92,102]. It is adaptable and can be used in situations with different severity of bone loss. Moreover, it can be used in periprosthetic fractures and is adjustable with extended trochanteric osteotomy. Distal stem fixation is the most successful strategy in terms of primary and secondary mechanical stability, bone osteointegration, and most importantly clinical results [4]. The main reason for its success is the fact that the implant is in contact with viable bone. Success rates of 90% to 95% have been reported with extensively coated monoblock stems over 10-year follow-up [105,115,158]. However, issues, such as thigh pain and proximal stress shielding, were reported frequently.
The principles of the Wagner stem are utilized in the tapered stems [156]. The cone prosthesis achieves good contact between the supportive distal diaphysis and the middle or distal third of the stem (Figure 6). The conical shape and the longitudinal splines promotes primary axial and rotational stability, which are prerequisites for osteointegration and long-lasting endurance of the cementless implant. The concept of modularity was introduced in the tapered stems with the advantages of versatile proximal fill and distal fit [76]. By modularity the sizes and shapes of the prosthesis can be increased by varying the diameter and shape of the proximal and distal part of the stem and locking them in different way. Modularity offers certain advantages such as correction and restoration of leg length, correction of offset and version, selection of optimal proximal fill, as well as compatibility with extended trochanteric osteotomy [4,92]. The potential problem of thigh pain was not associated with tapered stem design [156]. Disadvantages of modular taper stem designs include complexity, risk of stem fracture, fretting and corrosion of the junction, increased inventory, and higher cost.
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Lawrence et al. [95] | \n\t\t1993 | \n\t\t174 | \n\t\t7.4 | \n\t\t5.7 | \n\t\t1.1 | \n\t
Engh et al. [42] | \n\t\t1988 | \n\t\t127 | \n\t\t4.4 | \n\t\t1.6 | \n\t\t2.4 | \n\t
Kang et al. [76] | \n\t\t2008 | \n\t\t39 | \n\t\t2 (minimum) | \n\t\t2.6 | \n\t\t0 | \n\t
Krishnamurthy el al. [88] | \n\t\t1997 | \n\t\t297 | \n\t\t8.3 | \n\t\t1.7 | \n\t\t0.7 | \n\t
Harris et al. [65] | \n\t\t1988 | \n\t\t23 | \n\t\t2 (minimum) | \n\t\t0 | \n\t\t4.3 | \n\t
Moreland and Bernstein [106] | \n\t\t1995 | \n\t\t175 | \n\t\t5.0 | \n\t\t1.1 | \n\t\t4.2* | \n\t
Moreland and Moreno [105] | \n\t\t2001 | \n\t\t137 | \n\t\t9.3 | \n\t\t4 | \n\t\t- | \n\t
Results of cementless femoral revision.
* Mechanical failure
Cementless revision of Paprosky type 3A defect with a modular tapered stem (A) resulting in good initial (B) and mid-term stability at 2 years (C).
Various studies have reported favorable outcomes of various uncemented tapered distal fixation stems with high survival of more than 95% at 5 to 10-year follow-up [41,88,102]. The technique of cementless revision with distal fixation of the stem has been shown to be a reliable and straightforward. It ads no additional risks or complications. It can be used in all but the most severe segmental defects [4,14,41,102]. When the simple principles of the method are followed it provides stable and durable fixation of the revision implant. However, distal fixation does not restores host bone, thus making further revision surgery more difficult.
The goals of revision arthroplasty are to relieve pain and to improve function. In order to obtain these goals stable and durable fixation of the revision components must be achieved with restoration of hip center. Acetabular revision is the most difficult part of hip revision. Unfortunately, there is no single surgical technique to solve the problem of fixation. The achievement of stable initial and long-lasting fixation is challenged by the severity of different acetabular defects and soft tissue damage. The main acetabular reconstruction option is cementless pres-fit fixation of the cup with or without allograft [19,73]. When severe combined segmental and cavitary bone deficiencies, poor bone quality and viability or pelvic discontinuity are identified, other more complex options for acetabular reconstruction are required. These include trabecular metal (TM) cups, modular metallic augments, reconstruction cages, reinforcement rings, cup-cages, and structural or morsellized allografts that can be used to support the reconstruction.
In cases with no or moderate bone loss revision could be performed with simple cemented exchange of the implant. Historically, early revisions were performed with the same technique that had been used for primary arthroplasty. However, difficulties in achieving consistent long-term results had prevented use of this technique. Failure to achieve adequate cement interdigitation explained poor results reported with early cementing techniques. Key factors for good cementing technique are optimal exposure of cancellous bone, adequate containment of the cup, and a clean and dry socket [130]. Sutherland and colleagues demonstrated that preservation of the subchondral bone can increase stiffness and stress concentration at the bone-cement junction [150]. Callaghan et al [13] reported 4.3% revisions and 34% radiographic loosening at 3.6-year follow-up of cemented revisions. Similar high rates of loosening were reported by Pellicci et al at 3.4-year follow-up [122]. The long-term results after cemented revision were considerably worse [121]. Even with improvement of the cementing technology, the cemented acetabular fixation has not improved (Table 5).
At longer follow-up, using modern cementing techniques failure rates ranging from 35% to 65% were reported [78,112]. Ten-year survivorship of the acetabular component with radiographical loosening as the endpoint event was 72% [78]. Consequently, cement fixation of the acetabular component has become less popular among orthopedic surgeons. In contrast, hemispherous porous-coated cups with bone ingrowth potential were developed and demonstrated consistently better results.
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Raut et al. [127] | \n\t\t1995 | \n\t\t387 | \n\t\t5.5 | \n\t\t6.2 | \n\t\t18.8 | \n\t
Estok and Harris [43] | \n\t\t1994 | \n\t\t32 | \n\t\t11.7 | \n\t\t22.0 | \n\t\t19.0 | \n\t
Mulroy and Harris [109] | \n\t\t1996 | \n\t\t29 | \n\t\t15.1 | \n\t\t38.0 | \n\t\t44.0 | \n\t
Katz et al. [78] | \n\t\t1997 | \n\t\t79 | \n\t\t11.9 | \n\t\t16.0 | \n\t\t23.5 | \n\t
Eisler et al. [38]* \n\t\t | \n\t\t2000 | \n\t\t83 | \n\t\t3.6 | \n\t\t8.0 | \n\t\t22.0 | \n\t
Huo and Salvati [70] | \n\t\t1993 | \n\t\t113 | \n\t\t4.1 | \n\t\t1.0 | \n\t\t5.0 | \n\t
Results of acetabular revision using modern cementing technique.
* Third generation cementing technique
The approach to each individual case depends upon the severity and localization of host bone loss. Results after cementless revision of the acetabular component have outperformed cemented fixation [30,31,44]. With supportive and viable host bone and a reliable ingrowth surface a hemispheric metal shell supported with screws is a straightforward solution for acetabular reconstruction (Table 6). The success of the technique has been so dramatic that it is currently considered the gold standard by most arthroplasty surgeons in the USA.
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Della Valle CJ et al. [30] | \n\t\t138 | \n\t\t15.0 (minimum) | \n\t\t4.5* | \n\t\t1.5 | \n\t
Park et al. [117] | \n\t\t138 | \n\t\t20.0 (minimum) | \n\t\t8.0* | \n\t\t5.0 | \n\t
Wysocki et al. [162] | \n\t\t187 | \n\t\t5.0 (minimum) | \n\t\t2.0 | \n\t\t5.0 | \n\t
Lachiewicz and Hussamy [91] | \n\t\t60 | \n\t\t5.0 | \n\t\t0 | \n\t\t0 | \n\t
Tanzer et al. [152] | \n\t\t140 | \n\t\t3.4 | \n\t\t0.7 | \n\t\t4.3 | \n\t
Silverton et al. [145] | \n\t\t109 | \n\t\t8.3 | \n\t\t0 | \n\t\t5.0 | \n\t
Templeton et al. [153] | \n\t\t61 | \n\t\t12.9 | \n\t\t0 | \n\t\t3.0 | \n\t
Results of cementless cup revision.
*Combined wear and loosening
In minor or contained defects, hemispherical cup with/without grafting produced excellent results [30,31,44]. Cementless fixation is suitable for patients with Paprosky types 1, 2A and 2B defects: without hip center migration or pelvic discontinuity. As a general rule, at least 50% of the host bone is needed to be in contact with the implant in order to support a hemispherical cup. Transfixational screws are usually used to support ingrowth of the press-fit cup. Morcellized allografts could be used to fill the cavitary defects. In a deficient acetabulum with major bone loss such as Paprosky type 3 defects a hemispherical cup could be placed against the intact supportive roof ("high hip center"). Sometimes extra large (jumbo cup) or oblong cups can bypass severe bone defects and provide stable initial fixation for bone ingrowth. Cementless fixation results in a anatomical hip center or in a high hip center [26].
The failed acetabular components migrate in the direction of joint reaction forces creating a deficient acetabular bed with greater superoinferior dimension compared to the anteroposterior dimension. In such revision setting implantation of the cementless hemispheric press-fit cup in the anatomical hip center is not possible. A straightforward decision for treatment of such defects is to place a small hemispherical press-fit cup against the supportive bone at the roof of the acetabular defect - the so-called high hip center (Figure 7). Most authors consider arbitrary the hip center high if it is proximally greater than 35 mm to the inter-teardrop line [27].
Type 3A defect of the acetabulum (A) resulting in high placement of the cup (B).
Results after cementless press-fit fixation of the acetabular component inserted with screws outperformed cemented revision. With use of this approach, despite extensive acetabular bone loss excellent implant fixation was consistently reported. The durability of cementless acetabular fixation was proven in long-term studies, too. In the study of Templeton et al., none of the cementless cups have been revised for aseptic loosening at 12.9-year follow-up and only 3 cups have migrated [153]. In a study with minimum follow-up of 20 years, Park et al. demonstrated 95% survivorship with revision of the cup for aseptic loosening or radiographic signs for loosening as the end point [117]. However, with longer follow-up, the problem of polyethylene wear and osteolysis emerged. In their series, re-revisions for wear and osteolysis were first performed at approximately twelve years postoperatively [117]. At last follow-up 20 years after revision, the incidence of reoperations for polyethylene wear and/or osteolysis continued to increase.
The technique saves costs, time, and eliminates the use of structural allografts or cement. However, high rate of complications was reported [27,74]. This might reflect the complexity of the procedure. Certain disadvantage of the technique is restoration of limb-length discrepancy on the femoral side whereas the defect is on the acetabular side. This would result in abnormal hip biomechanics. Increased hip joint reactive forces with high hip center and impingement might partially explain the relatively higher rate of dislocation with this technique [117,162].
Considering the excellent results reported with porous coated press-fit acetabular components in terms of implant fixation, we believe that the use of press-fit cups should be considered in every revision setting if there is sufficient host bone stock to support the cup.
Extra-large cups offer certain advantages in maximizing the contact area between the cup and host bone when revising deficient acetabulum. There is no universally-accepted definition of the jumbo cup. Extra-large cups are arbitrary defined compared to the size of the pelvis, the hip joint, and the previous implant. Whaley and coworkers defined jumbo cups as having a minimum outside diameter of 66 mm (men) or 62 mm (women) [159]. This was based upon the fact that the revision cups used at their institution were 10 mm larger than the mean implant diameters used for primary hip arthroplasty.
The method has certain advantages [126]: the acetabulum is prepared straightforward by reaming to a large hemispere; the large implant fills in the deficiencies and bone grafting is usually unnecessary; the center of rotation is transferred inferiorly and to some extent laterally restoring hip biomechanics (Figure 8); the large implant provides greater contact area and greater lever arm. Disadvantage of the technique are the limitations in restoring bone stock. Moreover, most of the defects are oblong with a greater superoinferior dimension than anteroposterior dimension. Converting an oblong defect to a hemispherical with extensive reaming may disrupt posterior wall or column which is critical for cup stability [159]. This risk of host bone compromise may result in high implantation of the socket.
Whaley et al. reported on 89 acetabular revisions using extra-large hemispherical components from the Mayo clinic [159]. The probability of survivorship of the cup at eight years was 93% with removal for any reason as the end point, and 95% with radiographical loosening or revision for aseptic loosening as the end point [159]. Wedemeyer et al., Obenaus et al., and Dearborn and Harris published similar results with cup survivorship with an end point aseptic loosening higher than 94% at mid-term follow-up [26,113,157].
The technique saves costs, time, and eliminates the use of structural allografts or cement. However, the rate of complications reported was rather high. In the series of Park et al., the most common reason for revision in 11.6% of 138 hips was infection and dislocation [117]. Similar high rates of revision were reported by Dearborn and Harris [26] and Della Valle et al. [30]. This might reflect the complexity of the procedures.
Extra large cups are a reasonable alternative in patients with moderate defects (Paprosky type 2).
Correction of the center of rotation with a large oversized cup.
As described earlier, large oval contained defects cannot be filled-in superoinferiorly without excessive reaming of the anterior or posterior column of the acetabulum to produce hemisphere. Another option is high placement of the cup. Attractive alternative in such cases is oblong cup. Oblong cup has smaller anteroposterior and mediolateral dimensions compared to the superiorinferior dimension. By accommodating the implant to the defect oblong cups can restore hip center and increase implant contact with host bone. Advantages of the technique are: lack of increased reaming of the anterior or posterior columns or metallization of the cup; increased contact between the device and the host bone; restoration of hip center [19,73]; and avoidance of structural allografts [5]. Disadvantages include higher cost, difficulties in cases with insufficient contact [16], possible component malpositioning, failure to restore bone [5], and excessive bone removal in order to achieve press-fit [126].
In a multicenter study on 38 hips revised with oblong press-fit cups, Berry et al. published good results at mean 3 years after surgery [5]. There was only one failure for acetabular loosening that required re-revision. Mean Harris Hip Score (HHS) increased from 50 points preoperatively to 90 points after revision. The hip center was 37 mm above the inter-teardrop line before the operation and was corrected to 25 mm above the inter-teardrop line. Civinini et al. published good mid-term results after revising with oblong cup Paprosky type 2 and 3 acetabular defects [19]. In a series of 55 hips followed-up for an average of 7.2 years only one cup was revised for loosening. Similar good results were reported by DeBoer and Christie on 18 hips revised with oblong press-fit cups [28]. At the latest follow-up, 4.5 years after revision no component was loose and the mean HHS increased from 41 points preoperatively to 91 points after revision. The authors reported near anatomic restoration of the hip center to 17 mm above the inter-teardrop line after revision. Chen and Engh reported less favorable results in 37 revisions (29 with massive type 3 defects) followed-up for an average of 41 months [16]. Eight percent of the hips were probably loose and 16% were unstable. Eight of the 14 hips that had more than two centimeters of superior migration of the component and disruption of Koehler’s line on preoperative radiographs failed [16]. The authors found a correlation between loosening and average distance from the inferior edge of the cup and the interteardrop line. Five of the six unstable components initially had not reached to the level of the radiographic teardrop or distal to it [16]. In their early series, Sutherland [151] reported a 50% failure rate (3 of 6) after revision with an oblong cup of type 3 defects. Discouraging mid-term results were published by Babis et al. using a cementless oblong cup for revision of Paprosky 3A defects [3]. After a mean follow-up of 60.5 months 18 hips (29.0%) were revised and a further four hips (6.4%) were loose and awaited revision. Further analyses proved that careful patient selection is critical for the success of this revision technique.
Acetabular revision with an oblong cup is an attractive alternative, especially when the surgeon plans correction of an elevated hip center [16,108]. The technique is suitable for Paprosky type 2A, 2B and 3A defects where the acetabular defect is oval. Obtaining initial stability and supplementary fixation by screws are mandatory for the stability of the implant and are key factors for long-term success of the reconstruction. However, the medial wall should be intact and the failed component should not have migrated more than two centimeters. Pelvic discontinuity is also a contraindication for this technique. Alternative techniques such as structural allograft or cage should be considered in such revision settings.
Cemented acetabular revision yielded unacceptably high rate of loosening [13,80,81]. Possible reason is the deficient, weaken and sclerotic acetabular bone frequently found at revision. An attractive alternative for cup fixation in massive contained defects is impaction grafting where the cup is cemented on a premoulded bed of impacted morsellized cancellous bone. In such revision setting the contact with host bone is very limited if not absent. The morsellized bone has osteoinductive and osteocunductive properties and is used as a filler scaffold of contained defects. The technique of impaction bone grafting and cemented fixation of the cup was first described in 1984 by Slooff and coworkers [146], and later standardized by the same authors with minor modifications and technique-specific instrumentation [11,142]. Morsellized graft could be used with a cementless hemispherous cup if more than 50% of the cup is in contact with viable host bone [57]. Transfixing screws should be used for additional stabilization of the cup. In cases with less than 50% contact between the cup and viable host bone the cemented cup into impacted cancellous bone should be used [146].
The technique can provide stable and durable reconstruction of the hip joint. However, initial mechanical stability of the morsellized allograft-cemented cup composite is a prerequisite for a successful biological reconstruction. Subsequent remodeling and incorporation of grafts, provides long-term stability. In contrast to cementless revision, this technique could restore bone loss. The modern evolved technique consists of reconstruction of segmental and rim defects with use of a metal mesh or a solid graft. The sclerotic areas are perforated with multiple 2-mm drill-holes, and fresh-frozen morsellized bone chips are impacted layer by layer into the acetabulum. The clinical success of the of impaction grafting depends on the surgical technique and on the biological and mechanical properties of the morsellized bone graft. Various factors connected with the graft such as graft type (cancellous, cortical-cancellous, chemical composites, synthetic additives), graft processing (fresh frozen, freeze-dried, irradiated), graft particle size and grade influence the clinical result. The originators of the technique use fresh frozen allografts [11,142,143].
The technique of acetabular impaction grafting is well-established and various authors demonstrated reproducible results [20,51,143,154]. Schreurs et al. reported good results after acetabular revision with impaction allografting at 15 to 20-year follow-up [142]. With revision for aseptic loosening as the endpoint, cup survivorship was 84% at 15 years [142]. In a 20 to 28-year follow-up study, Busch et al. from the same study group evaluated 42 patients with impaction grafting younger than 50 years [11]. With revision for aseptic loosening as the end point, survivorship was 85% after twenty years and 77% after twenty-five years [11]. With end point event signs of loosening on radiographs, survival was 71% at twenty years and 62% at twenty-five years. Results declined over time, but the authors concluded that the technique is useful in younger patients with major bone defects [11].
Acetabular revision using impaction grafting is a reliable alternative for biologic restoration of hip joint mechanics. The procedure is technically demanding and exacting. Results comparable to those after revision with cementless hemispheric cups were obtained after use of correct surgical technique.
Reconstruction cages and antiprotrusio rings are an established method of treatment for severe acetabular bone loss if contact with 50% host bone could not be established [57]. They have the advantage of fixation into viable host bone of the ileum and ischium with flanges while protecting allograft (Figure 9). Failure rates higher than 60% at an average of 2.9 years have been reported in cases with massive allografts not supported by cages [116]. Because of the poor results following use of unsupported structural allograft use of reconstruction cages has been advised [148]. Reinforcement rings or reconstruction cages can provide adequate support for the reconstruction with massive allografts in Paprosky type 2C and type 3 defects. Favorable results were reported after use of reconstruction cages by different authors [50,68,107,125]. Recently, this treatment approach has been questioned as TM implants provide more favorable conditions for graft incorporation and bone ingrowth [148].
The reconstruction cages and antiprotrusio rings have definite advantages: the cage and ring allow for restoration of hip center; they provide uniform load to the allograft stimulating bone remodeling and incorporation into host bone [72]; cementing allows use of local antibiotic protection; allow correct placement of the cemented cup independent of the cage or ring. The cage protects either the morsellized or structural allograft while it remodels, and if the cage fails cementless revision can be done [55,57].
Reconstruction of a Paprosky type 2C defect (A) with a cage (B). Remodeling of the allograft at 2 years.
Disadvantages include higher cost, need for wide surgical exposure of the superolateral part of the ileum. The later may risk injury of the superior gluteal nerve and limping. The major concern with standard nonporous cages and rings is that they do not allow bone ingrowth. Finally, they loosen and break. However, this inability of bone ingrowth is compensated by the mechanical stability and incorporation of the graft reducing the risk of fatigue fracture of the cage. Close fit between the cage and the allograft as well as adequate fixation of the cage are a prerequisite for successful reconstruction. Cement augmentation of screws is recommended in cases with severe osteolysis or osteoporosis.
The limits of using antiprotrusio rings were demonstrated by Haentjens and coworkers and Zehntner and Ganz [63,163]. High rate of migration up to 44% (12/27) at mid-term follow-up of 7.2 years was reported [163]. Previous designs of reconstruction cages did not allow bone ingrowth and a failure rate of 16.4% due to loosening was reported on average 4.6 years after surgery [55]. Sporer et al. reported a 2- to 8-year follow-up of 45 hips where a cage was used for a type 3 defects [148]. Nine hips were revised for aseptic loosening, and an additional nine hips were radiographically loose.
In contrast, Winter et reported no loosening or revision in 38 hips followed-up at mean 7.3 years after revision with cage [160]. In a long-term study, 18 acetabular revisions for pelvic discontinuity have been reported on average 13.5 years after surgery [129]. Two cages were revised for aseptic loosening, and another two allografts showed signs of severe osteolysis. Survivorship of the acetabular component at 16.6 years with end points revision for any reason, loosening or nonunion of the allograft was 72%. The increased rate of loosening and revision is probably multifactorial and reflexes the increased case load. Frequent indication for use of reconstruction cages is pelvic discontinuity. However, designs without bone ingrowth do not have potential for biologic fixation and rely solely on mechanical fixation.
Antiprotrusio cages and rings are an effective technique for treatment of severe bone defects. However, in recent years, newer implant designs have gained popularity. In cases with more than 50% host bone support cementless cup transfixed with screws is the treatment method of choice. Trabecular metal implants, porous augments, and triflanged acetabular components are an attractive alternative for complex acetabular reconstructions, [33,57,148]. TM cups have been proposed if contact with viable host bone is 30% to 50%. If contact with viable host bone is less than 30% a cup-cage construct was suggested [57]. Longer follow-up studies are needed to support the clinical use of these new implants.
One of the most difficult scenarios in revision surgery is a reconstruction of a massive acetabular bone loss. Structural acetabullar allografts are a suitable revision option for uncontained bone defects (Paprosky type 2B, 3A and 3B). The size of the allograft may range from a femoral head in superolateral uncontained defects to total acetabular allograft when severe uncontained defects or pelvic discontinuity are present.
Advantages of the technique include restoration of hip center and restoration of bone stock for future revisions [50,68,90,125]. However, actual restoration of viable and mechanically competent bone is questionable. Moreover, results are unpredictable. The technique is demanding and associated with various complications.
Results after revision with structural allografts have been largely controversial. Harris initially reported successful results after reconstruction of severe acetabular defects with structural allografts [135]. However, the encouraging period of initial good functioning for 5 to 10 years was followed by later failures. In 1993, Kwong et al. reported 47% failures in 30 hips with a mean follow-up period of 10 years [90]. In 1997, the senior author reported total rate of revision or loosening 60% at an average of 16.5 years [144]. High hip center for placement of the cup was suggested in cases with severe acetabular bone loss [135].
In a series of 33 hips followed-up on average 7 years after revision with a structural allograft, Garbuz et al. reported 55% success rate [50]. Fifteen hips were revised: seven hips because of failure of the prosthesis and eight hips because of failure of both the allograft and the prosthesis. Gross et al. reported on 107 hips reconstructed with bulk allograft [58]. Thirty hips (28%) were revised and in 15.9% of cases (17 hips) the indication was aseptic loosening. The authors reported 76% successful results in the 33 hips with minimum duration of follow-up of 5 years (average, 7.1 years) after the revision. However, eight hips needed additional reoperation because of failure of the graft and another six hips were revised for loosening. Hooten et al. reported on a series of 31 revisions with structural allograft and cementless cup followed-up on average 46 months after surgery [68]. Twelve (44%) cups were radiographically loose and five of these hips were revised. In contrast, Paprosky et al. reported a failure rate of 19 per cent (6/31) at an average follow-up of 5.7 years after revision with use of a structural allograft [116]. The only failures in that series were in hips in which the allograft supported more than 50 per cent of the cup. In another study, Morsi et al. found a success rate of 86% (25/29) at mean follow-up of 7.1 years [107]. They used a minor bulk allograft that supported less than 50% of the cup.
Although results after revision with structural allograft are controversial, most authors agree that the rate of success increases if more than 50% of the cup is in contact with viable host bone [50,68,116]. According to Morsi et al. [107] and Pollock and Whiteside [125] a repeat revision does not mean failure of the reconstruction. This complex reconstruction can be considered successful if bone stock is restored for future revisions.
Revision with structural allograft is a suitable option for restoration of hip center. The role of the allograft is to support the cementless cup with partial stability until adequate ingrowth occurs. The success after the procedure is technically-related. In order to optimize result after revision with structural allograft a number of principles should be followed. Structural allografts combined with antiprotrusio cages, and a cemented cup should be considered only in cases with insufficient host bone to provide a stable fixation for a press-fit cup [26].
For an optimal result, an appropriate allograft must be selected to match the mechanical requirements of the desired reconstruction. The method of processing of the bone allografts is important for the clinical result. Greater success rate with fresh frozen bone allografts was obtained compared to freeze-dried allografts [58]. The trabecullae of the allograft should be in the direction of load for optimal stress transfer. After trimming of the allograft in order to obtain maximal contact with the host bone the allograft is fixed with 6.5 mm parallel screws in the direction of load. In case of pelvic discontinuity, the column should be fixed with a plate before fixating the allograft. Use of reinforcement cages improves results after reconstruction with structural allograft [50,138].
Custom triflanged prostheses have been proposed for treatment of massive acetabular defects and pelvic discontinuity, but the experience is limited and the rate of complications is high [75]. The implant is manufactured from 3-D CT data reconstruction of the degree and localization of bone loss as well as its spatial orientation.
In 2007, DeBoer et al. evaluated the outcome of revision with a custom-designed porous-coated triflanged acetabular implant in 20 hips at an average 10-year follow-up [28]. A definite healing of the pelvic discontinuity was found in 18 hips (90%). The remaining two implants were radiographically stable and did not migrate even when discontinuity persisted. However, the overall dislocation rate in the series was 25%. Christie et al. followed-up retrospectively 67 complex revisions with custom-made triflanged implant [18]. Two discontinuities persisted, but both were asymptomatic and no implant was revised. Six (7.8%) hips were revised for recurrent dislocation. Using custom triflanged acetabular components Dennis reported three failures in 24 revisions with mid-term follow-up of 4 years [33]. He questions the value of the technique in pelvic discontinuity unless supplemented with additional column plating.
The technique has high cost, it is time consuming, requires extensile exposure, and lacks modularity. It could not be used in urgent clinical situation where it is not possible to wait for manufacturing the product. With complex implant and technically challenging surgery custom-designed triflanged prosthesis should be reserved for cases where less costly and less technically demanding options could not be used. Many surgeons consider it a salvage procedure for cases where the bone loss is catastrophic.
Trabecular metal cups can be used in massive contained or uncontained defects. As tantalum provides favorable environment for biological fixation, TM cups have been suggested for revision of Paprosky type 3 defects [57,148] instead of an allograft-cage construct.
Early results with use of TM implants have been encouraging [111]. TM has decreased the need for at least 50% contact of the implant with viable host bone. In Paprosky 3A an 3B defects, because cages do not provide biologic fixation, Gross suggested use of a cup and cage construct (the so-called cup-cage technique) when less than 30% contact can be made with viable host bone [57]. The rationale behind the technique is that load will be taken off the cage, once bone ingrowth occurs into the trabecular metal cup. So early and mid-term failures of the cages will be prevented.
Sporer et al. reported on 13 hips with pelvic discontinuity revised with tantalum cups with or without augments [147]. At mean 2.6 years after revision 12 of the 13 cups were radiographically stable. Lakstein et al. reported on 53 revisions of contained defects with 50% or less contact with host bone using TM cups [93]. Two cups (4%) were revised, and two additional cups (4%) had radiographical evidence of probable loosening at a mean 45-month follow-up. The fact that some of the TM cups lacked contact with a viable host bone is impressive. Four hips (8%) dislocated and one (2%) sciatic nerve palsy was observed. In a large multicenter study, 263 revisions with tantalum TM cups were followed-up at an average 7 years after surgery. At the most recent follow-up, all cups were radiographically stable and no revision for loosening was reported. Eight dislocations (3%) in the series were successfully treated with closed reduction, and one sciatic palsy partially resolved at last follow-up. Kosashvili et al. reported on 26 revisions of pelvic discontinuities using cages combined with trabecular metal components and morsellized bone (cup-cage technique) [87]. At mean follow-up of 45 months 23 hips (88.5%) were radiographically stable.
Promising midterm results have been demonstrated after revision with use of these new techniques. Currently, the preference is to biological fixation whenever possible, and to alternative options when initial stability could not be obtained.
Modular metal augments of various sizes and shape are used to decrease defect size and to restore bone defect to contained one capable of supporting a revision cup (Figure 10).
The size and placement of augments is highly dependable on the bone loss pattern. Augments are secured with multiple screws to host bone and remaining defects are filled in with morsellized bone. The hemispherical cup is impacted into the defect with the interface between the shell and the metal augment cemented.
TM modular augments (courtesy of Zimmer, Warsaw, IN, USA).
During the last two decades, revision hip arthroplasty is constantly in the focus of orthopedic surgeons as the numbers of these difficult and risky surgeries are increasing. Up to date, he paradigms of revision surgery has been evolving constantly. From polyethylene wear, osteolysis and loosening, to complexities such as pelvic discontinuity, there is a wide range of surgical options for successful reconstruction. Analysis of clinical results from various studies outlines the preference for biological fixation of the revision implant whenever possible. It is vital for the surgeon to be familiar with different treatment approaches and to anticipate various intraoperative scenarios. Systematic approach with considerable preoperative evaluation and planning will achieve a good result. Prerequisite for a successful and durable revision include viable host bone, adequate surgical technique, and stable and endurable implant. Current improvements in surgical techniques, implant designs, as well as biomaterials and bearing surfaces are a significant contribution for obtaining favorable outcome after revision hip arthroplasty. However, we do not have complex solution. The optimal surgical approach for revision THA varies considerably among different settings. On the other hand, the economic burden of total joint replacement is increasing at a steep rate. This necessitates improved methods for evaluation of existing technology and particularly patient-derived outcomes assessment instruments. Further research and well-designed clinical studies are needed in order to provide optimal treatment to the increasing number of patients requiring revision surgery in the future.
Endometriosis an estrogen dependent disease characterized by ectopic growth of endometrial glands and stroma outside of the uterine cavity. It is estimated that endometriosis may affect anywhere from 5 to 45% of all women [1]. Although retrograde menstruation has become the most widely accepted theory for the development of endometriosis [2], it cannot account for endometriosis in distant organs such as the lung and brain. Therefore, alternative explanations are sought.
\nWhile the cause of endometriosis remains unknown, it most likely arises from a multifaceted origin involving the interaction of environment and genetics [3]. Among the different hypotheses advanced, a growing body of literature suggests that environmental factors including environmental toxicants may play a role in the pathophysiology of endometriosis. Lifestyle and medication use point to a role for environmental factors in endometriosis. While alcohol consumption and cigarette smoking have been associated with lower endometriosis risk [4], developmental exposure to diethylstilbestrol and early life exposure to soy formula as well as alcohol consumption in adulthood was linked with an increased risk of endometriosis [4, 5]. Support for an environmental toxicant influence on the development of endometriosis surged with the report of endometriosis in rhesus monkeys treated with 2,3,7,8-tetrachlorodibenzo-
Potential associations between exposure to environmental toxicants and women with endometriosis have been equivocal with several finding positive associations [8, 9, 10] whereas others were unable to document an association [11, 12, 13]. Since our last review of the subject [14, 15, 16, 17] numerous studies have emerged suggesting a potential link between environmental toxicant exposure and endometriosis [7, 18]. Herein, we describe a systematic review and critical appraisal of the recent literature linking exposure to environmental toxicants and endometriosis using a modified weight-of-evidence approach to evaluate the strength of potential associations.
\nWe conducted a systematic review of the literature between 2008 and present, to capture publications since our last review of the subject [14, 17]. An electronic search was performed using PubMed and web of science between October and November 2019. The following search terms were employed: endometriosis and environmental contaminants, environmental chemicals, environmental toxicants, endocrine disrupters, dioxins, polychlorinated biphenyls (PCBs), phthalates, bisphenol A, and metals. Inclusion criteria included biomonitoring, epidemiology studies reporting chemical concentrations in women with endometriosis compared to a reference population and associated risk. We also included articles describing experimental animal studies and
Our electronic search of the literature revealed 67 articles from which four articles with duplicate titles were excluded (Figure 1). We further excluded six review articles. An additional seven articles were excluded because they either did not report chemical concentrations or associated risk for the development of endometriosis. Consequently, 50 articles were retained for full assessment. The largest group of articles addressed the association between exposure to chlorinated organic compounds including polychlorinated biphenyls (PCBs), dioxins, and dioxin-like compounds with relatively few studies exploring the link between pesticide exposure and endometriosis. Of the chemicals with comparatively short half-lives relative to the chlorinated organic compounds and potential to disrupt endocrine signaling pathways, several reports linking phthalate esters and bisphenol A with endometriosis were found in our search whereas relatively few studies involving perfluoroalkyl compounds and metals studies were found.
\nFlow diagram summarizing the process of candidate article title identification in our electronic literature searches (PubMed and Web of Science) conducted between January 2018 and February 2019, screening, and article selection vs. exclusion. The number of articles included vs. excluded and reasons for exclusion are indicated.
PCBs are one of the most widely produced chemicals worldwide, with millions of pounds being produced globally over the last decade alone [19] for use a coolants in electrical transformers. With 209 possible congeners, PCB toxicity is dependent on chemical structure. For example, non-ortho or mono-ortho PCBs are far more toxic due to the loss of chlorine atoms on the 2,2′,6,6′ of the benzene rings [20]. Due to their diverse structures, PCBs share similar characteristics to estrogen, allowing them to have both agonistic and anti-estrogenic activity [21, 22]. PCBs have been known to disrupt several organs and tissue types throughout the human body; with particular damage to the liver, kidney, and the endocrine system [19]. Our search revealed several studies primarily focused on PCB exposure and endometriosis and additional studies that explored the link between dioxin and dioxin-like compounds and endometriosis (Table 1). Since these compounds are frequently found together in human tissues, we will discuss them together.
\nAuthors | \nCases vs. controls | \nExposure investigated | \nTissue | \nOutcome | \n
---|---|---|---|---|
Porpora et al. [23] | \n80:78 | \nPCBs 28, 52, 101, 105, 118, 138, 153, 156, 167, 170, and 180 | \nSerum | \nIncreased risk of endometriosis for DL-PCB-118 (OR = 3.79; 95% CI, 1.61–8.91), NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10) were all significant in case versus controls. | \n
Cai et al. [24] | \n10:7 | \nPCBs 77, 81, 126, 169, 105, 114, 118, 123, 156, 157, 167, and 189 | \nSerum | \nPCB concentrations were higher in peritoneal fluid than serum. However, the total TEQ LOD and dioxin-like PCBs were not significantly different between women with endometriosis and the controls. | \n
Trabert et al. [25] | \n251:538 | \nPCBs 18, 28, 44, 49, 52, 66, 74, 87, 99, 101, 118, 128, 138, 146, 149, 151, 153, 156, 157, 167, 170, 172, 177, 178, 180, 183, 187, 189, 194, 195, 196, 201, 206, and 209 | \nSerum | \nSeveral PCB congeners were associated with significantly lower risk (PCB 170 3rd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9) PCN196 (3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), PCB201 (2nd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; and 3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7) but not summed values (PCBs 170, 196, 201; OR = 1.3, CI 0.8–2.2) and estrogenic PCBs (OR = 1.1; 95% CI, 0.8–1.4). | \n
Ploteau et al. [26] | \n68:45 | \nPCBs 77, 81, 126, 169, 105, 114, 118, 123, 156, 157, 167, 189, 28, 47, 99, 100, 153, 154, 183, 209 | \nSerum, omental, and peritoneal adipose | \nSignificant correlations for PCB concentrations within the three biological compartments omental versus peritoneal adipose tissue were found ( | \n
Buck-Louis et al. [27] | \n190:283 and 14:113 | \nPCBs: 18, 28, 44, 49, 52, 66, 74, 87, 99, 101, 114, 118, 128, 138, 146, 149, 151, 153, 156, 157, 167, 170, 172, 177, 178, 180, 183, 187, 189, 194, 195, 196, 201, 206, and 209. | \nSerum and omental fat | \nHigher concentrations in omental fat than serum. PCB-74, and PCB-156 in fat were inversely associated with the odds of an endometriosis. | \n
Martínez-Zamora et al. [28] | \n30:30 | \n2,3,7,8-TCDD, 1,2,7,8-PeCDD, 1,2,3,4,7,8-HxCDD, 1,2,3,6,7,8-HxCDD, 1,2,3,7,8,9-HxCDD, 1,2,3,4,6,7,8-HpCDD, 2,3,7,8-TCDF, 1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF,1,2,3,6,7,8-HxCDF,2,3,4,6,7,8-HxCDF, 1,2,3,7,8,9-HxCDF, 1,2,3,4,6,7,8-HpCDF, 1,2,3,4,7,8,9-HpCDF, OCDF | \nAdipose tissue from the omentum | \nDioxins and DL-PCBs were significantly higher in patients with deep infiltrating endometriosis; TCDD, PeCDD, PeCDF were the most significant | \n
Simsa et al. [29] | \n96:106 | \nDLCs not specified | \nPlasma | \nDLC concentrations were marginally higher in patients with endometriosis (22.3±9.3 pg vs. 20.5±10.8 pg) and higher plasma levels of DLC were linked to a higher risk of endometriosis (aOR = 2.44; 95% CI 1.04–5.70; | \n
Vichi et al. [30] | \n181:162 | \nPCBs 118, 153, 138, 170, 180, and total PCBs | \nSerum | \nWith the presence of the GSTP1 wild type genotype, medium-high levels of PCB 153, high levels of PCB 180 and total PCBS were significantly associated with endometriosis risk (OR = 6.00; 95% CI, 1.88–19.18 and OR = 9.08; 95% CI, 2.14–44.4, respectively). | \n
Summary of exposures and outcomes from biomonitoring studies designed to quantify the concentration of polychlorinated biphenyl congeners, dioxins, dioxin-like compounds (DLCs) and non-dioxin-like compounds (NDL) in women with endometriosis compared to healthy controls.
In a pilot case–control study [24], involving 17 women (10 cases; 7 controls), superficial endometriosis was present in 90% of the cases. Of the 29 congeners measured in this study, both polychlorinated dibenzofurans (PCDFs) and dioxin-like (DL) -PCBs showed no significant difference between the case and control [24]. However, both were elevated in peritoneal fluid relative to the serum, with the reverse seen in polychlorinated dibenzo-
While several studies have provided evidence of a potential link significant associations between women with endometriosis and PCB levels could not be demonstrated by other investigators [25, 28, 31]. No significant association between PCBs and endometriosis risk was found in a study of 789 patients (251 cases; 538 controls); with 20 PCB congers measured in serum from surgically confirmed cases [25]. While the odds ratios (ORs) for several PCB congeners did show significant levels above and below the null; however, there was no specific pattern associated with endometriosis risk. Several PCBs were quantified in the serum of 473 women in an operative cohort (190 cases; 283 controls) and 127 patients from a general population cohort (14 cases; 113 controls), using omental fat in the operative cohort and serum in both [31]. Results were adjusted for confounding variables such as age, BMI, breast-feeding, cotinine, and lipids. Among the 35 PCB congers analyzed, geometric mean serum PCB levels were found to be inversely related in terms of risk in the operative cohort, with the opposite seen in the population cohort [31]. A similar relationship can be seen in omental fat, with sum PCB levels showing significantly higher levels in the non-endometriosis patients relative to the controls. Limitations of this study include the small number of women with endometriosis in the case population (only 11% of women had endometriosis), possible bias through the use of telephone directories, and use of controls without surgical confirmation of absence of disease suggest that results be interpreted with caution. The relationship between exposure to DLCs and deep infiltrating endometriosis (DIE) was explored in a case–control study of 30 cases and 30 controls [28]. Disease status was determined by clinical examination, magnetic resonance imaging (MRI), and transvaginal ultrasonography (TVUS), whereas the control population underwent laparoscopic surgery for adnexal benign gynecological disease. DLCs were analyzed omentum adipose tissue in both groups. The results suggest a significant increase of both dioxins and PCBs relative to the control, with the most toxic forms showing a significant difference (2,3,7,8-TCDD and 1,2,3,7,8-pentachlorodibenzo-
A biomonitoring study conducted in France [26], measured the concentrations of PCBs in serum, peritoneal and omental adipose tissue of 113 adult French women with deep infiltrating endometriosis (DIE) (45 controls, 68 cases). There was a significant difference between omental versus peritoneal adipose tissue PCB concentrations (
Potential gene–environment interaction among women with endometriosis was explored [30]. Specifically, the relationship between glutathione transferase (GST) gene polymorphisms PCB concentrations in a study of 343 Italian women (181 cases; 162 controls). Ability glutathione enzymes to regulate oxidative free radicals and thus oxidative stress and therefore genetic polymorphisms may influence tissue capacity to manage the damaging effects oxidative stress, in turn influencing disease susceptibility. No significant difference in genotype distribution (GSTM1, GSTA1, and GSTP1) between case and control patients could be elicited [30]. However, the GSTP1 wild-type with medium-high blood levels of PCB153, high levels of PCB180, or total PCB levels, showed a significant increase in potential risk, while GSTT1 null was negatively associated with the disease [30]. The potential association between five microsatellites and 28 single nucleotide polymorphisms among 10 dioxin detoxification genes (aryl hydrocarbon receptor (AhR), AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined in 242 women (100 case; 143 control) from Japan [32]. Accounting for disease stages I-IV, BMI, and smoking, no significant association was seen between the polymorphisms and the contribution to the etiology of endometriosis. Taken together, these data suggest that genetic polymorphisms in detoxification enzymes do not modulate endometriosis risk.
\nEstablishing a link between exposure to environmental toxicants and endometriosis using epidemiology and biomonitoring is difficult owing to challenges in diagnosis of endometriosis [33], lengthy diagnostic delays [34], and high prevalence of endometriosis in asymptomatic women [1] and thus the potential for misclassification error is high. Therefore, animal studies have been employed to better understand the potential hazard posed between toxicant exposure and endometriosis. Developmental exposure of mice to TCDD induced a progesterone-resistant phenotype in adult animals that persisted across generations [35]. Results of this study suggest that TCDD induced activation of the aryl hydrocarbon signaling pathway induces dysregulation of expression of tissue remodeling enzymes, and contributes to the inflammatory responses, cell migration, and proliferation seen in endometriosis patients. These data are supported by prior animal studies demonstrating PCB and dioxin effects in animal models of endometriosis [36, 37, 38].
\nTissue culture studies have been employed to elucidate potentially important toxicant regulated mechanisms. PCBs have been linked to an increased estradiol synthesis and creating an inflammatory milieu through the production of interleukin (IL)-6 and IL-8 [39]. Primary cultures of endometrial stromal cells (ESCs) were treated with both DL-PCBs and NDL-PCBs. Dioxin-like CB126 treatment increased 17β-estradiol (E2) biosynthesis in a dose dependent manner. CB126 exposure also increased 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) as well as decreased methylation of the HSD17B7 promoter leading to an increase in expression. Inflammatory markers were also elevated in cultured endometrial stromal cells. Increased inflammation and E2 synthesis were demonstrated in a mouse model of endometriosis [39]. Although PCB has shown to increase E2 biosynthesis, combining 17β-Estradiol with TCDD showed a synergistic effect and induces M2 activation with macrophages co-cultured with ESCs. STAT3 and P38 phosphorylation in macrophages were also increased differentiation of M2 macrophages, leading to an inflammatory milieu [40]. Several studies also analyzed the impact of TCDD exposure on progesterone-dependent mechanisms. TCDD was found to induce cannabinoid receptor type 1 CB1-R mRNA expression in endometrial stromal cells and steroid-induced expression of the gene was inhibited. Through the use of tissue obtained from women with and without endometriosis, TCDD treatment-induced dysregulation of cannabinoid signaling, immune cell migration into the endometrium during embryo uterine attachment [41] and thus we propose could be an important mechanism in the pathophysiology of endometriosis. PCB was also seen to activate endogenous aryl hydrocarbon receptor (AhR) signaling pathway in immortalized human telomerase reverse transcriptase (hTERT) endometrial epithelial cell (hTERT-EEC), specific to time, concentration, and congener. The changes induced were modulated by changes in estrogen levels, in turn increasing cell migration by hTERT-EEC. Proteomic analysis also identified cell stress responses and metabolism markers (such as heat shock proteins (HSP) 27 and HSP 70) [42]. These proteins are both critical markers for the regulation of apoptosis and cellular stress response pathways. In another study [43] primary cultures of ESCs from both case and control patients showed that PCB-104 exposure affects cell migration, invasion and resultant gene expression. Treatments induced a significant increase in cell migration and invasion of ESCs. Enzyme-linked immunosorbent assays showed a time and dose dependent increase in matrix metalloproteinase 3 (MMP-3) and MMP-10 protein in ESCs, whereas MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not. MMP-3 contributes to the breakdown of the extracellular matrix and promotes tissue remodeling and migration [43]. The results from this study suggest that PCB-104 increased migration and invasion of ESCs through increasing MMP-3 and MMP-10 [43]. Taken together, results from tissue culture studies elucidate PCB and dioxin induced dysregulation of mechanisms potentially important in the pathophysiology of endometriosis.
\nIn summary, several studies demonstrated a potential association between exposure to PCBs, dioxins, and dioxin-like compounds and increased risk of endometriosis; however, important study limitations decrease confidence in these study findings. Moreover, several studies were unable to evoke evidence of an association between exposure to these toxicants. While, animal studies are few, results from these studies provide evidence of biological plausibility. Results of tissue culture studies also provide evidence that PCBs and dioxins adversely affect mechanistic pathways important in the pathophysiology of endometriosis although the effective concentrations exceed human exposure. Consequently, we suggest that there is weak evidence linking exposure to PCBs and dioxin and DL-PCBs in the pathophysiology of endometriosis.
\nChlorinated organic pesticides (COPs) resist degradation in the environment, are lipophilic and thus bioaccumulate in adipose tissues, and concentrations are biomagnified with increasing trophic level. Moreover, COPs are able to travel long distances and remain stable for several decades in the environment, and thus widespread human exposure to these chemicals has frequently been documented. Despite widespread human exposure, the relationship between pesticides and endometriosis risk in general are equivocal.
\nThe concentrations of six COP levels were measured with gas chromatography and electron-capture, in blood samples of laparoscopically confirmed cases of endometriosis [44]. Results showed that aromatic fungicides had a five-fold increase in risk (aOR = 5.3; 95% CI, 1.2–23.6) when comparing the highest and lowest tertile after adjusting for smoking and serum lipids [44]. Chlordane (t-nonachlor) (aOR = 4.6; 95% CI, 0.5–41.6) and HCB (aOR = 6.4; 95% CI, 1.0–42.8) showed a similar trend [44]. Aldrin, β-hexachlorocyclohexane (β-BHC) and mirex also had increased ORs; however, few women had concentrations above the limit of detection preventing further analysis. Two other studies yielded similar results. Specifically, hexachlorocyclohexane (HCH) was associated with an increased risk of endometriosis in a large study with 248 surgically confirmed endometriosis cases and 538 controls [45]. β-HCH concentrations were significantly elevated in the serum (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0–2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8–2.4), as well as for mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0–2.2). The results were adjusted for participant age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Although trends were seen throughout multiple forms of endometriosis, the strongest association was seen in women with ovarian endometriosis. Similarly, γ-hexachlorocyclohexane (γ-HCH) had a significant association with endometriosis risk (adjusted OR (AOR) for age, body mass index, breast-feeding conditional on parity, cotinine, and lipids = 1.27; 95% CI: 1.01–1.59) [31]. Although these studies provide evidence for a link between exposure to different pesticides and increased risk of endometriosis, there are several limitations to note. In particular, while the authors adjusted their data for some potential confounding variables none appeared to adjust for BMI. Moreover, since multiple pesticides were quantified in each study, correction for multiple comparisons would add confidence to the findings and exclude the potential for type I error. Furthermore, the lack of a dose–response relationship [45] suggests that chance discovery cannot be excluded.
\nWe found no recent animal studies and only one
In summary, the epidemiological and biomonitoring studies suggest a potential association between exposure to chlorinated organic pesticides and increased risk of endometriosis; however, study limitations cannot exclude chance discovery owing to multiple comparisons, failure to adequately adjust for important confounders and lack of a dose–response relationship all weaken confidence in the link between COP exposure and endometriosis risk. A single tissue culture animal experiment conducted within the search window suggests that it is biologically plausible for COPs to promote endometriosis risk. Consequently, we suggest weak evidence linking exposure to COPs and endometriosis.
\nPerfluoroalkyl substances are a rather unique group of compounds due to their seemingly harmless properties. However, over the last decade, perfluoroalkyl and polyfluoroalkyl substances have been detected in blood and urine across the globe [47, 48]. Compromised of carbon-fluorine atoms, this extremely strong bond forms stable compounds that are used in clothing, cookware, carpets, and other common household items. Exposure to these compounds has been linked to adverse effects on metabolism, immune function, and fertility [49, 50, 51].
\nIn a case–control study [27], nine perfluorochemicals (PFCs) were measured in the blood of study participants by liquid chromatography–tandem mass spectrometry. Surgical visualization was used to confirm endometriosis in the operative population and MRI was used to confirm the absence of endometriosis in the control population. Both perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17–3.06]) and perfluorononanoic acid (PFNA) (2.20 [1.02–4.75]) were seen to be associated with endometriosis risk, where results were only moderately changed when adjusted for fecundity [27]. Patients with more severe stages of endometriosis (Stages III and IV) showed a higher concentration of perfluorooctane sulfonic acid (1.86 [1.05–3.30]) and PFOA (2.58 [1.18–5.64]) in their blood compared to controls [27]. Although this study shows a significant association between PFC exposure with an apparent dose response, there are a number of limitations to consider. First assignments of healthy study participants to the control population using MRI alone to exclude asymptomatic endometriosis cannot exclude women with endometriosis. Undiagnosed endometriosis was found in 45.3% of asymptomatic women undergoing laparoscopies for benign conditions [1] and thus the potential for misclassification error in this study weakens confidence in the purported association. Finally, circulating concentration of PFCs from the NHANES (2003–2006) study was compared in 753 women with self-reported diagnosis compared to healthy women without a diagnosis of endometriosis [52]. Results from this study showed that PFNA, PFOA, and perfluorooctane sulfonate (PFOS) were significantly higher among women with endometriosis compared to the control population. Women in the referent population of this study were significantly younger, non-Hispanic white, had more than one menstrual period in the last year and reported to be pregnant at the time of the exam. Furthermore, use of self-reported diagnosis of endometriosis may introduce group assignment bias and thus, these data must be interpreted with caution.
\nThe data linking exposure to Perfluoroalkyl substances and endometriosis are limited to the results of two biomonitoring studies. Although the results suggest that women with endometriosis have exposure to Perfluoroalkyl substances, any potential association with endometriosis is weak owing to limitations of these studies and absence of experimental animal studies or mechanistic experiments.
\nA monomeric compound, bisphenol A (BPA) is used to polymerize plastics and can be found in common household items such as toilet paper, water bottles, the lining of tin cans, cash register receipts, dental sealants, and building supplies [53]. With over a million tons of BPA being used in the United States alone, BPA has become ubiquitous in the environment leading to widespread human exposure. BPA is able to bind to both estrogen receptors (Esr1 and Esr2), activate the estrogen signaling cascade and thus is considered a xenoestrogen [54]. Estrogenic capacity has led some to postulate that BPA exposure may play a role in the pathophysiology of endometriosis (Table 2).
\nAuthors | \nCases vs. controls | \nExposure Investigated | \nTissue | \nOutcome | \n
---|---|---|---|---|
Simonelli et al. [55] | \n68:60 | \nBPA | \nUrine and peritoneal fluid | \nUrinary BPA levels were found in all analyzed samples; with a statistically significant difference between patients and controls. Urinary BPA concentrations were significantly greater ( | \n
Upson et al. [56] | \n143:287 | \nBPA | \nUrine | \nNo statistically significant association between total urinary BPA concentrations and endometriosis overall. However, significant results were seen in urine in relation to non-ovarian pelvic endometriosis (2nd quartile vs. lowest quartile: OR = 3.0; 95% CI: 1.2–7.3 and 3rd vs. lowest quartile: OR = 3.0; 95% CI: 1.1–7.6), but not ovarian endometriosis. | \n
Cobellis et al. [57] | \n58:11 | \nBPA and BPB | \nSerum | \nBPA was found in 51.7% and BPB was found in sera 27.6% but either could not be detected in all the control cases. Suggests an association between at least one of the compound endometriosis risk. | \n
Itoh et al. [58] | \n166 infertile women | \nBPA | \nUrine | \nNo significant ( | \n
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between Bisphenol A (BPA) exposure and endometriosis.
A population-based case–control study [56], analyzed the urine from 143 women with confirmed or suspected endometriosis (cases) and 287 healthy controls. Urinary creatinine concentrations, age, reference year, as well as both ovarian and non-ovarian pelvic endometriosis were taken into account. Overall, the urinary BPA concentrations in cases did not differ from the control group. However, unconditional logistic regression analysis revealed that the second versus lowest quartile and third versus lowest quartile had increased adjusted odds ratio (aOR 3.0; 95% CI: 1.2–7.3 and aOR 3.0; 95% CI: 1.1–7.6) for higher BPA concentrations in women with non-ovarian pelvic endometriosis; however, there was no association between urine BPA concentrations and ovarian endometriosis. Moreover, there was no relationship between the highest urine concentrations of BPA and endometriosis overall as well as for non-ovarian pelvic endometriosis and ovarian endometriosis. Furthermore, the lack of a dose–response relationship with increasing urine concentrations of BPA weakens confidence in the potential link between BPA exposure and endometriosis risk.
\nResults of biomonitoring studies revealed that mean BPA concentrations in the plasma of infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) combined (4.66 ± 3.52, 95% CI; 3.60–5.72 ng/ml) were significantly greater than in a control population (n = 34) of healthy fertile women (2.64 ± 3.99, 95% CI; 1.24–4.03 ng/ml) [59]. In women who reported a diagnosis of endometriosis, the mean ± (SD) concentration of BPA was 4.59 ± 1.22 ng/ml (range < LOQ – 5.31 ng/ml). Moreover, BPA concentrations were quantifiable in only 3% of study participants and comparisons with the fertile controls was not reported. Given the ubiquitous nature of BPA, the low detection frequency in this study is rather surprising and thus we interpret these findings with caution. The small sample size, self-reported diagnosis of endometriosis and associated potential for misclassification error are important limitations of this study. Results of a much larger cross-sectional study of 166 Japanese women [58], showed no significant difference in BPA levels in the urine. BPA concentrations were non-significantly (
In an animal study [60], BPA and bisphenol AF (BPAF) affected endometriosis lesion development in ovariectomized and hormonally intact mice specific to dose and hormonal status of the host mouse. Minced uterine tissue was injected into the peritoneal cavity of host mice. In this study, BPA treatment disrupted ovarian steroidogenic pathways resulting in lower progesterone levels and higher atretic oocyte numbers [60]. BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm. Both compounds mimicked estrogen, with BPAF having a stronger effect than estrogen [60]. Taken together, these data suggest that BPA and related compounds can affect mechanisms important in the pathophysiology of endometriosis. However, the concentrations of BPA needed to achieve these effects are higher than human exposure and thus are unlikely to be relevant at the concentrations of BPA measured in the general human population in contemporary studies.
\nResults of a tissue culture experiments demonstrated that BPA treatment arrested human ESCs at the G2/M phase of the cell cycle, allowing for cell migration. Progesterone amplifying receptors such as insulin growth factor binding protein 1 and prolactin were also increased in response to BPA treatment [61]. These results suggest that BPA exposure could modulate endometrial stromal cells function; however, the effective concentrations exceed human exposure. Consequently, ambiguous study results from biomonitoring studies and lack of animal studies suggests a lack of association between BPA exposure and risk of endometriosis.
\nPhthalate esters are used as a softener in polyvinyl chloride plastics to make plastics flexible and can be found in products such as cosmetics, building materials, and in medical equipment such as intravenous bags, tubing and rubber stoppers in syringes and blood collection tubes. Phthalates leach from finished products leading to ubiquitous human exposure [62, 63]. Exposure to phthalate esters has been linked with decreased circulating testosterone [64] and animal experiments have shown that phthalates are competitive antagonists of the androgen receptor that displace testosterone from the receptor increasing its availability for conversion to estrogens via aromatase [65]. Therefore, it is postulated that exposure to phthalates could be associated with increased risk of endometriosis (Table 3).
\nAuthors | \nCases vs. controls | \nExposure investigated | \nTissue | \nOutcome | \n
---|---|---|---|---|
Pednekar et al. [59] | \n34:45 | \nBPA, MMP, MBzP, MEHP, MEHHP, MiBP-d4 and BPA-d6 | \nPlasma | \nSignificantly higher plasma concentrations of MBzP (95% CI; 11.69–28.12 versus 3.34–8.10), BPA (95% CI; 3.60–5.72 versus 1.24–4.03), and MEHHP (95% CI; 5.10–8.43 versus 0.58–2.85). | \n
Nazir et al. [66] | \n50: 50 | \nDEHP | \nSerum | \nThe mean (± SD) DEHP concentration in cases was 65.29 ± 21.69 ng/ml and undetectable in controls. An increasing trend was seen across stages (I-IV). | \n
Buck Louis et al. [67] | \n495:131 | \nDEHP, mECPP, mCMHP, mEOHP, mEHHP, mEHP, mCPP, mMP, miBP, mBP, mCHP, mBzP, mNP, and mOP, | \nUrine | \nMBP, mCMHP, mECPP, mEHP, mEHHP, mEOHP, all showed a two-fold significant increase in the odds of diagnosis. | \n
Huang et al. [68] | \n28: 29 | \nMBP | \nUrine | \nIncrease in urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, | \n
Itoh et al. (2009) | \n57:80 | \nMEP, MBP, MBzP, MEHP, mEOHP, and MEHHP | \nUrine | \nNo significant ( | \n
Weuve et al. [69] | \nn = 1227 | \nMEHP, BMP, MEP, and MBzP | \nUrine | \nPositive associations for MBP (OR = 1.36; 95% CI, 0.77–2.41) for the highest versus lowest three quartiles, and inverse associations for MEHP in relation to endometriosis (OR = 0.44; 95% CI, 0.19–1.02) | \n
Huang et al. [70] | \n44:69 | \nMMP, MEP, MnBP, MBzP, MEHP, 5oxo-MEHP, 5OH-MEHP | \nUrine | \nMarginally increased level of urinary MEHP only. | \n
Upson et al. [45, 71] | \n92:195 | \nMEHP, MEHHP, MEOHP, MECPP, MBzP, MEP, MiBP, MnBP | \nUrine | \nGreater urinary concentrations of MBzP and MEP in the urine of women with endometriosis compared to controls. Strong inverse association between urinary MEHP and endometriosis risk (aOR 0.3, 95% CI: 0.1–0.7). | \n
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between phthalate exposure and endometriosis.
A large case–control study [67], examined 626 women (495 cases; 131 controls) from 14 clinical centers. Study participants in both groups had a laparoscopy or a pelvic MRI to diagnose the presence of endometriosis. Among the 14 phthalate metabolites, mono-n-butyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate, mono (2-ethyl-5-carboxyphentyl) phthalate, mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-hydroxyhexyl) phthalate, and mono (2-ethyl-5-oxohexyl), all showed two-fold significant increase in the odds of diagnosis. Results were adjusted for age, BMI, and creatinine. Depending on the method of diagnosis, monooctyl phthalate was restricted to surgical diagnosis of endometriosis with histological confirmation, whereas mono (2-ethylhexyl) phthalate was restricted to surgical diagnosis alone. However potential limitations may arise through adding concentrations as mECPP, mEHHP, mEOHP where all are metabolites of DEHP that were elevated in the operative cohort. Yet when summing DEHP metabolites (mECPP, mCMHP, mEHHP, mEOHP, and mEHP), there is a higher odds of endometriosis in the control population cohort. A further limitation is the lack of adjustment for multiple comparisons and thus chance discovery cannot be excluded. A large study from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), examined phthalate levels in 1227 women, with a self-reported history of endometriosis and uterine leiomyomata. MEHP, monobutyl phthalate (MBP), monoethyl phthalate (MEP), and MBzP levels were measured in patients with each disease as well as patients that reported both [69]. Comparing the highest versus lowest three quartiles of urinary phthalate levels, MBP had an OR of 1.36 (95% CI, 0.77–2.41), MEHP was 0.44 (95% CI, 0.19–1.02), with no association for MEP and MBzP in endometriosis patients. Significantly higher plasma concentration of DBP which is broken down into MBP was also seen [69]. However, the use of self-reported cases may be unreliable. Contrary to the NHANES study, an increased endometriosis risk with an increase in urinary MBzP and MEP was described although the results were not significant [71]. Moreover, an inverse relationship between endometriosis risk and urinary MEHP was found (OR = 0.3; 95% CI = 0.1–0.7) and an inverse relationship was also suggested for DEHP, MEHHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and ΣDEHP. Therefore, a compelling link between phthalate exposure and endometriosis has not been established.
\nResults of several biomonitoring studies have documented higher concentrations of phthalate metabolites in the urine of women with endometriosis compared to a reference population. Plasma concentrations of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were recently quantified by gas chromatography–mass spectrometry in infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) and 34 fertile women without evidence of gynecological disorders [59]. Overall, the mean (± SD) concentrations (ng/ml) of MBzP (19.9 ± 27.3 95% CI;11.69–28.12) and MEHHP (6.76 ± 5.54, 95% CI; 5.10–8.43) were significantly higher in infertile women compared to fertile women (5.72 ± 6.82, 95% CI; 3.34–8.10 and 1.71 ± 3.24, 0.58–2.85; respectively), whereas no differences were detected between groups for MMP and MEHP. The mean concentrations of MBzP and MEHHP in women with endometriosis were 40.9 ± 51.4 (range < LOQ – 116.5) and 5.43 ± 5.53 ng/ml (range < LOQ – 14.76), respectively. However, only 4–5% of women with endometriosis had concentrations of MBzP and MEHHP above the LOQ . Study participants were assigned to groups based upon self-reports of gynecological diagnoses which is open to misclassification error. In addition, the small sample size overall together with the limited number of study participants with quantifiable concentrations of phthalates are important limitations of this study.
\nRecently, differences in serum DEHP concentrations were found between women with endometriosis and control patients using high-performance liquid chromatography [66]. The mean ± SD concentration of DEHP in cases (n = 50) was 65.3 ± 21.7 ng/ml, whereas it was undetectable in the controls. Among the four stages of the disease, women with endometriosis showed a linear increase in DEHP concentration with more advanced stages, although the sample size for stage I was n = 1. Age groups did not impact DEHP serum levels. Controversy remains, as DEHP is broken down by glutathione S-transferase and P450 enzyme, which has been reported to be compromised in endometriosis patients [72]. This may explain the difference in serum concentration, as the control patients are able to metabolize DEHP into metabolites which were not recorded. A further weakness of this study is the measurement of DEHP in the serum rather than metabolites in either the serum or urine and thus the potential for sample contamination cannot be discounted.
\nA group from Taiwan investigated the association between GSTM1 polymorphisms and phthalates in adenomyosis, leiomyoma and endometriosis [68]. Although no relationship between the gene and the disease was found, there was an increase in urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine,
Our search failed to identify any experimental animal studies and only two mechanistic studies were located. MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression (PAK4) were increased in endometrial stromal cell cultures exposed to DEHP [73]. All five significantly elevated markers play a role in cellular division, actin cytoskeletal dynamics, motility, cell survival, and immune defense [73, 74]. Another study found that DEHP treatment increased ESC reactive oxygen species (ROS) generation and decreased expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme oxygenase (HO), and catalase (CAT). p-ERK/p-p38 and NF-κB were also increased [75]. This provides a potential explanation for the decreased expression of antioxidant enzymes and increased ROS. Lastly, Esr1 expression was also increase proportional to dose [75].
\nIn summary, while several studies revealed higher phthalate esters concentrations in women with endometriosis compared to controls the results of epidemiological studies remain equivocal. Moreover, the short half-life of 5–6 h for these chemicals suggests that higher concentrations detected in women with endometriosis compared to controls may be a consequence of the disease rather than a causal factor and thus reverse causation cannot be excluded. While
Trace metals are nearly impossible to avoid in one’s lifetime, as they are found both naturally in our bodies and are produced during industrial processes. Exposure to metals has been reported to interfere with cell proliferation, migration, cell degeneration, oxidative stress, and apoptosis, nearly all of which are properties of endometriosis [76]. Therefore, a link between circulating concentrations of metals and endometriosis has been explored by several groups.
\nA positive relationship between lead and endometriosis (adjusted OR = 2.59, 95% CI = 1.11–6.06) was found in Asian women whereas zinc levels were inversely associated with the disease (adjusted OR = 0.39, 95% CI = 0.18–0.88) [77]. While cadmium (Cd) levels were greater in women with endometriosis, the adjusted odds ratio was not significant [77]. Furthermore, no significant relationship was found between 20 trace elements quantified in the urine and three in blood [76]. Cases were surgically confirmed, whereas the controls were confirmed for the absence of endometriosis through MRI. Contrary to the findings by [24], Cd was inversely related to endometriosis risk, while urinary chromium and copper were marginally associated with endometriosis (aOR = 1.97; 95% CI: 1.21–3.19; aOR = 2.66; 95% CI: 1.26–5.64) [76]. Comparisons for each of the metals increase the probability of chance discovery and thus any association is considered suspect.
\nOur search of the literature failed to reveal any recent animal studies; however, a tissue culture study revealed that Cd treatment-induced higher ESC proliferation (
In summary, biomonitoring studies offer weak support for a potential link between metals exposure and endometriosis. Moreover, results from a tissue culture experiment suggest that Cd can adversely affect ESC proliferation but only at concentrations far in excess of human exposure. Consequently, we consider the evidence of a link between exposure to metals and risk of endometriosis to be speculative at best.
\nThe current literature fails to provide compelling evidence for an association between exposure to environmental toxicants and endometriosis risk. Although current evidence is weak, involvement of environmental toxicants in the pathophysiology of endometriosis cannot be excluded. However, we propose that establishing a link between exposure to environmental toxicants and endometriosis is particularly challenging. Endometriosis is a heterogeneous disease in which peritoneal and ovarian endometriomas may arise by mechanisms that differ from DIE [79] and thus environmental interactions may be different from other forms of the disease.
\nAbsence of diagnostic tools such as a blood test for endometriosis together with normalization of pelvic pain and use of oral contraceptives among other factors leads to lengthy delays in diagnosis. Importantly, the interval between the onset and symptoms and definitive diagnosis of disease can be lengthy varying between 6 and 12 years [34]. Thus, there is a temporal disconnection between collection of biological samples for analysis and the onset of disease. Hence, the use of case–control studies may not permit convincing evidence of an association and the potential for reverse causation cannot be excluded.
\nIdentification of appropriate control groups poses an additional challenge since the prevalence of endometriosis in asymptomatic women can be high [1]. Furthermore, the hallmarks of endometriosis include chronic pelvic pain and infertility. Women dealing with chronic pain and or infertility may adopt activities or behaviors to reduce their pain or improve their chances of conceiving that diverge from the healthy fertile population and thus their exposures may be a function of disease status rather than factors contributing to the pathophysiology of endometriosis. Consequently, in the absence of clinical tools to diagnosis endometriosis, the most appropriate control group in the future may be symptomatic women undergoing laparoscopy with careful inspection of the pelvic cavity to exclude the presence of endometriosis, even though this step is admittedly imperfect [80].
\nEpidemiological studies that adjust for potential confounders (e.g. age, BMI, parity, breast feeding, cigarette smoking, and alcohol consumption) and account for multiple comparisons could prove valuable in elucidating the role of exposure to environmental toxicants in the pathophysiology of endometriosis. Finally, it is unlikely that any group of women are exposed to a singly chemical or group of chemicals and thus quantification of chemicals from different chemical groups in a single study with an appropriate control, control for confounds and correction for multiple comparisons could prove informative.
\nIn the absences of robust epidemiological data experimental animal studies take on greater importance for establishing biological plausibility of a potential association. In general, there is a paucity of literature addressing the potential hazards of environmental toxicants in the survival and growth of endometriotic implants in animal models of endometriosis. While spontaneous endometriosis is predominately limited to humans and some non-human primates, animal xenotransplant models using dispersed cells from ectopic implants in women with endometriosis can provide valuable insight into potential chemical hazards relevant to endometriosis and mechanisms. However, dose levels used should include a concentration representative of human exposure. Similarly, tissue culture studies are essential for mechanistic insight; however, we propose that test concentrations should cover a range of doses that include concentrations below and representative of human exposure as well as high doses through to toxic levels.
\nWhile in general, the epidemiological studies are judged to provide weak evidence of an association between exposure to environmental toxicants and endometriosis, a potential link cannot be excluded. Animal and cell culture models suggest biologically plausible mechanisms between the environmental toxicant exposures and endometriosis risk; however, the effective concentrations exceed human exposure levels. Consequently, we conclude that a causal relationship between exposure to any environmental toxicant and endometriosis does not currently exist, but the evidence does not allow us to exclude a potential link.
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\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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Racism",subtitle:null,isOpenForSubmission:!1,hash:"f6a2562646c0fd664aca8335bc3b3e69",slug:"effective-elimination-of-structural-racism",bookSignature:"Erick Guerrero",coverURL:"https://cdn.intechopen.com/books/images_new/10914.jpg",editedByType:"Edited by",publishedDate:"May 25th 2022",editors:[{id:"294761",title:"Dr.",name:"Erick",middleName:null,surname:"Guerrero",slug:"erick-guerrero",fullName:"Erick Guerrero"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10664",title:"Animal Reproduction",subtitle:null,isOpenForSubmission:!1,hash:"2d66af42fb17d0a6556bb9ef28e273c7",slug:"animal-reproduction",bookSignature:"Yusuf Bozkurt and Mustafa Numan Bucak",coverURL:"https://cdn.intechopen.com/books/images_new/10664.jpg",editedByType:"Edited by",publishedDate:"May 25th 2022",editors:[{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10940",title:"Plant Hormones",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"5aae8a345f8047ed528914ff3491f643",slug:"plant-hormones-recent-advances-new-perspectives-and-applications",bookSignature:"Christophe Hano",coverURL:"https://cdn.intechopen.com/books/images_new/10940.jpg",editedByType:"Edited by",publishedDate:"May 25th 2022",editors:[{id:"313856",title:"Dr.",name:"Christophe",middleName:"F.E.",surname:"Hano",slug:"christophe-hano",fullName:"Christophe Hano"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10207",title:"Sexual Abuse",subtitle:"An Interdisciplinary Approach",isOpenForSubmission:!1,hash:"e1ec1d5a7093490df314d7887e0b3809",slug:"sexual-abuse-an-interdisciplinary-approach",bookSignature:"Ersi Kalfoğlu and Sotirios Kalfoglou",coverURL:"https://cdn.intechopen.com/books/images_new/10207.jpg",editedByType:"Edited by",publishedDate:"May 25th 2022",editors:[{id:"68678",title:"Dr.",name:"Ersi",middleName:null,surname:"Kalfoglou",slug:"ersi-kalfoglou",fullName:"Ersi Kalfoglou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"839",title:"Oceanography",slug:"oceanography",parent:{id:"125",title:"Earth Science",slug:"earth-science"},numberOfBooks:7,numberOfSeries:0,numberOfAuthorsAndEditors:111,numberOfWosCitations:52,numberOfCrossrefCitations:64,numberOfDimensionsCitations:107,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"839",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9280",title:"Underwater Work",subtitle:null,isOpenForSubmission:!1,hash:"647b4270d937deae4a82f5702d1959ec",slug:"underwater-work",bookSignature:"Sérgio António Neves Lousada",coverURL:"https://cdn.intechopen.com/books/images_new/9280.jpg",editedByType:"Edited by",editors:[{id:"248645",title:"Dr.",name:"Sérgio",middleName:null,surname:"Lousada",slug:"sergio-lousada",fullName:"Sérgio Lousada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8007",title:"Estuaries and Coastal Zones",subtitle:"Dynamics and Response to Environmental Changes",isOpenForSubmission:!1,hash:"ec140486c42d62e69ef428e6cf71b6d7",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",bookSignature:"Jiayi Pan and Adam Devlin",coverURL:"https://cdn.intechopen.com/books/images_new/8007.jpg",editedByType:"Edited by",editors:[{id:"179303",title:"Prof.",name:"Jiayi",middleName:null,surname:"Pan",slug:"jiayi-pan",fullName:"Jiayi Pan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7606",title:"Coastal and Marine Environments",subtitle:"Physical Processes and Numerical Modelling",isOpenForSubmission:!1,hash:"dd1227726856d58b88116129b0de8384",slug:"coastal-and-marine-environments-physical-processes-and-numerical-modelling",bookSignature:"José Simão Antunes Do Carmo",coverURL:"https://cdn.intechopen.com/books/images_new/7606.jpg",editedByType:"Edited by",editors:[{id:"67904",title:"Prof.",name:"José Simão",middleName:null,surname:"Antunes Do Carmo",slug:"jose-simao-antunes-do-carmo",fullName:"José Simão Antunes Do Carmo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6012",title:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"79ce8dc1cde58947a61fe4aea725d437",slug:"morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and-its-applications",bookSignature:"Takaaki Uda, Masumi Serizawa and Shiho Miyahara",coverURL:"https://cdn.intechopen.com/books/images_new/6012.jpg",editedByType:"Authored by",editors:[{id:"13491",title:"Dr.",name:"Takaaki",middleName:null,surname:"Uda",slug:"takaaki-uda",fullName:"Takaaki Uda"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored 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San Liang and Yuanzhi Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/8669.jpg",editedByType:"Edited by",editors:[{id:"210315",title:"Prof.",name:"X. San",middleName:null,surname:"Liang",slug:"x.-san-liang",fullName:"X. San Liang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored by"}},{type:"book",id:"6195",title:"Sea Level Rise and Coastal Infrastructure",subtitle:null,isOpenForSubmission:!1,hash:"4eb2fa7c0bf9d4a493375ee47276aa38",slug:"sea-level-rise-and-coastal-infrastructure",bookSignature:"Yuanzhi Zhang, Yijun Hou and Xiaomei Yang",coverURL:"https://cdn.intechopen.com/books/images_new/6195.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2221",title:"Tsunami - Analysis of a Hazard",subtitle:"From Physical Interpretation to Human Impact",isOpenForSubmission:!1,hash:"a7ce45cda9743300d394136417028a84",slug:"tsunami-analysis-of-a-hazard-from-physical-interpretation-to-human-impact",bookSignature:"Gloria I. Lopez",coverURL:"https://cdn.intechopen.com/books/images_new/2221.jpg",editedByType:"Edited by",editors:[{id:"146976",title:"Dr.",name:"Gloria",middleName:"I.",surname:"López",slug:"gloria-lopez",fullName:"Gloria López"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:7,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"64510",doi:"10.5772/intechopen.82320",title:"Introductory Chapter: Morphodynamic Model for Predicting Beach Changes Based on Bagnold’s Concept and Its Applications",slug:"introductory-chapter-morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and",totalDownloads:885,totalCrossrefCites:13,totalDimensionsCites:15,abstract:null,book:{id:"6012",slug:"morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and-its-applications",title:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications",fullTitle:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications"},signatures:"Takaaki Uda, Masumi Serizawa and Shiho Miyahara",authors:[{id:"13491",title:"Dr.",name:"Takaaki",middleName:null,surname:"Uda",slug:"takaaki-uda",fullName:"Takaaki Uda"}]},{id:"67923",doi:"10.5772/intechopen.87843",title:"Structure and Dynamics of Plumes Generated by Small Rivers",slug:"structure-and-dynamics-of-plumes-generated-by-small-rivers",totalDownloads:838,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"The total share of small rivers in the influxes of fluvial water and suspended matter to the world ocean is estimated at between 25 and 40%. On a regional scale, this contribution can be even more significant for many coastal regions. In this chapter, we show that dynamics of small river plumes is significantly different from that of plumes generated by large rivers. Spatial structure of small plumes is generally characterized by sharper horizontal and vertical gradients. As a result, small plumes exhibit more energetic temporal variability in response to external forcing. In this chapter, we address several dynamical features typical for small plumes. We describe and discuss the response of small plumes to wind forcing and river discharge variability, the interaction between neighboring small plumes, and the generation of high-frequency internal waves in coastal ocean by small rivers. We also substantiate the Lagrangian approach to numerical modeling of small river plumes.",book:{id:"8007",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",title:"Estuaries and Coastal Zones",fullTitle:"Estuaries and Coastal Zones - Dynamics and Response to Environmental Changes"},signatures:"Alexander Osadchiev and Peter Zavialov",authors:[{id:"296909",title:"Prof.",name:"Peter",middleName:null,surname:"Zavialov",slug:"peter-zavialov",fullName:"Peter Zavialov"},{id:"296910",title:"Dr.",name:"Alexander",middleName:null,surname:"Osadchiev",slug:"alexander-osadchiev",fullName:"Alexander Osadchiev"}]},{id:"41072",doi:"10.5772/51864",title:"The November, 1st, 1755 Tsunami in Morocco: Can Numerical Modeling Clarify the Uncertainties of Historical Reports?",slug:"the-november-1st-1755-tsunami-in-morocco-can-numerical-modeling-clarify-the-uncertainties-of-histori",totalDownloads:2398,totalCrossrefCites:4,totalDimensionsCites:10,abstract:null,book:{id:"2221",slug:"tsunami-analysis-of-a-hazard-from-physical-interpretation-to-human-impact",title:"Tsunami - Analysis of a Hazard",fullTitle:"Tsunami - Analysis of a Hazard - From Physical Interpretation to Human Impact"},signatures:"R. Omira, M.A. Baptista, S. Mellas, F. Leone, N. Meschinet de Richemond, B. Zourarah and J-P. Cherel",authors:[{id:"16693",title:"Prof.",name:"Maria Ana",middleName:null,surname:"Baptista",slug:"maria-ana-baptista",fullName:"Maria Ana Baptista"},{id:"16695",title:"Dr.",name:"Rachid",middleName:null,surname:"Omira",slug:"rachid-omira",fullName:"Rachid Omira"},{id:"92702",title:"Prof.",name:"Frederic",middleName:null,surname:"Leone",slug:"frederic-leone",fullName:"Frederic Leone"},{id:"148352",title:"MSc.",name:"Samira",middleName:null,surname:"Mellas",slug:"samira-mellas",fullName:"Samira Mellas"},{id:"148353",title:"Prof.",name:"Bendahou",middleName:null,surname:"Zourarah",slug:"bendahou-zourarah",fullName:"Bendahou Zourarah"},{id:"148356",title:"Prof.",name:"Jean-Philippe",middleName:null,surname:"Cherel",slug:"jean-philippe-cherel",fullName:"Jean-Philippe Cherel"},{id:"157593",title:"Prof.",name:"Nancy",middleName:null,surname:"Meschinet De Richemond",slug:"nancy-meschinet-de-richemond",fullName:"Nancy Meschinet De Richemond"}]},{id:"58729",doi:"10.5772/intechopen.73217",title:"Spatio-Temporal Analysis of Sea Surface Temperature in the East China Sea Using TERRA/MODIS Products Data",slug:"spatio-temporal-analysis-of-sea-surface-temperature-in-the-east-china-sea-using-terra-modis-products",totalDownloads:1044,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Sea surface temperature (SST) is an important parameter in determining the atmospheric and oceanic circulations, and satellite thermal infrared remote sensing can obtain the SST with very high spatio-temporal resolutions. The study first validated the accuracy of TERRA MODIS SST daytime and nighttime products with the timing SST measurements from the ships in the East China Sea (ECS) in February, May, August and November, 2001, and then the daily variation of daytime and nighttime SST difference was analyzed. Using 16-year MODIS SST monthly products data from February 2000 to January 2016, when all SST monthly products in February, May, August and November were averaged respectively, the seasonal spatial distribution pattern of SST in the ECS was discovered. After monthly sea surface temperature anomaly was finally processed by the empirical orthogonal function (EOF), the interannual variability of SST in the ECS was discussed. The results show that the MODIS SST daily products have a good accuracy with a mean absolute percentage error (MAPE) below 5%. The SST difference between day and night is the largest in winter, followed by spring, then for autumn and the smallest in summer, while the diurnal SST difference is very low for the same season in the different seas. The SST in the ECS displays the obvious seasonal spatial distribution pattern, in which the SST of winter is gradually increasing from north to south, while local temperature difference is the largest for 26.5°C in a year. In comparison, the SST in summer tends uniform and the difference is not more than 5°C in the whole sea. From the EOF analysis of SST anomaly, the interannual variability of SST in the ECS is affected by the East Asian monsoon, the latitudinal difference of solar radiation, the offshore circulation and the submarine terrain.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Shaoqi Gong and Kapo Wong",authors:[{id:"219135",title:"Dr.",name:"Shaoqi",middleName:null,surname:"Gong",slug:"shaoqi-gong",fullName:"Shaoqi Gong"},{id:"219138",title:"Mr.",name:"Wong",middleName:null,surname:"Kapo",slug:"wong-kapo",fullName:"Wong Kapo"}]},{id:"63609",doi:"10.5772/intechopen.80903",title:"Saltwater Intrusion in the Changjiang Estuary",slug:"saltwater-intrusion-in-the-changjiang-estuary",totalDownloads:1440,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Saltwater intrusion in the Changjiang Estuary and the impacts of river discharge, tide, wind, sea level rise, river basin, and major estuary projects on saltwater intrusion are studied in this chapter. There is a net landward flow in the NB (North Branch) when river discharge is low during spring tide, resulting in a type of saltwater intrusion known as the SSO (saltwater-spilling-over from the NB into the SB (South Branch)), which is the most striking characteristic of saltwater intrusion in the estuary. A three-dimension numerical model with HSIMT-TVD advection scheme was developed to study the hydrodynamic processes and saltwater intrusion in the Changjiang Estuary. Saltwater intrusion in the estuary is controlled mainly by river discharge and tide, but is also influenced by wind, sea level rise, river basin, and estuary projects. Saltwater intrusion is enhanced when river discharge decreases. There is more time for the reservoir to take freshwater from the river when river discharge is larger. The fortnightly spring tide generates greater saltwater intrusion than the neap tide. The saltwater intrusion in the SP (South Passage) is stronger than that in the NP (North Passage), and the intrusion in the NP is stronger than that in the NC (North Channel). The northerly wind produces southward currents along the Subei coast as well as the landward Ekman transport, which enhances the saltwater intrusion in the NC and NB and weakens the saltwater intrusion in the NP and SP. Saltwater intrusion becomes stronger as the sea level rises and is much stronger when river discharge is much small. The DWP (Deep Waterway Project) alleviates the saltwater intrusion in the NC and the lower reaches of the NP and enhances the saltwater intrusion in the SP and in the upper reaches of the NP. The Three Gorges Dam (TGD) increases river discharge in winter, which weakens saltwater intrusion, and is favorable for reducing the burden of freshwater supplement in the highly populated estuarine region. The Water Diversion South to the North Project (WDP) decreases river discharge, enhances saltwater intrusion, and is unfavorable for freshwater supply in the estuary.",book:{id:"8669",slug:"coastal-environment-disaster-and-infrastructure-a-case-study-of-china-s-coastline",title:"Coastal Environment, Disaster, and Infrastructure",fullTitle:"Coastal Environment, Disaster, and Infrastructure - A Case Study of China's Coastline"},signatures:"Jianrong Zhu, Hui Wu, Lu Li and Cheng Qiu",authors:[{id:"266207",title:"Dr.",name:"Jianrong",middleName:null,surname:"Zhu",slug:"jianrong-zhu",fullName:"Jianrong Zhu"}]}],mostDownloadedChaptersLast30Days:[{id:"70994",title:"Circulations in the Pearl River Estuary: Observation and Modeling",slug:"circulations-in-the-pearl-river-estuary-observation-and-modeling",totalDownloads:779,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter reports a cruise survey on the Pearl River Estuary (PRE) and adjacent costal water in the period between May 3, 2014 and May 11, 2014. The circulation and salinity structure were sampled for different tidal phases. With the cruise data, a “sandwich” structure of the lateral salinity distribution and a two-layer structure of longitudinal circulation were identified, together with high variations influenced by wind and tide. Furthermore, longitudinally orientated convergence or divergence of the lateral velocity close to the channel location for certain tidal conditions was observed. The finite volume community ocean model (FVCOM) is configured and run with high spatial resolution of 100 m in the PRE. An atmospheric model, the Weather Research and Forecasting (WRF) Model, is also run to provide high spatial and temporal resolution of atmospheric forcing for the FVCOM. The FVCOM modeling skill assessment is conducted using the cruise salinity and velocity data, as well as water levels, showing that the model can well simulate the velocity and salinity structures. The numerical model reveals that there is a strong neap-spring cycle for the PRE de-tided circulation with 0.37 m s−1 during the neap tide about 42% stronger than that (0.26 m s−1) during the spring tide in the surface layer.",book:{id:"8007",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",title:"Estuaries and Coastal Zones",fullTitle:"Estuaries and Coastal Zones - Dynamics and Response to Environmental Changes"},signatures:"Jiayi Pan, Wenfeng Lai and Adam Thomas Devlin",authors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"},{id:"302219",title:"Associate Prof.",name:"Jiayi",middleName:null,surname:"Pan",slug:"jiayi-pan",fullName:"Jiayi Pan"},{id:"309888",title:"Dr.",name:"Wenfeng",middleName:null,surname:"Lai",slug:"wenfeng-lai",fullName:"Wenfeng Lai"}]},{id:"41072",title:"The November, 1st, 1755 Tsunami in Morocco: Can Numerical Modeling Clarify the Uncertainties of Historical Reports?",slug:"the-november-1st-1755-tsunami-in-morocco-can-numerical-modeling-clarify-the-uncertainties-of-histori",totalDownloads:2398,totalCrossrefCites:4,totalDimensionsCites:10,abstract:null,book:{id:"2221",slug:"tsunami-analysis-of-a-hazard-from-physical-interpretation-to-human-impact",title:"Tsunami - Analysis of a Hazard",fullTitle:"Tsunami - Analysis of a Hazard - From Physical Interpretation to Human Impact"},signatures:"R. Omira, M.A. Baptista, S. Mellas, F. Leone, N. Meschinet de Richemond, B. Zourarah and J-P. Cherel",authors:[{id:"16693",title:"Prof.",name:"Maria Ana",middleName:null,surname:"Baptista",slug:"maria-ana-baptista",fullName:"Maria Ana Baptista"},{id:"16695",title:"Dr.",name:"Rachid",middleName:null,surname:"Omira",slug:"rachid-omira",fullName:"Rachid Omira"},{id:"92702",title:"Prof.",name:"Frederic",middleName:null,surname:"Leone",slug:"frederic-leone",fullName:"Frederic Leone"},{id:"148352",title:"MSc.",name:"Samira",middleName:null,surname:"Mellas",slug:"samira-mellas",fullName:"Samira Mellas"},{id:"148353",title:"Prof.",name:"Bendahou",middleName:null,surname:"Zourarah",slug:"bendahou-zourarah",fullName:"Bendahou Zourarah"},{id:"148356",title:"Prof.",name:"Jean-Philippe",middleName:null,surname:"Cherel",slug:"jean-philippe-cherel",fullName:"Jean-Philippe Cherel"},{id:"157593",title:"Prof.",name:"Nancy",middleName:null,surname:"Meschinet De Richemond",slug:"nancy-meschinet-de-richemond",fullName:"Nancy Meschinet De Richemond"}]},{id:"63921",title:"Eight Types of BG Models and Discretization",slug:"eight-types-of-bg-models-and-discretization",totalDownloads:933,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Eight types of the BG models are introduced in this chapter. The Type 1 is a model using wave parameters at the breaking point. In the Type 2, the effect of longshore sand transport due to the effect of the longshore gradient of breaker height is included with an additional term given by Ozasa and Brampton. In the Type 3, the intensity of sand transport P is assumed to be proportional to the third power of the amplitude of the bottom oscillatory velocity um due to waves, and in the Type 4, P is given by the wave energy dissipation rate due to wave breaking at a local point. In the Type 5, wave power is calculated using the coordinate system different from that for the calculation of beach changes to predict the topographic changes of an island or a cuspate foreland in a shallow water body under the action of waves randomly incident from every direction. In the Type 6, the height of wind waves is predicted using Wilson’s formula using the wind fetch distance and wind velocity, and then sand transport fluxes are calculated. The Type 7 is a model for predicting the formation of the ebb-tidal delta under the combined effect of waves and ebb-tidal currents with an analogy of the velocity distribution of ebb-tidal currents to the wave diffraction coefficient, which can be calculated by the angular spreading method for irregular waves. In the Type 8, the effect of the nearshore currents induced by forced wave breaking is incorporated into the model by calculating the nearshore currents, taking both the wave field and the current velocity at a local point into account.",book:{id:"6012",slug:"morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and-its-applications",title:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications",fullTitle:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications"},signatures:"Takaaki Uda, Masumi Serizawa and Shiho Miyahara",authors:[{id:"13491",title:"Dr.",name:"Takaaki",middleName:null,surname:"Uda",slug:"takaaki-uda",fullName:"Takaaki Uda"}]},{id:"57606",title:"Analysis of Dynamic Effects on the Brazilian Vertical Datum",slug:"analysis-of-dynamic-effects-on-the-brazilian-vertical-datum",totalDownloads:952,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This chapter presents a methodology of analyzing the dynamic effect from mean sea level variations, based on Global Navigation Satellite System (GNSS) data, velocity models, tide gauge observations, and satellite altimetry data. GNSS observations were processed in order to obtain the variation of up coordinate required to identify the possible crust movements. Velocity model served as a comparative basis to verify the obtained results from the GNSS data processing and served as a basis for analyzing the time periods without GNSS information. Tide gauge data were used to evaluate the sea level temporal evolution in the Imbituba Brazilian Vertical Datum (I-BVD). Satellite altimetry data were used for checking the results from the GNSS and the tide gauge time series. The analyses were based on time series of observations by GNSS from 2007 until 2016, tide gauge from 1948 until 1968 and 2001 until 2016, and satellite altimetry data from 1991 until 2015 from different missions. As basis for the analysis, it used GNSS SIRGAS-CON stations, the SIRGAS velocity model (VEMOS), and NUVEL velocity model. Considering the discrimination of the crust vertical movement (GNSS processing) from the results obtained with the tide gauge observations, it was observed that there is an evidence of mean sea level (MSL) rising approximately +2.24 ± 0.4 mm/year.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Luciana M. Da Silva, Sílvio R.C. De Freitas and Regiane Dalazoana",authors:[{id:"208387",title:"Dr.",name:"Luciana",middleName:"Maria",surname:"Da Silva",slug:"luciana-da-silva",fullName:"Luciana Da Silva"},{id:"209224",title:"Dr.",name:"Sílvio",middleName:null,surname:"De Freitas",slug:"silvio-de-freitas",fullName:"Sílvio De Freitas"},{id:"209225",title:"Dr.",name:"Regiane",middleName:null,surname:"Dalazoana",slug:"regiane-dalazoana",fullName:"Regiane Dalazoana"}]},{id:"58909",title:"Coastal Disasters and Remote Sensing Monitoring Methods",slug:"coastal-disasters-and-remote-sensing-monitoring-methods",totalDownloads:1113,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Coastal disaster is abnormal changes caused by climate change, human activities, geological movement or natural environment changes. According to formation cause, marine disasters as storm surges, waves, Tsunami coastal erosion, sea-level rise, red tide, seawater intrusion, marine oil spill and soil salinization. Remote sensing technology has real-time and large-area advantages in promoting the monitoring and forecast ability of coastal disaster. Relative to natural disasters, ones caused by human factors are more likely to be monitored and prevented. In this paper, we use several remote sensing methods to monitor or forecast three kinds of coastal disaster cause by human factors including red tide, sea-level rise and oil spilling, and make proposals for infrastructure based on the research results. The chosen method of monitoring red tide by inversing chlorophyll-a concentration is improved OC3M Model, which is more suitable for the coastal zone and higher spatial resolution than the MODIS chlorophyll-a production. We monitor the sea-level rise in coastal zone through coastline changes without artificial modifications. The improved Lagrangian model can simulate the trajectory of oil slick efficiently. Making the infrastructure planning according the coastal disasters and features of coastline contributes to prevent coastal disaster and coastal ecosystem protection. Multi-source remote sensing data can effectively monitor and prevent coastal disaster, and provide planning advices for coastal infrastructure construction.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Yan Yu, Shengbo Chen, Tianqi Lu and Siyu Tian",authors:[{id:"162887",title:"Prof.",name:"Shengbo",middleName:null,surname:"Chen",slug:"shengbo-chen",fullName:"Shengbo Chen"},{id:"220026",title:"Dr.",name:"Yan",middleName:null,surname:"Yu",slug:"yan-yu",fullName:"Yan Yu"}]}],onlineFirstChaptersFilter:{topicId:"839",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:289,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. Carvajal-Gámez, Guillermo Urriolagoitia-Sosa and Alberto J. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",institutionURL:null,country:{name:"Romania"}}}]},{type:"book",id:"9963",title:"Advances and Applications in Deep Learning",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9963.jpg",slug:"advances-and-applications-in-deep-learning",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"0d51ba46f22e55cb89140f60d86a071e",volumeInSeries:4,fullTitle:"Advances and Applications in Deep Learning",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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