\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Those are some of the topics that will be covered in this new book, with the objective to provide the interested reader, whether a student or an expert, with a practical reference approaching biomimetics from a realistic and translational perspective, discussing problems and offering solutions, via including studies from basics to the clinic to scale-up and industrial or go-to-market obstacles.
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Haidar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11453.jpg",keywords:"BioMechanics, 3D Printing, BioInspired Chemistry, Adaptive Structure, Self-Healing, Bioinspired Thermal Control, Self-Organization, Visco-Elastic Materials, Artificial Intelligence, Implantable Devices, Molecule Recognition, In Vitro",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 5th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"DDS, Cert Implantol, MSc OMFS, FRCS(C), with an MBA in HealthCare Organizations Management and Ph.D. in BioEngineering and nanoPharmaceuticals (McGill University, Montréal, Canada). Presently, a Full Professor, leading the BioMAT’X R&D&I HAIDAR LAB at the CiiB, UAndes, Santiago de Chile.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"222709",title:"Prof.",name:"Ziyad S.",middleName:null,surname:"Haidar",slug:"ziyad-s.-haidar",fullName:"Ziyad S. Haidar",profilePictureURL:"https://mts.intechopen.com/storage/users/222709/images/system/222709.jpg",biography:"Ziyad S. Haidar, DDS, Cert Implantol, MSC, FRCSc, MBA, Ph.D., is a Full Professor of Biomaterials and Tissue Engineering and the scientific director of the Facultad de Odontología (Faculty of Dentistry), Universidad de los Andes (UAndes), Santiago, Chile. He is also the founder and head of the Biomaterials, Pharmaceutical Delivery, and Cranio-Maxillo-Facial Tissue Engineering Laboratory (BioMAT\\'X R&D&I Chile – HAIDAR Lab). In addition, he serves as the head of innovation at the Centro de Investigación e Innovación Biomédica (CiiB), a faculty/theses member in the bioMedicine Doctoral (Ph.D. bioMedicina) Program at UAndes, and a visiting clinical and surgical professor at the MaxilloFacial Division of the Universidad de la Frontera and the Department of Head and Neck Surgery, Lautaru Hospital, both in Temuco, Chile.\n\nDr. Haidar is a trained dentist, implantologist, and an oral and maxillofacial surgeon with a Ph.D. in Nanobiomaterials, Pharmaceuticals, and Tissue Engineering from McGill University, Montréal, Canada. He completed a post-doctoral training residency in orthopedics at the Montréal Shriners Hospital, McGill University Health Center, Montréal, Canada. Before moving to Chile, he served as Associate Professor of Bioceramics and the Chair of Excellence in BioEngineering at the Université de Limoges, Limoges, France and was an assistant professor in the Department of Pharmaceutics and Pharmaceutical Chemistry (cross-appointment with the Department of BioEngineering), University of Utah, Salt Lake City, UT, USA. Between 2010 and 2012 Dr. Haidar served as an adjunct professor of Head and Neck Surgery and the scientific director of the joint Utah–Inha R&D Center, Inha University Hospital, Incheon, Seoul, South Korea. \n\nHe has won several prestigious awards from the International Bone and Mineral Society, Society for Biomaterials, Canadian Biomaterial Society, and the Canadian and Lebanese Societies of Plastic Surgeons, to name a few. His R&D&I focus on patient-oriented development and evaluation of bionanotechnology, biopolymers, bioceramics, and drug delivery systems for the repair, restoration, reconstruction, and regeneration of challenging craniofacial and orthopedic defects. Dr. Haidar is an international speaker with more than 125 publications, conference proceedings, textbooks, and patents to his credit. 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From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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It is also extremely important in complex liver operations, althaugh it might not be in cases of simple wedge resection for benign disease. As the presence of HCC is usually in the background of liver cirrhosis, the importance of anatomical resection to be able to clear the tumour and have sufficient amount of liver to avoid post-operative liver failure. In this chapter we will try to illustrate the importance of anatomical liver resection and give an idea of the latest liver anatomy with a demonstration on how to identify and resect each part of the liver.
As many general surgeons might like to do wedge non anatomical liver resections because it is less complicated and gets the tumour out. There are several reasons to perform anatomical resection:
In Hepato-Cellular carcinoma (HCC) which is the most common reason to perform liver resections, were it is the first line of treatment nowadays [1,2]. As the HCC are able to invade the portal veins and disseminate through its inter segmental branches [3] (cough reflux), segmentectomy is preferable. Intrahepatic metastasis [4,5] and invasion to the portal and hepatic venous system will affect the post operative prognosis. To improve the post surgical outcome the segmental liver resection is indicated. It involves the removal of the whole segment containing the tumor with its vasculature which might be affected by the tumor invasion [1,4 - 6]. Satellite micro metastasis will also be removed as their feeding vessel for that segment [3].
Anatomic liver resection is superior to non anatomic from the oncologic and anatomic aspects [7]. Anatomically based hepatectomy is the best means of achieving a negative margin[8].The recurrence rate within 2 years associated with aggressive tumor biology such as high tumor grade, satellite lesions and microvascular invasion [7], is higher in non anatomical resection.
In small HCC <4cm anatomic resection achieves better disease-free survival than limited resection without increasing the postoperative risk [9-10].
The overall survival and the disease-free survival rates were significantly better in the anatomic resection compared to the non anatomic resection group [1,11-12],as well as the recurrence disease free survival [10].
A meta-regression analysis was done and published in June 2012 that was conducted on 9036 patients from 1990-2011 and demonstrated that the 5 years disease free survival and the 5 year survival was significantly better in the anatomic resection group than the non anatomic resection group with no effect on the post operative mortality and morbidity[13].
Less bleeding with almost no need for transfusion in the intra-operative period as there is no transaction of the vessels. Also there is few vessels present in the inter segmental planes. Relatively the inter segmental area is a non-vascular plane, so segmental identification, control of the feeding vessels and the vascular pedicle will decrease the blood loss. This is one of the direct causes of decreased post operative morbidities and mortalities [3,14 - 16].
Segmental resection will preserve as much of the liver parenchyma [3] and will enable sufficient liver volume especially in cirrhotic patients [16] and in patients with multiple liver lesions [17] or in patients who will need another resection in the future. Also it will decrease the post operative liver insufficiency from small liver remnant in cirrhotic patients [3,14,15,16].
In colorectal metastasis segmental resection is superior to non anatomical resection as it results in better tumour clearance and free margins. Multiple studies demonstrated that it did affect the disease free survival, and the control of micro-metastasis through segmental portal branches. Segmentectomy offered disease-free and overall survival rates similar to those after major resection. [3,14]
For metastasis it has been found that with wedge resection the recurrence rate and positive margins were higher compared to the segmental resection. This resulted in inadequate tumour resection especially in deep lesions where the incidence of inadvertently cutting into the tumour is higher. Also the bleeding rate is high due to the difficult control of the venous branches that will obscure the resection plane.
Wedge resections are usually inadequate and potentially dangerous, especially for large tumours, and are often associated with greater blood loss and a greater incidence of positive histological margins.[8,11]. Liver failure due to parynchymal necrosis or small liver remnant are observed in non anatomical (wedge) liver resection. It also results in higher incidence of biliary fistula and infection because of the remnant devitalized liver tissue [18].
Non-anatomical liver resection (Wedge) can be done in certain circumstances; in resections where the tumour is small (<3cm) and located peripherally at the edge of a cirrhotic liver or when the tumour is situated at the border of several segments and its resection requires the removal of large volume which is not possible due to the liver status.
Also, in cases of benign liver resection were no safety margin is required and the surgeon would like to preserve as much liver volume as possible, so the lesion can be enucleated. However, care should be taken not to injure nearby vessels or bile ducts.
The understanding of liver segments was first established in 1953 by Healy [19] and was further reinforced by Couinaud in 1957 [20]. When trying to understand their description it might be somewhat confusing, however we will try to make it as simple as possible.
They both used the new division by Cantlie who disapproved the old terminology of the right and left liver which was divided by the falciform ligament and used his description of the right and left liver divided by the midline which is oblique and extended from the gallbladder bed to the right side of the inferior vena cava. Healy then divided the liver using the arteriobiliary segmentation. This lead to the division of the right liver into the two segments, the right anterior and the right posterior segments (called now sections). The left side was divided by the falciform into the left medial and left lateral segments (called now sections). However, Couinaud used the hepatic veins and divided the right liver into right anterior and right posterior sectors. The left side was divided by the left hepatic vein into the left medial and left lateral sectors, and the middle hepatic vein was running in the midplane of the liver (Cantile line). Then recently the terminology of segments that was described by Healy was changed to sections leading the way to the word section and sector that you see in all papers involving the liver anatomy. They both divided these sectors or sections to segments according to the portal vein anatomy and we reached to our 8 segments that we know today. Figure.1
Liver sections, plane and segments
When looking at these two description you will find that both agreed on the anatomy of the right liver cause there was no difference between the right anterior (segment 5&8) and the right posterior (segments 6&7) section or sector. However, on the left side there was a difference, because of the anatomical variations and we believe this is what led to this misunderstanding. The left medial section (segment 4) is not the same as the left medial sector (segment 3&4), and the left lateral section (segment 2&3) is not the same as the left lateral sector (segment 2). They also both agreed on the separation of segment 1 (caudate Lobe) as it has its own blood supply and drains directly to the inferior vena cava.
Another thing when looking to the terminology is the word “Lobe”. Some authors use the term left lobectomy to describe the resection of segments 2&3, which is the functional left lateral section. Also the right lobe as segments 4 to 8 were it is an extended right trisectionectomy. This description was based on the anatomical land mark of the liver using the falciform ligament and not the functioning liver segments as described above.
The use of many different terminologies and difficulty in understanding the description described above, were the European societies adopted Couinaud’s description and the American societies used the Healy’s description. So the scientific committee of the International Hepato-Pancreato-Biliary Association with experts around the world came up with the Brisbane 2000 Terminoloy of Liver Anatomy and resection which we have been using and will use for our description in this chapter [21].
To understand this terminology, first the liver is divided into two parts, the main liver and the caudate lobe (called the dorsal sector by Cauinaud). Then the main liver is divided into the right and left liver.
This part is called the first order division, where the liver is divided into the right liver or right hemiliver, and the left liver or the left hemiliver. Notice the word lobe has been removed completely for the confusion we mentioned above, so the resection of the right side is called right hepatectomy or right hemihepatectomy (segments 5 to 8). The left side is called; left hepatectomy or left hemihepatectomy (segments 2 to 4). Figure.2
Right (yellow) and left liver (green)
The second order division, where the right liver is divided into two parts. The right anterior section giving the right anterior sectionectomy (segment 5&8), the right posterior section leading to the resection of the right posterior sectionectomy (segments 6&7). On the left side there will be the left medial section giving the left medial sectionectomy (segment 4), and the left lateral section leading to the resection of the left lateral sectionectomy (segment 2&3). Figure.3
Sections Green: right posterior, orange: right anterior Yellow: left medial, red: left lateral
The third order division, is the division of each of these sections into segments as we mentioned above. The resection of any of these segments is called a segmentectomy and if two or more segments were resected that are not related as described in the second order division it is called bisegmentectomy or trisegmentectomy. This should not be coinfused with the trisectionectomy of the right or left side were we resect three sections and not segments. Figure.4
Segments, each with a different color
An addition was added also if the word sector were to be used instead of section. This is the same on the right side and on the left we had a left medial sector with a left medial secterectomy (segment 3&4), and the left lateral sector giving rise to the resection of the left lateral secterectomy (segment 2). So the term section or sector has to be used very cautiously on the left side to describe exactly what you mean.
As each liver segment can be resected separately, liver resection can be segment based
Segement 4, is divided into 4A and 4B. This was made because of multiple indications were segment 4A is rsected without the resection of segment 4B like in cases of gallbladder cancer. Also the resection of segment 4A is counted as the most difficult liver resection as it lies between the middle and the left hepatic vein.
This terminology has gained wide acceptance and has removed most of the confusion that use to exist in the past.
The extra hepatic portal triad is consisted of the portal vein, the hepatic artery and the common hepatic duct. These structures are enclosed in a connective tissue and peritoneum up to the hepatic hilum. The term Glissonian sheath is reserved for the part that extendeds into the intrahepatic portion of the liver beyond the hilum. This sheath surrounds the portal triad structure before they enter into each section, giving rise to the resection of each segment (liver unit) separately without affecting the other segments [22]. This gives rise to the aberrance of the central segments 4, 5 and 8 ramifications like a bush and fan shaped. Consequently, a single segment resection will require several Glissonian sheath at various depth and is much more difficult. Were the priphral segments 6, 7, 2 and 3 have long branches that travels a distance reaching to these segments giving the appearance of tree like making their resection less complicated and usually requiring a single Glissonian sheath ligation [23].
On the right side the portal vein is similar to the arteriobiliary segmentation. On the left side they differ from each other. The left portal vein consists of a transverse and an umbilical portion. The transverse portion only sends small branches to segment 4 and one or two branches to segment 1. All the larger branches arise beyond the attachment of the ligamentum venosum (umbilical portion of the left portal vein). Figure.5. This part of the vein gives right branches to segment 4 and on the left side it gives one branch to segment 2 and more than one to segment 3. The portal vein terminates where it joins the ligamentum teres at the edge of the liver. This unique structure explains the duael function of the left portal vein during in-utero and then in-adult life.
Portal vein with its divisions
On the right side the portal vein is usually very short and gives rise to the right anterior and right posterior branches. Each of these branches gives rise to two main segmental divisions. The right anterior gives both segment 5 and 8, where the right posterior gives segment 6 and 7. Figure.6.
A) right anterior portal branch (RAP) B) right posterior portal branch (RPP)
Usually there are very little variations in the portal vein. The commonest one is where the right anterior branch joins the left portal vein. This is very important to recognise especially when doing a left hepatectomy causes injury could happen to the right anterior section leading to the loss of segments 5 and 8. Another common anomaly is the absence of the main right portal vein giving rise to a trifurcation at the hilum of the portal vein to the left main, right anterior and the right posterior branches. This is important when doing a right hepatectomy to transect each branch separately not to injure the left portal vein [24-25].
For the clinical description of this part we will try to simulate what happens in clinical practice by dividing it to pre-operative radiology and intra-operative by intra-operative ultrasound.
To try and make this part as simple as possible for the reader we will try to identify land marks that you should look for in the ultrasound, CT or MRI. The ultrasound is the usual screening tool used to see the whole liver and identify cystic from solid lesions. Then most centres will request a Triphasic CT scan of the liver in the hope to identify the nature of the lesion and the location. A physician should not comment on any lesion seen until full examination of all three phases (arterial, venous and delayed) are examined and the lesion is seen on all three phases to give the best chance of reaching the right diagnosis.
As we described the anatomy of the liver by the first order division and its landmark the middle hepatic vein, it is the same here. The middle hepatic vein can be seen on any of the above mentioned x-ray investigation. This will lead to the division of the liver to the right and left liver and identifying the lesion in which liver it lies. Figure.7.
Middle hepatic vein (MHV) A) CT B) Ultrasound
The next step is to identify the falciform ligament and the right hepatic vein. This will divide the left liver to the medial and lateral sections and the right liver to the anterior and posterior sections alternatively. By this any lesion will be clearly seen in each section of the hemi-liver. Figure.8.
A) right hepatic vein (RHV) – with a lesion in seg 7 B) falciform (FL)
The last step is to identify the main portal vein and follow it till you reach to the bifurcation of the right and left branches which corresponds to the line that divides the liver into the upper and lower segments. This will give rise to the division of each section to its corresponded segments as described before in the anatomy part
Main portal vein (MPV), with a lesion seen in the right posterior lower segment (segment6)
If this simple technique is adopted a full idea of the lesions identity and location could be achieved with a high degree of certainty making the surgical planning much more feasible. Figure.10.
All segments identified on CT pre-opretive
This is usually carried out by the intra-operative ultrasound [26-30], which we believe no liver resection should be done without mastering its use especially in malignant liver lesions. There are six simple steps that should be followed to get the best results of the ultrasound. 1) General inspection the whole liver as CT is not the ideal tool to identify superficial liver lesions. 2) A systemic recognition of all three hepatic veins and the main portal veins with its branches to identify all the liver segments. 3) Localize the tumour and determine which segments are involved. 4) Determine which segments needs to be resected to achieve good margins and balance it with the state of the liver trying at all times to go thru the anatomical lines to get an anatomical liver resection when possible to achieve the advantages mentioned before. 5) Mark the liver resection line on the liver surface. 6) Redetermine the distance from the tumour and the resection lines to be certain not to be close or even worse go thru the lesion.
To identify the segments the same method that was done pre-operative on CT is adopted by the localisation of the middle hepatic vein and drawing a line on it to get the right and left livers. Figure.11.
Intra operative ultrasound middle hepatic vein. A) longitudinal B) sagetal
The falciform ligament which divides the left liver to the medial and lateral sections can be seen on the surface. The left hepatic vein that divides segment 2 and 3 can be identified. On the right side the right hepatic vein is seen and a line is made to divide the right liver to the anterior and posterior sections. Figure.12.
Intra operative ultrasound right hepatic vein.
The portal vein is then identified and followed to get all its branches and a line is made horizontally to get the upper and lower segments of the liver. Figure.13. After connecting all these lines the liver segments will be seen on the surface with the exception of segment 1 which is separate as we indicated before and can be seen over the IVC as the caudate lobe [31]. Figure.14
A) Right Portal veins (RPV) and its bifurcation to right anterior (RAPV) and right posterior (RPPV). B) Left portal vein (LPV) with its segmental branches
Liver segments on the liver intra operatively Portal vein (PV) in weight, middle hepatic vein (MHV), falciform ligament (FL), right hepatic vein (RHV)
A full pre-operative evaluation is necessary before embarking on a liver resection especially that most of the patients with HCC are also cirrhotic. There are multiple models to evaluate these patients and the most widely used one is the Child-Pugh score. This model stratifies patients into stage A, B, and C. Also the size of the tumour and the patient’s physiological function are very important. Therefor most recent staging systems for HCC has included three important factors to evaluate the patient before any liver resection, the tumour, the liver status and the patient factor. Although chronic liver disease is not an absolute contraindication to liver resection, the morbidity and mortality increases prohibitively with increasing hepatic dysfunction. Childs class C or late B patients are generally excluded from major resections whereas Childs A or early B patients may be candidates [8,31].
As we mentioned above radiological studies are important in determining the presence of portal hypertension, ascitis, tumour localization, feasibility of the resection, tumour extension, distance from the pedicles and segments necessary to be resected as well as extra-hepatic metastasis [8].
The patient is usually in supine position, with the arms extended 90° when possible [8]. To minimize risk of air embolism from disrupted hepatic veins[8] and to minimize blood loss from the resected raw liver surface[3]. The resection is performed with the patient in the Trendelenburg position and as recommended by all liver surgeon with a low central venous pressure of 0-5 mmHg(15°).Figure.15.
Skin incisions for liver surgery
Preparation of the operative field includes the area from the lower abdomen up to and including the chest, extending from axillary line to axillary line [8]. The majority of liver resections are performed with either a right subcostal incision with upper midline extension (inverted hockey stick) or a chevron (Mercedes) incision [8]. Intra-operative ultrasound is done as described above and the necessary ligaments are released according to the segments of the liver that needs to bee resected. Usually the falciform ligament is released to allow free mobilization of the liver and a better access for the ultrasound.
A liver surgeon should be familiar with all the techniques of liver resection because each has advantages and disadvantages making different resections more feasible.
This technique is started by dissection of the portal triad and the hilar plate, where the right and left portal veins are identified.Figure.16. This makes the ligation of each portal branch more feasible. Then the vascular line of demarcation is seen and with the aid of intra-operative ultrasound to identify the rest of the vascular structures and the tumour. The liver is then mobilized according to the part being resected. Parynchymal transaction is then carried out followed by ligation of the hepatic veins. This type is usually applied in patients with less liver fibrosis and a right or left liver resection is needed.
Anterior Approach. A) the tape is around the main and right hepatic artery. B) The yellow tape is around the left portal vein
The liver is mobilized according to the part being resected. This will give access to the right or left hepatic vein which is usually circled and controlled. Then two ways can be done, were some surgeons transect the vein followed by Pringle and transect the liver parenchyma by the fast technique in about 10-15 min. This is usually fast and has less bleeding and can be done in patients with right, left and both left lateral and right posterior (peripheral sections) liver resections specially if the patient has liver fibrosis because of the time and bleeding. However, this technique requires the excellent use of ultrasound to avoid injury to the main vascular structures, and prevent a long Pringle time for the unresected part of the liver.
The other way is to start with the liver transaction. This will not require the routine use of Pringle, however it can be associated with more blood lose, and longer transection time to control the bleeding. This is usually done in non cirrhotic patients specially in living related liver transplant.
By using also the posterior approach the portal pedicle will be transacted at the end in the liver. This will decrease the injury or the narrowing of the unresected pedicle.
This approach was adopted recently and was mainly applied in the right liver donors for living related liver transplant. This technique usually relies on the principle of keeping the liver well vascularised till the last minute to keep the liver viable.
The approach is done by using the avascular plane on the anterior part of the inferior vena cava and the window between the right and middle hepatic vein. This makes the passage of a tape from the inferior part of the liver to the superior part over the inferior vena cava. Figure.17. The live is then transacted over the tape slowly while maintaining good haemostasis. Then the right hepatic vein and the right pedicle are transacted.
Hanging technique
This method is used mainly in right liver resection, and the tape can be moved in any plane wanted with the aid of the ultrasound. It also has a non touch like technique, were the liver is not mobilized till the vascular inflow and outflow are transacted. However, it requires time and very experienced surgeon not to injure the inferior vena cava during insertion of the tape. It’s also time consuming and not applied in cirrhotic liver because bleeding will be more.
This technique is started by hilar plate dissection and reaching to each sectional branch or even to each segmental branch. Control of the inflow is done first followed by mobilization of the part intended to be resected. The liver resection is then carried out and the outflow is then transacted. Figure.18
Hillar dissection. Tapes around the sectional portal branches on the right and the main left portal vein on the left
This method is best for central liver resection, however the hilar dissection requires experience and cannot be carried out in cirrhotic livers as bleeding will be difficult to control. Intra-operative ultrasound is very important to locate the portal branches and the outflow veins to decrease its injury, also the tumor localization is important not to cut through it.
Peripheral and non anatomical liver resections are usually done by this approach. Intra-operative ultrasound is done to see the tumour and its blood supply. Mobilization followed by parenchymal transaction, were the inflow and outflow vessels are transacted in the liver.
The first description of RFA-assisted liver resection was published by Habib’s group [32]. This technique showed a major improvement of liver surgery with low/no morbidity and mortality observed [33]. It also showed decrease in the anesthetic time, operative time, hospital stay, and blood loss. Liver resection became a comparatively safer procedure [34].
Liver resection utilizing radiofrequency-induced resection plane coagulation as a safe alternative to the established resection techniques. The residual zone of coagulation necrosis remains basically unchanged during a follow up of three years, with a safety margins of 0.5-3.5 cm and Histopathological proof [35].
The RadioFrequency Assisted liver resection has 5 steps [32, 36]:
Before each probe removal, the saline infusion is stopped to increase the temperature close to the electrode. This results in coagulation of the needle tract during withdrawal and reduces the possibility of bleeding from the probe tract and the liver capsule.
This method combines total inflow and outflow vascular occlusion of the liver, isolating it completely from the systemic circulation. It is achieved after complete liver mobilization, application of inflow occlusion by Pringle manoeuvre, and then placing a clamp across the infra-hepatic IVC above the renal veins and the right adrenal vein followed by a supra-hepatic IVC clamp above the opening of the major hepatic veins. After the parenchymal transection and hemostasis, the clamps are removed in the reverse order[37]. Figure 19.
Total hepatic vascular occlusion
This results in a significant haemodynamic instability, with a substantial reduction in cardiac output, though blood pressure is usually maintained [38]. Around 10% of patients cannot tolerate it haemodynamically[39].
The ischaemic limit is 60-90 mins for patients with normal liver function [40]. In patients with cirrhosis, the maximal ischaemic time is halved and, in addition, the liver function before surgery must be at the better end of the spectrum[41]
However this technique is not done nowadays with the advanced surgical techniques except in rare conditions like tumour thrombus reaching the IVC or the atrium Figure 20. It also prevents intra-operative thrombus migration, and allows major hepatic veins or IVC reconstruction [37].
A case of HCC with atrial thrombus with total vascular occlusion. The thrombus is being removed from the right atrium.
However, with the development of liver surgery there has been use of some part of vascular occlusion done selectively or in compinations:
In-flow control:
Pringle manoeuvre; This is done by occluding the total inflow to the liver. This is usually in cases of central liver resection or majour resections where a large volume of blood is suspected to be lost. Figure 21
Pringles manoeuvre
Hemi-Hepatic control; This is done as described before in the right or left hemi-hepatectomy by controlling the right or left pedicle at the glissonian sheath. Figure 16
Sectional control; This is done by isolating and controlling the sectional branches as described in the (Hilar Plate Disection) as described above to be able to isolate each section without affecting other parts of the liver. Figure 17
Out-Flow Control:
Total hepatic control; this is achieved by either clamping of the IVC above and below or clamping the hepatic veins without affecting the flow of the IVC as nowadays done in piggy-back liver transplant.
Isolated hepatic vein control; this is done as described in the posterior approach where full mobilization of the liver is done and the right or left hepatic vein is isolated and clamped with-out affecting the IVC or the other hepatic veins
These all can be done separately or combined to achieve a bloodless liver resection and maintain patient stability.
Meyer-May described the use of Kocher-like clamps to crush liver parenchyma in 1939 [12,42] and haemostatic clamps such as Kelly clamps [43] are still used to crush small areas of the parenchyma, leaving the vessels intact.
Lortat-Jacob used the handle of a scalpel[9] and Lin described the use of finger fracture to remove parenchyma under inflow occlusion to isolate vessels and bile ducts for ligation[44,45].
Ultrasonic dissection has been developed using the CUSA (Cavitron Ultrasonic Surgical Aspirator)[42], this allows for delineation of the hepatic veins, particularly at the junction with the inferior vena cava, and prevents positive margin [45]. It has been shown to be very effective for division of the parenchyma with low blood losse [46,47].
Water-jet dissection [48-49] reduced blood loss, blood transfusion, and transaction time compared with CUSA, but there is increased risk of venous air embolism [45].
Harmonic Scalpel allows sealing of small vessels during the transaction of liver parenchyma. It can be used alone or in combination with clamp crushing or CUSA. It also have been adopted for laparoscopic resections [50,51] with limitation in the dissection around the main trunk of the hepatic veins [52]. Figure.22
Instruments used for liver resection
Ligasure designed to seal small vessels by a combination of Ultrasonic dissection of liver parenchyma using compression pressure and bipolar radiofrequency (RF) energy [45], it was found to be more useful in laparoscopic resection than open.
Tissue Link dissecting sealer, where saline runs to the tip of the electrode to couple RF energy to the liver surface and achieve coagulation [45].
All these instruments have been used and according to many authors each has been claimed to be better than the other. Our believe is that a surgeon should be familiar with all techniques and instruments as each hospital has its own and when instrument malfunction occurs he will have the ability to adopt and rise up to the situation.
Resection of the right hemiliver (segments 5, 6, 7 & 8) is one of the most common types of liver resection. It involves removing all hepatic parenchyma to the right of the middle hepatic vein [8]. This can be done by the Anterior, Posterior or the hanging techniques described above. However, it is important to see which approach will be better for each patient taking into consideration the tumour and the status of the liver.
This starts with mobilization of the right liver by division of the falciform, coronary and right triangular ligaments. Then vascular inflow and outflow control should take place. Three general approaches have been described for achieving vascular inflow control: 1) extrahepatic dissection within the porta hepatis, with division of the right hepatic artery and right portal vein prior to division of the parenchyma (anterior approach) 2) intrahepatic control of the main right pedicle within the substance of the liver prior to parenchymal transection (Intra-Hepatic ligation); and 3) intrahepatic control of the pedicle after parenchymal transaction (hanging technique or posterior approach) [8].
Then the right hepatic artery, right portal vein and the right hepatic duct are lighted and divided extrahepatic. The right liver is then dissected from the inferior vena cava either before or after according to which approach is being adopted. The short hepatic veins that drain from the right hemi liver to the inferior vena cava should be ligated and divided as well as the Hepato-caval ligament. The right hepatic vein is then dissected extrahepatic and ligated. After this step a clear line of demarcation will appear as the right hemi liver will became darker and ischemic. Liver parenchyma transaction will be done on the right border of the middle hepatic vein. Some vascular anomalies can cause the demarcation line of a right hepatectomy to be along the left border of the middle hepatic vein so care must tacked to preserve segment 4 branches or it will become congested. Blood loss control can be achieved by pringle\'s maneuver, using of low central pressure or extrahepatic clamping of the middle and left hepatic veins.Figure.23
Right Hepatectomy; a right liver specimen with tumor invasion in the right hepatic vein
Right hepatectomy + extrahepatic ligation and division of the branches of the hepatic artery, portal vein and bile ducts to segment 4 with the division of the right and middle hepatic veins leaving the left hepatic vein and portal triad supplying the left lateral section intact [18].
The left triangular ligament may be preserved to prevent liver rotation and venous outflow occlusion post resection [42].Figure.24
Right extended tri-sectionectomy; a CT scan of a liver tumor that was resected as shown in the drawing
This can be done in the same manner as the right liver resection, however it will require the identification of the left portal triad. Starting with mobilization of the left liver by division of the falciform and the left triangular ligaments. Extrahepatic division of the extrahepatic branches of the left hepatic artery, left portal vein and left hepatic duct. Isolation of the trunk of the middle and left hepatic vein. Parynchymal transaction done along the plane demarcated by the ischemic left liver along a plan on the left side of the middle hepatic vein. The same should be considered as the line of demarcation can be on the right of the middle hepatic vein. The left hepatic vein is ligated intrahepaticly. Blood Loss can be reduced by using Pringle\'s maneuver plus either low central venous pressure or selective hepatic vascular occlusion by clamping the right hepatic vein. Figure 25
A case of Left Liver resection; the middle hepatic vein seen in the remnant liver with a schematic demonstration
Similar to left hepatectomy in addition of the right anterior section. Care should be done to preserve the hepatic arterial, portal venous and bile duct branches to the right posterior section and the right hepatic vein. If the right inferior hepatic vein is large it should be preserved so the venous drainage to segment 6 will not be affected [18].
Isolated segment II or III resection is uncommonly performed because of the ease of combined segment II and III (left lateral section) and the small volume of each segment. In the presence of cirrhosis or when multiple segmental resections are performed, isolated resection may be necessary. The left hepatic vein is identified extrahepaticaly and the left lateral sectional portal triad is ligated at the umbilical vein and the falciform ligament.Figure.26. Then the hepatic transaction is carried out with very minimal blood lose.
A) left lateral section as seen on intra-operaive ultrasound. B) the specimen with tumour to check for margins
This can be achieved by most techniques described above depending on the tumour size and the status of the Liver. Full mobilization of the right liver with division of the posterior draining veins. The right portal pedicle is exposed, and the anterior and posterior branches are identified (Hilar plate approach). The posterior pedicle is clamped, and the line of demarcation is evident. The pedicle may be divided, and parenchymal dissection may be performed in standard fashion. The line of transection is horizontal and posterior to the right hepatic vein. However, the right vein may be sacrificed during this procedure since the anterior section will be adequately drained by the middle hepatic vein[8]. If the liver is cirrhotic we would advise the use of an extrahepatic approach like the posterior approach to minimize the blood lose and injury to the right anterior portal triad.
This is extreamly rare and very difficult because of its location between both the right and middle hepatic veins with the importance of not injuring any of them. This is why if it is done it is combined with segment IV (Central liver resection) to remove the middle hepatic vein and have a safe distance from the right hepatic vein. The approach is similar to the right posterior sectionectomy were the right anterior portal triad is seen and ligated to stop the inflow and get the line of demarcation.
For removal of either segment II or III, the inflow pedicle is ligated, but the main left hepatic vein is preserved because it provides the only venous drainage to the remaining segment. The inflow pedicles to segments II and III branches directly from the umbilical portion of the left main portal vein. To isolate these pedicles, the left lateral section is shifted cephalad using traction on the divided falciform ligament. If present, the parenchymal bridge between segment III and IV is divided with electrocautery. Dissection of the umbilical fissure to the left of the portal vein is performed. Ligation of either segment II or III pedicles demarcates the boundary between them. The left hepatic vein may be clamped to reduce blood loss, but clamping is generally unnecessary if the central venous pressure is low. Liver transection then proceeds in an oblique antero-cranial plane with attention to preserve the left hepatic vein [3].
To expose this segment dissection of the right triangular ligament is necessary. The vascular pedicle of segment VII originate from the right lateral glissoian pedicle and enters the parenchyma in a common trunk at segment VI, this will run deep and divide to two branches anterior to segment VI and posterior to segment VII.
After mobilizing the infindibulum of the gall bladder and dividing the lateral peritoneum of the hepato-duodenal ligament the lateral pedicle can be easily freed as well as the artery. Once this is identified with the bile duct, the right branch of the portal vein is freed. The bile ducts will never be dissected outside the parenchyma but only transparenchymaly at the end of the resection to prevent damage to the adjacent hepatic ducts. Clamping of the arterial branch will lead to blanching of the entire right anterior section. The fissure of the right hepatic vein will indicate the upper resection margin. The vein could be left in place or removed in case of neoplasm infiltration, also isolated resection of segment VII with ligation of the right hepatic vein can be safely performed, venous out flow of segment VI should be insured by preserving the accessory hepatic veins and the right inferior hepatic vein(present in 25%) to prevent the transitory venous congestion of segment VI with hemorrhage from the resection margins after isolated removal of segment VII. After clamping of the lateral glissonian pedicle the trunk of the right hepatic vein will be clamped and divided. Parenchymal dissection will follow the appearing ischemic demarcation line and the dissection plane will start from the top downward between segment VII and VIII. The pedicle will be exposed with the dissection once it have been divided the arterial and portal branches at the hilum can be unclamped, segment VI returns to its normal color and the inferior demarcation line will become evident.
Similar to segment VII, after mobilization of the right liver, ligation of the inferior or accessory suprahepatic vein if present and clamping of the arterial and portal brances which will produce the ischemic demarcation line.
The parenchyma is divided starting from the lower margin of the liver proceeding along an oblique plane from the right to the left and from the front to back. Deep in the parenchyma the lateral pedicle is ligated. The glissonian pedicle is then unclamped at the hilum and segment VII will return to the normal colour, the upper dissection margin will follow the ischemic line between the two segments VI and VII.
Segment IV is divided into two subsegments, IVA and IVB, based on the inflow pedicles. Isolated resection of IVB is usually done in a intra-hepatic ligation method and most often with segment V in cases of gallbladder carcinoma. Were outflow control for segment IV resection is usually not obtained until the liver is divided. After dissection of the hepatoduodenal ligament the left branches of the hepatic artery are identified and then the middle branch is ligated and divided. Dissection will be carried out along the gall bladder-inferior vena cava plane. Glissonian capsule divided above the hilar plate. The portal branch is usually seen with the hilar plate and dissection with control by Bull-dog clamps to see the line of demarcation. At this point segment IV will only be attached to the Middle Hepatic vein which will be transfixed.
This is the least popular liver resection as all the other segments can be done in an intra-hepatic ligation method or in a non-anatomical approach. However, the Caudate liver resection has its own unique location above the inferior vena cava and its own blood supply giving it the excellent challenge for any liver surgeon. There are 5 approaches:
Bilateral approach: For isolated caudate lobectomy, the caudate lobe is approached from both right and left side after complete mobilization of the liver with controll of the suprahepatic and intrahepatic inferior vena cava as well as the right hepatic vein and the common trunk of the middle and left hepatic veins. Then the caudate lobe is detached from the inferior vena cava along the anterior surface of the retro-haptic IVC and the short hepatic veins are identified and divided. The hepatogastric ligament is detached from the undersurface of the liver and the fibrous hepatocaval ligament need to be divided to free the spieglian lobe from the IVC and the diaphragm. All short hepatic veins are ligated and divided. So the caudate lobe is free from the inferior vera cava. The branches of the to the para caval portion of the caudate lobe from the right portal vein, right hepatic artery and duct, branches to the spiegelian lobe from the left portal vein, left hepatic artery and duct are ligated and divided. By carefull dissection the liver is detached from the surroundings and the right, middle and left hepatic veins. In this step; 2 important land marks for this dissection : A) the angle between the right hepatic vein and the inferior vans cava i.e the top of the caudate lobe. B) the meeting point between the caudate process and the right liver. An imaginary line joining these two points is considered as the caudate boundary for the liver transection. Meticulous care should be applied not to injure the major vessels or induce bleeding which will be difficult to control.
Left sided approach: Similar to the bilateral approach whit the exception that the dissection is mainly from the left side of the liver. In small tumours <3cm, if an isolated partial caudate lobecetomy or left hepatectomy combined with complete caudate lobecetomy is carried out. Figure 27
Caudate liver resection, A) the lobe is removed from the IVC and lifted up (left approach). B) The specimen of the caudate with the left liver and the CBD for cholangiocarcinoma
Right sided approach: Similar to the bilateral approach whit the exception that the dissection is mainly from the right side of the liver. In thin patients with right hepatectomy combined with caudate lobecetomy.
Anterior approach: This approach provides a better operative field by opening the mid plane of the liver widely so the major hepatic veins and the Hilar plate will be exposed to direct vision thus will facilitate tumour resection from the main vessels. For tumours >4cm especially when the tumour is located in the paracaval portion or in close contact with the major hepatic veins. With tha same technique of the bilateral approach. After freeing the caudate lobe from the reto-hepatic inferior vena cava, pringle\'s meneuver is then applied. The liver is transacted through the mid plane starting from the point between the root of the right and middle hepatic veins to the fossa of the gall bladder. This is better done using the hanging technique. When the transection reaches the Hilar plate at the hilum, the portal triade of the caudate lobe is isolated and divided. The caudate lobes then separated from the major hepatic veins in one block with the tumour. After removal of the specimen all bleeding points and bile leak should be controlled individually.
Retrograde caudate lobectommy: Used if the tumour is closely adherent to or infiltrating the inferior vena cava, or if the tumour is too large in size to be turned from one side to the other. Mobilization of the liver by the division of all the ligaments, control of the hepatoduodenal ligament, suprahepatic and intrahepatic inferior vena cava for possible occlusion if necessary. The liver is transected along the mid plane 1cm from the tumour, the hepatic veins are exposed under direct vision and carefully dissected from the specimen, ligation and division of the caudate portal triad from the right/left hepatic arteries and veins. In combined Left/right hepatectomy with caudate lobecetomy the hepatic pedicel can be transected accordingly. The specimen will be attached only to the inferior vena cava. The last step here will be the division of the short hepatic veins, and if the tumour is attached to the IVC part of it could be resected with the tumour and then it\'ll be repaired or reconstructed.
Segments IV, V, and VIII (also known as mesohepatectomy) is rarely performed. This resection involves ligation of inflow vessels from both the right and left portal pedicles. The resection is performed by combining the techniques of segment IV resection and right anterior sectionectomy. Dissection begins at the hilum and the umbilical fissure with the goal of inflow control. The right anterior sectional pedicle is isolated, as are the segment IV pedicles. The division of the liver parenchyma begins to the right of the umbilical fissure (or within it if the tumor is nearby). Figure.28.Care should be given to avoid ligating the left main portal umbilical branch. Dissection is continued upward to the main trunk of middle hepatic vein. The right anterior sectional pedicle is ligated to demarcate the boundary of the liver resection on the right side. Liver transection proceeds in the plane of the right hepatic vein until it meets the left resection plane. At this point, one should be cautious with handling the freely dangling central lobe. Excessive traction may tear the thin-walled middle hepatic vein, resulting in massive hemorrhage. Gently hold the lobe and divide the base of the middle hepatic vein. This procedure removes the gallbladder, central lobe, and middle hepatic vein en bloc, leaving the caudate, right posterior section, and left lateral section intact. The raw liver surface may be covered with a flap of omentum.
Central liver lesion as seen on CT scan and the same patient intra-operatively after resection
To minimize blood loss from the resected raw liver surface the patient is placed 15 degres in the Trendelenburg position [3]. Low venous pressure is maintained by minimizing fluid infusion and restricting intraoperative blood transfusion unless more than 25% of the blood volume is lost [53,54]. Systolic blood pressure is kept above 90 mm Hg, and intraoperative urine output is maintained at about 25 mL/hour [3].
Dissection and control of the hepatic veins performed prior to parenchymal transaction.[8].
Venous outflow draining is divided after dividing the inflow vessels[8], unless the posterior approach is adopted with a Pringles manoeuvre to prevent liver congestion.
Control of the suprahepatic and intrahepatic inferior vena cava [18], pringle\'s maneuver[3,18], and mobilization with parenchymal transection performed with a low central venous pressure < 5 mm Hg [3,11] can decrease the bleeding amount significantly.
The majority of patients suffering from acute pancreatitis will have a mild, self-limited and uncomplicated course. Pancreatic necrosis may develop in up to 10%-20% of patients, because of insufficient perfusion of pancreatic parenchyma to support metabolic requirements, leading to a prolonged clinical course with up to 30% mortality in case of infected necrosis [1]. Local and systemic complications, mild or life-threatening, such as pancreatic and/or peripancreatic fluid collections, walled-off necrosis, infected pancreatic necrosis, disconnected pancreatic duct syndrome and vascular complications can occur. The successful management of these patients needs a multidisciplinary team composed by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition. Intervention is generally required for infected pancreatic necrosis and less commonly in patients with sterile necrosis who are symptomatic (gastric or duodenal outlet or biliary obstruction) [2]. The surgical odyssey in managing necrotizing pancreatitis is a notable example of how evidence-based knowledge leads to improvement in patient care. Open surgical necrosectomy has been the traditional surgical treatment for years. However, although it provides a wide access but it is associated with high morbidity (34%-95%) and mortality (11-39%). In the last decades treatment has moved towards minimally invasive techniques: laparoscopy, retroperitoneal and endoscopic or percutaneous approaches. These can allow open surgery to be postponed in a sub-acute setting or even to avoid it [3, 4, 5, 6].
Local complications such as pancreatic and/or peripancreatic fluid collections can occur after an episode of acute pancreatitis or after recrudescence of chronic pancreatitis or a blunt, penetrating, iatrogenic pancreatic trauma. Peripancreatic fluid collections, with or without a necrotic component, are early manifestations of the pancreatic inflammatory process. They are not delimited by a well-defined inflammatory wall and often remain asymptomatic, ending in spontaneous resolution by a gradual reduction in size. After four weeks from the clinical manifestation, persistent collections usually become wall-defined, encapsulated, with (walled-off necrosis) or without (pancreatic pseudocyst) a necrotic component and a varying degree of pancreatic parenchyma involvement [7].
Management of pseudocysts and walled-off pancreatic necrosis (WOPN) rely on patient’s symptoms, location and characteristics of pancreatic and/or peripancreatic collections, local complications (such as pseudoaneurysm), expertise and availability of a multidisciplinary group [8].
In asymptomatic patients, clinical observation and periodic imaging follow up (every three-six months) represent the most successful management, due to the frequent reduction in size and spontaneous resolution of non-complicated homogeneous collections and to the morbidity associated to interventional (endoscopic or radiologic) treatment procedures. In these cases, it is possible to associate nutritional and pharmacological support (nasoenteric feeding reduces pain and improves nutritional status; proton pump inhibitors and somatostatin-analogue such as octreotide reduce pancreatic secretion).
Infection will develop in about one third of patients with pancreatic necrosis. It may arise at any time during the clinical course but peak incidence is between the 2nd and the 4th week after presentation [2]. Gram-negative bacteria are the main infectious species isolated, the most common of which are
Prognosis and management are greatly affected by the recognition between sterile and infected pancreatic necrosis. Clues of suspicion should arise in case of clinical signs of systemic inflammatory response syndrome (SIRS) (new-onset fever, tachycardia, leukocytosis) or organ failure [12]. A blood culture with positive bacterial results and gas in and around the pancreas on a CT scan may give indirect evidence of infection. Prophylactic antibiotic use in patients suffering from acute pancreatitis has not been proven to decrease infection rate and thus, according to the meta-analysis by Wittau et al. [13] it is not recommended a routine prophylaxis. The Cochrane review by Villatoro et al. [14] showed that antibiotic prophylaxis was not associated with a reduced incidence of pancreatic necrosis infection, even though it was associated with significantly decreased mortality. CT- or US-guided fine needle aspiration of pancreatic necrosis for bacteriologic analysis are an accurate, safe and reliable techniques with high accuracy (89.4%-100%) [15, 16].
In symptomatic patients, with rapidly enlarging pseudocysts or systemic manifestations of organ failure sustained by an infectious process, an interventional treatment is indicated. In this case endoscopic drainage approach is the first choice, especially when fluid collection is close to gastroduodenal lumen. A combination of techniques is possible in patients with large collections, extended in pelvis and paracolic gutters, or multiple collections [17].
Endoscopic drainage of a walled collection is the preferred method when the drainage criteria are met: mature collections delimited by a well-defined inflammatory capsule and with a mostly liquid content; cystic wall adherent to stomach or duodenum; and collection’s size at least 6 cm in size.
This procedure has to be performed by an endoscopist with expertise and when surgical or interventional radiology staffs are available [18]. Contraindications to endoscopic drainage are: presence of pseudoaneurysm due to gastroduodenal or splenic artery erosion, with high risk of bleeding; and collections without a mature wall.
Drainage techniques consist in [19]:
Transmural approach is adopted when large and symptomatic walled-off pancreatic fluid collection is close to gastroduodenal structures. Transmural puncture through gastroduodenal wall (where is endoscopically visible a bulge resulting by apposition to the cyst), is nowadays ecoendoscopically guided. This permits to accurately identify puncture site for cystenterostomy, avoiding vessels or other interposed structures and evaluating real distance to pass through [20]. Self-expanding metal stents or plastic double pig-tail stents can be both used. Lumen Apposing Metal Stent (LAMS) are associated with higher bleeding grade but allow immediate procedures such as endoscopic necrosectomy.
Drainage of turbid necrotic fluid suggests debris presence and can be managed with direct endoscopic debridement and/or with the placement of a naso-cystic catheter for post-procedural lavage. Repeated debridement or association with percutaneous drainage or percutaneous endoscopic gastrostomy can be necessary with unresolved fluid collections [21].
For patients with small pseudocysts derived from main pancreatic duct, transpapillary stent placement is indicated as first drainage approach. This provides continuous drainage of pancreatic fluid, leading to resolution of pancreatic ductal disruption that is responsible of pseudocyst. Follow up with CT or EUS is preferred after four to six weeks if necrotic debridement was not necessary and stents are then removed the fluid cavity is collapsed. More frequent imaging is obtained in patients who underwent necrosectomy, to determine if additional debridement is necessary. When collections are completely evacuated, stents are removed. Long-term stents seem to protect against recurrence allowing ongoing drainage of pancreatic secretions, although cystenterostomy tract matures and persists after eventual stent removal [22].
Percutaneous drainage remains an important treatment modality for patients with symptomatic collections. It may be used both as primary therapy or as an adjunct to other techniques. According to the last International [23], American [1] and Japanese [24] guidelines, percutaneous catheter (or endoscopic transmural drainage) should be the first step in the treatment of patients with suspected or confirmed (walled-off) infected necrotizing pancreatitis. This is applied to decompress retroperitoneal fluid collections, to provide a rapid and effective means for source control in patients with infected pancreatic necrosis. It favors clinical stabilization of patients before endoscopic or surgical debridement and is the first choice when endoscopic drainage is unavailable, unsuccessful, or not technically feasible [25].
The positioning can be performed via the transperitoneal or retroperitoneal approaches. It is technically feasible in >95% of patients [26]. Retroperitoneal route is generally preferred because it avoids peritoneal contamination, enteric fistulas and facilitates a possible step-up approach (see “Surgical approach” chapter). Moreover, the catheter tract can act as an entry portal for minimally invasive debridement methods, such as video assisted retroperitoneal or endoscopic debridement [1]. Catheters range from 8 Fr to 30 Fr in diameter; they allow for bedside irrigation and clearance of necrotic material, can be manipulated and replaced according to the evolution of the collections [27].
Percutaneous drainage alone may provide definitive therapy for a subset of patients. The prospective observational multicenter study by Horvath K. et al. in 2010, found that the decrease in the size of the collection of at least 75% after the first 10-14 days predicts successful percutaneous treatment. In 2011, a large prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis demonstrated that catheter drainage was the first intervention in 63% of cases and did not require additional necrosectomy in 35% of patients [28]. Two prospective randomized trials from the Dutch Pancreatitis Study Group compared various approaches to the management of symptomatic WON. They demonstrated that percutaneous drainage alone was successful in 35%-51% of patients and that a minimally invasive step-up approach was related to a lower rate of pancreatic fistulas, length of hospital stay and death, as compared with open necrosectomy [26, 29].
The risk of pancreatocutaneous fistula formation is the major potential drawback of this technique. The multicentre randomised trial by van Brunschot S. et al. demonstrated that the rate of pancreatic fistula formation was significantly higher in the percutaneous (32%) as compared to the video-assisted retroperitoneal debridement (VARD) group (5%) [29]. The rate is as high as 45% in those with disconnected duct syndrome [30].
The surgical odyssey in managing necrotizing pancreatitis is a notable example of how evidence-based knowledge leads to improvement in patient care. In the beginning of the 20th century surgeons such as Mayo Robson, Mickulicz, and Moynihan, in the context of the progression of anesthesia, were induced to deploy laparotomy in an effort to treat complications of severe acute pancreatitis [31]. Over the next decades surgical intervention became the therapy of choice despite a mortality rate greater than 50%. Extensive pancreatic resection became the treatment of choice in the 1960s and 1970s. Innovations and increased accuracy in radiological techniques led to new approaches for management. Surgeons were divided between those who reserved the intervention for cases of infected necrosis by proposing delayed exploration, and those who proposed early debridement for all patients with necrotizing pancreatitis. Since 1990s several studies proved that nonoperative management of patients with sterile pancreatic necrosis was superior to surgical intervention, and that delayed intervention provided improved surgical mortality rates. The treatment of infected necrosis shifted to a more conservative approach also thanks to a comprehensive knowledge of the physio-pathological process of the systemic inflammatory response and the adoption of novel antibiotics in curbing systemic toxicity and protecting against organ failure. Recently, endoscopic debridement and minimally invasive techniques has been introduced [31, 32].
The last guidelines of the Working Group of the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) published in 2013 [23] and of the American Gastroenterological Association (AGA) published in 2020 [1] on the management of acute pancreatitis and pancreatic necrosis list the common indications for intervention. A symptomatic sterile pancreatic necrosis is an indication for intervention (either radiological, endoscopical or surgical). Symptoms can be represented by: gastric, intestinal, or biliary obstruction due to the mass effect of walled-off necrosis, pain, persistent unwellness in patients without signs of infection [1]. In case of infected pancreatic necrosis invasive procedures (e.g. percutaneous catheter drainage, endoscopic transluminal drainage/necrosectomy, minimally invasive or open necrosectomy) should be delayed, where possible, until at least 4 weeks after initial presentation to permit the collection to become “walled-off”. A randomized clinical trial [33] that compared early surgery (within 72 h) and delayed surgery (11 days after onset) demonstrated mortality rates of 56% and 27%, respectively.
Percutaneous drainage, alone or in combination with other minimally invasive approaches, can be an effective means for source control in patients with infected pancreatic necrosis. A significant number of patients (23%–47%) will resolve their necrosis with percutaneous drainage alone. In those with persistent disease, a step up to operative intervention may be undertaken. The tract of the drain is utilized to access the retroperitoneal space for an intracavitary videoscopic necrosectomy by which drains are left in the cavity for lavage and fistula control [26, 34, 35]. The PANTER Study in 2010, a prospective randomized multicenter trial, compared the step-up approach to open necrosectomy and found a higher rate of new-onset multiple-organ failure in the open necrosectomy group (40% vs. 12%) and an equivalent mortality between the groups [26]. Surgical transgastric debridement is similar to endoscopic transgastric debridement, can be done laparoscopically or open, and is performed by an anterior gastrotomy to access the posterior wall of the stomach for transmural access to the necrosis cavity. Open surgical debridement is still an important resource in the management of these patients for the debridement of necrotic tissue.
Before surgical approach, abdominal imaging is helpful to determine intra-abdominal status. Diagnosis of infected pancreatic necrosis is made by identification of air bubbles in retroperitoneal necrosis (areas with lack of contrast enhancement) on CT scan. Diagnosis can be confirmed by CT-guided fine needle aspiration of necrotic material for culture. CT is also indicated to define extent and location of necrotic areas, for example into the mesenteric root and down the paracolic gutters; to demonstrate the presence of a disconnected pancreatic segment (a viable pancreatic portion separated by the rest of pancreas by a necrotic segment, that require external drainage to create a controlled external pancreatic fistula); and to evaluate the presence of other local complications, such as gastric outlet obstruction, splenic or portal vein thrombosis and colonic necrosis. Open debridement with external drainage still plays an important, albeit limited, role. After access to retroperitoneum, fluid is evacuated and necrotic dissection and debridement is made. In biliary pancreatitis, cholecystectomy should be practiced but it is associated with increased incidence of postoperative bile leak or biliary injury. Colon resection and colostomy have to be considered if mesocolon is involved in peripancreatic necrosis. A feeding enteral tube and at least two-four drainage tubes should be placed [36].
Video-assisted retroperitoneal debridement approach requires preoperative percutaneous retroperitoneal access. Radiological catheter insertion is a route to guide the subsequent procedure directly down into necrotic cavity and postoperative lavage. The advantage is minimizing the risk of peritoneal contamination, but the access is limited and precludes other procedures over debridement [34]. Postoperative complications are: intra-abdominal residual fluid collections, derived from pancreatic leak not well controlled by drains; bleeding, due to vascular lesion during debridement maneuvers or rupture of pseudoaneurysm, related to vascular erosion caused by mechanical drain damage or infection associated with uncontrolled pancreatic fistula; pancreatic fistulas: amylase-rich (concentration greater than three times the upper limit of normal serum amylase) fluid coming from drains; biliary injury; and pancreatic endocrine and exocrine insufficiency, that may requires supplemental insulin and oral pancreatic enzyme replacement.
Each approach has distinct peculiarities with pros and cons that must be weighted in each case planning: pattern of disease, physiology of the patient, expertise of the multidisciplinary team, and the resources of the center [1].
The term disconnected pancreatic duct syndrome (DPDS) refers to a subset of patients suffering from a disruption of the main pancreatic duct leading to a normal upstream pancreatic gland having no communication with the gastrointestinal tract [1, 37]. Up to 50% of patients with pancreatic fluid collections might have an underlying disconnected duct. It is best recognized using secretin-stimulated magnetic resonance cholangiopancreatography [38]. DPDS can be the result of acute necrotizing pancreatitis, chronic pancreatitis, and pancreatic trauma. Pancreatic juice is still secreted from the disconnected gland resulting in different resolutions that are a continuum of the same pathophysiologic process: recurrent acute pancreatitis, internal persistent pancreatic fistula (most often presenting as a peripancreatic fluid collection), external fistula, pancreatic pleural effusion, pancreatic ascites, or disconnected pancreatic tail syndrome [39, 40].
Internal fistulae are the result of ductal disruptions that are not contained by the inflammatory response. Anterior ductal disruptions result in pancreatic ascites, posterior ones result in pancreatic pleural effusions. Positive testing for a collection rich in pancreatic enzyme gives the secure diagnosis. A percutaneous drainage is the initial treatment to obtain a controlled fistula that in 70-82% of cases results in a spontaneous closure.
External fistulae may develop after pseudocyst percutaneous drainage. The stricture or the obstruction of the Wirsung result in ductal hypertension thus increasing the chance of developing this complication. Endoscopic retrograde pancreatography (ERP) with sphincterotomy or transpapillary stenting should be then performed, both in internal and in external fistulae, to reduce resistance of pancreatic juice flow to the duodenum [41].
If the disruption is in the body or the tail (disconnected pancreatic tail syndrome), open distal pancreatectomy and debridement associated with drainage are the traditional surgical procedures. These are characterized by a high periprocedural morbidity that is counterweighted by the single procedure and a concise overall course. Distal pancreatectomy can be undertaken during the first 30–60 days of illness, in the subacute setting [1].
The high morbidity and mortality associated with open surgical procedures, especially for poor surgical candidates, recommend a minimally invasive endoscopic [42]. Partial duct disruption can be treated with endoscopic transpapillary stent bridging with a fistula resolution rate of 56%, according to Varadarajulu et al. [43]. One possible endoscopic approach in case of complete duct disruption is the use of permanent indwelling transmural stents that allow the creation and maintenance of a fistulous tract into the gastrointestinal lumen [42].
Correct choice of procedure, as well as correct choice of timing of intervention, are mandatory for success.
Haemorrhage, pseudoaneurysm and thrombosis are the main vascular complications with an incidence ranging from 1% to 23% in patients with acute pancreatitis. Arterial complications are less frequent than venous complications (1.3-10% vs. 22%) [44].
The etiopathology of bleeding in patients with severe pancreatitis can be summarized in four main causes. The first one is due to the local spreading of lipolytic and proteolytic enzymes during a severe pancreatitis or necrosis that leads to the disruption of the tissue and the release of pancreatic fluids thus resulting in the arterial wall damage [45]. The second cause is related to a iatrogenic damage: improper surgical management of acute pancreatitis with an early operation for non-infected necrosis has been reported in Literature as a possible cause of wall arterial weakening thus leading to bleeding due to the activated enzymes [46]. Another iatrogenic source of damage is associated to the radiological positioning of drains that could give a direct trauma to the vessels and a continuous local inflammation that can diminish arterial wall integrity [47]. A third pathogenic mechanism is splenic vein thrombosis due to the necrotizing process, pseudocyst and severe inflammation that could lead to portal hypertension and, as a late sequelae, to esophageal varices formation [45]. The last remarkable pathogenic mechanism is the formation of a pseudoaneurysm that derived from the rupture of a vessels into a long-standing pseudocyst [48]. Symptoms are gastrointestinal bleeding, abdominal pain and splenomegaly and they depend on the localization of pseudoaneurysm. The most common vessels are splenic (35-50%), gastroduodenal (20%), and pancreaticoduodenal (20%) artery. Other vessels involved are tributaries of the gastric, colic and hepatic bloodstream [40, 49].
Ultrasound (US) and Computed Tomography (CT) are the gold standard to diagnose a vascular complication. Specially, CT imaging showed a higher sensibility in the diagnosis of pseudo-aneurysm, and US has an important role in identifying thrombosis or in patients with iodine allergy or renal insufficiency [50]. Enhanced-contrast CT locates necrotic areas, abscess cavity, pseudocysts, and bleeding site. Angiography is the gold standard technique for the location and the control of the bleeding [45]. Interventional radiology is the first line treatment in both elective and emergency management of vascular complications. Angiography followed by trans-arterial embolization (TAE) is the gold standard management [51]. Different techniques can be used: the one preferred is the sandwich technique with coil located proximally and distally to the pseudoaneurysm to minimize the risk of potential rebleeding [52]. Haemostasis can be implemented with glue, N-butyl cyanoacrylate (NBCA), thrombin, ethiodised oil or gelfoam. Patients with unsuccessful TAE or in which is technically impossible, an emergency haemostatic surgery should be performed. Ligation of bleeding arteries is the technique of choice although related to a high rate of rebleeding. In extreme cases, open packing or salvage emergency pancreatectomy may represent the only chances for survival [45].
Vascular complications are rare but potentially fatal with a difficult management that is why they should be treated in a tertiary centre.
Pancreatitis is a rare cause of chylous ascites (CA) and in Literature, only few cases about acute pancreatitis are reported since its discovered in 1984 [53, 54]. Other causes related to CA are abdominal trauma, malignancies, sarcoidosis, lymphangiomatosis, yellow nail syndrome, cirrhosis, and mycobacterial infections [55]. CA diagnosis is based on the presence of a milky triglyceride- rich fluid collection in the peritoneal cavity. Patients complain about abdominal pain, distension, weight loss, oedema, anorexia, and weakness.
Diagnosis requires peritoneal fluid sampling with documentation of a lipid rich fluid, triglyceride concentration > 1.2 mM (110 mg/dl), peritoneal-to-plasma protein concentration ratio of >0.5 and presence of microscopic fat. The minimum daily volume of CA considered significant ranges between 100 ml to 600 ml [56, 57].
The pathogenesis is not completely clarified especially when CA is due to acute pancreatitis. The main possible reason is the spreading of proteolytic and lipolytic enzymes associated to necrosis of pancreatic tissue that damage the lymphatic vessels thus provoking a lymph leakage. Other possible reasons are AP related and include: splenic vein thrombosis leading to portal vein hypertension thus causing the rupture of lymphatic vessels; and the severe inflammation that could cause lymphatic vessels obstruction and lymphatic exudation [58, 59].
CA treatment is multimodal. Conservative treatment is based on total parenteral nutrition (TPN) or medium chain triglyceride (MCT)-high protein enteral feeding with or without addition of octreotide and reaches the resolution in two to six weeks in 60-100% of cases [60, 61]. Interventional and surgical approaches should be reserved for cases in which conservative treatment has failed. A second line therapy is bipedal lymphangiography (BPLAG) with lipiodol. This technique permits to identify the normal lymphatic stream and locate the leakage site or the obstruction site. The accumulation of injected lipiodol determines an inflammatory response that acts as an embolic agent and determines leakage resolution in up to 70% of cases [62].
Van der Gaag and colleagues has considered any duration of chylous ascites, longer than 14 days despite therapy, a requirement for surgical intervention [63]. Surgical treatment may vary from a peritoneovenous shunt to open surgical ligation of the leaking lymphatics [64]. Surgical approach should be chosen only in case of persistent CA despite treatment, symptomatic patients, or impossibility to perform interventional radiology.
Biliary stricture (BS) and duodenal stenosis (DS) are uncommon complication of AP. Pathogenesis of these events is strictly related to the anatomical position between the pancreatic head, the common bile duct and the duodenum. BS and DS are, in most cases, early and transient conditions associated to severe inflammation [65]. The main causes for temporary BS are inflammatory oedema and pseudocyst formation and enlargement in the area proximal to the pancreatic head that create a compression of the common bile duct, thus causing jaundice, nausea, vomit, abdominal pain, pruritus, and fatigue to the patient [66].
A duodenal early complication is gastric outlet obstruction related to the abnormal peristaltic wave and following ileus caused by the severe inflammation and the possible compression of the duodenal loop by the enlarged neck of the pancreas that cause a lumen obstruction [67].
BS ad DS usually solve with a conservative treatment intended to overcome the acute inflammatory phase. Pseudocyst management is resumed in previous chapters.
In many studies, late BS is associated to pancreatic duct disruption (PDD) with pancreatic juice leakage when duct of the head/neck of pancreas is involved in pancreatic necrosis [68]. When PDD is suspected, contrast-enhanced CT should be performed to confirm it and after that an endoscopic retrograde cholangiopancreatography (ERCP) to localize the leakage and positioning a stent [69]. If this procedure failed, and a progression of the common duct stricture has developed, surgical procedure is indicated [53].
The process that leads a transient DS to an irreversible one is still unclear. Literature suggests that the underlaying cause is a possible ischemic and thrombotic event. Indeed, inflammation may induce arterial narrowing and/or thrombosis of the pancreaticoduodenal circulation producing local ischemia and resulting in chronic fibrosis [70]. Patients who present intermittent symptomatic episodes of upper gastrointestinal tract obstruction should undergo surgical bypass, chosen considering the pathophysiology (gastrojejunostomy or gastroenterostomy with vagotomy to prevent marginal ulcer)[71].
The majority of patients suffering from acute pancreatitis will have a mild, self-limited and uncomplicated course. Local and systemic complications, mild or life-threatening, such as pancreatic and/or peripancreatic fluid collections, walled-off necrosis, infected pancreatic necrosis, disconnected pancreatic duct syndrome and vascular complications can occur.
The successful management of these patients needs a multidisciplinary team composed by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition. However, it must be considered that the requisite technical expertise and judgment for many of these procedures is not widely available in all centres. Intervention is generally required for infected pancreatic necrosis and less commonly in patients with sterile necrosis who are symptomatic. The surgical odyssey in managing necrotizing pancreatitis has been described. Operative approaches to the treatment of acute pancreatitis complications have undergone a dramatic transformation over the past few decades. Prospective, randomized trials have further clarified the value of the latest minimally invasive approaches to the treatment of this disease. This is the notable example of how evidence-based knowledge leads to improvement in patient care.
The authors declare no conflict of interest.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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\n\n2. SUBMIT YOUR MANUSCRIPT
\n\nAfter approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
\n\n3. PEER REVIEW RESULTS
\n\nExternal reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
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\n\nWe will send you your price quote and after it has been accepted (by both the author and the publisher), both parties will sign a Statement of Work binding them to adhere to the agreed upon terms.
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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11403,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. 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