Postoperative outcomes: comparison between laparoscopic and open PD.
\r\n\t
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All these bacteria share a common feature, a distinctive multilaminate cell wall composed of peptidoglycan, complex polysaccharides, and both covalently linked lipids and free lipids/lipoglycans (Fig. 1). Among them, mycolic acids are the hallmark of these species. These long chain α-branched, β-hydroxylated fatty acids are covalently linked to the arabinogalactan polysaccharide layer. This mycolic acid layer is complemented by a glycolipid layer to form an outer “mycomembrane” analogous to the outer membrane of Gram-negative bacteria. [1, 2]. The outer leaflet of the mycomembrane is composed of a variety of lipids including trehalose dimycolates (TDMs), glycopeptidolipids (GPLs), phthiocerol dimycocerosates (PDIMs), sulfolipids, phenolic glycolipids (PGLs), and lipooligosaccharides. Some of these lipids are widely distributed while others are restricted to particular species. For example, TDMs and their structural equivalents are found in both mycobacteria and corynebacteria, while PDIMs and PGLs are restricted to a subset of mycobacteria. The structure and hydrophobic properties of the cell wall make it a potent permeability barrier that is responsible for intrinsic resistance of mycobacteria to an array of host microbiocidal processes, many antibiotics and sterilization conditions [3, 4]. Many of the cell wall components of pathogenic mycobacterial species are essential for pathogenesis and
Mycobacterial plasma membrane and cell wall with flow of key metabolic pathways. Some of the metabolites are exported to the mycomembrane. SLD, small lipid droplet; LD, lipid droplet; FA-CoA, fatty acyl-CoA. See text for other abbreviations used in the figure.
Studies on mycobacteria and corynebacteria provide a unique opportunity to illustrate the complexity and diversity of lipid metabolic pathways in bacteria. They have a significantly higher lipid content than other bacteria with cell wall lipids comprising ~40% of the dry cell mass.
The plasma membrane provides the platform for lipid metabolism. While some lipid metabolic reactions take place in the cytoplasm or cell wall, the plasma membrane is the pivotal site for the metabolism of lipids. At the same time, this membrane must perform many other functions associated with energy production, nutrient uptake, protein export, and various sensing/signaling reactions. Studies on how these metabolic and cellular processes might be organized within bacterial plasma membranes are in their infancy. Understanding the homeostasis of the plasma membrane is particularly important in Corynebacterineae organisms because this structure must support the high biosynthetic demands of sustaining such a lipid-rich cell wall. In this chapter, we focus our discussion on processes of lipid metabolism that are critical for the biogenesis and maintenance of the plasma membrane, and illustrate the recent progress on our understanding of plasma membrane biogenesis in mycobacteria and corynebacteria.
In this section we will describe the functions of plasma membrane lipids. First, we will describe the functions of major structural phospholipids. We will then describe quantitatively minor lipids, which have important metabolic/physiological functions. Lastly, we will discuss the functions of neutral lipids because their biosynthesis is closely linked to phospholipid metabolism and neutral lipid storage is a critical part of plasma membrane homeostasis.
Major structural components of the mycobacterial plasma membrane are phospholipids such as cardiolipin (CL), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and glycosylated PIs (
CL is widely found in both prokaryotes and eukaryotes. It forms aggregates within the membrane bilayer. Nonyl acridine orange (NAO) is a fluorescent dye which is proposed to bind the hydrophobic surface created by the CL cluster [14], allowing microscopic visualization of CL domains. Indeed, using NAO, CLs were found to be enriched in septa and poles of actively dividing
PE is another major class of glycerophospholipids in mycobacteria. Although PE is generally found in all organisms, it is particularly abundant in bacterial plasma membranes [26]. Mycobacteria are no exception [20], but corynebacteria apparently lack the capacity to synthesize PE [27]. Indeed, PE biosynthetic enzymes, such as PS synthetase and PS decarboxylase, appear to be absent in corynebacterial genomes.
PIs are an important class of phospholipids, and are known to be further modified by extensive glycosylation. The resultant lipoglycans, termed PIMs, LM, and LAM, are essential structural components of mycobacterial and corynebacterial cell walls. Furthermore, in pathogenic species, they have been suggested to perform additional roles in the modulation of host immune responses in favor of the pathogen through myriad effects on macrophages including cytokine production, inhibition of phagosome maturation and apoptosis [31-34]. PIMs are oligo-mannosylated PIs carrying up to 6 mannose residues while LM/LAM carry much longer mannose polymers with arabinan modifications. It remains controversial if these glycolipids are embedded in the plasma membrane or exported to the outer membrane. A recent study suggests that LM/LAM appear to be anchored to both the plasma membrane and outer membrane [35]. In
It is notable that some unusual phospholipids have been identified in corynebacteria. APG is an acylated form of PG which is widespread in corynebacteria [37-40], and is a major phospholipid species in
There are some examples of lipids that appear to play no structural roles in the plasma membrane. They often exist in low quantities but play important functional roles. Among these, polyprenol-phospho-sugars function as sugar donors. Two well-studied examples are polyprenol phosphomannose (PPM) and decaprenol phosphoarabinose (DPA). These molecules are the donors of mannose and arabinose, respectively, and their biosynthesis will be discussed in a later section.
PI 3-phosphate, recently identified in both
Carotenoids are photo-protective pigments and serve to scavenge free radicals or harvest light [45]. Several mycobacterial species are known to produce carotenoids with the notable exception of
Neutral lipids are an important reservoir of stored energy and carbon, and their metabolism is closely linked to plasma membrane phospholipid metabolism. Unlike many other bacteria which use polyhydroxyalkanoates as a lipid storage material [47], Actinobacteria use triacylglycerides (TAGs) as a major form of lipid storage, and the presence of TAGs has been reported in
Cholesterol has recently been suggested to be an alternative form of lipid storage in mycobacteria. Neither mycobacteria nor corynebacteria have the capacity to synthesize cholesterol. However, cholesterol is taken up by
Catabolism of cholesterol, amino acids and odd-chain-length/methyl branched fatty acids produces propionyl-coenzyme A (CoA). Propionate accumulation has been shown to be toxic in various organisms [59-61], and
In this section, we will describe the structure and metabolism of various lipids found in the plasma membrane of mycobacteria and corynebacteria in more detail. Lipids are categorized into the following four classes based on their key structural features.
Fatty acid biosynthesis pathways in mycobacteria. Point of inhibition by the front-line tuberculosis drug isoniazid is indicated. Product profile of FAS-I is bimodal, and C16-C18-CoA and C24-C26-CoA are produced. Dashed lines indicate that some of the fatty acid products are further utilized for mycolic acid production.
Surprisingly, members of the Corynebacterineae use a eukaryote-like FAS-I system for
The FAS-II system is commonly found in bacteria and plants and, unlike FAS-I, is composed of a series of separate enzymes, each performing one step in the pathway. FAS-II elongates medium chain fatty acids derived from FAS-I using malonyl-CoA, producing C18-C30 fatty acids [68]. FAS-II has been extensively studied in
β–ketoacyl-ACP reductase MabA reduces the β–keto group with concomitant oxidation of NADPH
β-hydroxyacyl-ACP dehydratase dehydrates the β-hydroxyl to enoyl-ACP
enoyl-ACP reductase InhA, a target of the first-line anti-tuberculosis drug isoniazid (INH) [71], reduces enoyl-ACP to acyl-ACP with concomitant oxidation of NADPH
β-ketoacyl-ACP synthase KasA/B elongates acyl-ACP by 2 carbon units, forming β-ketoacyl-ACP, which can feed back into step 1.
In this way, the hydrocarbon chain increases by 2 carbons each cycle. Further elongation and processing of the products of FAS-II produces the precursors of the long meromycolate chains that are condensed with the α-branches derived from FAS-I by the large polyketide synthase Pks13 [72]. Reduction of the β–keto group by CmrA forms the mature C60-C90 mycolic acid [73].
Glycerolipids include both nonpolar lipids and polar phospholipids. Their biosynthesis is overlapping and 1,2-diacyl-
Glycerolipid/phospholipid biosynthesis pathways. Some pathways such as TAG and PE biosynthesis (shown as green arrows) do not occur in corynebacteria while some others (shown as blue arrows) are known to occur only in corynebacteria. PG is abundant in corynebacteria, but is a minor species in mycobacteria.
The first step of PA biosynthesis is mediated by glycerol phosphate acyltransferase (GPAT) transferring an acyl chain from acyl-CoA to glycerol-3-phosphate, forming acyl-glycerol 3-phosphate. In general, this reaction produces 1-acyl-
TAG is
Under starvation conditions where stored TAG needs to be mobilized for energy production, TAG is catabolized by lipases. In 1977, TAG lipase was purified from stationary phase
In eukaryotes, lipid droplets form in between the two leaflets of the endoplasmic reticulum membrane [88]. In bacteria, a distinct mechanism of lipid body formation has been proposed. For example, in rhodococci, TAG is formed in the cytoplasmic surface of the plasma membrane. Small lipid droplets are then fused to each other, coated by a monolayer of phospholipids, and released from the surface of the plasma membrane into the cytoplasm as mature lipid droplets [89]. Although no endogenous proteins have been found to associate with lipid droplets in rhodococci or mycobacteria, heterologous expression of known lipid droplet-associated proteins resulted in correct targeting of these proteins to lipid droplets in both
In both eukaryotic and prokaryotic cells, PA is activated by CTP to form CDP-DAG, and this reaction is mediated by CDP-DAG synthase [92]. The synthesis of CDP-DAG commits the pathway to phospholipid biosynthesis, and CDP-DAG is a common precursor for the biosynthesis of all glycerophospholipids in mycobacteria and corynebacteria. The activity of CDP-DAG synthetase is associated with plasma membrane in
CL is composed of four acyl chains, three glycerols and two phosphates, and is structured in a 1,3-diphosphatidylglycerol configuration [94]. It is a common phospholipid in bacteria, and is one of the abundant phospholipids in mycobacteria and corynebacteria. To initiate CL synthesis, PG phosphate synthase first produces PG phosphate (PGP) using CDP-DAG and glycerol 3-phosphate as substrates. An
The precise structure of PE was recently reported as 1-
PI is a major phospholipid in both mycobacteria and corynebacteria and forms the anchor for the PIMs, which are substrates for heavy mannosylation to form LMs and additional arabinosylation to produce LAMs. PI is formed by the PI synthase PgsA (Rv2612c) from CDP-DAG and
All Corynebacterineae synthesize PIMs that are important components of the cell envelope. Polar PIM species can also serve as membrane anchors for LM and LAM. Many of the steps of PIM/LM/LAM biosynthesis have now been elucidated [106]. Extensive genetic and biochemical studies have demonstrated that the synthesis of PIMs occurs linearly in mycobacteria with PI as the starting substrate (reviewed in [107]) (Fig. 4A). Early steps of the pathway occur on the cytoplasmic face of the plasma membrane. A PIM biosynthetic membrane, enriched in the early steps, has been purified by sucrose gradient fractionation as a membrane subdomain termed PMf, which is distinct from the bulk plasma membrane [102]. Mannosyltransferases performing the early steps utilize the water-soluble mannose donor, GDP-Man, which can be produced from exogenously acquired mannose or via
Next,
The next enzyme in the pathway, PimC, has been identified in
AcPIM4 species can be further mannosylated to form more polar PIMs in reactions thought to take place on the periplasmic side of the cytoplasmic membrane. These reactions are performed by glycosyltransferases that require a lipid sugar donor in the form of PPM, since these reactions are amphomycin-sensitive [36, 125-128]. In mycobacteria, AcPIM4 is proposed to be a branch point for synthesis of polar PIM end products and LM/LAM. PimE (Rv1159) has been shown to elongate AcPIM4 with one or more α1-2 linked mannoses to form AcPIM6 [36]. This polytopic membrane protein has sequence similarities with eukaryotic PIG-M mannosyltransferases and localizes to a cell wall-associated plasma membrane subdomain in
Surprisingly, studies in
A subpopulation of PIMs (AcPIM4 in mycobacteria [128, 129, 132] and AcPIM2 in corynebacteria [133]) can be extended with chains of α1-6 linked mannose to form LM that is further modified with a number of single α1-2 mannose side chains [134-136]. MptB is a PPM-dependent mannosyltransferase involved in extending AcPIM2 to form the proximal α1-6 mannan backbone of LM in
While the general PI
Summary of Lipoglycan Biosynthesis Pathways in Corynebacterineae. A) The mycobacterial pathway and structures for LM-A/LAM are shown, although several steps are inferred from studies in
Polyprenol phosphate (Pol-P) is a key carrier lipid in synthesis of the core structures of the mycobacterial cell wall, including peptidoglycan and arabinogalactan. Unlike most bacteria, mycobacteria contain multiple types of Pol-P. For example,
PPM, a β-d-mannosyl-1-monophosphoryldecaprenol, is utilized by periplasmic mannosyltransferases for synthesis of polar PIM species and LMs [106]. C35/C50-P-Man
DPA is the only known donor of arabinose (Ara) for mycobacterial cell wall synthesis, contributing Ara
Carotenoids are isoprenoid pigments widely distributed in biology and mostly based on C40-polyene. Synthesis of these pigments has been poorly studied in mycobacteria but they have proven useful for taxonomic and identification purposes. Mycobacterial pigments are generally yellow or orange and most have been confirmed as carotenoids [171]. While carotenoid genetics has been best studied in plants, the key enzymes of the pathway have been identified in bacteria, including mycobacteria [172-174]. There are two classes of carotenoids in bacteria, carotenes and xanthophylls, the latter of which contain oxygen. Both classes are composed of eight isoprenoid units with a long central chain of double bonded carbons. A consensus pathway for carotenoid biosynthesis in bacteria has been elucidated with orthologues of key enzymes identified in several species of mycobacteria [175]. As described above for prenol lipids, the carotenoid pathway begins with isopentenyl diphosphate and dimethylallyl diphosphate derived from the MEP pathway [176]. Head-to-tail condensation of these terpenes produces geranylgeranyl pyrophosphate (GGPP) due to the activity of GGPP synthase (CrtE). Condensation of two GGPP molecules [177] is followed by desaturation to phytoene by phytoene synthase (CrtB). Phytoene desaturase (CrtI) converts phytoene to lycoprene followed by cyclization to β-carotene by lycoprene cyclase (CrtY) [178].
Lipid metabolism in mycobacteria and corynebacteria is a highly complex network of catabolic and anabolic reactions. While the metabolic pathways and many of the enzymes involved have been actively elucidated over the past decade, substantial efforts are still needed to draw a comprehensive map of lipid metabolism in these organisms. In particular, our understanding of regulatory mechanisms of lipid metabolism is currently at an early stage. In addition, there are very few studies describing the interactions between multiple metabolic pathways of lipid biosynthesis. One promising approach for the comprehensive understanding of lipid metabolism is lipidomics, which is the study of lipid biosynthetic and catabolic pathways at a global level [179]. In the past, metabolic pathways have generally been examined in isolation without consideration of how different pathways might interact with, and influence, one another. Since the plasma membrane is a shared platform for most lipid biosynthetic pathways, and some donors are shared between different pathways (see above), it seems unlikely that the various pathways are truly independent. Recent advances in mass spectrometry (
Minimally invasive techniques in pancreatic surgery were initially used only for diagnostic and stadiative purposes, palliative procedures, or the drainage of cysts and the enucleation of small solid lesions [1, 2]. In the last 10 years, with advances in technology and surgical techniques, there has been a growing application of minimally invasive surgery for the treatment of benign and malignant pancreatic neoplasms [3], and complex operations such as distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) have started to be performed [2]. Laparoscopic distal pancreatectomy (LDP) does not require the execution of anastomosis, resulting in quite easy performance and achieving worldwide acceptance. On the other hand, the laparoscopic pancreaticoduodenectomy (LPD) has obtained a marginal acceptance until now, raising doubts about its safety and reproducibility, due to its technical complexity and prolonged operating time [3].
Although the first LPD was performed by Gagner and Pomp more than 20 years ago for the treatment of a chronic pancreatitis involving the pancreatic head [4], the procedure had a slow diffusion [5], especially in comparison to the other applications of minimally invasive surgery in the field of oncological treatment [3].
This slow diffusion can be explained by three main reasons.
The first one is the technical complexity of LPD, especially due to the retroperitoneal position of the pancreas and the proximity to the duodenum and surrounding vascular structures; the fashioning of the laparoscopic anastomoses; and the laparoscopic dissection of the uncinate process from the large vessels [6, 7, 8].
The second one is the high complication rate of PD, heavily affecting postoperative recovery; this represents a limit to the potential advantages of mini-invasiveness [9].
Finally, there is a lack of international consensus about the benefits regarding the feasibility and oncological efficacy of LPD [10].
However, in the last decade, the growing number of publications about laparoscopic pancreatic surgery seems to assess its feasibility and safety [3], especially if performed in highly experienced centers [11].
In all the cases where PD is indicated, laparoscopic approach can be theoretically applied:
pancreatic adenocarcinoma
symptomatic chronic pancreatitis
neuroendocrine pancreatic tumors: functioning tumors, tumors with resectable metastases, tumors with diameters >2 cm, symptomatic nonfunctioning tumors, G3 with Ki67 > 20%, and neuroendocrine carcinoma
cystic pancreatic tumors
IPMN with high-risk stigmata (dilation of the Wirsung ≥10 mm, contrast-enhancing solid intracystic component ≥5 mm, causing obstructive jaundice, with positive cytology)
malignant tumors of the distal common bile duct
malignant tumors of the ampulla of Vater
malignant tumors of the duodenum
Since the learning curve for LPD is long, patients should be adequately selected. As reported in the literature [12], it is preferable to start with patients with low BMI and small ampullary tumors, duodenal adenocarcinomas, or tumors of the distal biliary tract and avoid ductal pancreatic adenocarcinomas because of their infiltrative nature.
Accurate selection of patients is essential to decrease the rate of conversion and avoid unnecessary laparoscopic attempts, which would only increase the operative time and the risk of intraoperative complications.
Suggested contraindications to LPD are significant comorbidities [1, 2, 13, 14, 15], previous upper-mesocolic abdominal surgeries [1, 14, 16, 17], and high BMI [17, 18].
On the contrary, age does not seem to be a contraindication. A study by Buchs et al. [13] compared LPD in patients younger and older than 70 years: post-operative outcomes in the two groups were similar, showing that age alone may not be a selection criterion for LPD.
Current studies about LPD are subject to high selection bias, since most centers are still in the learning curve and selecting only ideal candidates for the procedures.
A recent review by Wang et al. [19] analyzed studies that evaluated inclusion and exclusion criteria for mini-invasive PD, reporting 14 studies that only mentioned inclusion criteria, 20 that only mentioned exclusion ones, and 13 that reported both. This review showed that patients selected for LPD had small peri-ampullary tumors and low BMI. The most frequent contraindications were vascular invasion, previous upper-mesocolic procedures, and severe cardiovascular disease.
Indications and contraindications to LPD also depend on the experience of the surgical team [12]; with increased experience, it may also be performed for the treatment of tumors involving surrounding organs or vascular structures, and almost all contraindications to LPD may become relative. In this scenario, some pioneering groups have also started performing venous resections during LPDs [7, 8].
However, the majority of authors consider as exclusion criteria: large tumors [1, 16], chronic pancreatitis, tumors involving the superior mesenteric-portal vein confluence, the superior mesenteric artery or the hepatic artery [12, 13], and neoadjuvant radio-chemotherapy [20, 21], due to the local fibrosis caused by radiotherapy.
Many algorithms have been developed to help with LPD patient selection [22, 23].
Currently, there is no consensus on the best surgical option for LPD, neither for the demolitive phase nor for the reconstructive one.
Differences in the surgical technique concern as follows:
Preparatory phase: trocar placement, type of trocar used, access technique to peritoneum.
Demolitive phase: surgical steps, devices and materials, pylorus preservation or not.
Reconstructive phase: type of suture, anastomosis technique, surgical specimen extraction, drainages, stent placement in pancreatic duct to protect the pancreatico-jejunal anastomosis.
The number, type, and placement of trocars for LPD vary greatly throughout the literature. Most authors use 5 trocars (52.1%) [1, 24, 25]; some use 6 (30.4%) [26, 27]; more rarely, 4 [28, 29] or 7 [16] are used.
Pneumoperitoneum is usually induced using the “open” technique according to Hasson in periumbilical or supra-umbilical position [20, 24, 26, 28, 30], while rarely the “closed” technique with the Veress needle is used [1, 16, 27, 29].
Trocar placement varies between series, especially concerning the optic port and the port for the hepatic retractor. The optic port is more commonly placed in the umbilical region (41.7%). The port for the hepatic retractor is, in many cases, placed along the midline in the subxiphoid region, while in some cases, it is placed along the right anterior axillary line, just under the hepatic ridge.
Boggi et al. [31] published a systematic review that analyzed various aspects of the demolitive phase. Their results are summarized in this section.
Concerning materials, the majority of authors used energy devices (678 patients, 90.8% of cases). Some authors used a single energy device (in 10 cases ultrasonic shears, in 4 cases radiofrequency), while 8 used a dual energy device (6 ultrasound and radiofrequency, 1 ultrasound and bipolar, 1 ultrasound and monopolar).
The section of the pancreatic neck can be done using the ultrasonic shears, the electrocautery (104 patients, 15.9%), the stapler or ultrasonic shears (100 patients, 15.3%), electrocautery or ultrasonic shears (65 patients, 9.9%), only stapler (12 patients 1.8%), or only radiofrequency (6 patients, 0.9%) (Figures 1–3).
Retropancreatic tunnel.
Pancreatic neck section using ultrasonic shears.
Pancreatic neck section using ultrasonic scissors.
The method used to section the gastroduodenal artery is another relevant technical aspect, since the arterial stump is a frequent site of bleeding in case of pancreatic fistula.
In the majority of cases (274 patients, 54.5%), the use of clips was reported, while some authors (100 patients, 19.9%) reported only ligature. Other options are vascular stapler plus suture (1 article, 50 patients, 9.9%), clips plus suture (1 article, 35 patients, 6.9%), vascular stapler only (1 article, 24 patients, 2.7%), and radiofrequency only (1 article, 11 patients, 2.1%) (Figures 4 and 5).
Gastroduodenal artery closure using clips.
Gastroduodenal artery closure using vascular stapler.
The specimen is often extracted via an umbilical (42.2%), supra-pubic (15.7%), or subxiphoid (15%) mini-laparotomy; other sites for extraction are sub-umbilical (8.9%), the right inferior quadrant (8.8%), or supraumbilical (4.9%) one.
Finally, the surgeon must decide whether to preserve the pylorus (Traverso-Longmire intervention) or resect the gastric antrum (classic Whipple procedure).
Pylorus-preserving surgery is more commonly performed (55%) than gastric antrum resection among 21 authors (636 patients), 6 always preserve the pylorus (262 patients, 41.1%), 8 always section the gastric antrum (13 patients, 17.7%), while 7 used both techniques (261 patients, 41%).
Pylorus preservation in oncological cases is a controversial topic; it was compared with the Whipple technique without significant differences between the two techniques in terms of overall survival (
There is a lack of data about laparoscopic “artery first approach” to PD and total mesopancreas excision (TMpE), because no details about this important topics were reported in the literature.
Great variability in the reconstructive phase is reported in the literature, both in materials (type of suture) and in fashioning anastomoses.
The management of the pancreatic stump represents one of the most important steps of the entire procedure [33, 34], especially when dealing with a soft gland, as it is one of the main risk factors for the development of a POPF [35, 36].
Pancreaticojejunostomy (PJ; 84% of cases; Figures 6 and 7) and pancreaticogastrostomy (PG; 9.8% of cases) are the most commonly performed anastomoses; on the other hand, the duct occlusion has mostly been abandoned (6.8% of cases) [31].
Duct-to-mucosa anastomosis.
Pancreato-jejunal anastomosis.
In order to reduce the risk of POPF, the majority of the authors (72.8%) positioned a stent in the Wirsung, either routinely or selectively; the pancreatic anastomosis was in most cases performed with a double layer (90.6%) and interrupted sutures (74.6%).
The gastro/duodenal-jejunal (GJ/DJ) anastomosis was antecolic in 76.3% of cases (Figure 8), retromesenteric in 13.4% of cases, and retrocolic in 10.2% of cases.
Antecolic gastro-jejunal anastomosis.
The majority of GJ and DJ anastomoses were handsewn (
In a randomized multicentric study on 440 patients, Keck et al. [37] compared the outcomes of PG vs. PJ: although POPF rate was 20%, without significant differences between the two techniques, the rate of anastomotic bleeding was higher for PG.
Surprisingly in a meta-analysis [38] based on 676 patients underwent to PD, a significantly lower rate of POPF was found in favor of PG, while there were no differences in the incidence of BL, PPH, or DGE between the two anastomoses.
Despite the technical and technological progress made in recent years, postoperative morbidity for PD remains high (30–50%) [39].
The most frequent postoperative complications for PD are DGE (19–23% of cases), POPF (9–18%), intra-abdominal abscess (9–10%), and intra-abdominal or GI bleeding (1–8%) [40].
Many authors questioned the possibility to improve postoperative outcomes through the use of mini-invasiveness.
Compared to open PD, LPD has been found to require longer operative time [30, 41, 42, 43] (Tables 1 and 2); however, it leads to
reduce intraoperative blood loss and the need for transfusions [6, 26, 30, 41, 43, 44, 45]
reduce postoperative pain [30]
reduce intensive care unit (ICU) monitoring [42].
reduce length of hospitals stay (LOS) [6, 30, 41, 42, 43, 45, 46] with differences varying between 2 and 5 days.
reduce number of unscheduled readmissions [46].
Thirty-day mortality and morbidity, including POPF, DGE, PPH, BL, and surgical site infection (SSI), are comparable between laparoscopic and open PD [30, 42, 43, 44, 45, 46, 47].
Author | Year | No of patients | Operative time (min) | Intraop blood loss (ml) | Postop LOS (days) | 30-days mortality | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
VL | Op | VL | Op | VL | Op | VL | Op | VL | Op | ||
Stauffer | 2016 | 58 | 193 | 375 | 518 | 250 | 600 | 6 | 9 | — | — |
Sharpe | 2015 | 384 | 4037 | nr | nr | nr | nr | 10 | 12 | 5.2 | 3.7 |
Song | 2015 | 104 | 576 | 482 | 348 | 570 | 609 | 14 | 19 | — | — |
Speicher | 2014 | 25 | 84 | 381 | 326 | 200 | 425 | 8 | 10 | — | 1.2 |
Dokmak | 2014 | 46 | 46 | 342 | 264 | 368 | 293 | 23 | 25 | 2 | — |
Croome | 2014 | 108 | 214 | 379 | 387 | 492 | 866 | 6 | 9 | 1 | 2 |
Mesleh | 2013 | 75 | nr | 551 | nr | nr | nr | 7 | nr | — | nr |
Asbun | 2012 | 53 | 215 | 541 | 401 | 195 | 1032 | 8 | 12 | 5.7 | 8.8 |
Postoperative outcomes: comparison between laparoscopic and open PD.
Abbreviations: N, number; min, minutes; Intraop, intraoperative; Postop, postoperative; VL, laparoscopic; Op, open.
Author | Year | Compl rate (CD > 3) | POPF rate | PPH rate | Median | R0 rate | Reop rate | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
VL | Op | VL | Op | VL | Op | VL | Op | VL | Op | VL | Op | ||
Stauffer | 2016 | 22 | 30 | 8 | 9 | 7 | 4 | 27 | 17 | 80 | 84 | 2 | 6 |
Sharpe | 2015 | nr | nr | nr | nr | nr | nr | 16 | 18 | 80 | 74 | nr | nr |
Song | 2015 | 7.5 | 5.4 | 6.5 | 6.5 | nr | nr | 15 | 16 | 72 | 81 | nr | nr |
Speicher | 2014 | nr | nr | 16 | 22.6 | nr | nr | 14.5 | 12 | 83.3 | 78.6 | 8.7 | 10.7 |
Dokmak | 2014 | 28 | 20 | 44 | 32 | 24 | 7 | 20 | 23 | 60 | 50 | 24 | 11 |
Croome | 2014 | 6 | 14 | 11 | 12 | 7 | 6 | 21.4 | 20.1 | 77.8 | 76.6 | nr | nr |
Mesleh | 2013 | 31 | 31 | 9 | 6 | nr | nr | nr | nr | nr | nr | 2 | 4 |
Asbun | 2012 | 24.5 | 24.7 | 7.1 | 5.1 | 9.4 | 5.6 | 23.4 | 16.8 | 95 | 83 | 3.8 | 7 |
Postoperative outcomes: comparison between laparoscopic and open PD.
Abbreviations: Compl, complication; CD, Clavien-Dindo; POPF, postoperative pancreatic fistula; PPH, postpancreatectomy hemorrage; LNs, lymph nodes; Reop, reoperation; VL, laparoscopic; Op, open.
Regarding oncological radicality, laparoscopic PD appears to be at least noninferior to open PD.
Considering tumors of similar size and histological type, the number of harvested lymph nodes and the rate of negative resection margins have been found to be either comparable [20, 30, 45, 46, 48] between laparoscopic and open PD or superior in laparoscopic PD [6, 26, 41, 42, 43].
Overall survival between laparoscopic and open PD is comparable [6, 30, 45]. However, the reduction in postoperative pain and physical impairment, paired with the reduced rate of surgical site complications, may allow for a broader access to adjuvant chemotherapy and an earlier start of treatment in patients who underwent laparoscopic PD [11, 49].
Current studies comparing laparoscopic PD vs. open PD have been criticized because they may suffer from selection bias, as many of them excluded patients with vascular involvement, high intraoperative risk, and multiple previous abdominal operations, all of which have higher chances of undergoing an open procedure.
However, the results from Croome et al. [6] and the review from Wang et al. [43] showed promising results also in complex cases, which required vascular resections.
The learning curve for LPD is particularly steep and represents an obstacle to a more widespread use of the procedure; it seems that learning curve can be shortened with specific training strategies, e.g., ex vivo training, proctoring, and simulation in loco.
The majority of studies about surgical learning curves define it as the number of procedures needed to achieve a decrease in operative time and blood loss and in the number of conversions.
With increased experience in those kinds of procedures, the surgeon is also able to deal laparoscopically with more technical complex situations, such as vascular resections (portal, mesenteric, and arterial), without increasing postoperative complications.
As shown in the review published by De Rooij et al. [12], there are three strategies to learn how to carry out PD completely laparoscopically (i.e., not only the demolitive phase, which is more commonly performed laparoscopically, but also the reconstructive one, which represents a considerable obstacle for some).
The first strategy consists of tutoring. The second one is a hybrid approach, i.e., performing the demolitive phase through laparoscopy and the reconstructive phase through a service minilaparotomy. The third one is also a hybrid approach, but the reconstructive phase is carried out robotically.
Each strategy has its own learning curve and needs to be performed only in specialized centers with high volumes of pancreatic surgeries to avoid unnecessarily high rates of morbidity and mortality. Recent studies suggest that using hybrid techniques before performing the procedure completely laparoscopically might be useful. A cut off of 10 hybrid procedures is considered enough to start with full laparoscopy, although 50 hybrid procedures are required for significant improvements in operative outcomes to appear/significant improvements in operative outcomes appear after 50 hybrid procedures.
A study by Speicher et al. [41] shows that laparoscopic PD’s learning curve goes through a slow and difficult initial phase (first 10 cases), a much faster improvement phase (10–20 cases), and finally a plateau with a slow but steady improvement with time (after 50 cases).
However, these considerations can only be applied to surgeons with great expertise in open PD and in advanced laparoscopic surgery; it is often difficult to satisfy both conditions, as many centers with high volumes of pancreatic surgeons do not have high volumes of laparoscopic surgery and vice versa.
Many years are required to overcome the learning curve and reach an adequate outcome level [50]. Pancreatic surgery should be centralized in dedicated centers, as this has been shown in many studies to improve outcomes [51, 52].
A review by Gumbs et al. [53] that analyzed 285 LPDs shows that the length of hospital stay and the operative time for the procedure decrease proportionally to the higher volume of cases of the center.
Different studies show that, as one moves along the learning curve, there is a decrease in operative time, blood loss, morbidity, and open conversions, resulting in a reduced length of hospital stay.
Kim et al. [24] analyzed 100 consecutive cases of pylorus-preserving LPD, of which all performed by the same surgeon and divided them in three time periods. With increased experience, operative time decreased from 9.8 hours in the first-time period to 6.6 in the third. Length of hospital stay went from 20.4 to 11.5 days. Morbidity, including pancreatic fistula, intraoperative bleeding, delayed gastric emptying, and ileus, decreased from 33.3 to 17.6%.
Similar results, demonstrating an improvement in the surgical outomes increasing the learning curve, also reported by Speicher et al. [41], with diminished operative time and blood loss with increased experience, and Song et al. [30].
Song et al. divided LPD’s cases into two cohorts (the first 47 consecutive cases vs. the next 50 cases). The second cohort had decreased operative time (399.4 vs. 566.5 minutes,
Another cohort study shows that rates of postoperative pancreatic fistulas diminished from 36 to 18% after only 11 LPDs [1]. Other study also confirmed that morbidity is inversely proportional to the number of procedures performed in a single center [9, 20, 30].
Mortality also decreased with an increase in experience [54]; analyzing a national database with over 7000 patients who underwent PD from 2010 to 2011, higher 30-day mortality with LPD than with open PD was found. However, this result only applied to those centers with less than 10 LPDs in 2 years, where 30-day mortality was twice that of open PD. In centers with more than 10 LPDs, 30-day mortality was similar in laparoscopic and open procedures.
The dramatic improvement shown by these authors as they progress along the learning curve is encouraging and may bring much more surgeons to perform PD laparoscopically.
Most of the financial benefit of laparoscopic vs. open PD is attributed to the reduced length of hospital stay [15, 17, 20, 30]. However, laparoscopy significantly increases operative time (usually by 2 hours) [30] and requires expensive materials with an increase in cost of 35%,
Speicher et al. and Mesleh et al. compared open vs. laparoscopic PD costs [41, 44]. They concluded that total costs were comparable. According to Speicher et al. [41], laparoscopic PD costs 24,590 dollars vs. 19,720 dollars in open technique (
According to Mesleh et al. [44], laparoscopic PD is significantly more expensive (
Morbidity and postoperative length of hospital stay were comparable and did not influence the overall cost. However, the post-operative management for open PD is slightly more expensive than laparoscopic PD when single categories are taken into account (expenses for nursing, anaesthesia, drugs, labs, and imaging).
As recovery expenses represent 65–70% of the overall cost, the decreased postoperative cost of laparoscopic PD balances out its increased intra-operative cost when compared to open PD.
LPD is a safe, standardizable, and oncologically adequate surgical technique, but only if performed by surgeons with extensive experience both in pancreatic surgery and in laparoscopy and, at least at the beginning of the learning curve, on appropriately selected cases.
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Culture scholars argue that organizational culture—commonly defined as the beliefs, values, attitudes, and practices of the members of an organization—is a powerful force in determining the health and well-being of an organization. Scholars also suggest the existence of different dimensions of organizational culture. Although they do not agree in naming these dimensions, commonalities are found in their understanding. How organizational culture is practiced by the frontline bureaucrats in Bangladesh has not been studied much. A study was designed to know how the frontline public bureaucrats practice organizational culture and how they differ in their practices along their service lines. Four dimensions of organizational culture—power distance, uncertainty avoidance tendency, participation, and team orientation—were considered. The chosen culture dimensions impact the overall management of any public sector organization. Three hundred and twenty-six frontline public bureaucrats were studied using a survey questionnaire. Both descriptive and inferential statistics have been used for analyzing the collected data. Findings from independent samples t-tests revealed that the frontline bureaucrats significantly differ along their service lines in practicing the culture dimensions.",book:{id:"7807",slug:"a-closer-look-at-organizational-culture-in-action",title:"A Closer Look at Organizational Culture in Action",fullTitle:"A Closer Look at Organizational Culture in Action"},signatures:"Md. Morshed Alom",authors:[{id:"314259",title:"Ph.D.",name:"Md. Morshed",middleName:null,surname:"Alom",slug:"md.-morshed-alom",fullName:"Md. 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The chapter focuses on the importance of creating shared organizational culture on the basis of four communication conditions from social interaction theory. (1) In communicative processes, senders need to secure the attention of audiences. (2) Senders and audiences need to have a sufficiently similar understanding of the language that is used. (3) Senders and audiences need to interpret communicative acts in a sufficiently similar way. (4) The attitudes and values that audiences ascribe to senders must correspond to the values and attitudes that senders actually have. After having clarified these conditions, the chapter applies them to analyse fundamental organizational challenges. The final part of the chapter argues that the conditions can, typically on management levels, constitute conceptual tools for creating unifying communicative cultures. Furthermore, using the conditions (1)–(4) actively as a means for securing communication across a diversity of individual perspectives can contribute to reaching organizational goals, no matter how they are defined.",book:{id:"7807",slug:"a-closer-look-at-organizational-culture-in-action",title:"A Closer Look at Organizational Culture in Action",fullTitle:"A Closer Look at Organizational Culture in Action"},signatures:"Halvor Nordby",authors:[{id:"212169",title:"Prof.",name:"Halvor",middleName:null,surname:"Nordby",slug:"halvor-nordby",fullName:"Halvor Nordby"}]},{id:"72534",title:"Effects of Information Technologies on Organizational Culture: A Discussion Based on the Key Role of Organizational Structure",slug:"effects-of-information-technologies-on-organizational-culture-a-discussion-based-on-the-key-role-of-",totalDownloads:1063,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter discusses the influences of information technologies on cultural features of organizations with an emphasis on the concept of “organizational structure” because research shows that organizational culture and organizational structure are in a very close relationship. In this regard, it argues that information technologies can have direct and indirect effects on organizational cultures based on the information technologies’ influences on organizational structures and the processes, activities, and human relations within these structures. Underlining different and controversial approaches and findings in the literature, this study makes some deductions by referring to important features of information technologies and organizational culture. Therefore, the approaches and evaluations given here are thought to be useful for the practitioners and students who are interested in the subject and the academic staff who are interested in doing research on this subject.",book:{id:"7807",slug:"a-closer-look-at-organizational-culture-in-action",title:"A Closer Look at Organizational Culture in Action",fullTitle:"A Closer Look at Organizational Culture in Action"},signatures:"Eser Erdurmazlı",authors:[{id:"318514",title:"Ph.D.",name:"Eser",middleName:null,surname:"Erdurmazlı",slug:"eser-erdurmazli",fullName:"Eser Erdurmazlı"}]}],onlineFirstChaptersFilter:{topicId:"443",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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