Orlin Belyaev

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial

BACKGROUND The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. METHODS This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. FINDINGS Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. INTERPRETATION Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. FUNDING German Federal Ministry of Education and Research.

Improving outcomes in hernia repair by the use of light meshes--a comparison of different implant constructions based on a critical appraisal of the literature.

BackgroundDespite convincing advantages offered by meshes, their use in hernia surgery remains controversial because of fears concerning the long-term effects of their implantation. To improve biocompatibility, a large variety of newly developed light meshes has been introduced to the market.This overview of the literature aimed to establish whether absolute material reduction (g per implanted mesh), use of absorbable components, and coating by inert materials are evidence-based ways to improve biocompatibility of meshes.MethodA review of the current English and German language literature on the outcome of groin und incisional hernia mesh repair was performed. Both basic research and clinical trials were used as sources of data. Meta-analyses and randomized controlled trials were given priority and were referred to whenever possible.ResultsOperative technique was an independent prognostic factor for the clinical outcome. Mesh construction and composition as characterized by pore size and filament structure appeared to be more important determinants of foreign body reaction after implantation than absolute material reduction of 1 g or more per implant. No data exist about an oncogenic effect of alloplastic materials in humans, but disturbed fertility in animal studies remains an issue of concern and should be further investigated.ConclusionsAccording to data from current randomized controlled trials and retrospective studies, light meshes seem to have some advantages with respect to postoperative pain and foreign body sensation. However, their use is associated with increased recurrence rates. Light meshes offer no advantages with respect to alleviating severe chronic groin pain. At the same time, experimental data reveal that material composition and mesh structure may significantly affect foreign body reaction.

Partial Pancreatectomy in Adult Humans Does Not Provoke β-Cell Regeneration

OBJECTIVE—β-Cell regeneration has been proposed as a possible treatment for diabetes, but the capacity for new β-cell formation in humans is yet unclear. In young rats, partial pancreatectomy prompts new β-cell formation to restore β-cell mass. We addressed the following questions: In adult humans: 1) Does partial pancreatectomy provoke new β-cell formation and increased β-cell mass? 2) Is β-cell turnover increased after partial pancreatectomy? RESEARCH DESIGN AND METHODS—Protocol 1: human pancreatic tissue was collected from 13 patients who underwent two consecutive partial pancreas resections, and markers of cell turnover were determined in both tissue samples, respectively. Protocol 2: pancreas volumes were determined from abdominal computer tomography scans, performed in 17 patients on two separate occasions after partial pancreatectomy. RESULTS—Protocol 1: fasting glucose concentrations increased significantly after the 50% pancreatectomy (P = 0.01), but the fractional β-cell area of the pancreas remained unchanged (P = 0.11). β-Cell proliferation, the overall replication index (Ki67 staining), and the percentage of duct cells expressing insulin were similar before and after the partial pancreatectomy. The overall frequency of apoptosis (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) was slightly increased following the partial pancreatectomy (P = 0.02). Protocol 2: pancreatic volume was ∼50% reduced to 35.6 ± 2.6 ccm3 by the partial pancreatectomy. The total pancreatic volume was unchanged after an interval of 247 ± 160 days (35.4 ± 2.7 ccm3; P = 0.51). CONCLUSIONS—Unlike in rodents, a 50% pancreatectomy does not prompt β-cell regeneration in adult humans. This explains the high incidence of diabetes after pancreatic resections. Such differences in β-cell turnover between rodents and humans should be born in mind when evaluating new treatment options aiming to restore β-cell mass in patients with diabetes.

Experimental comparison of monofile light and heavy polypropylene meshes : Less weight does not mean less biological response

BackgroundMesh implantation is a standard procedure in hernia repair. It provides low recurrence rate but increases complication rate due to foreign-body reaction induced by alloplastic materials in surrounding tissues. It is believed that biocompatibility of meshes may be improved by reducing their weight per meter squared (m2) and altering the implant structure.AimThe aim of this study was to evaluate the effect of weight and structure as determinants of mesh biocompatibility.MethodThirty-six Wistar rats were studied. In 12 animals, conventional polypropylene (heavy) meshes (HM) were implanted; in other 12, material-reduced (light) microporous polypropylene meshes (LM); and the remaining 12 served as a sham-operated control group. Meshes were explanted after 21 and 90 days (6 animals per group). All samples were examined by light and electron microscopies. Integration of meshes in surrounding tissue, inflammatory response, fibrotic reactions, and structural changes were recorded. Quantification of the inflammatory response was achieved by CD-68 marking of macrophages and counting their number per surface unit.ResultsAfter 21 days, there was no significant difference in thickness of surrounding connective tissue between meshes in all groups studied. After 90 days, thickness of connective tissue decreased in both groups, and fibrotic reaction in the mesh bed was significantly less in the HM group. Total amount of macrophages per millimeter squared (mm2) decreased with time in HM and LM samples but was significantly lower in the HM group on day 21 (43.5%) and day 90 (46.7%).ConclusionThis study found worse biocompatibility of LM compared with HM. Thus, the amount of implanted mesh was not the main determinant of biocompatibility (expressed as successful incorporation and diminished foreign-body reaction) but the size of the pores.

Reduced Pancreatic Volume and β-Cell Area in Patients With Chronic Pancreatitis

BACKGROUND & AIMS Chronic pancreatitis (CP) often leads to the development of diabetes. To understand better this pathogenic mechanism, we investigated whether islet cell area and pancreatic volume are reduced in CP patients, islet cell turnover increases in CP patients, and islet cells are less vulnerable to apoptosis than acinar cells. METHODS Pancreatic tissues from 43 patients with CP and 27 controls were examined by immunohistochemistry and quantitative morphometry. Pancreas volume was determined using abdominal computed tomography data. RESULTS The pancreatic volumes were 64.9 +/- 4.3 cm(3) in CP patients and 82.3 +/- 6.7 cm(3) in controls (P = .035). beta-cell areas were 0.69% +/- 0.08% in CP patients and 0.97% +/- 0.08% in controls (P = .017), whereas alpha-cell areas did not differ between the groups (P = .47). There were no differences in the frequencies of replication among groups of alpha-cells, beta-cells, duct cells, or acinar cells nor were there differences in numbers of apoptotic alpha-cells or beta-cells between CP patients and controls. However, CP patients had an approximately 10-fold increase in numbers of apoptotic acinar cells compared with controls (P < .0001). CONCLUSIONS Pancreatic volume was reduced by 21%, and the area comprising beta-cells was reduced by 29% in patients with CP. The lack of increased beta-cells turnover in CP patients, despite an approximately 10-fold increase in the number of apoptotic acinar cells, suggests that the damage to the pancreas is highly specific for the exocrine compartment and affects the endocrine islets to a lesser extent.

Indications and early outcomes for total pancreatectomy at a high-volume pancreas center.

Background. This study aimed to analyse the most common current indications for total pancreatectomy (TP) at a high-volume pancreas center. Method. Prospectively collected data on indications and short-term outcome of all TPs performed from January 2004 until June 2008 were analysed. Results. The total pancreatectomies (TP) were 63, i.e., 6.7% of all pancreatic procedures (n = 948). Indications for TP were classified into 4 groups: tumors of advanced stage, n = 23 (36.5%), technical problems due to soft pancreatic tissue, n = 18 (28.6%), troubles due to perioperative surgical complications, n = 15 (23.8%), and therapy-resistant pain due to chronic pancreatitis, n = 7 (11.1%). Surgical complications occurred in 23 patients (36.5%). The mortality in elective TP was 6.25%. Median postoperative stay was 21 days. Mortality, morbidity and the other perioperative parameters differed substantially according to the indication for pancreatectomy. Conclusion. Total pancreatectomy is definitely indicated for a limited range of elective and emergency situations. Indications can be: size or localisation of pancreatic tumor, trouble, technical diffuculties and therapy-refractory pain in chronic pancreatitis. A TP due to perioperative complications (troubles) after pancreatic resections is doomed by extremely high morbidity and mortality and should be avoided.

Amino acid malnutrition in patients with chronic pancreatitis and pancreatic carcinoma.

Objectives: Chronic pancreatitis (CP) and pancreatic cancer (CA) have been associated with intestinal malabsorption and inflammation. However, little is known about the changes in amino acid metabolism in such patients. Methods: The circulating amino acid levels were determined in 12 patients with CP, 12 CA patients, and 12 controls. Results: Total amino acid concentrations were 2850 ± 71 &mgr;mol/L in controls, 2640 ± 96 &mgr;mol/L in CP patients, and 2210 ± 123 &mgr;mol/L in CA patients (P < 0.001). In CP patients, significant reductions in the concentrations of citrulline, &ggr;-aminobutyric acid, taurine, and aspartic acid were found (P < 0.05), whereas in CA patients, the levels of phosphoethanolamine, &ggr;-aminobutyric acid, aspartic acid, taurine, arginine, threonine, alanine, citrulline, and tryptophan were reduced. There was a significant inverse relationship between the total amino acid levels and the white blood cell counts (r = −0.44, P = 0.008). Conclusions: Both patients with CP and with CA exhibit alterations in amino acid levels. The mechanisms underlying these defects may involve intestinal malabsorption as well as systemic inflammation. Providing selective amino acid supplementation to such patients may minimize the excess morbidity and mortality associated with protein malnutrition.

Intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are now a well-recognized category of slowly growing tumors with a remarkably better prognosis, even when malignant, than pancreatic ductal adenocarcinoma. Their clinical and pathohistologic features have been increasingly attracting the attention of clinicians since their first description 25 years ago. Despite its burgeoning volume recently, accumulated literature devoted to IPMN still provides a low level of evidence with regard to diagnosis, treatment, and prognosis. Therefore, we performed a Medline-based systematic review of the literature aimed at clearly defining the clinicopathologic characteristics of pancreatic IPMN and determining the best currently available evidence-based principles of diagnosis and management of patients with this disease.

Neosphincter Surgery for Fecal Incontinence: A Critical and Unbiased Review of the Relevant Literature

Up until about 15 years ago the only realistic option for end-stage fecal incontinence was the creation of a permanent stoma. There have since been several developments. Dynamic graciloplasty (DGP) and artificial bowel sphincter (ABS) are well-established surgical techniques, which offer the patient a chance for continence restoration and improved quality of life; however, they are unfortunately associated with high morbidity and low success rates. Several trials have been done in an attempt to clarify the advantages and disadvantages of these methods and define their place in the second-line treatment of severe, refractory fecal incontinence. This review presents a critical and unbiased overview of the current status of neosphincter surgery according to the available data in the world literature.

Role of endogenous glucocorticoid metabolism in human acute pancreatitis

Objective:This study aimed to observe how levels of total cortisol, calculated free cortisol, corticosteroid-binding globulin, and adrenocorticotropic hormone change during the early course of human acute pancreatitis and to describe how these changes affect the development of pancreatic necrosis. Design and Patients:In a total of 109 consecutive patients with acute pancreatitis (74 with edematous pancreatitis, 35 with necrotizing pancreatitis), serial daily blood monitoring of total and free cortisol, adrenocorticotropic hormone, and corticosteroid-binding globulin was done after hospital admission, up to day 6 after the onset of pain; 30 healthy individuals served as controls. Measurements:Corticosteroid-binding globulin and total cortisol were measured by immunoassays, and free cortisol was calculated according to Coolens et al. The adrenocorticotropic hormone was measured with an enzyme-linked immunoassay. Results:Initially, highly elevated levels of calculated free cortisol (median, 86.2 ng/mL; quartile ranges, 50.6–106.7 ng/mL) and total cortisol (41.2 &mgr;g/dL, 30.4–51.1 &mgr;g/dL) and depressed levels of adrenocorticotropic hormone (0.2 pg/mL, 0.1–2.0 pg/mL) and corticosteroid-binding globulin (30.6 &mgr;g/mL, 24.1–35.5 &mgr;g/mL) were observed. Further, daily measurements revealed increasing adrenocorticotropic hormone levels, whereas cortisol levels decreased. Conclusions:Although an increase in adrenocorticotropic hormone levels is suggested to increase corresponding cortisol levels, cortisol levels decreased during the development of necrotizing acute pancreatitis. This phenomenon, along with the continuously decreasing corticosteroid-binding globulin levels, brings up the hypothesis of a relative adrenal insufficiency, which favors acinar cell apoptosis and hence may trigger the development of necrosis in the initial vulnerable phase of acute pancreatitis.