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Background Laparoscopic Cholecystectomy and bile duct exploration remain the gold standard treatment for gallstone disease associated with bile duct stones. However, interval two session management with ERCP followed by Laparoscopic Cholecystectomy should be avoided. It exposes patients to preventable risk of perforation, bleeding, and pancreatitis, especially if the patient is fit and keen for surgery. Trans-Cystic bile duct exploration (TC BDE) appears to have less morbidity than Trans- Ductal bile duct exploration (TD BDE). However, large bile duct stones remain the main challenge for Trans-Cystic approach along with distorted anatomy. Methods We present a 48-year-old female with symptomatic gallstone disease and a complex past surgical history. Results Trial of ERCP failed despite Needle-knife papillotomy due to large mobile and hard papilla. Unfortunately, the patient suffered post ECRP pancreatitis that was complicated by an abdominal collection around the head of the pancreas. The collection required radiologic drainage through the anterior abdominal wall, 13 days post-pancreatitis. The patient recovered well and was listed for a Laparoscopic Cholecystectomy and bile duct exploration with high risk of conversion to open, 6 weeks after discharge. The operation was challenging due to presence of adhesions and shrunken gallbladder (Nassar grade IV). Trans-Cystic BDE was performed using basket inside catheter (BIC) technique. SpyGlass™ Discover choledochoscopy showed a clear distal CBD and a large 12mm stone in the common hepatic duct. The stone was hard and required a high setting of lithotripsy (30, Max). The stone was fragmented successfully, and all fragments extracted using baskets. The cystic duct was closed by suturing using 3.0 Vicryl and two Robinson abdominal drains were left in the abdomen; one in Morrison's pouch and one in the sub-diaphragmatic space. The patient had an uncomplicated post-operative recovery and was discharged home after 5 days. Follow-up 8 months later was satisfactory. Conclusions Trans-Cystic bile duct exploration has become increasingly safe and feasible even for large bile duct stones using new technology. ERCP should be avoided in young fit patients, especially females due to the higher risk of post-ERCP pancreatitis.

Aim Formalin-embalmed cadavers have traditionally been used as an integral part of anatomy teaching and surgical training. Cadaveric tissue can, however, be compromised by distorted appearance, shrinkage, rigidity and unnatural colouration. The Thiel embalming process produces more ‘life-like’ specimens and it could be postulated that these may be more suitable for surgical training. This study aimed to provide quantifiable and repeatable measurements for the mechanical tissue properties of Thiel embalmed cadavers. Methods Four gallbladders were removed from Thiel Embalmed cadavers and eleven from living patients during laparoscopic cholecystectomies. The specimens were prepared into a uniform ‘hour-glass’ shape. The cadaveric specimens were loaded onto the Instron tensometer and the patient specimens were loaded onto a portable hand-held tensometer. The samples were extended until complete tensile failure occurred allowing measurement of the tissues’ tensile strength and strain. Results Nine samples were obtained from the four Thiel embalmed gallbladders and 27 samples yielded from the 11 living patients’ gallbladders. The mean ultimate tensile strength of the Thiel samples was 2.16 ± 0.91 MPa compared with 2.24 ± 1.40 MPa in the living patient group (p = 0.85). The Thiel embalmed cadaveric samples had a lower measured mean strain than the living patient gallbladders of (123 ± 33% vs. 233 ± 91%, p Conclusion This study demonstrates that, while tissue strength is well preserved, there may be some differences in how the tissues feel, related to differences in elongation during handling in Thiel embalmed gallbladder tissue.

Pancreaticoduodenectomy (PD) is the only chance of cure for periampullary cancers. This study aims to evaluate survival and complication rates for PD with additional vascular resection performed for local vascular involvement and compare to standard PD.A retrospective cohort analysis of a departmental hepato-pancreatobiliary database from 2004 to 2014 was performed. All patients (n = 92) who underwent PD without vascular resection (n = 72), with venous resection (n = 16), with both arterial and venous resection (n = 4) were included in the study. Patients who received palliative double bypass (n = 6) were also included for survival analysis. Survival and post-operative complications were assessed.Median survival for standard PD and PD with venous resection was 21 months and 18 months respectively (P = 0.588). Patients who received PD with venous and arterial resection had a median survival of 7 months, significantly less than standard PD (P = 0.044). Median survival in the palliative bypass group was 4 months, comparable to PD with venous and arterial resection (P = 0.191). There was a significant survival advantage in patients who received an R0 resection (median survival 24 months) compared to those who received an R1 resection (median survival 18 months) (P 0.02). Patients with a lymph node ratio0.2 had a median survival of 25 months, which was significantly higher than that of patients who had a lymph node ratio ≥0.2 (9 months) (P 0.005).PD with venous resection has similar survival to standard PD with no increased risk of procedure specific post-operative complications. On the other hand, PD with venous resection and additional arterial resection has no survival benefit and may be a step too far in our experience.

OBJECTIVES This study evaluated the impact of methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection on postoperative complications and patient outcome after pancreatoduodenectomy (PD). METHODS Seventy-nine patients who underwent PD were monitored for hospital-acquired MRSA. The patients were grouped as (1) no MRSA infection, (2) skin colonization with MRSA, and (3) systemic MRSA infection. RESULTS Forty (51%) of the 79 patients were MRSA positive during hospital admission. Fourteen of the 40 patients swabbed for MRSA were found positive (skin colonization), and 26 patients (33%) developed systemic MRSA infection after PD. The sites of MRSA infection included (1) abdominal drain fluid (16/26; 42%), (2) sputum (4/26; 15%), (3) blood cultures (2/26; 8%), and (4) combination of sites (9/26; 35%). The patients with systemic MRSA infection had a longer postoperative stay (31 vs 22 days; P = 0.005) and increased incidence of chest infections compared with MRSA-negative patients (14 vs 4; P = 0.02). Four of the 16 patients with MRSA-positive drain fluid had a postpancreatectomy hemorrhage compared with 3 of the 63 patients with no MRSA infection in drain fluid (P = 0.02). CONCLUSION Of the 79 patients admitted for PD, 51% became colonized with MRSA infection. Systemic hospital-acquired MRSA infection in 33% was associated with prolonged postoperative stay, increased wound and chest infections, and increased risk of postoperative hemorrhage.

With advances in laparoscopic instrumentation and acquisition of advanced laparoscopic skills, laparoscopic common bile duct exploration (LCBDE) is technically feasible and increasingly practiced by surgeons worldwide. Traditional practice of suturing the dochotomy with T-tube drainage may be associated with T-tube-related complications. Primary duct closure (PDC) without a T-tube has been proposed as an alternative to T-tube placement (TTD) after LCBDE. The aim of this meta-analysis was to evaluate the safety and effectiveness of PDC when compared to TTD after LCBDE for choledocholithiasis. A systematic literature search was performed using PubMed, EMBASE, MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials databases for studies comparing primary duct closure and T-tube drainage. Studies were reviewed for the primary outcome measures: overall postoperative complications, postoperative biliary-specific complications, re-interventions, and postoperative hospital stay. Secondary outcomes assessed were: operating time, median hospital expenses, and general complications. Sixteen studies comparing PDC and TTD qualified for inclusion in our meta-analysis, with a total of 1770 patients. PDC showed significantly better results when compared to TTD in terms of postoperative biliary peritonitis (OR 0.22, 95 % CI 0.06–0.76, P = 0.02), operating time (WMD, −22.27, 95 % CI −33.26 to −11.28, P

During the past decades, the classic Whipple resection (cWhipple) and the pylorus-preserving Whipple (ppWhipple) operation have been advanced for the resection of cancer of the pancreatic head. However, no definitive answer exists as to whether the more conservative ppWhipple operation indeed equalizes the short- and long-term results of the cWhipple procedure. Therefore we conducted a randomized prospective trial in a nonselected series of consecutive patients. Demographics, diagnostic, intraoperative, and histologic findings (tumor type and tumor stage of these patients) as well as postoperative mortality, morbidity, and follow-up after discharge were analyzed. For statistical evaluation Kruskal-Wallis and chi-square tests were used where appropriate. Survival was analyzed according to Kaplan-Meier curves, and differences were examined using the log-rank test. From June 1996 to April 1999, a total of 114 patients with suspected pancreatic or periampullary tumors were prospectively randomized to undergo either a cWhipple or a ppWhipple (intention to treat) operation. Based on the inclusion and exclusion criteria, 77 of these patients were included in the final analysis. Forty had a cWhipple and 37 had a ppWhipple resection. There were no differences with regard to age, sex distribution, ASA classification, histologic classification, UICC stage, length of stay in the intensive care unit, and length of hospital stay. The ppWhipple group had a significantly shorter operative time, reduced blood loss, and fewer blood transfusions. There was no difference in mortality, but the cWhipple group showed a significantly higher total morbidity. The incidence of delayed gastric emptying was identical in both groups. For long-term follow-up, a total of 61 patients with histologically proven pancreatic or periampullary carcinoma were analyzed. There were no differences in tumor recurrence or in long-term survival at a median follow-up of 1.1 years (range 0.1 to 2.9 years). Our initial results demonstrate that the cWhipple and ppWhipple operation are equally radical. However, ppWhipple may be the procedure of choice for the treatment of pancreatic and periampullary cancer.

Pancreatic cancer is the third leading neoplasm of the gastrointestinal system and has a dismal prognosis. The majority of patients are no more suitable for resection at time of diagnosis due to early development of distant metastases or major infiltrations of adjacent structures. However, due to the resistance of pancreatic cancers against chemoradiation, curative resection represents the only therapy with a potential for cure. For the surgical treatment of pancreatic head cancer, the classical Whipple operation is still the standard procedure but during the last two decades, pylorus-preserving duodenopancreatectomy has been evolved as a more conservative procedure in order to omit the consequences of partial gastrectomy. For cancer of the pancreatic body and tail, distal pancreatectomy or total pancreatectomy represent the current standard treatment. More radical methods like regional pancreatectomy and resection with extended lymph node dissection have failed so far to demonstrate any improvements in long-term survival compared to the standard types of resection. To further improve the treatment of pancreatic cancer, prospectively randomised trials are needed to compare these extended surgical procedures with the standard types of resection.

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma.To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma.All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio.Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P0.001) and tumour size (greater than 2 cm; P=0.008).A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Current management of late post-pancreatectomy haemorrhage in a university hospital.Haemorrhage after pancreaticoduodenectomy is a serious complication. We report on risk factors and outcome following management by radiological intervention.Tertiary care centre in Scotland.Sixty-seven consecutive patients who underwent pancreaticoduodenectomy.All pancreaticoduodenectomies over a 3-year period were reviewed. International Study Group on Pancreatic Surgery (ISGPS) definition of post-pancreatectomy haemorrhage was used.Endpoints were incidence of haemorrhage, pancreaticojejunal anastomosis leak, methicillin-resistant Staphylococcus aureus (MRSA) infection and mortality.Seven patients (10.4%) developed post-pancreatectomy haemorrhage out of 67 pancreaticoduodenectomies. Median age was 71 years. All post-pancreatectomy haemorrhage were late onset (median 23 days; range: 3-35 days), extraluminal and ISGPS grade C. Post-pancreatectomy haemorrhage arose from hepatic artery (n=4), superior mesenteric artery (n=1), jejunal artery (n=1), and splenic artery (n=1). Angiographic treatment was successful in all patients by embolisation (n=5) or stent grafting (n=2). Pancreatic fistula rate was similar in post-pancreatectomy haemorrhage and "no-haemorrhage" groups (57.1% vs. 40.0%; P=0.440); MRSA infection was significantly higher in post-pancreatectomy haemorrhage group (57.1% vs. 16.7%; P=0.030). Mortality from post-pancreatectomy haemorrhage despite successful haemostasis was 42.9%. Univariate and multivariate analysis identified MRSA infection as a risk factor for post-pancreatectomy haemorrhage.CT angiogram followed by conventional catheter angiography is effective for treatment of late extraluminal post-pancreatectomy haemorrhage. MRSA infection in the abdominal drain fluid increases its risk and therefore aggressive treatment of MRSA and high index of suspicion are indicated.

INTRODUCTION There is debate on optimal techniques that reduce bile duct injury during laparoscopic cholecystectomy (LC). A national survey of Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) members was carried out to determine current surgical practice for gallstones, including the use of intra-operative cholangiography (IOC) or critical view of safety to reduce the risk of bile duct injury. SUBJECTS AND METHODS An anonymous postal survey was sent to all 417 AUGIS members. Data on grade of surgeon, place of work (district general hospital, teaching), subspecialty, number LC per year, use of IOC, critical view of safety, and management of stones detected during surgery were collated. RESULTS There was a 36% (152/417) response – 134 (88%) from consultant surgeons (36, HPB; 106,OG; 64, DGH; 88, teaching hospital). Of these, 38% performed > 100 LC per year, 36% 50–100 LC per year, and 22% 25–50 LC per year. IOC was routine for 24%; and selective for 72%. Critical view of Calot's triangle was advocated by 82%. Overall, 55% first clip and divide the cystic artery, whereas 41% first clip and divide the cystic duct. Some 39% recommend IOC and 23% pre-oper-ative MRCP if dilated common bile duct (CBD) is noted on pre-operative ultrasound. When bile duct stones are identified on IOC, 61% perform laparoscopic CBD exploration (LCBDE), 25% advise postoperative ERCP, and 13% perform either LCBDE or ERCP. Overall, 88% (n = 134) recommend index cholecystectomy for acute pathology, and this is more likely in a teaching hospital setting (P= 0.003). Laparoscopic CBD exploration was more likely to be performed in university hospitals (P< 0.05). CONCLUSIONS A wide dissection of Calot's triangle to provide a critical view of safety is the technique most commonly recommended by AUGIS surgeons (83%) to minimise risk of bile duct injury, in contrast to 24% that recommend routine IOC. The majority (88%) of AUGIS surgeons advise index admission cholecystectomy for acute gallbladder disease.

Background There is minimal data on the outcome of early laparoscopic cholecystectomy (LC) for acute gallbladder disease when performed by trainees. This study assesses the outcomes of a policy of same admission LC incorporated into a surgical training programme in a major teaching hospital. Methods 447 index LCs performed over a 3-year period were reviewed retrospectively. The indications, operating surgeon, operating time, use of IOC, conversion rates, reasons for conversion and post-operative stay were analysed. Multivariate analysis of reasons for conversion was performed. Results 150 LCs were performed by consultants and 297 by registrars; 67 were performed by year 1–3 specialist registrars (SpR) and 230 by year 4–6 SpRs. The indications were biliary colic ( n =7), acute cholecystitis ( n =180), chronic cholecystitis ( n =260), carcinoma ( n =1). No difference was found in demographics, operating time (105min Vs 115min), use of IOC (34% Vs 29%; P =0.2) and post–operative stay (2 days Vs 1 day) between consultants and registrars. The conversion rates were higher for consultants compared to registrars (29 (19%) Vs 28 (9%), P =0.004). The overall conversion rate was 11%. There were no bile duct injuries. Predictors for conversion were CRP>50 at admission and acute cholecystitis. Conclusion In a teaching hospital setting most acute admission LCs (66%) were performed by trainees. A step wise training programme with active consultant supervision of all index LCs results in low morbidity, low conversion rates, and a short post-operative stay for acute gallbladder disease. This model of same admission cholecystectomy provides a good training opportunity in emergency general surgery.

Current management of gallstone pancreatitis in a university hospital.Comparison of current management of gallstone pancreatitis with recommendations in national guidelines.Tertiary care centre in Scotland.One-hundred consecutive patients admitted with gallstone pancreatitis.All patients that presented with gallstone pancreatitis over a 4-year period were audited retrospectively. Data were collated for radiological diagnosis within 48 hours, ERCP within 72 hours, CT at 6-10 days, and use of high-dependency or intensive therapy units in severe gallstone pancreatitis, and definitive treatment of gallstone pancreatitis within 2 weeks as recommended in national guidelines.Forty-six patients had severe gallstone pancreatitis and 54 patients mild pancreatitis. Etiology was established within 48 hours in 92 patients. Six (13.0%) out of the patients with severe gallstone pancreatitis were managed in a high dependency unit. Fifteen (32.6%) patients with severe gallstone pancreatitis underwent CT within 6-10 days of admission. Four (8.7%) of the 46 patients with severe gallstone pancreatitis had urgent ERCP (less than 72 hours). Overall 22/100 patients unsuitable for surgery underwent endoscopic sphincterotomy as definitive treatment. Seventy-eight patients had surgery, with 40 (51.3%) of these patients undergoing an index admission cholecystectomy, and 38 (48.7%) patients were discharged for interval cholecystectomy. Overall 81 patients with gallstone pancreatitis had definitive therapy during the index to same admission (cholecystectomy or sphincterotomy). Two (5.3%) patients were readmitted whilst awaiting interval cholecystectomy: one with acute cholecystitis and one with acute pancreatitis. There were no mortalities in this cohort.This study has highlighted difficulties in implementation of national guidelines, as the use of critical care, timing of ERCP and CT, and definitive treatment prior to discharge did not concur with national targets for gallstone pancreatitis.

Reduction in hospital stay, blood loss, postoperative pain and complications are common findings after laparoscopic liver resection, suggesting that the laparoscopic approach may be a suitable alternative to open surgery. Some concerns have been raised regarding cost effectiveness of this procedure and potential implications of its large-scale application. Our aim has been to determine cost effectiveness of laparoscopic liver surgery by a case-matched, case-control, intention-to-treat analysis of its costs and short-term clinical outcomes compared with open surgery.Laparoscopic liver segmentectomies and bisegmentectomies performed at Ninewells Hospital and Medical School between 2005 and 2007 were considered. Resections involving more than two Couinaud segments, or involving any synchronous procedure, were excluded. An operation-magnitude-matched control group was identified amongst open liver resections performed between 2004 and 2007. Hospital costs were obtained from the Scottish Health Service Costs Book (ISD Scotland) and average national costs were calculated. Cost of theatre time, disposable surgical devices, hospital stay, and high-dependency unit (HDU) and intensive care unit (ICU) usage were the main endpoints for comparison. Secondary endpoints were morbidity and mortality. Statistical analysis was performed with Student's t-test, chi(2) and Fisher exact test as most appropriate.Twenty-five laparoscopic liver resections were considered, including atypical resection, segmentectomy and bisegmentectomy, and they were compared to 25 matching open resections. The two groups were homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence of liver cirrhosis and indications. Operative time (p0.03), blood loss (p0.0001), Pringle manoeuvre (p0.03), hospital stay (p0.003) and postoperative complications (p0.002) were significantly reduced in the laparoscopic group. Overall hospital cost was significantly lower in the laparoscopic group by an average of 2,571 pounds sterling (p0.04).Laparoscopic liver segmentectomy and bisegmentectomy are feasible, safe and cost effective compared to similar open resections. Large-scale application of laparoscopic liver surgery could translate into significant savings to hospitals and health care programmes.

Background: Delayed gastric emptying is one of the most frequent postoperative complications after Whipple resection. In the present study we evaluated the role of enteral nutrition in the development of delayed gastric emptying after Whipple resection. Patients and methods: Between January 1996 and June 1998, 64 patients (30 female, 34 male) underwent a classic (n = 27) or pylorus-preserving (n = 37) Whipple resection. Two patients were excluded; 30 patients received enteral and 32 patients received no-enteral nutrition. Results: Delayed gastric emptying occurred significantly more in patients with enteral (17 of 30, 57%) than in patients with no-enteral nutrition (5 of 32, 16%) (P

Background Pancreatic resections can be performed with great safety. However, the morbidity rate is reported to be 40–60 per cent with a high prevalence of pancreatic complications. The aim of this study was to analyse complications after pancreatic head resection, with particular attention to morbidity and pancreatic fistula. Methods From November 1993 to May 1999, perioperative and postoperative data from 331 consecutive patients undergoing pancreatic head resection were recorded prospectively. Data were analysed and grouped according to the procedure performed: classic Whipple resection, pylorus-preserving pancreatoduodenectomy (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Results Pancreatic head resection had a mortality rate of 2·1 per cent; the difference in mortality rate between the three groups (0·9–3·0 per cent) was not significant. Total and local morbidity rates were 38·4 and 28 per cent respectively. DPPHR had a lower morbidity, both local and systemic, than pancreatoduodenectomy. The prevalence of pancreatic fistula was 2·1 per cent in 331 patients, and was not dependent on the procedure or the aetiology of the disease. Reoperations were performed in 3·9 per cent of patients, predominantly for bleeding and non-pancreatic fistula. None of the patients with pancreatic fistula required reoperation or died in the postoperative course. Conclusion A standardized technique and a continuing effort to improve perioperative management may be responsible for low mortality and surgical morbidity rates after pancreatic head resection. Pancreatic complications occur with Whipple, PPPD and DPPHR procedures with a similar prevalence. Pancreatic fistula no longer seems to be a major problem after pancreatic head resection and rarely necessitates surgical treatment.

The typical histologic characteristics of chronic pancreatitis (CP) are fibrosis due to accumulation of fibroblasts and collagen replacing the exocrine parenchyma, and calcifications in the pancreatic ducts and ductules. 1–3 Further, various amounts of inflammatory cell infiltrates, acinar cell degeneration, and the dedifferentiation of acinar cells into ductlike tubular complexes, as well as to a minor extent ductal cell proliferation, are typical histologic characteristics of CP. 3–5 The destruction of the exocrine pancreatic parenchyma leads to various degrees of maldigestion. The other dominant clinical symptom in CP is recurrent abdominal pain, which occurs in approximately 80% to 90% of the patients. 2,6 Although different concepts of pain generation in CP have been postulated during the past decades, none can completely explain the pain syndrome in this disease. 6–11 Present pain hypotheses include acute inflammation of the pancreas, increased pressure within the pancreatic ductal system and parenchyma, recurrent ischemia of the parenchyma, and extrapancreatic causes such as common bile duct or duodenal stenosis. 8–11 The most recent pain concept in CP concerns direct alterations of pancreatic nerves as one major pathophysiologic event of pain generation. 7,12,13 Recently, it has been reported that CP is associated with increased nerve numbers and enlargement of pancreatic nerves in association with visible destruction of the perineurium, as seen on electron microscopy. 7 In addition, the presence and quantity of growth-associated protein-43, a marker of neuroplasticity in enlarged pancreatic nerves and pancreatic neurons, is associated with abdominal pain intensity in CP. 13 Further, intense immunoreactivity for the sensory neurotransmitters substance P and calcitonin gene-related peptide (CGRP) in enlarged pancreatic nerves points to the possible role of various neurotransmitters in pain processing and inflammation. 12 These observations indicate that alterations in neural structures seem to contribute significantly to pain generation in patients with CP. However, the mechanisms that contribute to the enlargement of pancreatic nerves are unclear and have yet to be analyzed. Nerve growth factor (NGF) belongs to the neurotrophin (NT) family, which also includes brain-derived neurotrophic factor and NT-3, -4, -5, and -6. 14–17 NGF was the first neurotrophin discovered, and it plays a role in neuroblast proliferation and neuronal maturation, affecting neuronal phenotype and maintaining neuronal survival. 14–17 Nerve growth factor binds to two types of cell surface receptors—the p75 NGF receptor and the Trk (tyrosine kinase)-receptor subtypes. 18 The p75 NGF receptor is a transmembrane glycoprotein that binds all neurotrophins with low affinity. 18 It contains no obvious signaling motif, and its role in transduction of the neurotrophin-mediated signal cascade remains uncertain. 14,18 The three Trk receptors (TrkA, TrkB, and TrkC) are all transmembrane tyrosine kinases that are activated on binding of neurotrophins. 14 Each of the Trk receptors shows a high degree of discrimination in binding members of the NT family. The preferred ligands are NGF for the TrkA receptor; brain-derived neurotrophic factor, NT-4, and NT-5 for the TrkB receptor; and NT-3 for the TrkC receptor. Whether NT-6 binds to any of these receptors is not known. 13–18 Recently, it has been reported that NGF and Trk-A might augment chronic pain and the inflammatory reaction in some disorders, such as arthritis, cystitis, and inflammatory dermatosis. 19–22 Taking into consideration that the main characteristics of CP are inflammation and pain and that characteristic neural changes in this disease have been demonstrated, we investigated the presence of NGF and of the TrkA receptor in the normal human pancreas and in pancreatic tissues from patients with CP, and correlated the molecular findings with clinical parameters.

Transient sublethal hyperthermia followed by recovery from heat stress, referred to as heat shock preconditioning, exerts a protective effect on ischemia/reperfusion-induced injury in many systems. This effect is considered to be correlated to heat shock proteins (HSPs) and might be a critical factor in kidney graft function and survival. This study was designed to examine the impact of heat shock preconditioning on kidney isograft function and survival in a model utilizing non-heart-beating (NHB) donors. Four groups of male Lewis rats (n = 10/group) subjected either to whole body hyperthermia (groups A and C) or to sham anesthesia (groups B and D) were allowed 24 h recovery. Thereafter, 20 min of warm ischemia (A/B), and in a separate set of experiments 40 min of warm ischemia (C/D), were induced by suprarenal aortic cross clamping before renal procurement. After 24-h preservation with University of Wisconsin solution at 4 degrees C, orthotopic kidney transplantations were performed to syngeneic bilaterally nephrectomized recipients. Tissue specimens were taken to determine HO-1/HSP32, 72, and 90 induction by Western blot analysis. Renal function was measured by means of serum creatinine and creatinine clearance on days 0, 3, and 7 as well as urine volume, protein content, and creatinine levels daily. HO-1/HSP32 and HSP72 were found to be expressed constitutively. Moreover, heat shock strongly induced renal HSP72 and HSP32/HO-1, and to a lesser extent HSP90, expression. For recipients of group A grafts, the graft survival rate was 10/10, whereas it was 7/10 (70 %) in recipients of group B grafts (log rank p < 0.05). Following 40 min of warm ischemia, 6/10 (60 %) recipients survived, whereas all sham treated animals died with anuria within 6 days (log rank p = 0.01). Heat shock preconditioning strongly improved graft viability and reduced functional impairment. Creatinine clearance (CRC) on day 3 post Tx was 0.43 +/- 0.24 ml/min in preconditioned animals (group A) and 0.07 +/- 0.09 ml/min (p < 0.001) in sham preconditioned (group B), whereas it was 0.91 +/- 0.33 ml/min and 0.03 +/- 0.02 ml/min (p < 0.00 001) on day 7 post Tx. Following 40 min NHB time, CRC in survivors of preconditioned graft recipients (group C) was 0.32 +/- 0.2 ml/min (day 3 post Tx) and 0.23 +/- 0.08 ml/min (day 7 post Tx) and was significantly better than CRC of group B (p < 0.01 and p < 0.00001, respectively). CRCs prior to NHB procedures were comparable in all animals ranging between 1.31 and 1.72 ml/min. Serum creatinine as well as proteinuria were significantly increased after transplantation in both groups but recovered within 5 days in recipients of preconditioned grafts, whereas kidneys from donors without HP did not recover function. Histological alterations were also diminished following HP. Hyperthermic preconditioning induces strong and long lasting HO-1/HSP32, HSP72, and HSP90 expression in rat kidneys. HP increases survival following transplantation and improves renal graft function including proteinuria, volume output, and creatinine clearance. HSP induction might be used to develop novel approaches in clinical transplantation.