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Introduction: Hypocalcemia is not uncommon during acute pancreatitis and is associated with a poor outcome. Whilst the mechanisms responsible for its development remain unclear, there is evidence to implicate endotoxemia in other models of sepsis. Aim: To investigate the potential role of systemic endotoxin exposure in the development of hypocalcemia in patients with acute pancreatitis. Methodology: Adjusted serum calcium was measured daily, and the lowest value within 72 hours of admission for acute pancreatitis was determined. Serum endotoxin and both IgG and IgM antiendotoxin core antibodies (EndoCAbs) were measured on admission. Attacks were classified as mild (n =51) or severe (n = 21) according to the criteria of the Atlanta International Symposium of 1992. Results: Hypocalcemia was significantly more frequent (86% versus 39%, p < 0.001) and reached significantly lower levels during severe attacks than during mild attacks (median [interquartile range], 2.06 [1.78-2.17] mmol/L, versus 2.23 [2.15-2.30] mmol/L; p < 0.001). Endotoxemia was present in a significantly greater proportion of patients with severe disease (71% versus 41%; p = 0.037), and serum IgM and IgG EndoCAbs were significantly depleted during severe attacks in comparison with mild attacks (p = 0.007 and p = 0.039, respectively). A negative and significant correlation was observed between endotoxemia and both the admission and lowest serum concentrations of adjusted calcium (r = -0.424 and p = 0.022; r = -0.383 and p = 0.037, respectively), and the latter correlated significantly with serum IgG EndoCAb concentrations (r = 0.251; p = 0.036). Conclusion: Systemic endotoxin exposure appears to play a significant role in the development of hypocalcemia in patients with acute pancreatitis

Nitric oxide represents a potential key mediator of the local and systemic manifestations of acute pancreatitis (AP) in experimental models but its role in human disease is uncertain. We therefore sought to assess if systemic nitric oxide (NO) production is elevated in severe AP and determine whether this is a reflection of biochemical severity or endotoxin exposure.Patients were recruited within 72 hours of pain onset. NO derived nitrite excretion determined from a 24 hour sterile urine collection was correlated with intestinal macromolecular permeability (polyethylene glycol excretion ratio), markers of systemic endotoxin exposure (IgG:IgM endotoxin core antibody (EndoCAb) ratio), disease severity, and the magnitude of systemic inflammation (peak C reactive protein (CRP) and Acute Physiology and Chronic Health Evaluation score II (APACHE-II)).In patients with a severe attack (n=20), nitrite excretion was increased significantly compared with patients with a mild attack (n=45, 20.6 micro g v 15.65 micro g; p0.00) and the latter with healthy controls (n=20, p=0.004). Nitrite excretion correlated strongly with both intestinal permeability (r=0.7, p=0.006) and EndoCAb ratio (r=0.7, p0.01) but not with CRP or APACHE-II scores (p0.1).Total urinary nitrite excretion is increased in patients with severe AP, and may not be simply a reflection of systemic inflammation, but potentially a consequence of endotoxin mediated upregulation of inducible NO synthase activity.

Background Calcitonin precursors are sensitive markers of inflammation and infection. The aim of this study was to evaluate the role of plasma calcitonin precursor levels on the day of admission in the prediction of severity of acute pancreatitis, and to compare this with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. Methods Plasma concentrations of calcitonin precursors were determined on admission in 69 patients with acute pancreatitis. APACHE II scores were calculated on admission. Attacks were classified as mild (n = 55) or severe (n = 14) according to the Atlanta criteria. Plasma calcitonin precursor levels were determined with a sensitive radioimmunoassay. Results On the day of hospital admission, plasma levels of calcitonin precursors were significantly greater in patients with a severe attack compared with levels in those with a mild attack of pancreatitis (median 64 versus 25 fmol/ml; P = 0·014), but the APACHE II scores were no different (median 9 versus 8; P = 0·2). The sensitivity, specificity, positive predictive and negative predictive values, and accuracy for the prediction of severe acute pancreatitis were 67, 89, 57, 93 and 85 per cent respectively for plasma calcitonin precursor levels higher than 48 fmol/ml, and 69, 45, 23, 86 and 50 per cent respectively for an APACHE II score greater than 7. Differences in the specificity and accuracy of the two prognostic indicators were significant (P < 0·001 and P = 0·001 respectively). A plasma calcitonin precursor concentration of more than 160 fmol/ml on admission was highly accurate (94 per cent) in predicting the development of septic complications and death. Conclusion The assay of plasma calcitonin precursors on the day of admission to hospital has the potential to provide a more accurate prediction of the severity of acute pancreatitis than the APACHE II scoring system.

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P0.001), CRP (r = 0.51; P0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis.

Purpose/Background Impairment of gut barrier function has been demonstrated in patients with severe acute pancreatitis and may contribute to the development of local and systemic septic complications. The underlying mechanisms, however, remain unclear. Against this background, our aims were to investigate the small intestinal epithelial morphology and mucosal immunity in patients with severe acute pancreatitis. Methods Segments of terminal ileum from three patients with severe necrotizing acute pancreatitis who underwent pancreatic debridement and ileocolic resection for doubtful or evident segmental colonic viability were available for the study. Control specimens were available from seven patients who underwent gastric bypass and distal ileal resection for morbid obesity. Sections were cut and stained with hematoxylin and eosin for the measurement of villous height and crypt depth, and with toluidine blue for the determination of mucosal mast cell counts. Only adequately oriented specimens were deemed suitable for computer-aided image analysis. Results were expressed as the villous height/crypt depth ratio (VH/CD) and mucosal mast cell index (ratio of mast cell count/length of muscularis mucosa). Results Microscopy of the small intestine from controls was normal. The villous height and VH/CD were significantly reduced in patients with acute pancreatitis compared with controls (median, 0.47 mm vs 0.68 mm, and 1.9 vs 2.8, respectively; P < 0.00001). The mast cell index was significantly reduced in patients with acute pancreatitis compared with controls (median, 5.88 cells/mm vs 8.58 cells/mm; P = 0.001). A positive correlation was observed between the mast cell index and the height of the villi (r = 0.23; P = 0.027). Conclusions Patients with necrotizing acute pancreatitis have an altered intestinal morphology and depleted mucosal mast cells. These factors may contribute to the impairment of gut barrier function in patients with severe acute pancreatitis.

Summary: We report a case of an acute strangulated gastric volvulus in a hernia of Bochdalek in an adult female patient that was repaired successfully via the laparoscopic approach. A left-sided diaphragmatic hernia contained a strangulated but viable gastric volvulus and a noncompromised colon. The contents of the hernia were reduced, and the 4-cm congenital diaphragmatic defect was primarily repaired with nonabsorbable sutures. The patient was discharged on the second postoperative day and remained symptom-free at 7 months. Unlike the very few previous reports of elective laparoscopic repair of uncomplicated Bochdalek hernias, this appears to be the first report of an urgent laparoscopic repair of a complicated hernia of this type.

Safer alternatives are needed to traditional test Obesity affects a quarter of adult women in the UK, western Europe, and Canada, and a third in the US. More women than men have bariatric surgery every year,1 and most are of childbearing age. Of 12 869 women in the UK who had primary bariatric surgery in 2011-13, 8469 (66%) were younger than 50.1 Furthermore, fertility in obese women generally improves after bariatric surgery as menstrual irregularity and ovulatory problems resolve with weight loss.23 Thus, increasing numbers of women with obesity start or complete their families after bariatric surgery. Despite weight loss after surgery, many women still require screening for gestational diabetes mellitus during pregnancy. A history of bariatric surgery has important implications for the choice of test since an oral glucose tolerance test can trigger dumping syndromes, with serious adverse effects. The two most common primary bariatric procedures, Roux-en-Y gastric bypass (54%) and sleeve gastrectomy (20%),1 can both cause …

Background and aims: We have recently demonstrated that high-density lipoproteins (HDL) transport microRNAs (miRNAs) in the plasma. Here we aim to investigate how HDL-associated miRNAs are regulated in morbidly obese subjects and more importantly, how weight loss after bariatric surgery affected HDL-miRNAs in these subjects. Methods: Plasma HDL were isolated from morbidly obese subjects (n=23) before, 6 months and 12 months after bariatric surgery by immunoprecipitation using goat anti-human apoA-I microbeads. We also isolated HDL from 12 normal subjects using the same methods. miRNAs were extracted from the isolated HDL and miR-223, miR-24 and miR-126 levels were determined by TaqMan miRNA assays. Results: miR-223, miR-24 and miR-126 were present on HDL from obese subjects before and after bariatric surgery. Before surgery, levels of miR-223, miR-24 and miR-126 on HDL from morbidly obese subjects were significantly higher than the levels on HDL from normal subjects. At 12 months after bariatric surgery, miR-223, miR-24 and miR-126 levels on HDL from obese subjects were increased by 2.9-fold, 2.3-fold and 2.7-fold (p Conclusion: HDL-associated miRNAs are differentially regulated in healthy versus morbidly obese subjects. miR-223, miR-24 and miR-126 are sensitive to weight loss induced by bariatric surgery.

Background Laparoscopic sleeve gastrectomy (LSG) has become an established primary bariatric procedure. Gastric stenosis after LSG has been reported in a few studies and often occurs at the level of incisura or midbody because of a technical operative error and could be associated with a leak. This can be managed by endoscopic dilations or revision surgery. The objective of this study is to describe a novel technique to deal with sleeve stenosis and its outcome. Methods Two patients presented with sleeve stenosis after LSG and underwent a novel technique. The patients were followed up for 18 months. Results We describe a novel technique of laparoscopic median gastrectomy in 2 patients that involved resection of the stenotic segment followed by a hand-sewn, gastrogastric, end-to-end anastomosis. Both patients had successfully recovered from stenosis related symptoms, although one required an endoscopic dilation of the anastomosis. Conclusion Laparoscopic median gastrectomy is a feasible and effective option in patients who have failed conservative management of stenosis after LSG and in whom there is a desire to avoid seromyotomy or conversion to gastric bypass.

To the editor, We agree that it is best to avoid laparoscopic common bile duct exploration (LCBDE) in patients with small diameter bile ducts (amongst our 120 patients who underwent LCBDE, one had a diameter of 3 mm, 3 of 4 mm and 4 of 5 mm). However, exploration of these is possible with the use of a 3-mm choledochoscope or via a trans-cystic duct approach. Whilst single-stage LCBDE is not the preferable option in high-risk patients, at times it becomes unavoidable when the endoscopic approach to management of ductal stones has failed. In our experience, LCBDE with primary closure can be performed in both elective and emergency cases. We performed emergency LCBDE in ten patients and encountered a postoperative chest infection in one and urinary tract infection in another but no bile leaks or duct strictures. Clearly though, patients with cholangitis, deep jaundice and coagulopathy should be optimised preoperatively and consideration should be given to preoperative percutaneous transhepatic biliary drainage as a temporising measure before embarking on LCBDE. With the use of a transverse choledochotomy and interrupted 4–0 Vicryl suture closure of non-dilated bile ducts (\6 mm diameter) at LCBDE (n = 8), we have encountered no postoperative bile leaks or bile duct strictures. We agree that endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic nasobiliary drainage have their application in the management of bile leak due to retained stones after LCBDE. However, re-laparoscopy has its role in patients with generalised abdominal signs and systemic disturbance as it facilitates a thorough abdominal washout as well as removal of retained duct stones with re-suturing of the bile duct. Nasobiliary drainage is not commonly adopted in the United Kingdom.

Efficient use of operating time has become a key concern. The aim of this study was to determine preoperative factors that can predict extended duration of operating time (90 min) for laparoscopic cholecystectomy (LC).Data collected prospectively on 827 consecutive patients who underwent elective LC between 1990 and 1997 were analyzed. Factors evaluated included age, gender; body mass index; comorbidity; duration of symptoms; history of jaundice, pancreatitis, or abdominal surgery; dilated common bile duct or thick-walled gallbladder on ultrasound; preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES); and surgeon experience. Univariate and multivariate analyses were performed to identify factors predicting a long operation.Operating time was longer than 90 min in 276 patients (33%). Predictors of extended operation time were age older than 55 years (odds ratio [OR] = 9.7), preoperative ES (OR = 2.8), and a thick-walled gallbladder on ultrasound (OR = 2.5).These predictors may be useful in planning theater lists and anesthesia management, and in selecting patients for day surgery.

The routine use of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy remains controversial.A retrospective review of 950 consecutive laparoscopic cholecystectomies performed during an 8-year period was performed. For the first 2 years, IOC was performed selectively, and thereafter routinely.Attempted in 896 patients, IOC was successful in 734 (82%). Bile duct stones were found in 77 patients (10%), dilated ducts without stones in 47 patients (6%), and anatomic variations in 4 patients (0.5%). There were four (0.4%) minor intraoperative complications related to the IOC, with no consequences for the patients. There were three (0.3%) minor injuries of the bile duct, which were identified with IOC and repaired at the time of cholecystectomy without any consequences for the patients. In two of these patients, the structure recognized and catheterized as the cystic duct was revealed by IOC to be the bile duct. Thus IOC prevented extension to a major common bile duct (CBD) injury.Findings show that IOC is a safe technique. Its routine use during laparoscopic cholecystectomy may not prevent bile duct injuries, but it minimizes the extent of the injury so that it can be repaired easily without any consequences for the patient. The prevention of a major bile duct injury makes IOC cost effective.

A rare case of finger-print-like zymogen granules shown by electron microscopy is reported. The patient was a 75-year-old man who was histologically and ultrastructurally confirmed to have acinar cell carcinoma of the pancreas. Frozen section and postmortem examination revealed that the tumor was made up of solid nests of cells resembling the appearance of normal pancreatic acini, showing polygonal cells which had round or oval nuclei, and rare mitotic figures. Zymogen-like granules, shown by eosinophilic granular staining, were abundant in the cytoplasm. Electron microscopy showed that the tumor cells were closely packed, occasionally forming small intercellular spaces resembling pancreatic acini (microtubules). The cytoplasm contained characteristic zymogen granules with dark-to-medium electron density, measuring 660 nm +/-213 SD in diameter. The granules of medium density were large, and showed finger-print-like patterns. Investigation of more cases is necessary to identify whether these finger-print-like patterns are an important factor in the genesis of acinar cell carcinoma.

Background. Biliary-enteric anastomotic strictures may complicate pancreaticoduodenectomy. Anastomotic ischaemia and reflux of gastric and enteric contents with secondary bacterobilia and cholangitis may contribute. Methods. Four patients (3 females, 1 male) with a mean age of 50 yr (range 26–73 yr) presented 1–12 yr following pancreaticoduodenectomy with features suggestive of biliary-enteric anastomotic stricture formation. These included recurrent cholangitis, obstructive jaundice, and liver abscess. Diagnosis was confirmed by percutaneous or endoscopic cholangiography. Endoscopic and radiological management were unsuccessful, and revision surgery in the form of a Roux-en-Y hepaticojejunostomy was required. Results. Three patients remain asymptomatic 10–30 mo postoperatively. Jaundice recurred at 15 mo in one patient owing to re-stricture formation and the development of secondary biliary cirrhosis; a liver transplantation is being considered. Conclusion. Early diagnosis and prompt management of biliary-enteric stricture is essential if secondary biliary cirrhosis is to be avoided. Definitive therapy is best accomplished with a Roux-en-Y hepaticojejunostomy that places the gastric and biliary anastomoses onto separate jejunal limbs.

The recent introduction of limited resections of the ventral pancreas for benign disease and for low-grade malignancies calls for a thorough understanding of its anatomy. The two embryonic anlagen were characterized and distinguished through a comprehensive study of their macroscopic, histologic, and immunohistochemical characteristics in 20 autopsy specimens before reconstruction. Sections were histologically stained with hematoxylin-eosin and Grimelius and immunohistochemically stained with antibodies to insulin, glucagon, somatostatin, and pancreatic polypeptide by the avidin biotin complex method. The ventral and dorsal anlagen of the pancreas were reconstructed from eight autopsy specimens, using the "macroserial" method, after serial sectioning and immunohistochemical staining with anti-pancreatic polypeptide antibodies. Compared with the dorsal pancreas, the ventral pancreas was characterized by the presence of smaller and more closely packed lobuli, irregular rather than uniform islets of Langerhans, and rich immunostaining with anti-pancreatic polypeptide. Construction of the two anlagen showed that the dorsal pancreas consisted of the anterior part of the head of the pancreas, and the body and tail of the pancreas, while the ventral pancreas consisted of the posterior part of the head of the gland and the upper two-thirds (62.5%) or all (37.5%) of the uncinate process. The ventral pancreas was related to the right lateral surface of the superior mesenteric vein extending to the back. However, it did not extend across the front surface of the superior mesenteric vein to the left as previously described. The uncinate process was also located posterior to but not anterior to the superior mesenteric vein. The contributions of the ventral and dorsal anlagen to the anatomy of the pancreas gland as demonstrated in this study differ, in some relevant features, from the classical descriptions in the medical literature. The current anatomical findings add essential knowledge for the pancreatic surgeon who contemplates tissue-preserving resections.

BACKGROUND AND AIMS Gallstone ileus (GSI) is an uncommon complication of gallstone disease that usually occurs in debilitated elderly patients in whom the minimal trauma of laparoscopic surgery might be advantageous. The outcome of laparoscopic surgery in 3 consecutive patients with GSI is presented, and its role is discussed. METHODS The laparoscopic approach was attempted in all patients with suspected GSI. RESULTS Three consecutive patients (2 female) aged 64 to 85 years with a median American Society of Anesthesiology score of 3E were admitted with small bowel obstruction. A laparoscopic enterolithotomy was carried out in all patients, and was completed successfully with a median operative time of 90 minutes. There were no intraoperative or postoperative complications, and the median postoperative hospital stay was 5 days. CONCLUSIONS Small bowel obstruction due to GSI may be safely managed using minimally invasive surgery with suggested benefits in these elderly patients.

Leukotrienes play a role in inflammation, and their participation in airway inflammation and bronchoconstriction in patients with severe asthma can be ameliorated by a new class of drugs known as leukotriene modulators. The role of leukotrienes in increasing vascular permeability in experimental peritonitis and in inducing chemotaxis of inflammatory cells has recently been documented. Steroids have been incriminated in the development of bacterial translocation in animal models in association with the suppression of mucosal immunity. The development of spontaneous bacterial peritonitis is recognized in cirrhotic patients with ascites and in those with nephrotic syndrome. The onset of bacterial peritonitis in the absence of these predisposing conditions or other underlying cause, such as perforated viscus, is termed 'primary bacterial peritonitis', and has never been described in asthmatic patients. We present an asthmatic patient who developed primary bacterial peritonitis while receiving a leukotriene modulator in combination with prednisolone therapy. The hypothesis that leukotriene receptor blockade might predispose to the development of primary bacterial peritonitis in patients receiving steroid therapy is discussed.

Pancreatic cancer (PC) often presents late with poor survival. While role of immunosuppressive cells in preclinical studies provided help to develop immunotherapeutic agents, these cells remain under investigation in PC. The aim of this study was to characterise the different subsets of myeloid-derived suppressor cells (MDSCs) and evaluate their level and function in the circulation and tissue of PC patients. Significant increases in circulating and tumour-infiltrating granulocytic (Lin-HLA-DR-CD33+CD11b+CD15+), but not monocytic (Lin-HLA-DR-CD14+), MDSCs were detected in PC patients when compared with healthy donors and patients with chronic pancreatitis. The circulating MDSCs from PC patients expressed arginase 1, which represents their functional state. Blood levels of MDSCs showed no association with PC stage or preoperative levels of tumour markers. These findings provide a first characterisation of the phenotype of different subsets of peripheral and local MDSCs in PC patients and suggest that the frequency and contribution of these cells are predominantly granulocytic. This information demonstrates that MDSCs play a role in pancreatic cancer and future large validation studies may help in the development of new immunotherapeutic strategies to inhibit or eliminate MDSC function.

Laparoscopic Roux-en-Y gastric bypass is the most commonly adopted bariatric procedure. The predominant majority of surgeons construct the anastomoses using stapled techniques. We describe our technique of complete laparoscopically sutured gastrojejunal anastomosis (GJA) and its outcomes.Electronic database was used to collect data retrospectively for patients undergoing laparoscopic gastric bypass at the senior author's bariatric institutions. The results shown represent median (interquartile range).Between April 2002 and April 2012, 1,754 consecutive patients (78 % female) aged 43 (35-50) years with BMI 51 (44.5-56.7) kg/m(2) underwent laparoscopic gastric bypass (1,679 primary bypasses, 75 revision procedures). All the GJA were hand-sutured. The operative mortality was 0.17 %. Four patients (0.22 %) developed GJA/gastric pouch leak of whom two died, while a further three patients (0.17 %) needed endoscopic dilatation of GJA stricture during the initial 2 years after surgery.In the hands of an experienced laparoscopic surgeon, laparoscopic hand-sutured GJA in patients undergoing gastric bypass is safe and effective with very low anastomotic leak and stricture rates.

Immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs) and T regulatory cells, downregulate antitumour immunity and cancer immunotherapy. MDSCs are a heterogeneous group of immature myeloid cells that negatively regulate the immune responses during tumour progression, inflammation and infection. Whilst there have been extensive laboratory investigations aimed at characterising the MDSC subsets in cancer, there remains a significant gap in our understanding of their phenotypical and functional heterogeneity. In this article, we review data concerning the phenotypical and functional role of MDSCs in cancers. Importantly, we analyse the value of MDSCs as a prognostic factor in various clinical settings and the possible therapeutic approaches towards elimination of their immunosuppressive activity and enhancement of beneficial antitumour immune responses. MDSCs promote tumour immune evasion by inhibiting T-cell responses, as well as by supporting tumour progression. Accumulation of MDSCs is associated with the progression of human cancers, and their elimination was shown to improve anti-tumour immune responses. Phenotypical characterisation of MDSCs has been poorly investigated in many human cancers and lacks comprehensive clinicopathological correlation data. Although the need for effective therapeutic agents to eliminate the MDSC suppressive effect is immense, their role has been examined only in a few clinical settings.

Laparoscopic gastric banding is an established approach for the surgical correction of morbid obesity. Fixation of the reservoir to the anterior abdominal wall is a cumbersome procedure that invariably involves an extension of the skin incision and rather tedious suturing in the depth of the wound. Inadequate completion of this step may lead to tilting of the reservoir, which may hinder future band inflations. This paper describes a simple technique to overcome this difficulty.

Background Although marginal ulceration and perforation at the gastrojejunal anastomosis is an established, albeit rare, risk after laparoscopic Roux-en-Y gastric bypass (LRYGB) for morbid obesity, little is known about the risk of late perforation at the jejuno-jejunal (J-J) anastomosis. The objective of this study was to identify the incidence of J-J perforation and describe management options and sequelae. Methods This is a retrospective review of the database of all patients who underwent LRYGB. The results are presented as mean (range) where appropriate. Results Between April 2002 and April 2012, 1652 patients underwent LRYGB (1577 primary and 75 revision procedures). The operative mortality was .18%. Three patients developed late perforation of the J-J anastomosis (.18%) at 7, 9, and 18 weeks, respectively. Two patients were managed with resection and reanastomosis of the perforation by laparotomy, and a third patient was managed laparoscopically with peritoneal lavage and transcutaneous tube jejunostomy of the perforation. All patients recovered well postoperatively. However, the third patient represented 42 days later with sepsis and died secondary to recurrent J-J ulcer perforation. Conclusion Perforation of the J-J anastomosis is a rare and life-threatening delayed complication after LRYGB and usually presents within 2–8 months postoperatively. It poses difficulties with diagnosis and management and should be dealt with judiciously.

Obesity has become a global public heath challenge affecting almost one-half billion adults (1) and an estimated 40 million children (2). Large artery disease is very common in obese patients and manifests clinically as myocardial infarction, stroke, and hypertension (3). Small artery disease is also common in obesity and contributes to the development of hypertension and microvascular disease due to changes in peripheral resistance and local autoregulation (4). Historically, the small artery dysfunction in obesity has been attributed to damage to the endothelium (5), most notably to generation and release of nitric oxide (NO) (6). More recently, however, appreciation has grown for an additional mechanism by which vascular damage occurs in obesity; the function of fat surrounding arteries, or perivascular adipose tissue (PVAT). The PVAT surrounds the majority of blood vessels in the body and, in addition to adipocytes, contains inflammatory cells, stem cells, and microvasculature. In health, PVAT modulates the contractile tone of adjacent small arteries by secreting vasodilatory molecules. These adipose-derived vasodilators act independently of the endothelium and include adiponectin (7), NO (7), hydrogen sulfide (8), and palmitic acid methyl ester (9). In 2009, we performed the first human small artery study of PVAT and showed that subcutaneous gluteal PVAT from lean healthy individuals reduced adrenergic constriction in adjacent arteries, an “anticontractile” effect. However, in patients with metabolic syndrome the vasodilatory effect of the PVAT was entirely lost, due to dual processes of adipose tissue hypoxia and inflammation, both of which are established sequelae of obesity in fat depots (7). More recently, we have seen that macrophage activation in adipose tissue contributes to the attenuation in PVAT anticontractile effect (10). Bariatric surgery has been performed for nearly 60 years and is established as the most effective clinical intervention to achieve both significant and sustained weight-loss in severely obese individuals. There are 3 types of bariatric surgical procedures: restrictive, malabsorptive, and combined operations (11). Gastric bypass surgery is a combination of restriction and malabsorption and has been shown to achieve a significantly higher degree of weight loss than restrictive bariatric surgery (12). Bariatric surgery also dramatically improves cardiovascular risk profiles in obese patients and reduces overall mortality (13,14). The mechanisms that underlie these cardiovascular improvements remain unclear, however. In the present study we investigated the effects of bariatric surgery achieved by the gastric bypass method on the vasodilatory properties of PVAT. We report amelioration of inflammation in PVAT with complete restoration of anticontractile activity as a consequence of improved adiponectin and NO bioavailability, despite persisting obesity.

Background and aims The macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-β (TGF-β) superfamily that can serve as a potential immune-therapeutic target and/or a prognostic biomarker for the treatment of some cancers. This article reviews the current published data on the molecular and clinical application of MIC-1 in cancer. Methods Literature review was conducted using Medline, PubMed, Embase and Cochrane databases. Results MIC-1 is the only known secreted p53-regulated cytokine and therefore can serve as a biomarker for p53 activation both in vitro and in vivo. MIC-1 gene can be activated by cyclooxygenase inhibitors and has pro-apoptotic and anti-tumour activities. Although MIC-1 may induce anti-tumour role in the early stages of cancer, it can promote the invasiveness and metastatic behaviour in advanced stages. Greater concentration of MIC-1 was associated with the induction of cancer-related anorexia and weight loss in animals and humans. Of clinical interest, MIC-1 out-performs all available biomarkers including CA19-9 in the differentiation of patients with resectable pancreatic cancer from patients with benign pancreatic disease. MIC-1 gene was over-expressed in colorectal cancer (CRC), and a progressive rise of MIC-1 serum levels was noted in patients with adenomatous polyps and further in patients with CRC. Conclusions MIC-1 cytokine has the potential characteristics for a new diagnostic biomarker and a target for cancer treatment. Further research however is required to characterise MIC-1 receptors and to revalidate its diagnostic power in larger and better-standardised clinical studies.

Obesity, arguably the single most important public health challenge of our times, is directly linked to diseases including type 2 diabetes mellitus, hypertension, ischaemic heart disease, obstructive sleep apnoea, osteo-arthritis and various cancers.

Although treatment with statins reduces cardiovascular (CV) events in patients with dyslipidemia, a residual 60 - 70% CV risk remains. This CV risk may be inversely related to high-density lipoprotein-cholesterol (HDL-C). Interest in niacin has re-emerged because of its HDL-C raising effects. The flushing associated with niacin which has previously affected patient compliance can now be significantly blocked with laropiprant (LRPT).This review aims to assess the efficacy, clinical effectiveness and safety of extended-release niacin (ERN) with LRPT. The authors searched PubMed and MEDLINE for literature published between January 2006 and November 2011, for efficacy, clinical effectiveness and safety reports of ERN with LRPT.Niacin has been shown to prevent CV events, reduce mortality and has beneficial effects on vascular endothelial function. Evidence suggests that this is due to its broad-spectrum lipid altering properties, including lowering lipoprotein (a) (Lp(a)), and its pleiotropic actions. While side effects associated with niacin have limited its use in the past, the extended-release formulations and co-administration of LRPT have increased its tolerability, particularly by reducing flushing. The authors advise that ERN should be used in patients with a high risk of cardiovascular disease, who have failed to reach conventional targets.

Background Laparoscopic surgery has extended its applications to resection of malignancies with favorable results. We report the first successful simultaneous laparoscopic subtotal colectomy and pancreaticoduodenectomy (PD) in a patient with familial adenomatous polyposis (FAP). Case report A 37-year-old man presented with obstructive jaundice. Gastroscopy and biopsies revealed a large ampullary tubulovillous adenoma with mild dysplasia (Spigelman stage III). A colonoscopy for suspicion of FAP revealed numerous right-sided polyps with left-sided sparing. Computed tomography showed a double duct sign. A simultaneous laparoscopic subtotal colectomy and PD was performed successfully. The operative time was 225 minutes for the colectomy and 390 minutes for the PD. Histology showed an R0 resection of ampullary adenocarcinoma (20 negative nodes) and colonic polyps with low-grade dysplasia. Genetic screening confirmed a diagnosis of FAP. Conclusions A simultaneous laparoscopic subtotal colectomy and PD in patients with FAP and ampullary neoplasia seems safe with favorable clinical and oncologic outcomes.

Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments.Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role.To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery.A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination.No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR.Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance.

Background: The surgical management of acute appendicitis presenting with appendicular mass remains controversial. The aim of this study was to evaluate the role of early laparoscopy and laparoscopic appendectomy (LA) in the management of appendicular mass. Methods: During a 1-year period, 62 patients underwent LA for suspected appendicitis (n = 50), generalized peritonitis (n = 2), and an appendicular mass (n = 10). Another patient who presented with an appendicular mass was found at laparoscopy to have an ileo-ileal intussusception. Results: All appendectomies were attempted and completed laparoscopically. Postoperative complications occurred in two patients; there were no deaths. None of the patients treated for an appendicular mass developed complications. There was no difference between the patients who underwent LA during the index admission for an appendicular mass and those who had surgery for non-mass-forming appendices with regard to the operative time (median [interquartile range]: 45 [36–60] vs 40 [25–50] min, p = 0.085) and postoperative hospital stay (median [interquartile range]: 2 [1–2] vs [1–2] days, p = 0.1). Conclusion: Early LA during the index admission of patients with an appendicular mass is feasible and safe, obviates the need for a second hospital admission, and avoids misdiagnoses.

Patients with duodenal polyps associated with familial adenomatous polyposis (FAP) have a considerable risk of developing duodenal carcinoma. Prophylactic resection of the duodenum for Spigelman stage III disease is the treatment of choice to prevent progression to cancer. Pancreaticoduodenectomy and pancreas-preserving total duodenectomy (PPTD) are the techniques that have been described for the surgical treatment of duodenal polyposis. We report the first case of laparoscopic PPTD in a patient with previous total colectomy for FAP and Spigelman stage III duodenal polyposis. A laparoscopic total dissection of the duodenum was carried out and the restoration was achieved performing pancreatico-biliary-jejunostomy and gastrojejunostomy. The postoperative period was uneventful. Laparoscopic PPTD can be performed safely in selected cases for the management of FAP.

Introduction: Niacin is one of the oldest drugs used in the treatment of dyslipidemia. Previously its use has been limited because of excessive flushing. Now an agent laropiprant (LRP) has been developed, which blocks the flushing pathway. Therefore, it is time to collate available information to assess the safety and tolerability of combining niacin with LRP. Areas covered: The authors searched PubMed and MEDLINE for literature published between January 2006 and July 2011, for safety and tolerability reports of extended-release niacin (ERN) with LRP. Expert opinion: The addition of LRP to ERN, by reducing the side effect ‘flushing’, may enable lipidologists and physicians to use niacin more widely as part of lipid modification therapy, especially since the combination can be safely added to statins. However, it has to be accepted that the addition of LRP does not completely abolish flushing. The favorable safety profile supports the use of LRP to achieve higher therapeutic dosing of niacin.

The Pringle maneuver has its applications to minimize blood loss during hepatic resection. Splenic rupture during the Pringle maneuver in open liver surgery was described only in few cases. This is the first report of such a complication during laparoscopic surgery.A 58-year-old woman sustained major splenic capsular rupture during laparoscopic right lateral hepatic sectionectomy (resection of segments VI to VII) for a colorectal metastasis. Surgery was carried out with the patient in the left lateral position. She became hypotensive during the second application of the Pringle maneuver secondary to spontaneous rupture of the splenic capsule. This was controlled with application of thrombogenic hemostatic agents. The patient received 12 units of blood transfusion. Her subsequent recovery was uneventful, and she was discharged on the sixth postoperative day.Unexplained hypotension during laparoscopic liver resection and the application of the Pringle maneuver should raise suspicion of splenic hemorrhage and prompt a timely and adequate intervention.

Lymphoepithelial cysts (LECs) of the pancreas are rare true pancreatic cysts. Their cause is not known. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. In this study, we report the largest LEC of the pancreas to have been resected laparoscopically. A 43-year-old man presented with upper abdominal pain, a 7.5 cm mutlioculated cystic mass in the pancreatic body and tail on imaging, and a raised serum cancer antigen-19-9. Laparoscopic distal pancreatectomy and splenectomy was performed. Histologic examination revealed a LEC. This study discusses the diagnostic difficulties and management decisions which face surgeons treating pancreatic cysts.

OBJECTIVES This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients. METHODS A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially. RESULTS Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002). CONCLUSIONS Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

The laparoscopic approach for biliary bypass surgery is a contemporary management option. This article reviews the evidence available for its role and effectiveness.A computerised search was made of the MEDLINE, PubMed, and EMBASE databases for English language publications from the first report of laparoscopic biliary bypass in 1992 to January 2010.Some 89 patients featured in 19 reports underwent 89 laparoscopic biliary bypass procedures for benign (n=17) and malignant (n=72) indications. Of those, 52 patients underwent biliary bypass alone, while 37 patients underwent biliary bypass combined with gastric bypass. The procedures included cholecystojejunostomy (n=64), hepaticojejunostomy (n=14), and choledochoduodenostomy (n=11). The overall success rate in achieving resolution of jaundice was 98.9%, with a morbidity rate of 12.3% and a mortality rate of 5.6%. More than one procedure was required in 1.1% of patients to achieve resolution of obstructive jaundice. During a reported median follow-up period of 13 months, obstructive jaundice recurred in none of the patients.The laparoscopic approach to biliary bypass surgery is safe and has a high initial success rate, low reintervention rate, and low morbidity and mortality rates. Longer follow-up data and comparative studies with open surgery and endoscopic stenting are needed.

To evaluate the benefits of aspirin in people with diabetes mellitus for the primary prevention of cardiovascular disease.We searched MEDLINE and Cochrane database for randomized, controlled trials of aspirin in people with diabetes and no cardiovascular disease. Relative risks were determined using random-effects meta-analysis.Risk reduction of aspirin compared with control groups for major cardiovascular events.Six trials consisting of 7374 patients with diabetes showed no benefits of aspirin compared with non-aspirin users with regard to overall mortality, risk reduction (relative risk (RR) = 0.96, 95% CI 0.78 - 1.18, p = 0.71), major cardiovascular events (RR = 0.90, 95% CI 0.78 - 1.05, p = 0.17) and myocardial infarction (RR = 0.95, 95% CI 0.76 - 1.18, p = 0.63). Risk of major bleeding in the aspirin compared with the non-aspirin group was not significant (RR = 2.49, 95% CI 0.70 - 8.84, p = 0.16).Aspirin therapy did not reduce the risk of cardiovascular events. Existing trials were limited by small patient numbers and low cardiovascular event rates. The use of aspirin cannot be routinely recommended for primary prevention of cardiovascular events in diabetes.

Background Some one-fifth of patients may have accessory spleens (AcS) and require their removal at the time of splenectomy to achieve and maintain hematological response. The purpose of this study was to evaluate the benefit of computed tomography (CT) in patients undergoing laparoscopic splenectomy (LS). Methods All patients who required splenectomy were offered LS and underwent preoperative contrast-enhanced CT scan to detect and locate AcS. The surgeon was not blinded to the result of the CT scan. Patients were followed up to determine if there was recurrent disease. Results Between 2000 and 2007, 58 consecutive patients (31 men) were referred for splenectomy and all underwent LS. Preoperative CT scan detected 11 AcS in 11 patients (19%), of which 9 were confirmed during LS; the remaining 2 patients suffered with ITP preoperatively and had a good hematologic response to LS. At LS, 14 AcS were found in 13 patients (22%), of which 4 patients had negative preoperative CT scan; those additional AcS were readily found and were located close to the lower pole or hilum of the spleen. All removed AcS were confirmed histologically. In one patient who had LS and removal of AcS for ITP a further AcS within the tail of the pancreas was detected 1 year postoperatively on CT after thrombocytopenia relapsed. The sensitivity and specificity of CT scan for the detection of AcS were 60% and 95.6%, and the corresponding values for laparoscopy were 93.3% and 100%, respectively. Pairwise comparison of the ROC curves identified laparoscopy to be associated with a significantly higher area under the curve compared with CT scan (0.967 vs. 0.673; P = 0.004). Conclusions Accessory spleens can be readily detected at laparoscopy in the vicinity of the spleen; preoperative CT scan for their detection and localization may not be necessary.

BACKGROUND: Gastroenterology is a beneficial treatment of morbidly obese type 2 diabetes mellitus (T2DM). We aimed to identify the predictors for the treatment of T2DM obese patients. METHODS: A retrospective study consisting of 531 patients undergoing laparoscopic gastric banding (LGB), laparoscopic mini-gastric bypass (LMGB) and laparoscopic sleeve gastrectomy (LSG) from January 2004 to May 2007 was performed. Patients with preoperative fasting serum glucose concentration of more than 126 mg/dl were diagnosed as T2DM. A postoperatively fasting serum glucose level of less than 110 mg/dl was considered to be remission of T2DM. RESULTS: Of the 531 patients, 62 (11.6%) were diagnosed as T2DM, including 23 men and 39 women, with a mean age of 31.8 ± 9.2 years, and a mean body mass index (BMI) of 40.0 kg/m(2). The mean glucose at 3, 6, and 12 months after surgery were 100.1 mg/dl, 95.1 mg/dl and 91.8 mg/dl, respectively. The mean body weight loss one year after surgery was 9.4% for LGB, 31.4% for LSG and 37.1% for LMGB, respectively. Among these operation methods (LGB, LMGB and LSG), the BMI, body weight, waist circumference, serum lipid profile and serum factors associated with glucose metabolism were significantly different during the one-year postoperative follow-up. Remission rate of T2DM was achieved in 84.8%, 58.8% and 58.3% of patients for LMGB, LGB and LSG, respectively. The best operative method for the remission of T2DM was LMGB. Using an artificial neural network (ANN) data mining technique, waist circumference, operative methods and C-peptide were significantly predictors for the remission of T2 DM. CONCLUSION: One year after gastrointestinal surgery, improvement of serum lipid profiles and serum data related to glucose metabolism in the different operative methods were noticed. LMGB seems to be the most effective procedure for the reduction of serum glucose levels compared with LAGB and LSG.

Pancreatic pseudocysts (PP) that complicate acute necrotizing pancreatitis (ANP) and require internal drainage may be managed laparoscopically. We present our experience with the laparoscopic endogastric and transgastric approaches to pseudocyst-gastrostomy (PCG).Seven patients (4 female) aged 25-75 (median, 60) years with large (median, 12cm), symptomatic and persistent (median, 5 months) retrogastric PP underwent PCG. All procedures were attempted laparoscopically. The endogastric approach was applied in the initial three patients and was replaced with the transgastric approach in the subsequent four patients. All patients underwent concomitant necrosectomy for sterile pancreatic necrosis. Patients were followed up with regular abdominal ultrasonography. Results shown represent median (range).There were no conversions to open surgery. The operating time was 135 (60-200) minutes and was longer with the endogastric approach (165 vs. 112 minutes). There were no postoperative complications and the postoperative hospital stay was 2 (1-4) days. There were no recurrences at a follow-up of 12 (2-21) months.Laparoscopic PCG with concomitant necrosectomy for PP that complicate ANP is feasible and safe and is associated with smooth and rapid recovery. The transgastric approach provides better access and is simpler to apply than that of the endogastric approach.

Objective: Percutaneous transhepatic biliary intervention (PTBI) plays an important role in the management of biliary obstruction, and this may be complicated by acute pancreatitis. The aim of this study was to assess the incidence of acute pancreatitis following PTBI. Patients and methods: Patients who underwent PTBI between January 1992 and December 2003 in a tertiary referral centre were identified from the hospital database. Patients who did not have their amylase measured post-procedure were excluded, as acute pancreatitis might have been missed. Acute pancreatitis was defined as hyperamylasaemia of three times or more above normal in association with abdominal pain. Results: Over a 12-year period, 331 patients underwent 613 procedures. Serum amylase was measured after 134 procedures (21.9%) and was elevated in 26 of those (19.4%). There was no difference in the frequency of hyperamylasaemia between proximal and distal PTBI (14/73 [19.2%] vs 12/61 [19.7%] procedures, p= NS). However, acute pancreatitis developed after 4 of 61 (6.6%) distal PTBI (stent, n= 3; internal–external catheter insertion, n= 1) but not after proximal PTBI (cholangiography or external drainage) (p= 0.041). The attacks were mild in three of the four patients. No pancreatitis-related deaths occurred. Conclusion: The risk of acute pancreatitis after distal PTBI is under-recognized and should be considered as a consent issue in patients scheduled for distal PTBI and when post-procedure abdominal pain ensues.

Insulinomas are generally benign tumors ideally suited to laparoscopic resection. Surgical management has changed over the years. Small benign tumors of the endocrine pancreas, including insulinomas, can be enucleated if their location is separate from the main pancreatic duct. Those over 2 cm and those close to the main pancreatic duct are generally treated by resection of the distal pancreas. Such a resection may be done as a spleen-preserving operation, or may include splenectomy. This chapter explores options in surgical treatment of a 2-cm insulinoma.

Morbidly obese patients are predisposed to developing abdominal wall hernias with the potential complication of small bowel obstruction. We report a patient who developed an obstructed paraumbilical hernia a few days after laparoscopic gastric bypass and died of aspiration pneumonia after re-laparoscopy. The controversy regarding the optimal time and method of repair of abdominal wall hernias in patients undergoing laparoscopic gastric bypass is discussed with emphasis placed on either a simultaneous repair or to split the omentum to one side leaving incarcerated omentum that is plugging the hernia defect in place for a delayed repair.

Gastric bezoars are rare, and are commonly observed in female children with mental or emotional disorders. Large bezoars may not be suitable for endoscopic extraction and are conventionally removed at laparotomy. We present a 19-year-old girl who had trichotillomania with a symptomatic abdominal mass that represented a 17-cm gastric trichobezoar. This was removed laparoscopically through a gastrotomy in a water-impervious bag and was extracted piecemeal through a 4-cm extension of one of the port wounds. The bezoar weighed 720 g. She was discharged home on the third postoperative day and remains symptom-free at 12-month follow-up. Laparoscopic removal of large gastric trichobezoars is feasible and appears safe.