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Bouveret's syndrome is a rare complication resulting from gallstone disease. Both surgical and endoscopical procedures are performed, with the disease to be seen as strictly interdisciplinary. There are no well-established recommendations for this condition. In this paper, we want to describe our experience from 6 cases in 3 Swiss hospitals from 2015 to 2017 with emphasis on the endoscopic technique of electrohydraulic lithotripsy followed by balloon dilatation and propose a treatment algorithm.Das Bouveret-Syndrom ist eine seltene Komplikation des Gallensteinleidens. Es werden sowohl chirurgische als auch endoskopische Interventionen durchgeführt, wobei die Krankheit streng interdisziplinär zu sehen ist. Etablierte Empfehlungen zum Vorgehen existieren nicht. In diesem Beitrag wollen wir über unsere Erfahrungen aus 6 Fällen in 3 Schweizer Spitälern von 2015 bis 2017 berichten. Wir beschreiben ein endoskopisches Vorgehen, das die elektrohydraulische Lithotripsie mit einer anschliessenden Ballondilatation kombiniert, und schlagen einen Behandlungsalgorithmus vor.

Metabolic surgery in patients with poorly controlled type 2 diabetes and low BMI Abstract. Bariatric surgery has been established as an efficient therapy for morbid obesity. Metabolic surgery represents the operative treatment of type 2 diabetes and other metabolic disorders. Metabolic surgery does not focus on weight loss, as many mechanisms, which are responsible for the improvement of the glycemic control are independent from weight loss. There are many studies, which show the efficient effect of metabolic surgery in diabetic patients with class II obesity. Furthermore, there is growing evidence, that metabolic surgery does also work in patients with a BMI below 35 kg / m2. Multiple surgical and endocrinological associations have endorsed these facts and adopted their guidelines. In obese type 2 diabetics with a BMI below 35 kg / m2 and a poor glycemic control metabolic surgery should be considered as a therapeutic option.

Despite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy. ispartof: Annals of the New York Academy of Sciences vol:1434 issue:1 pages:254-273 ispartof: location:United States status: Published online

Background Living-donor nephrectomy (LDN) is challenging, as surgery is performed on healthy individuals. Minimally invasive techniques for LDN have become standard in most centers. Nevertheless, numerous techniques have been described with no consensus on which is the superior approach. Both hand-assisted retroperitoneoscopic (HARS) and hand-assisted laparoscopic (HALS) LDNs are performed at Zurich University Hospital. The aim of this study was to compare these two surgical techniques in terms of donor outcome and graft function. Method Retrospective single-center analysis of 60 consecutive LDNs (HARS n = 30; HALS n = 30) from June 2010 to May 2012, including a one-year follow-up of the recipients. Results There was no mortality in either group and little difference in the overall complication rates. Median warm ischemia time (WIT) was significantly shorter in the HARS group. The use of laxatives and the incidence of postoperative vomiting were significantly greater in the HALS group. There was no difference between right- and left-sided nephrectomies in terms of donor outcome and graft function. Conclusions Both techniques appear safe for both donors and donated organs. The HARS technique is associated with a shorter WIT and a reduced incidence of postoperative paralytic ileus. Therefore, we consider HARS LDN a valuable alternative to HALS LDN.

The aims of the present study were to assess whether planned secondary wound closure at the insertion site of the circular stapler reduces wound infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric bypass (RYGB) and to identify independent predictive factors increasing the risk for wound infections after RYGB. This paper is a retrospective single-center analysis of a prospectively collected database of 1400 patients undergoing RYGB surgery in circular technique between June 2000 and June 2016. Planned secondary wound closure at the circular stapler introduction site was performed at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a historical control of 1109 (79.2%) consecutive patients with primary wound closure. Independent predictive factors for wound infection were assessed by multivariable analysis. Secondary wound closure significantly decreased wound infection rate from 9.3% (103/1109) to 1% (3/291) (p

Metabolic surgery in patients with poorly controlled type 2 diabetes and low BMI

OBJECTIVE Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS). METHODS Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ± 11 kg/m, mean age was 43 ± 5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications. RESULTS Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ± 21.9% vs. 76.6 ± 20.9%, P = 0.139; 2 years: 74.7 ± 29.8% vs. 77.7 ± 30%, P = 0.513; 3 years: 70.9 ± 23.8% vs. 73.8 ± 23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively. CONCLUSIONS In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB.

Zusammenfassung: Diese Übersichtsarbeit hat zum Ziel, die aktuellen chirurgischen Strategien bei der Behandlung des Ösophagus- und Magenkarzinoms zusammenzufassen. Neben den etablierten Standardverfahren wird auf die limitierten Resektionen bei Frühkarzinomen und den Stellenwert der Chirurgie im multimodalen Behandlungskonzept bei lokal fortgeschrittenen T3/4-Tumoren eingegangen. Das Plattenepithelkarzinom und das Adenokarzinom (Barrett-Karzinom) der Speiseröhre werden aufgrund der unterschiedlichen Pathogenese und Tumorbiologie sowie differenzierter unterschiedlicher Vorgehensweisen separat dargestellt. Aufgrund der überwiegend distalen Lokalisation der Barrett-Karzinome ist eine Abgrenzung zu den echten Kardiakarzinomen und Tumoren, die im Magen ihren Ursprung nehmen und die distale Speiseröhre infiltrieren, erforderlich. Basierend auf der Klassifikation nach Siewert wird das Barrett-Karzinom deshalb zusammen mit den so genannten Adenokarzinomen des ösophagogastralen Übergangs (AEG) behandelt. Für die Weiterentwicklung der chirurgischen Therapiestrategien beim Magenkarzinom haben sich die asiatischen, insbesondere japanischen und südkoreanischen Kollegen große Verdienste erworben. Moderne, dort entwickelte, aber noch nicht in der westlichen Welt etablierte Strategien werden neben den Standardverfahren gebührend berücksichtigt. Für alle diese Tumoren gilt, dass die chirurgische Therapie ein elementarer Bestandteil im Rahmen eines kurativen Behandlungskonzepts ist. Sie ist aber differenzierter und Teil eines komplexen interdisziplinären Algorithmus; deshalb ist eine weitere Spezialisierung zum Wohle der Patienten ratsam

Postoperative enteral nutrition is a widely accepted route of application for nutrition formulas due to a low complication rate, a good acceptance by patients. and a favorable cost-effectiveness. We report three cases of bezoar ileus after early postoperative enteral nutrition, using a fine needle jejunostomy (FNJ) in two cases and a nasoduodenal tube in one case. A male patient who underwent gastric resection for a gastrointestinal stroma tumor and was nourished through an fine needle jejunostomy developed an acute abdomen on the seventh postoperative day. Surgical exploration revealed a mechanical ileus caused by denaturated nutrition formula distal to the catheter tip. The second case, a female patient, underwent gastric resection for a gastric cancer and on the fourth postoperative day developed acute onset of abdominal pain. Intraoperative findings were the same as described in the first case. The third case, a male patient with necrotizing cholecystitis, underwent open cholecystectomy. Postoperative enteral feeding was performed using a nasoduodenal tube. He developed a small bowel obstruction on the 17th postoperative day that was caused by an intraluminal bezoar. In conclusion, bezoar formation represents an underestimated complication of postoperative enteral feeding. Acute onset of abdominal pain and the development of small bowel obstruction are the main clinical symptoms of this severe complication. The pathogenesis of bezoar formation remains unclear.

Laparoscopic gastric banding and Roux-en-Y gastric bypass are widely used for the treatment of morbid obesity. The impact of these two procedures on health-related quality of life has not been analyzed in comparative studies. Methods: A matched-pair analysis of a prospectively collected database was performed. Fifty-two consecutive patients with laparoscopic gastric bypass were randomly matched to fifty-two patients with laparoscopic gastric banding according to age, BMI, and gender. Quality of life was assessed using two standardized questionnaires (SF 36 and Moorehead-Ardelt II). Results: Mean preoperative BMI was 45.7kg/m2 for the bypass patients and 45.3kg/m2 for the banding patients. Mean BMI after 3years follow-up of was 30.4kg/m2 and 33.1kg/m2 (p = 0.036). In the SF 36 questionnaire, gastric bypass patients yielded a mean total score of 613 versus 607 points in the gastric banding group (p = 0.543), which is comparable to the normal population in Europe. In the Moorhead-Ardelt II questionnaire, the gastric bypass patients scored a mean total of 1.35 points and the gastric banding patients 1.28 points (p = 0.747). Of the patients, 97% with a gastric bypass and 83% with a gastric banding were satisfied with the result of the operation (p = 0.145). Conclusion: The patients after laparoscopic gastric bypass and laparoscopic gastric banding have a high level of satisfaction 3years after the operation and have similar quality of life scores compared to the normal population. Quality of life indexes were not different between the two procedures and were independent of weight loss in successfully operated patients

Brucellosis is a common, worldwide zoonosis. Clinical presentation is protean and often goes unrecognized. Hepatic brucelloma is a rare local complication of chronic brucellosis. We report a case in which magnetic resonance imaging and positron emission tomography imaging prompted suspicion of a hepatic malignancy. Diagnosis was ultimately made by serology and polymerase chain reaction of resected liver tissue.

BACKGROUND: We previously documented that a stringent implementation of a preemptive cytomegalovirus (CMV) prevention protocol reduced the number of CMV disease episodes after kidney transplantation, when compared with a routine preemptive protocol. The impact on overall costs was assessed. METHODS: Cost comparisons were made for inpatient and outpatient costs and overall costs, using costs provided by the financial department. Variables were analyzed using the Wilcoxon rank-sum test. A multivariable global linear model evaluated the effect of all co-variables on cost differences. In Cohort 1 (n = 84), 74% were followed with a standard CMV preemptive protocol, and 26% received prophylaxis. In Cohort 2 (n = 74), an intensified CMV surveillance protocol was applied in 74% of patients, and 26% were given prophylaxis. RESULTS: Overall, Cohort 1 had significantly higher treatment costs as compared with Cohort 2 (mean Swiss francs [CHF] 104,548 and CHF 76,983, respectively, P = 0.0005). Excluding patients who received prophylaxis reduced these costs to CHF 89,318 in Cohort 1 and CHF 73,652 in Cohort 2. Outcome between Cohort 1 and 2 was comparable. CONCLUSION: A stringent adherence to the CMV prevention protocol was associated with a significant reduction in overall costs. Whether this benefit is because of the demonstrated reduction in the rate of CMV disease needs to be assessed in a randomized trial.

OBJECTIVE The long-term follow up data of 2 prospective phase II trials is reported (NCT00072033, NCT00445861), which investigated neoadjuvant chemoradiation followed by surgery in patients with esophageal carcinoma. Postoperative complications as well as prognostic factors and patterns of relapse during long-term observation are shown. SUMMARY OF BACKGROUND DATA Long-term follow-up is often missing in the complex setting of multimodal treatments of esophageal carcinoma; this leads to rather undifferentiated follow-up guidelines for this tumor entity. METHODS In the first trial, patients received induction chemotherapy followed by chemoradiation and surgery. In the second trial, cetuximab was added to the same neoadjuvant treatment concomitant with induction chemotherapy and chemoradiation. RESULTS Eighty-two patients underwent surgery; the median follow-up time was 6.8 and 6.4 years, respectively. Fifty-five percent were diagnosed with adenocarcinoma, 80% clinically node-positive, 68% received transthoracic esophagectomy, and 32% transhiatal or transmediastinal resection. Five patients died postoperatively in-hospital due to complications (6%). The median overall survival was 4.3 years, and the median event-free survival was 2.7 years. Patients with adenocarcinoma rarely relapsed after a 3-year event-free survival. Whereas patients with residual tumor cells after neoadjuvant therapy primarily experienced relapse within the first 2 postoperative years, this in contrast to several patients with complete remission who also experienced late relapses 4 years after surgery. CONCLUSION After curative surgery in a multimodal setting, the histological type and the response to neoadjuvant therapy predicted the time frame of relapse; this knowledge may influence further follow-up guidelines for esophageal carcinoma.

// Theresia Reding 1, * , Cristian Palmiere 2, * , Clinsyjos Pazhepurackel 1 , Marc Schiesser 1 , Daniel Bimmler 1 , Andrea Schlegel 1 , Ursula Suss 1 , Sabrina Steiner 1 , Leandro Mancina 1 , Gitta Seleznik 1 , Rolf Graf 1 1 Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland 2 Department of Legal Medicine, Lausanne, Switzerland * These authors contributed equally to this work Correspondence to: Rolf Graf, email: Rolf.graf@usz.ch Keywords: sepsis, acute phase reaction, regenerating proteins, pancreas, intestine Received: February 07, 2017 Accepted: March 08, 2017 Published: March 16, 2017 ABSTRACT Introduction: In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. Results: PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Materials and methods: Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. Conclusions: The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas.

This study aims to determine the long-term prognostic value of coronary CT angiography (CCTA) prior to bariatric surgery in severely obese patients with a body mass index (BMI) ≥35 kg/m2. Seventy consecutive patients undergoing cardiac CT for coronary assessment prior to bariatric surgery were prospectively included. Images were analysed for the presence of coronary calcification and for non-obstructive ( 50% stenosis) coronary artery disease (CAD). A median clinical follow-up of 6.1 years in 54 patients was obtained for major adverse cardiovascular events (MACEs), defined as death, non-fatal myocardial infarction or coronary revascularisation. Weight loss and BMI decrease following bariatric surgery were recorded. The median BMI prior to surgery was 46.9 kg/m2. The median percentage of excess BMI loss after surgery was 75%. CT showed coronary calcification in 26 (48%) patients, whereas 28 (52%) patients had no calcification. CCTA revealed normal coronaries in 47 (87%) and non-obstructive CAD in 7 (13%) patients. No obstructive CAD was found. All patients successfully underwent bariatric surgery, and no MACE occurred neither perioperatively nor in the follow-up period. The negative predictive value of CCTA was 100% (95% confidence interval of 90.1–100.0%). In severely obese patients, the absence of obstructive CAD in cardiac CT prior to bariatric surgery with subsequently marked weight reduction has strong long-term prognostic implications for ruling out major adverse cardiac events in the postoperative period.

OBJECTIVE The aim of this study was to assess the influence of regional lymph node (RLN) retrieval on stage migration and survival in pancreatic cancer. METHODS A total of 7685 stage I and II pancreatic cancer patients were identified in the Surveillance, Epidemiology, and End Results database in 2004-2011. The impact of RLN was assessed using Cox regression, propensity score methods, and joinpoint regression. RESULTS In 3079 patients, 1 to 10 RLNs were retrieved; in 2799 patients, 11 to 19 RLNs, and in 1807 patients, 20+ RLNs. The rate of node-positive pancreatic cancer increased with the number of retrieved RLN. This trend continued beyond 10 retrieved RLN (P < 0.001). In unadjusted analysis, retrieval of RLN did not influence survival (P = 0.178). When adjusting for significant bias in staging variables (P < 0.001), retrieval of 20+ RLNs compared to 11 to 19 RLNs was associated with an increased survival in node-negative (hazard ratio, 0.78; 95% confidence interval, 0.62-0.98; P = 0.033) and node-positive cancer (hazard ratio, 0.83; 95% confidence interval, 0.74-0.93; P = 0.002). CONCLUSIONS This population-based propensity score-adjusted investigation demonstrated that more retrieved RLNs in pancreatic cancer decreases the rate of stage migration and improves the oncological outcome in node-negative and positive cancer. Contradictory results may be explained by a bias in the cancer characteristics for a different extent of RLN retrieval.

Currently, there are two laparoscopic stapling techniques to perform the gastrojejunostomy in gastric bypass surgery: the linear stapling and circular stapling techniques. The aim of the study was to compare the two techniques regarding postoperative morbidity and weight loss at an accredited bariatric reference center in Switzerland. We compared two consecutive cohorts at a single institution between November 2012 and June 2014 undergoing laparoscopic gastric bypass surgery. The frequency of complications and weight loss at 1 year was assessed in 109 patients with the 21-mm circular stapling technique (CSA) and 134 patients with the linear stapling technique (LSA). Postoperative complications were more frequent in the CSA group with 23.9 versus 4.5% in the LSA group (p =

Background: Management of leakages of the gastrojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass (LRYGB) can be complex. New endoscopic techniques such as covered stents and over-the-scope clips (OTCs) have been developed and are valuable alternative therapeutic options to reoperation and drainage. The aim of this study was to compare the value of stents and OTCs with surgical treatment options for the therapy of anastomotic leakages after LRYGB. Methods: Results of patients who were treated surgically with reoperation, local irrigation and drain placement (n = 9) were compared with results of patients who were treated endoscopically with stent and/or OTC placement (n = 5). Success rate, length of hospital stay, mortality, number of OTC applications/stent placement and percutaneous drainage placements were analyzed. Results: Overall, 14 of 1,046 patients (1.34%) developed a leakage of their gastrojejunal anastomosis after LRYGB between 2000 and 2012. While the success rate in surgically treated patients was 88%, the endoscopic treatment using a sequential approach with stenting, OTC application and percutaneous placement of drainages resulted in a 100% closure rate. The mortality rate and length of stay were not substantially different after both treatment regimens. Conclusion: Endoscopic management of anastomotic leakages after LRYGB may constitute a valuable alternative therapeutic option to surgical reoperation and drainage placement.

Obesity has been steadily increasing over the last three decades and is one of the leading causes of increased health costs due to its associated comorbidities. Unfortunately, conservative treatment including lifestyle changes did not achieve the desired results. Bariatric surgery, on the other hand, has emerged as an effective and safe treatment for obesity and its related comorbidities such as type 2 diabetes. Much time has passed since the first Roux-en-Y gastric bypass was performed in the 1960s, and the operation technique has since evolved. New variations such as the distal gastric bypass as well as the omega loop bypass have been developed. Today, the laparoscopic gastric bypass is still the most widely applied bariatric operation technique, followed by laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. The refinement of the surgical technique and the introduction of laparoscopy have resulted in low perioperative morbidity and mortality after gastric bypass surgery. In this article, we will be discussing the history of gastric bypass surgery as well as presenting current data on excessive weight loss and resolution of comorbidities with a focus on diabetes. We will be looking into newer techniques such as omega loop bypass and their efficacy compared to the standard gastric bypass. Furthermore, we will be addressing the most important early and long-term complications, their diagnostic strategies as well as their management.

Bariatric surgery is the most effective therapy to treat obesity and its sequelae. With the increasing incidence of obesity, the number of bariatric procedures has dramatically increased in recent years. The perioperative morbidity reached a very low level, and nearly all revisional bariatric procedures are primarily minimally invasive today. About 10-25% of the patients undergoing bariatric surgery require a revision at some point after their initial operation. Consequently, revisional bariatric surgery has emerged as a distinct practice, performed mainly at tertiary centers, to resolve complications caused by the primary operation and to provide satisfactory weight loss. In this review, our personal experience with revisional bariatric surgery is discussed against the background of the available literature. We further attempt to define major indications for revisional bariatric surgery and balance them with perioperative and long-term morbidity as well as the surgical outcome.

Anastomotic ulcers (AUs) after Roux-en-Y gastric bypass (RYGB) occur in up to 16% of patients. In an international survey among members of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), current preventative and therapeutic strategies in AU were analyzed.An Internet-based survey was performed.One hundred eighty-nine surgeons completed the survey. Preoperative screening for Helicobacter pylori is performed by 65%. Eighty-eight percent of them prophylactically prescribe antacids for 3 months after surgery (interquartile range (IQR) 1-6). In case of AU, 99% of participants opt for proton pump inhibitors (PPIs) either alone (60%) or in combination with sucralfate (39%). After ulcer resolution, 52% continue PPI for 6 (3-6) months. In case of AU recurrence, 56% continue with conservative treatment. In contrast, 41% of them favor a renewal of the gastrojejunal anastomosis either combined with truncal vagotomy (18%) or with gastric remnant resection (13%), and only 2% choose to resect both gastric pouch and gastric remnant with subsequent reconstruction by esophagojejunostomy. In case of recurrence after surgical revision, 46% of participants opt again for a conservative approach, while 36% chose to redo the gastrojejunostomy once again.The majority of bariatric surgeons recommend preoperative screening and eradication of H. pylori as well as prophylactic use of PPI. If an AU is diagnosed, the role of PPI as a first-line treatment seems to be undisputed. However, dosage and duration of therapy remain unclear. In refractory AU, there is no consensus among bariatric surgeons whether conservative treatment or surgical revision should be performed.

OBJECTIVE Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective alternative to the current standard procedure laparoscopic Roux en Y gastric bypass (LRYGB). Prospective data comparing both procedures are rare. Therefore we performed a randomized clinical trial assessing the effectiveness and safety of these 2 operative techniques. METHODS Two hundred seventeen patients were randomized at 4 bariatric centers in Switzerland. One hundred seven patients underwent LSG using a 35 F bougie with suturing of the stapler line and 110 patients underwent LRYGB with a 150 cm antecolic alimentary and a 50 cm biliopancreatic limb. The mean body mass index of all patients was 44 ± 11.1 kg/m the mean age was 43 ± 5.3 years and 72 were female. RESULTS The 2 groups were similar in terms of body mass index age sex comorbidities and eating behavior. The mean operative time was less for LSG than for LRYGB (87 ± 52.3 minutes vs 108 ± 42.3 minutes; P = 0.003). The conversion rate was 0.9 in both groups. Complications (

Roux en Y gastric bypass (RYGB) surgery leads to bone loss in humans which may be caused by vitamin D and calcium malabsorption and subsequent secondary hyperparathyroidism. However because these conditions occur frequently in obese people it is unclear whether they are the primary causes of bone loss after RYGB. To determine the contribution of calcium and vitamin D malabsorption to bone loss in a rat RYGB model adult male Wistar rats were randomized for RYGB surgery sham operation ad libitum fed or sham operation body weight matched. Bone mineral density calcium and phosphorus balance acid base status and markers of bone turnover were assessed at different time points for 14 wk after surgery. Bone mineral density decreased for several weeks after RYGB. Intestinal calcium absorption was reduced early after surgery but plasma calcium and parathyroid hormone levels were normal. 25 hydroxyvitamin D levels decreased while levels of active 125 dihydroxyvitamin D increased after surgery. RYGB rats displayed metabolic acidosis due to increased plasma lactate levels and increased urinary calcium loss throughout the study. These results suggest that initial calcium malabsorption may play a key role in bone loss early after RYGB in rats but other factors including chronic metabolic acidosis contribute to insufficient bone restoration after normalization of intestinal calcium absorption. Secondary hyperparathyroidism is not involved in postoperative bone loss. Upregulated vitamin D activation may compensate for any vitamin D malabsorption. © 2013 the American Physiological Society.

Introduction BK viremia and polyomavirus-associated nephropathy (PVN) represent a significant problem after kidney transplantation. Both are associated with intensified immunosuppression, but other risk factors and the impact of a screening program on outcome are incompletely understood. Methods Here, we report on the short- and long-term outcome of a cohort of patients, who were transplanted in 2006/2007 and included in a newly introduced systematic 3-monthly screening for BK viremia at the University Hospital Zurich. In patients testing positive for BK viremia, screening frequency was intensified and immunosuppression reduced. Patients with suspected PVN underwent transplant biopsy. Results Among 152 included patients, 49 (32%) tested positive for BK viremia, but only 8 developed biopsy-proven PVN. BK viremia had a significant impact on estimated glomerular filtration rate and proteinuria in the first 2 years. Acute rejection episodes and the number of human leukocyte antigen (HLA) mismatches were the strongest independent predictors of BK viremia in a multiple logistic model. In contrast, no particular immunosuppressive agent or regimen was associated with enhanced risk. Conclusion Taken together, systematic BK viremia screening led to detection of a high percentage of viremic patients. With adjustment of immunosuppression, an excellent outcome was achieved. The independent association of HLA mismatches with BK viremia suggests impaired polyomavirus immunosurveillance in highly mismatched allografts.

This paper presents commentaries on neoadjuvant treatment esophagectomy; the prognostic and predictive effects of single nucleotide polymorphisms (SNP) in the multimodality therapy of esophageal cancer; optimal preoperative treatment prior to surgery for esophageal cancer; a possible role for trastuzumab in treating esophageal adenocarcinoma or any esophageal dysplasia/intra-epithelial neoplasia; surgery after chemoradiation in resectable esophageal cancer; whether para-aortic lymph node dissection should be performed in esophagogastric junction (EGJ) tumors; and transhiatal esophagectomy in treatment of the esophageal cancer.

Combined pancreas and kidney transplantation is the therapy of choice for type I diabetes patients with associated end-stage renal disease. To counterbalance increasing waiting lists, there is a clear need to extend the organ donor pool. Although results following simultaneous pancreas and kidney transplantation (SPK) using pediatric organs are encouraging, there is still reluctance in accepting them. This reflects the fear of graft thrombosis and graft failure because of small vessels and little absolute islet cell mass. Simpler transplant techniques for pediatric SPK might lower this threshold. In this article, a novel technique using a "piggy-back" implantation of the pancreas onto the conduits of en-bloc grafted kidneys, performed in two consecutive cases, is presented. This technique is associated with less vascular manipulation, requiring only one arterial anastomosis onto the frequently arteriosclerotic arteries of the recipient for all three organs. One-year follow-up (14 and 12 months) proved excellent graft function of kidneys and pancreas.

Background and objectives Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation. Design, setting, participants, & measurements We used data from the Efficacy Limiting Toxicity Elimination Symphony Study (1190 patients between 2002 and 2004) to model risk of rejection and infection in the first year after kidney transplantation. External validation was performed in a study population from the Fixed-Dose Concentration-Controlled Trial (630 patients between 2003 and 2006). Results Despite different temporal dynamics, rejections and severe infections had similar overall incidences in the first year after transplantation (23.4% and 25.5%, respectively), and infections were the principal cause of death (43.2% of all deaths). Recipient older age, deceased donor, higher number of HLA mismatches, and high risk for cytomegalovirus disease were associated with infection; deceased donor, higher number of HLA mismatches, and immunosuppressive therapy including cyclosporin A (compared with tacrolimus), with rejection. These factors were integrated into a two dimensional risk stratification model, which defined four risk groups: low risk for infection and rejection (30.8%), isolated risk for rejection (36.1%), isolated risk for infection (7.0%), and high risk for infection and rejection (26.1%). In internal validation, this model significantly discriminated the subgroups in terms of composite end point (low risk for infection/rejection, 24.4%; isolated risk for rejection and isolated risk for infection, 31.3%; high risk for infection/rejection, 54.4%; P

Der Diabetes mellitus Typ 2 stellt ein schwerwiegendes gesundheitsökonomisches Problem in der westlichen Welt dar. Übergewicht ist ein entscheidender Risikofaktor für das Auftreten eines Diabetes mellitus Typ 2. Nach bariatrischer Chirurgie (BMI >35 kg/m2) wurde bei einem Grossteil der Patienten bereits kurz postoperativ ein Verschwinden des Diabetes mellitus Typ 2 beobachtet. Zudem konnte gezeigt werden, dass die Magenbypassoperation die diabetesspezifische Letalität günstig beeinflusst. Diese Erkenntnisse eröffneten das Feld der metabolen Chirurgie. Die Beeinflussung des Glukosemetabolismus und damit des Diabetes mellitus Typ 2 durch operative Verfahren ist bislang erst in Kohorten mit kleinen Fallzahlen (Patienten mit BMI

Importance Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. Objective To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. Design, Setting, and Participants The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. Interventions Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). Main Outcomes and Measures The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. Results Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, −7.18%; 95% CI, −14.30% to −0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and Relevance Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. Trial Registration clinicaltrials.gov Identifier: NCT00356213

We report an intrahepatic sarcoma of the follicular dendritic cells in a 76-year-old woman with a medical history of a hyaline-vascular type of Castleman's disease. We discuss the clinico-pathological findings, the pathogenesis and the differential diagnosis of this rare tumour entity.

BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers.Methods. A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed.Results. In young rats (8-13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An M regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20-24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences.Conclusions. In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers. (c) 2009 Elsevier Inc. All rights reserved.

Malnutrition is a recognized risk factor for perioperative morbidity, but there is currently no standardized definition of malnutrition. The Nutrition Risk Screening 2002 score was recently proposed to identify patients at nutritional risk who may benefit from nutritional support therapy, and has been officially adopted by the European Society of Parenteral and Enteral Nutrition. The aim of this study was to assess the value of the Nutrition Risk Screening 2002 score in predicting the incidence and severity of postoperative complications in gastrointestinal surgery.We prospectively evaluated 608 patients admitted for elective gastrointestinal surgery. Nutritional risk was defined by the Nutrition Risk Screening 2002 score and correlated to the incidence and severity of postoperative complications. Complications were classified using an established surgical complication classification.The overall incidence of nutritional risk was 14%. We observed a significantly higher complication rate of 40% (35 out of 87) in patients at nutritional risk, compared to 15% (81 out of 521) in patients with a normal score (p0.001). The incidence of severe complications was significantly higher in patients at nutritional risk (54% versus 15%; p0.001). The odds ratio to develop a complication was 2.8 in patients at risk (p=0.001), and 3.0 in patients with malignant disease (p0.001). The median length of stay in nutritional risk patients was significantly longer (10 versus 4 days, p0.001).The prevalence of nutritional risk patients in gastrointestinal surgery is high. We showed that nutritional risk screening using the NRS 2002 strongly predicts the incidence and severity of complications.

Summary Background & aims The aim of the study was to implement nutritional risk screening (NRS-2002) and to assess the association between nutritional risk and clinical outcome. Methods NRS-2002 was implemented in 26 hospital departments (surgery, internal medicine, oncology, intensive care, gastroenterology and geriatrics) in Austria, the Czech Republic, Egypt, Germany, Hungary, Lebanon, Libya, Poland, Romania, Slovakia, Spain and Switzerland. Being a prospective cohort study, randomly selected adult patients were included at admission and followed during their hospitalisation. Data were collected on the nutritional risk screening, complications, mortality, length of stay and discharge. The correlation between risk status and clinical outcome was assessed and adjusted for confounders (age, speciality, diagnoses, comorbidity, surgery, cancer and region) by multivariate regression analysis. Results Of the 5051 study patients, 32.6% were defined as ‘at-risk’ by NRS-2002. ‘At-risk’ patients had more complications, higher mortality and longer lengths of stay than ‘not at-risk’ patients and these variables were significantly related to components of NRS-2002, also when adjusted for confounders. Conclusions Components of NRS-2002 are independent predictors of poor clinical outcome.

An increasing fraction of gastric cancer patients present with distant metastases at diagnosis. The objective of the present 11-year population-based trend analysis was to assess the survival rates in patients who underwent and in patients who did not undergo palliative gastrectomy. Patients with metastatic gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2009. Time trend and impact of palliative gastrectomy on survival were assessed by both a multivariate Cox proportional hazards model and propensity score matching. We identified 8249 patients with stage IV gastric cancer. The rate of metastatic disease increased from 31.0 % in 1998 to 37.5 % in 2009 (P

BACKGROUND We developed a multicentric Swiss protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. The aim of this study was to assess efficacy and safety of immunoadsorption column reuse in ABO-incompatible kidney transplantation. METHODS We performed a multicentric prospective trial including all ABO-incompatible kidney transplantations in Switzerland from 2005 to 2011. Patients received rituximab and standardized immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Antigen-specific perioperative immunoadsorption was performed. Immunoadsorption columns were reused after restoration. Graft survival, patient survival, kidney function, rejections, number of columns, adverse events after column reuse, and anti-A/anti-B antibody titers were assessed. RESULTS Seventy-one ABO-incompatible patients underwent antigen-specific immunoadsorption and could be transplanted across the blood group barrier. Kaplan-Meier estimates for both, patient-censored and death-censored graft survivals were both 97.2% at 5 years. Allograft function was excellent with a mean estimated glomerular filtration rate of 54 mL per min after 1 year. The median number of pretransplant immunoadsorptions was 5. All centers performed column reuse. A total of 394 immunoadsorption procedures were performed with reused filters. Patient survival, graft survival, and adverse events did not differ when filters were reused. Column reuse resulted in cost savings of 21,458 USD per patient. CONCLUSION We have introduced a national protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. Column reuse was efficient and safe.

En raison de la grande prevalence de l’obesite, un traitement chirurgical n’est disponible que pour une minorite de patients obeses. La selection des patients, le suivi medical et le choix de la technique operatoire par les specialistes sont decisifs pour un traitement reussi, et doivent s’effectuer de maniere interdisciplinaire en suivant les standards internationaux en vigueur.

Aufgrund der hohen Pravalenz der Adipositas ist eine chirurgische Therapie nur fur einen kleinen Prozentsatz der adiposen Patienten verfugbar. Patientenselektion, Nachsorge und die Wahl der Operationstechnik durch die Spezialisten sind entscheidend fur eine erfolgreiche Therapie und sollten interdisziplinar nach international gultigen Standards erfolgen.

Background Regenerating protein ( reg ) and pancreatic stone protein (PSP) have been discovered independently in the fields of diabetes and pancreatitis. Materials and methods These proteins are identical; however, because of the gap between the endocrine and exocrine field, there was never a consensus and the nomenclature has not been rectified. Since the time of the initial discovery, more isoforms have been unified. Historically, PSP was discovered long before reg , yet, in many areas outside of the pancreatitis research field, reg is being used. Results For PSP/ reg , a role in proliferation and regeneration of islet cells has been postulated. A hitherto insufficiently understood phenomenon is the massive up-regulation of PSP/ reg in pancreatic tissue and juice under conditions of stress. Similarly, PAP (pancreatitis-associated protein)/ reg III has been attributed various functional roles. Structurally, the ability to form fibrils after tryptic cleavage is a striking common features of both proteins. However, this biochemical transformation is in itself not enough to gain functional insight. Thus, physiological and genetic approaches are required to further characterize the role of these proteins in the pancreas. Recently, more evidence has been presented in support of the theory that PSP/ reg plays a key role in islet neogenesis/regeneration. Conclusions In this review we discuss the debate on the localization and functional roles of PSP/ reg and PAP/ regIII . Therefore, we have summarized hypotheses and experimental results supporting such hypotheses.

While pancreas transplantation has evolved within two decades from a frustrating and poorly-accepted therapeutic option to a highly successful procedure, the respective benefits of the successive surgical and immunosuppressive developments have remained unclear. The aim of this study was to determine using an evidence-based methodology, which novel approaches have contributed to the current results and whether pancreas transplantation is cost-effective. Out of 2481 articles, 102 analyzed either surgical or immunosuppressive aspects of pancreas transplantation. Urological complications were more frequent in bladder over enteric drainage (range: 62-63% vs. 12-20%, p = 0.0001), but without significant difference in patient or graft survival. Portal drainage was associated with a trend toward fewer complications and better hyperinsulinemia control over systemic drainage in retrospective studies. Immunosuppression combining induction therapy, a calcineurin inhibitor, mycophenolate mophetil (MMF) and corticosteroids were associated with a 40% decreased incidence of rejection (p = 0.01) and an increase in graft survival above 90% at 1 year (p < 0.05). Pancreas transplantation is highly cost-effective compared to conservative alternatives. We conclude that despite a paucity of large studies, enteric drainage should be recommended but the benefits of portal venous drainage remain debated. Quadruple immunosuppression protocols including induction therapy should be the standard regimen.

Secretory stress proteins (SSP) are a family of proteins including isoforms of pancreatitis-associated protein (PAP) and pancreatic stone protein (PSP/reg). In vitro exposure to trypsin results in the formation of insoluble fibrillar structures. SSP are constitutively secreted into pancreatic juice at low levels. The WBN/Kob rat is a model for chronic pancreatitis, displaying focal inflammation, destruction of the parenchyma and changes in the architecture of the acinar cell; the synthesis and secretion of SSP are also increased. We have investigated the secretory apparatus by SSP immunohistochemistry at the light- and electron-microscopical (EM) levels. Immunocytochemistry of PSP/reg in Wistar control rats reveals low levels, with individual acinar cells exhibiting high immunoreactivity in zymogen granules. PAP is not detectable. In the WBN/Kob rat, PSP/reg and PAP immunoreactivity is markedly increased. Double immunofluorescence for PSP/reg and PAP I or II demonstrates that these proteins colocalize to the same cell. Acinar cells change their secretory architecture by fusion of zymogen granules and elongation of the fused organelles. The immunogold technique has demonstrated an increase of SSP in zymogen granules in WBN/Kob rats. PSP/reg-positive zymogen granules fuse to form elongated structures with fibrillar contents. An extensive PSP/reg-positive fibrillar network is established in the cytosol. Extracellular fibrils have been observed in several ductules. Thus, SSP-derived fibrils form concomitantly with acinar damage in the WBN/Kob rat. Based on the known tryptic cleavage site of SSP, the in vivo generation of fibrils is presumably the result of premature trypsin activation.

Background. Pancreatic stone protein (PSP/ reg ) is a constitutively secreted protein in pancreatic juice. Pancreatitis-associated protein (PAP) belongs to the same family of proteins. PAP is highly increased during acute pancreatitis, while no exact data exist regarding PSP/ reg protein synthesis and secretion. Recently, an attempt to determine PSP/ reg and PAP levels in sera of rats with acute pancreatitis showed a significant increase in PAP but failed to demonstrate changes in PSP/ reg . Others reported that surgical manipulation of the pancreas, including sham controls, affected mRNA levels of PSP/ reg . Neither report determined protein levels of PSP/ reg . Methods. Rats were treated intraperitoneally with a supramaximal dose of caerulein to induce pancreatitis, a physiological dose of caerulein, or a saline injection. Pancreata were analyzed for PAP and PSP/ reg using ELISAs. RNA was extracted for Northern blot analysis of PAP I, II, and III and PSP/ reg mRNA. Results. Experimental induction of acute pancreatitis caused a coordinate increase in both PSP/ reg and PAP. PAP showed an acute response and returned to low levels within 48 h while PSP/ reg exhibited a more sustained response. Intraperitoneal application of a physiological dose of caerulein and even a saline injection caused an increase in PSP/ reg . Conclusion. PSP/ reg and PAP levels are increased through similar mechanisms by physiological and supramaximal doses of caerulein. However, PSP/ reg regulation appears to sustain high levels while PAP levels are more transient. Since the regulation of this protein family is affected even under mild stress, we define them as secretory stress proteins.

Recent genetic investigations into cationic trypsinogen and pancreatic secretory trypsin inhibitor (PSTI) led to the conclusion that mutations in either gene can contribute to the development of (hereditary) chronic pancreatitis. Since genetic animal models are not available yet, we have studied the Wistar-Bonn/Kobori (WBN/Kob) rat, a model for chronic pancreatitis (CP). To explore the possibility that PSTI may be secreted at lower levels or contain a mutation in the WBN/Kob rat, we investigated the masses of PSTI-I and -II and asked whether the ratio of PSTI/trypsinogen is decreased in animals with CP.We collected pancreatic juice from WBN/Kob and Wistar rats aged 6-36 weeks and measured PSTI-I (ELISA) and trypsin.PSTI-I and -II were identified in Wistar and WBN/Kob rats by mass spectrometry and N-terminal sequencing. Using a newly developed PSTI-I ELISA, we can show that the PSTI-I/trypsinogen ratio is not decreased but rather increased in WBN/Kob rats compared to healthy Wistar rats. No evidence for a PSTI mutation was found.Our data does not support the hypothesis that a dysbalance of PSTI/trypsinogen ratio is a causative factor for CP.

Bariatric surgery is the most effective treatment of obesity and its associated diseases like type 2 diabetes mellitus. Given the obesity epidemic and the efficacy of surgical treatment, the number of surgical weight loss procedures has grown in recent years. Nevertheless, there is little consensus regarding the extent of preoperative investigations required prior to patients undergoing surgery. This article aims to discuss the available evidence on which preoperative tests are useful for the detection and treatment of conditions such as venous thromboembolism, obstructive sleep apnea syndrome and Helicobacter pylori-positive gastritis prior to an operation. The present literature suggests that only a few preoperative investigations are essential, but that preoperative multidisciplinary care is beneficial.

Introduction Major abdominal surgery leads to a postoperative systemic inflammatory response, making it difficult to discriminate patients with systemic inflammatory response syndrome from those with a beginning postoperative infectious complication. At present, physicians have to rely on their clinical experience to differentiate between the two. Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP), both secretory proteins produced by the pancreas, are dramatically increased during pancreatic disease and have been shown to act as acute-phase proteins. Increased levels of PSP have been detected in polytrauma patients developing sepsis and PSP has shown a high diagnostic accuracy in discriminating the severity of peritonitis and in predicting death in intensive care unit patients. However, the prognostic value of PSP/PAP for infectious complications among patients undergoing major abdominal surgery is unknown. Methods and analysis 160 patients undergoing major abdominal surgery will be recruited preoperatively. On the day before surgery, baseline blood values are attained. Following surgery, daily blood samples for measuring regular inflammatory markers (c-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α and leucocyte counts) and PSP/PAP will be acquired. PSP/PAP will be measured using a validated ELISA developed in our research laboratory. Patient9s discharge marks the end of his/her trial participation. Complication grade including mortality and occurrence of infectious postoperative complications according to validated diagnostic criteria will be correlated with PSP/PAP values. Total intensive care unit days and total length of stay will be recorded as further outcome parameters. Ethics and dissemination The PSP trial is a prospective monocentric cohort study evaluating the prognostic value of PSP and PAP for postoperative infectious complications. In addition, a comparison with established inflammatory markers in patients undergoing major abdominal surgery will be performed to help evaluate the role of these proteins in predicting and diagnosing infectious and other postoperative complications. Institution ethics board approval ID KEKZH-Nr. STV 11-2009. Trial registration ClinicalTrials.gov: NCT01258179.

This paper presents commentaries on neoadjuvant treatment esophagectomy; the prognostic and predictive effects of single nucleotide polymorphisms (SNP) in the multimodality therapy of esophageal cancer; optimal preoperative treatment prior to surgery for esophageal cancer; a possible role for trastuzumab in treating esophageal adenocarcinoma or any esophageal dysplasia/intra-epithelial neoplasia; surgery after chemoradiation in resectable esophageal cancer; whether para-aortic lymph node dissection should be performed in esophagogastric junction (EGJ) tumors; and transhiatal esophagectomy in treatment of the esophageal cancer.