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Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay., Methods/design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA., Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival., Trial Registration Number: NCT02231086 (Clinicaltrials.gov).

Background: Post-operative nutritional deficiencies are a common complication following bariatric surgery. The incidence and time of occurrence are not clear, and the efficacy of supplementation remains questionable. Clear guidelines for nutritional follow-up and counselling are needed., Methods: Preoperative and post-operative deficiencies were determined in a group of 427 gastric bypass patients. The predictive value of preoperative laboratory findings for the development of post-operative deficiencies, the time of occurrence and the effect of supplementation of common deficiencies was studied., Results: Most common preoperative deficiencies were of folic acid (21.3%), vitamin D3 (17.5%) and iron (21.8%). Post-operative, a significant increase in the number of patients with anaemia and deficiencies of ferritin and vitamin B12 was found. Most deficiencies occur between 12 and 15 months post-operatively, but vitamin D3 deficiency occurs significantly earlier at 9.7 months. A preoperative iron, folic acid or ferritin deficiency results in a significant higher risk for developing a post-operative deficiency despite supplementation, and ferritin deficiency occurs significantly earlier in these patients. Oral treatment of post-operative vitamin B12 and vitamin D3 deficiencies was successful in more than 80% of the patients in contrast to oral treatment of anaemia which was only successful in 62.5% of the patients., Conclusion: Our study emphasizes the importance of preoperative assessment and treatment of nutritional deficiencies in morbidly obese patients undergoing gastric bypass surgery. Despite limited efficacy, post-operative oral supplementation should be encouraged as it decreases the incidence of deficiencies.

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the only curative option for patients with peritoneal carcinomatosis of colorectal origin. Despite meticulous preoperative assessment, CRS and HIPEC appear to be impossible in a subset of patients at the time of surgery. This study investigated which clinical factors may identify these patients before surgery and reported on factors influencing survival., Methods: All patients with PC of colorectal origin between April 2005 and November 2013 who underwent exploratory surgery to determine whether cytoreduction and HIPEC was feasible were included in this study. Details concerning preoperative patient characteristics, perioperative outcomes, treatment and survival were compared., Results: In total, 350 patients with PC were referred to evaluate the possibility of CRS + HIPEC of which 268 (76.6 %) underwent CRS and HIPEC and 82 (23.4 %) had an open-close procedure. The main reason for discontinuing surgery was widespread peritoneal disease (50 %). A preoperative ostomy and an ASA score of 3 were associated with an increased risk for "open and close" (O&C). Median survival was 11.2 months in patients treated with palliative chemotherapy (75 %) compared with 2.7 months with palliative care only., Conclusions: CRS and HIPEC were deemed unsuitable in almost a quarter of all patients undergoing surgery. No strong clinical predictors for O&C were found, stressing the need for better preoperative imaging modalities. Survival in these patients is limited, but the majority could be treated with palliative chemotherapy resulting in survival of almost 1 year.

Background: Experience with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in a pioneer hospital resulted in a treatment protocol that has become the standard in the Netherlands. Outcome of CRS and HIPEC was reviewed to assure differences between the pioneer phase and the period wherein the Dutch HIPEC protocol was clinically implemented., Methods: The first consecutive 100 CRS and HIPEC procedures performed in the Netherlands were included as pioneer cohort (1995-1999). Two-hundred and seventy-two procedures that were performed in three participating HIPEC centres after the implementation of the Dutch HIPEC protocol were included as the implementation cohort (2005-2012). Another 100 recent patients of the first centre were included as a control group (2009-2011). Indications for the CRS and HIPEC treatment were peritoneal carcinomatosis (PC) from colorectal carcinoma and pseudomyxoma peritonei (PMP)., Results: Of the 472 included procedures, 327 (69 %) procedures were performed for PC from colorectal carcinoma and 145 for PMP (31 %). Compared with the implementation phase, the pioneer phase was characterized by more affected abdominal regions (mean 4.3 vs. 3.5, p < 0.001), more resections (mean 3.8 vs. 3.4, p < 0.001), less macroscopic radical cytoreductions (66 vs. 86 %, p < 0.001) and more patients with major morbidity (grade III-V) (64 vs. 32 %, p < 0.001). Other determinants of morbidity were high tumour load and multiple organ resections. Outcome of the implementation phase was similar to the control group., Conclusions: This study determined that outcome had improved ever since the Dutch HIPEC protocol has been implemented based on completeness of cytoreduction and decreasing morbidity.

Background: Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC., Methods: Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations., Results: Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05)., Conclusion: Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC., (© 2014 Wiley Periodicals, Inc.)

Objective: To compare the diagnostic accuracy of conditional CT strategy, i.e. CT if ultrasound findings are negative or inconclusive, with immediate CT strategy for patients with suspected appendicitis., Design: Subanalysis of a prospective multicenter diagnostic accuracy study., Method: Only data of patients with signs of appendicitis based on medical history, physical examination, and laboratory tests were analyzed. All patients underwent both ultrasound and CT. Images of each were read by different observers who were blinded to the results of the other imaging modality. The observer then selected the most likely diagnosis. These diagnoses were compared with the reference standard, i.e. final diagnoses as assigned by an expert panel based on all available data and at least 6 months of follow-up., Results: A total of 422 patients with suspected appendicitis were included. In 251 patients the final diagnosis was acute appendicitis (59%). In 199 patients (47%), ultrasound findings were inconclusive or negative. Use of conditional CT strategy resulted in correctly identified number of correctly identified patients with appendicitis, i.e. 96% (95% CI 93-98), versus 95% identified by immediate CT (95% CI 91-97). However, conditional CT strategy resulted in more false positive diagnoses compared with immediate CT (39 versus 22), had an accompanying lower specificity of 77% (95% CI 70-83) versus 87% (95% CI 81-91), and a lower positive predictive value of 86% (95% CI 81-90) versus 92% (95% CI 87-95)., Conclusion: Use of a conditional CT strategy results in exactly the same number of patients with correctly identified acute appendicitis while halving the number of CTs needed. However, conditional strategy results in more false positive diagnoses.

Aim: To investigate whether cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is a feasible and effective option for patients with urological involvement of peritoneal carcinomatosis from colorectal cancer (CRC-PC)., Patients and Methods: The characteristics of patients with CRC-PC treated with CRS+HIPEC, with or without a urological procedure, between April 2005 and June 2013 in two tertiary Centres were analyzed., Results: Thirty-eight patients (14%) out of 267 CRC-PC patients treated with CRS+HIPEC had a urological procedure during cytoreduction. The median survival was not significantly different between patients with or without a urological procedure (26.9 versus 32.1 months, p=0.29). Severe complications occurred more in patients with a urological procedure (47% versus 20%, p<0.001). In patients with a urological procedure, the most frequent complications were gastrointestinal leakage (n=9) and intra-abdominal abscess formation (n=5)., Conclusion: Urological resections as a part of CRS+HIPEC in patients with peritoneal carcinomatosis of colorectal origin are feasible and effective. Severe complications are prevalent in these patients but survival is comparable to patients without involvement of the urinary system., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: In absence of specific dosing guidelines, the optimal dose of low molecular weight heparins for thrombosis prophylaxis in morbidly obese patients (BMI>40 kg/m(2)) remains unknown. In order to guide dosing in this patient group, a pharmacodynamics model is developed for nadroparin in morbidly obese and non-obese patients using anti-Xa levels as an endpoint, thereby characterizing the influence of excessive body weight on different pharmacodynamic model parameters., Methods: Twenty-eight morbidly obese and seven non-obese patients receiving 5700 IU and 2850 IU subcutaneous (s.c.) nadroparin for surgery, respectively, were included with a mean total body weight (TBW) of 135 kg (range 72-252 kg). Up to 11 anti-Xa levels were collected from the start until 24 h after nadroparin administration. Population pharmacodynamic modelling with covariate analysis was performed using NONMEM., Results: In a two-compartment pharmacodynamic model with baseline endogenous anti-Xa levels, the effect of nadroparin was found to be delayed and could be best described using a transit compartment. TBW was the most predictive covariate for clearance (CL=23.0 mL/min × (TBW/70)), while lean body weight (LBW) proved the most predictive covariate for central volume of distribution (V1=7.0 L × (LBW/60))., Conclusions: A pharmacodynamic model was developed characterizing anti-Xa levels after s.c. administration of nadroparin in patients weighing between 72 and 252 kg with TBW and LBW as the major determinants for clearance and volume of distribution, respectively.

Objective: Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels., Research Design and Methods: We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention., Results: BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced., Conclusions: Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Early enteral feeding through a nasoenteric feeding tube is often used in patients with severe acute pancreatitis to prevent gut-derived infections, but evidence to support this strategy is limited. We conducted a multicenter, randomized trial comparing early nasoenteric tube feeding with an oral diet at 72 hours after presentation to the emergency department in patients with acute pancreatitis., Methods: We enrolled patients with acute pancreatitis who were at high risk for complications on the basis of an Acute Physiology and Chronic Health Evaluation II score of 8 or higher (on a scale of 0 to 71, with higher scores indicating more severe disease), an Imrie or modified Glasgow score of 3 or higher (on a scale of 0 to 8, with higher scores indicating more severe disease), or a serum C-reactive protein level of more than 150 mg per liter. Patients were randomly assigned to nasoenteric tube feeding within 24 hours after randomization (early group) or to an oral diet initiated 72 hours after presentation (on-demand group), with tube feeding provided if the oral diet was not tolerated. The primary end point was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up., Results: A total of 208 patients were enrolled at 19 Dutch hospitals. The primary end point occurred in 30 of 101 patients (30%) in the early group and in 28 of 104 (27%) in the on-demand group (risk ratio, 1.07; 95% confidence interval, 0.79 to 1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% and 26%, respectively; P=0.87) or death (11% and 7%, respectively; P=0.33). In the on-demand group, 72 patients (69%) tolerated an oral diet and did not require tube feeding., Conclusions: This trial did not show the superiority of early nasoenteric tube feeding, as compared with an oral diet after 72 hours, in reducing the rate of infection or death in patients with acute pancreatitis at high risk for complications. (Funded by the Netherlands Organization for Health Research and Development and others; PYTHON Current Controlled Trials number, ISRCTN18170985.).

Background: Preoperative differentiation between malignant and benign pancreatic tumors can be difficult. Consequently, a proportion of patients undergoing pancreatoduodenectomy for suspected malignancy will ultimately have benign disease. The aim of this study was to compare preoperative clinical and diagnostic characteristics of patients with unexpected benign disease after pancreatoduodenectomy with those of patients with confirmed (pre)malignant disease., Methods: We performed a multicenter retrospective cohort study in 1,629 consecutive patients undergoing pancreatoduodenectomy for suspected malignancy between 2003 and 2010 in 11 Dutch centers. Preoperative characteristics were compared in a benign:malignant ratio of 1:3. Malignant cases were selected from the entire cohort by using a random number list. A multivariable logistic regression prediction model was constructed to predict benign disease., Results: Of 107 patients (6.6 %) with unexpected benign disease after pancreatoduodenectomy, 86 fulfilled the inclusion criteria and were compared with 258 patients with (pre)malignant disease. Patients with benign disease presented more often with pain (56 vs. 38 %; P = 0.004), but less frequently with jaundice (60 vs. 80 %; P < 0.01), a pancreatic mass (13 vs. 54 %, P < 0.001), or a double duct sign on computed tomography (21 vs. 47 %; P < 0.001). In a prediction model using these parameters, only 19 % of patients with benign disease were correctly predicted, and 1.4 % of patients with malignant disease were missed., Conclusions: Nearly 7 % of patients undergoing pancreatoduodenectomy for suspected malignancy were ultimately diagnosed with benign disease. Although some preoperative clinical and imaging characteristics might indicate absence of malignancy, their discriminatory value is insufficient for clinical use.

Background/objectives: Acute pancreatitis has a highly variable clinical course. Early and reliable predictors for the severity of acute pancreatitis are lacking. Proteinuria appears to be a useful predictor of disease severity and outcome in a variety of clinical conditions. This study aims to investigate the predictive value of proteinuria on admission for the severity of acute pancreatitis compared with other commonly used predictors; the APACHE II score, Modified Glasgow score and C-reactive protein (CRP)., Methods: This is a post-hoc analysis of 64 patients admitted with acute pancreatitis treated in one teaching hospital, who participated in a previous randomized trial. Proteinuria was defined as a Protein/Creatinine (P/C) ratio >23 mg/mmol. The primary endpoint was severe acute pancreatitis. Secondary endpoints included infectious complications, need for invasive intervention, ICU stay and in-hospital mortality., Results: Proteinuria was present in 30/64 patients (47%). Eleven patients (17%) had severe acute pancreatitis. There was no difference in incidence of severe acute pancreatitis between patients with and without proteinuria: 6/30 patients (20%) versus 5/34 patients (15%) respectively (p = 0.58). Likewise, the occurrence of infectious complications, need for intervention and ICU stay and mortality did not differ significantly (p = 0.58, p = 0.99, p = 0.33 and p = 0.60 respectively). The diagnostic performance of the P/C ratio for the prediction of severe pancreatitis was inferior to the Modified Glasgow score (p = 0.04) and CRP (p = 0.03)., Conclusion: Proteinuria on admission does not seem to be a reliable predictor for disease severity in acute pancreatitis. The diagnostic performance of the P/C ratio is inferior to the Modified Glasgow score and CRP., (Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Aims/hypothesis: Not all obese individuals develop type 2 diabetes. Why some obese individuals retain normal glucose tolerance (NGT) is not well understood. We hypothesise that the biochemical mechanisms that underlie the function of adipose tissue can help explain the difference between obese individuals with NGT and those with type 2 diabetes., Methods: RNA sequencing was used to analyse the transcriptome of samples extracted from visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of obese women with NGT or type 2 diabetes who were undergoing bariatric surgery. The gene expression data was analysed by bioinformatic visualisation and statistical analyses techniques., Results: A network-based approach to distinguish obese individuals with NGT from obese individuals with type 2 diabetes identified acetyl-CoA metabolic network downregulation as an important feature in the pathophysiology of type 2 diabetes in obese individuals. In general, genes within two reaction steps of acetyl-CoA were found to be downregulated in the VAT and SAT of individuals with type 2 diabetes. Upon weight loss and amelioration of metabolic abnormalities three months following bariatric surgery, the expression level of these genes recovered to levels seen in individuals with NGT. We report four novel genes associated with type 2 diabetes and recovery upon weight loss: ACAT1 (encoding acetyl-CoA acetyltransferase 1), ACACA (encoding acetyl-CoA carboxylase α), ALDH6A1 (encoding aldehyde dehydrogenase 6 family, member A1) and MTHFD1 (encoding methylenetetrahydrofolate dehydrogenase)., Conclusions/interpretation: Downregulation of the acetyl-CoA network in VAT and SAT is an important feature in the pathophysiology of type 2 diabetes in obese individuals. ACAT1, ACACA, ALDH6A1 and MTHFD1 represent novel biomarkers in adipose tissue associated with type 2 diabetes in obese individuals.

Background: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers., Methods: Twenty morbidly obese patients [mean body weight 144 kg (range 112-186 kg) and mean body mass index 47 kg/m(2) (range 40-68 kg/m(2))] participated in the study. All patients received a midazolam 7.5 mg oral and 5 mg intravenous dose (separated by 159 ± 67 min) and per patient 22 samples over 11 h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM(®)., Results: In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar [0.36 (4 %) L/min], while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (P < 0.001). Central and peripheral volumes of distribution increased substantially with body weight (both P < 0.001) and absorption rate (transit rate constant) was lower in morbidly obese patients [0.057 (5 %) vs. 0.130 (14 %) min(-1), P < 0.001]., Conclusions: In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings.

Background: Choledochocystolithiasis can be managed by endoscopic retrograde cholangiopancreaticography (ERCP) or laparoscopically by transcystic (TC) or transductal (TD) stone extraction., Objective: The aim of this study was to systematically review safety and effectiveness of combined endoscopic/laparoscopic management versus total laparoscopic management for choledochocystolithiasis with specific emphasis on TC versus TD stone extraction., Methods: MEDLINE/PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched systematically to identify trials on combined endoscopic/laparoscopic and total laparoscopic management for choledochocystolithiasis. Laparoscopic common bile duct (CBD) exploration was divided into TD and TC approach. Primary outcomes were successful stone clearance from CBD, postoperative/procedural morbidity, and mortality., Results: Eight randomized trials with 965 patients were included. Successful bile duct clearance varied between 52.6 and 97 % in the ERCP groups, 80.4 and 100 % in the TC groups, and 58.3 and 100 % in the TD groups. There were more bile leaks after TD stone extraction (11 %) than after ERCP (1 %) and TC stone extraction (1.7 %). Total morbidity varied between 9.1 and 38.3 % in the ERCP groups, 7 and 10.5 % in the TC groups, and 18.4 and 26.7 % in the TD groups. Methodological and statistical heterogeneity among the trials precluded a meaningful meta-analysis., Conclusion: Stone clearance rates are comparable between the three modalities, but TD stone extraction is associated with a higher risk of bile leaks and should only be performed by highly experienced surgeons. TC stone extraction seems a more accessible technique with lower complication rates. If unsuccessful, per- or postoperative endoscopic stone extraction is a viable option.

Background: When peritoneal carcinomatosis (PC) is diagnosed during emergency surgery for colorectal cancer (CRC), further treatment with curative intent may seem futile given the known poor prognosis of both PC and emergency surgery. The aim of the current study was to investigate the feasibility and effectiveness of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC patients who previously underwent emergency surgery in the presence of PC., Methods: All patients with synchronous PC of CRC referred to two tertiary centers between April 2005 and November 2013 were included in this study. Operative, postoperative and survival details were compared between patients presenting in an emergency or elective setting., Results: In total, 149 patients with synchronous PC underwent CRS and HIPEC. Amongst these patients, 36 (24.2 %) initially presented with acute symptoms requiring emergency surgery. Acute presentation did not result in a longer interval between the initial operation and HIPEC (2.2 vs. 2.1 months; P = 0.09). When comparing operative outcomes, no significant differences were found in blood loss (P = 0.47), operation time (P = 0.39), or completeness of cytoreduction (P = 0.97). In addition, complication rates, degree and types of complication did not differ between the groups. Median survival was 36.1 months for emergency presentation compared with 32.1 in the elective group (P = 0.73)., Conclusion: CRS + HIPEC may be performed safely in patients with PC of colorectal origin presenting with acute symptoms requiring emergency surgery. More importantly, the 5-year survival rate in these patients was equal to elective cases. This should be regarded as promising and therefore considered for these patients.

Purpose: Anastomotic leakage is a serious complication after colorectal surgery, and many risk factors for this problem have so far been identified. The aim of this study was to assess the association between visceral arterial occlusive disease and anastomotic leakage., Methods: The preoperative abdominal computed tomography scans from all consecutive patients who underwent colorectal surgery with anastomosis in 2010 were retrospectively analyzed., Results: A total of 242 patients were included, with a median age of 65 years (interquartile range 55-74). Anastomotic leakage occurred in 14 % of cases (n = 34). The mortality rate was 3 % (n = 8). There was no association between atherosclerosis of the visceral or iliac arteries and anastomotic leakage. There was also no association between right-sided or left-sided resections and total occlusion of the superior or inferior mesenteric artery, respectively., Conclusion: Asymptomatic visceral artery occlusive disease is not a risk factor for anastomotic leakage after colorectal surgery, and additional radiological imaging or percutaneous transluminal angioplasty for occluded visceral vessels is not indicated prior to colorectal surgery.

Background: It is generally accepted that patients following an episode of diverticulitis should have additional colonoscopy screening to rule out a colorectal malignancy. We aimed to investigate the rate of CRC found by colonoscopy after an attack of uncomplicated diverticulitis., Methods: MEDLINE, Embase, and Cochrane databases were searched systematically for clinical trials or observational studies on colonic evaluation by colonoscopy after the initial diagnosis of acute uncomplicated diverticulitis, followed by hand-searching of reference lists., Results: Nine studies met the inclusion criteria and included a total number of 2,490 patients with uncomplicated diverticulitis. Subsequent colonoscopy after an episode of uncomplicated diverticulitis was performed in 1,468 patients (59%). Seventeen patients were diagnosed with CRC, having a prevalence of 1.16% (95% confidence interval 0.72-1.9% for CRC). Hyperplastic polyps were seen in 156 patients (10.6%), low-grade adenoma in 90 patients (6.1%), and advanced adenoma was reported in 32 patients (2.2%)., Conclusion: Unless colonoscopy is regarded for screening in individuals aged 50 years and older, routine colonoscopy in the absence of other clinical signs of CRC is not required.

Background and Objectives: CytoReductive Surgery (CRS) combined with Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has an established role in the treatment of peritoneally metastasized colorectal cancer. The aim of the study was to describe the recurrence patterns and to evaluate treatment options and related survival., Methods: Patients treated with CRS + HIPEC in two tertiary referral centers between April 2005 and March 2013 were analyzed retrospectively. The prognostic value of several parameters was calculated using Cox Regression., Results: One hundred thirty two of 287 patients (46%) with peritoneal carcinomatosis treated with complete CRS and HIPEC were diagnosed with recurrent disease, after a median disease-free interval of 11.4 months. Recurrence were locoregional (43%), distant metastases (26%) or both (31%). Thirty-two of the 132 patients with recurrences (24%) were treated surgically with curative intent, which extended the median survival from 12 months to 43 months, compared to palliative treatment (best supportive care or chemotherapy; P < 0.001). Initial nodal status (P = 0.01) and the number of affected regions at initial CRS (P = 0.02) were significantly correlated to survival after disease recurrence., Conclusion: Disease recurrence after CRS and HIPEC is common; in selected patients, an aggressive surgical approach may be beneficial and extend survival., (© 2014 Wiley Periodicals, Inc.)

Objective: Roux-en-Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very-low-calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose-tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM)., Design: Controlled, nonrandomized observational trial., Patients and Measurements: Four groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT-GB (n = 11), NGT-RYGB (n = 16), T2DM-RYGB (n = 15) and T2DM-VLCD (n = 12). Normal weight controls (n = 12) were studied once., Results: At baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP-1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vs RYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP-1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels., Conclusions: These data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP-1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short-term metabolic benefits of RYGB in obese T2DM patients., (© 2013 John Wiley & Sons Ltd.)

Purpose: Impaired functional outcome is common after a low anterior resection (LAR). Pelvic floor rehabilitation (PFR) might improve functional outcome after a LAR. The aim of this systematic review is to evaluate the effectiveness of PFR in improving functional outcome., Methods: PubMed, Embase, and the Cochrane Library were searched using the terms fecal incontinence, colorectal neoplasm/surgery, LAR, rectal cancer, anterior resection syndrome, bowel habit, pelvic floor, training, therapy, physical therapy, rehabilitation and biofeedback. Of the 125 identified records, 5 articles were included., Results: The 5 included studies reported on 321 patients, of which 286 patients (89%) underwent pelvic floor training. Three studies included patients with anterior resection syndrome after a LAR while the remaining studies included a series of patients after a LAR. Functional outcome was mostly assessed by using the Wexner incontinence scale. Quality of life was assessed in one study, and in three studies, rectal manometry was performed. After PFR, the functional outcome was improved in four studies, as was the quality of life., Conclusion: This systematic review demonstrated that PFR is useful for improving the functional outcome after a LAR. The data are extracted from studies of limited quality, but the available evidence points to the effectiveness of the procedure.

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy improves outcome of patients with peritoneal carcinomatosis (PC) of colorectal carcinoma. Data on the occurrence of PC in T4 colorectal carcinoma are scarce. We investigated the occurrence and risk factors for PC in these patients., Methods: This was a retrospective cohort study of patients undergoing a first resection of a T4 colorectal carcinoma in a tertiary hospital between January 2000 and December 2007. Primary outcome was the occurrence of synchronous or metachronous PC. The association with PC and several patient and tumor characteristics was evaluated using logistic regression., Results: A total of 200 patients underwent resection of a T4 colorectal carcinoma. Median follow-up censored for death was 66 months (18-89 months). Synchronous PC was found in 46 of 200 patients (23 %) and metachronous PC in 33 of 154 patients (21 %). In univariable analysis, factors associated with PC were: age (OR 0.97; 95 % CI 0.94-0.99; P = 0.03), radical resection (OR 0.32; 95 % CI 0.11-0.91; P = 0.03), and N stage (OR 1.63; 95 % CI 1.36-2.34; P = 0.008). In multivariable analysis, only N stage was associated with PC (OR 1.62; 95 % CI 1.12-2.34; P = 0.01). This association was not significant for the 154 patients at risk for metachronous PC., Conclusions: Around 1 in 5 patients undergoing resection of a T4 colorectal carcinoma either have PC during primary resection or develop PC during follow-up. N stage was associated with PC in the entire study population. However, none of the clinical or pathological variables were associated with the risk of metachronous PC and therefore cannot be used to develop targeted surveillance strategies.

Background: Anastomotic leakage is one of the most life-threatening complications after colonic surgery. Correct diagnosis and treatment is important to reduce morbidity and mortality. An abdominal CT scan is one of the main diagnostic tools in diagnosing anastomotic leaks. The aim of this study was to examine the accuracy of abdominal CT scanning to detect anastomotic leakage and to evaluate the consequences of a false-negative CT outcome., Methods: All consecutive patients who underwent colonic resection for malignant disease between 2009 and 2011 or for benign disease in 2010 were reviewed. Patients in whom a postoperative abdominal CT scan was performed to detect anastomotic leakage were included., Results: In 97 of 524 patients who underwent colonic surgery, an abdominal CT scan was performed for the suspicion of anastomotic leakage. Overall leakage rate was 10.9 % (n = 57). Mortality rate after leakage was 21.1 % (n = 12). Results from all abdominal CT scans revealed an overall sensitivity of 0.59 (95 % CI 0.43-0.73), a specificity of 0.88 (95 % CI 0.75-0.95), positive predictive value 0.82 (95 % CI 0.64-0.92), negative predictive value 0.70 (95 % CI 0.57-0.81), and an accuracy of 74 %. Delayed reintervention for anastomotic leakage due to a false-negative CT outcome resulted in death in 62.5 % (n = 5)., Conclusion: The sensitivity of abdominal CT scanning after colonic surgery is relatively low. A negative CT scan does not rule out anastomotic leakage. Even with a negative CT scan, we should remain equally alert at clinical deterioration as an argument for timely intervention.

Background: Laparoscopic adjustable gastric banding (LAGB) is a commonly performed bariatric procedure. LAGB is frequently complicated by slippage. Possible treatment for slippage is rebanding, but long-term effects are unknown. The aim of this study was to investigate whether rebanding after gastric band slippage is associated with weight loss failure., Methods: This was a post hoc analysis of a prospectively collected database of 627 consecutive LAGB patients. Rebanding for slippage was performed in 81 patients. The effect of rebanding on weight loss was evaluated by three analyses: (1) in 81 rebanded patients, weight loss was compared before and after rebanding, separately for patients in whom primary LAGB was successful or unsuccessful; (2) 81 rebanded patients were matched to 81 patients without slippage for prognostic variables and compared for weight loss after rebanding; (3) multivariate logistic regression was performed whether rebanding was independently associated with weight loss failure., Results: The chance of a fair result of rebanding for patients following primary successful (n = 34) and unsuccessful LAGB (n = 22) was 62 and 27 % after median follow-up of 113 and 97 months, respectively. There was no difference in weight loss failure between 81 rebanded patients and 81 matched patients: 54 vs 59 % (P = 0.43). In multivariate analysis, rebanding was not significantly associated with weight loss failure: adjusted odds ratio 1.42; 95 % confidence interval 0.85-2.38; P = 0.18., Conclusion: In general, rebanding after LAGB has no negative effect on weight loss. However, patients in whom LAGB was unsuccessful prior to rebanding have poor long-term weight loss results.

Objectives: As morbidly obese patients are prone to surgical site infections, adequate blood and subcutaneous tissue concentrations of prophylactic antibiotic agents during surgery are imperative. In this study we evaluated cefazolin subcutaneous adipose tissue distribution in morbidly obese and non-obese patients, thereby quantifying the influence of morbid obesity on cefazolin pharmacokinetics and enabling Monte Carlo simulations for subsequent dose adjustments., Methods: Nine morbidly obese patients [body mass index (BMI) 47 ± 6 kg/m(2)], of whom eight were evaluable, and seven non-obese patients (BMI 28 ± 3 kg/m(2)) received cefazolin 2 g intravenously before surgery (NCT01309152). Using microdialysis, interstitial space fluid (ISF) samples of subcutaneous adipose tissue were collected together with total and unbound plasma cefazolin samples until 240 min after dosing. Using NONMEM, population pharmacokinetic modelling, covariate analysis and Monte Carlo simulations were performed., Results: The unbound (free) cefazolin ISF penetration ratio (fAUC(tissue)/fAUC(plasma)) was 0.70 (range 0.68-0.83) in morbidly obese patients versus 1.02 (range 0.85-1.41) in non-obese patients (P < 0.05). A two-compartment model with saturable protein binding was identified in which the central volume of distribution and cefazolin distribution from the central compartment to the ISF compartment proved dependent on body weight (P < 0.001 and P < 0.01, respectively). Monte Carlo simulations showed reduced probability of target attainment for morbidly obese versus non-obese patients for MIC values of 2 and 4 mg/L., Conclusions: This study shows that cefazolin tissue distribution is lower in morbidly obese patients and reduces with increasing body weight, and that dose adjustments are required in this patient group.

Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. The aim of the current study was to provide reliable population-based data on the incidence, risk factors and prognosis of PC of gastric origin. All patients diagnosed with gastric cancer in the area of the Eindhoven Cancer Registry between 1995 and 2011 were included. Incidence and survival were computed and risk factors for peritoneal carcinomatosis were determined using multivariate logistic regression analysis. In total, 5,220 patients were diagnosed with gastric cancer, of whom 2,029 (39%) presented with metastatic disease. PC was present in 706 patients (14%) of whom 491 patients (9%) had PC as the only metastatic site. Younger age (<60 years), female gender, advanced T- and N-stage, primary tumor of signet ring cells or linitis plastica and primary tumors covering multiple anatomical locations of the stomach were all associated with a higher odds ratios of developing PC. Median survival of patients without metastases was 14 months, but only 4 months for patients with PC. PC is a frequent condition in patients presenting with gastric cancer, especially in younger patients with advanced tumor stages. Given the detrimental influence of PC on survival, efforts should be undertaken to further explore the promising results that were obtained in preventing or treating this condition with multimodality strategies., (Copyright © 2013 UICC.)

Objectives: The impact of postoperative complications after Major Abdominal Surgery (MAS) is substantial, especially when socio-economical aspects are taken into account. This systematic review focuses on the effects of preoperative exercise therapy (PEXT) on physical fitness prior to MAS, length of hospital admission and postoperative complications in patients eligible for MAS, and on what is known about the most effective kind of exercise regime., Methods: A systematic search identified randomised controlled trials on exercise therapy and pulmonary physiotherapy prior to MAS. The methodological quality of the included studies was rated using the 'Delphi List For Quality Assessment of Randomised Clinical Trials'. The level of agreement between the two reviewers was estimated with Cohen's kappa., Results: A total of 6 studies were included, whose methodological quality ranged from moderate to good. Cohen's kappa was 0.90. Three studies reported on improving physical fitness prior to MAS with the aid of PEXT. Two studies reported on the effect of training on postoperative complications, showing contradictory results. Three studies focused on the effect of preoperative chest physiotherapy on postoperative lung function parameters after MAS. While the effects seem positive, the optimal training regime is still unclear., Conclusion: Preoperative exercise therapy might be effective in improving the physical fitness of patients prior to major abdominal surgery, and preoperative chest physiotherapy seems effective in reducing pulmonary complications. However consensus on training method is lacking. Future research should focus on the method and effect of PEXT before high-risk surgical procedures., (Copyright © 2013 Surgical Associates Ltd. All rights reserved.)

Purpose: This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol., Methods: In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival., Results: Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III-V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0-166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36-46 months). Median progression-free survival was 15 months (95 % CI 13-17 months) for CRC patients and 53 months (95 % CI 40-66 months) for PMP patients. Overall median survival was 33 (95 % CI 28-38 months) months for CRC patients and 130 months (95 % CI 98-162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients., Conclusions: The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.

Objective: Obesity and weight loss influence thyroid hormone physiology. The effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) in obese subjects have not been studied in parallel. We hypothesized that differences in transient systemic inflammation and catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology., Design and Methods: We recruited 12 lean and 27 obese females with normal fasting glucose (normal glucose tolerant (NGT)) and 27 obese females with type 2 diabetes mellitus (T2DM) for this study. Weight loss was achieved by restrictive treatment (gastric banding or high-protein-low-calorie diet) or by RYGB. Fasting serum leptin, TSH, triiodothyronine (T₃), reverse T₃ (rT₃), and free thyroxine (fT₄) concentrations were measured at baseline and 3 weeks and 3 months after the start of the interventions., Results: Obesity was associated with higher TSH, T₃, and rT₃ levels and normal fT₄ levels in all the subjects when compared with the controls. After 3 weeks, calorie restriction and RYGB induced a decline in TSH levels and a rise in rT₃ and fT₄ levels. The increase in rT₃ levels correlated with serum interleukin 8 (IL8) and IL6 levels. After 3 months, fT₄ and rT₃ levels returned to baseline levels, whereas TSH and T₃ levels were persistently decreased when compared with baseline levels. No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM subjects were observed at any time point., Conclusions: In summary, weight loss directly influences thyroid hormone regulation, independently of the weight loss strategy used. The effects may be explained by a combination of decreased leptin levels and transient changes in peripheral thyroid hormone metabolism.

Background: The Pittsburgh Rating Scale is the only validated classification system of skin deformities occurring after massive weight loss. The purpose of this study was to replicate the validation of the Pittsburgh Rating Scale classification and to evaluate its usefulness in the treatment of massive weight-loss patients in The Netherlands., Methods: Thirteen trained observers applied the Pittsburgh Rating Scale to photographs of 25 patients. These photographs showed the 10 regions of the body for which the Pittsburgh Rating Scale is designed. Six of the observers were medical specialists, three were medical interns in plastic surgery and four observers were specialised nurse practitioners. As a measure of inter-rater agreement we calculated the intraclass correlation with a threshold value of 0.6 for good validity. The observers also answered 11 questions about the scale's usefulness in daily practice., Results: In two consecutive tests the photographs of 10 regions were scored, which resulted in a total of 20 observations per patient. Sixty percent of the intraclass correlation values were below the threshold of 0.6 for good validity. The mean intraclass correlation value was 0.577., Conclusions: The Pittsburgh Rating Scale could not be validated as a reliable classification system for skin deformities after massive weight loss. The scale however seems to be a good first step in a challenging task. There was no doubt among the observers that a good classification system would be beneficial for adequate treatment. A modified Pittsburgh Rating Scale should include, besides anatomical parameters, functional disability and hygienic impairment scores and perioperative risk factors., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Timely diagnosis of anastomotic leakage after colorectal surgery and adequate treatment is important to reduce morbidity and mortality. Abdominal computed tomography (CT) scanning is the diagnostic tool of preference, but its value may be questionable in the early postoperative period. The accuracy of CT scanning for the detection of anastomotic leakage and its role in timing of intervention was evaluated., Methods: A systematic literature search was performed. Relevant publications were identified from four electronic databases between 1990 and 2011. Inclusion criteria were human studies, studies published in English or Dutch, colorectal surgery with primary anastomosis, and abdominal CT scan with reported outcome for the detection of anastomotic leakage. Exclusion criteria were cohort of fewer than five patients, other gastrointestinal surgery, no anastomosis, and radiological imaging other than CT., Results: Eight studies, including 221 abdominal CT scans, fulfilled the inclusion criteria. Overall, the methodological quality of the studies was poor. The overall sensitivity of CT scanning to diagnose leakage was 0.68 (95 % confidence interval 0.59-0.75) for colonic resection. Data on the sequelae of false-negative CT scanning was not available., Conclusion: There is limited good-quality evidence to determine the value of CT scans in the detection of anastomotic leakage. To prevent delay in diagnosis and appropriate treatment of anastomotic leakage, the relatively low sensitivity of CT scanning must be taken into account.

Background: Endoscopic retrograde cholangiography (ERCP) with endoscopic sphincterotomy (ES) followed by a laparoscopic cholecystectomy (LC) is generally accepted as the treatment of choice for patients with choledochocystolithiasis who are eligible for surgery. Previous studies have shown that LC after ES is associated with a high conversion rate. The aim of the present study was to assess the complexity of LC after ES compared with standard LC for symptomatic uncomplicated cholecystolithiasis., Methods: The study population consisted of two patient cohorts: patients who had undergone a previous ERCP with ES for choledocholithiasis (PES) and patients with cholecystolithiasis who had no previous intervention prior to LC (NPES)., Results: The PES group consisted of 93 patients and the NPES group consisted of 83 consecutive patients. Patients in the PES group had higher risks for longer [more than 65 min, odds ratio (OR) = 4.21 (95% confidence interval (CI) 1.79-9.91)] and more complex [higher than 6 points, on a 0-10 scale, OR 3.12 (95% CI 1.43-6.81)] surgery. The conversion rate in the PES and NPES group (6.5% versus 2.4%, respectively) and the complication rate (12.9% versus 9.6%, respectively) were not significantly different., Discussion: A laparoscopic cholecystectomy after ES is lengthier and more difficult than in uncomplicated cholelithiasis and should therefore be performed by an experienced surgeon., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Bariatric surgery for morbid obesity results in massive weight loss and improvement of health and quality of life. A downside of the major weight loss is the excess of overstretched skin, which may influence the patient's quality of life by causing functional and aesthetic problems. The purpose of the current study was to evaluate the patient's quality of life long-term after body contouring following bariatric surgery., Methods: Quality of life was measured with the Obesity Psychosocial State Questionnaire in 33 post-bariatric surgery patients 7.2 years (range, 3.2 to 13.3 years) after body contouring surgery. Data were compared with previous assessments 4.1 years (range, 0.7 to 9.2 years) after body contouring surgery of the quality of life at that time and before body contouring surgery., Results: Compared with appraisals of quality of life before body contouring surgery, a significant, mostly moderate to large, sustained improvement of quality of life was observed in post-bariatric surgery patients 7.2 years after body contouring surgery in six of the seven psychosocial domains. A small deterioration occurred between 4.1- and 7.2-year follow-up on two of the seven domains except for the domain efficacy toward eating, which showed a significant improvement. At 7-year follow-up, 18 patients (55 percent) were satisfied with the result of body contouring surgery., Conclusions: This study indicates a sustained quality-of-life improvement in post-bariatric surgery patients after body contouring surgery. This suggests the importance of including reconstructive surgery as a component in the multidisciplinary approach in the surgical treatment of morbid obesity., Clinical Question/level of Evidence: Therapeutic, IV.

Objectives: To determine the risk of recurrent biliary events in the period after mild biliary pancreatitis but before interval cholecystectomy and to determine the safety of cholecystectomy during the index admission., Background: Although current guidelines recommend performing cholecystectomy early after mild biliary pancreatitis, consensus on the definition of early (ie, during index admission or within the first weeks after hospital discharge) is lacking., Methods: We performed a systematic search in PubMed, Embase, and Cochrane for studies published from January 1992 to July 2010. Included were cohort studies of patients with mild biliary pancreatitis reporting on the timing of cholecystectomy, number of readmissions for recurrent biliary events before cholecystectomy, operative complications (eg, bile duct injury, bleeding), and mortality. Study quality and risks of bias were assessed., Results: After screening 2413 studies, 8 cohort studies and 1 randomized trial describing 998 patients were included. Cholecystectomy was performed during index admission in 483 patients (48%) without any reported readmissions. Interval cholecystectomy was performed in 515 patients (52%) after 40 days (median; interquartile range: 19-58 days). Before interval cholecystectomy, 95 patients (18%) were readmitted for recurrent biliary events (0% vs 18%, P < 0.0001). These included recurrent biliary pancreatitis (n = 43, 8%), acute cholecystitis (n = 17), and biliary colics (n = 35). Patients who had an endoscopic retrograde cholangiopancreatography had fewer recurrent biliary events (10% vs 24%, P = 0.001), especially less recurrent biliary pancreatitis (1% vs 9%). There were no differences in operative complications, conversion rate (7%), and mortality (0%) between index and interval cholecystectomy. Because baseline characteristics were only reported in 26% of patients, study populations could not be compared., Conclusions: Interval cholecystectomy after mild biliary pancreatitis is associated with a high risk of readmission for recurrent biliary events, especially recurrent biliary pancreatitis. Cholecystectomy during index admission for mild biliary pancreatitis appears safe, but selection bias could not be excluded.

Context: Most patients with infected necrotizing pancreatitis require necrosectomy. Surgical necrosectomy induces a proinflammatory response and is associated with a high complication rate. Endoscopic transgastric necrosectomy, a form of natural orifice transluminal endoscopic surgery, may reduce the proinflammatory response and reduce complications., Objective: To compare the proinflammatory response and clinical outcome of endoscopic transgastric and surgical necrosectomy., Design, Setting, and Patients: Randomized controlled assessor-blinded clinical trial in 3 academic hospitals and 1 regional teaching hospital in The Netherlands between August 20, 2008, and March 3, 2010. Patients had signs of infected necrotizing pancreatitis and an indication for intervention., Interventions: Random allocation to endoscopic transgastric or surgical necrosectomy. Endoscopic necrosectomy consisted of transgastric puncture, balloon dilatation, retroperitoneal drainage, and necrosectomy. Surgical necrosectomy consisted of video-assisted retroperitoneal debridement or, if not feasible, laparotomy., Main Outcome Measures: The primary end point was the postprocedural proinflammatory response as measured by serum interleukin 6 (IL-6) levels. Secondary clinical end points included a predefined composite end point of major complications (new-onset multiple organ failure, intra-abdominal bleeding, enterocutaneous fistula, or pancreatic fistula) or death., Results: We randomized 22 patients, 2 of whom did not undergo necrosectomy following percutaneous catheter drainage and could not be analyzed for the primary end point. Endoscopic transgastric necrosectomy reduced the postprocedural IL-6 levels compared with surgical necrosectomy (P = .004). The composite clinical end point occurred less often after endoscopic necrosectomy (20% vs 80%; risk difference [RD], 0.60; 95% CI, 0.16-0.80; P = .03). Endoscopic necrosectomy did not cause new-onset multiple organ failure (0% vs 50%, RD, 0.50; 95% CI, 0.12-0.76; P = .03) and reduced the number of pancreatic fistulas (10% vs 70%; RD, 0.60; 95% CI, 0.17-0.81; P = .02)., Conclusion: In patients with infected necrotizing pancreatitis, endoscopic necrosectomy reduced the proinflammatory response as well as the composite clinical end point compared with surgical necrosectomy., Trial Registration: isrctn.org Identifier: ISRCTN07091918.

BACKGROUND: Morbidly obese patients (BMI > 40 kg/m(2)) are at increased risk for venous thromboembolism, especially after surgery. Despite limited evidence, morbidly obese patients are often administered a double dose of nadroparin for thromboprophylaxis compared to non-obese patients. The aim of this study was to evaluate the influence of different body size descriptors on anti-Xa levels after a double dose of nadroparin (5,700 IU) in morbidly obese patients. METHODS: In 27 morbidly obese patients with a mean total body weight of 148 kg (range 107-260 kg), anti-Xa levels were determined peri-operatively until 24 h after administration of a subcutaneous dose of 5,700 IU of nadroparin. RESULTS: Anti-Xa level 4 h after administration (A(4h), mean 0.22 ± 0.07 IU/ml) negatively correlated strongly with lean body weight (r = -0.66 (p < 0.001)) and moderately with total body weight (r = -0.56 (p = 0.003)) and did not correlate with body mass index (r = -0.26 (p = 0.187)). The area under the anti-Xa level-time curve from 0 to 24 h (AUA(0-24h), mean 2.80 ± 0.97 h IU/ml) correlated with lean body weight (r = -0.63 (p = 0.007)), but did not correlate with total body weight (r = -0.44 (p = 0.075)) or body mass index (r = -0.10 (p = 0.709)). CONCLUCIONS: Following a subcutaneous dose of nadroparin 5,700 IU, A(4h) and AUA(0-24h) were found to negatively correlate strongly with lean body weight. From these results, individualized dosing of nadroparin based on lean body weight should be considered in morbidly obese patients.

Background: Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice., Methods/design: The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs., Discussion: The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients., Trial Registration: Netherlands Trial Register (NTR): NTR2666.

Background: Internal herniation following a laparoscopic Roux-en-Y gastric bypass (LRYGB) operation is a complication whereby the small bowel herniates through to the newly formed peritoneal compartment. Medical history, physical examination and laboratory tests are often non-specific and could lead to misdiagnosis., Case Description: A 46-year-old male with a history of a gastric bypass came to the emergency department with colicky upper-abdominal pain. The patient was initially diagnosed with symptomatic cholelithiasis and a laparoscopic cholecystectomy was performed. However, the pain persisted and the internal hernia was finally identified and repaired during the third abdominal operation., Conclusion: Internal herniation must be considered in patients with a history of laparoscopic Roux-en-Y gastric bypass and upper-abdominal pain, especially because such operations are being performed more frequently. When there is a high suspicion of internal herniation, a diagnostic laparoscopy must be performed and the entire small intestine must be systematically inspected.

Emotional eating, the tendency to eat when experiencing negative affect, is prevalent in morbid obesity and may indicate that ways to deal with emotions are disturbed. Our aim was to compare emotion processing and regulation between 102 women with morbid obesity who apply for bariatric surgery and 102 women from the general population (control group) and to examine in the group with morbid obesity the association of emotion processing and regulation with emotional eating. The group with morbid obesity reported higher scores on difficulty identifying feelings (alexithymia, p = 0.002) and suppression of emotions (p = 0.003) than the control group. In the women with morbid obesity, more negative affect and a higher difficulty identifying feelings were correlated with more emotional eating (r = 0.36 and r = 0.35, p < 0.001). Our study suggests that negative emotions and unhealthy emotion processing may play a role in emotional eating, and it indicates the possible relevance of emotion processing and emotional regulation as initiating or perpetuating mechanisms in morbid obesity.

Background: Physical activity after bariatric surgery is associated with sustained weight loss and improved quality of life. Some bariatric patients engage insufficiently in physical activity. This may be due to exercise cognitions, i.e., specific beliefs about benefits of and barriers to physical exercise. The aim of this study was to examine whether and to what extent both physical activity and exercise cognitions changed at 1 and 2 years post-surgery and whether exercise cognitions predict physical activity., Methods: Forty-two bariatric patients (38 women, 4 men; mean age 38 ± 8 years, mean body mass index prior to surgery 47 ± 6 kg/m(2)) filled out self-report instruments to examine physical activity and exercise cognitions pre- and post-surgery., Results: A large increase in physical activity and favorable changes in exercise cognitions were observed after surgery, viz. a decrease of fear of injury and embarrassment and an increase of the perception of exercise benefits and confidence in exercising. Perceiving less exercise benefits and having less confidence in exercising before surgery predicted less physical activity 2 years after surgery. High fear of injury 1 year after surgery predicted less physical activity 2 years after surgery., Conclusions: After bariatric surgery, favorable changes in physical activity and beliefs about the benefits and barriers of exercising are observed. Our results suggest that targeting exercise cognitions before and after surgery might be relevant to improve physical activity.

Background: Acute calculous cholecystitis is a frequently encountered problem in surgical practice; laparoscopic cholecystectomy (LC) is the standard treatment. LC for acute cholecystitis can be a more difficult procedure than elective LC for cholelithiasis and is associated with increased operating time, higher conversion rate, and more postoperative complications. In the elderly patient with comorbidity, surgery can result in serious complications and even mortality. Percutaneous drainage (percutaneous cholecystostomy; PC) may be an alternative treatment. There is no hard evidence in current literature regarding the safety, success rate, and specific technique of this procedure, nor is there consensus on the indications., Aim: To evaluate the safety and efficacy of PC in treatment of acute calculous cholecystitis in high-risk surgical patients., Methods: From January 2009 until May 2010, 101 patients with acute calculous cholecystitis were treated, of whom 27 with PC. Of these 27 patients, comorbidity and American Society of Anesthesiologists (ASA) classification were determined, indication for drainage instead of cholecystectomy was recorded, and procedure-related data were collected. Primary outcomes were overall morbidity, mortality, and recurrent biliary events. Secondary outcomes were time to recovery and need for and difficulty of interval laparoscopic cholecystectomy., Results: The cohort included 15 male and 12 female patients with median age of 83 years (range 69-90 years). Most patients were ASA 3 (n = 18) or ASA 2 (n = 8); one patient was ASA 4. Indication for drainage was age and/or comorbidity in 24 cases and duration of symptoms in 3 cases. Antibiotic treatment was given in all but seven patients. The drain was in situ for a median period of 19 days (range 5-57 days). Relief of symptoms occurred in 26 patients; drain luxation occurred in nine patients, only in two patients with clinical consequences. Overall mortality rate was 14.8% (n = 4) with a procedure-related mortality rate of 3.7%. Median time to full recovery was 8 days. With median follow-up of 8 weeks, four patients underwent interval cholecystectomy., Conclusions: Percutaneous drainage in acute calculous cholecystitis in high-risk patients seems to be a safe and successful treatment option in patients less eligible for surgery. There are many controversies in the current literature, and evidence-based guidelines for the indication of PC in treatment of acute calculous cholecystitis are needed.

Background and Objectives: In view of the increasing prevalence of morbidly obese patients, the influence of excessive total bodyweight (TBW) on the pharmacokinetics and pharmacodynamics of propofol was characterized in this study using bispectral index (BIS) values as a pharmacodynamic endpoint., Methods: A population pharmacokinetic and pharmacodynamic model was developed with the nonlinear mixed-effects modelling software NONMEM VI, on the basis of 491 blood samples from 20 morbidly obese patients (TBW range 98-167 kg) and 725 blood samples from 44 lean patients (TBW range 55-98 kg) from previously published studies. In addition, 2246 BIS values from the 20 morbidly obese patients were available for pharmacodynamic analysis., Results: In a three-compartment pharmacokinetic model, TBW proved to be the most predictive covariate for clearance from the central compartment (CL) in the 20 morbidly obese patients (CL 2.33 L/min × [TBW/70]^[0.72]). Similar results were obtained when the morbidly obese patients and the 44 lean patients were analysed together (CL 2.22 L/min × [TBW/70]^[0.67]). No covariates were identified for other pharmacokinetic parameters. The depth of anaesthesia in the morbidly obese patients was adequately described by a two-compartment biophase-distribution model with a sigmoid maximum possible effect (E(max)) pharmacodynamic model (concentration at half-maximum effect [EC(50)] 2.12 mg/L) without covariates., Conclusion: We developed a pharmacokinetic and pharmacodynamic model of propofol in morbidly obese patients, in which TBW proved to be the major determinant of clearance, using an allometric function with an exponent of 0.72. For the other pharmacokinetic and pharmacodynamic parameters, no covariates could be identified. Trial registration number (clinicaltrials.gov): NCT00395681.

Background & Aims: Treatment of patients with necrotizing pancreatitis has become more conservative and less invasive, but there are few data from prospective studies to support the efficacy of this change. We performed a prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis., Methods: We collected data from 639 consecutive patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome., Results: Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An intervention was performed in 242 patients (38%), with 27% mortality; this included early emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days, 26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003). Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and mortality (20% vs 9%, P<.001)., Conclusions: Approximately 62% of patients with necrotizing pancreatitis can be treated without an intervention and with low mortality. In patients with infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the pharmacokinetics and protein binding of cefazolin in morbidly obese patients undergoing bariatric surgery, to study the influence of bodyweight measures and age on pharmacokinetic parameters and to evaluate unbound cefazolin concentrations over time in this population., Methods: Twenty morbidly obese patients (bodyweight 112-260 kg, body mass index 38-79 kg m(-2)) were studied following the administration of cefazolin 2 g at induction of anaesthesia. Blood samples were collected up to 4 h post-dosing to determine total and unbound plasma cefazolin concentrations. Non-compartmental pharmacokinetic data analysis was performed., Results: Cefazolin clearance was 4.2 ± 1.0 L h(-1) (mean ± standard deviation) and showed a negative correlation with age (p = 0.003) but not with bodyweight measures (p > 0.05). Volume of distribution was 13.0 ± 3.1 L and correlated positively with bodyweight measures (p ≤ 0.001). Saturable protein binding was observed with a median protein binding of 79% (interquartile range 74-82), which proved similar to reported protein binding in non-obese patients. In all patients, unbound cefazolin concentrations remained above 1 mg L(-1) (minimal inhibitory concentration for 90% (MIC(90)) of methicillin-sensitive isolates of Staphylococcus aureus in Europe) until 4 h post-dosing., Conclusions: Younger age--and not bodyweight--was significantly associated with higher cefazolin clearance. However, as in all patients with bodyweights up to 260 kg, unbound plasma cefazolin concentrations remained above 1 mg L(-1) until 4 h after the intravenous administration of a 2-g dose. As such, re-dosing within 4 h or dosing with another antibiotic class should only be considered in the case of a higher MIC(90) of the local isolates.

Background: In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission., Methods/design: The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission.During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective., Discussion: The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis., Trial Registration: ISRCTN: ISRCTN18170985.

Objective: Body contouring surgery is in high demand following the increase in bariatric surgery. Massive weight loss leads to an excess of lax, overstretched skin causing physical and psychosocial discomfort. Plastic surgical procedures can give rise to an improvement in quality of life, but the relative high complication rate could negatively affect these potential gains. The purpose of this study is to identify predictors of complications in order to optimize outcomes in this patient population., Methods: Out of a group of 465 post-bariatric patients, 61 patients underwent body contouring surgery following massive weight loss. A total of 43 respondents were reviewed retrospectively for demographic data, pre- and post-operative weight status and co-morbidities. Medical complications were categorized according to the modified Clavien classification. All cases were analyzed for risk factors., Results: A stable weight over a period of at least 3 months prior to body contouring surgery is associated with a significant lower complication rate (odds ratio 0.24; CI 0.07-0.79) and the percentage excess weight loss (odds ratio 0.96; 95% CI 0.92-1.00) was an independent predictor for the occurrence of complications. The overall complication rate was 27.9% with a major complication rate of 8.8%. Most frequent procedures were abdominoplasty (61%) and breast reduction/ mammapexy (25%)., Conclusion: This study emphasizes the importance to strive for a stable weight close to normal before surgery to minimize the risk of complications. The positive effects of the long-term results of bariatric surgery tolerate the relative high complications rate. Careful pre-operative planning and patient selection are essential to optimize the results of body contouring surgery of post-bariatric patients., (Copyright © 2011 S. Karger AG, Basel.)

What Is Already Known About This Subject: Different conflicting reports have been published for the use of atracurium in morbidly obese patients. Dosing of atracurium based on lean body mass, total body weight, and total body weight with a dose reduction for every 10 kg more than 70 kg have been proposed., What This Study Adds: The current prospective randomized double-blind study compares atracurium 0.5 mg kg(-1) ideal body weight vs. 0.5 mg kg(-1) total body weight when used as a muscle relaxant in morbidly obese patients undergoing bariatric surgery. Based on our results in patients with body weights varying from 112 to 260 kg, we have concluded that atracurium 0.5 mg kg(-1) ideal body weight results in a predictable profile of muscle relaxation allowing for adequate intubation conditions and recovery of muscle strength within 60 min with lack of need for antagonism. A dose-dependent prolongation of action is shown when dosing is based on total body weight., Aims: This double-blind randomized study evaluated atracurium dosing based on ideal body weight vs. total body weight for muscle relaxation in morbidly obese patients undergoing bariatric surgery., Methods: Twenty patients (body weight 112-260 kg, BMI 38-79 kg m(-2) ) were randomized to receive atracurium 0.5 mg kg(-1) ideal body weight vs. 0.5 mg kg(-1) total body weight. Primary endpoint was neuromuscular blockade using train-of-four ratios (TOF ratios) and secondary endpoints were intubation conditions and need for antagonism with neostigmine., Results: In the ideal body weight group, times to recovery of TOF ratio from 0 to 5%, 50% and 75% were significantly shorter [TOF ratio from 0 to 5%: mean difference 30 min (95% CI 23, 39 min)] and with lower variability compared with the total body weight group. In the total body weight group there was a significant correlation between atracurium dose and time to a TOF ratio of 5% (r= 0.82, P < 0.001), which was absent in the ideal body weight group (r= 0.24). In both groups, intubation conditions were good while 70% of the patients in the total body weight group needed neostigmine at the end of surgery compared with 0% in the ideal body weight group., Conclusion: In morbid obesity (112-260 kg), atracurium 0.5 mg kg(-1) ideal body weight results in a predictable profile of muscle relaxation allowing for adequate intubation conditions and recovery of muscle strength to a TOF ratio >90% within 60 min with lack of need for antagonism. A dose-dependent prolongation of action is shown when dosing is based on total body weight., (© 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.)

Patients with choledochocystolithiasis are usually treated by endoscopic retrograde cholangiography with endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (LC). LC after ES is more difficult than in uncomplicated gallstone disease, possibly due to bacterial colonization of the common bile duct. The goal of this study was to evaluate if bactobilia influences the peri- and postoperative outcomes. Data were obtained from a randomized trial on the timing of LC after ES. Ninety-six patients were randomized after ES to LC either within 72 h (early LC [ELC]) or in 6-8 weeks (delayed LC [DLC]). In 64 of 96 patients bile samples were obtained peroperatively. The overall prevalence of bactobilia was 62.5% [40/64; 50% of ELC patients (n = 13) vs. 71.1% in the DLC group (n = 27); p = 0.088]. Age and group (i.e. ELC/DLC) were independent and significant predictors for the presence of bactobilia. The presence of bactobilia did not influence operating time and difficulty or conversion rate. Patients with bactobilia developed more biliary events in the period between ES and LC (44 vs. 28%). After ES for choledochocystolithiasis, 62.5% of patients have bactobilia at the time of surgery. The prevalence of bactobilia increases with age and time. Patients with bactobilia tend to develop more biliary-related complications awaiting surgery., (Copyright © 2011 S. Karger AG, Basel.)

Background: The aim of the study was to evaluate the results of laparoscopic adjustable gastric banding (LAGB) in patients lost to follow-up., Methods: Patients lost to follow-up were identified from a consecutive cohort of 495 patients who underwent LAGB between November 1995 and September 2006. These patients were asked to return to follow-up and their actual weight was assessed., Results: Of 93 patients lost to follow-up, 73 were motivated to reattend. Of these, 60 per cent (44 patients) had lost less than 25 per cent of excess weight, compared with 16.3 per cent (P < 0.001), 27.0 per cent (P < 0.001) and 42 per cent (P = 0.026) of patients after 2, 4 and 8 years of regular follow-up., Conclusion: Patients lost to follow-up are more likely to have poor weight loss, emphasizing the importance of follow-up after LAGB. Outcome after surgery for morbid obesity should include patients lost to follow-up as a measure of overall success.