Donald L. van der Peet

Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial

BACKGROUND Surgical resection is regarded as the only curative option for resectable oesophageal cancer, but pulmonary complications occurring in more than half of patients after open oesophagectomy are a great concern. We assessed whether minimally invasive oesophagectomy reduces morbidity compared with open oesophagectomy. METHODS We did a multicentre, open-label, randomised controlled trial at five study centres in three countries between June 1, 2009, and March 31, 2011. Patients aged 18-75 years with resectable cancer of the oesophagus or gastro-oesophageal junction were randomly assigned via a computer-generated randomisation sequence to receive either open transthoracic or minimally invasive transthoracic oesophagectomy. Randomisation was stratified by centre. Patients, and investigators undertaking interventions, assessing outcomes, and analysing data, were not masked to group assignment. The primary outcome was pulmonary infection within the first 2 weeks after surgery and during the whole stay in hospital. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. FINDINGS We randomly assigned 56 patients to the open oesophagectomy group and 59 to the minimally invasive oesophagectomy group. 16 (29%) patients in the open oesophagectomy group had pulmonary infection in the first 2 weeks compared with five (9%) in the minimally invasive group (relative risk [RR] 0·30, 95% CI 0·12-0·76; p=0·005). 19 (34%) patients in the open oesophagectomy group had pulmonary infection in-hospital compared with seven (12%) in the minimally invasive group (0·35, 0·16-0·78; p=0·005). For in-hospital mortality, one patient in the open oesophagectomy group died from anastomotic leakage and two in the minimally invasive group from aspiration and mediastinitis after anastomotic leakage. INTERPRETATION These findings provide evidence for the short-term benefits of minimally invasive oesophagectomy for patients with resectable oesophageal cancer. FUNDING Digestive Surgery Foundation of the Unit of Digestive Surgery of the VU University Medical Centre.

Laparoscopic sigmoid resection for diverticulitis decreases major morbidity rates: a randomized control trial. Short-term Results of the Sigma-trial

Background:No randomized controlled trial has compared laparoscopic sigmoid resection (LSR) to open sigmoid resection (OSR) for symptomatic diverticulitis of the sigmoid colon. This study tested the hypothesis that LSR is associated with decreased postoperative complication rates as compared with OSR. Methods:This was a prospective, multicenter, double-blind, parallel-arm, randomized controlled trial. Eligible patients were randomized to either LSR or OSR. Endpoints included postoperative mortality, and complications were classified as major and minor. The generator of the allocation sequence was separated from the executor. Blinding was ensured using an opaque wound dressing to cover the abdomen. Symptomatic diverticulitis of the sigmoid colon was defined as recurrent disease Hinchey I, IIa, IIb, symptomatic stricture, or severe rectal bleeding. The decision to discharge patients was made by independent physicians blind to the allocation sequence. Data were analyzed according to the intention to treat principle. Results:From 2002 to 2006, 104 patients were randomized in 5 centers. All patients underwent the allocated intervention. Fifty-two LSR patients were comparable to 52 OSR patients for gender, age, BMI, ASA grade, comorbid conditions, previous abdominal surgery, and indication for surgery. LSR took longer (P = 0.0001) but caused less blood loss (P = 0.033). Conversion rate was 19.2%. Mortality rate was 1%. There were significantly more major complications in OSR patients (9.6% vs. 25.0%; P = 0.038). Minor complication rates were similar (LSR 36.5% vs. OSR 38.5%; P = 0.839). LSR patients had less pain (Visual Analog Scale 1.6; P = 0.0003), systemic analgesia requirement (P = 0.029), and returned home earlier (P = 0.046). The short form-36 questionnaire showed significantly better quality of life for LSR. Conclusions:LSR was associated with a 15.4% reduction in major complication rates, less pain, improved quality of life, and shorter hospitalization at the cost of a longer operating time.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

BackgroundRecently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).Methods/DesignIn this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmanns procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmanns procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.DiscussionThe Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.Trial registrationNederlands Trial Register NTR2037

MR Enteroclysis in the Diagnosis of Small-Bowel Neoplasms

PURPOSE To evaluate the diagnostic accuracy and interobserver variance of magnetic resonance (MR) enteroclysis in the diagnosis of small-bowel neoplasms, with small-bowel endoscopy, surgery, histopathologic analysis, and follow-up serving as standards of reference, and to identify MR enteroclysis characteristics capable of enabling discrimination between benign and malignant small-bowel neoplasms. MATERIALS AND METHODS This study was performed in accordance with the guidelines of the institutional review board, and the requirement for informed consent was waived. MR enteroclysis studies of 91 patients (43 women, 48 men; age range, 18-83 years) were retrospectively evaluated by two radiologists blinded to clinical details. Only studies explicitly performed to investigate or exclude the presence of small-bowel neoplasms were included. Radiologic findings were compared with findings of double-balloon endoscopy (n = 45), surgery (n = 18), esophagogastroduodenoscopy (n = 3), ileocolonoscopy (n = 2), autopsy (n = 2), and clinical follow-up for more than 18 months (n = 21). Efficacy parameters were calculated with 95% confidence intervals. Tumor characteristics were compared with the Student t test and the Fisher exact test. RESULTS Readers 1 and 2 interpreted 31 and 33 studies, respectively, as depicting a small-bowel neoplasm and 19 and 17 studies, respectively, as depicting small-bowel malignancy. In 32 patients, the presence of small-bowel neoplasm was confirmed. In 19 of these patients, the neoplasm was malignant. Sensitivity and specificity in the diagnosis of small-bowel neoplasms was 0.91 and 0.95, respectively, for reader 1 and 0.94 and 0.97, respectively, for reader 2; the kappa value was 0.95. Factors associated with malignancy were the presence of longer solitary nonpedunculated lesions, mesenteric fat infiltration, and enlarged mesenteric lymph nodes. CONCLUSION Eighty-six of 91 studies were correctly interpreted, resulting in an overall diagnostic accuracy of 0.95 for MR enteroclysis in the detection of small-bowel neoplasms. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090828/-/DC1.

Indications for elective sigmoid resection in diverticular disease

Introduction:To prevent an acute surgery, classic indications for elective sigmoid resections concerning diverticulitis have usually been based on the number of recurrent episodes. Since 2005 these indications have been challenged, primarily because the majority of patients first present themselves with acute complications at their first episode. Methods:Between 1990 and 2000, a cohort analysis was conducted involving all patients admitted to the VU University Medical Center with the diagnosis of diverticulitis, with a follow-up until January 2009. To identify those patients who might benefit from elective sigmoid resection, several risk factors were analyzed. Results:Of 291 patients examined, 111 (38%) were treated conservatively and 180 (62%) underwent surgery, of which 108 acute and 72 elective. The conservatively treated episodes of diverticulitis showed a recurrence rate of 48% (88 patients). Indications for elective surgery were recurrent attacks of diverticulitis with persistent complaints (36%), complaints of stenosis (40%), fistula (14%), persistent abscesses (3%), and recurrent diverticular bleeding (7%). Of the 74% of the patients approached laparoscopically, the overall morbidity was 22% with no mortality. The main indication for an AO was perforation with general peritonitis, holding for 57% of the acutely operated patients. Other indications were abscesses (22%), stenosis with obstruction (11%), failure of conservative therapy (6%), or diverticular bleeding (4%). Hartmanns procedure was the most frequently performed procedure (58%). This acutely operated population was associated with high morbidity (56%) and mortality (13%), perforation leads to 10% mortality and other causes to 3%. Of those patients undergoing acute surgery, 20% had a history of diverticulitis. Moreover, risk factor analysis showed that those patients having one or more of the following indications: (1) using immunosuppression therapy, (2) having chronic renal failure, or (3) collagen-vascular diseases, had a significant 5-fold greater risk (36% vs. 7%) of a perforation in recurrent episodes of diverticulitis. Conclusion:In the treatment of diverticular disease, indications for an elective sigmoid resection should not be based on the number of episodes only. Clear indications for elective sigmoid resections are complaints of stenosis, fistulas, or recurrent diverticular bleeding. Furthermore, an elective sigmoid resection might be justified in high-risk patients, after a conservatively treated episode of diverticulitis, who use immunosuppression therapy and have chronic renal failure or collagen-vascular diseases.

Review of current classifications for diverticular disease and a translation into clinical practice

IntroductionDiverticular disease of the sigmoid colon prevails in Western society. Its presentation may vary greatly per individual patient, from symptomatic diverticulosis to perforated diverticulitis. Since publication of the original Hinchey classification, several modifications and new grading systems have been developed. Yet, new insights in the natural history of the disease, the emergence of the computed tomography scan, and new treatment modalities plead for evolving classifications.MethodsThis article reviews all current classifications for diverticular disease.ResultA three-stage model is advanced for a renewed and comprehensive classification system for diverticular disease, incorporating up-to-date imaging and treatment modalities.

Traditional invasive vs. minimally invasive esophagectomy: a multi-center, randomized trial (TIME-trial)

BackgroundThere is a rise in incidence of esophageal carcinoma due to increasing incidence of adenocarcinoma. Probably the only curative option to date is the use of neoadjuvant therapy followed by surgical resection. Traditional open esophageal resection is associated with a high morbidity and mortality rate. Furthermore, this approach involves long intensive care unit stay, in-hospital stay and long recovery period. Minimally invasive esophagectomy could reduce the morbidity and accelerate the post-operative recovery.Methods/DesignComparison between traditional open and minimally invasive esophagectomy in a multi-center, randomized trial. Patients with a resectable intrathoracic esophageal carcinoma, including the gastro-esophageal junction tumors (Siewert I) are eligible for inclusion. Prior thoracic surgery and cervical esophageal carcinoma are indications for exclusion. The surgical technique involves a right thoracotomy with lung blockade and laparotomy either with a cervical or thoracic anastomosis for the traditional group. The minimally invasive procedure involves a right thoracoscopy in prone position with a single lumen tube and laparoscopy either with a cervical or thoracic anastomosis. All patients in both groups will undergo identical pre-operative and post-operative protocol. Primary endpoint of this study are post-operative respiratory complications within the first two post-operative weeks confirmed by clinical, radiological and sputum culture data. Secondary endpoints are the operative data, the post-operative data and oncological data such as quality of the specimen and survival. Operative data include duration of the operation, blood loss and conversion to open procedure. Post-operative data include morbidity (major and minor), quality of life tests and hospital stay.Based on current literature and the experience of all participating centers, an incidence of pulmonary complications for 57% in the traditional arm and 29% in the minimally invasive arm, it is estimated that per arm 48 patients are needed. This is based on a two-sided significance level (alpha) of 0.05 and a power of 0.80. Knowing that approximately 20% of the patients will be excluded, we will randomize 60 patients per arm.DiscussionThe TIME-trial is a prospective, multi-center, randomized study to define the role of minimally invasive esophageal resection in patients with resectable intrathoracic and junction esophageal cancer.Trial registration (Netherlands Trial Register)NTR2452

Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease.

Objectives: Obesity and insulin resistance cause fatty infiltration of many organs, including the pancreas (pancreatic steatosis [PS]) and the liver (nonalcoholic fatty liver disease [NAFLD]). In contrast to NAFLD, pathophysiological mechanisms and clinical relevance of PS remain unknown. This study aimed to identify a possible relation between PS and NAFLD. Methods: In this study including postmortem collected material of 80 patients, clinical and histological data were collected and revised. Patients with hepatic or pancreatic disease and alcohol abuse were excluded. Nonalcoholic fatty liver disease activity score was used for grading the histology of the liver, whereas pancreatic lipomatosis score assessed PS. Ordinal logistic regression was used to analyze correlations. Results: Interlobular and total pancreatic fat were both related to NAFLD activity score in patients without steatogenic medication (P = 0.02 and P = 0.03, respectively). When corrected for body mass index, no relation could be found. Total pancreatic fat was a significant predictor for the presence of NAFLD (P = 0.02). Presence of intralobular pancreatic fat was related to nonalcoholic steatohepatitis; however, total fat was not. Conclusions: This study demonstrates that NAFLD and PS are related. This relationship seems to be mediated by general obesity. Intralobular pancreatic fat is associated with nonalcoholic steatohepatitis.Abbreviations: BMI - body mass index, PL - pancreatic lipomatosis, PS - pancreatic steatosis, NAFLD - nonalcoholic fatty liver disease, NASH - nonalcoholic steatohepatitis, NAFPD - nonalcoholic fatty pancreas disease, NAS - NAFLD activity score, T2DM - type 2 diabetes mellitus

Double-balloon endoscopy as the primary method for small-bowel video capsule endoscope retrieval

BACKGROUND Capsule retention in the small bowel is a known complication of small-bowel video capsule endoscopy. Surgery is the most frequently used method of capsule retrieval. OBJECTIVE To determine the incidence and causes of capsule retention and to describe double-balloon endoscopy (DBE) as the primary technique used for capsule retrieval. DESIGN Retrospective analysis of all video capsule studies was performed at our center, and evaluation of the outcome of DBE was the first method used to retrieve entrapped video capsules. SETTING Tertiary referral center. PATIENTS A total of 904 patients who underwent small-bowel video capsule endoscopy. INTERVENTIONS Capsule retrieval by DBE. MAIN OUTCOME MEASUREMENTS The number of patients in whom capsule retention occurred and the number of patients in whom an entrapped capsule could be retrieved by using DBE. RESULTS Capsule retention occurred in 8 patients (incidence 0.88%; 95% CI, 0.41%-1.80%) and caused acute small-bowel obstruction in 6 patients. All retained capsules were successfully removed during DBE. Five patients underwent elective surgery to treat the underlying cause of capsule retention. One patient required emergency surgery because of multiple small-bowel perforations. LIMITATIONS Retrospective design. CONCLUSIONS In our series, the incidence of capsule retention was low. DBE is a reliable method for removing retained capsules and might prevent unnecessary surgery. If surgery is required, preoperative capsule retrieval allows preoperative diagnosis, adequate staging in case of malignancy, and optimal surgical planning.

Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: Prevalence of nodular regenerative hyperplasia

Objective. Nodular regenerative hyperplasia (NRH) and sinusoidal dilatation have been described in relation to thiopurine use in patients with inflammatory bowel disease (IBD). However, there is a dearth of data on the prevalence of these histological abnormalities in general. The aim of our study was to describe the prevalence of these histological liver changes in a thiopurine-naïve IBD cohort. Material and methods. Liver biopsy specimens were obtained from patients who were treated in a referral center and who underwent gastrointestinal surgery for IBD. Patients were excluded if thiopurines were ever used. The liver specimens were pathohistologically assessed with special attention to NRH. Results. A total of 83, properly stained, liver specimens (Crohns disease 61%) were evaluated. NRH was observed in 6% compared to sinusoidal dilatation of varying degree in 34% of specimens. An older age at biopsy was correlated with NRH (p=0.015). Fibrosis and steatosis of varying degrees were detected in 31% and 36% of liver biopsies, respectively. No cases of liver cirrhosis were observed. Conclusions. Pathohistological hepatic abnormalities are common in non-thiopurine using IBD patients. The association between thiopurine use, NRH and sinusoidal dilatation may be weaker than as reported in recent literature, as there is relatively high background prevalence in selected series.