Added value of digital FDG-PET/CT in disease staging and restaging in patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: We studied the added value of digital FDG-PET/CT in disease staging and restaging compared to the standard work-up with contrast enhanced CT (ceCT) and CA19-9 in patients with resectable or borderline resectable pancreatic cancer who received neo-adjuvant therapy. Primary endpoints were tumor response compared to ceCT and CA19.9 as well as the ability to detect distant metastatic disease. METHODS: 35 patients were included in this dual-center prospective study. FDG-PET using digital photon counting technology combined with CT scans were acquired before (T1) and after neo-adjuvant therapy (T2). Patients were staged and restaged based on standard protocol with ceCT and CA 19.9, while all PET/CT scans were stored securely and not included in clinical decision making. After the pancreatic resection, an expert team retrospectively assessed the CT tumor diameter, CA19-9, tumor FDG-uptake, and appearance of metastatic disease of all patients for both time points. RESULTS: CA19-9 levels, CT tumor diameter, and tumor FDG-uptake on PET significantly decreased from T1 to T2 (p = 0.017, p = 0.001, and p < 0.0001). The change in FDG-uptake values showed a strong positive correlation with the change in CT tumor diameter and change in CA19-9 (R = 0.75 and R = 0.73, respectively). In addition, small-volume liver lesions were detected on digital PET/CT in 5/35 patients (14%), 4 of which were pathology confirmed at laparotomy. Only one of these five cases was detected on baseline staging ceCT (3%). CONCLUSION: We found that adding digital PET/CT strengthens restaging after neo-adjuvant therapy based on the observed strong correlation with ceCT tumor diameter and Ca19.9. Also, digital PET/CT was found to detect occult metastatic disease not visualized on ceCT, that would have resulted in altered disease staging and therapeutic strategy in a substantial proportion of patients.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Reliability of residents' assessments of their postgraduate medical education learning environment: an observational study.

BACKGROUND: Even in anonymous evaluations of a postgraduate medical education (PGME) program, residents may be reluctant to provide an honest evaluation of their PGME program, because they fear embarrassment or repercussions from their supervisors if their anonymity as a respondent is endangered. This study was set up to test the hypothesis that current residents in a PGME program provide more positive evaluations of their PGME program than residents having completed it. We therefore compared PGME learning environment evaluations of current residents in the program to leaving residents having completed it. METHODS: This observational study used data gathered routinely in the quality cycle of PGME programs at two Dutch teaching hospitals to test our hypothesis. At both hospitals, all current PGME residents are requested to complete the Scan of Postgraduate Education Environment Domains (SPEED) annually. Residents leaving the hospital after completion of the PGME program are also asked to complete the SPEED after an exit interview with the hospital's independent residency coordinator. All SPEED evaluations are collected and analysed anonymously. We compared the residents' grades (on a continuous scale ranging from 0 (poor) to 10 (excellent)) on the three SPEED domains (content, atmosphere, and organization of the program) and their mean (overall department grade) between current and leaving residents. RESULTS: Mean (SD) overall SPEED department grades were 8.00 (0.52) for 287 current residents in 39 PGME programs and 8.07 (0.48) for 170 leaving residents in 39 programs. Neither the overall SPEED department grades (t test, p = 0.53, 95% CI for difference - 0.16 to 0.31) nor the department SPEED domain grades (MANOVA, F(3, 62) = 0.79, p = 0.51) were significantly different between current and leaving residents. CONCLUSIONS: Residents leaving the program did not provide more critical evaluations of their PGME learning environment than current residents in the program. This suggests that current residents' evaluations of their postgraduate learning environment were not affected by social desirability bias or fear of repercussions from faculty.

Colon ischemia: Right-sided colon involvement has a different presentation, etiology and worse outcome. A large retrospective cohort study in histology proven patients.

BACKGROUND: Colon ischemia (CI), is generally considered a non-occlusive mesenteric ischemia disorder that usually runs a benign course, but right-sided involvement (RCI) has been associated with worse outcome. The poor outcome of RCI has been associated with comorbidity, but more recently also with occlusions of the mesenteric arteries. We performed a retrospective analysis of a large cohort of CI-patients to assess differences in presentation, etiology, and comorbidity between right-sided colon ischemia (RCI) and non-right-sided colon ischemia (NRCI), and their relation to outcome. METHODS: We performed a retrospective cohort study in two centers from 2000 to 2011 for CI and analyzed clinical presentation, etiology, treatment and outcome. Diagnosis was based on full colonoscopy and/or surgical findings and confirmed by histopathology. RESULTS: 239 patients were included (mean age 69, 52% female). RCI was found in 48% and NRCI in 52%. Patients with NRCI presented more often with rectal bleeding (87% vs. 45%; p<0.001). In RCI more nausea (58% vs. 39%; p=0.013), weight loss (56% vs. 19%; p<0.001), paralytic ileus (32% vs. 18%; p=0.018) and peritoneal signs (27% vs. 7%; p<0.001) was observed compared to NRCI. The cause of CI was more often idiopathic in NRCI (46% vs. 26%; p=0.002); an occlusive cause was seen more often in RCI (26.3 vs 2.4%, p<0.0001). RCI patients had longer hospital stay (15 vs. 8 days, p<0.001), need for surgery (61% vs. 34%, p<0.001), and trend toward higher 30-day in-hospital mortality (20% vs. 12%, p=0.084). CONCLUSIONS: RCI ischemia has different etiology, presentation, and outcome. The series shows a high proportion of - treatable - vessel occlusion. It reinforces the advice to perform CT angiography in RCI as means to improve its poor outcome.

Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer.

PURPOSE: Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval. PATIENTS AND METHODS: Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings. RESULTS: A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant. CONCLUSION: In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas.

Comparison of cecal intubation and adenoma detection between hospitals can provide incentives to improve quality of colonoscopy.

BACKGROUND AND STUDY AIMS: Cecal intubation rate (CIR) and adenoma detection rate (ADR) have been found to be inversely associated with the occurrence of post-colonoscopy colorectal cancer. Depicting differences in CIR and ADR between hospitals could provide incentives for quality improvement. The aim of this study was to compare quality parameters of routine colonoscopies between seven hospitals in The Netherlands in order to determine the extent to which possible differences were attributable to procedural and institutional factors. PATIENTS AND METHODS: Consecutive patients undergoing colonoscopy were prospectively included between November 2012 and January 2013 at two academic and five nonacademic hospitals. Patients with inflammatory bowel disease or hereditary colorectal cancer syndromes were excluded. Main outcome measures were CIR and ADR. RESULTS: A total of 3129 patients were included (mean age 59 ±â€Š15 years; 45.5 % male). The majority of patients (86.2 %) had a Boston Bowel Preparation Scale (BBPS) score ≥ 6. Overall CIR was 94.8 %, ranging from 89.4 % to 99.2 % between hospitals. After adjustment for case mix (age, sex, American Society of Anesthesiologists score, and indication for colonoscopy), factors associated with CIR were hospital and a BBPS score ≥ 6. Overall ADR was 31.8 % and varied between hospitals, ranging from 24.8 % to 46.8 %. Independent predictors for ADR were hospital, BBPS score ≥ 6, and cecal intubation. By combining CIR and ADR for each hospital, a colonoscopy quality indicator (CQI) was developed, which can be used by hospitals to stimulate quality improvement. CONCLUSION: Differences in the quality of colonoscopy between hospitals can be demonstrated using CIR and ADR. As both indicators are affected by institution and bowel preparation, a comparison between hospitals based on the newly developed CQI could assist in further improving the quality of colonoscopy.

Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score.

BACKGROUND: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. OBJECTIVE: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. DESIGN: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. SETTING: Four centers, including one academic and three medium-to-large size nonacademic centers. PATIENTS: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 ± 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score <6. RESULTS: A total of 1331 colonoscopies were included in the development cohort, of which 172 (12.9%) had an inadequate bowel preparation. Independent factors included in the prediction model were American Society of Anesthesiologists Physical Status Classification System score ≥3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. LIMITATIONS: Study design partially retrospective, no data on patient compliance. CONCLUSION: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy.

[Rectal bleeding during pregnancy]. / Rectaal bloedverlies tijdens de zwangerschap.

BACKGROUND: Ischaemic colitis is a relatively rare disease that predominantly affects elderly patients. This disorder has varying underlying causes and diverse clinical symptoms. CASE DESCRIPTION: A 29-year-old primigravida was admitted to our hospital with rectal bleeding and diffuse abdominal pain. The number of leucocytes and the CRP were elevated. Because the patient was pregnant a sigmoidoscopy without sedation was performed. The endoscopic image and histopathology of the biopsies revealed ischaemic colitis. Our patient recovered quickly under conservative treatment. CONCLUSION: Ischaemic colitis is usually self-limiting and a conservative treatment will suffice. Ischaemic colitis during pregnancy has been reported extremely rarely and the aetiology is unknown.

Argon plasma coagulation for radiation proctitis.

BACKGROUND: Rectal blood loss is a common late sequel of radiation proctitis. Teleangiectasias appear in the mucosa in 2-5% of patients after radiotherapy of the pelvis. Since pharmacotherapy is usually not beneficial, local treatment modalities with formalin irrigation, Nd:YAG laser and argon plasma coagulation (APC) have been advocated, but experience is still limited. METHODS: Between January 1997 and August 2001, 50 consecutive patients with rectal bleeding due to radiation proctitis were included for treatment with APC. Thirteen patients suffered from anaemia, six of whom required blood transfusion. Nine patients were receiving anticoagulant therapy and 10 patients used low-dose aspirin. APC was performed, applying the no-touch spotting technique at an electrical power of 50 Watt and an argon gas flow of 2.0 l/min. Pulse duration was less than 0.5 s. Treatment sessions were carried out at intervals of 3 weeks. RESULTS: In 47 out of 48 patients (98%) in whom the effect could be assessed, APC led to persistent clinical and endoscopic remission of rectal bleeding after a median of three sessions. One patient developed recurrent blood loss after resuming anticoagulant therapy for his aortic valve prosthesis. No adverse effects were encountered after initial treatment. One serious complication occurred in a patient with recurrent blood loss when he was prescribed aspirin for a transient ischaemic attack 2 years after the initial APC. Re-treatment resulted in a major rectal bleeding from a small ulcer with a visible vessel. CONCLUSIONS: APC is a safe, effective and well-tolerated treatment for blood loss due to radiation proctitis. The use of anticoagulants and aspirin seems to be a co-factors that induces bleeding.

Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis.

BACKGROUND: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon. METHODS AND MATERIALS: BALB/c mice were exposed to a 10% dextran sulphate sodium drinking water solution for 7 days to induce a mild colitis, while control mice received normal tap water. Intestinal segments were placed in an oxygenated organ bath containing Krebs buffer. Permeability was measured by the transport of the marker molecules 3H-mannitol and 14C-polyethyleneglycol 4000. Contractility was measured through a pressure sensor. Smooth muscle relaxation was obtained by salbutamol and l-phenylephrine, whereas contraction was achieved by carbachol and 1-(3-chlorophenyl)-biguanide. RESULTS: The intensity of mucosal inflammation increased throughout the colon. Also, regional differences were observed in intestinal permeability. In both normal and inflamed distal colon segments, permeability was diminished compared with proximal colon segments and the non-inflamed ileum. Permeability in inflamed distal colon segments was significantly decreased compared with normal distal segments. Pharmacologically induced relaxation of smooth muscles did not affect this diminished permeability, although an increased motility positively affected permeability in inflamed and non-inflamed distal colon. CONCLUSIONS: Inflammation and permeability is inversely related. The use of pro-kinetics could counteract this disturbed permeability and, in turn, could regulate the disturbed production of inflammatory mediators.

Intestinal blood flow in murine colitis induced with dextran sulfate sodium.

The aim of this study was to assess whether colitis induced by dextran sulfate sodium (DSS; 10% in tap water for 7 days) in BALB/c mice is associated with changes in intestinal blood flow. After anaesthesia, systemic hemodynamic variable and regional blood flows and resistances in various organs were measured in both control and DSS-treated mice. Mean arterial blood pressure was significantly lower in DSS-treated mice than in controls (56 +/- 4 vs 66 +/- 3 mm Hg; P < 0.05), but no differences were found in regional blood flows to or vascular resistances in the lungs, liver, stomach, small intestine (upper, middle, and lower part), cecum, mesentery + pancreas, spleen, kidneys, brain, and skin. However, compared to the control mice, blood flows in the middle (0.88 +/- 0.13 vs 0.55 +/- 0.09 ml/min/g; P < 0.05) and distal (0.69 +/- 0.11 vs 0.29 +/- 0.05 ml/min/g; P < 0.05) colon were significantly higher, and vascular resistances in the proximal (0.87 +/- 0.21 vs 1.36 +/- 0.21 mm Hg min/ml/100 g; P < 0.05), middle (0.60 +/- 0.10 vs 1.46 +/- 0.35 mm Hg min/ml 100 g; P < 0.05) as well as distal (0.90 +/- 0.25 vs 2.67 +/- 0.49 mm Hg min/ml/100 g; P < 0.05) colon were significantly lower in mice with experimental colitis. Interestingly, there was a gradient in the intestinal blood flow in control mice from the upper small intestine (2.79 +/- 0.72 ml/min/g) down to the distal colon (0.29 +/- 0.05 ml/min/g); such a gradient was also present in the colitis mice. It is concluded that DSS-induced colitis in mice is associated with microcirculatory disturbances in the colon, mainly in its middle and distal parts.