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Background At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. Methods In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. Discussion The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. Trial registration clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

IntroductionIn pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk.MethodsA prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT’s plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed.Results53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients’ characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%.ConclusionsFor PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated.Trial registration number:Dutch Trial Registry (NTR3142).

Background Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. Methods The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. Conclusion This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. Trial registration Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .

Background The effect of thoracic epidural analgesia (TEA) on splanchnic blood flow during abdominal surgery remains unclear. The purpose of this study was to examine whether the hemodynamic effects of TEA resulted in microcirculatory alterations to the intestinal serosa, which was visualized using incident dark-field (IDF) videomicroscopy. Methods An observational cohort study was performed. In 18 patients, the microcirculation of the intestinal serosa was visualized with IDF. Microcirculatory and hemodynamic measurements were performed prior to (T1) and after administering a bolus of levobupivacaine (T2). If correction of blood pressure was indicated, a third measurement was performed (T3). The following microcirculatory parameters were calculated: microvascular flow index, proportion of perfused vessels, perfused vessel density and total vessel density. Data are presented as median [IQR]. Results Mean arterial pressure decreased from 73 mmHg (68–83) at T1 to 63 mmHg (±11) at T2 ( p  = 0.001) with a systolic blood pressure of 114 mmHg (98–128) and 87 (81–97), respectively ( p  = 0.001). The microcirculatory parameters of the bowel serosa, however, were unaltered. In seven patients, blood pressure was corrected to baseline values from a MAP of 56 mmHg (55–57), while microcirculatory parameters remained constant. Conclusion We examined the effects of TEA on the intestinal serosal microcirculation during abdominal surgery using IDF imaging for the first time in patients. Regardless of a marked decrease in hemodynamics, microcirculatory parameters of the bowel serosa were not significantly affected. Trial registry number ClinicalTrials.gov identifier NCT02688946.

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 Complication rates after a laparoscopic cholecystectomy are still up to 10 %. Knowledge of individual patient risk profiles could help to reduce morbidity. Aim The aim of this study is to create risk profiles for specific complications to anticipate on individual outcome. Patients and methods Individual patient outcome for a specific post-operative complication was assessed from a retrospective database of two major teaching hospitals, using uni- and multivariable analyses. Results A total of 4359 patients were included of which 346 developed one or more complications (8 %). Five risk profiles were found to predict specific complications: older patients (>65 year) are at risk for pneumonia (OR 7.0, 95 % CI 3.3–15.0, p  < 0.001) and bleeding (OR 2.2, 95 % CI 1.2–3.9, p  = 0.014), patients with acute cholecystitis are at risk for intra-abdominal abscess (OR 5.9, 95 % CI 3.4–10.1, p  < 0.001), bile leakage (OR 3.6, 95 % CI 2.0–6.6, p  < 0.001) and pneumonia (OR 3.5, 95 % CI 1.6–7.6, p  < 0.002), previous history of cholecystitis is predictive for wound infection (OR 5.1, 95 % CI, (2.7–9.7), p  < 0.001), intra-abdominal abscess (OR 6.1, 95 % CI 2.8–13.8, p  < 0.001), post-operative bleeding (OR 4.8, 95 % CI 2.1–11.1, p  < 0.001), bile leakage (OR 7.2, 95 % CI 3.4–15.4, p  < 0.001) and pneumonia (OR 3.9, 95 % CI 1.3–11.9, p  = 0.018), pre - operative ERCP is predictive for intra-abdominal abscess (OR 3.3, 95 % CI 2.0–5.7, p  < 0.001), post-operative bleeding (OR 2.1, 95 % CI 1.2–3.9, p  = 0.058) and pneumonia (OR 3.8, 95 % CI 1.9–7.8, p  = 0.001), and converted patients are at risk for wound infection (OR 4.0, 95 % CI 2.1–7.7, p  < 0.001) and intra-abdominal abscess (OR 3.5, 95 % CI 1.6–7.7, p  = 0.002). Conclusion Individual risk prediction of outcome after laparoscopic cholecystectomy is feasible. This facilitates individual pre-operative doctor–patient communication and may tailor surgical strategies.

Background Executive functioning (EF) is an umbrella term for various cognitive functions that play a role in monitoring and planning to effectuate goal-directed behavior. The 22q11.2 deletion syndrome (22q11DS), the most common microdeletion syndrome, is associated with a multitude of both somatic and cognitive symptoms, including EF impairments in school-age and adolescence. However, results vary across different EF domains and studies with preschool children are scarce. As EF is critically associated with later psychopathology and adaptive functioning, our first aim was to study EF in preschool children with 22q11DS. Our second aim was to explore the effect of a congenital heart defects (CHD) on EF abilities, as CHD are common in 22q11DS and have been implicated in EF impairment in individuals with CHD without a syndromic origin. Methods All children with 22q11DS ( n  = 44) and typically developing (TD) children ( n  = 81) were 3.0 to 6.5 years old and participated in a larger prospective study. We administered tasks measuring visual selective attention, visual working memory, and a task gauging broad EF abilities. The presence of CHD was determined by a pediatric cardiologist based on medical records. Results Analyses showed that children with 22q11DS were outperformed by TD peers on the selective attention task and the working memory task. As many children were unable to complete the broad EF task, we did not run statistical analyses, but provide a qualitative description of the results. There were no differences in EF abilities between children with 22q11DS with and without CHDs. Conclusion To our knowledge, this is the first study measuring EF in a relatively large sample of young children with 22q11DS. Our results show that EF impairments are already present in early childhood in children with 22q11DS. In line with previous studies with older children with 22q11DS, CHDs do not appear to have an effect on EF performance. These findings might have important implications for early intervention and support the improvement of prognostic accuracy.

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.

Patients who undergo endoscopic sphincterotomy for common bile-duct stones, who have residual gallbladder stones, are referred for laparoscopic cholecystectomy. However, only 10% of patients who do not have this operation are reported to develop recurrent biliary symptoms. We aimed to assess whether a wait-and-see policy is justified. We did a prospective, randomised, multicentre trial in 120 patients (age 18–80 years) who underwent endoscopic sphincterotomy and stone extraction, with proven gallbladder stones. Patients were randomly allocated to wait and see (n=64) or laparoscopic cholecystectomy (56). Primary outcome was reoccurrence of at least one biliary event during 2-year follow-up, and secondary outcomes were complications of cholecystectomy and quality of life. Analysis was by intention to treat. 12 patients were lost to follow-up immediately. Of 59 patients allocated to wait and see, 27 (47%) had recurrent biliary symptoms compared with one (2%) of 49 patients after laparoscopic cholecystectomy (relative risk 22·42, 95% CI 3·16–159·14, p<0·0001). 22 (81%) of 27 patients underwent cholecystectomy, mainly for biliary pain (n=13) or acute cholecystitis (7). Conversion rate to open surgery was 55% in patients allocated to wait and see who underwent cholecystectomy compared with 23% in those who were allocated laparoscopic cholecystectomy (p=0·0104). Morbidity was 32% versus 14% (p=0·1048), and median hospital stay was 9 versus 7 days. Quality of life returned to normal within 3 months after either treatment policy. A wait-and-see policy after endoscopic sphincterotomy in combined cholecystodocholithiasis cannot be recommended as standard treatment, since 47% of expectantly managed patients developed at least one recurrent biliary event and 37% needed cholecystectomy. No major biliary complications arose, but conversion rate was high.

BackgroundThe PERISCOPE I study was designed to assess the safety and feasibility of (sub)total gastrectomy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and docetaxel for gastric cancer patients who have limited peritoneal dissemination. The current analysis investigated changes in perioperative management together with their impact on postoperative outcomes.MethodsPatients with resectable gastric cancer and limited peritoneal dissemination were administered (sub)total gastrectomy, CRS, and HIPEC with oxaliplatin (460 mg/m2) and docetaxel (escalating scheme: 0, 50, 75 mg/m2). Of the 25 patients who completed the study protocol, 14 were treated in the dose-escalation cohort and 11 were treated in the expansion cohort (to optimize perioperative management).ResultsA significant proportion of the patients in the dose-escalation cohort (n = 7, 50%) had ileus-related complications. In this cohort, enteral nutrition was started immediately after surgery at 20 ml/h, which was increased on day 1 to meet nutritional needs. In the expansion cohort, enteral nutrition was administered at 10 ml/h until day 3, then restricted to 20 ml/h until day 6, supplemented with total parenteral nutrition to meet nutritional needs. Ileus-related complications occurred for two patients (18%) of the expansion cohort. The intensive care unit (ICU) readmission rate decreased from 50 (n = 7) to 9% (n = 1; p = 0.04).ConclusionThe implementation of a strict nutritional protocol during the PERISCOPE I study was associated with a decrease in postoperative complications. Based on these results, a perioperative care path was described for the gastric cancer HIPEC patients in the PERISCOPE II study.