Perioperative Management of Gastric Cancer Patients Treated With (Sub)Total Gastrectomy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Lessons Learned.

BACKGROUND: The 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. METHODS: Patients 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). RESULTS: A 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). CONCLUSION: The 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.

Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial.

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 .

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results.

BACKGROUND: The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS: Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS: Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION: Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.

ANTECEDENTES: El papel de la cirugía citorreductora (cytoreductive surgery, CRS) combinado con la quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) en el cáncer gástrico no está definido. Este estudio fase I-II no aleatorizado de escalado de dosis fue diseñado para evaluar la seguridad y la viabilidad de HIPEC, después de la quimioterapia sistémica, en pacientes con cáncer gástrico con diseminación peritoneal limitada. Además, se exploró la máxima dosis tolerada (maximum tolerated dose, MTD) de docetaxel intraperitoneal normotérmico en combinación con una dosis fija de oxaliplatino intraperitoneal. MÉTODOS: Se incluyeron pacientes con adenocarcinoma gástrico cT3-cT4a resecable con metástasis peritoneales limitadas y/o citología peritoneal positiva. Se utilizó una técnica HIPEC abierta con 460 mg/m2 de oxaliplatino hipertérmico (30 minutos) seguido de docetaxel normotérmico (90 minutos) en dosis crecientes (0, 50, 75 mg/m2 ). RESULTADOS: Entre 2014 y 2017, se incluyeron 37 pacientes. De los 25 pacientes que completaron la totalidad del protocolo del estudio, 4 pacientes fueron tratados en el nivel de dosis 1 (0 mg/m2 de docetaxel), 6 pacientes en el nivel de dosis 2 (50 mg/m2 ) y 4 pacientes en el nivel de dosis 3 (75 mg/m2 ). En el nivel de dosis 3, se produjeron dos casos de toxicidad limitante de dosis (dose-limiting toxicities, DLTs), ambas asociadas con un íleo postoperatorio. Posteriormente, otros 11 pacientes fueron tratados con el nivel de dosis 2, y no se produjeron más DLTs. La MTD de docetaxel intraperitoneal fue de 50 mg/m2 . Se registraron efectos adversos graves en 17 de 25 pacientes. La tasa de reoperación fue del 16% (n = 4) y la mortalidad relacionada con el tratamiento fue del 8% (n = 2; ambos en el nivel de dosis 3).

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II).

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.

The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal.

BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

Effects of Thoracic Epidural Anaesthesia on the Serosal Microcirculation of the Human Small Intestine.

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.

Can sidestream dark field (SDF) imaging identify subtle microvascular changes of the bowel during colorectal surgery?

BACKGROUND: Recognition of a non-viable bowel during colorectal surgery is a challenging task for surgeons. Identifying the turning point in serosal microcirculatory deterioration leading up to a non-viable bowel is crucial. The aim of the present study was to determine whether sidestream darkfield (SDF) imaging can detect subtle changes in serosal microcirculation of the sigmoid after vascular transection during colorectal surgery. METHODS: A prospective observational clinical study was performed at a single medical centre. All eligible participants underwent laparoscopic sigmoid resection and measurements were taken during the extra-abdominal phase. Microcirculation was measured at the transected bowel and 20 cm proximal to this point. Microcirculatory parameters such as Microvascular Flow Index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD), total vessel density (TVD) and the Heterogeneity Index were determined. Data are presented as median (interquartile range) or mean ± standard deviation. RESULTS: A total of 60 SDF images were acquired for 10 patients. Perfusion parameters and perfused vessel density were significantly lower at the transected bowel compared with the non-transected measurements [MFI 2.29 (1.96-2.63) vs 2.96 (2.73-3.00), p = 0.007; PPV 74% (55-83) vs 94% (86-97), p = 0.007; and PVD 7.61 ± 2.99 mm/mm2 versus 10.67 ± 1.48 mm/mm2, p = 0.009]. Total vessel density was similar between the measurement locations. CONCLUSIONS: SDF imaging can identify changes of the bowel serosal microcirculation. Significantly lower serosal microcirculatory parameters of the vascular transected bowel was seen compared with the non-transected bowel. The ability of SDF imaging to detect subtle differences holds promise for future research on microvascular cut-off values leading to a non-viable bowel.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis.

BACKGROUND: Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. METHODS: For this randomized controlled non-inferiority trial, adult patients with mild acute calculous cholecystitis undergoing cholecystectomy at six major teaching hospitals in the Netherlands, between April 2012 and September 2014, were assessed for eligibility. Patients were randomized to either a single preoperative dose of cefazolin (2000 mg), or antibiotic prophylaxis for 3 days after surgery (intravenous cefuroxime 750 mg plus metronidazole 500 mg, three times daily), in addition to the single dose. The primary endpoint was rate of infectious complications within 30 days after operation. RESULTS: In the intention-to-treat analysis, three of 77 patients (4 per cent) in the extended antibiotic group and three of 73 (4 per cent) in the standard prophylaxis group developed postoperative infectious complications (absolute difference 0·2 (95 per cent c.i. -8·2 to 8·9) per cent). Based on a margin of 5 per cent, non-inferiority of standard prophylaxis compared with extended prophylaxis was not proven. Median length of hospital stay was 3 days in the extended antibiotic group and 1 day in the standard prophylaxis group. CONCLUSION: Standard single-dose antibiotic prophylaxis did not lead to an increase in postoperative infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. Registration number: NTR3089 (www.trialregister.nl).

Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer.

INTRODUCTION: In 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. METHODS: A 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. RESULTS: 53 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%. CONCLUSIONS: For 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).

Role of omentectomy as part of radical surgery for gastric cancer.

BACKGROUND: A complete omentectomy is recommended as part of radical (sub)total gastrectomy for gastric cancer, but there is little evidence to suggest any survival benefit. The aim of this study was to evaluate the incidence of, and risk factors for, metastases in the greater omentum in patients undergoing gastrectomy for gastric cancer. METHODS: This was a multicentre prospective cohort study (OMEGA trial) of consecutive patients with gastric cancer undergoing (sub)total gastrectomy with complete en bloc omentectomy and modified D2 lymphadenectomy. After resection, the omentum was separated from the gastrectomy specimen distal to the gastroepiploic vessels and sent separately for pathological examination. The primary endpoint was the presence of metastases in the greater omentum. RESULTS: Of 100 included patients, five (5·0 per cent) had metastases in the greater omentum. Pathology results showed advanced tumours in all five (pT4b N1 M1, pT4b N2 M1, ypT4a N1 M1, ypT3 N2 M0, ypT3 N3 M0). The resection was microscopically non-radical at the proximal (3) or distal (2) resection margin in all of these patients. Metastases in the greater omentum correlated significantly with a microscopically non-radical resection, tumour expansion in the oesophagus or duodenum, linitis plastica or a proximal gastric tumour with diameter of at least 5 cm, stage III-IV disease and (y)pM1 category. CONCLUSION: In resectable gastric cancer, the incidence of metastases in the greater omentum is low, and when present associated with advanced disease and non-radical features. Thus, omentectomy as part of a radical gastrectomy may be omitted. REGISTRATION NUMBER: NCT02050659 ( http://www.clinicaltrials.gov).

Cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis in the PONCHO trial.

BACKGROUND: Same-admission cholecystectomy is indicated after gallstone pancreatitis to reduce the risk of recurrent disease or other gallstone-related complications, but its impact on overall costs is unclear. This study analysed the cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis. METHODS: In a multicentre RCT (Pancreatitis of biliary Origin: optimal timiNg of CHOlecystectomy; PONCHO) patients with mild gallstone pancreatitis were randomized before discharge to either cholecystectomy within 72 h (same-admission cholecystectomy) or cholecystectomy after 25-30 days (interval cholecystectomy). Healthcare use of all patients was recorded prospectively using clinical report forms. Unit costs of resources used were determined, and patients completed multiple Health and Labour Questionnaires to record pancreatitis-related absence from work. Cost-effectiveness analyses were performed from societal and healthcare perspectives, with the costs per readmission prevented as primary outcome with a time horizon of 6 months. RESULTS: All 264 trial participants were included in the present analysis, 128 randomized to same-admission cholecystectomy and 136 to interval cholecystectomy. Same-admission cholecystectomy reduced the risk of acute readmission for recurrent gallstone-related complications from 16·9 to 4·7 per cent (P = 0·002). Mean total costs from a societal perspective were €234 (95 per cent c.i. -1249 to 738) less per patient in the same-admission cholecystectomy group. Same-admission cholecystectomy was superior to interval cholecystectomy, with a societal incremental cost-effectiveness ratio of -€1918 to prevent one readmission for gallstone-related complications. CONCLUSION: In mild biliary pancreatitis, same-admission cholecystectomy was more effective and less costly than interval cholecystectomy.

Sidestream dark field imaging of the serosal microcirculation during gastrointestinal surgery.

AIM: The study aimed to describe the serosal microcirculation of the human bowel using sidestream dark field imaging, a microscopic technique using polarized light to visualize erythrocytes through capillaries. We also compared its feasibility to the current practice of sublingual microcirculatory assessment. METHOD: In 17 patients sidestream dark field measurements were performed during gastrointestinal surgery. Microcirculatory parameters like microvascular flow index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD) and total vessel density (TVD) were determined for every patient, sublingually and on the bowel serosa. RESULTS: Sixty measurements were done on the bowel of which eight (13%) were excluded, five owing to too much bowel peristalsis and three because of pressure artefacts. Image stability was in favour of sublingual measurements [pixel loss per image, bowel 145 (95% CI 126-164) vs sublingual 55 (95% CI 41-68); P < 0.001] and time to acquire a stable image [bowel 96 s (95% CI 63-129) vs. sublingual 46 s (95% CI 29-64); P = 0.013]. No difference in the MFI was observed [bowel 2.9 (interquartile range 2.87-2.95) vs sublingual 3.0 (interquartile range 2.91-3.0); P = 0.081]. There was a difference in the PPV [bowel 95% (95% CI 94-96) vs sublingual 97% (95% CI 97-99); P < 0.001], PVD [bowel 12.9 mm/mm2 (95% CI 11.1-14.8) vs sublingual 17.4 mm/mm2 (95% CI 15.6-19.1); P = 0.003] and the TVD [bowel 13.6 mm/mm2 (95% CI 11.6-15.6) vs sublingual 17.7 mm/mm2 (95% CI 16.0-19.4); P = 0.008]. CONCLUSION: Sidestream dark field imaging is a very promising technique for bowel microcirculatory visualization and assessment. It is comparable to sublingual assessment and the analysis produces a similar outcome with slightly differing anatomical features.

Anticipation of complications after laparoscopic cholecystectomy: prediction of individual outcome.

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.

A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol).

BACKGROUND: Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. DESIGN AND METHODS: The SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician's knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients' symptoms and treatment and work performance, and ultimately, cost-effectiveness. DISCUSSION: The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 http://www.zonmw.nl/nl/projecten/project-detail/scrutinizing-inefficient-use-of-cholecystectomy-a-randomized-trial-concerning-variation-in-practi/samenvatting/.

Endoscopic sphincterotomy and cholecystectomy in acute biliary pancreatitis.

BACKGROUND: This review discusses current insights with regard to biliary tract management during and after acute biliary pancreatitis. METHODS: A MEDLINE and EMBASE search was done and studies were selected based on methodological quality and publication date. The recommendations of recent guidelines are incorporated in this review. In absence of consensus in the literature, expert opinion is expressed. RESULTS: There is no role for early endoscopic retrograde cholangiopancreatography (ERCP) in patients with (predicted) mild biliary pancreatitis to improve outcome. In case of persisting choledocholithiasis, ERCP with stone extraction is scheduled electively when the acute event has subsided. Whether early ERCP with sphincterotomy is beneficial in patients with predicted severe pancreatitis remains subject to debate. Regardless of disease severity, in case of concomitant cholangitis urgent endoscopic sphincterotomy (ES) is recommended. As a definitive treatment to reduce the risk of recurrent biliary events in the long term, ES is inferior to cholecystectomy and should be reserved for patients considered unfit for surgery. After severe biliary pancreatitis, cholecystectomy should be postponed until all signs of inflammation have subsided. In patients with mild pancreatitis, cholecystectomy during the primary admission reduces the risk of recurrent biliary complications. CONCLUSION: Recent research has provided valuable data to guide biliary tract management in the setting of acute biliary pancreatitis with great value and benefit for patients and clinicians. Some important clinical dilemmas remain, but it is anticipated that on-going clinical trials will deliver some important insights and additional guidance soon.

High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery.

BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the relationship between postoperative high-sensitive cardiac troponin T elevations and non-cardiac complications in patients after major abdominal surgery. METHODS: This prospective observational single-centre cohort study included patients at risk for coronary artery disease undergoing elective major abdominal surgery. Cardiac troponin was measured before surgery and at day 1, 3, and 7. Multivariable logistic regression analysis was performed to examine the adjusted association for different cut-off concentrations of postoperative myocardial injury and non-cardiac outcome. RESULTS: In 203 patients, 690 high-sensitive cardiac troponin T measurements were performed. Fifty-three patients (26%) had a non-cardiac complication within 30 days after surgery. Hospital mortality was 4% (8/203). An increase in cardiac troponin T concentration ≥100% compared with baseline was a superior independent predictor of non-cardiac postoperative clinical complications (adjusted odds ratio 4.3, 95% confidence interval 1.8-10.1, P<0.001) and was associated with increased length of stay (9 days, 95% confidence interval 7-11 vs 7 days, 95% confidence interval 6-8, P=0.004) and increased hospital mortality (12 vs 2%, P=0.028). CONCLUSIONS: A postoperative high-sensitive cardiac troponin T increase ≥100% is a strong predictor of non-cardiac 30 day complications, increased hospital stay and hospital mortality in patients undergoing major abdominal surgery. CLINICALTRIALSGOV IDENTIFIER: NCT02150486.

Peritoneal carcinomatosis in t4 colorectal cancer: occurrence and risk factors.

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.

Staged multidisciplinary step-up management for necrotizing pancreatitis.

BACKGROUND: Some 15 per cent of all patients with acute pancreatitis develop necrotizing pancreatitis, with potentially significant consequences for both patients and healthcare services. METHODS: This review summarizes the latest insights into the surgical and medical management of necrotizing pancreatitis. General management strategies for the treatment of complications are discussed in relation to the stage of the disease. RESULTS: Frequent clinical evaluation of the patient's condition remains paramount in the first 24-72 h of the disease. Liberal goal-directed fluid resuscitation and early enteral nutrition should be provided. Urgent endoscopic retrograde cholangiopancreatography is indicated when cholangitis is suspected, but it is unclear whether this is appropriate in patients with predicted severe biliary pancreatitis without cholangitis. Antibiotic prophylaxis does not prevent infection of necrosis and antibiotics are not indicated as part of initial management. Bacteriologically confirmed infections should receive targeted antibiotics. With the more conservative approach to necrotizing pancreatitis currently advocated, fine-needle aspiration culture of pancreatic or extrapancreatic necrosis will less often lead to a change in management and is therefore indicated less frequently. Optimal treatment of infected necrotizing pancreatitis consists of a staged multidisciplinary 'step-up' approach. The initial step is drainage, either percutaneous or transluminal, followed by surgical or endoscopic transluminal debridement only if needed. Debridement is delayed until the acute necrotic collection has become 'walled-off'. CONCLUSION: Outcome following necrotizing pancreatitis has improved substantially in recent years as a result of a shift from early surgical debridement to a staged, minimally invasive, multidisciplinary, step-up approach.

The predictive value of proteinuria in acute pancreatitis.

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.

Routine colonoscopy is not required in uncomplicated diverticulitis: a systematic review.

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.