Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study.

BACKGROUND: Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. PATIENTS AND METHODS: An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. RESULTS: Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Nationwide validation of the distal fistula risk score (D-FRS).

PURPOSE: Distal pancreatectomy (DP) is associated with a high complication rate of 30-50% with postoperative pancreatic fistula (POPF) as a dominant contributor. Adequate risk estimation for POPF enables surgeons to use a tailor-made approach. Assessment of the risk of POPF prior to DP can lead to the application of preventive strategies. The current study aims to validate the recently published preoperative and intraoperative distal fistula risk score (D-FRS) in a nationwide cohort. METHODS: This nationwide retrospective Dutch cohort study included all patients after DP for any indication, all of whom were registered in the Dutch Pancreatic Cancer Audit (DPCA) database between 2013 and 2021. The D-FRS was validated by filling in the probability equations with data from this cohort. The predictive capacity of the models was represented by an area under the receiver operating characteristic (AUROC) curve. RESULTS: A total of 896 patients underwent DP of which 152 (17%) developed POPF of whom 144 grade B (95%) and 8 grade C (5%). The preoperative D-FRS, consisting of the variables pancreatic neck thickness and pancreatic duct diameter, showed an AUROC of 0.73 (95%CI 0.68-0.78). The intraoperative D-FRS, comprising pancreatic neck, duct diameter, BMI, operating time, and soft pancreatic aspect, showed an AUROC of 0.69 (95%CI 0.64-0.74). CONCLUSION: The current study is the first nationwide validation of the preoperative and intraoperative D-FRS showing acceptable distinguishing capacity for only the preoperative D-FRS for POPF. Therefore, the preoperative score could improve prevention and mitigation strategies such as drain management, which is currently investigated in the multicenter PANDORINA trial.

Completion pancreatectomy or a pancreas-preserving procedure during relaparotomy for pancreatic fistula after pancreatoduodenectomy: a multicentre cohort study and meta-analysis.

BACKGROUND: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. METHODS: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). CONCLUSION: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.

Effects of bariatric surgery on telomere length and T-cell aging.

BACKGROUND: Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. METHODS: WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4+ and CD8+ T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. RESULTS: Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8+ T-cell differentiation. Patients with MetS had significant lower CD4+ RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4+ T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. CONCLUSIONS: In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

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.

Patients' preferences for treatment after neoadjuvant chemoradiotherapy for oesophageal cancer.

BACKGROUND: After neoadjuvant chemoradiotherapy (nCRT) plus surgery for oesophageal cancer, 29 per cent of patients have a pathologically complete response in the resection specimen. Active surveillance after nCRT (instead of standard oesophagectomy) may improve health-related quality of life (HRQoL), but patients need to undergo frequent diagnostic tests and it is unknown whether survival is worse than that after standard oesophagectomy. Factors that influence patients' preferences, and trade-offs that patients are willing to make in their choice between surgery and active surveillance were investigated here. METHODS: A prospective discrete-choice experiment was conducted. Patients with oesophageal cancer completed questionnaires 4-6 weeks after nCRT, before surgery. Patients' preferences were quantified using scenarios based on five aspects: 5-year overall survival, short-term HRQoL, long-term HRQoL, the risk that oesophagectomy is still necessary, and the frequency of clinical examinations using endoscopy and PET-CT. Panel latent class analysis was used. RESULTS: Some 100 of 104 patients (96·2 per cent) responded. All aspects, except the frequency of clinical examinations, influenced patients' preferences. Five-year overall survival, the chance that oesophagectomy is still necessary and long-term HRQoL were the most important attributes. On average, based on calculation of the indifference point between standard surgery and active surveillance, patients were willing to trade off 16 per cent 5-year overall survival to reduce the risk that oesophagectomy is necessary from 100 per cent (standard surgery) to 35 per cent (active surveillance). CONCLUSION: Patients are willing to trade off substantial 5-year survival to achieve a reduction in the risk that oesophagectomy is necessary.

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).

Comparison of a low Hartmann's procedure with low colorectal anastomosis with and without defunctioning ileostomy after radiotherapy for rectal cancer: results from a national registry.

AIM: This study used a national registry to compare the outcome after a low Hartmann's procedure (LHP), defined as removal of most of the rectum to leave a short anorectal stump and an end colostomy, and low anterior resection (LA) with or without a diverting ileostomy (DI) in rectal cancer patients all of whom had received preoperative neoadjuvant radiotherapy (RT). METHOD: Patients who underwent LHP or LA with or without DI for rectal cancer after RT between 2009 and 2013 were identified from the Dutch Surgical Colorectal Audit. The postoperative outcome was compared between the three groups and risk of complications, reoperation and mortality were analysed in a multivariable model. RESULTS: The study included 4288 patients were included, of whom 27.8% underwent LHP, 20.2% LA and 52.0% LA with DI. Thirty-day mortality was higher after LHP (3.2% vs 1.3% and 1.3% for LA with or without DI, P < 0.001), but LHP was not an independent predictor of mortality in multivariable analysis. LHP and LA with DI were associated with a lower rate of abdominal infective complications (6.5% and 10.1% vs 16.2%, P < 0.001) and reoperation (7.3% and 8.1% vs 16.5%, P < 0.001). In multivariable analysis, LHP (OR 0.35, 95% CI 0.26-0.47) and LA with DI (OR 0.43, 95% CI 0.33-0.54) were associated with a lower risk of reoperation than LA alone. LHP was associated with a lower risk of any postoperative complication than LA with or without DI (OR 0.81, 95% CI 0.66-0.98). CONCLUSION: LHP and LA with DI were associated with fewer infective complications and reoperations than LA alone. The rate of any complication was less after LHR than LA with or without DI.

PROMISE: effect of protein supplementation on fat-free mass preservation after bariatric surgery, a randomized double-blind placebo-controlled trial.

INTRODUCTION: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS AND ANALYSIS: Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA). ETHICS AND DISSEMINATION: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022.

Preoperative staging of perforated diverticulitis by computed tomography scanning.

BACKGROUND: Treatment of perforated diverticulitis depends on disease severity classified according to Hinchey's preoperative classification. This study assessed the accuracy of preoperative staging of perforated diverticulitis by computerized tomography (CT) scanning. METHODS: All patients who presented with perforated diverticulitis between 1999 and 2009 in two teaching hospitals of Rotterdam, the Netherlands, and in addition had a preoperative CT scan within 24 h before emergency surgery were included. Two radiologists reviewed all CT scans and were asked to classify the severity of the disease according to the Hinchey classification. The CT classification was compared to Hinchey's classification at surgery. RESULTS: Seventy-five patients were included, 48 of whom (64 %) were classified Hinchey 3 or 4 perforated diverticulitis during surgery. The positive predictive value of preoperative CT scanning for different stages of perforated diverticulitis ranged from 45 to 89 %, and accuracy was between 71 and 92 %. The combination of a large amount of free intra-abdominal air and fluid was strongly associated with Hinchey 3 or 4 and therefore represented a reliable indicator for required surgical treatment. CONCLUSIONS: The accuracy of predicting Hinchey's classification by preoperative CT scanning is not very high. Nonetheless, free intra-abdominal air in combination with diffuse fluid is a reliable indication for surgery as it is strongly associated with perforated diverticulitis with generalized peritonitis. In 42 % of cases, Hinchey 3 perforated diverticulitis is falsely classified as Hinchey 1 or 2 by CT scanning.

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery.

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.

Long-term survival after perforated diverticulitis.

AIM: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. METHOD: All patients who underwent emergency surgery for perforated diverticulitis in five hospitals in Rotterdam, the Netherlands, between 1990 and 2005, were included. The association between type of surgery (Hartmann's procedure or primary anastomosis) and long-term survival was analysed using multivariate Cox regression analysis, taking into account age American Society of Anesthesiology (ASA) classification, Hinchey score, Mannheim Peritonitis Index (MPI) and surgeon's experience. In addition, survival of the patients was compared with that of the matched general Dutch population. RESULTS: Of 340 patients included in the study, 250 were discharged alive from hospital. The overall 5-year survival was 53%. Survival was significantly impaired compared with the expected matched gender-, age- and calendar time-specific survival. Overall survival was significantly related to age and ASA classification. Hinchey score, MPI, number of re-interventions, the surgeon's experience and type of procedure did not influence long-term survival, although a trend was found for Hartmann's procedure to be a risk factor for poorer survival compared with primary anastomosis (hazard ratio for mortality: 1.88; 95% confidence interval, 0.96-3.67; P = 0.07). CONCLUSION: Long-term survival of patients after perforated diverticulitis is limited and mainly caused by the poor general condition of the patients, rather than by the severity of the primary disease or calendar-time and type of procedure.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Microscopic resection margin status in pancreatic ductal adenocarcinoma - A nationwide analysis.

INTRODUCTION: First, this study aimed to assess the prognostic value of different definitions for resection margin status on disease-free survival (DFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC). Second, preoperative predictors of direct margin involvement were identified. MATERIALS AND METHODS: This nationwide observational cohort study included all patients who underwent upfront PDAC resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit. Patients were subdivided into three groups: R0 (≥1 mm margin clearance), R1 (<1 mm margin clearance) or R1 (direct margin involvement). Survival was compared using multivariable Cox regression analysis. Logistic regression with baseline variables was performed to identify preoperative predictors of R1 (direct). RESULTS: 595 patients with a median OS of 18 months (IQR 10-32 months) months were analysed. R0 (≥1 mm) was achieved in 277 patients (47%), R1 (<1 mm) in 146 patients (24%) and R1 (direct) in 172 patients (29%). R1 (direct) was associated with a worse OS, as compared with both R0 (≥1 mm) (hazard ratio (HR) 1.35 [95% and confidence interval (CI) 1.08-1.70); P < 0.01) and R1 (<1 mm) (HR 1.29 [95%CI 1.01-1.67]; P < 0.05). No OS difference was found between R0 (≥1 mm) and R1 (<1 mm) (HR 1.05 [95% CI 0.82-1.34]; P = 0.71). Preoperative predictors associated with an increased risk of R1 (direct) included age, male sex, performance score 2-4, and venous or arterial tumour involvement. CONCLUSION: Resection margin clearance of <1 mm, but without direct margin involvement, does not affect survival, as compared with a margin clearance of ≥1 mm. Given that any vascular tumour involvement on preoperative imaging was associated with an increased risk of R1 (direct) resection with upfront surgery, neoadjuvant therapy might be considered in these patients.

Local application of gentamicin collagen implants in the prophylaxis of surgical site infections following gastrointestinal surgery: a review of clinical experience.

BACKGROUND: Surgical site infection (SSI) is a common type of healthcare-associated infection in gastrointestinal (GI) surgical procedures, which often has major consequences for patient recovery and increased healthcare costs due to prolonged hospital stay. This article provides an overview of the efficacy and safety of prophylactic application of resorbable gentamicin-containing collagen implants (GCI) in the prevention of SSI following high-risk GI surgical procedures. METHOD: Nine publications were identified using the PubMed online database and search terms 'gentamicin collagen implant' plus 'surgical site infection', 'wound infection' and 'gastrointestinal surgery'. RESULTS: Data from 483 patients treated prophylactically have demonstrated that GCI can reduce the wound infection rate in high-risk GI surgical procedures and improve wound healing after pilonidal sinus excision. In a study of 221 patients who underwent colorectal surgery, the wound infection rate was reduced to 5.6% in the GCI group compared to 18.4% in the control group (P < 0.01). GCI also positively influences the post-operative course for patients undergoing particularly risky procedures e.g. abdominoperineal resection (APR) combined with neoadjuvant radiotherapy. In one such patient series, GCI reduced the wound infection rate by over 70% and the length of hospital stay by 40%. Few side effects of GCI were noted in the 9 clinical studies. CONCLUSIONS: This review demonstrates that GCI can have a positive effect on wound infection rates in high-risk GI surgery and can also improve wound healing after pilonidal sinus excision.

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Restoration of bowel continuity after surgery for acute perforated diverticulitis: should Hartmann's procedure be considered a one-stage procedure?

OBJECTIVE: Hartmann's procedure (HP) still remains the most frequently performed procedure in acute perforated diverticulitis, but it results in a end colostomy. Primary anastomosis (PA) with or without defunctioning loop ileostomy (DI) seems a good alternative. The aim of this study was to assess differences in the rate of stomal reversal after HP and PA with DI and to evaluate factors associated with postreversal morbidity in patients operated for acute perforated diverticulitis. METHOD: All 158 patients who had survived emergency surgery for acute perforated diverticulitis in five teaching hospitals in The Netherlands between 1995 and 2005 and underwent HP or PA with DI were retrospectively studied. Age, gender, ASA-classification, severity of primary disease, delay of stoma reversal, surgeon's experience, surgical procedure and type of anastomosis were analysed in relation to outcome after stoma reversal. RESULTS: Of the 158 patients, 139 had undergone HP and 19 PA with DI. The reversal-rate was higher in patients with DI (14/19; 74%) compared to HP (63/139; 45%) (P = 0.027) Delay between primary surgery and stoma reversal was shorter after PA with DI compared with HP (3.9 vs 9.1 months; P < 0.001). Cumulative postreversal morbidity after HP was 44%. Early surgical complications occurred in 22 of 63 patients. Morbidity after DI reversal was 15% (P < 0.001). Three patients died after HP reversal, none died after DI reversal. Anastomotic leakage was observed in 10 patients after HP reversal. This was less frequently observed when the operation was performed by a specialist colorectal surgeon (10%vs 33%; P = 0.049) and when a stapled anastomosis was performed (4%vs 24%; P = 0.037). CONCLUSIONS: Reversal of HP should only be performed by an experienced colorectal surgeon, preferably performing a stapled anastomosis, or probably not be performed at all, as it is accompanied by high postoperative morbidity and even mortality. It is important that these findings are taken in account for when performing primary emergency surgery for acute perforated diverticulitis.

Is less more? A prospective trial on one trocar appendectomy.

One trocar appendectomy is a combination of laparoscopic and open appendectomy. The advantage, along with improved cosmesis, is the possibility to introduce a dissection instrument through the optical trocar without an additional incision. In this prospective study the sense of one trocar appendectomy is evaluated in daily practise for a cohort of consecutive patients with suspected acute appendicitis. Twenty-two patients were enrolled. One-trocar appendectomy was successful in 13 patients. In 8 patients one extra 2, 5 or 10 millimetre trocar was necessary. In one patient a third trocar was necessary. Conversion to an open appendectomy through a grid iron incision was not necessary. The pathologist confirmed the diagnosis of acute appendicitis in all patients. The average operation time was 53 minutes. Complications included one wound abscess and one wound haematoma. In conclusion one trocar appendectomy is a good and safe technique in patients with the suspicion of acute appendicitis, provided that the operative team must be experienced in laparoscopic surgery and the constitution of the patient is suitable for this technique.

COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.

INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. TRIAL DESIGN: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).

The impact of chronic smoking on rectal mucosal blood flow.

BACKGROUND: Chronic smoking adversely affects peripheral vasculature. The aim of the present study was to investigate the effect of chronic cigarette smoking on rectal microvascular blood flow. METHODS: Rectal mucosal blood flow (MBF) was measured in 80 subjects (44 smokers and 36 non-smokers). The MBF was measured in the four quadrants of the rectum by laser Doppler flowmetry. RESULTS: Rectal perfusion was found to be significantly lower in posterior midline compared to the other sites. In chronic smokers the observed MBF measured at the posterior and ventral sites was significantly lower compared to non-smokers (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: Our results suggest that rectal mucosal blood flow is reduced in chronic smokers.