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HPB : official journal of The international Hepato-Pancreato-Biliary Association 24(9), 1492-1500 (2022). doi:10.1016/j.hpb.2022.03.005, Published by Elsevier, [London]

Introduction: Routine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. Methods: This was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. Results: Of 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. Conclusion: In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone.

BACKGROUND: Laparoscopic and robotic minimally invasive liver surgery (MILS) is gaining popularity. Recent data and views on the implementation of laparoscopic and robotic MILS throughout Europe are lacking.METHODS: An anonymous survey consisting of 46 questions was sent to all members of the European-African Hepato-Pancreato-Biliary Association.RESULTS: The survey was completed by 120 surgeons from 103 centers in 24 countries. Median annual center volume of liver resection was 100 [IQR 50-140]. The median annual volume of MILS per center was 30 [IQR 16-40]. For minor resections, laparoscopic MILS was used by 80 (67%) surgeons and robotic MILS by 35 (29%) surgeons. For major resections, laparoscopic MILS was used by 74 (62%) surgeons and robotic MILS by 33 (28%) surgeons. The majority of the surgeons stated that minimum annual volume of MILS per center should be around 21-30 procedures/year. Of the surgeons performing robotic surgery, 28 (70%) felt they missed specific equipment, such as a robotic-CUSA. Seventy (66%) surgeons provided a formal MILS training to residents and fellows. In 5 years' time, 106 (88%) surgeons felt that MILS would have superior value as compared to open liver surgery.CONCLUSION: In the participating European liver centers, MILS comprised about one third of all liver resections and is expected to increase further. Laparoscopic MILS is still twice as common as robotic MILS. Development of specific instruments for robotic liver parenchymal transection might further increase its adoption.

Background The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. Methods This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014–2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. Results In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (−1.71 (95 per cent c.i. −2.27 to −1.05) and −3.05 (95 per cent c.i. −4.03 to −1.80) respectively) and overall survival (−1.92 (95 per cent c.i. −2.60 to −1.16) and −3.49 (95 per cent c.i. −4.84 to −2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (−5.38 (95 per cent c.i. −9.27 to −1.94)) and overall survival (−6.32 (95 per cent c.i. −10.43 to −1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. Conclusion Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.

Contains fulltext : 251531.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

Purpose In the pre-clinical setting, hepatocellular bile salt accumulation impairs liver regeneration following partial hepatectomy. Here, we study the impact of cholestasis on portal vein embolization (PVE)-induced hypertrophy of the future liver remnant (FLR). Methods Patients were enrolled with perihilar cholangiocarcinoma (pCCA) or colorectal liver metastases (CRLM) undergoing PVE before a (extended) right hemihepatectomy. Volume of segments II/III was considered FLR and assessed on pre-embolization and post-embolization CT scans. The degree of hypertrophy (DH, percentual increase) and kinetic growth rate (KGR, percentage/week) were used to assess PVE-induced hypertrophy. Results A total of 50 patients (31 CRLM, 19 pCCA) were included. After PVE, the DH and KGR were similar in patients with CRLM and pCCA (5.2 [3.3–6.9] versus 5.7 [3.2–7.4] %, respectively, p = 0.960 for DH; 1.4 [0.9–2.5] versus 1.9 [1.0–2.4] %/week, respectively, p = 0.742 for KGR). Moreover, pCCA patients with or without hyperbilirubinemia had comparable DH (5.6 [3.0–7.5] versus 5.7 [2.4–7.0] %, respectively, p = 0.806) and KGR (1.7 [1.0–2.4] versus 1.9 [0.8–2.4] %/week, respectively, p = 1.000). For patients with pCCA, unilateral drainage in FLR induced a higher DH than bilateral drainage (6.7 [4.9–7.9] versus 2.7 [1.5–4.2] %, p = 0.012). C-reactive protein before PVE was negatively correlated with DH (ρ = − 0.539, p = 0.038) and KGR (ρ = − 0.532, p = 0.041) in patients with pCCA. Conclusions There was no influence of cholestasis on FLR hypertrophy in patients undergoing PVE. Bilateral drainage and inflammation appeared to be negatively associated with FLR hypertrophy. Further prospective studies with larger and more homogenous patient cohorts are desirable.

Background: Despite a lack of high-level evidence, current guidelines recommend laparoscopic left lateral sectionectomy (LLLS) as the routine approach over open LLS (OLLS). Randomized studies and propensity score matched studies on LLLS vs OLLS for all indications, including malignancy, are lacking.Methods: This international multicenter propensity score matched retrospective cohort study included consecutive patients undergoing LLLS or OLLS in six centers from three European countries (January 2000-December 2016). Propensity scores were calculated based on nine preoperative variables and LLLS and OLLS were matched in a 1:1 ratio. Short-term operative outcomes were compared using paired tests.Results: A total of 560 patients were included. Out of 200 LLLS, 139 could be matched to 139 OLLS. After matching, baseline characteristics were well balanced. LLLS was associated with shorter operative time (144 (110-200) vs 199 (138-283) minutes, P < 0.001), less blood loss (100 (50-300) vs 350 (100-750) mL, P = 0.005) and a 3-day shorter postoperative hospital stay (4 (3-7) vs 7 (5-9) days, P < 0.001).Conclusion: This international multicenter propensity score matched study confirms the superiority of LLLS over OLLS based on shorter postoperative hospital stay, operative time, and less blood loss thus validating current guideline advice.

OBJECTIVE: To describe outcome after pancreatic surgery in the first six years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between three time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after pancreatoduodenectomy and 1118 after distal pancreatectomy. After pancreatoduodenectomy, failure to rescue improved from 13% to 7.4% (OR 0.64, 95%CI 0.50-0.80, P75 years (18% to 22%, P=0.006), ASA score ≥3 (19% to 31%, P

Background Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. Methods We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. Findings From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0middot48, 95% CI 0middot38-0middot61; p

BACKGROUNDLaparoscopic liver surgery is currently considered the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after laparoscopic hepatectomy (LH) in overweight patients are still sparse and its benefit compared to open hepatectomy (OH) is a matter of debate.AIMTo analyze postoperative outcomes in overweight [body mass index (BMI) over 25 kg/m(2)] and obese (BMI over 30 kg/m(2)) patients undergoing LH and compare postoperative outcome with patients undergoing OH.METHODSPerioperative data of 68 overweight (BMI over 25 kg/m(2)) including a subcohort of obese (BMI over 30 kg/m(2)) patients (n = 27) who underwent LH at our institution between 2015 and 2019 were retrospectively analyzed regarding surgical outcome and compared to an equal number of patients undergoing OH.RESULTSThe mean BMI was 29.8 +/- 4.9 kg/m(2) in the LH group and 29.7 +/- 3.6 kg/m(2) in the OH group with major resections performed in 20.6% (LH) and 26.5% (OH) of cases, respectively. Operative time (194 +/- 88 min vs 275 +/- 131 min; P < 0.001) as well as intensive care (0.8 +/- 0.7 d vs 1.1 +/- 0.8 d; P = 0.031) and hospital stay (7.3 +/- 3.6 d vs 15.7 +/- 13.5 d; P < 0.001) were significant shorter in the LH group. Also, overall complications (20.6% vs 45.6%; P = 0.005) and major complications (1.5% vs 14.7%, P = 0.002) were observed less frequently after LH. An additional investigation analyzing the subgroup of obese patients who underwent LH (n = 27) and OH (n = 29) showed a shorter operative time (194 +/- 81 min vs 260 +/- 137 min; P = 0.009) and a reduced length of hospitalization (7.7 +/- 4.3 d vs 17.2 +/- 17 d; P < 0.001) but no difference in postoperative complications or overall cost.CONCLUSIONLH is safe and cost-effective in overweight and obese patients. Furthermore, LH is significantly associated with fewer postoperative complications and reduced hospital stay compared to OH in these patients.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers.METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed.RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival.CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

BACKGROUND: Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection.METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival.RESULTS: Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively.CONCLUSION: In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival.SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence.RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001].CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.

Contains fulltext : 239076.pdf (Publisher’s version ) (Closed access) OBJECTIVE: This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection). BACKGROUND: Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking. METHODS: Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015-December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS. RESULTS: Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222-0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01). CONCLUSIONS: Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.

Contains fulltext : 239059.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVES: Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. METHODS: From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. RESULTS: A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c-index: 0.79). CONCLUSIONS: Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients.

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale. Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume. Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0–13%, mortality

PLOS ONE 16(6), 0253506 (2021). doi:10.1371/journal.pone.0253506, Published by PLOS, San Francisco, California, US

Journal of hepato-biliary pancreatic sciences 9(6), 609-617 (2021). doi:10.1002/jhbp.1020, Published by Wiley, Tokyo [u.a.]

Introduction: Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC.Materials and methods: Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 until December 2017. A centralized expert panel reviewed response according to RECIST v1.1 and potential surgical resectability. Primary outcome was median overall survival (mOS), stratified for primary treatment strategy.Results: Overall, 422 patients were included, of whom 77% (n = 326) received chemotherapy. The majority started with FOLFIRINOX (77%, 252/326) with a median of six cycles (IQR 4-10). Gemcitabine monotherapy was given to 13% (41/326) of patients and nab-paclitaxel/gemcitabine to 10% (33/326), with a median of two (IQR 3-5) and three (IQR 3-5) cycles respectively. The mOS of the entire cohort was 10 months (95%CI 9-11). In patients treated with FOLFIRINOX, gemcitabine monotherapy, or nab-paclitaxel/gemcitabine, mOS was 14 (95%CI 13-15), 9 (95%CI 8-10), and 9 months (95%CI 8-10), respectively. A resection was performed in 13% (32/252) of patients after FOLFIRINOX, resulting in a mOS of 23 months (95%CI 12-34).Conclusion: This multicenter unselected cohort of patients with LAPC resulted in a 14 month mOS and a 13% resection rate after FOLFIRINOX. These data put previous results in perspective, enable us to inform patients with more accurate survival numbers and will support decision-making in clinical practice. (C) 2020 The Authors. Published by Elsevier Ltd.

Scientific reports 11(1), 2926 (2021). doi:10.1038/s41598-021-82378-y, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Contains fulltext : 229783.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. METHODS: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. RESULTS: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P

Background: The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients' quality of life. Contemporary data on postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking.Methods: We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006-2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes.Results: Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P < .05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P = .03) and daily health status (0.83 vs 0.87, P < .01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes.Conclusion: This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes. (C) 2019 Elsevier Inc. All rights reserved.

OBJECTIVE: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery.BACKGROUND: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination.METHODS: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements.RESULTS: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee.CONCLUSION: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

Background: An inverse relation between chemotherapy-associated liver injury (CALI) and tumour response to chemotherapy has been reported. The aim was to validate these findings, and further investigate the impact of CALI on survival in patients who underwent partial hepatectomy for colorectal liver metastases (CRLM).Methods: Patients who received neoadjuvant chemotherapy and underwent partial hepatectomy for CRLM between 2008 and 2014 were included. Liver and tumour specimens were histologically examined for CALI (steatosis, steatohepatitis, sinusoidal dilatation [SD], nodular regeneration) and tumour regression grade (TRG). TRG 1-2 was defined as complete tumour response.Results: 166 consecutive patients were included with a median survival of 30 and 44 months for recurrence-free and overall survival, respectively. Grade 2-3 SD was found in 44 (27%) and TRG 1-2 was observed in 33 (20%) patients. Of studied CALI, only grade 2-3 SD was associated with increased TRG 3-5 (odds ratio 3.99, 95% CI 1.17-13.65, p = 0.027). CALI was not significantly related to survival. TRG 1-2 was associated with prolonged recurrence-free (hazard ratio 0.47, 95% CI 0.25-0.89, p = 0.020) and overall survival (hazard ratio 0.35, 95% CI 0.18-0.68, p = 0.002).Conclusion: CALI was not directly related to survival. CALI was, however, associated with diminished complete tumour response, and diminished complete tumour response, in turn, was associated with decreased survival.

OBJECTIVES: Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank.METHODS: The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit.RESULTS: Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples.CONCLUSIONS: Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

Background: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery.Methods: All patients with complete liver volume data in the associating liver partition and portal vein ligation for staged hepatectomy registry were included in this study. Estimate total liver volume and estimated future remnant liver volume were calculated for 16 published formulas. The median over- or underestimation compared with actual measured volumes were determined for estimate total liver volume and future remnant liver volume. The proportion of patients with an under- or overestimated future remnant liver volume for each formula were compared with each other using a 25% cut-off for each formula.Results: Among 529 studied patients, the formulas ranged from a 19% underestimation to a 63% overestimation of estimate total liver volume. Estimation of future remnant liver volume lead to a 10% underestimation to a 5% overestimation among the formulas. Of all studied formulas, the Vautheyl formula was the most accurate, generating underestimation of future remnant liver volume in 20% and overestimation of future remnant liver volume in 6% of patients.Conclusion: Validation of 16 published total liver volume formulas in a multicenter international cohort of 529 patients that underwent staged hepatectomy revealed that the Vauthey formula (estimate total liver volume =18.51 x body weight + 191.8) provides the most accurate prediction of the actual future remnant liver volume. (C) 2019 Elsevier Inc. All rights reserved.

Background Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. Methods A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo–Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively. Results Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 (95% CI: 9.2–27.8) months, respectively; P

OBJECTIVES: The objective of this study was to identify predictors for successful minimally invasive catheter drainage (ie, survival without relaparotomy) for pancreatic fistula after pancreatoduodenectomy.METHODS: Included were consecutive patients undergoing catheter drainage as first intervention for pancreatic fistula after pancreatoduodenectomy (2005-2013) in 9 Dutch centers. Possible prognostic factors for successful catheter drainage (ie, survival without relaparotomy) were selected using Akaike information criterion.RESULTS: Included were 227 patients after 2196 pancreatoduodenectomies. Primary catheter drainage was successful in 175 (77%) of 227 patients. Multivariable logistic regression revealed the following negative prognostic factors for success: male sex (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-1.00; P = 0.049), higher age (for every 5 years over 50; OR, 0.69; 95% CI, 0.57-0.84; P < 0.001), and respiratory failure at time of catheter drainage (OR, 0.10; 95% CI, 0.03-0.33; P < 0.001). A prognostic model incorporating these factors yielded an area under the curve of 0.76 and demonstrated a success range of 98% to 14%.CONCLUSIONS: Male sex, higher age, and respiratory failure are associated with a low success rate of catheter drainage in patients with pancreatic fistula after pancreatoduodenectomy. These patients might benefit from an intensified postoperative monitoring for early detection and management of pancreatic fistula to prevent respiratory failure.

International audience; OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200?mL (60-400) vs 300?mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P \textless 0.001] were lower after MIDP. Clavien-Dindo grade >=3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P \textgreater 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P \textless 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P \textless 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Objective: This trial followed a structured nationwide training program in minimally invasive distal pancreatectomy (MIDP), according to the IDEAL framework for surgical innovation, and aimed to compare time to functional recovery after minimally invasive and open distal pancreatectomy (ODP).Background: MIDP is increasingly used and may enhance postoperative recovery as compared with ODP, but randomized studies are lacking.Methods: A multicenter patient-blinded randomized controlled superiority trial was performed in 14 centers between April 2015 and March 2017. Adult patients with left-sided pancreatic tumors confined to the pancreas without vascular involvement were randomly assigned (1:1) to undergo MIDP or ODP. Patients were blinded for type of surgery using a large abdominal dressing. The primary endpoint was time to functional recovery. Analysis was by intention to treat. This trial was registered with the Netherlands Trial Register (NTR5689).Results: Time to functional recovery was 4 days [interquartile range (IQR) 3-6) in 51 patients after MIDP versus 6 days (IQR 5-8) in 57 patients after ODP (P = III complication rate was 25% versus 38% (P = 0.21). Delayed gastric emptying grade B/C was seen less often after MIDP (6% vs 20%; P = 0.04). Postoperative pancreatic fistulas grade B/C were seen in 39% after MIDP versus 23% after ODP (P = 0.07), without difference in percutaneous catheter drainage (22% vs 20%; P = 0.77). Quality of life (day 3-30) was better after MIDP as compared with ODP, and overall costs were non-significantly less after MIDP. No 90-day mortality was seen after MIDP versus 2% (n = 1) after ODP.Conclusions: In patients with left-sided pancreatic tumors confined to the pancreas, MIDP reduces time to functional recovery compared with ODP. Although the overall rate of complications was not reduced, MIDP was associated with less delayed gastric emptying and better quality of life without increasing costs.

Background: The feasibility of the liver-first approach for synchronous colorectal liver metastases (CRLM) has been established. We sought to assess the short-term and long-term outcomes for these patients.Methods: Outcomes of patients who underwent a liver-first approach for CRLM between 2005 and 2015 were retrospectively evaluated from a prospective database.Results: Of the 92 patients planned to undergo the liver-first strategy, the paradigm could be completed in 76.1%. Patients with concurrent extrahepatic disease failed significantly more often in completing the protocol (67% versus 21%; p = 0.03). Postoperative morbidity and mortality were 31.5% and 3.3% following liver resection and 30.9% and 0% after colorectal surgery. Of the 70 patients in whom the paradigm was completed, 36 patients (51.4%) developed recurrent disease after a median interval of 20.9 months. The median overall survival on an intention-to-treat basis was 33.1 months (3-and 5-year overall survival: 48.5% and 33.1%). Patients who were not able to complete their therapeutic paradigm had a significantly worse overall outcome (p = 0.03).Conclusion: The liver-first approach is feasible with acceptable perioperative morbidity and mortality rates. Despite the considerable overall-survival-benefit, recurrence rates remain high. Future research should focus on providing selection tools to enable the optimal treatment sequence for each patient with synchronous CRLM.

Background Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. Methods In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix® software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. Results A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95–508) vs. 358 (96–684) µg/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116–2685) vs. 1533 (869–2852) mL, P = 0.079] compared with non-obese patients. Weight (r = −0.40), body surface area (r = −0.32), estimated body-fat% (r = −0.43) and body mass index (r = −0.47) showed a weak but significant negative (all P

Background: In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low-and high-mortality hospitals are compared, and independent predictors for FTR investigated.Methods: Patients undergoing pancreatoduodenectomy in 2014 and 2015 in The Netherlands were included. Hospitals were divided into quartiles based on mortality rates. The rate of major complications (Clavien-Dindo >= 3) and death after a major complication (FTR) were compared between these quartiles. Independent predictors for FTR were identified by multivariable logistic regression analysis.Results: Out of 1.342 patients, 391 (29%) developed a major complication and in-hospital mortality was 4.2%. FTR occurred in 56 (14.3%) patients. Mortality was 0.9% in the first hospital quartile (4 hospitals, 327 patients) and 8.1% in the fourth quartile (5 hospitals, 310 patients). The rate of major complications increased by 40% (25.7% vs 35.2%) between the first and fourth hospital quartile, whereas the FTR rate increased by 560% (3.6% vs 22.9%). Independent predictors of FTR were male sex (OR = 2.1, 95% CI 1.2-3.9), age > 75 years (OR = 4.3, 1.8-10.2), BMI >= 30 (OR = 2.9, 1.3-6.6), histopathological diagnosis of periampullary cancer (OR = 2.0, 1.1-3.7), and hospital volume Conclusions: Variations in mortality between hospitals after pancreatoduodenectomy were explained mainly by differences in FTR, rather than the incidence of major complications.

Despite the established advantages of laparoscopy, bleeding control during laparoscopic liver resection (LLR) is a liver-specific improvement. The 2nd International Consensus Conference on Laparoscopic Liver Resection was held in October 2014 at Morioka, Japan. One of the most capital questions was: What is essential in bleeding control during LLR? In order to correctly address this question, we conducted a comprehensive review of the literature. Essential points based on personal experience of the expert panel are also discussed. A total of 54 publications were identified. Based on this analysis, the working group built these recommendations: (1) a pneumoperitoneum of 10-14 mmHg should be used as it allows a good control of the bleeding without significant modifications of hemodynamics; (2) a low central venous pressure (

Dear Editor, I read with interest the article from our colleagues from Maastricht and Aachen, which describes a video-assisted approach to debridement of multi-loculated or so-called “honey-comb” liver abscesses,1 which are notoriously difficult to treat by simple percutaneous drainage alone. The article describes access via an open flank incision, with subsequent debridement facilitated by the insertion of a laparoscope through the incision. This is a technique synonymous with an approach to video-assisted pancreatic necrosectomy, popularised predominantly by groups from the Netherlands. I would like to report similar success in treating these abscesses via a percutaneous approach – again reported previously for the treatment of infected pancreatic necrosis.2 For this approach, I have used a balloon dilator to enlarge the tract of a percutaneous pig-tail drain and performed a debridement via the drain tract using a nephroscope. This alternative technique has the advantage of producing only a 24F drain tract wound, which carries far less morbidity than an open flank incision and simplifies the subsequent management of any potential biliary fistula. A speedy resolution of the abscess following debridement was achieved (Fig. 1). Figure 1 CT Scans showing response to percutaneous debridement of large multi-loculated liver abscess using a drain-tract approach

Item does not contain fulltext BACKGROUND: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. METHODS: Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. RESULTS: Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade >/= III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. CONCLUSIONS: The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level.

BACKGROUND: An enhanced recovery after surgery (ERAS) program aims to reduce the stress response to surgery and thereby accelerate recovery. It is unclear whether these programs can be safely implemented for elderly patients, especially in highly complex surgery such as pancreaticoduodenectomy (PD). The objective of this study was to evaluate the feasibility of an ERAS program in elderly patients undergoing PD. METHODS: Implementation of the ERAS protocol was studied prospectively in a consecutive series of patients undergoing PD between January 2009 and August 2013. Patients were divided into two groups: /= 70 years. Endpoints were length of stay (LOS), readmissions, morbidity, mortality, and compliance with ERAS targets. RESULTS: Of a total of 110 patients, 55 were /= 70 years (median 77). Median LOS was 14 days in both groups. In patients without complications median LOS was 9 days. Both mortality and readmissions did not differ between groups (mortality n = 3 (5.5 %) in younger versus n = 6 (10.9 %) in older patients, p = 0.49, readmissions: n = 11 (20 %) versus n = 7 (12.7 %), p = 0.44). CT-drainage and relaparotomy-rates were not different between groups, nor was overall morbidity (n = 31 (56.3 %) in the older versus n = 35 (63.3 %) in the younger group, p = 0.44). There were no differences in compliance with elements of the ERAS protocol between groups. CONCLUSION: An ERAS program seems feasible and safe for patients >/= 70 years of age undergoing PD.

Background: Pancreaticoduodenectomies (PDs) are complex surgical procedures that require high-standard perioperative care. The objective of this study was to evaluate the effects of implementing an Enhanced Recovery After Surgery (ERAS) program for PD on patient outcome. Methods: 230 patients undergoing PD in the Maastricht University Medical Centre between January 1995 and January 2012 were included. Group 1 (no ERAS; 1995-2005) received traditional care. From January 2006, several elements of an ERAS pathway for pancreatic surgery were implemented (group 2: ‘ERAS-like'). From 2009 onwards the ERAS pathway was fully implemented (group 3: ERAS). Mortality, complications, readmissions and length of hospital stay (LOS) were evaluated in the subgroups and compared. Results: Median LOS was significantly reduced from 20 days in group 1 to 13 days in group 2 and 14 days in group 3 (p = 0.001). Median LOS of patients without complications was 16, 10 and 9 days in groups 1, 2 and 3, respectively (p < 0.0001). Over time, the average age of patients undergoing PD increased significantly. Complication rates as well as mortality and readmission rates did not change over time. Conclusion: Implementing an ERAS program contributed to a decrease of LOS without compromising other outcomes. Mortality, morbidity and readmission rates stayed unchanged and more complications were managed non-operatively.