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Abstract Background Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. Methods/design Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. Discussion PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente et al., 2007; Bassi et al., 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., 2016; Pratt et al., 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., 2022; Asbun and Stauffer, 2011).

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Consumer wearables health data may reflect the impact of pancreatic cancer and its treatment on cardiorespiratory fitness and the subsequent recovery after treatment. The patient is a 65-year-old male treated for borderline resectable pancreatic cancer. Treatment consisted of four courses of FOLFIRINOX neoadjuvant chemotherapy, a Whipple procedure with a right hemicolectomy and venous segment resection, and eight courses of adjuvant FOLFIRINOX chemotherapy. Physical activity and moderate to vigorous physical activity declined after the onset of symptoms, increased in the weeks before surgery, declined after surgery and then gradually recovered during and after adjuvant chemotherapy. Estimated VO 2 max remained stable during neoadjuvant chemotherapy, sharply decreased after surgery and then gradually recovered. Heart rate at rest increased and heart rate variability decreased after the onset of symptoms reaching their highest and lowest values after surgery. Both gradually returned to baseline seven months after the last course of chemotherapy. The physical impact of pancreatic cancer and its treatment and recovery was in this case reflected on consumer wearable health data. Seven months after the last chemotherapy recovery was close to baseline values., Competing Interests: CPvdS researched literature and conceived the study. All authors reviewed and edited the manuscript and approved the final version of the manuscript. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, Surgery 52:205-22, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C., Methods/design: Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., Surgery 142:20-5, 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality., Discussion: PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente etal., Surgery 142:20-5, 2007; Bassi et al., Surgery 161:584-91, 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., Surgery 159:1013-22, 2016; Pratt et al., J Gastrointest Surg 10:1264-78, 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., Ann Surg 2022; Asbun and Stauffer, Surg Endosc 25:2643-9, 2011)., (© 2022. The Author(s).)

Background: Minimally invasive distal pancreatectomy (MIDP) shortens time to functional recovery and improves 30-day quality of life (QoL), as compared with open distal pancreatectomy (ODP) for nonmalignant disease. The impact of MIDP on QoL, cosmetic satisfaction, and overall major complications beyond 1-year follow-up is currently unknown., Study Design: The Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD) trial randomized 108 patients to MIDP (laparoscopic or robotic) or ODP in 14 Dutch centers (April 2015 to March 2017). The primary outcome measure of this study was quality-adjusted life years (QALYs), as assessed with the EQ-5D. QoL was assessed using subscales of the EORTC QLQ-C30, PAN-26, and a body image questionnaire. The latter included a cosmetic satisfaction score (range 3-24), and a body image score (range 5-20). Differences between MIDP and ODP for QALYs, generic, and disease-specific QoL and body image were analyzed. Missing QoL data were imputed using multiple imputation., Results: In total, 84 patients were alive, with a median follow-up of 44 months; 62 of these patients (74%) completed the questionnaires (27 MIDP, 35 ODP). There was no significant difference in QALYs between the 2 groups (mean score 2.34 vs 2.46 years, p = 0.63), nor on the QoL subscales. Significant overall change in EQ-5D health utilities were found for both groups over time (p < 0.001). Patients in the MIDP group scored higher on cosmetic satisfaction (21 vs 14, p = 0.049). No differences between the 2 groups were observed for clinical outcomes such as major complications, readmissions, and incisional hernias., Conclusions: More than 3 years after distal pancreatectomy, no improvement in QALYs and overall QoL was seen after MIDP, whereas cosmetic satisfaction was higher after MIDP as compared with ODP., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands., Method: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups., Results: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004)., Conclusion: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 <1%). In centers which performed ≥20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117-239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040)., Conclusion: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor., Background: Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations., Methods: The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS., Results: For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05)., Conclusion: The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

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 < 0.001). The conversion rate of MIDP was 8%. Operative blood loss was less after MIDP (150 vs 400 mL; P < 0.001), whereas operative time was longer (217 vs 179 minutes; P = 0.005). The Clavien-Dindo grade ≥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.

Introduction: Surgical specialists and residents lack knowledge to adequately manage frail older patients. This study aims to evaluate the effects of an interactive online course regarding attitude, self-confidence and knowledge in perioperative management of the elderly patient., Methods: The six-weeks course consisted of expert videos, literature readings, quizzes and forum discussions. Surgical consultants with geriatric expertise and geriatricians moderated online discussions and stimulated interaction. Knowledge, self-confidence and attitude of course participants were compared at the beginning and end of the course., Results: 206 medical practitioners started the course. Knowledge scores improved significantly from 49% to 65% (p < 0.005). Participants felt more secure (p < 0.005) in the treatment of the older patient at the end of the course. A better attitude correlated with a higher total knowledge score in surgeons and surgical residents (p = 0.02)., Conclusion: A six-week interactive online course on perioperative management of elderly patients increases relevant geriatric knowledge and improves self-confidence of residents and faculty., (Copyright © 2018. Published by Elsevier Inc.)

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 <30 (OR = 3.9, 1.6-9.6)., Conclusions: Variations in mortality between hospitals after pancreatoduodenectomy were explained mainly by differences in FTR, rather than the incidence of major complications., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting., Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs., Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting., Trial Registration: Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

Objective: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP)., Summary of Background Data: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown., Methods: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015)., Results: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12)., Conclusion: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.

Background: Microscopically radical (R0) resection of pancreatic, periampullary, or colon cancer may occasionally require a pancreatoduodenectomy with colon resection (PD-colon), but the benefits of this procedure have been disputed, and multicenter studies on morbidity and oncologic outcomes after PD-colon are lacking. This study aimed to assess complications and survival after PD-colon., Methods: Patients who had undergone PD-colon from 2004-2014 in 1 of 13 centers were analyzed retrospectively. Ninety-day morbidity was scored using the Clavien-Dindo score and the Comprehensive Complication Index (CCI, 0 = no complications, 100 = death). Survival was analyzed per histopathologic diagnosis., Results: After screening 3,218 consecutive PDs, 50 (1.6%) PD-colon patients (median age 66 years [interquartile range 55-72], 33 [66%] men) were included. Twenty-three (46%) patients had pancreatic ductal adenocarcinoma (PDAC), 19 (38%) other pathology, and 8 (16%) colon cancer. Ninety-day Clavien-Dindo ≥3 complications occurred in 30 (60%) patients without differences per diagnosis (P > .99); mean CCI was 39 (standard deviation 27). Colonic anastomosis leak, pancreatic fistula, and 90-day mortality occurred in 3 (6%), 2 (4%), and 4 (8%) patients, respectively. A total of 11/23 (48%) patients with PDAC and 8/8 (100%) patients with colon cancer underwent an R0 resection. Patients with PDAC had a median postoperative survival of 13 months (95% confidence interval = 5-21). One-, 3-, and 5-year cumulative survival was 56%, 21%, and 14%, respectively. Median survival after R0 resection for PDAC was 21 months (95% confidence interval = 6-35). All patients with colon cancer were alive at end of follow-up (median 24 months [95% confidence interval = 9-110])., Conclusion: In this retrospective, multicenter study, PD-colon was associated with considerable complications and acceptable survival rates when a tumor negative resection margin was achieved., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node biopsy (SLNB) in melanoma is currently performed using the standard dual technique (radioisotope and blue dye). The magnetic technique is non-radioactive and provides a brown color change in the sentinel lymph node (SLN) through an intradermal injection of a magnetic tracer, and utilizes a handheld magnetometer. The MELAMAG Trial compared the magnetic technique with the standard technique for SLNB in melanoma., Methods: Clinically node-negative patients with primary cutaneous melanoma were recruited from four centers. SLNB was undertaken after intradermal administration of both the standard (blue dye and radioisotope) and magnetic tracers. The SLN identification rate per patient, with the two techniques, was compared., Results: A total of 133 patients were recruited, 129 of which were available for final analysis. The sentinel node identification rate was 97.7 % (126/129) with the standard technique and 95.3 % (123/129) with the magnetic technique [2.3 % difference; 95 % upper confidence limit (CL) 6.4; 5.4 % discordance]. With radioisotope alone, the SLN identification rate was 95.3 % (123/129), as with the magnetic technique (0 % difference; 95 % upper CL 4.5; 7.8 % discordance). The lymph node retrieval rate was 1.99 nodes per patient overall, 1.78 with the standard technique and 1.87 with the magnetic technique., Conclusions: The magnetic technique is feasible for SLNB in melanoma with a high SLN identification rate, but is associated with skin staining. When compared with the standard dual technique, it did not reach our predefined non-inferiority margin.

Aim: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol., Methods: This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease., Results: 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013)., Conclusion: The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort., Methods: Breast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient., Results: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%., Conclusion: The results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The worldwide introduction of multimodal enhanced recovery programs has also changed perioperative care in patients who undergo liver resection. This study was performed to assess current perioperative practice in liver surgery in 11 European HPB centers and compare it to enhanced recovery after surgery (ERAS) principles., Methods: In each unit, 15 consecutive patients (N = 165) who underwent hepatectomy between 2010 and 2012 were retrospectively analyzed. Compliance was classified as "full," "partial," or "poor" whenever ≥ 80, ≥ 50, or <50 % of the 22 ERAS protocol core items were met. The primary study end point was overall compliance with the ERAS core program per unit and per perioperative phase., Results: Most patients were operated on for malignancy (91 %) and 56 % were minor hepatectomies. The median number of implemented ERAS core items was 9 (range = 7-12) across all centers. Compliance was partial in the preoperative (median 2 of 3 items, range = 1-3) and perioperative phases (median 5 of 10 items, range: 4-7). Median postoperative compliance was poor (median 2 of 9 items, range = 0-4). A statistically significant difference was observed between median length of stay and median time to recovery (7 vs. 5 days, P < 0.001)., Conclusion: Perioperative care among centers that perform liver resections varied substantially. In current HPB surgical practice, some elements of the ERAS program, e.g., preoperative counselling and minimal fasting, have already been implemented. Elements in the perioperative phase (avoidance of drains and nasogastric tube) and postoperative phase (early resumption of oral intake, early mobilization, and use of recovery criteria) should be further optimized.

Background: The SentiMAG Multicentre Trial evaluated a new magnetic technique for sentinel lymph node biopsy (SLNB) against the standard (radioisotope and blue dye or radioisotope alone). The magnetic technique does not use radiation and provides both a color change (brown dye) and a handheld probe for node localization. The primary end point of this trial was defined as the proportion of sentinel nodes detected with each technique (identification rate)., Methods: A total of 160 women with breast cancer scheduled for SLNB, who were clinically and radiologically node negative, were recruited from seven centers in the United Kingdom and The Netherlands. SLNB was undertaken after administration of both the magnetic and standard tracers (radioisotope with or without blue dye)., Results: A total of 170 SLNB procedures were undertaken on 161 patients, and 1 patient was excluded, leaving 160 patients for further analysis. The identification rate was 95.0 % (152 of 160) with the standard technique and 94.4 % (151 of 160) with the magnetic technique (0.6 % difference; 95 % upper confidence limit 4.4 %; 6.9 % discordance). Of the 22 % (35 of 160) of patients with lymph node involvement, 16 % (25 of 160) had at least 1 macrometastasis, and 6 % (10 of 160) had at least a micrometastasis. Another 2.5 % (4 of 160) had isolated tumor cells. Of 404 lymph nodes removed, 297 (74 %) were true sentinel nodes. The lymph node retrieval rate was 2.5 nodes per patient overall, 1.9 nodes per patient with the standard technique, and 2.0 nodes per patient with the magnetic technique., Conclusions: The magnetic technique is a feasible technique for SLNB, with an identification rate that is not inferior to the standard technique.

Purpose: To evaluate adherence with follow-up criteria as suggested by the national guideline for breast cancer patients., Method: Patients diagnosed with breast cancer in 2003 in two hospitals were identified from the Netherlands Cancer Registry (n = 198). Compliance with the guideline was assessed retrospectively by extracting follow-up care data from patient files for a period of five years., Results: Follow-up data were available for 196 patients. In the first year of follow-up, fewer consultations were performed compared to guideline standards. In the second through the fifth year of follow-up, more consultations were performed, with nearly double the number of consultations in the third until the fifth year compared to the guideline (p < 0.05). This excess usage was mainly associated with the fact that women had received radiotherapy (p < 0.01). Physical examinations were performed during 97 percent of consultations. Mammograms were performed slightly less often than suggested., Conclusions: Among women receiving follow-up care after breast cancer, more consultations were provided compared to the guideline recommendations. Mammograms were performed slightly less often than recommended. With regard to the performance of physical examinations, the guideline was followed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aims: To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects., Materials and Methods: Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055)., Results: An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]., Conclusions: The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.

Aim: Local recurrence and needle track seeding are serious complications after local ablation for liver malignancies and potentially affect long-term survival. The aim of this study was to assess the incidence of viable tissue adherent to the needle applicators after ablation to gain insight into the possible mechanisms of local recurrence and needle track seeding., Methods: A total of 40 consecutive patients underwent 59 local liver ablations. Cells and tissue attached to the needle applicators were analysed for morphology (HE, PAP and Giemsa staining) and viability (G6PD staining)., Results: Macroscopic tissue adherence was visible following 31 of the ablative procedures, all with radiofrequency ablation. Four applications were performed percutaneously and 27 during an open procedure. Morphologically intact tumour cells could be identified in 8 patients (20%), and viable tumour cells in 5 patients (12.5%). Morphologically intact tumour cells or viable tumour cells could only be demonstrated when track ablation was not performed., Conclusion: Viable tumour cells adherent to the needle applicators were found in an alarming 12.5% of patients after local ablation. We recommend track ablation not only after the procedure but also during any shifting and (re-)positioning to prevent shedding of viable tumour cells during or after ablation., (Copyright (c) 2009 S. Karger AG, Basel.)

The authors review their experience of 4 years with isolated limb perfusion for the application of high dose TNF-alpha associated to IFN-gamma and melphalan for the treatment of regionally advanced tumours such as malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. In malignant melanoma, the complete remission rate reaches 91%. In irresectable soft tissue sarcoma, this treatment when used as a neoadjuvant treatment saves the limb from amputation in 87.5% of the cases. Similar results are obtained for epidermoid carcinoma. With the regional application of high doses of TNF-alpha associated to chemotherapy and IFN-gamma, it has been possible to validate the concept of a strategy based on a dual targeting, that is the selective impact of the intratumoral vessels by TNF-alpha and of the tumour cells by chemotherapy. This approach appears to be the treatment of choice for locally advanced tumours of the limbs. However, as a single therapy, this procedure should be considered in melanoma as an induction therapy, and in sarcoma, as a preoperative treatment.

Recombinant tumor necrosis factor alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the effective dose in animals. Isolated perfusion of the limbs (ILP) allows the delivery of high-dose rTNF alpha in a closed system with acceptable side effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In patients with melanoma-in-transit metastases (stage IIIA or AB), we obtained a 91% complete response rate compared with 52% after ILP with melphalan alone. In unresectable soft tissue sarcomas, this protocol was found to produce a 50% complete response with 87.5% limb salvage, since most tumors became removable. Release of nanograms levels of TNF alpha in the systemic circulation was evident, but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells, while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.

Recombinant tumor necrosis factor-alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side-effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNF alpha in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.