Robotic Pancreatoduodenectomy: Patient Selection, Volume Criteria, and Training Programs

INTRODUCTION: There has been a rapid development in minimally invasive pancreas surgery in recent years. The most recent innovation is robotic pancreatoduodenectomy. Several studies have suggested benefits as compared to the open or laparoscopic approach. This review provides an overview of studies concerning patient selection, volume criteria, and training programs for robotic pancreatoduodenectomy and identified knowledge gaps regarding barriers for safe implementation of robotic pancreatoduodenectomy. MATERIALS AND METHODS: A Pubmed search was conducted concerning patient selection, volume criteria, and training programs in robotic pancreatoduodenectomy. RESULTS: A total of 20 studies were included. No contraindications were found in patient selection for robotic pancreatoduodenectomy. The consensus and the Miami guidelines advice is a minimum annual volume of 20 robotic pancreatoduodenectomy procedures per center, per year. One training program was identified which describes superior outcomes after the training program and shortening of the learning curve in robotic pancreatoduodenectomy. CONCLUSION: Robotic pancreatoduodenectomy is safe and feasable for all indications when performed by specifically trained surgeons working in centers who can maintain a minimum volume of 20 robotic pancreatoduodenectomy procedures per year. Large proficiency-based training program for robotic pancreatoduodenectomy seem essential to facilitate a safe implementation and future research on robotic pancreatoduodenectomy

C-reactive protein is superior to white blood cell count for early detection of complications after pancreatoduodenectomy: a retrospective multicenter cohort study

Background: Early detection of major complications after pancreatoduodenectomy could improve patient management and decrease the “failure-to-rescue” rate. In this retrospective cohort study, we aimed to compare the value of C-reactive protein (CRP) and white blood cell count (WBC) in the early detection of complications after pancreatoduodenectomy. Methods: We assessed pancreatoduodenectomies between January 2012 and December 2017. Major complications were defined as grade III or higher according to the Clavien-Dindo classification. Postoperative pancreatic fistula (POPF) was a secondary endpoint. ROC-curve and logistic regression analysis were performed for CRP and WBC. Results were validated in an external cohort. Results: In the development cohort (n = 285), 103 (36.1%) patients experienced a major complication. CRP was superior to WBC in detecting major complications on postoperative day (POD) 3 (AUC:0.74 vs. 0.54, P < 0.001) and POD 5 (AUC:0.77 vs. 0.68, P = 0.031), however not on POD 7 (AUC:0.77 vs. 0.76, P = 0.773). These results were confirmed in multivariable analysis and in the validation cohort (n = 202). CRP was also superior to WBC in detecting POPF on POD 3 (AUC: 0.78 vs. 0.54, P < 0.001) and POD 5 (AUC: 0.83 vs. 0.71, P < 0.001). Conclusion: CRP appears to be superior to WBC in the early detection of major complications and POPF after pancreatoduodenectomy

Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): Study protocol for a randomized controlled trial

Background: Data from observational studies suggest that minimally invasive pancreatoduodenectomy (MIPD) is superior to open pancreatoduodenectomy regarding intraoperative blood loss, postoperative morbidity, and length of hospital stay, without increasing total costs. However, several case-matched studies failed to demonstrate superiority of MIPD, and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume (< 10 MIPDs annually) centers. Randomized controlled multicenter trials are lacking but clearly required. We hypothesize that time to functional recovery is shorter after MIPD compared with open pancreatoduodenectomy, even in an enhanced recovery setting. Methods/design: LEOPARD-2 is a randomized controlled, parallel-group, patient-blinded, multicenter, phase 2/3, superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs. A total of 136 patients with symptomatic benign, premalignant, or malignant disease will be randomly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhan

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival. Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007–2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use. Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007–2011 to 37% in 2012–2016 (p <.001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007–2011: 12–67%, 2012–2016: 20–54%) whereas overall survival increased from 5.6 months to 6.4 months (p <.001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015–2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015–2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy. Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): Design and rationale of a randomized controlled trial

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. Methods/Design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. Trial registration: Netherlands Trial Register [, 11 October 2013]

Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model

Background: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. Methods: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005–2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0–5 years after resection was calculated using the Kaplan–Meier method. A prediction model was constructed. Results: Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17–18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. Conclusions: This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers

Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma

Background: In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC. Materials and methods: Patients wi

Cachexia, dietetic consultation, and survival in patients with pancreatic and periampullary cancer: A multicenter cohort study

It is unclear to what extent patients with pancreatic cancer have cachexia and had a dietetic consult for nutritional support. The aim was to assess the prevalence of cachexia, dietitian consultation, and overall survival in these patients. This prospective multicenter cohort study included patients with pancreatic cancer, who participated in the Dutch Pancreatic Cancer Project and completed patient reported outcome measures (2015–2018). Additional data were obtained from the Netherlands Cancer Registry. Cachexia was defined as self-reported >5% body weight loss, or >2% in patients with a BMI <20 kg/m2 over the past half year. The Kaplan–Meier method was used to analyze overall survival. In total, 202 patients were included from 18 centers. Cachexia was present in 144 patients (71%) and 81 of those patients (56%) had dietetic consultation. Cachexia was present in 63% of 94 patients who underwent surgery, 77% of 70 patients who received palliative chemotherapy and 82% of 38 patients who had best supportive care. Dietitian consultation was reported in 53%, 52%, and 71%, respectively. Median overall survival did not differ between patients with and without cachexia, but decreased in those with severe weight loss (12 months (IQR 7–20) vs. 16 months (IQR 8–31), p = 0.02), as compared to those with <10% weight loss during the past half year. Twothirds of patients with pancreatic cancer present with cachexia of which nearly half had no dietetic consultation. Survival was comparable in patients with and without cachexia, but decreased in patients with more severe weight loss

Outcomes After Minimally-invasive Versus Open Pancreatoduodenectomy: A Pan-European Propensity Score Matched Study

OBJECTIVE: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. BACKGROUND: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. METHODS: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3). RESULTS: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001). CONCLUSIONS: In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed

Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG)

Background: Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy