RESEARCH & PROJECTS

Completed Projects

Histopathologic predictors of survival and recurrence in resected ampullary adenocarcinoma (Annals of Surgery 2019)
In this international multicenter cohort study, we aimed to define histopathologic characteristics that predict survival and recurrence after resection of ampullary adenocarcinoma. A cohort of 887 patients was analyzed and revealed that N-stage, perineural invasion and adjuvant chemotherapy were associated with survival, when accounted for other risk factors. Sensitivity analysis demonstrated that adjuvant chemotherapy was associated with an improved survival only in the pancreaticobiliary subtype, but not in the intestinal subtype. 
Moekotte, A.L., et al., Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study. Ann Surg, 2020. 272(6): p. 1086-1093. DOI: 10.1097/SLA.0000000000003177
 
Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma (BJ Surgery in print, 2020)
In this international multicenter cohort study, the objective was to compare overall survival between patients who received adjuvant chemotherapy versus patients who did not receive adjuvant chemotherapy after resection of ampullary adenocarcinoma. A total of 520 patients received adjuvant chemotherapy and 456 patients did not. Propensity score matching was performed to create comparable groups. In the matched cohort of all subtypes, median survival was not reached in patients receiving adjuvant chemotherapy group vs 60 months in the group without adjuvant chemotherapy, p=0.05. In the pancreaticobiliary/mixed subtype a survival benefit was seen; median survival was not reached in patients receiving adjuvant chemotherapy vs 32 months in the group without chemotherapy, p=0.02. The intestinal subtype did not show survival benefit from adjuvant chemotherapy.
Moekotte, A.L., et al., Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study. Br J Surg, 2020. 107(9): p. 1171-1182.
 
Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma (European Journal of Surgical Oncology, 2020) 
In this international multicenter cohort study, the aim was to develop and externally validate a prediction model for survival after resection of ampullary adenocarcinoma. A derivation cohort of 1007 patients was available and predictors were selected using a LASSO Cox proportional hazards model. Predictors of the final model included age, resection margin, tumor differentiation, pT-stage and pN-stage. Model performance was expressed by a C-statistic of 0.75 (95% CI 0.73-0.77). The validation cohort consisted of 462 patients and demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. Based on nomogram scores, four risk groups were created. Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. 
Moekotte, A.L., et al., Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma. Eur J Surg Oncol, 2020. 46(9): p. 1717-1726. DOI: https://doi.org/10.1016/j.ejso.2020.04.011 
 
Long-term Outcomes after Laparoscopic, Robotic and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: an International Propensity score-matched Cohort Study (Annals of Surgery, 2022)
This study compared the surgical and oncological outcomes of minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). The study included 478 patients from 8 centers in 5 countries. MIPD was associated with less blood loss, longer operation time, and less surgical site infections compared to OPD. The median overall survival and disease-free interval did not differ significantly between MIPD and OPD. Robotic pancreatoduodenectomy (RPD) was associated with a higher lymph node yield and less major morbidity compared to laparoscopic pancreatoduodenectomy (LPD).

Uijterwijk, B. A., Kasai, M., Lemmers, D., Ielpo, B., Van Hilst, J., Song, K. B., … & Hilal, M. A. (2022). Minimally invasive vs. open pancreatoduodenectomy in selected patients with peri-ampullary, non-pancreatic cancer: A systematic review and individual patient data meta-analysis. International Journal of Surgery, 100, 106544. DOI: 10.1097/SLA.0000000000005743
 
Minimally invasive versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: Individual patient data meta-analysis of randomized trials (European Journal of Surgical Oncology, 2023) 
This Individual patient data meta analysis aimed to compare the outcomes of minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for patients with pancreatic ductal adenocarcinoma (PDAC). Four randomized controlled trials (RCTs) were identified, including 275 patients with resectable PDAC. Laparoscopic MIPD was found to be non-inferior to OPD regarding radicality, lymph node yield, major complications, and 90-day mortality. Laparoscopic MIPD was associated with less blood loss and shorter hospital stay, but longer operation time. Long-term survival and recurrence outcomes of robotic MIPD should be studied in future RCTs.
Uijterwijk, B. A., et al. (2023). Minimally invasive versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: Individual patient data meta-analysis of randomized trials. European Journal of Surgical Oncology. DOI: https://doi.org/10.1016/j.ejso.2023.03.227 
 
 

Ongoing Projects

 
Minimally invasive vs Open pancreatoduodenectomy for ampullary adenocarcinoma: short-term outcomes (manuscript in preparation)
The aim of this study is to assess surgical and oncological outcomes after minimally invasive (laparoscopic + robotic) pancreatoduodenectomy versus open prancreaticoduodenectomy for ampullary adenocarcinoma, in a propensity score matched cohort.
 
Comparison of the histopathologic subtypes of ampullary adenocarcinoma (manuscript in preparation)
The aim of this study is twofold. First, we sought to describe the differences in survival and histopathologic characteristics between the two main subtypes (pancreaticobiliary vs intestinal). Second, we aimed to identify and describe difficulties in the classification of the subtypes, by revising the specimen of a single center.

 

 

Adjuvant chemotherapy following curative intent resection for ampullary adenocarcinoma, Cochrane review

The aim of this review is to assess the effects of adjuvant chemotherapy follow curative-intent resection of ampullary adenocarcinoma on survival, quality of life, adverse events and toxicity.

 

 

Impact of lymph node ratio on survival in the histopathological subtypes of resected ampullary cancer: a retrospective international multicenter cohort study.

The aim of this study is to investigate the prognostic predictive value of LNR adjusted for factors influencing survival in patients with resected AAC.

 

 

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

The purpose of this study is to assess the prognostic accuracy of the 7th and 8th AJCC staging system for AAC and to externally validate the 8th edition of the AJCC for resected ampullary cancer in an international cohort.

 

 

The management of ampullary cancer: international survey among surgeons and medical oncologists

The purpose of this study is to assess the current management worldwide of patients with ACC and to study what factors influence the treatment strategies and counselling of patients with AAC.

 

Minimally invasive pancreatoduodenectomy in non-pancreatic periampullary cancer: an individual patient data meta-analysis
The purpose of this study is to asses the evidence for the minimally invasive approach in the separate non-pancreatic periampullary tumors 

 

PERIPAN consensus meeting – Pathology consensus meeting for non-pancreatic periampullary neoplasms
See www.isgaca.com/PERIPAN, Meeting passed, manuscript in preperation

 

Future Projects

Adjuvant chemotherapy in ampullary adenocarcinoma, the ADAPTA trial: an observational double single arm clinical trial (study protocol in preparation) see tab “ADAPTA”.
Interobserver agreement for the histopathologic subtypes of ampullary adenocarcinoma (study protocol in preparation)
 
Consensus meeting to define the histopathologic subtypes (organization in preparation)