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 
 

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis
This study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.
Uijterwijk, B. A. et al., 2023. The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis. Langenbeck’s Archives of Surgery, 408(1), 311.https://doi.org/10.1007/s00423-023-03047-4


The management of ampullary cancer: international survey among surgeons and medical oncologists
This international survey study was performed to gain insight in the current daily practice of AAC. This international survey highlights the existing variation in the management of patients with AAC, especially regarding the use of (neo)adjuvant therapy. More data from trials and international registries are needed to develop evidence-based guidelines on surgical and oncological management with the ultimate aim to improve outcomes for patients with AAC.
De Jong, E. J. M., Lemmers, D. et al. “Oncologic management of ampullary cancer: International survey among surgical and medical oncologists.” Surgical Oncology 44 (2022): 101841.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study
This study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.
Uijterwijk, Bas A., et al. “Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.” Cancers 16.5 (2024): 899.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review
This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.
Uijterwijk, B.A., et al. “Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.” Annals of Surgical Oncology (2024): 1-11.

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.

 

 

 

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)