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Background: Familial-adenomatous-polyposis (FAP) is a rare inherited cancer predisposition syndrome. The treatment for FAP-related ampullary lesions (AL) is challenging and the role of endoscopic papillectomy (EP) is not elucidated yet. Data of FAP associated AL are limited and showed, at least in part, inconclusive results. We retrospectively analyzed the outcomes of EP in matched cohorts of FAP-related and sporadic ampullary lesions (SAL). Methods: The ESAP study included 1422 EPs. A propensity-score matching (nearest-neighbor-method) including age, gender, comorbidity, histologic subtype and size was performed. Main outcomes were complete resection (R0), technical success, complications and recurrence. Results: Propensity-score-based matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP-patients were mainly asymptomatic (79.2% [95%CI 71.2-87.3] vs. 46.5% [95%CI 36.6-56.4]), p<0.001). The initial R0-rate was significantly lower in FAP-patients (63.4% [95%CI 53.8-72.9] vs. 83.2% [95%CI 75.8-90.6], p=0.001). After repeated (mean: 1.30 per patient) interventions, R0 was comparable (FAP 93.1% [95%CI 88.0-98.1] vs. SAL 97.0% [95%CI 93.7-100], p=0.194). The overall complication rate was 28.7%. Pancreatitis and bleeding were most common adverse events in both groups. Severe complications were very rare (3.5%). Twenty-one patients in the FAP-group (20.8% [95%CI 12.7-28.8]) and sixteen patients in the SAL-group (15.8% [95%CI 8.6-23.1], p=0.363) had a reccurence . Recurrences occurred later in FAP-patients (25 [95%CI 18.3-31.7] vs. 2 [95%CI CI 0.06-3.9] months). Conclusions: EP is safe and effective in FAP-related ampullary lesions Criteria for endoscopic resection of AL can be extended to FAP-patients. FAP-patients have a life-time risk to relapse even after complete resection and require long-time-surveillance.

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Purpose Hematotoxicity is a common side-effect of cytotoxic gastrointestinal (GI) cancer therapies. An unsolved problem is to predict the individual risk in order to decide on treatment adaptions. We applied an established biomathematical prediction model and primarily evaluated its predictive value in patients undergoing chemotherapy for GI cancers in curative intent. Methods In a prospective, observational multicenter study on patients with gastro-esophageal or pancreatic cancer (n = 28) receiving myelosuppressive adjuvant or neoadjuvant chemotherapy (FLO(T) or FOLFIRINOX), individual model parameters were learned based on patients’ observed laboratory values during the first chemotherapy cycle and further external data resources. Grades of hematotoxicity of subsequent cycles were predicted by model simulation and compared with observed data. Results The most common high-grade hematological toxicity was neutropenia (19/28 patients (68%)). For the FLO(T) regimen, individual grades of thrombocytopenia and leukopenia could be well predicted for cycles 2–4, as well as grades of neutropenia for cycle 2. Prediction accuracy for neutropenia in the third and fourth cycle differed by one toxicity grade on average. For the FOLFIRINOX-regimen, thrombocytopenia predictions showed a maximum deviation of one toxicity grade up to the end of therapy (8 cycles). Deviations of predictions were less than one degree on average up to cycle 4 for neutropenia, and up to cycle 6 for leukopenia. Conclusion The biomathematical model showed excellent short-term and decent long-term prediction performance for all relevant hematological side effects associated with FLO(T)/FOLFIRINOX. Clinical utility of this precision medicine approach needs to be further investigated in a larger cohort.