Miller, Richard Max

ABSTRACT Background and Objectives NCCN guidelines recommend right hemicolectomy (RHC) for appendiceal neuroendocrine tumors (aNETs) > 2 cm and observation for < 1 cm. However, optimal surgical management of 1–2 cm tumors remains controversial. This study compared long‐term survival and recurrence between patients undergoing RHC versus appendectomy (APY) for 1–2 cm aNETs. Methods Patients with pathologically confirmed 1–2 cm aNETs treated at three Mayo Clinic sites (1972–2024) were included. Primary outcomes were recurrence and all‐cause mortality after resection. Associations with lymph node (LN) metastasis were assessed in patients with lymphadenectomy. Results Sixty‐five patients were identified: 29 (45%) underwent APY, 35 (54%) RHC, and one ileocecectomy. Median age at diagnosis was 39 years; 71% were female and 94% white. LN positivity was 15.2% for tumors with nodes examined. Tumor size > 1.5 cm, stage T3/T4, and lymphovascular invasion were not associated with nodal metastasis. No survival differences were observed between APY and RHC. LN positivity did not impact survival. No recurrences occurred during a median follow‐up of 6.25 years (IQR 2.44–12.63). Conclusions Among patients with 1–2 cm aNETs, RHC conferred no survival benefit over APY. Absence of recurrence and the limited prognostic value of nodal disease suggest APY alone may suffice for this population.

Summary of Background Data: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). Objective: To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. Methods: Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. Results: In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. Conclusion: After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.