# Evaluating the Role of Morphological Subtypes in the Classification of Periampullary Adenocarcinomas

## TL;DR

This study shows that the microscopic appearance of periampullary tumors and lymph node involvement can predict patient survival after surgery.

## Contribution

The study demonstrates that tumor morphology and lymph node burden are independent prognostic factors in periampullary cancers.

## Key findings

- Tumors with an intestinal pattern had significantly better survival than pancreatobiliary or pancreatic types.
- Lymph node ratio independently predicted worse survival in periampullary cancer patients.
- Morphological subtype and lymph node burden can improve postoperative risk stratification and treatment decisions.

## Abstract

Periampullary adenocarcinomas are uncommon cancers that develop near the junction of the pancreas, bile duct, and small intestine. Although surgery is the main treatment, survival varies widely among patients, even when tumors appear similar. This study analyzed 120 patients who underwent curative surgery at a university hospital to explore whether microscopic tumor appearance could predict patient outcomes. We found that patients whose tumors showed an intestinal pattern lived much longer than those with pancreatobiliary or pancreatic patterns. Tumors with more lymph node involvement also had worse survival. These findings show that microscopic tumor subtype and lymph node burden provide valuable information for predicting prognosis after surgery. Incorporating these factors into clinical practice may help doctors better estimate survival, select adjuvant treatments, and design more precise studies in the future.

Background: Morphological subclassification may refine prognosis after curative pancreaticoduodenectomy (PD) for periampullary cancers. Methods: We conducted a single-center retrospective cohort including 120 consecutive PDs performed between 2005 and 2022. Tumors were classified as intestinal (INT), pancreatobiliary (PB), or pancreatic ductal adenocarcinoma (PAN). Clinicopathologic variables included T stage, margin status, lymphovascular and perineural invasion, and lymph node ratio (LNR; cutoff 0.154 determined by ROC/Youden). Overall survival (OS) was the primary endpoint and was analyzed using Kaplan–Meier with log-rank tests and multivariable Cox regression. Results: INT tumors were associated with earlier T stage, fewer adverse histologic features, and higher R0 resection rates compared with PB and PAN. In multivariable analysis, mortality risk was higher for PB (HR 4.41; 95% CI 1.25–15.53) and PAN (HR 13.96; 95% CI 3.99–48.75) relative to INT. LNR ≥ 0.154 independently predicted worse OS (HR 1.93; 95% CI 1.11–3.35). Mean OS was 108.8 months for INT, 62.0 months for PB, and 22.7 months for PAN (log-rank p < 0.001). Conclusions: Morphological subtype and LNR are independent prognostic factors after PD for periampullary malignancies. Integrating morphology and nodal burden into risk models may improve postoperative stratification and guide adjuvant therapy.