Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, as tumors evolve faster than therapies. Resistance is ecological, not merely KRAS driven, involving overlooked players like high-grade pancreatic intraepithelial neoplasias (PanINs), peripancreatic fat, stromal mechanics, myeloid-neural circuits, metabolic rewiring, and systemic host responses. We propose precision interception targeting PanIN/intraductal papillary mucinous neoplasm (IPMN) biology, spatial-functional-proteogenomic classification beyond transcriptomics, the Heracles Protocol (measure, prime, strike, and adapt), and integrated technologies from AI pathology to exosomal delivery and CRISPR-based synergy mapping, together making PDAC more tractable.

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Background Early recurrence in intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is poorly defined. Predictors are lacking and needed for patient counseling, risk stratification, and postoperative management. This study aimed to define and predict early recurrence for patients in resected IPMN-derived PDAC and guide management. Methods A lowest p value for survival after recurrence (SAR) was used to define early recurrence in resected IPMN-derived PDAC from five international centers. Overall survival (OS) and SAR were compared using log-rank tests. A multivariable logistic regression identified odds ratios (ORs) with 95 % confidence intervals (CIs) for early recurrence. Rounded ORs were used to stratify patients into low-, intermediate-, and high-risk groups using upper and lower quartile score distributions. Adjuvant chemotherapy was assessed by Cox regression and log-rank tests for OS in risk groups. Results Recurrence developed in 160 (42 %) of 381 patients. Early recurrence was defined at 10.5 months and observed in 61 patients (38 % of recurrences). The median SAR for the patients with early recurrence was 8.3 months (95 % CI, 3.1–16.1 months) compared with 12.9 months (95 % CI, 5.2–27.5 months) for the patients with late recurrence. The independent predictors of early recurrence were CA19-9 (OR, 3.80; 95 % CI, 1.54–9.41) and N2 disease (OR, 7.29; 95 % CI, 3.22–16.49). The early recurrence rates in the low-, intermediate-, and high-risk groups were respectively 1 %, 14 %, and 32 %. Adjuvant chemotherapy was associated with improved OS only for the high-risk patients (hazard ratio, 0.50; 95 % CI, 0.32–0.79). Conclusion In IPMN-derived PDAC, the optimal cutoff for early recurrence is 10.5 months. Both CA19-9 and N stage predict early recurrence. Adjuvant chemotherapy is associated with survival benefit only for high-risk patients.

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4月のコラムで、知人の膵臓（すいぞう）がんを早期に発見し、手術を受けてもらったエピソードを紹介しました。今回は後日談です。もともと糖尿病があり、「膵管内乳頭状粘液性腫瘍（IPMN）」という良性腫瘍もありました。ともに膵臓がんを増やすリスク因子です。IPMNは膵臓にできる腫瘍の1つで、膵管（膵臓の中にある消化液を含む、膵液の流れる管）の中に盛り上がるように増殖する腫瘍です。粘液を産生するため、