Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

AIMS: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. METHODS: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. RESULTS: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. CONCLUSIONS: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS: This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS: Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION: In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

Identification of high-risk features in mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms of the pancreas are uncommon tumors that have the potential of becoming cancer. There is no consensus regarding the high-risk features of these tumors. Our study aimed to identify the preoperative demographic, clinical, or radiologic factors that can predict the presence of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. METHODS: We identified 157 patients who underwent resection and fulfilled the pathologic criteria for mucinous cystic neoplasms of the pancreas in a prospectively maintained database spanning 3 decades (1990-2020). Multivariable logistic regression was used to identify predictors of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. RESULTS: The rate of high-grade dysplasia or invasive carcinoma was 11%. Tumor size ≥4 cm (P < .001), mural nodularity (P = .04), and a serum CA 19-9 level >37 U/mL (P < .001) were associated with high-grade dysplasia or invasive carcinoma. In the multivariable analysis, tumor size ≥4 cm (odds ratio 16.9, 95% confidence interval 2.04-140, P = .009) and a CA 19-9 level >37 U/mL (odds ratio 5.68, 95% confidence interval 1.52-21.3, P = .010) were predictors of high-grade dysplasia or invasive carcinoma. There were no tumors with high-grade dysplasia or invasive carcinoma in patients with tumor size <4 cm in the absence of an elevated CA 19-9 or mural nodularity. CONCLUSION: Tumors with a size ≥4 cm and/or a high CA 19-9 level should be considered for prompt surgical resection. Conversely, tumors <4 cm with no other high-risk features have a negligible risk for high-grade dysplasia or invasive carcinoma and may benefit from nonoperative surveillance. Mural nodularity is an additional suspicious feature. These findings may contribute to future guidelines.