Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.

In this study, we aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured on ¹⁸F-FDG PET/CT in pancreatic cancer patients who underwent resection with curative intent. Methods: Eighty-seven patients with pancreatic ductal adenocarcinoma who underwent ¹⁸F-FDG PET/CT and subsequent surgical resection with curative intent with (30 patients) or without (57 patients) neoadjuvant therapy were retrospectively enrolled. The maximum standardized uptake value (SUVmax), MTV, and TLG were measured on ¹⁸F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and tumor factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: Of the 87 patients, 57 (64%) experienced recurrence during the follow-up period. The tumor size, pathologic T (pT) stage, SUVmax, MTV, and TLG were significant prognostic factors for both RFS and OS (P < 0.05) on univariate analyses, and the presence of lymph node metastasis showed significance only for predicting RFS (P < 0.05). On multivariate analyses, the tumor size, MTV, and TLG were independent prognostic factors for RFS, and pT stage, MTV, and TLG were independent prognostic factors for OS. For the 57 patients who did not undergo neoadjuvant treatment, MTV and TLG remained significant predictive factors for tumor recurrence, along with tumor size and SUVmax. Conclusion: MTV and TLG are independent prognostic factors for predicting RFS and OS in patients with pancreatic cancer. Thus, ¹⁸F-FDG PET/CT can provide useful prognostic information for patients undergoing resection of pancreatic cancer with curative intent irrespective of neoadjuvant treatment.

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. Graphical

Solid pseudopapillary tumors (SPTs) of the pancreas are still considered a surgical enigma. Many clinical research trials have failed to identify prognostic factors that predict the malignant behavior of SPTs. This work was a retrospective multicenter study that included a total of 17 medical institutions. Data from 351 patients who underwent surgical resection from January 1990 to December 2008 were retrospectively collected using standardized case report forms requesting clinicopathologic features. Thirty-four patients (9.7%) were male, and 317 (90.3%) were female, with a mean age of 36.8 ± 12.4 years. Recently, minimally invasive (P < 0.001) and parenchyma or function-preserving limited surgeries (P = 0.016) have been more frequently applied for the treatment of pancreatic SPTs. Ninety-eight patients (27.9%) had microscopic malignant features. Only 9 patients (2.6%) experienced tumor recurrence after the initial pancreatic SPT resection. Multivariate analysis showed that a tumor size larger than 8 cm [Exp (β) = 7.385, P = 0.018], microscopic malignant features [Exp (β) = 10.009, P = 0.011], and stage IV [Exp (β) = 42.003, P = 0.002] were significant prognostic factors for tumor recurrence. When combined with stage IV, the microscopic malignant features and 2010 World Health Organization definition of solid pseudopapillary carcinoma more successfully differentiated future recurrence risk groups (P < 0.001). More specific pathologic descriptions need to be employed in pathologic report forms to provide proper information to predict SPT recurrence after resection. Future studies emphasizing the standardized pathologic evaluation of pancreatic SPTs may unveil the enigmatic nature of pancreatic SPTs.