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BACKGROUND Guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations are characteristic of intraductal papillary mucinous neoplasms (IPMNs). Pancreatic ductal adenocarcinomas (PDACs) harboring GNAS mutations originate in IPMNs. GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions, NESP55, GNASAS, GNASXL, GNAS1A, and GNAS. AIM To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts. METHODS GNAS locus methylation was analyzed in archival pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific–multiplex ligation dependent probe amplification. Results were normalized and analyzed using Coffalyser.Net software. RESULTS Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied. The final diagnoses were surgical (11) and clinicopathological (41), including 30 benign cysts, 14 pre-malignant cyst, and eight malignant cysts. Methylation changes at NESP55, GNASAS, GNAS1A, and especially GNASXL were more frequent in malignant cysts, and NESP55 and GNASAS were useful for diagnosis. A combined variable defined as “GNAS locus methylation changes” was significantly associated with malignancy (6/8 malignant cysts and only 2/20 benign cysts) and improved classification. Hypermethylation in both maternally (NESP55) and paternally (GNASXL) derived promoters was found in 3/3 PDACs. CONCLUSION This is the first study to identify methylation changes in the GNAS locus, improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.

Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

Highlights • Distal pancreatectomy is the surgical operation of choice for cysts located on the body and tail of pancreas. • Distal pancreatectomy for pancreatic body cysts can result in loss of healthy distal pancreatic tissue. • Central pancreatectomy is an alternative surgical operation of choice of cysts located on pancreatic body. • Central pancreatectomy preserves distal healthy pancreas tissue. • Distal pancreas tissue can be anastomosed to the stomach when central pancreatectomy is performed., Introduction Surgical management of pancreatic cysts differ according to the specific location of the cyst on the pancreas. Cysts located on the pancreatic head require a radical procedure such as pancreaticoduodenectomy (Whipple procedure). Cysts of the pancreatic body or tail, however, require distal pancreatectomy as the standard surgical approach. An alternative surgical approach for cysts located in the mid-pancreas is central pancreatectomy with distal pancreaticogastrostomy. Presentation of case In this report, we present a case of a 22-year-old woman with a cyst located on the mid-pancreas consistent with a solid pseudopapillary neoplasia. Central pancreatectomy with distal pancreaticogastrostomy was the surgical technique of choice performed in this case. Discussion Central pancreatectomy has emerged as an alternative surgical approach to mid-pancreatic cysts which includes only the removal of a segment of the pancreas, thereby sparing the distal parenchyma. Compared with the traditional approach, this technique of partial resection of the pancreatic tissue is desirable due to its organ-sparing function. Conclusion Central pancreatectomy with distal pancreaticogastrostomy can be an alternative to distal pancreatectomy for cysts located in the mid-pancreatic region. This rare procedure prevents any unnecessary healthy pancreatic tissue loss, reduces the risk of developing complications, and is an alternative treatment of choice to distal pancreatectomy.

BACKGROUND: Mucinous pancreatic cystic lesions (PCLs) express different mucin (MUC) types according to their histomorphologic types. High cystic fluid viscosity may help in the detection of mucinous PCLs. We hypothesized that high cystic fluid viscosity may be suggestive of a certain MUC type in mucinous PCLs. METHODS: Prespecified MUC types (MUC1, MUC2, MUC4, MUC5AC, and MUC6) were evaluated in 18 definitively diagnosed mucinous PCLs with sufficient tissue material and prediagnostic cyst fluid viscosity evaluation—string sign (SS)—test. We evaluated the agreement of MUC expression with positive SS test results. Later, we compared cystic fluid carcinoembryonic antigen (CEA) between the prespecified MUC expressing and nonexpressing cyst types. RESULTS: A total of 18 mucinous PCL patients, 11 females, with mean age ± SD (59.7 ± 13.3) were included. Almost all malignant mucinous PCLs expressed MUC1 (71.4%) (P = .023). We found no significant agreement between the prespecified MUC types and positive SS, except MUC4 which had mild agreement. Also, no significant relation was found between cystic fluid CEA levels and MUC expression (P = .584). CONCLUSION: We did not detect a significantly moderate or good agreement between the prespecified MUC types and SS test. MUC1 was highly expressed in malignant mucinous cysts; however, it was incompatible with the SS test. MUC4 expression showed mild agreement with the SS test in a small number of patients.