Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing

We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r = − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.

LAMN as a differential diagnosis for abdominal pain: a case report from Syria

Low-grade appendiceal mucinous neoplasms (LAMNs) are papillary or flat mucinous tumors with low-grade cytologic atypia found in <0.3% of appendectomy specimens among older population. They are the most frequent source of pseudomyxoma peritonei. They can be easily misdiagnosed, due to unspecific symptoms, with acute appendicitis, retroperitoneal tumors or adnexal mass. Macroscopically, the appendix may appear normal or be variably dilated. Microscopic study determines whether the studied specimen is LAMN or mucinous adenocarcinomas. We report a 77-year-old patient presented with 15-day abdominal pain accompanied with chills and hyperthermia. Decision was made for right hemicolectomy as a result of the findings on ultrasound and computed tomography scan. Diagnosis was made after the pathologic study, which revealedLAMN.

Analyzing Intraductal Papillary Mucinous Neoplasms Using Artificial Neural Network Methodologic Triangulation

Intraductal papillary mucinous neoplasms (IPMN) are a type of mucinous pancreatic cyst. IPMN have been shown to be pre-malignant precursors to pancreatic cancer, which has an extremely high mortality rate with average survival less than 1 year. The purpose of this analysis is to utilize methodological triangulation using artificial neural networks and regression to examine the impact and effectiveness of a collection of variables believed to be predictive of malignant IPMN pathology. Results indicate that the triangulation is effective in both finding a new predictive variable and possibly reducing the number of variables needed for predicting if an IPMN is malignant or benign.

Prognostic prediction of preoperative nutritional status in low-grade appendiceal mucinous neoplasms

Background To describe the preoperative nutritional status of Low-grade Appendiceal Mucinous Neoplasms (LAMNs) and identify prognostic factors for survival. Methods Medical records from 165 patients with LAMNs who attended the Aerospace Center Hospital, Beijing, China between January 2017, and December 2018 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model. Results Among 165 patients, 59 (36%) were male and 106 (64%) were female. Patient’s median age was 58 years (range, 20 to 78 years). Univariate analysis indicated that gender, weight loss, prior surgical score (PSS), red blood cell, albumin, peritoneal cancer index (PCI), completeness of cytoreduction (CCR), and hyperthermic intraperitoneal chemotherapy (HIPEC) were related to prognosis. Multivariate analysis showed that PSS, CCR and HIPEC were independent predictors of prognosis. Conclusions The preoperative nutritional status of patients plays an important role in predicting prognosis. Patients can benefit from a complete cytoreductive surgery (CCRS) and HIPEC in an experienced institution for the first medical treatment.

A novel staging system and clinical predictive nomogram for more accurate staging and prognosis of malignant pancreatic intraductal papillary mucinous neoplasms: a population-based study

Background The current guidelines of the American Joint Committee on Cancer (AJCC) for the staging of exocrine pancreatic tumors seem inapplicable to malignant pancreatic intraductal papillary mucinous neoplasms (IPMN). Therefore, we aimed to improve the accuracy of clinical staging and prognosis for malignant IPMN by modifiing current AJCC system. Methods We extracted data of 2001 patients with malignant IPMN from the Surveillance, Epidemiology, and End Results database between 2000 and 2016. Of these, 1401 patients were assigned to the primary cohort and 600 patients to the validation cohort. Results In Kaplan–Meier analysis of the primary cohort, the current AJCC guidelines were unable to distinguish between certain tumor substages (IA and IB in the 7th, IB and IIA in the 8th). The modified system that we regrouped based on the median overall survival and hazard ratios, was superior in tumor stage classifications. Age > 70 years, tumors located in the body or tail, high-grade differentiated tumors, surgery, chemotherapy, and tumor, lymph node, and metastasis (TNM) stage were identified as independent predictive factors for overall survival. Compared to that of TNM-based systems, the concordance index of the clinical predictive nomogram significantly improved (0.819; 95% confidence interval, 0.805–0.833), with excellent area under the receiver operating characteristic curves (1-, 3-, and 5-year: 0.881, 0.889, and 0.879, respectively). The calibration curves also showed good agreement between prediction and actual observation. The analysis of treatment modalities revealed that surgery resulted in better survival for all resectable malignant IPMN. The analysis of chemotherapy data reveals its potential in improving the prognosis of treatment for patients with locally advanced or distant metastases. Conclusions Our modified staging system improves the distinction of tumor stages. The nomogram was a more accurate and clinically reliable tool for prognosis prediction of patients with malignant IPMN.

P-P23 Adjuvant chemotherapy in the treatment of intraductal papillary mucinous neoplasms of the pancreas: systematic review and meta-analysis

Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Methods A systematic search of Medline, Pubmed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced risk of death in the overall cohort (HR 0.57, 95%-CI:0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95%-CI:0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95%-CI:3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95%-CI:0.20-1.43, p = 0.209). High heterogeneity (I2>75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy were reported for patients with stage III/IV disease, tumour size >2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusions Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

Prognostic prediction of preoperative nutritional status in low-grade appendiceal mucinous neoplasms

Background To describe the preoperative nutritional status of Low-grade Appendiceal Mucinous Neoplasms (LAMNs) and identify prognostic factors for survival. Methods Medical records from 165 patients with LAMNs who attended the Aerospace Center Hospital, Beijing, China between January 2017, and December 2018 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model. Results Among 165 patients, 59 (36%) were male and 106 (64%) were female. Patient’s median age was 58 years (range, 20 to 78 years). Univariate analysis indicated that gender, weight loss, prior surgical score (PSS), red blood cell, albumin, peritoneal cancer index (PCI), completeness of cytoreduction (CCR), and hyperthermic intraperitoneal chemotherapy (HIPEC) were related to prognosis. Multivariate analysis showed that PSS, CCR and HIPEC were independent predictors of prognosis. Conclusions The preoperative nutritional status of patients plays an important role in predicting prognosis. Patients can benefit from a complete cytoreductive surgery (CCRS) and HIPEC in an experienced institution for the first medical treatment.