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Purpose: KRAS, P16, TP53, and SMAD4/DPC4 mutations are common in pancreatic ductal adenocarcinoma (PDAC). The study aimed to evaluate the association between gene mutations in pre‐treatment endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) samples and clinical outcomes of patients with PDAC. Methods: There were 43 patients with resectable (R) PDAC and 41 patients with borderline resectable (BR) PDAC. CDKN2A/p16, TP53, and SMAD4/DPC4 were evaluated through immunohistochemistry (IHC) of pretreatment EUS‐FNA (n = 84) and resected specimens (n = 71). All patients received neoadjuvant therapy. Results: IHC of EUS‐FNA specimens revealed p16 loss in 61 (73%), abnormal p53 in 61 (73%), and Smad4 loss in 38 (45%) patients. Abnormal p53 was associated with a lower resection rate (p =.017). Abnormal p53 and Smad4 loss were associated with recurrence within 6 months post‐pancreatectomy (p =.03, p =.03, respectively). Univariate Cox regression analysis was conducted to reveal that abnormal p53 (p =.07), p16 loss and abnormal p53 (p =.04), and Smad4 and p16 loss (p =.03) were associated with poor prognosis. Conclusions: Pre‐treatment abnormal labeling of p53 in EUS‐FNA specimen was associated with a lower resection rate and an early recurrence in R or BR PDAC cases. [ABSTRACT FROM AUTHOR]

Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma. [ABSTRACT FROM AUTHOR]

Background: Inflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT).Methods: A total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series.Results: The median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p < 0.001). In multivariate analysis, high pre-NACRT mGPS (2 or 1; p = 0.0478) and significant increase in CRP/Alb ratio after NACRT (≧ 0.077; p = 0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧ 0.077) and the group with low ΔCRP/Alb ratio (< 0.077). The group with high ΔCRP/Alb ratio after NACRT (n = 13) not only had higher post-NACRT CRP levels (p < 0.001) but also had lower post-NACRT Alb levels (p = 0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p = 0.03).Conclusion: In addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT. [ABSTRACT FROM AUTHOR]

Recent studies have reported that immune checkpoint inhibitors are effective against various defective mismatch repair (dMMR)/microsatellite instability-high (MSI-H) cancers. A limited number of reports are available on the frequency of dMMR/MSI-H carcinoma in biliary tract cancer (BTC), describing its clinicopathological characteristics and prognosis. The latter carcinoma is also associated with Lynch syndrome (LS). The present study was performed to investigate the frequency of patients with dMMR/MSI-H in BTC and the clinical characteristics of BTC with dMMR/MSI-H in a single institution in Japan. A total of 116 patients with BTC who underwent curative surgical resection at Kagawa University Hospital between January 2008 and December 2017 were included. The protein expression levels of the mismatch repair (MMR) genes [mutL homolog 1 (MLH1), mismatch repair endonuclease PMS2 (PMS2), MutS homolog (MSH)2 and MSH6] were assessed by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tissue specimens. Subsequently, MSI testing was performed on patients who exhibited loss of MMR protein expression. Loss of expression of one or more proteins was detected in five cases (4.3%). Loss of MLH1/PMS2 expression was observed in one case of intrahepatic cholangiocarcinoma, whereas loss of PMS2 expression was noted in one case of perihilar cholangiocarcinoma. Loss of MSH2/MSH6 and MSH6 expression was noted in two cases of distal cholangiocarcinoma and loss of PMS2 expression in one case of ampullary carcinoma. Out of the five patients, two demonstrated MSI-H. Microsatellite stability was observed in two cases and for one case, no data were available. Two MSI-H cases were patients with loss of expression of MLH1/PMS2 and MSH2/MSH6. None of the five patients exhibited a past medical history or family history of suspected LS. The frequency of dMMR in BTC was ~5%, which was similar to that reported by similar studies performed in other countries. In the present study, IHC appeared to be more useful than MSI testing for detecting MMR abnormalities with regards to the detection rate. Furthermore, there may only be a limited number of patients with BTCs who are likely to benefit from the therapeutic effects of treatment with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]