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Objectives: Sarcopenia has been reported as a prognostic risk factor in patients with gastrointestinal (GI) and hepatobiliary pancreatic (HBP) cancers. This study aimed to investigate whether the loss of muscle mass or strength is a stronger prognostic factor, and explore the cutoff values of skeletal muscle mass index (SMI) and handgrip strength (HGS) based on the survival outcome in patients with GI and HBP cancers., Methods: A total of 480 elderly patients with primary GI and HBP cancers who underwent their first resection surgery were analyzed retrospectively. Patients were divided into four groups: Appropriate SMI and HGS, low SMI alone, low HGS alone, and low SMI and HGS. Low SMI was derived from a bioelectrical impedance analysis, and low HGS was defined according to the Asian Working Group for Sarcopenia 2019 criteria., Results: The multivariate analysis showed that low SMI was a significant risk factor for mortality in men only, but low HGS was significant in both sexes. From the multivariate analysis of the four groups, low HGS alone and low SMI and HGS showed a significantly higher hazard ratio than appropriate SMI and HGS in both sexes. An SMI of 7.21 kg/m 2 and HGS of 28 kg were obtained as cutoff values based on the 3-y survival outcomes in men., Conclusions: Low muscle strength was a stronger prognostic factor than low muscle mass. Therefore, measuring muscle strength in all patients is essential., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m 2 for men and 15 kg/m 2 for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival.

Background & Aims: The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers., Methods: A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models., Results: The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08-2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m 2 was an independent poor prognostic factor., Conclusions: EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m 2 is most associated with prognosis in patients with preoperative GI and HBP cancers., Competing Interests: Declaration of competing interest None., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Pancreatic cancer is associated with an exceedingly poor prognosis, warranting the development of novel therapeutic strategies and discovery of prognostic predictors. Given that chemoresistance‑related molecules are reportedly associated with the poor prognosis of pancreatic cancer, the present study aimed to identify molecules that could be efficacious therapeutic targets for pancreatic cancer. First, 10 patient‑derived xenografts (PDXs) were established from patients with pancreatic cancer. Subsequently, after treating tumor tissue generated from the PDXs with standard drugs, next‑generation sequencing (NGS) was performed using these tissues. The results of NGS analysis and immunohistochemical analysis on 80 pancreatic cancer tissues revealed that human epididymis protein 4 (HE4) expression in the anticancer drug‑treated PDX group was higher than that in the untreated PDXs. In addition, chemoresistance ability was observed in tumor cell lines overexpressing HE4. Furthermore, Kaplan‑Meier analysis of tumor tissues from 80 patients with pancreatic cancer was performed and it was found that patients with a high HE4 expression level had a poor survival rate compared with those who had a low HE4 expression level. Multivariate analysis also indicated the high expression level of HE4 was an independent poor prognostic biomarker. Thus, it was concluded that high gene and protein expression levels of HE4 mediate chemoresistance and are independent prognostic factors for pancreatic cancer.

Pancreatic cancer has extremely poor prognosis, warranting the discovery of novel therapeutic and prognostic markers. The expression of polymeric immunoglobulin receptor (pIgR), a key component of the mucosal immune system, is increased in several cancers. However, its clinical relevance in pancreatic cancer remains unclear. In the present study, the prognostic value of pIgR in pancreatic cancer patients after surgical resection was assessed and it was determined that the expression of pIgR was correlated with poor prognosis. Ten pancreatic cancer patient‑derived xenograft (PDX) lines were established, followed by next‑generation sequencing of tumor tissues from these lines after standard chemotherapy. Immunohistochemical analysis of chemoresistance‑related molecules using 77 pancreatic cancer tissues was also performed. The expression of pIgR mRNA in the PDX group treated with anticancer drugs was higher than in the untreated group. High pIgR expression in tissue specimens from 77 pancreatic cancer patients was significantly associated with poor prognosis and was revealed to be an independent prognostic factor, predicting poor outcomes. High pIgR mRNA and protein levels were independent prognostic factors, indicating that pIgR could be a novel predictor for poor prognosis of pancreatic cancer patients.

Pancreatic cancer has an extremely poor prognosis, and identification of novel predictors of therapeutic efficacy and prognosis is urgently needed. Chemoresistance-related molecules are correlated with poor prognosis and may be effective targets for cancer treatment. Here, we aimed to identify novel molecules correlated with chemoresistance and poor prognosis in pancreatic cancer. We established 10 patient-derived xenograft (PDX) lines from patients with pancreatic cancer and performed next-generation sequencing (NGS) of tumor tissues from PDXs after treatment with standard drugs. We established a gene-transferred tumor cell line to express chemoresistance-related molecules and analyzed the chemoresistance of the established cell line against standard drugs. Finally, we performed immunohistochemical (IHC) analysis of chemoresistance-related molecules using 80 pancreatic cancer tissues. From NGS analysis, we identified olfactomedin-4 (OLFM4) as having high expression in the PDX group treated with anticancer drugs. In IHC analysis, OLFM4 expression was also high in PDXs administered anticancer drugs compared with that in untreated PDXs. Chemoresistance was observed by in vitro analysis of tumor cell lines with forced expression of OLFM4. In an assessment of tissue specimens from 80 patients with pancreatic cancer, Kaplan-Meier analysis showed that patients in the low OLFM4 expression group had a better survival rate than patients in the high OLFM4 expression group. Additionally, multivariate analysis showed that high expression of OLFM4 was an independent prognostic factor predicting poor outcomes. Overall, our study revealed that high expression of OLFM4 was involved in chemoresistance and was an independent prognostic factor in pancreatic cancer. OLFM4 may be a candidate therapeutic target in pancreatic cancer., Competing Interests: The authors have read the journal’s policy and the authors of this paper have the following competing interests: HI is paid employees of Noile-Immune Biotech, Inc., clinical stage biotechnology company. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon., Materials and Methods: The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated., Results: MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05)., Conclusion: Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The patient was a 60-year-old man without any particular complaints, but he underwent abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) due to a fatty liver, which revealed two similar cystic lesions regarded as branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) in the pancreatic body [BD-IPMN (b), 16 mm in size] and tail [BD-IPMN (t), 13 mm in size] without a "high-risk stigmata" or "worrisome features". He subsequently received follow-up by MRCP every 6 months. Two years later, MRCP showed prominent dilation of the main pancreatic duct (MPD) and mural nodule formation within the dilated MPD adjacent to the BD-IPMN (b). Distal pancreatectomy specimens revealed that the BD-IPMN (b) was lined by low-papillary gastric mucinous epithelium with low-to-intermediate-grade dysplasia and involved the MPD, forming a malignant mural nodule showing pancreatobiliary-type IPMN. In contrast, the BD-IPMN (t) was lined by flat, monolayer columnar gastric mucinous epithelium without atypia, which suggested the possibility of a "simple mucinous cyst". A genetic analysis showed KRAS mutation only in BD-IPMN (b). Differences in the histological and genetic findings between two similar BD-IPMNs in the present case may suggest what kinds of examinations should be performed in patients with BD-IPMNs without any worrisome features.

Pagetoid reticulosis is a rare cutaneous T-cell lymphoma with striking epidermotropism similar to that present in Paget's disease. There are two forms of pagetoid reticulosis: localized and disseminated. Reported herein is an autopsy case of disseminated pagetoid reticulosis with CD4(-)/CD8(-) phenotype T cells and massive invasion of the lungs and pancreas. The abnormal cells in the epidermis expressed a protein derived from a rearranged T-cell receptor beta gene, and this feature was used to confirm the monoclonality of these cells by polymerase chain reaction. At present, the World Health Organization (WHO) classification system considers pagetoid reticulosis to be an indolent form of primary cutaneous T-cell lymphoma and a variant of mycosis fungoides/Sezary syndrome with prominent epidermotropism. Some differences have been observed between pagetoid reticulosis and mycosis fungoides in terms of clinical course, tumor cell phenotype, and genetic findings; and these differences are highlighted in the present case. The relation between disseminated pagetoid reticulosis, CD4(-)/CD8(-) cutaneous T-cell lymphoma, and gammadelta T-cell lymphoma, including whether pagetoid reticulosis is a variant of mycosis fungoides, remains unclear.

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embryonic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which was generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically 5 days after tumor cell inoculation. Thus, N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter-driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis.