The efficacy of preoperative neoadjuvant chemoradiotherapy ( NAC ) in cases of pancreatic cancer with extremely poor prognoses has been reported. In this study, we aimed to identify novel biomarkers that reflect prognoses following chemoradiotherapy using tertiary lymphoid organs ( TLO ) expressed in the tumor microenvironment. Resected tumor specimens were obtained from 140 pancreatic cancer patients. We retrospectively investigated the clinical relevance of TLO by categorizing patients into those who underwent upfront surgery (surgery first [ SF ]) and those who received NAC. The immunological elements within TLO were analyzed by immunohistochemistry ( IHC ). In the IHC analysis, the proportions of CD 8+ T lymphocytes, PNA d+ high endothelial venules, CD 163+ macrophages and Ki‐67+ cells within the TLO were higher in the NAC group than in the SF group. In contrast, the proportion of programmed cell death‐1+ immunosuppressive lymphocytes within TLO was lower in the NAC group than in the SF group. The NAC group demonstrated favorable prognoses compared with the SF group. In the multivariate analysis, the TLO /tumor ratio was determined as an independent predictive prognostic factor. In conclusion, the administration of preoperative chemoradiotherapy may influence the immunological elements in the tumor microenvironment and result in favorable prognoses in pancreatic ductal adenocarcinoma patients.
budding grade is associated with invasive clinicopathological features, adverse postoperative prognosis and EMT status in extrahepatic cholangiocarcinoma.
Objective: IgG4-related sclerosing cholecystitis is generally associated with IgG4-related sclerosing cholangitis and presents with diffuse, circumferential thickening of the gallbladder wall. We report a rare case of localized IgG4-related sclerosing cholecystitis without IgG4-related sclerosing cholangitis, which was difficult to differentiate from gallbladder cancer preoperatively. Patient: A 56-year-old man with suspected IgG4-related disease or gallbladder cancer was admitted to our ward. The serum IgG4 level was elevated at 721 mg/dL. Computed tomography (CT) demonstrated focal wall thickening of the gallbladder fundus. Drip infusion cholecystocholangiography with CT revealed no dilation, stenosis, or border irregularity of the bile duct. Results: For diagnostic and treatment purposes, cholecystectomy with wedge resection of the gallbladder bed was performed. The pathological diagnosis was IgG4-related sclerosing cholecystitis. Conclusion: It is difficult to differentiate IgG4-related sclerosing cholecystitis from gallbladder cancer in cases involving localized thickening of the gallbladder wall. In similar cases, surgical resection with cancer in mind might be performed based on present clinical knowledge.
BackgroundPrimary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. There are few reports of early-stage cases in which tumor invasion reached the lamina propria or muscularis mucosae, as in the present case. A standard treatment for early-stage PMME has not yet been established. The present study aimed to summarize previous reports and to discuss the indications for surgical treatment of early-stage primary malignant melanoma of the esophagus.Case presentationA 70-year-old woman with PMME was referred to our hospital. She underwent thoracoscopic and laparoscopic subtotal esophagectomy with lymphadenectomy. The resected specimen showed melanocytosis and junctional activity. Melanoma-specific antigens melan-A, S-100, and HMB45 were detected by immunohistochemical staining. The pathological diagnosis was pT1a-MM, pN0, pM0, and pStage IA. She remains alive without evidence of recurrence 39 months later.ConclusionSubtotal esophagectomy with regional radical lymphadenectomy could be recommended to patients with early-stage primary malignant melanoma of the esophagus, and curative surgical resection could improve their prognosis.
BackgroundChromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo.MethodTheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects.ResultDN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR.ConclusionThe cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.
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