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.
Background: Outcomes of proximal parenchymal pancreatectomy (PPP) as compared to pancreatoduodenectomy (PD) have not been reported. The aim of this study was to describe the short-and longterm outcomes of patients with low-grade pancreatic head lesions who underwent PPP or PD. Methods: Patients who underwent PPP or PD for low-grade lesions between 2009 and 2017 were included. Operative factors including postoperative complications and nutritional indicators during the first-year postoperatively were compared. Results: A total of 13 and 14 patients underwent PPP and PD respectively. The PPP group demonstrated significantly less intraoperative blood loss and shorter postoperative hospital stay than the PD group. No significant differences were noted in the incidence of postoperative complications between the two groups. Nutritional indices were significantly better in the PPP group at 3 months post-surgery, but these nutritional indices were not significantly different at 6 months and 1-year. None of 12 patients who underwent PPP and did not require biliary resection developed postoperative cholangitis. None of the 12 PPP patients without preoperative diabetes developed impaired glucose tolerance after surgery. Discussion: The complication rate of PPP is equivalent to that of PD. PPP demonstrated better shortterm nutritional status than PD. Moreover, preservation of the total duodenum and bile duct may reduce the risk of developing postoperative diabetes and cholangitis.
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.
A 69‐year‐old woman was referred to our department with complaints of abdominal discomfort in the standing position. She had undergone robot‐assisted radical cystectomy and ileal conduit urinary diversion for bladder cancer 10 months earlier. Abdominal CT revealed a parastomal hernia. Laparoscopic parastomal hernia repair using the Pauli technique was performed successfully with no recurrence after a 4‐month follow‐up. Although there are concerns about potential mesh‐related complications and long‐term results, this novel approach can be a successful option for parastomal hernia repair. As far as we know, this is the first English‐language report on the application of Pauli parastomal hernia repair combined with a pure laparoscopic approach.
Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body–tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body–tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body–tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.
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