Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC.Methods: Forty‐two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors.Results: Twenty‐two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut‐off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse‐free survival (hazard ratio [HR], 3.92; P = .044) and overall survival (HR, 14.08; P = .023).Conclusions: PERCIST was more accurate in determining NAT’s therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC.

Formalin‐fixed paraffin‐embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer‐related gene mutations including driver genes in PDAC, using next‐generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse‐free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77‐10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93‐23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.

Mouse kidney allografts are spontaneously accepted in select, fully mismatched donor-recipient strain combinations, like DBA/2J to C57BL/6 (B6), by natural tolerance. We previously showed accepted renal grafts form aggregates containing various immune cells within 2 weeks post-transplantation referred to as Treg-rich Organized Lymphoid Structures (TOLS) which are a novel regulatory Tertiary Lymphoid Organ. To characterize the cells within TOLS, we performed single-cell RNA-sequencing (scRNA-seq) on CD45+ sorted cells from accepted and rejecting renal grafts from 1-week to 6-months post-transplantation. Analysis of scRNA-seq data revealed a shifting T cell dominant to a B cell rich population by 6-months with an increased regulatory B cell signature. Furthermore, B cells were a greater proportion of the early infiltrating cells in accepted versus rejecting grafts. Flow cytometry of B cells at 20-weeks post-transplantation revealed TIM-1+ B cells, potentially implicating a regulatory role in the maintenance of allograft tolerance. Lastly, B cell trajectory analysis revealed intra-graft differentiation from precursor B cells to memory B cells in accepted allografts. In summary, we show a shifting T cell to B cell-rich environment and a differential cellular pattern among accepted versus rejecting kidney allografts, possibly implicating B cells in the maintenance of kidney allograft acceptance.

Although the rates of surgical site infection are decreasing, surgical site infection after pancreatectomy remains frequent because of postoperative pancreatic fistula. Recent studies suggested a relationship between postoperative pancreatic fistula and pathogens cultured from drainage fluids after pancreatectomy. This study aimed to assess and evaluate high-risk pathogens cultured from postoperative drainage fluids for postoperative pancreatic fistulas or severe postoperative complications after pancreatectomy. We retrospectively enrolled patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2012 and 2019. We assessed clinical characteristics and microbiological results of drainage cultures of pancreaticoduodenectomy or distal pancreatectomy patients, and we investigated the risk factors for clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status using univariate and multivariate analyses. Finally, we detected high-risk pathogens from drainage cultures and analyzed the correlation between these pathogens and the severity of clinically relevant postoperative pancreatic fistula or Clavien-Dindo status. Four hundred and twenty-nine patients were enrolled: 257 underwent pancreaticoduodenectomy and 172 underwent distal pancreatectomy. Clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status ≥ III were more frequently seen in pancreaticoduodenectomy patients than in distal pancreatectomy patients, namely grade C postoperative pancreatic fistula, which was observed in 19 pancreaticoduodenectomy patients. The most common pathogen found from drainage cultures was Enterococcus species, followed by Enterobacter species and Candida species. All pathogens were associated with clinically relevant postoperative pancreatic fistulas; however, Candida species was a dominant microorganism of clinically relevant postoperative pancreatic fistulas grade C, Clavien-Dindo status ≥ IV, and hemorrhage due to pseudoaneurysm. The presence of Candida species in the drainage fluid culture after pancreaticoduodenectomy can be a predictive factor of severe infectious complications, including postoperative pancreatic fistulas; thus, we should regularly collect cultures from drainage fluids and monitor for Candida infection.

The patient was a 54-year-old female who presented with the chief complaint of melena. Lower gastrointestinal endoscopy detected a type 1 tumor extending from the anal canal to the rectum. CT did not detect any distant metastasis. Proximal D3 lymphadenectomy with laparoscopic abdominoperineal resection was performed for stage IA rectal cancer. In the histopathological examination, the tumor was identified as stage IIIa adenosquamous carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with S-1, a recurrent left lateral lymph node tumor was detected on CT and PET 12 months later. The patient underwent the treatment with mFOLFOX + bevacizumab for 6 months. However, the tumor continued to progress, and therefore, extended lateral lymphadenectomy was performed 21 months after the first surgery. The patient did not undergo postoperative adjuvant therapy and is alive without recurrence 90 months after the first surgery and 70 months after the reoperation. Adenosquamous carcinoma of the rectum is a rare histological type of colorectal cancer for which there is no effective treatment besides surgical resection, and its prognosis is known to be worse than that of adenocarcinoma. Since there has been no report of long-term survival after extended lateral lymphadenectomy for recurrent lateral lymph node tumors following surgery for adenosquamous carcinoma of the rectum, herein, we report the case with a review of the literature.