Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance.

Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8 KO recipients resulted in acceptance and not rejection. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.

Intragraft B cell differentiation during the development of tolerance to kidney allografts is associated with a regulatory B cell signature revealed by single cell transcriptomics.

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 posttransplant, referred to as regulatory T cell-rich organized lymphoid structures, which are a novel regulatory tertiary lymphoid organ. To characterize the cells within T cell-rich organized lymphoid structures, we performed single-cell RNA sequencing on CD45+ sorted cells from accepted and rejected renal grafts from 1-week to 6-months posttransplant. Analysis of single-cell RNA sequencing data revealed a shifting from a 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 vs rejecting grafts. Flow cytometry of B cells at 20 weeks posttransplant revealed T cell, immunoglobulin domain and mucin domain-1+ B cells, potentially implicating a regulatory role in the maintenance of allograft tolerance. Lastly, B cell trajectory analysis revealed intragraft 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 vs rejecting kidney allografts, possibly implicating B cells in the maintenance of kidney allograft acceptance.

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm.

OBJECTIVES: Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. METHODS: We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN. RESULTS: Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-to-lymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (OR, 3.28; 95% CI, 0.52-20.80 vs 1.85; 95% CI, 0.78-4.41; OR, 2.44; 95% CI, 0.81-7.34 vs 1.24; 95% CI, 0.67-2.30, respectively). CONCLUSIONS: Understanding the interactions between background factors can effectively prevent IPMNs' malignant transformation.

Diagnostic Utility of Presepsin in Infections After Liver Transplantation: A Preliminary Study.

BACKGROUND Infectious complications after solid organ transplantation can be fatal, and early diagnosis and intervention are important. To the best of our knowledge, no study has examined the diagnostic utility of presepsin, a known accurate biomarker, for infectious complications after liver transplantation. This study aimed to evaluate the utility of presepsin for detecting infection and perioperative kinetics of presepsin after liver transplantation. MATERIAL AND METHODS This single-institutional prospective, observational study included 13 patients who underwent living-donor or deceased-donor liver transplantation. Perioperative serum presepsin level was measured 6 times within a week to evaluate its association with infectious complications and compare it with procalcitonin and C-reactive protein levels and leukocyte count. Postoperatively, patients were followed up for 15 days for infectious complications. RESULTS Five of the 13 patients developed infectious complications after liver transplantation. The median time for infection diagnosis was 9 postoperative days (25th-75th percentile, 7-10). Presepsin levels on 5 and 7 postoperative days were significantly higher in patients with infection than in those without (P=0.019 and P=0.011, respectively). In receiver operating characteristic analysis, area under the curve values of presepsin on 5 and 7 postoperative days (0.881 and 0.905, respectively) were higher than those of other biomarkers. The optimal cut-off value of presepsin was 1361 pg/mL on postoperative day 5 and 1375 pg/mL on postoperative day 7. CONCLUSIONS Although this study included a small number of patients, presepsin levels on postoperative days 5 and 7 may be useful indicators for infectious complications after liver transplantation.

New strategy for evaluating pancreatic tissue specimens from endoscopic ultrasound-guided fine needle aspiration and surgery.

BACKGROUND AND AIM: Preoperative histological evaluation of pancreatic neoplasms is important for guiding the resection strategy and preventing postoperative adverse events. However, conventional endoscopic methods have technical limitations that reduce the accuracy of the histopathological examination. Probe electrospray ionization mass spectrometry (PESI-MS) may be a useful technique for rapidly evaluating small specimens. METHODS: This single-center prospective study included patients with pancreatic neoplasms between October 2018 and December 2019. Pancreatic ductal adenocarcinoma (PDAC) specimens were obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and non-neoplastic tissue was obtained via surgery. Specimens were subjected to PESI-MS and the mass spectra were analyzed using partial least squares regression-discriminant analysis. RESULTS: The study included 40 patients with 20 nonneoplastic specimens and 19 PDAC specimens (1 case of neuroendocrine carcinoma was omitted). All nonneoplastic specimens were sufficient for PESI-MS analysis, although only 7 of 19 PDAC specimens were sufficient for PESI-MS analysis because of poor sample quality or insufficient quantity (<1 mg). Among the 27 analyzed cases, the mass spectra clearly differentiated between the PDAC and nonneoplastic specimens. CONCLUSIONS: This study revealed that PESI-MS could differentiate between PDAC and nonneoplastic specimens, even in cases where EUS-FNA produced very small specimens.

Clinical Impact of Portal Vein Distance on Computed Tomography for Postoperative Pancreatic Fistula after Pancreatoduodenectomy.

BACKGROUND: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area. METHODS: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011-2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus. RESULTS: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830). CONCLUSIONS: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting.

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata.

BACKGROUND/OBJECTIVES: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. METHODS: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. RESULTS: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). CONCLUSIONS: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

Usefulness of selective arterial calcium injection tests for functional pancreatic neuroendocrine tumors.

The selective arterial calcium injection (SACI) test is useful for patients with functional pancreatic neuroendocrine tumors (F-PNETs). This study evaluated which patients with F-PNETs would benefit from the SACI test. We retrospectively analyzed the preoperative findings of patients on computed tomography (CT), magnetic resonance imaging (MRI), CT angiography (CTA), and the SACI test. Fourteen patients who underwent pancreatectomy between January 1997 and September 2016 for F-PNETs were evaluated. We classified these patients into groups A, B, and C; group A, one tumor detected by either CT or MRI; group B, multiple tumors detected; and group C, the tumor location was accordant on CT, MRI, and CTA, but the SACI test revealed another tumor. In group A, the tumor was also detected by CTA and the SACI test was positive on calcium injection. In group B, the focus tumor among the multiple tumors was detected by the SACI test. In group C, another tumor was identified by the SACI test, whose location was different from that detected using CT and MRI. The SACI test is more useful for multiple F-PNETs on CT or MRI. If CT or MRI detects a single tumor, the SACI test or CTA may be unnecessary.

Extra-adrenal pheochromocytoma with initial symptom of haemoptysis: a case report and review of literature.

BACKGROUND: Pheochromocytoma is a catecholamine-secreting tumour that leads to various symptoms. Haemoptysis is rarely caused by a pheochromocytoma occurring outside the bronchus or thoracic cavity. Here, we report the case of an extra-adrenal abdominal pheochromocytoma initially manifesting as haemoptysis/dyspnoea during exercise without classic symptoms. CASE PRESENTATION: A 22-year-old man with a history of severe dyspnoea experienced difficulties in breathing following a marathon owing to haemoptysis that required ventilator management 1 year before presentation. His father had undergone surgery for ectopic pheochromocytoma. Computed tomography (CT) revealed a 30-mm tumour between the inferior vena cava and pancreatic head while urinalysis revealed abnormally high noradrenaline levels. He was clinically diagnosed with an extra-adrenal abdominal ectopic pheochromocytoma. After controlling blood pressure, surgery was performed, and the tumour was successfully removed. Histopathology revealed chromogranin A (+), synaptophysin (+), S100 protein (+), and MIB-1 index of 1%. Therefore, the patient was finally diagnosed with extra-adrenal abdominal ectopic pheochromocytoma. CONCLUSIONS: Haemoptysis is a rare manifestation of abdominal ectopic paraganglioma. Prompt consideration of pheochromocytoma/paraganglioma when patients experience haemoptysis without any other possible aetiology may prevent inappropriate diagnosis and treatment and ultimately fatalities.

O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer.

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.

Urgent distal pancreatectomy for intraperitoneal hemorrhage due to the spontaneous rupture of a pancreatic metastatic tumor from synovial sarcoma: a case report.

BACKGROUND: Synovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy. CASE PRESENTATION: A 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery. CONCLUSIONS: While the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.

High risk pathogens and risk factors for postoperative pancreatic fistula after pancreatectomy; a retrospective case-controlled study.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer.

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.

The perioperative presepsin as an accurate diagnostic marker of postoperative infectious complications after esophagectomy: a prospective cohort study.

BACKGROUND: Presepsin is suggested to be an accurate sepsis diagnostic biomarker, playing an important role in distinguishing infection from no-infection status. However, to date, there is no study determining presepsin's role in diagnosing post-esophagectomy infectious complications. METHODS: Thirty patients who underwent esophagectomy for esophageal carcinoma were included in this prospective observational study. We investigated preoperative presepsin levels' changes and evaluated the relationship between infectious complications and presepsin levels. Moreover, we analyzed the classification and regression tree (CART) to determine presepsin's optimal cutoff values for discriminating infectious complications. RESULTS: For 10 patients with infectious complications, median presepsin levels were 168, 337, 303, 271, 314, 978, and 752 pg/ml, pre- and immediately post-surgery, and 1, 2, 3, 5, 7 days post-surgery, respectively. Presepsin levels were significantly higher in the infectious complication group exclusively from preoperation to POD 7 (p = 0.048). Furthermore, area under the curve's value of presepsin on POD 5 and 7 was higher than the other three biomarkers included for discriminating infectious complications (i.e., procalcitonin, leukocyte, and C-reacted protein). We set an optimal cutoff value for presepsin calculated by CART. Specifically, on POD 5, the cutoff was 888 pg/ml with a sensitivity of 60% and a specificity of 90%, and on POD 7, the cutoff was 668 pg/ml with a sensitivity of 60% and a specificity of 85%. CONCLUSIONS: Presepsin levels on POD 5 and 7 after esophagectomy are a valuable indicator of infectious complication's detection vs. leukocyte, C-reacted protein, and procalcitonin.

Usefulness of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography for predicting the prognosis and treatment response of neoadjuvant therapy for pancreatic ductal adenocarcinoma.

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.

A case of pancreatic hamartoma with characteristic radiological findings: radiological-pathological correlation.

Pancreatic hamartoma is a rare benign tumor. Its preoperative diagnosis is challenging. We present a case of pancreatic hamartoma whose radiological-pathological correlation was evaluated in detail. A 53-year-old man was referred to our institution for diagnosis and treatment. Contrast-enhanced computed tomography (CT) and magnetic resonance image revealed a 3.5 cm long tumor arising from the head of the pancreas with cystic and solid components, the latter of which was gradually and inhomogeneously enhanced in the delayed phase. Fluorodeoxyglucose (FDG) positron emission tomography/CT revealed slight FDG uptake in the solid component. Histologically, a number of pancreatic lobule-like structures, which were mainly composed of aggregates of small ducts embedded in concentric fibrous stroma with no apparent islets or peripheral nerves, were observed in the solid component, whereas multiple dilated ducts were seen in the cystic region. The solid component also contained a narrow area of edematous fibrous stroma with low vessel density, which corresponded with the unenhanced part in the inhomogeneously enhanced solid component. There was no remarkable cytological atypia throughout the mass. A pathological diagnosis of pancreatic hamartoma was made. The radiological findings agree well with the pathological findings. When a pancreatic tumor is of the solid type, preoperatively diagnosing it as pancreatic hamartoma is not possible. However, when a pancreatic tumor with cystic and solid components is inhomogeneously enhanced in contrast-enhanced studies, a diagnosis of pancreatic hamartoma can be considered.

Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature.

BACKGROUND: Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT). CASE SUMMARY: The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE. CONCLUSION: This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.

Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: study protocol for a multicentre, single-blind, randomised controlled clinical trial.

INTRODUCTION: The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries. METHODS AND ANALYSIS: We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method. ETHICS AND DISSEMINATION: The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: UMIN 000031560; Pre-results.

Long-term survival with extended lateral lymphadenectomy for lateral lymph node recurrence after laparoscopic abdominoperineal resection for rectal adenosquamous carcinoma: a case report.

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.