The ratio of intratumoral CD15+ neutrophils to CD8+ lymphocytes predicts recurrence in patients with gastric cancer after curative resection.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is an independent prognostic indicator of various cancers. AIMS: In this study, we aimed to investigate the prognostic relevance of the intratumoral immune cell balance in gastric cancer. METHODS AND RESULTS: The study included 82 patients who underwent curative resection for gastric cancer. The intratumoral cluster of differentiation (CD) 15- and CD8-positive cells were evaluated using immunohistochemical staining. Additionally, clinicopathological factors and prognoses were analyzed. Patients with high intratumoral CD15/CD8 ratios had significantly lower overall survival (OS) and relapse-free survival (RFS) compared to those with low CD15/CD8 ratios (p = .0026 and p < .0001, respectively). Additionally, a high CD15/CD8 ratio was associated with lymph node metastasis (p = .019). Patients with high NLR had a significantly lower RFS than those with low NLR (p = .0050). Multivariate analysis revealed that the intratumoral CD15/CD8 ratio, NLR, and venous invasion were independent prognostic indicators of RFS (CD15/CD8 ratio: p < .001, hazard ratio (HR) = 14.7, 95% confidence interval (CI) = 3.8-56.8; NLR: p = .010, HR = 5.4, 95% CI = 1.5-19.6; venous invasion: p = .005, HR = 7.4, 95% CI = 1.8-29.7). CONCLUSION: In summary, we found that the intratumoral CD15/CD8 ratio is an independent prognostic factor following gastric cancer resection and its increase is associated with lymph node metastasis and microscopic lymph vessel invasion. Immunological evaluation with additional aspects of innate immunity may be useful in predicting cancer prognosis.

Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

Tissue-Engineered Hepatocyte Sheets Supplemented with Adipose-Derived Stem Cells.

The ability to engineer biologically viable hepatocytes and tissue matrices with long-term functional maintenance has attracted considerable interest in the fields of hepatocyte transplantation and liver tissue engineering. Here, newly developed hepatocyte sheets supplemented with adipose-derived stem cells (ADSCs) were evaluated to assess the effects of ADSCs on hepatocyte function and engraftment into the subcutaneous space. Eight-week-old male C57BL/6J mice were used as donors, and 6-week-old male C.B-17/Icr-scid/scid mice were used as recipients. Hepatocyte-ADSC composite sheets were developed using temperature-responsive culture dishes. Hepatocyte viability in the hepatocyte-ADSC composite sheets was evaluated in an in vitro assay, and the outcome of subcutaneous transplantation of the sheet was evaluated. Hepatocyte viability was sustained in the hepatocyte-ADSC composite sheets in vitro. Albumin secretion was significantly higher (p = 0.015) in the hepatocytes of the hepatocyte-ADSC composite sheets (70.5 µg/mL) than in hepatocyte-only sheets (24.0 µg/mL). Cytokine assays showed that hepatocyte growth factor and interleukin-6 were contributed by ADSCs and not hepatocytes, which were not capable of constitutively secreting them. Immunohistochemically, phosphorylated STAT3 and c-MET expression in hepatocytes in the hepatocyte-ADSC composite sheets was significantly higher than that in the hepatocyte-only sheets. Engraftment of the transplanted hepatocyte-ADSC composite sheets was significantly enhanced without pretreatment of the subcutaneous tissue to induce a vascular network. In the hepatocyte-ADSC composite sheets, the viability of the hepatocytes was significantly maintained as the co-cultured ADSCs provided cytokines, enhancing pivotal cell signaling necessary for hepatocyte activity. Impact statement Hepatocyte transplantation is a safe, less invasive bridge treatment for liver transplantation, but its effectiveness is low and transitory. Herein, we introduce newly developed hepatocyte-adipose-derived stem cell composite sheets with improved strength, easier transplantation, and increased hepatocyte viability in the subcutaneous transplantation compared with hepatocyte-only sheets.

[A Case of Pancreatic Cancer That Developed Peritoneal Recurrence after Radical Surgery following Neoadjuvant Chemoradiation Therapy(NACRT)with Pathological Complete Response(pCR)].

A 71-year-old woman was diagnosed with a tumor in the pancreatic head on CT imaging, which was performed as a close examination of an exacerbation of diabetes mellitus. The pancreatic tumor was diagnosed as resectable pancreatic cancer, and after preoperative adjuvant chemoradiotherapy, pancreatoduodenectomy was performed as a radical surgery. There were no residual tumor cells in the resected specimen histopathologically, and the patient was judged to have a pathological complete response(pCR). Six months of postoperative adjuvant chemotherapy was administered, but peritoneal recurrence was observed at 20 months postoperatively, and the patient is currently undergoing treatment for recurrence. There have been other reports of recurrence even after pCR was achieved with preoperative treatment, so it is important to follow up carefully, keeping in mind that pancreatic cancer is a latent systemic disease.

Predicting Post-Hepatectomy Liver Failure Using Intra-Operative Measurement of Indocyanine Green Clearance in Anatomical Hepatectomy.

BACKGROUND: Prediction of post-hepatectomy liver failure (PHLF) based on remnant liver function reserve is important for successful hepatectomy. The aim of this study was to investigate whether intraoperative indocyanine green (ICG) clearance in a future remnant liver was a predictor of PHLF. METHODS: This prospective study enrolled 31 consecutive patients who underwent anatomical hepatectomy between June 2016 and August 2019. Intraoperative ICG plasma disappearance rate (ICG-PDR) and ICG retention rate at 15 min (ICG-R15) were measured after clamping the selective hepatic inflow to the liver to be resected. The discriminative performance of the ICG-associated variables for the prediction of PHLF grade B/C was evaluated by receiver operator curve (ROC) analysis. RESULTS: Of the operations performed, 87.1% were major hepatectomy. PHLF Grade B/C was observed in eight patients (25.8%) with no mortality. The concordance indices of intraoperative ICG-PDR and ICG-PDR for predicting PHLF were 0.834 (95% CI, 0.69-0.98) and 0.834 (95% CI, 0.69-0.98), respectively. A subgroup analysis of patients with preoperative biliary drainage (BD) (n = 17) showed that the concordance indices of intraoperative ICG-PDR increased to 0.923 (95% CI, 0.79-1.00). CONCLUSIONS: Intraoperative ICG clearance in the remnant liver was a promising predictor for PHLF in patients undergoing anatomical hepatectomy, especially in patients with BD.

Accuracy comparison of MR elastography and biological markers in detecting liver fibrosis and predicting postoperative ascites.

BACKGROUND: This retrospective study aimed to compare the discriminative performance between magnetic resonance elastography (MRE) and biological markers in detecting liver fibrosis and in predicting postoperative ascites (PA). METHODS: We enrolled 77 patients consecutively who underwent hepatectomy between March 2017 and June 2019. Liver fibrosis was histopathologically graded using the METAVIR scoring system as reference. Discriminative performance of non-invasive assessments in detecting different stages of liver fibrosis and predicting PA was evaluated by receiver-operator curve analysis. RESULTS: The concordance indices (C-indices) for MRE and biological markers for detecting significant fibrosis (≥F2) and cirrhosis (F4) were: MRE, 0.84 and 0.86; Wisteria floribunda agglutinin + Mac-2 binding protein (WM2BP), 0.63 and 0.71; Hyaluronic acid (HA), 0.72 and 0.75; 7 S-type 4 collagen (T4C), 0.61 and 0.66; APRI, 0.76 and 0.83; and Fib-4, 0.75 and 0.76. Univariable logistic analysis for predicting PA showed that C-indices were 0.751 (p = 0.007), 0.798 (p = 0.106), 0.771 (p = 0.050), 0.674 (p = 0.855), 0.655 (p = 0.263), and 0.560 (p = 0.640) for MRE, WM2BP, Fib-4, HA, APRI, and T4C, respectively. CONCLUSION: MRE has a higher diagnostic performance than biological markers in detecting the stages of liver fibrosis and is a predictor for PA after hepatectomy.

Comprehensive analysis of gene expression of isolated pancreatic islets during pretransplant culture.

BACKGROUND: The aim of this study was to investigate the effect of pretransplant culture on the survival of pancreatic islet grafts, and to determine the biological characteristics of isolated islets during pretransplant culture. METHODS: The survival of islets from Wistar rats, transplanted to diabetic C57BL/B6 mice, was compared between fresh islets and cultured islets. A comprehensive gene expression analysis was employed to investigate biological processes during pretransplant culture, and in vitro validation studies were performed. RESULTS: Survival of cultured xenografts was significantly prolonged as compared to that of fresh islets (fresh:12.5 ± 1.9 days, 1-day cultured:16.0 ± 1.3 days (p= 0.017), 3-day cultured:17.0 ± 2.6 days (p= 0.014)). Comprehensive gene expression analysis identified significant upregulation of annotated functions associated with inflammation in cultured groups. Six proinflammatory genes, including heme oxygenase 1 (HO-1) and IL-6, were significantly upregulated during culture.　Validation studies revealed significantly higher levels of IL-6 in the supernatant of cultured islets and HO-1 in the cultured islets when compared with fresh islets. CONCLUSION: Transplantation of cultured islets induced significant but minimal prolongation of graft survival in xenogeneic combinations. Comprehensive analysis of gene expression in cultured islets showed biological processes associated with proinflammation during culture.

Early intra-abdominal infection following pancreaticoduodenectomy:associated factors and clinical impact on surgical outcome.

Early intra-abdominal infection (IAI) following pancreaticoduodenectomy (PD) is an initial event relating to morbidities caused by postoperative pancreatic fistula (POPF). The aims of this study were to determine factors associated with IAI, and to investigate its impact on postoperative outcome.Consecutive patients, 113 in total, who underwent PD at Fukushima Medical University Hospital between January 2012 and September 2017 were included in this retrospective study. IAI was defined by positive bacterial culture from intra-abdominal drainage fluid any time through postoperative day 3 (POD3). Logistic regression analysis was used to identify the relevant factors associated with IAI. The clinical impact of the POD3 infection indicators related to POPF were assessed by multivariate analysis.The incidence of IAI, POPF, and mortality were 36.1%, 36.1%, and 0%, respectively. Independent factors associated with IAI were preoperative biliary drainage (PBD) (OR = 2.91, CI = 1.16-7.33, p = 0.023) and soft pancreas (OR = 8.67, CI = 2.37-31.77, p = 0.001). Among infection markers on POD3, the significant factors for POPF were CRP (OR = 1.18, CI = 1.08-1.30, p < 0.001), IAI (OR = 7,37, CI = 2.53-21.5, p < 0.001), and drain amylase (OR = 1.00, CI = 1.00-1.01, p = 0.001).In conclusion, PBD, soft pancreas, and higher age were associated with IAI. IAI has a significantly negative impact on postoperative outcome.

[FOLFIRINOX for Locally Advanced and Recurrent Pancreatic Cancer with UGT1A1 *6 and or UGT1A1*28 Polymorphisms-A Report of Two Cases].

Treatment containing FOLFIRINOX was planned to be administered to a 51-year-old man with locally advanced pancreatic cancer as second-line chemotherapy and to a 66-year-old woman with recurrent pancreatic cancer as third-line chemotherapy in their treatments. Since both patients were revealed to harbor UGT1A1 polymorphisms, which were highly associated with irinotecan-induced toxicity(the former: UGT1A1 *6/*28, the latter: UGT1A1*6/*6), there was no alternative hopeful treatment other than FOLFIRINOX for them. Therefore, FOLFIRINOX was administered very carefully. Although both patients showed Grade 4 neutropenia during the initial course, it was controllable with G-CSF administration and following stepwise reduction of the irinotecan dose. Severe diarrhea and other adverse events were not observed in both cases. Since the determined regimen of FOLFIRINOX for patients with high-risk UGT1A1 polymorphisms has not been developed yet, it would be critical to accumulate and review an experience of FOLFIRINOX administration for these patients.

Pancreaticobiliary maljunction diagnosed long after laparotomy in the neonatal period for annular pancreas: report of a case.

BACKGROUND: Although annular pancreas concurrent with pancreaticobiliary maljunction has rarely been reported, some reports have pointed out a possibility that both anomalies have a common pathogenesis in pancreatic development. We herein report a case with pancreaticobiliary maljunction diagnosed long after surgical treatment for annular pancreas. CASE PRESENTATION: A 34-year-old female, with a surgical history of duodenal obstruction due to annular pancreas in the neonatal period, was referred to our hospital for further examination of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed choledocholithiasis, pancreatic lithiasis, and pancreaticobiliary maljunction without biliary dilatation. Choledocholithotomy and cholecystectomy were performed, and highly elevated levels of amylase in bile from the common bile duct were found intraoperatively. CONCLUSION: The present case highlights a possible association of pancreaticobiliary maljunction in a patient with annular pancreas.

Huge Hepatocellular Carcinoma Treated with Radical Hepatectomy after Drug-eluting Bead Transarterial Chemoembolization.

We performed split drug-eluting bead transarterial chemoembolization (DEB-TACE) in a patient with huge unresectable hepatocellular carcinoma and multiple intrahepatic metastases. However, TACE was discontinued at the fourth application because the tumor was fed by the cholecystic artery. As most intrahepatic metastases disappeared following DEB-TACE, the patient was able to undergo radical hepatectomy, and has maintained a complete response. DEB-TACE enables cancer treatment without reducing the liver or renal function. However, it is associated with a risk of ischemia in other organs in patients whose arteries feed both tumors and other organs; thus appropriate selection is required.

Prognostic impact of soluble intercellular adhesion molecule-1 in hepatocellular carcinoma.

The identification of novel biomarkers for hepatocellular carcinoma (HCC) is of great importance in improving the outcome of patients with HCC. The present study aimed to determine the prognostic significance of the soluble intercellular adhesion molecule (sICAM)-1 in patients with HCC. The present study prospectively collected clinicopathological data from 36 patients with HCC who had undergone successful hepatectomy. An analysis using a receiver operating characteristic (ROC) curve was performed to determine the cut-off value for predicting prognosis. Overall survival (OS), recurrence-free survival (RFS) and potential prognostic factors were analyzed. The ROC curve analysis revealed a sICAM-1 cut-off value of 440 ng/ml. HCC patients with sICAM-1 ≥440 ng/ml exhibited a poorer OS and RFS than those with sICAM-1 <440 ng/ml (P=0.002). sICAM-1 ≥440 ng/ml (hazard ratio=3.623; 95% confidence interval: 1.145-11.458; P=0.028) and Child B (hazard ratio=1.514; 95% confidence interval: 1.066-2.150; P=0.021) were independent prognostic factors for OS, and sICAM-1 ≥440 ng/ml was an independent prognostic factor for RFS (hazard ratio=3.625; 95% confidence interval: 1.233-10.659; P=0.019). Serum sICAM-1 may be a promising predictor for the overall and recurrence-free survival of patients with HCC.

[A Case of Long-Term Survival of Metastatic and Recurrent Duodenal Gastrointestinal Stromal Tumor Treated with Multimodality Managements].

We hereby report a case of long-term survival of metastatic and recurrent duodenal gastrointestinal stromal tumor(GIST) treated with multimodality managements. A 59-year-old man was diagnosed with duodenal GIST and underwent surgical resection of a primary lesion of the duodenum. Since the pathological findings on mitotic rate indicated its high risk of recurrence, the systemic treatment by imatinib mesylate was given shortly after the surgery. Six months later, metastatic lesions being considered to be imatinib-resistant were observed in the remnant liver. Since there were no other drugs available for GISTs in clinic at that time, surgery of central bisegmentectomy with partial resection of the liver was performed to eliminate all metastatic lesions. However, recurrences had been repeatedly diagnosed afterward. In response to them, four more surgery for recurrent liver or peritoneal tumors, two transcatheter arterial chemoembolizations(TACE)and one radiofrequency ablation(RFA)were performed on the basis of its resectability. Sunitinib malate had been given since it was approved for imatinib-resistant GISTs in clinic. Eventually, as long as 99 months had passed since we observed the first evidence of the resistance to imatinib mesylate when he died from the GIST.

Clinical significance of serum transthyretin level in patients with hepatocellular carcinoma.

BACKGROUND: Although serum albumin has been reported to be useful as a prognostic biomarker for various malignancies, it is not suitable for prognosis of patients with hepatocellular carcinoma (HCC) due to impaired liver function. We aimed to determine whether serum transthyretin (TTR) level can be used as a novel prognostic biomarker. METHODS: Serum levels of TTR, as well as other nutritional and inflammatory parameters including angiogenic factors, were examined in 25 patients with HCC. RESULTS: The serum TTR levels exhibited a statistically significant inverse correlation with interleukin-6 (r = -0.412, P = 0.041), and showed statistically significant correlations with retinol-binding protein (r = 0.919, P < 0.001) and albumin (r = 0.442, P = 0.027). The patients with TTR <11.4 mg/dL (P = 0.012), those with ≥T2 (P = 0.011) and those with a retention rate of indocyanine green after 15 min ≥15.5 (P = 0.037) showed poorer prognoses than the counterparts of each parameter. The TTR level <11.4 mg/dL (hazard ratio: 4.837, 95% confidence interval: 1.118-20.926, P = 0.035) and ≥T2 (hazard ratio: 5.011, 95% confidence interval: 1.243-20.203, P = 0.023) were independent prognostic factors of HCC patients. CONCLUSION: Serum TTR measurement can be useful for predicting the prognosis of patients with HCC.

[A Case of Long-Term Survival of the Pancreatic Tail Cancer with the Concomitant Small Liver Metastasis].

We hereby report a case of long-term survival of the pancreatic tail cancer with a synchronous small liver metastasis. A 62- year-old male with pancreatic tail cancer was incidentally diagnosed with single tiny metastasis in the left medial section of the liver duringthe distal pancreatectomy. The lesion was also resected together with primary lesion. Since then, systemic chemotherapies such as gemcitabine(GEM)plus S-1 combination therapy, GEM alone therapy and S-1 alone therapy had been given to escape from recurrence. However, the recurrences were found in the liver at 21 months after surgery. Left hepatectomy was performed for metastatic lesions. Afterwards, proton radiation therapy was twice performed for the metastatic lesions in the liver which were unable to be removed by surgery alone. Partial resection of transverse colon was also needed to be performed for the bowel obstruction caused by recurrence on the surgical margin of the liver. Systemic chemotherapies includingS -1 therapy, FOLFIRINOX therapy and GEM plus nab-paclitaxel therapy have been continued throughout his entire treatment history after recurrence. He has been keepingin good physical condition with these multidisciplinary therapies, even though 51 months have passed since the first evidence of liver metastasis was diagnosed.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. MATERIALS AND METHODS: Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. RESULTS: The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. CONCLUSIONS: IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

Utility of magnetic resonance elastography for predicting ascites in patients with chronic liver disease.

OBJECTIVE: This study aimed to evaluate the utility of magnetic resonance elastography (MRE) as a non-invasive method for predicting ascites in patients with chronic liver disease (CLD). METHODS: A total of 208 CLD patients underwent MRE to measure liver stiffness (LS) at our institution from March 2013 to June 2015. We evaluated the diagnostic performance of MRE for predicting the presence of ascites using receiver-operating characteristic (ROC) curve analysis and compared the performance with that of serum fibrosis markers. Multivariate logistic regression analysis was performed to identify factors associated with the presence of ascites. The cumulative incidence of ascites was examined in patients without ascites at baseline. The pathological stage of liver fibrosis was evaluated in 81 CLD patients using histopathologic diagnosis. RESULTS: Of the 208 patients, 41 had ascites. The optimal cut-off LS value for the presence of ascites was 6.0 kPa (area under the ROC curve = 0.87). The area under the ROC curve for the presence of ascites was significantly higher for MRE than that for fibrosis markers. Multivariate analysis revealed that LS >6.0 kPa is an independent risk factor for the presence of ascites. The cumulative incidence of ascites was significantly higher among those with LS values >6.0 kPa. There was significantly greater diagnostic accuracy for liver fibrosis stage ≥4 with MRE than that with fibrosis markers. CONCLUSIONS: Compared with serum fibrosis markers, MRE has higher diagnostic performance in predicting the presence of ascites. MRE-based LS has the potential to predict the presence of ascites in CLD patients.

Successful Endoscopic Closure Using Polyglycolic Acid Sheets with Fibrin Glue for Nonhealing Duodenal Ulcer with Perforation after Proton Beam Therapy of Liver Tumor.

We describe the first case of a nonhealing duodenal ulcer with perforation after proton beam therapy (PBT) of a liver tumor that was successfully treated endoscopically using polyglycolic acid (PGA) sheets with fibrin glue. A 69-year-old man received PBT for a liver tumor. Esophagogastroduodenoscopy (EGD) 3 months after PBT revealed a duodenal ulcer. A proton pump inhibitor was administered for 7 weeks, and the ulcer healed. Six months after the EGD, recurrence of the duodenal ulcer with perforation occurred. An emergency open surgery with placement of the omental patch was performed. However, 5 days after the surgery, because the EGD revealed a perforation site in the duodenal ulcer that was not closed, the conservative treatment was continued. Twenty-eight days after the surgery, EGD revealed that the perforation size had increased. Therefore, we conducted endoscopic closure therapy using PGA sheets with fibrin glue. Eleven days after the closure procedure, the EGD showed that the perforation site was filled with granulation tissue and was closed. Forty-nine days after the procedure, EGD revealed that the ulcer had healed. This endoscopic closure treatment was effective for a nonhealing duodenal ulcer with perforation after PBT of a liver tumor.

Ex vivo Pretreatment of Islets with Mitomycin C: Reduction in Immunogenic Potential of Islets by Suppressing Secretion of Multiple Chemotactic Factors.

Strategies to reduce the immunogenicity of pancreatic islets and to prevent the activation of proinflammatory events are essential for successful islet engraftment. Pretransplant islet culture presents an opportunity for preconditioning to improve outcomes of islet transplantation. We previously demonstrated that ex vivo mitomycin C (MMC) pretreatment and subsequent culture significantly prolonged graft survival. Fully understanding the biological process of pretreatment could result in the development of a protocol to improve the survival of islet grafts. Microarrays were employed to conduct a comprehensive analysis of genes expressed in untreated or MMC-treated rat islets that were subsequently cultured for 3 d. A bioinformatics software was used to identify biological processes that were most affected by MMC pretreatment, and validation studies, including in vivo and in vitro assay, were performed. The gene expression analysis identified significant downregulation of annotated functions associated with cellular movement and revealed significant downregulation of multiple genes encoding proinflammatory mediators with chemotactic activity. Validation studies revealed significantly decreased levels of interleukin 6 (IL-6), monocyte chemoattractant protein 3 (MCP-3), and matrix metallopeptidase 2 (MMP2) in culture supernatants of MMC-treated islets compared with controls. Moreover, we showed the suppression of leukocyte chemotactic activity of MMC-treated islets in vitro. We also showed that MMC-treated islets secreted lower levels of chemoattractants that synergistically reduced the immunogenic potential of islets. Histological and immunohistochemical analyses of the implant site revealed that infiltration of monocytes, CD3-positive T cells, and B cells was decreased in MMC-treated islets. In conclusion, the ex vivo pretreatment of islets with MMC and subsequent culture can reduce the immunogenic potential and prolong the survival of islet grafts by inducing the suppression of multiple leukocyte chemotactic factors.

Significance of Circulating Galectin-3 in Patients with Pancreatobiliary Cancer.

BACKGROUND/AIM: Pancreatobiliary cancer is a disease associated with a dismal prognosis and limited treatment options. The aim of the present study was to clarify the usefulness of circulating galectin-3 in pancreatobiliary cancer. PATIENTS AND METHODS: We examined serum galectin-3 concentrations in 45 patients with pancreatobiliary cancer. Receiver operating characteristic curves were utilized to evaluate the accuracy of circulating galectin-3 to discriminate pancreatobiliary cancer patients from controls and predict the prognostic outcomes. RESULTS: Circulating galectin-3 had diagnostic value at the cut-off level of 6.2 ng/ml, and the patients' overall survival was predictable at the cut-off level of 10.3 ng/ml. Furthermore, circulating galectin-3 ≥10.3 ng/ml was an independent prognostic marker in pancreatobiliary cancer. Regarding biliary cancer, higher galectin-3 was associated with malnutrition. On the other hand, regarding pancreatic cancer, higher galectin-3 levels were associated with higher inflammatory parameters. CONCLUSION: Galectin-3 can be a useful biomarker in patients with pancreatobiliary cancer.