ASO Author Reflections: Potential of Peripheral Plasma Exosomal miRNA: miR-6855-5p Could Predict Radiosensitivity in Patients with Pancreatic Cancer, and Enhances Radioresistance.

The efficacy of preoperative treatment for pancreatic cancer (PC) has been reported in randomized controlled trials, but the optimal regimen and the appropriateness of combining radiotherapy remain controversial. Therefore, predicting the efficacy of preoperative treatment using biomarkers and determining whether to combine chemotherapy or radiotherapy based on the biology of individual tumors could help personalize treatment and maximize therapeutic outcomes. In this study, a microRNA (miRNA) microarray analysis was performed using peripheral blood plasma exosomes from 10 PC patients who underwent neoadjuvant chemoradiotherapy, leading to the identification of miR-6855-5p as a candidate miRNA. miR-6855-5p was found to induce radioresistance in PC cells. In another cohort of 28 patients, it was observed that those with higher expression levels of miR-6855-5p in peripheral blood plasma exosomes tended to have increased radioresistance (r = - 0.5964). In future, measuring plasma exosomal miR-6855-5p before treatment could potentially lead to precision medicine by personalizing the decision of whether to include radiotherapy in the treatment plan.

Prognostic impact of dysphagia scores in patients with advanced resectable esophageal cancer who underwent radical esophagectomy after preoperative treatment.

BACKGROUND: Dysphagia caused by tumor strictures is a major symptom in patients with advanced esophageal cancer. However, the prognostic effect of dysphagia in resectable cases is insufficiently investigated. This study aimed to investigate the prognostic value of dysphagia scores in resectable advanced esophageal cancer who underwent radical esophagectomy after preoperative treatment. METHODS: This retrospective study enrolled 302 consecutive patients with advanced resectable esophageal cancer who received preoperative treatment. The preoperative dysphagia score was used to assess the relationship between tumor stricture and clinical outcomes. RESULTS: Almost half of the patients had dysphagia scores of 2 to 4 (n = 152 [50.3%]). Lower body mass index, circumferential tumors, and noncurative resection were significantly more common as dysphagia scores worsened. Patients with dysphagia had significantly more advanced ypT stage and worse histopathologic response than those without dysphagia. The 5-year disease-free survival and overall survival (OS) rates for dysphagia scores of 0 to 1, 2 to 3, and 4 were 52.9%, 35.3%, and 26.7% and 60.7%, 40.4%, and 26.7%, respectively. Multivariate analysis identified dysphagia score as an independent factor of OS, similar to surgical curability and ypN stage. The postoperative recurrence rate was significantly higher among patients with dysphagia scores of 2 to 3 (56%) and 4 (67%) than among those with dysphagia scores of 0 to 1 (36%) (P < .001 and P = .037, respectively). Furthermore, distant recurrence in dysphagia scores of 2 to 3 and 4 was higher than in dysphagia scores of 0 to 1 (26%, 46%, and 42%, respectively). CONCLUSION: The dysphagia score before initial treatment is associated with postoperative survival in patients with resectable advanced esophageal cancer.

Preoperative treatment response prediction for pancreatic cancer by multiple microRNAs in plasma exosomes: Optimization using machine learning and network analysis.

BACKGROUND/OBJECTIVES: MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction. METHODS: A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response. RESULTS: In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders. CONCLUSIONS: Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.

miR-6855-5p Enhances Radioresistance and Promotes Migration of Pancreatic Cancer by Inducing Epithelial-Mesenchymal Transition via Suppressing FOXA1: Potential of Plasma Exosomal miR-6855-5p as an Indicator of Radiosensitivity in Patients with Pancreatic Cancer.

BACKGROUND: Whether radiation should be added to neoadjuvant treatment remains controversial, and liquid biopsy has not been reported to predict radioresistance in pancreatic cancer (PC). We aimed to identify microRNAs (miRNAs) governing radioresistance in PC by utilizing peripheral plasma exosome samples and to verify their usefulness as biomarkers. METHODS: miRNA microarray analysis was conducted using pretreatment peripheral plasma exosomes from 10 patients with PC receiving neoadjuvant chemoradiotherapy (NACRT) in the discovery cohort. Patients were categorized into two groups (good and poor responders) based on treatment responses, and candidate miRNAs exhibiting differential expression between the two groups were identified. The radiosensitivity of PC cells was examined after miR-6855-5p overexpression. Next-generation sequencing (NGS) and TargetScan were used to explore the mechanisms of radioresistance. We investigated the correlation between miR-6855-5p expression levels in the pretreatment peripheral plasma exosomes of 28 patients in the validation cohort and the response to NACRT. RESULTS: miR-6855-5p expression was higher in poor responders than in good responders. miR-6855-5p induces radioresistance in PC cells. NGS showed that epithelial-mesenchymal transition (EMT) was involved in miR-6855-5p-related radioresistance. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-6855-5p using NGS and TargetScan. Clinical examination of samples from the validation cohort revealed a tendency for patients with higher expression of miR-6855-5p in peripheral plasma exosomes to exhibit increased radioresistance (r = -0.5964). CONCLUSIONS: miR-6855-5p regulates the radioresistance of PC by inducing EMT via suppressing FOXA1, and miR-6855-5p in peripheral plasma exosomes may be a biomarker for radioresistance of PC.

Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.

A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer.

BACKGROUND: Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. METHOD: We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). RESULTS: Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. CONCLUSION: A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.

Survival Impact of Inflammation-based Prognostic Scores in Metastatic or Unresectable Esophageal Cancer Treated With Pembrolizumab Plus Chemotherapy.

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival.

Assessing Intra-abdominal status for clinically relevant postoperative pancreatic fistula based on postoperative fluid collection and drain amylase levels after distal pancreatectomy.

Aim: The aim of this study was to evaluate the intra-abdominal status related to postoperative pancreatic fistula by combining postoperative fluid collection and drain amylase levels. Methods: We retrospectively reviewed the data of 203 patients who underwent distal pancreatectomy and classified their postoperative abdominal status into four groups based on postoperative fluid collection size and drain amylase levels. We also evaluated the incidence of clinically relevant postoperative pancreatic fistula in each group according to C-reactive protein values. Results: The incidence of clinically relevant postoperative pancreatic fistula in the entire cohort (n = 203) was 28.1%. Multivariate analysis revealed that postoperative fluid collection, drain amylase levels, and C-reactive protein levels are considerable risk factors for clinically relevant postoperative pancreatic fistula. In the subgroup with large postoperative fluid collection and high drain amylase levels, 65.9% of patients developed clinically relevant postoperative pancreatic fistula. However, no significant difference was observed in C-reactive protein levels between patients with clinically relevant postoperative pancreatic fistula and those without it. In contrast, in the subgroup with a large postoperative fluid collection size or a high amylase level alone, a significant difference was observed in C-reactive protein values between the patients with clinically relevant postoperative pancreatic fistula and those without it. Conclusion: Postoperative fluid collection status and the C-reactive protein value provide a more precise assessment of intra=abdominal status related to postoperative pancreatic fistula after distal pancreatectomy. This detailed analysis may be a clinically reasonable approach to individual drain management.

Multiple infusions of ex vivo-expanded regulatory T cells promote CD163+ myeloid cells and kidney allograft survival in non-lymphodepleted non-human primates.

Clinical verification of adoptively transferred regulatory T cell (Treg) efficacy in transplantation remains challenging. Here, we examined the influence of autologous ex vivo-expanded polyclonal Tregs on kidney graft survival in a clinically relevant non-human primate model. Peripheral blood Tregs were isolated and expanded using artificial antigen presenting cells. Immunosuppression was comprised of tapered tacrolimus and CTLA4 immunoglobulin, in five animals each without or with Treg infusions. Escalating Treg doses were administered 6, 10, 13, 16, 20, 23, 27 and 30 days after transplant. Infused Tregs were monitored for Treg signature, anti-apoptotic (Bcl-2) and proliferation (Ki67) marker expression. Treg infusions prolonged median graft survival time significantly from 35 to 70 days. Treg marker (Ki67 and Bcl-2) expression by infused Tregs diminished after their infusion but remained comparable to that of circulating native Tregs. No major changes in circulating donor-reactive T cell responses or total Treg percentages, or in graft-infiltrating T cell subsets were observed with Treg infusion. However, Treg infusion was associated with significant increases in CD163 expression by circulating HLA-DR+ myeloid cells and elevated levels of circulating soluble CD163. Further, graft-infiltrating CD163+ cells were increased with Treg infusion. Thus, multiple Treg infusions were associated with M2-like myeloid cell enhancement that may mediate immunomodulatory, anti-inflammatory and graft reparative effects.

Significance of Comprehensive Analysis of Preoperative Sarcopenia Based on Muscle Mass, Muscle Strength, and Physical Function for the Prognosis of Patients with Esophageal Cancer.

BACKGROUND: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer. METHODS: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated. RESULTS: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts. CONCLUSIONS: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer.

Short-term Outcomes of Adjuvant Nivolumab After Neoadjuvant Chemotherapy in Patients With Resected Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: CheckMate 577 evaluated adjuvant nivolumab therapy after neoadjuvant chemoradiotherapy and surgery for esophageal cancers. However, the efficacy of this treatment in patients who received neoadjuvant chemotherapy remains unknown. This study investigated the short-term outcomes of adjuvant nivolumab therapy in patients with advanced esophageal squamous cell carcinoma post-neoadjuvant chemotherapy. PATIENTS AND METHODS: Out of 956 patients with thoracic esophageal cancer who underwent radical esophagectomy, 227 who exhibited ypN1-3 after neoadjuvant chemotherapy and surgery were included in this study. RESULTS: Among 227 patients, 30 received adjuvant nivolumab and 197 received non-nivolumab adjuvant therapy. The nivolumab group displayed a higher number of lymph node metastases compared to the control group. Patients with ypN1-2 tended to have longer recurrence-free survival (RFS) in the nivolumab group than in the non-nivolumab group (p=0.095). In the propensity score-matched cohort, no differences in patient characteristics were observed. Adjuvant nivolumab therapy significantly prolonged RFS in patients who received neoadjuvant chemotherapy (p=0.013). Patients with ypN1-2 in the nivolumab group had significantly longer RFS than their counterparts in the non-nivolumab group (p=0.001), but not in ypN3 (p=0.784). The 1-year postoperative recurrence rates were 59% for the non-nivolumab group and 24% for the nivolumab group (p=0.007). Nivolumab-related adverse events in patients receiving neoadjuvant chemotherapy were mostly consistent across all grades, while the frequency of increased aspartate aminotransferase (AST) levels was relatively higher compared to CheckMate577. CONCLUSION: Adjuvant nivolumab was more likely to prolong 1-year RFS in patients receiving neoadjuvant chemotherapy, especially in those with ypN1-2, and had acceptable adverse events.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy.

INTRODUCTION: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. METHODS: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. RESULTS: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. CONCLUSION: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

Clinical Impact of Enhanced Recovery After Esophagectomy in Patients With Esophageal Cancer.

BACKGROUND/AIM: The enhanced recovery after surgery (ERAS) program is expected to improve perioperative outcomes in patients with esophageal cancer. However, how ERAS impacts the postoperative body composition and factors related to compliance rate of ERAS have not been fully investigated. PATIENTS AND METHODS: The study included 252 consecutive patients with thoracic esophageal cancer who underwent minimally invasive esophagectomy. We compared the postoperative outcomes including body composition between the old perioperative program and the new one that aimed to shorten postoperative length of stay (LOS). Compliance-related clinical factors were also examined. RESULTS: From 252 patients, 129 underwent the old program and 123 the new program. Postoperative LOS, postoperative complications, and hospital costs were reduced with the new program. Body weight loss was significantly improved with the new program at discharge and 3-months after esophagectomy (94.9% vs. 96.6%, p=0.013, 89.5% vs. 91.1%, p=0.028, respectively). Patients in the new program had better body composition at discharge than those in the old program [body fat mass (91.6% vs. 94.1%), lean body mass (95.2% vs. 97.2), and skeletal muscle mass (95.3% vs. 97.0%)]. Major reasons for incompliance were dysphagia, pneumonia, and anastomotic leakage. Multivariate analysis revealed that age ≥70 years at surgery and sex (male) were independent risk factors for incompliance with the postoperative program. CONCLUSION: The new ERAS program aimed to shorten postoperative LOS had clinical benefits in body composition early after esophagectomy. Personalized ERAS programs based on age might lead to better postoperative outcomes because of low compliance rates for older patients.

Long-Term Feasibility of Rescue Reconstruction for Isolated Bile Ducts With Using Cystic Duct in Living Donor Liver Transplantation.

BACKGROUND: The isolated bile duct is sometimes observed in the right liver graft of living donor liver transplantation (LDLT). Even though, as a rescue option, it is known to use the recipient's cystic duct (CyD) for duct-to-duct anastomosis, the long-term feasibility of rescue duct-to-CyD (D-CyD) anastomosis remains unclear. METHODS: We prospectively collected data in the right liver-LDLT cohort and compared rescue D-CyD anastomosis (n = 4) with standard duct-to-hepatic duct (D-HD, n = 45) anastomosis (D-CyD group, n = 4). RESULTS: The observation period was over 5 years (range, 68-171 mo) after LDLT. The D-CyD group included the following anastomosis procedures: anastomosis between the intrahepatic bile duct of the graft and the CyD of the recipient and anastomosis between the posterior HD and the CyD. Surgical outcomes between the 2 groups are similar, excluding the time for the biliary reconstruction (D-CyD, 116 ± 13 min vs D-HD, 57 ± 3 min). During the period, one recipient in the D-CyD group exhibited postoperative biliary stricture and biliary stone, and 6 recipients underwent those complications in the D-HD group (D-CyD, 25.0% vs D-HD, 13.3%) All recipients in the D-CyD group are presently alive and have not experienced liver dysfunction. CONCLUSIONS: Our findings suggest that rescue D-CyD anastomosis for an isolated bile duct in a right liver LDLT is acceptable as a life-saving option in terms of long-term feasibility.

Preoperative FDG-Positive Lymph Nodes Predict the Postoperative Prognosis in Resectable Biliary Tract Cancers.

BACKGROUND: F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) has been used to diagnose and stage various cancers. In regard to biliary tract cancer (BTC), due to cholangitis it is difficult to evaluate FDG uptake caused by cancer. We previously showed that FDG-positive lymph nodes (LNs) of resectable BTC had a possibility of predicting postoperative prognosis. OBJECTIVE: This study aimed to validate the usability of FDG-PET for LNs using another cohort and to investigate in detail the relationship between FDG-positive LNs and the prognosis of BTC. METHODS: We measured the preoperative maximum standardized uptake value (SUVmax) at each of the 190 surgically dissected LN areas in 67 patients and investigated the prognosis using our previously determined SUVmax cut-off values of ≥ 2.8. RESULTS: Regarding the prognosis of patients with resectable BTC, a LN SUVmax ≥ 2.8 [PET N (+)] was a poor prognostic factor for recurrence-free survival (RFS) compared with a LN SUVmax < 2.8 [PET N (-)]. It was confirmed that the hazard ratio forest plot [PET N (+)/PET N (-)] for RFS indicated a similar tendency among subcategories. Moreover, we investigated patients with pN0 disease and demonstrated that the PET N (+) group also had a significantly worse RFS outcome compared with the PET N (-) group. Recurrence of the PET N (+) group has significantly occurred more often in LNs than that of the PET N (-) group. CONCLUSION: High LN SUVmax was confirmed to be the preoperatively diagnosed prognostic risk factor for RFS in resectable BTC and could be helpful for clinical decision making regarding the perioperative treatment strategy.

Modified Cavoportal Hemitransposition for Severe Portal Vein Thrombosis Contributed to Long-term Survival After Deceased Donor Liver Transplantation-Insight Into Portal Modulation for Improving Survival: A Case Report.

BACKGROUND: Severe/massive portal vein thrombosis (PVT) deteriorates peri-liver transplantation outcomes. Cavoportal hemitransposition (CPHT) is a rescue procedure for severe PVT, and short-term outcomes have been well studied. However, CPHT is associated with some long-term issues caused by portal flow modulation via extraordinary reconstruction. We describe a patient with Yerdel grade 4 PVT who underwent a liver transplant and achieved long-term survival with CPHT and a portosystemic shunt. CASE REPORT: A 50-year-old man with liver cirrhosis underwent a deceased donor liver transplant. Preoperative examinations indicated Yerdel grade 4 PVT; thus, we planned a CPHT. In liver transplant surgery, we confirmed diffusely complete PVT and removed them as possible. After placing a liver graft, we performed CPHT and confirmed that the graft received sufficient portal vein flow. However, the gastroepiploic vein pressure increased significantly. Therefore, we added a portosystemic shunt between the splenic vein and the inferior vena cava, and the pressure improved. The patient was discharged after an uneventful hospital stay, and he reported no unfavorable events for over 12 years. CONCLUSIONS: This case study suggested that a modified CPHT with a portosystemic shunt for Grade 4 PVT was useful in preventing post-liver transplant PVT development and improved the outcome.

Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). METHODS: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. RESULTS: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC-GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. CONCLUSION: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.