Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Clinical significance of colonoscopy before laparoscopic bariatric/metabolic surgery in Japanese patients.

PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma.

BACKGROUND: The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA. METHODS: Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502. RESULTS: S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502. CONCLUSION: Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.

Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors.

BACKGROUND: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.

Appropriate indications for laparoscopic repeat hepatectomy.

BACKGROUND: Laparoscopic repeat hepatectomy (LRH) has increased, but appropriate indications for LRH are unclear. This study aimed to clarify appropriate indications for LRH. METHODS: We retrospectively compared surgical outcomes between open RH (ORH) (n = 57) and LRH (n = 40) groups. To detect difficult cases of complete pure LRH, we examined patients with unplanned intraoperative hand-assisted laparoscopic surgery (HALS)/open conversion (n = 6). RESULTS: In the LRH versus ORH group, as previous hepatectomy, laparoscopic (75% vs. 12%, p < 0.001) and partial hepatectomy (Hr0) (73% vs. 37%, p = 0.002) were more frequently performed, and as RH procedure, partial hepatectomy (Hr0) (88% vs. 47%, p = 0.0002) was more frequently performed. S1 tumor cases were higher in ORH group (11% vs. 0%), but S2-6 cases were higher in LRH group (73% vs. 49%) (p = 0.02). In LRH group, compared to the pure LRH patients, HALS/open conversion patients underwent significantly more previous hepatectomy with more than lobectomy (Hr2-3) (33% vs. 2.9%, p = 0.033) and more RH procedures with segmentectomy (HrS) (33% vs. 2.9%, p = 0.03). All LRH requiring a repeat hepatic hilar approach were HALS conversions. CONCLUSION: Appropriate indications for LRH were previous hepatectomy was laparoscopic partial hepatectomy (Hr0), and RH procedure was partial hepatectomy (Hr0) for S2-6 tumor location. When RH is more than segmentectomy (HrS) requiring a repeat hepatic hilar approach, planned HALS or ORH may be a better approach than pure LRH.

Clinical Efficacy of Pre-Hospital Electrocardiogram Transmission in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Rapid reperfusion by primary percutaneous coronary intervention (pPCI) is an established strategy for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Pre-hospital electrocardiogram (PH-ECG) transmission by the emergency medical services (EMS) facilitates timely reperfusion in these patients. However, evidence regarding the clinical benefits of PH-ECG in individual hospitals is limited.This retrospective, observational study investigated the clinical efficacy of PH-ECG in STEMI patients who underwent pPCI. Of a total of 382 consecutive STEMI patients, 237 were enrolled in the study and divided into 2 groups: a PH-ECG group (n = 77) and non-PH-ECG group (n = 160). Door-to-balloon time (D2BT) was significantly shorter in the PH-ECG group (66 [52-80] min), compared to the non-PH-ECG group (70 [57-88] minutes, P = 0.01). The 30-day all-cause mortality rate was 6% in the PH-ECG group, which was significantly lower than that in the non-PH-ECG group (16%) (P = 0.037, hazard ratio [HR]: 0.38, 95% CI: 0.15-0.98). This trend was particularly evident in severely ill patients when stratified by GRACE score.The use of PH-ECG improved the survival rate of STEMI patients undergoing pPCI due to the improved pre-arrival preparation based on the EMS information. Coordination between EMS and PCI-capable institutes is essential for the management of PH-ECG.

Distinct propagation patterns of right pulmonary veins through multiple epicardial connections during right atrial pacing and sinus rhythm.

A 47-year-old man with symptomatic paroxysmal atrial fibrillation (AF) underwent AF ablation. Activation maps during right atrial pacing and sinus rhythm before the ablation revealed distinctive left atrial (LA) propagations with multiple LA breakthrough sites via epicardial connections. A wide area circumferential ablation was not able to achieve a right pulmonary vein (RPV) isolation and required an inner PV ablation to isolate the RPV. Activation maps during different rhythms before the ablation may be helpful to unmask multiple epicardial connections between the RPV and right atrium.

Risk factors of unplanned intraoperative conversion to hand-assisted laparoscopic surgery or open surgery in laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection (LLR) is possible in many patients, but pure LLR is sometimes difficult to complete, and unplanned intraoperative hand-assisted laparoscopic surgery (HALS) or open conversion is sometimes necessary. However, appropriate indications and timing for conversion are unclear. This study aimed to clarify the indications for HALS and open conversion from pure LLR. METHODS: We collected data from 208 patients who underwent LLR from January 2010 to February 2021 in our department. We retrospectively examined these data between cases of unplanned intraoperative HALS conversion, open conversion, and pure LLR, and clarified risk factors and indications for HALS or open conversion. RESULTS: There were 191 pure LLRs, nine HALS conversions, and eight open conversions. In the HALS conversion group versus pure LLR group, body mass index (BMI) (27.0 vs. 23.7 kg/m2, p = 0.047), proportions of patients with history of upper abdominal surgery (78% vs. 33%; p = 0.006), repeat hepatectomy (56% vs. 15%; p = 0.002), S7 or S8 tumor location (67% vs. 35%; p = 0.049), and difficulty score (DS) ≥ 7 (56% vs. 19%; p = 0.008) were significantly higher, and surgical time (339 vs. 239 min; p = 0.031) was significantly longer. However, postoperative states were not significantly different between the two groups. The BMI cutoff value for risk of unplanned intraoperative conversion determined by receiver operating characteristic curve analysis was 25 kg/m2, and the proportion of patients with BMI ≥ 25 kg/m2 (89% vs. 31%, p < 0.001) was significantly higher in the HALS conversion versus pure LLR group. In the open conversion group, although there were no significant differences compared to the HALS group in clinicopathological factors except for sex, blood loss was greater (1425 vs. 367 mL; p < 0.001). CONCLUSION: Risk factors for considering HALS during LLR were patients with a history of upper abdominal surgery including repeat hepatectomy, BMI ≥ 25 kg/m2, S7 or S8 tumor location, DS ≥ 7, and prolonged surgical time. Furthermore, uncontrollable intraoperative bleeding was an indication for open conversion.

Surgical and oncological outcomes of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma.

PURPOSE: To compare the outcomes of laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) with those of open RAMPS (O-RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We reviewed, retrospectively, the medical records of 50 patients who underwent RAMPS for PDAC without resection of major vessels and adjacent organs between 2007 and 2019, and analyzed the relationship between the operative method and surgical and oncological outcomes. RESULTS: Nineteen of the 50 patients underwent L-RAMPS and 31 patients underwent O-RAMPS. L-RAMPS was associated with significantly less blood loss (P = 0.034) but a longer operative time (P = 0.001) than O-RAMPS. There were no significant differences in patient characteristics, tumor factors, or postoperative course; or in the rates of recurrence-free survival (P = 0.084) or overall survival (P = 0.402) between the L-RAMPS and O-RAMPS groups. CONCLUSION: L-RAMPS for PDAC resulted in less blood loss but a longer operative time than O-RAMPS. Although L-RAMPS may be feasible, the operative time needs to be reduced by standardizing the procedure.

Predictors of early withdrawal from follow-up visits after laparoscopic sleeve gastrectomy in a Japanese institution.

PURPOSE: Postoperative weight loss is related to postoperative adherence to follow-up after bariatric/metabolic surgery, but many patients stop attending follow-up visits early. The aim of this study was to clarify predictors of early withdrawal from follow-up after laparoscopic sleeve gastrectomy (LSG) in a Japanese institution. METHODS: One hundred and fifty-three patients who underwent LSG were retrospectively included in this study. Multivariate analysis was performed to evaluate independent predictors of withdrawal from follow-up visits within 12 months after LSG among significant or nearly significant factors in the univariate analyses. The discrimination power of significant factors was estimated using area under the receiver operating characteristic curve (AUC). RESULTS: Within 12 months after LSG, 25 of the 153 patients withdrew from follow-up visits. The multivariate analysis showed that age was the only significant predictor of withdrawal. The AUC for age was 0.685, and the cut-off value was < 40 years. The younger patients (< 40 years old) had a significantly higher rate of withdrawal compared with the older patients (≥ 40 years) (27.0% vs. 8.9%). CONCLUSION: Older Japanese patients (≥ 40 years old) may be better candidates for LSG. We consider it significant to continue to emphasize the importance of follow-up visits in younger patients after LSG.

Impact of Frailty on Bleeding Events Related to Anticoagulation Therapy in Patients With Atrial Fibrillation.

BACKGROUND: Although anticoagulation is the key treatment to prevent stroke in patients with atrial fibrillation (AF), including elderly patients, anticoagulation is sometimes withheld for elderly people because of concerns about frailty. However, it remains unknown whether frailty increases bleeding events.Methods and Results:A total of 120 consecutive non-valvular AF patients admitted with symptoms of AF or congestive heart failure were included in this study. Frailty was assessed using the Cardiovascular Health Study (CHS) frailty index. We performed a retrospective analysis of the risk factors associated with major bleeding events. After a median follow-up of 518 days, major bleeding events occurred in 17 (14.2%) patients. Patients with major bleeding events had a higher CHS frailty index (P=0.015). The cutoff value for high-risk CHS frailty index was 2 (area under the ROC curve: 0.68 [95% confidence interval (CI): 0.57-0.78]). The event-free rates at 2 years were 97.6% (95% CI: 83.9-99.7) in patients with a CHS frailty index <2 and 59.6% (95% CI: 27.9-81.0) for those with a CHS frailty index ≥2 (P<0.001). CONCLUSIONS: Frailty is associated with increased bleeding events related to anticoagulant therapy in patients previously hospitalized with AF. Greater care should be taken with patients with a CHS frailty index ≥2.

Short internal pancreatic stent reduces pancreatic fistula in pancreatoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a major complication of pancreatoduodenectomy (PD). A pancreatic stent is usually used for drainage of the pancreatic duct, but the best type of the stent remains unclear. The aim of this study was to investigate perioperative factors and their influence on the risk of CR-POPF following PD. METHODS: From 2006 to 2019, the records of 246 patients who underwent PD were retrospectively reviewed, and the relationship between perioperative factors including type of pancreatic stent and CR-POPF was investigated. External or internal pancreatic stents were used for drainage of the pancreatic duct, and the internal stent was inserted 1 cm into the jejunum to decrease stent obstruction. RESULTS: External and internal pancreatic stents were used in 137 and 109 patients, respectively. Multivariate analysis revealed that the diameter of the main pancreatic duct (odds ratio = 0.292, 95% confidence interval = 0.140-0.605, P = 0.001), diagnosis (odds ratio = 3.359, 95% confidence interval = 1.498-7.693, P = 0.003), and type of pancreatic stent (odds ratio = 0.435, 95% confidence interval = 0.203-0.934, P = 0.033) were independent factors related to CR-POPF after PD. Internal stent was associated with a low rate of CR-POPF (P < 0.001) and short postoperative hospital stay (P < 0.001) compared to external stent. CONCLUSION: A short pancreatic internal stent could decrease the incidence of CR-POPF.

Relationship between the tumor location and clinicopathological features in left-sided pancreatic ductal adenocarcinoma.

PURPOSE: Although the same distal pancreatectomy (DP) is performed regardless of the location of left-sided pancreatic ductal adenocarcinoma (PDAC), the clinicopathological features may differ depending on the tumor location. The present study investigated the relationship between the tumor location and clinicopathological features in patients with left-sided PDAC. METHODS: The records of 59 patients who underwent DP for PDAC were enrolled. The relationship between the tumor location and clinicopathological features was investigated. The tumor location was classified into three groups according to the 7th AJCC/UICC TNM classification: body (Pb), body and tail (Pbt), and tail (Pt). RESULTS: Tumors were located at the Pb in 26 patients, Pbt in 15, and Pt in 18. There was no metastasis to the lymph nodes around the common hepatic artery in Pt. The rate of peritoneal dissemination in the Pt was higher than that in the Pb (P = 0.034) or Pbt (P = 0.002). There were no significant differences in the overall survival among the three groups. CONCLUSION: There was no metastasis to the lymph nodes around the common hepatic artery, and peritoneal dissemination was the most common site of recurrence in Pt tumors.

Port-sharing techniques for laparoscopic cholecystectomy and sleeve gastrectomy.

In Japan, the number of bariatric surgeries performed has remained low. Thus, concomitant laparoscopic cholecystectomy (LC) with laparoscopic sleeve gastrectomy (LSG) is still relatively uncommon, but is increasing. We developed new port-sharing techniques for LC and LSG, which we performed on 26 obese Japanese patients with gall bladder (GB) diseases, using the LSG trocar arrangement and one additional trocar. We performed LC first, and after exchanging a port for a liver retractor in the epigastrium, we then completed LSG. One patient with an anomalous extrahepatic bile duct required one additional port. The mean LC time was 55 min, and the transition to LSG just after LC was smooth in all the patients. One patient suffered postoperative intraperitoneal hemorrhage, which was managed conservatively. Concomitant LC with LSG using port-sharing techniques is feasible and safe for obese Japanese patients with GB diseases.

[Long‒Term Survival after Lung Resection for Lung Metastasis of Pancreatic Cancer-A Report of Two Cases].

Some reports have shown that the prognosis of recurrent lung metastases after resection of pancreatic cancer is better than that for other organs. We report on 2 cases of long‒term survival after lung resection for lung metastases from pancreatic cancer. Case 1: A 73‒year‒old man underwent distal pancreatectomy for pancreatic body cancer. Adjuvant chemotherapy of S‒1 was administered for 6 months. At 3 years after surgery, 2 small metastatic nodules were detected in the right lung, and the patient underwent thoracoscopic right upper lobectomy. At 5 years and 9 months after the initial surgery, he is alive without recurrence. Case 2: An 81‒year‒old woman underwent pylorus‒preserving pancreatoduodenectomy for pancreatic head cancer. Adjuvant chemotherapy of S‒1 was administered for 4 months. At 1 year and 9 months after surgery, a metastatic nodule was detected in the left upper lung, and the patient underwent thoracoscopic left upper lobectomy. At 4 years and 6 months after initial surgery, radiation therapy was performed for localized bone metastasis. At 5 years and 1 month after the initial surgery, she is alive without other recurrences. In conclusion, recurrent lung metastases of pancreatic cancer with a small number of metastases may result in long‒term survival following resection.

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.

BACKGROUND: Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation. METHODS: We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein ß-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans. RESULTS: Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis. CONCLUSION: Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.

Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: High rate of early recurrence and its predictors.

AIM: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a very rare subtype of primary liver carcinoma; therefore, its clinicopathological characteristics have not yet been elucidated in detail. The aim of the study was to reveal the clinicopathological characteristics and prognostic factors of cHCC-CCA after hepatic resection (HR) METHODS: A total of 124 patients who underwent curative HR for cHCC-CCA between 2000 and 2016 were enrolled in this multi-institutional study conducted by the Kyushu Study Group of Liver Surgery. Clinicopathological analysis was performed from the viewpoint of patient prognosis. RESULTS: A total of 62 patients (50%) had early recurrence within 1.5 years after HR, including 36 patients (58%) with extrahepatic recurrence. In contrast, just four patients (3%) had late recurrence occurring >3 years after HR. The independent predictors of early recurrence were as follows: des-gamma carboxyprothrombin >40 mAU/mL (odds ratio 26.2, P = 0.0117), carbohydrate antigen 19-9>37 IU/l (odds ratio 18.0, P = 0.0200), and poorly differentiated HCC or CCA (odds ratio 11.2, P = 0.0259). CONCLUSIONS: Half of the patients with cHCC-CCA had early recurrence after HR. Preoperative elevation of des-gamma carboxyprothrombin or carbohydrate antigen 19-9 and the existence of poorly differentiated components of HCC or CCA in resected specimens are predictors of its early recurrence.

Fucosyltransferase 8 plays a crucial role in the invasion and metastasis of pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is an aggressive malignancy associated with poor prognosis because of recurrence, metastasis, and treatment resistance. Aberrant glycosylation of cancer cells triggers their migration and invasion and is considered one of the most important prognostic cancer biomarkers. The current study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC. METHODS: Using a lectin microarray, we evaluated glycan expression in 62 PDAC samples. Expression of fucosyltransferase 8 (FUT8), the only enzyme catalyzing core fucosylation, was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model. RESULTS: The microarray data demonstrated that core fucose-binding lectins were significantly higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was significantly higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was significantly associated with lymph-node metastases and relapse-free survival. FUT8 knockdown significantly reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model. CONCLUSIONS: The findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.

Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.