Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

Albumin-indocyanine green evaluation of future liver remnant predicts liver failure after anatomical hepatectomy for hepatocellular carcinoma: A dual-center retrospective study.

Aim: The albumin-indocyanine green evaluation (ALICE) score is a useful predictor of post-hepatectomy liver failure (PHLF); however, its usefulness in combination with future liver remnant (FLR), measured by 3-D volumetry, has not been investigated. This study aimed to investigate the relationship between the ALICE of the FLR (ALICE-FLR) score and severe PHLF. Methods: The clinical data of 215 patients who underwent anatomical hepatectomy for hepatocellular carcinoma without portal vein embolization at two institutes between January 2010 and December 2021 were analyzed retrospectively. PHLF occurrence and severity were determined according to the International Study Group of Liver Surgery's definition. Grades B and C PHLF were defined as severe PHLF. The ALICE-FLR, ALICE scores, and indocyanine green clearance of FLR (ICGK-FLR) were evaluated for severe PHLF prediction. Results: Severe PHLF was observed in 40 patients (18.6%). The areas under the curve (AUCs) for the ALICE-FLR, ALICE scores, ICGK-FLR, and FLR were 0.76, 0.64, 0.73, and 0.69, respectively. The AUC of the ALICE-FLR score was significantly higher than that of the ALICE score. The ALICE-FLR score was identified as an independent predictor of severe PHLF (the odds ratio for every 0.01 increment in the ALICE-FLR score was 1.24; 95% confidence interval, 1.070-1.453; p = 0.004). Among patients with severe PHLF, the ALICE-FLR score was significantly higher in the grade C than in the grade B PHLF group. Conclusion: The combination of liver function models, including indocyanine green, albumin, and FLR is considered compatible for predicting severe PHLF.

Refractory postoperative pancreatic fistula following laparoscopic distal pancreatectomy for pancreatic cancer caused by incomplete pancreas divisum: a case report.

Pancreas divisum (PD) represents a prevalent congenital pancreatic variant, typically arising from the failure of fusion between the ventral and dorsal pancreatic ducts. This condition is frequently associated with recurrent pancreatitis. We herein present a case involving an incomplete PD diagnosis following the identification of a refractory postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (DP) for pancreatic cancer. A 74-year-old female patient, who had undergone laparoscopic DP for pancreatic cancer, developed a POPF accompanied by intraabdominal bleeding, necessitating urgent intervention radiology to avert life-threatening complications. Following this, intraabdominal drainage was performed through an intraoperative drainage root. Subsequent fistulography and endoscopic retrograde pancreatography unveiled the presence of an incomplete PD for the first time. Consequently, a stent was placed in the Santorini duct. However, the volume of pancreatic juice from the intraabdominal drainage tube exhibited no reduction. Despite repeated attempts to access the pancreatic duct via a guidewire through the drainage tube, these endeavors proved futile. Paradoxically, the removal of the external drainage tube led to a recurrence of intraabdominal abscess formation. Consequently, reinsertion of the drainage tube became imperative. Consideration was given to draining the abscess under endoscopic ultrasonography and performing pancreatic duct drainage. However, due to the diminution of the abscess cavity through the external fistula drainage procedure, coupled with the absence of pancreatic duct dilation and its tortuous course, it was deemed a formidable challenge. the patient necessitated a lifestyle adaptation with a permanently placed percutaneous drainage tube.

Dorsal approach in laparoscopic extended left hemi-hepatectomy: A case series.

RATIONALE: The utility of the dorsal approach has been reported for laparoscopic left hemi-hepatectomy. PATIENT CONCERNS: The aim of the present study is to show the usefulness of the dorsal approach for laparoscopic extended left-hemi-hepatectomy while ensuring safe identification of hepatic veins and dissection of the dorsal tumor margin. DIAGNOSES: Tumors requiring extended left hemi-hepatectomy. INTERVENTIONS: After mobilization of the lateral sector and division of the Arantius plate, parenchyma above the Arantius plate is removed to expose the root of the middle hepatic vein and left hepatic vein. Each of these veins can be isolated separately either intra- or extra-hepatically. After removing the parenchyma on the cranial side of the left Glissonean pedicle continuous with the exposed hepatic veins, the left Glissonean pedicle is isolated using the Glissonean pedicle transection method. After division of the left hepatic vein and Glissonean pedicle, segment 4 (in which the main part of the tumor is commonly located) is dissected from the anterior plane of the paracaval portion of the caudate lobe by the dorsal approach, along with the hepatic hilum. Following dissection of the dorsal side of the tumor, and division of parenchyma from the anterior edge of the liver, the anterior Glissonean branches and middle hepatic vein are divided safely and the specimen is resected. OUTCOMES: Three patients underwent laparoscopic extended left hemi-hepatectomy, with no open conversions. Operative time and blood loss were 331 (concomitant with another partial hepatectomy), 277, and 315 minutes; and 200, 100, and 100 g, respectively. The postoperative courses were uneventful. LESSONS: The dorsal approach maximizes the advantages of laparoscopic extended left hemi-hepatectomy and can be performed safely.

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

PURPOSE: Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. METHODS: We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. RESULTS: Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). CONCLUSION: Prolonged WIT is associated with intractable PBS following LDLT.

C-Reactive Protein-to-Albumin Ratio to Predict Tolerability of S-1 as an Adjuvant Chemotherapy in Pancreatic Cancer.

Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs.

Novel embryological classifications of hepatic arteries based on the relationship between aberrant right hepatic arteries and the middle hepatic artery: A retrospective study of contrast-enhanced computed tomography images.

BACKGROUND: Variations in hepatic arteries are frequently encountered during pancreatoduodenecomy. Identifying anomalies, especially the problematic aberrant right hepatic artery (aRHA), is crucial to preventing vascular-related complications. In cases where the middle hepatic artery (MHA) branches from aRHAs, their injury may lead to severe liver ischemia. Nevertheless, there has been little information on whether MHA branches from aRHAs. This study aimed to investigate the relationship between aRHAs and the MHA based on the embryological development of visceral arteries. METHODS: This retrospective study analyzed contrast-enhanced computed tomography images of 759 patients who underwent hepatobiliary-pancreatic surgery between January 2011 and August 2022. The origin of RHAs and MHA courses were determined using three-dimensional reconstruction. All cases of aRHAs were categorized into those with or without replacement of the left hepatic artery (LHA). RESULTS: Among the 759 patients, 163 (21.4%) had aRHAs. Five aRHAs patterns were identified: (Type 1) RHA from the gastroduodenal artery (2.7%), (Type 2) RHA from the superior mesenteric artery (SMA) (12.7%), (Type 3) RHA from the celiac axis (2.1%), (Type 4) common hepatic artery (CHA) from the SMA (3.5%), and (Type 5) separate branching of RHA and LHA from the CHA (0.26%). The MHA did not originate from aRHAs in Types 1-3, whereas in Type 4, it branched from either the RHA or LHA. CONCLUSIONS: Based on the developmental process of hepatic and visceral arteries, branching of the MHA from aRHAs is considered rare. However, preoperative recognition and intraoperative anatomical assessment of aRHAs is essential to avoid injury.

Clamp-crushing Pancreatic Transection in Minimally Invasive Distal Pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy has become a widely accepted procedure for tumors located in the pancreatic body or tail. However, pancreatic transection by linear stapler is generally avoided for pancreatic body tumors located above the portal vein because the surgical margin width is narrowed after taking into account the cutting allowance for insertion of the stapling device. Herein, we report a parenchymal clamp-crushing procedure that provides a sufficient surgical margin in pancreatic transection. METHODS: Two patients with suspected early pancreatic cancer underwent pancreatic transection using the clamp-crushing procedure. The planned pancreatic transection line was set just to the left of the gastroduodenal artery in both cases. Robotic and laparoscopic distal pancreatectomy were performed in 1 patient each. Patients were positioned supine with split legs. Parenchymal transection was performed with crushing by VIO 3 (ERBE Elektromedizin) operated in softCOAG Bipolar mode with Effect 2/modulation 50. After crushing, remnant tissue was cut in autoCUT Bipolar mode operated by VIO 3 with Effect 2/modulation 50, or cut after secured by clipping. RESULTS: The surgical duration was 253 and 212 minutes, and estimated blood loss was 0 and 50 mL in the 2 patients, and both were discharged with uneventful courses. Pathologic examination confirmed a negative surgical margin in both patients. CONCLUSION: Clamp-crushing pancreatic transection for distal pancreatectomy might be a suitable treatment option for achieving sufficient surgical margin in pancreatic body tumors located close to the portal vein.

Impact of the inferior vena cava morphology on fluid dynamics of the hepatic veins.

We reported previously that a large vertical interval between the hepatic segment of the inferior vena cava (IVC) and right atrium (RA), referred to as the IVC-RA gap, was associated with more intraoperative bleeding during hemi-hepatectomy. We conducted a computational fluid dynamics (CFD) study to clarify the impact of fluid dynamics resulting from morphologic variations around the liver. The subjects were 10 patients/donors with a large IVC-RA gap and 10 patients/donors with a small IVC-RA gap. Three-dimensional reconstructions of the IVC and hepatic vessels were created from CT images for the CFD study. Median pressure in the middle hepatic vein was significantly higher in the large-gap group than in the small-gap group (P = 0.008). Differences in hepatic vein pressure caused by morphologic variation in the IVC might be one of the mechanisms of intraoperative bleeding from the hepatic veins.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

OBJECTIVE: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. RESULTS: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. CONCLUSION: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Diagnostic value of quantification of cell-free DNA for suspected gallbladder cancer.

Background and Aim: An accurate preoperative diagnosis as the basis for deciding the most appropriate surgical procedure is essential for patients with suspected gallbladder cancer (GBC). The aim of this study was to investigate the usefulness of cell-free DNA (cfDNA) for the preoperative detection of ≥T2 invasion in patients with suspected GBC. Methods: Twenty-four patients who underwent resection for suspected GBC were enrolled. The concentration of cfDNA obtained from blood samples preoperatively was measured and evaluated in two distributions. The first peak (less than 200 base pairs) of cfDNA distribution was defined as the shorter fragment cfDNA, considered to originate mainly from apoptosis; and the second peak (200 base pairs or more) was defined as the longer fragment cfDNA, originating mainly from necrosis. Results: Pathological analysis identified benign disease in 12 patients and GBC in 12 patients, of whom 6 patients had ≥pT2 GBC. Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 were significantly higher in the ≥pT2 GBC group than in the benign/

Geriatric Nutritional Risk Index Predicts Tolerability of S-1 as Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Surgery plus adjuvant chemotherapy (AC) for resectable pancreatic ductal adenocarcinoma (PDAC) has been shown to prolong survival compared with surgery alone. Thus, it is of clinical importance that these patients receive a continuous dose of S-1. The aim of this study was to examine whether the geriatric nutritional risk index (GNRI) is a predictor for the completion of S-1 as AC for PDAC. METHODS: Seventy-seven patients who were administered S-1 as AC after pancreatectomy for PDAC between January 2010 and October 2021 were retrospectively enrolled. Predictive markers were statistically analyzed for S-1 completion, which was defined as continued oral administration with relative dose intensity of >80%. RESULTS: Patients were divided into the S-1 complete group (n = 55; 71.4%) and S-1 incomplete group (n = 22; 28.6%). There was a significant association of higher GNRI ( P = 0.013) at the onset of AC with the completion of S-1. Receiver operating characteristic curve analysis revealed 94.4 as the optimal cutoff value of GNRI for predicting the completion of S-1. Univariate and multivariate analyses confirmed that GNRI >94.4 was independently associated with the completion of S-1 ( P = 0.007). CONCLUSIONS: High GNRI value is a predictive marker for the completion of S-1 as AC for PDAC.

Living Donor Liver Transplantation in Patients with Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies Using Preoperative Desensitization Therapy According to Intensity of Donor-Specific Antibodies: A Single-Center Study.

BACKGROUND In liver transplantation (LT), preoperative desensitization therapy is considered necessary in patients positive for donor-specific anti-human leukocyte antigen antibodies (DSAs). However, the relationship between DSA intensity and the necessary desensitization therapy is unclear. MATERIAL AND METHODS A total of 37 adult living donor (LD) LTs performed between January 2016 and March 2022 were examined. Mycophenolate mofetil (MMF) was administered preoperatively in DSA-positive cases with positive lymphocyte cross-matching who underwent LDLT. In those with strongly positive DSA (mean fluorescence intensity 10 000), rituximab was administered 2 weeks before LDLT in addition to MMF. Cross-reactive epitope group antigen (CREG)-alone-positive cases were also treated with preoperative MMF when lymphocyte cross-matching was positive. RESULTS Of the 37 patients, 9 were DSA-positive, 7 were CREG-alone-positive, and the others were double-negative. Of 9 DSA-positive cases, desensitization therapy was performed in 7, among which rituximab administration was performed in 3 strongly DSA-positive cases. Of 7 CREG-alone-positive cases, 2 were lymphocyte cross-match-positive and underwent desensitization therapy. The 1-year survival rate was 100% in both DSA- and CREG-alone-positive cases. The frequency of T-cell mediated rejection in DSA-positive, CREG-alone-positive, and double-negative cases was 22%, 43%, and 29%, respectively, with no significant difference. Antibody-mediated rejection occurred in only 1 patient, who was strongly DSA-positive and blood-group incompatible. There was also no significant difference among the 3 groups in terms of the frequency of biliary complications or 90-day mortality. CONCLUSIONS Satisfactory LDLT results were achieved in DSA- and CREG-alone-positive cases following desensitization therapy.

Demethylation in promoter region of severely damaged hepatocytes enhances chemokine receptor CXCR4 gene expression.

The liver is known to possess remarkable regenerative potential, but persistent inflammation or severe acute injury can lead to liver fibrosis and incomplete regeneration, ultimately resulting in liver failure. Recent studies have shown that the axis of two types of CXCL12 receptors, CXCR4 and CXCR7, plays a crucial role in liver fibrosis and regeneration. The present study aimed to investigate the regulatory factors involved in CXCR4 expression in injured liver. Immunohistochemical screening of liver tissue samples collected during liver transplantation revealed a reciprocal expression pattern between CXCR4 and MeCP2. An in vitro system involving cultured cell lines and H2O2 treatment was established to study the impact of oxidative stress on signaling pathways and epigenetic alterations that affect CXCR4 mRNA expression. Operating through distinct signaling pathways, H2O2 treatment induced a dose-dependent increase in CXCR4 expression in both hepatocyte- and intrahepatic cholangiocyte-derived cells. Treatment of the cells with trichostatin and azacytidine modulated CXCR4 expression in hepatocytes by modifying the methylation status of CpG dinucleotides located in a pair of TA repeats adjacent to the TATA box of the CXCR4 gene promoter. Only MeCP2 bound to oligonucleotides representing the TATA box region when the cytosine residues within the sequence were methylated, as revealed by electrophoretic mobility shift assay (EMSA). Methylation-specific PCR analysis of microdissected samples revealed a correlation between the loss of CpG methylation and the upregulation of CXCR4 in injured hepatocytes, replicating the findings from the in vitro study. Besides the conventional MEK/ERK and NF-κB signaling pathways that activate CXCR4 in intrahepatic cholangiocytes, the unique epigenetic modifications observed in hepatocytes might also contribute to a shift in the CXCR4-CXCR7 balance towards CXCR4, leading to irreversible liver injury and fibrosis. This study highlights the importance of epigenetic modifications in regulating CXCR4 expression in liver injury and fibrosis.

Epstein-Barr Virus-Associated Latent Malignant Lymphoma With Acute Exacerbation After Living Donor Liver Transplantation: Case Report.

Concomitant malignant lymphoma at the time of transplantation is usually considered a contraindication to liver transplantation (LT). We report a case of Epstein-Barr virus (EBV)-associated malignant lymphoma that was latent preoperatively and rapidly became aggravated after LT. A 69-year-old man was referred to our hospital with an exacerbation of abdominal distension due to polycystic liver. As cystic infection, ascites, and deteriorated liver reserve function occurred after hepatic artery embolization, he underwent living-donor LT with his daughter as the donor. His respiratory condition worsened, and he was moved to the intensive care unit on postoperative day 34. Histopathologic examination of the excised liver returned around the same time revealed findings suggestive of EBV-associated malignant lymphoma in lymph nodes near the gallbladder. Subsequent computed tomography scans showed apparent neoplastic lesions in the abdominal cavity and worsening pleural effusion and ascites. Numerous atypical lymphocytes were observed in the pleural effusion and ascites, and the patient was diagnosed with exacerbation of EBV-associated malignant lymphoma. He was treated unsuccessfully with rituximab and died 66 days after LT. Caution should be exercised in elderly immunocompromised transplant candidates who may have comorbid EBV-associated lymphoproliferative disease.

Association Between Preoperative Pancreatic Exocrine Function and Pathological Evaluation With Postoperative Pancreatic Fistulas Following Pancreaticoduodenectomy.

BACKGROUND/AIM: Postoperative pancreatic fistula (POPF) may cause severe complications. In this study, risk factors for postoperative pancreatic fluid leakage after pancreaticoduodenectomy (PD) were investigated, with a particular focus on preoperative pancreatic exocrine function and pathological evaluations of the resected pancreas. PATIENTS AND METHODS: A total of 67 patients underwent the N-benzoyl-L-tyrosyl-para-aminobenzoic acid (BT-PABA) test and PD in our department between June 2003 and March 2018. The endpoint was the development of POPF. Patients' clinical characteristics, preoperative test results, surgery-related parameters, and pathological evaluations of the resected samples were investigated. Preoperative pancreatic exocrine function was evaluated by the BT-PABA test, and the proportion of residual acinar tissue and the fibrosis rate of the resected pancreatic tissue were assessed. RESULTS: 17 (25.4%) patients with Grade B and C POPF were compared with 50 patients without POPF. On univariate analysis, pancreatic carcinoma (p=0.028), BT-PABA test results higher than 66.3% (p=0.030), and main pancreatic duct (MPD) diameter lower than 5.0 mm (p=0.006) were identified as risk factors for postoperative pancreatic fluid leakage. On multivariate analysis, pancreatic carcinoma (p=0.008), BT-PABA test results higher than 66.3% (p=0.036), MPD diameter lower than 5.0mm (p=0.029) were significant risk factors. BT-PABA test results have a moderate correlation with both the proportion of pancreatic acinar tissue (r=0.421, p=0.028) and the pancreatic fibrosis rate (r=-0.443, p=0.021). CONCLUSION: The preoperative BT-PABA test results higher than 66.3% were an independent risk factor for POPF. This suggests that the development of POPF may be attenuated by diminished exocrine function with poor pancreatic fluid flow and the progression of fibrosis.

Early Postoperative Varicella-Zoster Virus Encephalitis After Adult ABO-Incompatible Living Donor Liver Transplantation: A Case Report.

There have never been any reports of adult varicella-zoster virus (VZV) encephalitis cases. Here, we report a case of VZV encephalitis after adult ABO-incompatible living donor liver transplantation (LDLT). A 38-year-old man with decompensated liver cirrhosis caused by the hepatitis C virus was referred to our hospital as an LDLT candidate. Rituximab was administered 3 weeks before the operation, and immunosuppression agents were administered 1 week before the LDLT. Plasma exchange was performed 3 times before the LDLT. The right lobe from his mother's liver was used for the ABO-incompatible LDLT. On postoperative day (POD) 9, vascular stenting for intraabdominal bleeding from the common hepatic artery was performed by interventional radiology and was followed by re-laparotomy for abdominal drainage of the hematoma. However, there were various degrees of continued bleeding thereafter. On POD 12, due to a convulsion seizure with loss of consciousness, the patient was started on anticonvulsant therapy. On POD 15, there was an increased frequency of convulsion attacks and a prolonged loss of consciousness. A lumbar puncture was performed on POD 20 due to the appearance of shingles. The positive polymerase chain reaction of the VZV-DNA from the cerebrospinal fluid was detected, and he was diagnosed with VZV encephalitis. He rapidly regained alertness, and there were no further observed convulsion attacks after administration of a steroid pulse and acyclovir. Brain magnetic resonance imaging performed on 2 subsequent postoperative months showed findings that matched with VZV encephalitis. He was discharged as he had recovered and was ambulatory 3 months after LDLT.

The impact of cystic duct tube on the onset time of postoperative bile leakage after hepatectomy: A propensity score-matched analysis.

BACKGROUND: The cystic duct tube (C-tube) was used to reduce bile leakage (BL) incidence after hepatectomy. Nevertheless, delayed BL is sometimes experienced even using C-tube. This study investigates the impact of C-tube use on the onset time of post-hepatectomy BL. METHODS: Data from 455 consecutive patients who underwent hepatectomy without biliary reconstruction between November 2007 and July 2020 were analyzed retrospectively. A C-tube was used for intraoperative biliary injury or in consideration of BL risk. BL was divided into two groups according to the postoperative onset time: early onset and late onset. To assess the association between C-tube use and BL, propensity score matching in a 1:1 ratio was performed to match BL risk factors between the C-tube and no-C-tube groups. RESULTS: BL occurred in 30 (6.6%) of the 455 included patients. C-tubes were used in 51 patients (11.2%) with open hepatectomy, high-risk hepatectomy, massive blood loss, long operation time, or prophylactic drain placement. After propensity score matching, BL occurred in 17 of 102 patients (16.7%). Early-onset BL occurred significantly less frequently in the C-tube group than in the no-C-tube group (3.9% vs. 15.7%, p = 0.046); however, late-onset BL was more common in the C-tube group (9.8% vs. 3.9%, p = 0.24). Six of seven patients (85.7%) with BL with C-tube use developed BL after C-tube removal. CONCLUSION: C-tube drainage may reduce early-onset BL in cases having risk factors for BL. Conversely, since late-onset BL often occurs after C-tube removal, attention should be paid to those cases.

Simple Symptom-Based Prediction of COVID-19: A Single-Center Study of Outpatient Fever Clinic in Japan.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) symptoms are not fully understood in non-hospitalized individuals in Japan, and COVID-19 differentiation by symptoms alone remained challenging. Therefore, this study aimed to examine COVID-19 prediction from symptoms using real-world data in an outpatient fever clinic. METHODS: We compared the symptoms of COVID-19-positive and negative patients who visited the outpatient fever clinic at Imabari City Medical Association General Hospital and tested for COVID-19 from April 2021 to May 2022. This retrospective single-center study enrolled 2,693 consecutive patients. RESULTS: COVID-19-positive patients had a higher frequency of close contact with COVID-19-infected patients compared with COVID-19-negative patients. Moreover, patients with COVID-19 had high-grade fever at the clinic compared with patients without COVID-19. Additionally, the most common symptom in patients with COVID-19 was sore throat (67.3%), followed by cough (62.0%), which was approximately twice as common in patients without COVID-19. COVID-19 was more frequently identified in patients having a fever (≥37.5℃) with a sore throat, a cough, or both. The positive COVID-19 rate reached approximately half (45%) when three symptoms were present. CONCLUSION: These results suggested that COVID-19 prediction by combinations of simple symptoms and close contact with COVID-19-infected patients might be useful and lead to recommendations for testing of COVID-19 in symptomatic individuals.

The histone demethylase Utx controls CD8+ T-cell-dependent antitumor immunity via epigenetic regulation of the effector function.

CD8+ T cells play a central role in antitumor immune responses. Epigenetic gene regulation is essential to acquire the effector function of CD8+ T cells. However, the role of Utx, a demethylase of histone H3K27, in antitumor immunity remains unclear. In this study, we examined the roles of Utx in effector CD8+ T-cell differentiation and the antitumor immune response. In a murine tumor-bearing model, an increased tumor size and decreased survival rate were observed in T-cell-specific Utx KO (Utx KO) mice compared with wild-type (WT) mice. The number of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) was significantly decreased in Utx KO mice. We found that the acquisition of effector function was delayed and attenuated in Utx KO CD8+ T cells. RNA sequencing revealed that the expression of effector signature genes was decreased in Utx KO effector CD8+ T cells, while the expression of naïve or memory signature genes was increased. Furthermore, the expression of Cxcr3, which is required for the migration of effector CD8+ T cells to tumor sites, was substantially decreased in Utx KO CD8+ T cells. These findings suggest that Utx promotes CD8+ T-cell-dependent antitumor immune responses partially through epigenetic regulation of the effector function.