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A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC. [ABSTRACT FROM AUTHOR]

We herein report a case of heterotopic gastric mucosa in the hilar bile duct. An asymptomatic 58-year-old male was noted to have mild liver dysfunction in March 2009 during the follow-up for angina pectoris. Abdominal-enhanced CT revealed wall thickening from the upper common hepatic bile duct to the left hepatic bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis at the junction of the left hepatic bile duct. Although the patient's serum tumor markers were all within the normal ranges, the possibility of malignant disease of the biliary tree could not be ruled out. Left hepatectomy with the caudate lobe and resection of the extrahepatic bile duct were performed. Histopathologically, the resected specimen showed a polypoid lesion measuring 2 × 2 cm in size that projected into the lumen of the left hepatic bile duct. Microscopic examination revealed this polypoid lesion to be composed of mucous glands resembling gastric fundic glands, with parietal and chief cells. We also review eight other reports of heterotopic gastric mucosa in the biliary tree previously published in the English literature. [ABSTRACT FROM AUTHOR]

It is essential to elucidate the molecular mechanisms underlying liver transplant tolerance and rejection. In cases of mouse liver transplantation between inbred strains, immunological rejection of the allograft is reduced with spontaneous apoptosis without immunosuppressive drugs, which differs from the actual clinical result. This may be because inbred strains are genetically homogeneous and less heterogeneous than others. We exploited outbred CD1 mice, which show highly heterogeneous genotypes among individuals, to search for biomarkers related to immune responses and to construct a model for predicting the outcome of liver allografting. Of the 36 mice examined, 18 died within 3 weeks after transplantation, while the others survived for more than 6 weeks. Whole-exome sequencing of the 36 donors revealed more than 9 million variants relative to the C57BL/6 J reference. We selected 6517 single-nucleotide and indel variants and performed machine learning to determine whether or not we could predict the prognosis of each genotype. Models were built by both deep learning with a one-dimensional convolutional neural network and linear classification and evaluated by leave-one-out cross-validation. Given that one short-lived mouse died early in an accident, the models perfectly predicted the outcome of all individuals, suggesting the importance of genotype collection. In addition, linear classification models provided a list of loci potentially responsible for these responses. The present methods as well as results is likely to be applicable to liver transplantation in humans. [ABSTRACT FROM AUTHOR]

The presence of Helicobacter pylori (H. pylori) in the natural environment has been demonstrated in a number of studies. However, its route of infection into humans is unknown. To study this further, we attempted to detect H. pylori in the natural environment in a region of Japan with a high infection rate. Tap and well water and field soil samples were collected from around the residences of subjects who had participated in an epidemiological survey in 1996. Samples of water from rivers and ponds, and specimens of flies and cow faeces were collected in the region. DNA was extracted from the water, field soil and faecal samples after selective collection of H. pylori by the immunomagnetic-bead separation technique. H. pylori-specific DNA was detected in water, field soil, flies and cow faeces by nested polymerase chain reaction (PCR), and the ureA partial sequences of the PCR products were aligned. The nucleotide sequences of the samples amplified by PCR were highly homologous (96-100%) with the H. pylori sequence in the GenBank database and the H. pylori-specific DNA sequences were highly homologous with each other. These findings suggest the existence of H. pylori in the natural environment and a possible transmission route. [ABSTRACT FROM AUTHOR]

Campylobacter fetus subspecies fetus rarely causes cellulitis associated with bacteremia in debilitated hosts. We have identified this infection in two patients with systemic lupus erythematosus and in one with liver cirrhosis. All three patients had eaten raw beef, liver, or improperly cooked pork before the manifestations of the illness. C. fetus subspecies fetus was recovered from blood and feces from the three patients. This organism was also isolated from a subcutaneous aspirate of the cellulitis lesion in one patient. DNA macrorestriction endonuclease profiles analyzed by pulsed field gel electrophoresis differed for the isolates from the three patients but were identical for the blood and fecal isolates or the aspirate and fecal isolates from each patient. These findings suggest that cellulitis associated with bacteremia arises from ingestion of C. fetus subspecies fetus organisms and that clinicians and microbiologists should be aware of this infection in debilitated hosts. [ABSTRACT FROM PUBLISHER]

• LMNC-NK cells demonstrate enhanced anti-tumor efficacy. • LMNCs exhibit a distinct gene expression profile. • LMNC-derived NK cells from liver perfusate offer promising HCC therapy. Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro , and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions. [ABSTRACT FROM AUTHOR]

Purpose: Various approaches to portal vein (PV) reconstruction have been described; however, there is still scope to improve the safety and efficiency of how PV anastomosis is performed in infants. Methods: We analyzed, retrospectively, the predictive factors for PV reanastomosis during living donor liver transplantation (LDLT) in 117 infants (< 1 year old) with biliary atresia (BA). Results: Twenty-six infants required PV reanastomosis because of intraoperative PV thrombosis in 21 and insufficient PV flow in 5. Univariate analysis identified multiple previous laparotomies and a prolonged anhepatic phase (AHP) as significant risk factors for repeated PV anastomosis. The AHP cutoff value for identifying patients requiring PV reanastomosis was 134 min. Multivariate analysis revealed prolonged AHP > 134 min (odds ratio, 15.98; 95% confidence interval, 5.05–50.6; P < 0.001) as an independent risk factor for repeated PV anastomosis. The plasma D-dimer and fibrinogen degradation product concentration just after reperfusion were significantly higher in patients requiring PV reanastomosis (P < 0.001). Patients requiring reanastomosis of the PV had a higher incidence of PV complications after LDLT than those who did not need PV reanastomosis (P = 0.01). Conclusion: Attempting to minimize the AHP is indispensable for successful LDLT in infants with BA. [ABSTRACT FROM AUTHOR]

• This study demonstrated a significant inverse correlation between donor age and natural killer cell activity. • Liver-resident natural killer cells have potent antitumor activity. • Useful information was found for cell therapy in liver transplantation. Natural killer (NK) cells are involved in innate immunity and have been reported to play an important role in hepatocellular carcinoma recurrence and post-liver transplantation (LT) infection. However, the relationship between donor age and liver-resident NK cell activity remains to be elucidated. We successfully performed NK cell immunotherapy in 19 living donor LT recipients to prevent post-LT bloodstream infections. Liver mononuclear cells (LMNCs) were collected from the liver graft perfusate and stimulated with interleukin 2 for 3 days. Liver-resident NK cells were analyzed using flow cytometry and a chromium release assay before and after cell culture. The median donor age was 44 years (range, 24-64 years). The graft weight was 492 g (range, 338-642 g), and the median number of LMNCs was 584 million cells (range, 240-1472 million cells). The proportion of NK cells before and after culture was 22% and 33%, respectively. A significant correlation was found between graft weight and the number of LMNCs. However, no correlation was found between donor age and the number or percentage of NK cells in the liver. Moreover, donor age showed a significant inverse correlation with NKp46 and NKp44 expression before culture and with NKp44, tumor necrosis factor-related apoptosis-inducing ligand, and CD69 expression after culture. A significant inverse correlation was observed between donor age and NK cell activity in the liver. This information may be useful for cell therapy during LT. [ABSTRACT FROM AUTHOR]