Prognostic significance of hypoxia-inducible factor-1α expression in advanced pharyngeal cancer without human papillomavirus infection.

OBJECTIVE: This study aimed to clarify the association between both hypoxia-inducible factor-1α and glucose transporter type-1 expression and survival outcome in advanced pharyngeal cancer without human papillomavirus infection. METHOD: Twenty-five oropharyngeal and 55 hypopharyngeal cancer patients without human papillomavirus infection were enrolled. All patients had stage III-IV lesions and underwent concurrent chemoradiotherapy or surgery. Hypoxia-inducible factor-1α and glucose transporter type-1 expression were investigated in primary lesions by immunohistochemistry. RESULTS: There were 41 and 39 cases with low and high hypoxia-inducible factor-1α expression, and 28 and 52 cases with low and high glucose transporter type-1 expression, respectively. There was no significant correlation between hypoxia-inducible factor-1α and glucose transporter type-1 expression. In univariate analysis, nodal metastasis, clinical stage and high hypoxia-inducible factor-1α expression, but not glucose transporter type-1 expression, predicted significantly worse prognosis. In multivariate analysis, hypoxia-inducible factor-1α overexpression was significantly correlated with poor overall survival, disease-specific survival and recurrence-free survival. CONCLUSION: High hypoxia-inducible factor-1α expression was an independent risk factor for poor prognosis for advanced human papillomavirus-unrelated pharyngeal cancer.

C-reactive protein : albumin ratio in patients with resectable intrahepatic cholangiocarcinoma.

BACKGROUND: The C-reactive protein : albumin ratio (CAR) has been reported as a novel prognostic marker in several cancers. The aim of this study was to investigate the prognostic value of CAR in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: This was a single-centre retrospective study of patients who underwent surgery for ICC in a university hospital in Japan between 1998 and 2018. CAR, Glasgow Prognostic Score (GPS) and modified GPS (mGPS) were calculated. Their correlation with recurrence-free survival (RFS) and overall survival (OS) was analysed with Cox proportional hazards models. RESULTS: Seventy-two patients were included in the study. Patients were divided into two groups according to the optimal CAR cut-off value of 0·02. CAR above 0·02 was associated with higher carbohydrate antigen 19-9 levels (20·5 versus 66·1 units/ml for CAR of 0·02 or less; P = 0·002), larger tumour size (3·2 versus 4·4 cm respectively; P = 0·031) and a higher rate of microvascular invasion (9 of 28 versus 25 of 44; P = 0·041). RFS and OS were shorter in patients with CAR above 0·02: hazard ratio (HR) 4·31 (95 per cent c.i. 2·02 to 10·63) and HR 4·80 (1·85 to 16·40) respectively. In multivariable analysis CAR above 0·02 was an independent prognostic factor of RFS (HR 3·29 (1·33 to 8·12); P < 0·001), but not OS. CONCLUSIONS: CAR was associated with prognosis in patients who had hepatic resection for ICC.

ANTECEDENTES: La relación proteína C reactiva/albumina (C-reactive protein/albumin ratio, CAR) ha sido descrita como un marcador pronóstico novedoso en varios tipos de cáncer. El objetivo de este estudio fue investigar el valor pronóstico de CAR en pacientes con colangiocarcinoma intrahepático (intrahepatic cholangiocarcinoma, ICC). MÉTODOS: Se trata de un estudio retrospectivo y unicéntrico de pacientes sometidos a cirugía por ICC en un hospital universitario de Japón entre 1998 y 2018. Se calcularon CAR, puntuación pronóstica de Glasgow (Glasgow prognostic score, GPS), y GPS modificada (mGPS). Se analizó su correlación con la supervivencia libre de recidiva (recurrence-free survival, RFS) y con la supervivencia global (overall survival, OS) mediante modelos de riesgos proporcionales de Cox. RESULTADOS: Se incluyeron un total de 72 pacientes. El valor de corte óptimo de CAR fue de 0,02. Los pacientes se dividieron en dos grupos de acuerdo a este valor de corte. La presencia de CAR > 0,02 se asoció con niveles más elevados de antígeno carbohidrato 19-9 (20,5 U/ml versus 66,1 U/ml; P = 0,002), mayor tamaño tumoral (3,2 cm versus 4,4 cm; P = 0,031) y una tasa más elevada de invasión microvascular (32,1% versus 56,8%; P = 0,041). La RFS y OS fueron más cortas en pacientes con CAR > 0,02 (cociente de riesgos instantáneos, hazard ratio, HR 4,305; i.c. del 95% 2,016-10,63 y HR 4,803; i.c. del 95% 1,846-16,40, respectivamente). En los análisis multivariables, CAR de > 0,02 fue un factor pronóstico independiente para RFS (HR 3,286; i.c. del 95% 1,330-8,118; P < 0,001), pero no para la OS. CONCLUSIÓN: CAR se asoció con el pronóstico en pacientes sometidos a resección hepática por ICC.

Right hepatic venous system variation in living donors: a three-dimensional CT analysis.

BACKGROUND: The right hepatic venous system consists of the right hepatic vein (RHV) and inferior RHVs (IRHVs). When the right posterior section is used as a graft for liver transplantation, understanding variations and relationships between the RHV and IRHVs is critical for graft venous return and hepatic vein reconstruction. This study aimed to evaluate variations in the hepatic veins and the relationships between them. METHODS: The medical records and CT images of patients who underwent hepatectomy as liver donors were assessed retrospectively. The relationship between the veins was evaluated by three-dimensional CT. RESULTS: The configuration of the posterior section was classified into one of eight types based on the RHV and IRHVs in 307 patients. Type 1a (103 of 307), type 1b (139 of 307) and type 2a (40 of 307) accounted for 91·9 per cent of the total. The diameter of the RHV extending towards the inferior vena cava had a significant inverse correlation with that of the IRHV (r2  = -0·615, P < 0·001). Type 1a, which had no IRHVs, had the RHV with the largest diameter; conversely, type 2a, which had a large IRHV, had the RHV with the smallest diameter. CONCLUSION: The hepatic venous system of the right posterior section was classified into eight types, with an inverse relationship between RHV and IRHV sizes. This information is useful for segment VII resection or when the right liver is used as a transplant graft.

ANTECEDENTES: El sistema venoso hepático derecho consiste en la vena hepática derecha (right hepatic vein, RHV) y las RHVs inferiores (IRHVs). Cuando se utiliza la sección posterior derecha hepática como injerto para el trasplante hepático, es fundamental conocer las variaciones e interrelaciones entre la RHV y las IRHVs para el retorno venoso del injerto y la reconstrucción de la vena hepática. El objetivo de este estudio fue determinar las variaciones en las venas hepáticas y sus interrelaciones. MÉTODOS: Se evaluaron retrospectivamente las historias clínicas y las imágenes de la tomografía computarizada de los pacientes que se sometieron a una hepatectomía como donantes vivos para trasplante hepático. La interrelación entre las venas se evaluó mediante imágenes de CT tridimensional. RESULTADOS: La configuración de la sección posterior clasificó a 307 pacientes en base a la RHV y a las IRHVs. Se clasificaron en 8 tipos, de los cuales el Tipo 1a (103/307), el Tipo 1b (139/307) y el Tipo 2a (40/307) representaron el 92% del total. El diámetro de la RHV que se extiende hacia la vena cava inferior presentó una correlación inversa significativa con la de las IRHV (r2: −0,632, P < 0,0001). El diámetro mayor de la RHV se observó en el Tipo 1a, que no presentaba IRHVs; por el contrario, el diámetro más pequeño se observó en el Tipo 2a que presentaba una IRHV grande. CONCLUSIÓN: El sistema venoso hepático de la sección posterior derecha se clasificó en 8 subtipos con una relación inversa entre los tamaños de la RHV y las IRHV. Esta información es útil cuando se practica una resección del segmento 7 o cuando se utiliza el hígado derecho como injerto para el trasplante.

Rendezvous Technique Using Double Balloon Endoscope for Removal of Multiple Intrahepatic Bile Duct Stones in Hepaticojejunostomy After Living Donor Liver Transplant: A Case Report.

Cholangitis is a major complication following transplantation. We report a living donor liver transplant (LDLT) patient with cholangitis due to multiple stones in the intrahepatic bile duct during hepaticojejunostomy anastomosis, who was successfully treated with the rendezvous technique using double balloon endoscope. A 64-year-old woman underwent LDLT with right lobe graft and hepaticojejunostomy for Wilson disease. There was bile leakage with biliary peritonitis, which was treated conservatively after transplant. Two years after surgery, she developed reiterated cholangitis due to stenosis of hepaticojejunostomy anastomosis and multiple stones in the intrahepatic bile ducts. Percutaneous transhepatic biliary drainage was performed. The size of the drainage tube was increased, and the anastomotic area was dilated in a stepwise manner using a balloon catheter. The stones were crushed and lithotomy was performed using electronic hydraulic lithotripsy through cholangioscopy. Finally, lithotomy was performed for the remaining stones through endoscopic retrograde cholangiography with the rendezvous technique using the double balloon endoscope. Rendezvous approach with percutaneous transhepatic biliary drainage and double balloon endoscopic retrograde cholangiography was an effective treatment for the multiple intrahepatic stones in hepaticojejunostomy following LDLT with right lobe graft.

Real-Time Ultrasound-Guided Thrombectomy for Extensive Portal Vein Thrombosis in Living Donor Liver Transplantation.

Thrombectomy is a routine or common practice for treating organized portal vein thrombosis (PVT) during liver transplantation. However, this procedure is often performed in a blinded fashion and can result in insufficient thrombectomy or devastating consequences such as injury to the retropancreatic portal vein where prompt repair is very difficult. To overcome these drawbacks for blind thrombectomy, we herein describe a new technique that makes complex thrombectomy safe and easy under direct ultrasound vision. This procedure is readily available and highly reproducible and can be used as the standard procedure for treating extensive PVT.

Functional Analysis of Human Hepatocytes Isolated From Chimeric Mouse Liver.

Chimeric mice with humanized liver were first established by transplanting primary human hepatocytes (PHHs) isolated from a Japanese 27-year-old donor into complementary DNA-urokinase-type plasminogen activator/severe combined immunodeficiency mice. The PHHs from the Japanese donor increased more than 100-fold in the mouse liver, and human hepatocytes purified from the chimeric mouse liver (hcPHs) were successfully transplanted into second-passaged mice. These PHHs and hcPHs can produce human albumin and preserve many liver-specific enzyme genes, which are important for liver function. Interestingly, hepatitis B virus can be infected with these chimeric mice; hepatitis B viral DNA and hepatitis B surface antigen levels were detectable. In conclusion, hcPHs can be an ideal cell source for analysis of human hepatocytes.

Publisher Correction: Immediate tool incorporation processes determine human motor planning with tools.

This corrects the article DOI: 10.1038/ncomms5524.

Successful Recombinant Thrombomodulin Treatment for Thrombotic Microangiopathy After Liver Transplantation: A Case Report.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was administered for 4 days. The patient's clinical symptoms and laboratory data rapidly improved. He has been followed up for 6 months and has not shown any complications. The pathogenesis of TA-TMA is endothelial damage in the vasculature. Recombinant thrombomodulin, an endothelial cell-protecting agent, is a promising new therapeutic choice for TA-TMA after liver transplantation.

Clinical Outcomes of Living Liver Transplantation According to the Presence of Sarcopenia as Defined by Skeletal Muscle Mass, Hand Grip, and Gait Speed.

BACKGROUND: Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined. METHODS: This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods. RESULTS: The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality. CONCLUSIONS: The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients.

In Situ Posterior Graft Segmentectomy for Large-for-Size Syndrome in Deceased Donor Liver Transplantation in Adults: A Case Report.

Large-for-size syndrome (LFSS) is controversial in pediatric living donor liver transplantation patients and is associated with a poor graft outcome. Similar situations in deceased donor liver transplantation (DDLT) in adults have not been reported frequently, and there are no official guidelines worldwide. Deceased donation is extremely limited in Japan, and when a larger liver is allocated for a very sick small recipient in Japan, transplantation with a plan to address LFSS might be necessary. The patient is a 58-year-old female patient who had acute liver failure with coma. The graft-recipient weight ratio (GRWR) was 2.74%. Although the graft was enlarged by reperfusion, the intraoperative Doppler ultrasound, performed after reperfusion, showed sufficient graft in-flow and out-flow. However, when the liver graft was situated appropriately into the right phrenic space supported by the rib cage and diaphragm, the blood flow in the hepatic vein and portal vein was significantly reduced. Graft blood flow did not improve without removing it from the right subphrenic space. Therefore, we decided to perform an in situ graft posterior segmentectomy, so that the graft right lobe was properly accommodated in the patient's right subphrenic space. After the segmentectomy of the graft, an intraoperative Doppler sonogram showed significantly improved blood flow. LFSS could be a significant operative challenge in adult DDLT, especially in areas with limited chances of DDLT. In situ posterior segmentectomy in the demarcated area could be a solution for treating patients with LFSS.

Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation for Primary Sclerosing Cholangitis: Report of a Case.

Although Roux-en Y hepaticojejunostomy was previously recommended for the biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to-duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage biliary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions.

In Situ Procurement of a Recipient's Portal Vein for a Right Lobe Liver Graft With Multiple Venous Orifices: A Case Report.

Reconstruction of multiple venous orifices of a right lobe graft is a time-consuming and troublesome procedure in right lobe living-donor liver transplantation. In the current study, we present a new venous reconstruction technique for a right lobe graft with multiple and complex hepatic vein (HV) orifices, in which procurement of the recipient's left portal vein was performed in situ to keep the anhepatic period to a minimum. All of the HV orifices were reconstructed together at the back table, while maintaining patency of the recipient's systemic and splanchnic circulation. A homologous vein graft and veno-venous bypass were not necessary. All HVs were patent during the follow-up and the patient was free from complications. In conclusion, the present technique is readily available for reconstruction of complex and multiple HV tributaries, while avoiding a long anhepatic time and the use of veno-venous bypass.

Salvage Splenic Artery Embolization for Saving Falling Living Donor Graft due to Portal Overflow: A Case Report.

Portal decompression is an approach for reducing portal overflow caused by small-for-size syndrome. We report the case of a patient who recovered from rapidly progressing hyperbilirubinemia caused by a small graft by decompressing portal overflow with splenic artery embolization following a living donor liver transplantation (LDLT). The patient was a 54-year-old man with end-stage liver disease secondary to alcoholic liver cirrhosis; the donor was his 54-year-old wife. The graft volume of the left lobe was 444 mL, which was 34.8% of the standard liver volume (SLV) and insufficient for the recipient; thus, the plan was to use the right lobe for the graft. The patient underwent LDLT with a right lobe graft; the volume to SLV ratio was 39.1%, and the graft-to-recipient-weight ratio was 0.72%. Although portal pressure was low during the operation, the patient eventually developed small-for-size syndrome after LDLT. It was conceivable that because the patient had splenomegaly, portal decompression would be effective. Splenic arterial embolization was performed successfully on postoperative day (POD) 7. The patient's total bilirubin level was increased to 40 mg/dL on POD16. Decreased portal flow, which was shown by ultrasound screening to be "to-and-flo," increased again on POD23 to one-third of that on POD1. He was discharged without any infectious complications. Additional splenic artery embolization after LDLT may be a convenient option for reducing portal overflow for patients with splenomegaly if the portal decompression was not performed for some reason at the surgery.

Living-Donor Liver Transplantation for Hepatic Metastasis From Meningeal Hemangiopericytoma: A Case Report.

We report the case of a 58-year-old man referred to our hospital for liver tumor treatment. The patient had a history of neurosurgery for a meningeal hemangiopericytoma 16 years previously. Pre-operative imaging revealed a hypervascular tumor extending from Couinaud segment 4 to segment 8 of the liver, measuring 95 mm in diameter, indicating an atypical hepatocellular carcinoma. Because right trisectionectomy of the liver was considered to be high risk, living-donor liver transplantation (LDLT) was indicated. After transcatheter arterial embolization, LDLT was performed with the use of a left-lobe liver graft from the patient's son. Post-operative histological findings of the liver tumor were identical to those for meningeal hemangiopericytoma, therefore the patient was diagnosed with meningeal hemangiopericytoma that had metastasized to the liver. After LDLT, the patient had a healthy, active life for 2 years; then, a subcutaneous relapse was discovered in the left chest. The patient did not undergo any systemic chemotherapy in response to the relapse. After thoracic and orthopedic surgeries and radiotherapy for multiple metastases, the patient died 5 years and 5 months after LDLT. LDLT could be an effective treatment for localized metastatic hemangiopericytoma in the liver, but it should be indicated only for carefully selected patients.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium WST-1.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria (NTM) using a colorimetric microbial viability assay based on the reduction of the water-soluble tetrazolium salt {2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1)} using 2,3,5,6-tetramethyl-1,4-benzoquinone as an electron mediator was developed. Using the Clinical and Laboratory Standards Institute (CLSI) method, a long-term incubation time (7-14 days) was required to determine the minimum inhibitory concentrations (MICs) of the slowly growing NTM. The MICs for a variety of different antibiotics against the slowly growing NTM were determined by the WST-1 colorimetric method and compared with those obtained using the broth microdilution methods approved by the CLSI. Good agreement was found between the MICs determined after 3-4 days using the WST-1 colorimetric method and those obtained after 10-14 days using the broth microdilution method. The results suggest that the WST-1 colorimetric assay is a useful method for the rapid determination of the MICs for the slowly growing NTM.