Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study.

BACKGROUND: Surgical treatment for hepatocellular carcinoma (HCC) is advancing, but a robust prediction model for survival after resection is not available. The aim of this study was to propose a prognostic grading system for resection of HCC. METHODS: This was a retrospective, multicentre study of patients who underwent first resection of HCC with curative intent between 2000 and 2007. Patients were divided randomly by a cross-validation method into training and validation sets. Prognostic factors were identified using a Cox proportional hazards model. The predictive model was built by decision-tree analysis to define the resection grades, and subsequently validated. RESULTS: A total of 16 931 patients from 795 hospitals were included. In the training set (8465 patients), four surgical grades were classified based on prognosis: grade A1 (1236 patients, 14.6 per cent; single tumour 3 cm or smaller and anatomical R0 resection); grade A2 (3614, 42.7 per cent; single tumour larger than 3 cm, or non-anatomical R0 resection); grade B (2277, 26.9 per cent; multiple tumours, or vascular invasion, and R0 resection); and grade C (1338, 15.8 per cent; multiple tumours with vascular invasion and R0 resection, or R1 resection). Five-year survival rates were 73.9 per cent (hazard ratio (HR) 1.00), 64.7 per cent (HR 1.51, 95 per cent c.i. 1.29 to 1.78), 50.6 per cent (HR 2.53, 2.15 to 2.98), and 34.8 per cent (HR 4.60, 3.90 to 5.42) for grades A1, A2, B, and C respectively. In the validation set (8466 patients), the grades had equivalent reproducibility for both overall and recurrence-free survival (all P < 0.001). CONCLUSION: This grade is used to predict prognosis of patients undergoing resection of HCC.

Significance of the surgical hepatic resection margin in patients with a single hepatocellular carcinoma.

BACKGROUND: The impact of a wide surgical margin on the outcome of patients with hepatocellular carcinoma (HCC) has not been evaluated in relation to the type of liver resection performed, anatomical or non-anatomical. The aim of this study was to evaluate the impact of surgical margin status on outcomes in patients undergoing anatomical or non-anatomical resection for solitary HCC. METHODS: Data from patients with solitary HCC who had undergone non-anatomical partial resection (Hr0 group) or anatomical resection of one Couinaud segment (HrS group) between 2000 and 2007 were extracted from a nationwide survey database in Japan. Overall and recurrence-free survival associated with the surgical margin status and width were evaluated in the two groups. RESULTS: A total of 4457 patients were included in the Hr0 group and 3507 in the HrS group. A microscopically positive surgical margin was associated with poor overall survival in both groups. A negative but 0-mm surgical margin was associated with poorer overall and recurrence-free survival than a wider margin only in the Hr0 group. In the HrS group, the width of the surgical margin was not associated with patient outcome. CONCLUSION: Anatomical resection with a negative 0-mm surgical margin may be acceptable. Non-anatomical resection with a negative 0-mm margin was associated with a less favourable survival outcome.

ANTECEDENTES: El impacto de un margen quirúrgico (surgical margin, SM) amplio en el resultado de pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) no ha sido evaluado en relación con el tipo de resección hepática realizada: anatómica o no anatómica. El objetivo del presente estudio fue evaluar el impacto del estado del SM en los resultados en pacientes sometidos a resección anatómica o no anatómica por un HCC solitario. MÉTODOS: Los datos de pacientes con un HCC solitario sometidos a resección parcial no anatómica (grupo Hr0) o resección anatómica de un segmento de Couinaud (grupo HrS) entre 2000 y 2007 se obtuvieron a partir de una base de datos nacional de Japón. En los grupos Hr0 y HrS se evaluaron la supervivencia global y la supervivencia libre de recidiva asociadas al estado microscópico del SM y a la amplitud del SM. RESULTADOS: Se incluyeron un total de 4.457 pacientes en el grupo Hr0 y 3.507 en el grupo HrS. Un SM microscópico positivo se asoció con una pobre supervivencia global en ambos grupos. Un SM negativo, pero a una distancia de 0 mm se asoció con una peor supervivencia global y libre de recidiva en comparación con aquellos asociados a un SM más amplio, solo en el grupo Hr0. En el grupo HrS, la amplitud del SM no se asoció con los resultados del paciente. CONCLUSIÓN: La resección anatómica con un SM negativo a una distancia de 0 mm puede ser aceptable. La resección no anatómica con un SM negativo a una distancia de 0 mm se asoció con resultados de supervivencia menos favorables.

Performance of a modified three-level classification in stratifying open liver resection procedures in terms of complexity and postoperative morbidity.

BACKGROUND: Traditional classifications for open liver resection are not always associated with surgical complexity and postoperative morbidity. The aim of this study was to test whether a three-level classification for stratifying surgical complexity based on surgical and postoperative outcomes, originally devised for laparoscopic liver resection, is superior to classifications based on a previously reported survey for stratifying surgical complexity of open liver resections, minor/major nomenclature or number of resected segments. METHODS: Patients undergoing a first open liver resection without simultaneous procedures at MD Anderson Cancer Center (Houston cohort) or the University of Tokyo (Tokyo cohort) were studied. Surgical and postoperative outcomes were compared among three grades: I (wedge resection for anterolateral or posterosuperior segment and left lateral sectionectomy); II (anterolateral segmentectomy and left hepatectomy); III (posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, central hepatectomy and extended left/right hepatectomy). RESULTS: In both the Houston (1878 patients) and Tokyo (1202) cohorts, duration of operation, estimated blood loss and comprehensive complication index score differed between the three grades (all P < 0·050) and increased in stepwise fashion from grades I to III (all P < 0·001). Left hepatectomy was associated with better surgical and postoperative outcomes than right hepatectomy, extended right hepatectomy and right posterior sectionectomy, although these four procedures were categorized as being of medium complexity in the survey-based classification. Surgical outcomes of minor open liver resections also differed between the three grades (all P < 0·050). For duration of operation and blood loss, the area under the curve was higher for the three-level classification than for the minor/major or segment-based classification. CONCLUSION: The three-level classification may be useful in studies analysing open liver resection at Western and Eastern centres.

ANTECEDENTES: Las clasificaciones tradicionales de la resección hepática abierta (open liver resection, OLR) por número de segmentos resecados, no siempre se asocian con la complejidad quirúrgica y la morbilidad postoperatoria. El objetivo de este estudio fue comprobar si una clasificación de 3 niveles para estratificar la complejidad quirúrgica en función de los resultados quirúrgicos y postoperatorios, ideada originalmente para la resección hepática laparoscópica, es superior a las clasificaciones basadas en una encuesta descrita previamente para estratificar la complejidad quirúrgica de los procedimientos de OLR, nomenclatura menor/mayor, o número de segmentos resecados. MÉTODOS: Se estudiaron pacientes sometidos a una primera OLR sin otros procedimientos quirúrgicos concomitantes en el hospital MD Anderson (cohorte de Houston) o en la Universidad de Tokio (cohorte de Tokio). Se compararon los resultados quirúrgicos y postoperatorios entre 3 grados: I (resección limitada para el segmento anterolateral o posterosuperior y seccionectomía izquierda); II (segmentectomía anterolateral y hepatectomía izquierda); III (segmentectomía posterosuperior, seccionectomía posterior derecha, hepatectomía derecha, hepatectomía central y hepatectomía ampliada izquierda/derecha). RESULTADOS: En ambas cohortes de Houston (n = 1.878) y Tokio (n = 1.202), el tiempo operatorio, las pérdidas estimadas de sangre, y el índice de complejidad integral (comprehensive complication index) variaba en los 3 grados (todos P < 0,05) y aumentaba paso a paso desde los grados I a III (todos P < 0,05). La hepatectomía izquierda se asociaba con mejores resultados quirúrgicos y postoperatorios que la hepatectomía derecha, hepatectomía derecha ampliada, y seccionectomía posterior derecha, aunque estos cuatro procedimientos fueron categorizados como de complejidad intermedia en la clasificación basada en la encuesta. Los resultados quirúrgicos de las OLRs menores también variaron en los 3 grados (todos P < 0,05). Para el tiempo operatorio y la pérdida sanguínea, el área bajo la curva fue mayor para la clasificación de 3 niveles en el estudio actual, que para la clasificación menor/mayor o la clasificación basada en los segmentos. CONCLUSIÓN: La clasificación en 3 niveles puede ser útil en estudios que analizan las resecciones hepáticas abiertas en centros occidentales y orientales.

Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Sarcopenia, the depletion of muscle mass, an independent predictor of respiratory complications after oncological esophagectomy.

Surgery for esophageal carcinoma is known to be associated with high morbidity. Recent studies have reported a correlation of nutritional and inflammatory parameters with postoperative course. This study aims to clarify the risk factors for operative morbidity after resection of esophageal carcinoma. Consecutive patients who underwent esophagectomy for esophageal squamous cell carcinoma at our institute were included (n = 102; 89 males and 13 females; mean age: 67.3 years). Clinicopathological characteristics, presence or absence of sarcopenia, and modified Glasgow prognostic score were assessed, and their correlation with postoperative complications was investigated using univariate and multivariate analyses. Sarcopenia was defined using a combination of muscle mass area and body mass index. Of the included 102 patients, 45 (44.1%) exhibited sarcopenia (sarcopenia group), while 57 (55.9%) did not (non-sarcopenia group). No significant difference was observed between the groups regarding surgical procedures and tumor stage; furthermore, there was no mortality. Twenty-six patients developed respiratory complications (including 20 cases of pneumonia). On univariate analysis, sarcopenia, modified Glasgow prognostic score, and American Society of Anesthesiologists physical status were found to be significantly associated with the development of postoperative respiratory complications. On multivariate analysis, sarcopenia was found to be an independent risk factor for postoperative respiratory complications after esophagectomy. We believe that identifying patients at risk and providing preoperative nutritional support as well as physical therapy aimed at strengthening of body muscles may help reduce the incidence of postoperative respiratory complications in such patients.

Predicting prognosis of resected hepatocellular carcinoma by radiomics analysis with random survival forest.

RATIONALE AND OBJECTIVES: To investigate the impact of random survival forest (RSF) classifier trained by radiomics features over the prediction of the overall survival of patients with resectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The dynamic computed tomography data of 127 patients (97 men, 30 women; mean age, 68 years) newly diagnosed with resectable HCC were retrospectively analyzed. After manually setting the region of interest to include the tumor within the slice at its maximum diameter, texture analyses were performed with or without a Laplacian of Gaussian filter. Using the extracted 96 histogram based texture features, RSFs were trained using 5-fold cross-validation to predict the individual risk for each patient on disease free survival (DFS) and overall survival (OS). The associations between individual risk and DFS or OS were evaluated using Kaplan-Meier analysis. The effects of the predicted individual risk and clinical variables upon OS were analyzed using a multivariate Cox proportional hazards model. RESULTS: Among the 96 histogram based texture features, RSF extracted 8 of high importance for DFS and 15 for OS. The RSF trained by these features distinguished two patient groups with high and low predicted individual risk (P=1.1×10-4 for DFS, 4.8×10-7 for OS). Based on the multivariate Cox proportional hazards model, high predicted individual risk (hazard ratio=1.06 per 1% increase, P=8.4×10-8) and vascular invasion (hazard ratio=1.74, P=0.039) were the only unfavorable prognostic factors. CONCLUSIONS: The combination of radiomics analysis and RSF might be useful in predicting the prognosis of patients with resectable HCC.

Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping.

BACKGROUND: Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. METHODS: Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon ), veno-occlusive regions (FIVO ) and ischaemic regions (FIIS ) were calculated using luminance analysing software. RESULTS: Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30-458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS /FINon was lower than median FIVO /FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. CONCLUSION: ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.

Outflow Reconstruction Using Cryopreserved Homologous Venous Grafts in Living Donor Liver Transplantation.

OBJECTIVES: The techniques and outcomes of outflow reconstruction in living donor liver transplantation (LDLT) using cryopreserved homologous veins at the University of Tokyo Hospital are presented. METHODS: We performed 540 LDLTs from January 1996 to March 2015. Graft types included right liver graft (n = 262), left liver graft (n = 196), left lateral sector graft (n = 53), and posterior sector graft (n = 28). We routinely use cryopreserved homologous vein grafts for the hepatic vein reconstructions to secure the large outflow of the graft. In addition to the presentation of our techniques, the cases with symptomatic outflow obstruction and the treatments were also investigated. RESULTS: The 1-, 3-, and 5-year graft survival rates were 90.6%, 86.1%, and 83.5%, respectively. The incidence of severe complications (Clavien-Dindo grade IIIb and more) was 38%. The overall incidence of outflow obstruction requiring invasive treatment was 1.9% (10/540), including 3 left liver grafts (1.5%, 3/196) and 7 right liver grafts (2.7%, 7/262). Regarding the patency of the reconstructed veins, the left hepatic vein, middle hepatic vein, and right hepatic vein achieved nearly 100% patency. On the contrary, venous tributaries such as V5, V8, and inferior right hepatic vein were frequently occluded in the postoperative course. CONCLUSIONS: Outflow reconstruction is a key for the successful LDLT. Cryopreserved homologous vein graft is useful for the promising hepatic vein reconstruction.

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel mechanisms of HCC progression through Sharpin overexpression. In our study, Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that Versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in Sharpin-expressing stable cells. Versican expression increased in the majority of HCC tissues and knocking down of Versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of Versican transcription synergistically with Wnt/ß-catenin pathway activation. Furthermore, Sharpin-overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes Versican expression synergistically with the Wnt/ß-catenin pathway, potentially contributing to HCC development. A Sharpin/Versican axis could be an attractive therapeutic target for this currently untreatable cancer.

Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection.

BACKGROUND: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated. METHODS: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group. RESULTS: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3-1570) ml (P = 0·048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0·043). CONCLUSION: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm).

Living Liver Donor Selection and Resection at the University of Tokyo Hospital.

OBJECTIVES: Donor selection and operative procedures for adult-to-adult living donor liver transplantation at the University of Tokyo are presented. METHODS: Donor selection criteria are as follows: age between 20 and 65 years, within 3 degrees of consanguinity, without coercion, free from any major comorbidities, body mass index (BMI) < 30, and ABO blood type identical or compatible. Liver biopsy is indicated for BMI > 25 kg/m(2) or any liver function abnormality, and those with macroscopic steatosis >10% are rejected. Thereafter, an indocyanine green retention test and dynamic computed tomography are evaluated. Graft type is determined based on computed tomography volumetry. An estimated graft volume of 40% to recipient standard liver volume ratio is the lower limit. For donor safety, the left liver is the first choice, provided that it satisfies the lower limit. Otherwise, right liver harvesting is indicated, providing that the estimated remnant liver volume is >30% of the donor's total liver volume. A posterior sector graft is a possible option. RESULTS: Between 1996 and 2014, 462 donor hepatectomies were performed, with 257 right livers, 179 left livers, and 26 posterior sectors. There was no mortality, and the incidence of morbidity grades I, II, IIIa, and IIIb was 16%, 5%, 5%, and 3%, respectively, without a difference between right and left liver grafts. The left liver was used without impairing recipient outcome. Two aborted hepatectomies (0.4%) and 3 near-miss events (0.6%) were encountered. CONCLUSIONS: Maximal effort should be applied to donor selection and operation for donor safety.

Use of a Right Lateral Sector Graft in Living Donor Liver Transplantation Is Feasible, but Special Caution Is Needed With Respect to Liver Anatomy.

Right lateral sector (RLS) grafting has been introduced to enlarge the potential donor pool for living donor liver transplantation (LDLT); however, evidence of its feasibility is limited. Data from 437 LDLTs carried out between 2000 and 2013 were analyzed retrospectively. LDLTs using a right liver graft (n = 251) were compared with those using a RLS graft (RLSG; n = 28). No donor mortality occurred, and the major complication rates were similar between the two groups. Postoperative liver function preservation was better in the RLSG donors. Concerning the recipients, the mortality and overall survival rates were similar between the two groups. The complication rate for the recipients was higher when more than two arterial or biliary anastomoses were necessary. A systematic literature search identified four reports on LDLT using RLSGs. Among 66 LDLTs, including the present series, there were no cases of donor death, and the rates of major and minor complications in the donors were 6% and 29%, respectively. The major complication and overall mortality rates in the recipients were 29% and 6%, respectively. LDLT using an RLSG is feasible, with an acceptable survival rate among the recipients.

Differential diagnosis of liver tumours using intraoperative real-time tissue elastography.

BACKGROUND: Real-time tissue elastography is an innovative tool that informs the surgeon about tissue elasticity by applying the principle of ultrasonography. The aim of this study was to investigate the accuracy of intraoperative real-time tissue elastography (IORTE) for the detection and characterization of liver tumours. METHODS: Between October 2010 and November 2011, IORTE was performed for liver lesions after the completion of routine B-mode intraoperative ultrasonography (IOUS). The elasticity images of all tumours, except those of cysts, were classified into six categories according to modified criteria (types 1-6), according to the degree of strain contrast with the surrounding liver. The concordance of IORTE with pathological examination of the tumour, B-mode IOUS and clinical diagnosis after follow-up was assessed. RESULTS: Images were obtained from 92 hepatocellular carcinomas (HCCs), 92 adenocarcinomas, 19 other malignant tumours and 18 benign tumours in 158 patients. Using a minilinear probe, 73 of 88 HCCs were classified as having a 'HCC pattern' (type 3, 4 or 5), resulting in a sensitivity of 83·0 per cent, a specificity of 67·2 per cent and an accuracy of 73·7 per cent. Some 66 of 90 adenocarcinomas were classified as 'adenocarcinoma pattern' (type 6), resulting in a sensitivity of 73·3 per cent, specificity of 95·1 per cent and accuracy of 85·9 per cent. IORTE detected seven new lesions (8 per cent). CONCLUSION: IORTE is useful for the detection and characterization of liver tumours.

Adult right living-donor liver transplantation with special reference to reconstruction of the middle hepatic vein.

Two hundred fifty-three consecutive living-donor liver transplant recipients with a right liver graft (RLG) were divided into three groups: an extended right liver graft (ERLG) group (n = 47) in which the middle hepatic vein (MHV) trunk was included in the graft, a modified right liver graft (MRLG) group (n = 114) in which the MHV tributaries were reconstructed with cryopreserved homologous veins and a simple RLG group (n = 92) in which the MHV tributaries were sacrificed. The volume of the anterior sector was significantly impaired in the RLG group compared to the other two groups, whereas the volume of the posterior sector was significantly improved in the RLG group, indicating that the impaired anterior sector regeneration by MHV deprivation was compensated by the posterior sector regeneration. The regeneration rate of the anterior sector was highest in the ERLG group (92%), moderate in the MRLG group (71%) and lowest in the RLG group (52%). The whole graft regeneration rate of the ERLG group was significantly higher than that of the other two groups. Poor regeneration, however, was not correlated with delayed functional recovery or long-term outcome. Short-term, the patency of reconstructed MHV tributaries was over 90%, but occlusion occurred frequently over the long-term, especially in V5.

First case report of de novo ulcerative colitis developing after orthotopic liver transplantation successfully treated by granulocyte and monocyte apheresis.

BACKGROUND: Immunosuppressants such as tacrolimus and cyclosporine are prescribed long-term after orthotopic liver transplantation (OLT) to prevent allograft rejection. Although these immunosuppressants are known to effectively control ulcerative colitis (UC), some post-OLT patients develop exacerbation of preexisting UC or de novo UC. Although aminosalicylates and corticosteroid courses are usually effective to treat such UC, several patients have developed uncontrollable disease and required colectomies. CASE REPORT: We have reported a patient who developed de novo UC after OLT to treat liver cirrhosis and hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. Existence of the HBV infection made us avoid to increase the corticosteroid dose or to use other immunosuppressants such as azathioprine or infliximab. CONCLUSIONS: In this patient, granulocyte and monocyte apheresis was highly effective in terms of inducing remission of de novo UC. No adverse event was noted.

Establishment of educational program for multiorgan procurement from deceased donors.

INTRODUCTION: Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. MATERIALS AND METHODS: Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. RESULTS: The risk factors for early outcome of the recipients were cold ischemia time (≥ 10 hours), Model for End-stage Liver Disease score (≥ 20), and donor age (≥ 55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. CONCLUSION: The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.

Surgical resection of peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma.

BACKGROUND: Peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma (HCC) occur occasionally after biopsy, percutaneous therapy or resection, and spontaneously, with no effective treatment available. The objective of this study was to clarify the indications for, and benefits of, surgical resection of such HCC implants. METHODS: This was a retrospective analysis of patients who underwent resection for peritoneal or chest wall implants from HCC over 14 years (1997-2011). Indications for surgery for implanted HCC were: limited number of implanted lesions including those found incidentally during surgery; intrahepatic lesion absent or predicted to be locally controllable; and absence of ascites with sufficient hepatic functional reserve. Prognostic factors affecting survival after resection were determined by univariable and multivariable analysis. RESULTS: A total of 32 patients underwent 36 resections. Cumulative 1-, 3- and 5-year overall survival rates were 71, 44 and 39 per cent respectively, with a median survival time of 34.5 months. Univariable and multivariable analysis revealed that poor perioperative intrahepatic disease control was associated with poor survival. CONCLUSION: Surgical resection of implanted HCC may improve long-term survival in selected patients as long as intrahepatic disease is absent or well controlled.

Analysis of the hepatic functional reserve, portal hypertension, and prognosis of patients with human immunodeficiency virus/hepatitis C virus coinfection through contaminated blood products in Japan.

BACKGROUND: As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. AIM: The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. PATIENTS AND METHODS: In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. RESULTS: In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/µL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/µL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P < .05). CONCLUSION: These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan.

A single-center experience of the use of interleukin-2 receptor antagonists for various situations in liver transplant recipients.

BACKGROUND: Interleukin-2 receptor antagonists (IL2Ra) are used mainly for (1) induction as an adjunct to conventional immunosuppression, (2) induction to facilitate calcineurin inhibitor (CNI) or steroid minimization, and (3) induction to facilitate steroid avoidance in hepatitis C virus (HCV)-positive recipients. The aim of this study was to present our strategy for IL2Ra rescue therapy and its outcome. METHODS: A total of 20 patients were treated with IL2Ra at our institute for the following indications: (1) rescue for acute rejection (n = 13), (2) CNI sparing in cases of CNI toxicity (n = 5), and (3) induction for complicated cases (n = 2). RESULTS: Rescue therapy for steroid-resistant rejection and rejection in HCV-positive recipients was successful in 11 cases, but 2 grafts were lost due to uncontrollable rejection. CNI cessation was successfully achieved with IL2Ra treatment in 3 cases with thrombotic microangiopathy and 2 cases of encephalopathy, with complete cure of these life-threatening complications of CNI. Induction with IL2Ra was successful in 2 complicated cases, 1 for CNI sparing due to renal failure and the other for adjunct immunosuppression in a case of positive lymphocytotoxic crossmatch. The overall patient/graft survival and the rate of infectious complications were comparable between those with and without IL2Ra treatment. CONCLUSIONS: IL2Ra could be safely and effectively used after liver transplantation in various situations.