Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals.

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.

Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.

BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric cancer, especially in terms of its association with the staining pattern. METHODS: Tissue specimens from 110 gastric cancer patients were immunohistochemically examined. The staining proportion and intensity of mesothelin expression in tumour cells were analysed, and the localisation of mesothelin was classified into luminal membrane and/or cytoplasmic expression. RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin expression was correlated with lymph-node metastasis. Furthermore, luminal membrane staining of mesothelin was identified in 16 cases, and the incidence of luminal membrane expression was also correlated with pT factor, pStage, lymphatic permeation, blood vessel permeation, recurrence, and poor patient outcome. Multivariate analysis showed that luminal membrane expression of mesothelin was an independent predictor of overall patient survival. CONCLUSION: We described that the luminal membrane expression of mesothelin was a reliable prognostic factor in gastric cancer, suggesting the functional significance of membrane-localised mesothelin in the aggressive behaviour of gastric cancer cells.

Left lobe living donor liver transplantation in adults.

Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndrome was higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT.

Impact of human T cell leukemia virus type 1 in living donor liver transplantation.

Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development.

The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation: significant lessons from a dual graft case.

IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.

Modulation of CD4⁺ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis.

Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV-related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV-related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4(+) T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4(+) T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4(+) regulatory T cells and PD-L1- and PD-L2-expressing cells than controls. Blocking of PD-1/PD-1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)-γ to interleukin (IL)-10 and a reduction of PD-1-expressing CD4(+) T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up-regulated expression of PD-1 ligands.

Expression profiles of genes associated with viral entry in HCV-infected human liver.

Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers.

Prognostic importance of the gross classification of hepatocellular carcinoma in living donor-related liver transplantation.

BACKGROUND: The gross classification of hepatocellular carcinoma (HCC) has been reported to be a significant prognostic factor for patients with HCC undergoing partial hepatectomy. The present study investigated whether the gross classification of HCC is also a prognostic factor in living donor-related liver transplantation (LDLT). METHODS: Some 119 patients undergoing LDLT for HCC were identified retrospectively from a prospective institutional database containing information on all LDLTs carried out between 1996 and 2009. Patients were divided into three groups according to the gross classification of the largest tumour in the explanted liver: type 1 HCC, single nodular type (81 patients); type 2, single nodular type with extranodular growth (21); and type 3, contiguous multinodular type (17). Clinicopathological factors and recurrence-free survival rates were compared. RESULTS: Recurrence-free survival rates for the whole group were 87·7 per cent at 1 year, 83·5 per cent at 3 years and 81·0 per cent at 5 years after LDLT. Type 3 HCC was associated with large tumour size, poor histological grade, a high incidence of microvascular invasion and multiple tumours. Independent predictors of poor recurrence-free survival were preoperative serum level of des-γ-carboxy prothrombin exceeding 300 mAU/ml, microvascular invasion and type 3 HCC. CONCLUSION: The gross classification of HCC was an independent predictor for recurrence of HCC in patients undergoing LDLT.

Deceleration of regenerative response improves the outcome of rat with massive hepatectomy.

Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS-398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS-398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS-398 treatment. In the 90% PH model, administration of NS-398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver.

Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARalpha-MDR3 pathway.

OBJECTIVE: Bezafibrate (BF) has been used to treat biliary damage, particularly in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has been demonstrated. The mechanism of action is thought to involve activation of the PPARalpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this hypothesis in patients with hepatobiliary disease. METHODS: The levels of serum gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile components were examined before and after BF administration in patients with obstructive jaundice undergoing percutaneous transhepatic biliary drainage (PTBD). Hepatic expression of PPARalpha and MDR3 was quantified by real-time PCR in patients with PBC or non-alcoholic fatty liver disease (NAFLD). RESULTS: In patients with obstructive jaundice, BF decreased the serum levels of biliary enzymes and increased the bile concentration of PL. In patients with PBC or NAFLD, the expression levels of MDR3 were already up-regulated before starting the BF treatment. Although BF treatment did not further up-regulate MDR3 expression in NAFLD patients, PPARalpha expression was significantly increased. CONCLUSIONS: BF enhanced the secretion of PL into bile in cholestatic patients undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent cholesterol overload, MDR3 was already expressed at a high level to compensate for bile acids overproduction, and its expression was hardly affected by BF. In patients with chronic liver diseases such as PBC, BF may induce clinical effects via mechanisms independent of PL secretion.

Intermittent pneumatic compression versus additional prophylaxis with enoxaparin for prevention of venous thromboembolism after laparoscopic surgery for gastric and colorectal malignancies: multicentre randomized clinical trial.

BACKGROUND: The role of antithrombotic chemoprophylaxis in prevention of venous thromboembolism (VTE) in laparoscopic surgery for gastric and colorectal malignancies is unknown. This study compared the addition of enoxaparin following intermittent pneumatic compression (IPC) with IPC alone in patients undergoing laparoscopic surgery for gastrointestinal malignancy. METHODS: In this multicentre RCT, eligible patients were older than 40 years and had a WHO performance status of 0 or 1. Exclusion criteria were prescription of antiplatelet or anticoagulant drugs and history of VTE. Patients were allocated to IPC or to ICP with enoxaparin in a 1 : 1 ratio. Stratification factors included sex, location of cancer, age 61 years and over, and institution. Enoxaparin was administered on days 1-7 after surgery. Primary outcome was VTE, evaluated by multidetector CT on day 7. RESULTS: Of 448 patients randomized, 208 in the IPC group and 182 in the IPC with enoxaparin group were evaluated. VTE occurred in ten patients (4·8 per cent) in the IPC group and six (3·3 per cent) in the IPC with enoxaparin group (P = 0·453). Proximal deep vein thrombosis and/or pulmonary embolism occurred in seven patients (3·4 per cent) in the IPC group and one patient (0·5 per cent) in the IPC with enoxaparin group (P = 0·050). All VTE events were asymptomatic and non-fatal. Bleeding occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient needed a transfusion. All bleeding events were managed by discontinuation of the drug. CONCLUSION: IPC with enoxaparin after laparoscopic surgery for gastric and colorectal malignancies did not reduce the rate of VTE. Registration number: UMIN000011667 ( https://www.umin.ac.jp/).

ANTECEDENTES: El papel de la quimioprofilaxis para la prevención del tromboembolismo venoso (venous thromboembolism, VTE) en la cirugía laparoscópica de los tumores malignos gástricos y colorrectales se desconoce. El objetivo de este estudio fue comparar la quimioprofilaxis antitrombótica (enoxaparina) y la compresión neumática intermitente (intermittent pneumatic compression, IPC) en pacientes sometidos a cirugía laparoscópica de tumores malignos abdominales. MÉTODOS: Se efectuó un ensayo aleatorizado, controlado y multicéntrico de pacientes sometidos a cirugía laparoscópica de tumores gástricos y colorrectales en Japón. Los criterios de inclusión eran pacientes mayores de 40 años de edad y con un estado funcional de WHO de 0-1. Los criterios de exclusión fueron la prescripción al paciente de fármacos antiagregantes o anticoagulantes y la historia de VTE. Los pacientes fueron asignados a IPC y ICP con la adición de enoxaparina en una relación 1:1. Los factores de estratificación incluyeron el sexo, la localización del cáncer, la edad mayor o menor de 61 años, y la institución. La enoxaparina fue administrada en los días postoperatorios (postoperative day, POD) 1-7. El resultado primario fue la VTE evaluada mediante tomografía computarizada multidetector en el POD7. Los cálculos de la potencia determinaron que se requerían 184 pacientes en cada grupo. RESULTADOS: De los 448 pacientes aleatorizados, se evaluaron finalmente 208 pacientes en el grupo IPC y 182 pacientes en el grupo IPC más enoxaparina. La VTE ocurrió en 10 de 208 pacientes en el grupo IPC (4,8%) y 6 de 182 pacientes en el grupo IPC más enoxaparina (3,3%) (P = 0,45). La trombosis venosa profunda proximal (proximal deep vein thrombosis, DVT) y/o el embolismo pulmonar (pulmonary embolism, PE) ocurrieron en 7 de 208 pacientes en el grupo IPC (3,4%) y 1 de 182 pacientes en el grupo IPC más enoxaparina (0,55%) (riesgo relativo 0,163, i.c. del 95% 0,020-1,314, P = 0,0503). Todos los eventos de VTE fueron asintomáticos y no mortales. Se produjo una hemorragia en 11 de 202 pacientes en el grupo IPC con enoxaparina (5,4%, i.c. del 95% 3,1%-9,5%, P < 0,001), y un paciente precisó transfusión. Todos los eventos hemorrágicos pudieron ser tratados con la interrupción del fármaco. CONCLUSIÓN: La IPC con la adición de enoxaparina tras cirugía laparoscópica de los tumores malignos gástricos y colorrectales no disminuye la VTE.

Impact of technically qualified surgeons on laparoscopic colorectal resection outcomes: results of a propensity score-matching analysis.

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) was introduced in Japan to improve the quality of laparoscopic surgery. This cohort study investigated the short- and long-term postoperative outcomes of colorectal cancer laparoscopic procedures performed by or with qualified surgeons compared with outcomes for unqualified surgeons. METHODS: All laparoscopic colorectal resections performed from 2010 to 2013 in 11 Japanese hospitals were reviewed retrospectively. The procedures were categorized as performed by surgeons with or without the ESSQS qualification and patients' clinical, pathological and surgical features were used to match subgroups using propensity scoring. Outcome measures included postoperative and long-term results. RESULTS: Overall, 1428 procedures were analysed; 586 procedures were performed with ESSQS-qualified surgeons and 842 were done by ESSQS-unqualified surgeons. Upon matching, two cohorts of 426 patients were selected for comparison of short-term results. A prevalence of rectal resection (50·3 versus 40·5 per cent; P < 0·001) and shorter duration of surgery (230 versus 238 min; P = 0·045) was reported for the ESSQS group. Intraoperative and postoperative complication and reoperation rates were significantly lower in the ESSQS group than in the non-ESSQS group (1·2 versus 3·6 per cent, P = 0·014; 4·6 versus 7·5 per cent, P = 0·025; 1·9 versus 3·9 per cent, P = 0·023, respectively). These findings were confirmed after propensity score matching. Cox regression analysis found that non-attendance of ESSQS-qualified surgeons (hazard ratio 12·30, 95 per cent c.i. 1·28 to 119·10; P = 0·038) was independently associated with local recurrence in patients with stage II disease. CONCLUSION: Laparoscopic colorectal procedures performed with ESSQS-qualified surgeons showed improved postoperative results. Further studies are needed to investigate the impact of the qualification on long-term oncological outcomes.

ANTECEDENTES: El Sistema de Certificación de Habilidades Quirúrgicas Endoscópicas (Endoscopic Surgical Skill Qualification System, ESSQS) fue introducido en Japón para mejorar la calidad de la cirugía laparoscópica. En este estudio de cohortes se investigaron los resultados postoperatorios a corto y a largo plazo de las intervenciones laparoscópicas de cáncer colorrectal realizadas por o con la asistencia de cirujanos con certificación en comparación con cirujanos no certificados. MÉTODOS: Todas las resecciones colorrectales laparoscópicas realizadas entre 2010 y 2013 en 11 hospitales japoneses fueron revisadas retrospectivamente. Los procedimientos se clasificaron en función de si habían sido realizados por cirujanos con o sin certificación del ESSQS, y las características clínicas, patológicas y quirúrgicas de los pacientes se utilizaron para emparejar los subgrupos mediante puntuaciones de propensión. Las variables de resultado incluyeron los resultados postoperatorios y a largo plazo RESULTADOS: En total se analizaron 1.428 procedimientos, incluyendo 586 y 842 procedimientos realizados con y sin cirujanos certificados por ESSQS, respectivamente. Tras el emparejamiento, se seleccionaron dos cohortes de 426 pacientes para la comparación de resultados a corto plazo. Se observó una mayor prevalencia de resecciones rectales (50,3% versus 40,1%, P = 0,0001) y un tiempo quirúrgico más corto (230 versus 238 min, P = 0,04) en el grupo ESSQS. Las tasas de complicaciones intra- y postoperatorias y de reoperaciones fueron significativamente más bajas en el grupo ESSQS que en el grupo no ESSQS (1,2%, 4,6% y 1,9% versus 3,6%, 7,5% y 3,9%, P = 0,01; 0,03, y 0,02, respectivamente). Estos hallazgos se confirmaron tras el análisis de emparejamiento por puntaje de propensión. El análisis de regresión de Cox mostró que la no participación de cirujanos certificados con ESSQS (razón de oportunidades, odds ratio, OR 12,3; i.c. del 95%, 1,28-119,1; P = 0,03) se asoció independientemente con la recidiva local en los casos en estadio II. CONCLUSIÓN: Los procedimientos colorrectales laparoscópicos realizados por cirujanos certificados por ESSQS presentaron mejores resultados postoperatorios. Son necesarios más estudios para determinar el impacto de la certificación en los resultados oncológicos a largo plazo.

Living donor liver transplantation using dual grafts from two donors: a feasible option to overcome small-for-size graft problems?

Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks.

Sequential pancreaticoduodenectomy after living donor liver transplantation for cholangiocarcinoma.

Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease.

Estimation of standard liver volume for Japanese adults.

INTRODUCTION: Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. METHODS: We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 x body surface area [BSA] - 220), Urata (LV = 706.2 x BSA + 2.4), Noda (LV = 50.12 x BW(0.78)), Heinemann (LV = 1072.8 x BSA - 345.7), Vauthey (LV = 18.51 x BW + 191.8) and Yoshizumi (LV = 772 x BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. RESULTS: Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm(3). When the Yoshizumi formula was applied, the number of donors with an acceptable difference (+/-15%) between CTV and estimated LV was 55 (78.6%). CONCLUSIONS: The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates.

Donor age in living donor liver transplantation.

BACKGROUND: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. METHODS: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age < or =50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age < or =50, n = 61). We compared post-LDLT graft functions. RESULTS: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. CONCLUSION: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT.

Successful ABO incompatible living donor liver transplantation in a patient with high isoagglutinin titer using high-dose intravenous immunoglobulin.

The optimal management in living donor liver transplantation using an ABO incompatible donor with a high isoagglutinin titer is still uncertain. Our patient was a 20-year-old woman with fulminant hepatitis. The only available donor was her 54-year-old father-in-law of an incompatible blood type. The initial isoagglutinin titer was 2048x. She received 375 mg/m2 of anti-CD20 antibody 3 days before the living donor liver transplantation with concomitant splenectomy. Despite daily plasma exchanges after transplantation, the isoagglutinin titer started to shoot up to its maximum value of 2048x, with a sudden decline in the bile output. High-dose intravenous immunoglobulin (0.6 g/kg) was given after the plasma exchanges; thereafter, her liver function tests stabilized without a further increase in the isoagglutinin titer. We showed the effectiveness of high-dose intravenous immunoglobulin for the management of the rebound elevation of isoagglutinin titer. The combination of anti-CD20 antibody and daily plasma exchanges seemed ineffective for such a situation. This strategy might be another management option for ABO incompatible liver transplantation.

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.