Sumihito Tamura

Real‐time identification of liver cancers by using indocyanine green fluorescent imaging

We have often encountered difficulties in identifying small liver cancers during surgery. Fluorescent imaging using indocyanine green (ICG) has the potential to detect liver cancers through the visualization of the disordered biliary excretion of ICG in cancer tissues and noncancerous liver tissues compressed by the tumor.

Living donor liver transplantation for hepatocellular carcinoma: Tokyo University series.

Background/Aims: Hepatocellular carcinoma (HCC) is one of the major indications for living donor liver transplantation (LDLT). Unlike in deceased donor liver transplantation, however, there exist no universally adopted selection criteria for the potential candidates with HCC in LDLT. Our institutional guideline for HCC in LDLT has been up to 5 nodules with a maximum diameter of 5 cm (5-5 rule). Methods: A total of 78 adult patients underwent adult living donor liver transplantation at University of Tokyo between April 1996 and October 2005. Results: Overall and recurrence-free survival at 5 years after transplantation were 75 and 90%, respectively, with a median follow-up of 2 years. When stratified by the 5-5 rule, recurrence-free survival at 3 years for patients fulfilling the criteria and those exceeding the criteria was 94 and 50%, respectively. Conclusions: In LDLT, the indication for HCC might be expanded from the Milan criteria, with equivalent outcomes. Further study, however, is necessary to justify the general application of the 5-5 rule.

Intraoperative Fluorescent Cholangiography Using Indocyanine Green: A Biliary Road Map for Safe Surgery

F T i m k c 8 nlike blood vessels, the biliary tract lies in the Glissonian heath and is buried in the perivascular connective tissue, o it is difficult to clearly visualize and isolate it during epatobiliary surgery. Intraoperative cholangiography IOC), which was originally introduced by Mirizzi in 937, has been widely used to delineate the biliary tract natomy in this setting. For example, routine IOC was ecently recommended during cholecystectomy to prevent ile duct injury. IOC is also considered an essential proedure during donor hepatectomy because it enables the ile duct to be divided at the appropriate level to ensure ider and fewer residual orifices. But conventional raiographic IOC is disadvantageous in that it exposes the atient and the medical staff to radiation and usually reuires a large and expensive C-arm fluoroscopy machine nd the additional human resources involved. Recently, intraoperative angiography using a fluorescent maging technique with IV injection of indocyanine green ICG) has been used to assess coronary artery bypass graft atency. This technique is based on the principle that CG binds to plasma proteins and that protein-bound ICG mits light with a peak wavelength of about 830 nm when lluminated with near-infrared light. Because human ile also contains plasma proteins that bind with ICG, we ypothesized that fluorescent images of the biliary tract ould be obtained with intrabiliary injection of ICG. We lso hypothesized that IV injection of ICG would provide luorescent images of the biliary tract without necessitating

Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor.

The skin of the toad Bufo bufo gargarizans Cantor is known to be rich in bufadienolides, peptides and alkaloids. It has been found to be a source of some extracts and biologically active compounds with antitumor activity. Cinobufacini (Huachansu), a Chinese medicine prepared from the dried toad skin, has been widely used in clinical therapy for various cancers in China. Bufadienolides, such as bufalin, cinobufagin, resibufogenin, and telocinobufagin, are the major active compounds derived from the toad skin. They are the maker biologically active compounds of cinobufagin while the antitumor activity of cinobufagin may be due to this kind of components. Experimental research has suggested that cinobufacini and its active compounds (e.g. bufalin and cinobufagin) exhibit significant antitumor activity, including inhibition of cell proliferation, induction of cell differentiation, induction of apoptosis, disruption of the cell cycle, inhibition of cancer angiogenesis, reversal of multi-drug resistance, and regulation of the immune response. Clinical data have indicated that cinobufacini may have effective anticancer activity with low toxicity and few side effects. Data to date suggest it may also enhance quality of life for patients with cancer. Thus, this review briefly summarizes recent studies on the anticancer activity of cinobufacini and some of its active compounds from the skin of the toad Bufo bufo gargarizans Cantor. This might provide additional evidence for further study of the extracts and active compounds from the toad skin in cancer treatment.

Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green

BACKGROUND & AIMS Although recent advances in preoperative imaging have enabled accurate estimation of the regional liver volume with venous occlusion, the extent of functional decrease in such regions remains unclear. In this study, the portal uptake function in postoperative veno-occlusive regions and non-veno-occlusive regions was evaluated by intraoperative fluorescent imaging after intravenous injection of indocyanine green (ICG). METHODS In 22 liver resection patients and 23 recipients and 18 donors of liver transplantation, fluorescent intensity on the remnant liver or the liver graft was evaluated in real time following intravenous injection of ICG (0.0025 mg per 1 ml of remnant liver volume). RESULTS Plateau ICG concentrations were significantly lower in the veno-occlusive regions (C(VO)) than in the non-veno-occlusive regions (C(Non)) in liver resection patients (median [range], 0.75 [0.29-2.0]μg/ml vs. 3.0 [0.46-6.4]μg/ml, p<0.001), donors (0.69 [0.29-1.9]μg/ml vs. 2.4 [0.46-6.4]μg/ml, p<0.001), and recipients (0.75 [0.34-1.8]μg/ml vs. 1.8 [0.54-6.4]μg/ml, p<0.001). Distributions of the C(VO)/C(Non) and the ratio of the hepatic uptake rate constant in the veno-occlusive regions to that in non-veno-occlusive regions were both around 40% (mean ± standard deviation, 0.36 ± 0.17 and 0.42 ± 0.16, respectively). When the functional remnant liver volume was calculated as a sum of non-veno-occlusive regions and veno-occlusive regions multiplied by C(VO)/C(Non), its ratio to the total liver volume was correlated with the improved postoperative/preoperative ratio of prothrombin time. CONCLUSIONS Portal uptake function in veno-occlusive regions is approximately 40% of that in non-veno-occlusive regions. Intraoperative ICG-fluorescent imaging enables real-time evaluation of the extent of the functional decrease in veno-occlusive regions, enhancing accurate estimation of the hepatic functional reserve for determining the surgical indications and procedures.

Portal vein reconstruction in adult living donor liver transplantation using cryopreserved vein grafts

No data are available for the management of venous jump or interposition conduits for portal vein (PV) reconstruction in adult living donor liver transplantation (LDLT). The feasibility of using cryopreserved vein grafts as PV conduits was examined. Cryopreserved vein (n = 23) was used as a patch, interposition, or jump graft. The patency results were compared with those of anastomosis without vein patch (n = 217) or those with vein autografts (n = 10). The 5‐yr primary and secondary patency rates of the cryopreserved vein grafts were 58% and 79%, respectively. In conclusion, our data indicate that the use of cryopreserved vein grafts should be limited as conduits in PV reconstruction in adult LDLT. Liver Transpl 12:1233‐1236, 2006.

Splenectomy and preemptive interferon therapy for hepatitis C patients after living-donor liver transplantation

Abstract:  Recurrent hepatitis C after liver transplantation is a major cause of graft failure. We routinely perform preemptive interferon and ribavirin therapy in patients after living‐donor liver transplantation indicated for hepatitis C‐related cirrhosis. One of the obstacles for the therapy includes blood cytopenia. To overcome this problem, we recently performed splenectomy concurrently with liver transplantation. Thirty‐five patients underwent liver transplantation and received preemptive therapy for hepatitis C. They were divided into two groups: those with splenectomy (group A, n = 21) and those without (group B, n = 14). There was no significant difference in the frequency of morbidity between the groups. Platelet counts were well maintained in group A patients during the therapy, and cytopenia led to the discontinuation of the therapy in one group B patient. The results of the preliminary study warrant a randomized control trial to examine the feasibility of splenectomy and preemptive viral therapy during liver transplantation for hepatitis C.

Outcomes After Living Donor Liver Transplantation for Acute Liver Failure in Japan: Results of a Nationwide Survey

Nationwide surveys of acute liver failure (ALF) are conducted annually in Japan, and 20% of patients with ALF undergo liver transplantation (LT). We extracted data for 212 patients who underwent LT for ALF from the nationwide survey database of the Intractable Liver Diseases Study Group of Japan. After the exclusion of 3 patients who underwent deceased donor LT, 209 recipients of living donor liver transplantation (LDLT) were analyzed. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the diseases onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late‐onset hepatic failure (LOHF). Long‐term follow‐up data were obtained from the registry of the Japanese Liver Transplantation Society. The 2 data sets were merged, and descriptive and survival data were analyzed. A Cox regression analysis was performed to define factors predicting overall mortality, short‐term mortality (≤90 days after LT), and long‐term mortality (>90 days after LT). One hundred ninety of the analyzed patients (91%) were adults (age ≥ 18 years); 70 patients (34%) were diagnosed with acute ALF, 124 (59%) were diagnosed with subacute ALF, and 15 (7%) were diagnosed with LOHF. Hepatitis B virus was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy–induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The cumulative patient survival rates 1, 5, and 10 years after LT were 79%, 74%, and 73%, respectively. Patient age was associated with short‐ and long‐term mortality after LT, whereas ABO incompatibility affected short‐term mortality, and donor age affected long‐term mortality. In conclusion, the long‐term outcomes of LDLT for ALF in this study were excellent, regardless of the etiology or classification. The majority of the donors were living donors. Increasing the deceased donor pool might be an urgent necessity. Liver Transpl, 2012.

Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma.

Tumor markers [alpha‐fetoprotein (AFP) or des‐gamma‐carboxyprothrombin (DCP)] and neutrophil/lymphocyte ratio (NLR) reportedly correlate with long‐term outcomes for hepatocellular carcinoma (HCC). However, no standardized method has been established for evaluating the pretransplant data. One hundred and twenty‐four patients who underwent living donor liver transplantation (LDLT) were retrospectively reviewed. The best predictive parameters for tumor recurrence were maximum values for AFP or DCP and 90‐day mean values for NLR, respectively, and multivariate analysis confirmed these values were correlated with tumor recurrence. However, receiver operating characteristic analysis revealed that discriminative powers were sufficient only in maximum AFP [area under the curve (AUC) 0.88, P < 0.001] and maximum DCP (AUC 0.76, P < 0.001), while mean NLR was less predictive (AUC 0.62, P = 0.20). When incorporating AFP and DCP to the Tokyo criteria (≤5 tumors with each tumor ≤5 cm), the presence of at least two of the following factors: (i) beyond the Tokyo criteria, (ii) AFP>250 ng/ml, and (iii) DCP > 450 mAu/ml (>450 ng/ml), was correlated with a worse 5‐year disease‐free survival rate (20.0% vs. 96.8%, P < 0.001) and 5‐year overall survival rate (20.0% vs. 84.0%, P < 0.001). The prognosis of patients undergoing LDLT for HCC strongly relies on maximum AFP or DCP values before transplantation, while the prognostic impact of NLR is limited.

Bloodstream infection after living donor liver transplantation

There are no detailed studies on the prevalence or clinical magnitude of bloodstream infection (BSI) following living donor liver transplantation (LDLT). The study aimed to assess the incidence and analyze the risk factors for BSI after LDLT. Univariate and multivariate analyses were performed to identify the independent risk factors for postoperative BSI. Postoperatively, 26 episodes of BSI occurred in 21 of 242 studied adult patients by median postoperative d 35. Five patients had primary BSI. The source was unknown in 3 patients and an intravascular catheter in 2. The other 16 patients had secondary BSI. Secondary BSI was caused by surgical site infection in 8 patients, followed by intra-abdominal infection in 5, pneumonia in 2, and both surgical site infection and intra-abdominal infection in 1. The most frequent pathogen isolated was MRSA, which was detected in 4 patients. Surveillance culture detected the same isolates prior to BSI in 14 of 26 (50%) episodes. Diabetes mellitus and serum albumin level less than 2.4 g/dl independently predicted postoperative BSI. Perioperatively, screening for and taking actions against pathogen including MRSA should be performed in LDLT patients.