Tetsuo Tomonaga

Elective living donor liver transplantation by hybrid hand-assisted laparoscopic surgery and short upper midline laparotomy

BACKGROUND Although the technique of liver transplantation is well developed, the invasiveness of the operation can be decreased with laparoscopic procedures. METHODS We performed elective living donor liver transplantation (LDLT) through a short midline incision combined with hand-assisted laparoscopic surgery (HALS). Nine selected patients with end stage liver disease underwent the procedure between July, 2010 and February, 2011 (median age 60, median Child-Pugh 9, median MELD score 14). Splenectomy was performed simultaneously in 7 cases. The liver (and spleen) were mobilized by a sealing device under a HALS procedure with an 8-cm upper midline incision, followed by explantation of the diseased liver (and spleen) through the upper midline incision which was extended to 12 to 15 cm. Partial liver grafts were implanted through the upper midline incision. RESULTS The median duration of the operation was 741 minutes, the median time needed for anastomosis was 48 minutes, the median blood loss was 3,940 g, and the median liver weight was 866 g. Eight recipients are alive and have good graft function. A difficult implantation for one patient required an additional right transverse incision. When compared with 13 recent liver recipients who underwent LDLT with a regular Mercedes-Benz-type incision, no clinically relevant drawbacks of the HALS hybrid procedure were observed. CONCLUSION We have shown the feasibility and safety of LDLT performed through a short midline incision without abdominal muscle disruption with the aid of HALS.

Liver Transplantation for Patients with Human Immunodeficiency Virus and Hepatitis C Virus Coinfection with Special Reference to Hemophiliac Recipients in Japan

Liver transplantation for patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) remains challenging. The advent of highly active antiretroviral therapy (HAART) for HIV has reduced mortality from opportunistic infection related to acquired immunodeficiency syndrome dramatically, while about 50% of patients die of end-stage liver cirrhosis resulting from HCV. In Japan, liver cirrhosis frequently develops after HCV-HIV coinfection resulting from previously transfused infected blood products for hemophilia. The problems of liver transplantation for those patients arise from the need to control calcineurin inhibitor with HAART drugs, the difficulty of using interferon after liver transplantation with HAART, and the need to control intraoperative coagulopathy associated with hemophilia. We review published reports of liver transplantation for these patients in the updated world literature.

Transition of serum alkaline phosphatase isoenzymes during liver regeneration in humans.

BACKGROUND/AIMS Serum alkaline phosphatase (ALP) levels tend to increase after hepatectomy, however, no previous examinations have yet focused on the relationship between liver regeneration and the individual ALP isoenzymes levels. METHODOLOGY Forty living liver transplantation donors who underwent hemi-hepatectomy were herein investigated. We evaluated the serum ALP levels and ALP isoenzyme levels preoperatively and postoperatively. The liver regeneration rate (LRR) was calculated using volumetry. According to the LRR, we divided the donors into two groups, consisting of a high regeneration group (HG) and a low regeneration group (LG). RESULTS The total serum ALP levels increased gradually after hepatectomy and peaked on postoperative days (POD) 14. ALP-1 was not detected in any donor preoperatively; however it was detected after hepatectomy, peaking on POD 7. The serum ALP-2 level increased after hepatectomy, reaching a peak level on POD 14. The ALP-2 levels gradually increased after hepatectomy and reached peak levels on POD 14 in both groups. However, the ALP-2 level on POD 14 was significantly higher in HG than LG. CONCLUSIONS The serum ALP- 2 levels after POD 14 might therefore be a useful indicator of favorable liver regeneration following hepatectomy, especially in patients who have a normal liver function.BACKGROUND/AIMS Serum alkaline phosphatase (ALP) levels tend to increase after hepatectomy. However, no previous examinations have yet focused on the relationship between liver regeneration and the individual ALP isoenzymes levels. METHODOLOGY Forty living liver transplantation donors who underwent hemi-hepatectomy were herein investigated. We evaluated the serum ALP levels and ALP isoenzyme levels preoperatively and postoperatively. The liver regeneration rate (LRR) was calculated using volumetry. According to the LRR, we divided the donors into two groups, consisting of a high regeneration group (HG) and a low regeneration group (LG). RESULTS The total serum ALP levels increased gradually after hepatectomy and peaked on postoperative day (POD) 14. ALP-1 was not detected in any donor preoperatively. However, it was detected after hepatectomy, peaking on POD 7. The serum ALP-2 level increased after hepatectomy, reaching a peak level on POD 14. The ALP-2 levels gradually increased after hepatectomy and reached peak levels on POD 14 in both groups. However, the ALP-2 level on POD 14 was significantly higher in HG than LG. CONCLUSIONS The serum ALP-2 levels after POD 14 might therefore be a useful indicator of favorable liver regeneration following hepatectomy, especially in patients who have a normal liver function.

Hemophagocytic syndrome after liver transplantation: Report of two cases

We report two cases of hemophagocytic syndrome (HPS), a rare but fatal complication after living-donor liver transplantation (LDLT). Despite their recovery from pancytopenia following treatment with steroid pulse therapy, granulocyte stimulating factor, and intravenous γ-globulin, both patients died. The outcomes reported in cases published in English are devastating, with only 4 survivors among the total 14 patients including ours. Pancytopenia is frequently recognized postoperatively in liver transplant recipients, although its cause is difficult to establish. When pancytopenia accompanying persistent high fever is recognized in LDLT recipients, HPS should be suspected and bone marrow aspiration performed as promptly as possible because of the poor prognosis of this syndrome. There is still no optimal treatment for HPS after liver transplantation.

Indocyanine Green Dye Excretion in Bile Reflects Graft Function After Living Donor Liver Transplantation

There are many biochemical parameters that can be used to assess the function of partial liver graft; however, a definitive marker remains to be identified. For example, the color of bile has been reported anecdotally to reflect graft function, but its value has not yet been fully evaluated. Recently, indocyanine green (ICG) K value, that is ICG clearance, was found to be valuable in assessing the function of a whole or partial graft after living donor liver transplantation (LDLT) (1). However, the measurement of ICG dye concentrations in serum is not valid in hyperbilirubinemic patients because of interference while using the spectrophotometer (2). We previously reported the value of ICG dye concentration in the bile in an ICG challenge test in patients undergoing liver resection for bile duct cancer, because ICG is a relatively hydrophobic organic anion that has a high hepatic extraction ratio and is excreted extensively and remains unchanged in bile (3). It has also been reported that ICG excretion in bile could be a good parameter for assessing preoperative liver function in biliary drainage patients because it reflects adenosine triphosphate levels in the liver (4, 5). Thus, this study evaluates ICG excretion in bile after LDLT as a potential novel parameter of partial liver graft function. This prospective study was approved by the local institutional review board, and written informed consent was obtained from all patients. Of 37 consecutive patients who underwent liver transplantation between April 2005 and March 2007, 32 patients who received duct-to-duct biliary reconstruction were studied (median age 53 years; right lobe graft:left-sided graft 19:13; and graft volume/standard liver volume median 46%). One week after LDLT, we performed a fasting ICG injection test (0.5 mg/kg; Diagnogreen Inj.; Daiichi Seiyaku, Tokyo, Japan), and bile was collected through biliary external stenting reported earlier (6) while blocking natural light. ICG concentrations in bile at 0, 30, 120, and 360 min after injection were measured by spectrophotometer at a wavelength of 805 nm. Blood samples were also taken before ICG injection and 15 min after injection. All data were expressed as median values with ranges. The pattern of change in ICG excretion after ICG injection showed distinct two patterns. Type I (n 24) showed a steep increase and a peak within 2 hr and returned to baseline within 6 hr, whereas type II (n 8) showed a low peak of less than 1 micromole per liter during the 6-hr observation period. Table 1 shows various detailed parameters of type I and type II patients and their LDLTs. The parameters that correlated with ICG patterns were compared between the two groups, and donor age and graft type were found to have a significant influence on the type of ICG excretion in bile. Also, it shows the relationship between the type of ICG excretion in bile and various graft functions such as jaundice, prothrombin activity, and ICG retention rate at 15 min. In fact, because retention rate of ICG at 15 min after injection was correlated with type of ICG excretion in bile, ICG retention rate at 15 min can substitute the excretion pattern in bile. Several type II patients had prolonged jaundice after LDLT due to outflow block (n 1), acute cellular rejection (n 2), or unknown cause (n 5). To clarify changes in ICG pattern over time, the same challenge test was performed at 3 months after LDLT. Most patients remained or became type I (data not shown). Six of the eight patients who were classified as type II at 1 week after LDLT were classified as type I at 3 months after LDLT. Remaining two patients had prolonged jaundice until approximately 6 months after LDLT and recovered without jaundice. These two patients were complicated with biliary

Transplanted fibroblast cell sheets promote migration of hepatic progenitor cells in the incised host liver in allogeneic rat model

Cell sheet engineering has been noted as a new and valuable approach in the tissue‐engineering field. The objective of this study was to explore a procedure to induce hepatic progenitor cells and biliary duct structures in the liver. Sprague–Dawley rat dermal fibroblast (DF) sheets were transplanted into the incised surface of the liver of F344 nude rats. In the control group, an incision was made without transplantation of the DF sheets. Bile duct (BD)‐like structures and immature hepatocyte‐like cells were observed in the DF sheet transplant sites. These BD‐like structures were cytokeratin‐8‐positive, while the hepatocyte‐like cells were both OV‐6‐positive and α‐fetoprotein‐positive as well. The proliferation and differentiation of liver progenitor cells were not influenced by hepatectomy. We also transplanted DF sheets transfected with a plasmid encoding the enhanced yellow fluorescent protein target to mitochondria (pEYFP–Mito) by electroporation, and found that the new structures were pEYFP–Mito‐negative. We observed new BD‐like structures and immature hepatocytes after transplantation of DF sheets onto incised liver surfaces, and clarified that the origin of these BD‐like structures and hepatocyte‐like cells was the recipient liver. The present study described an aspect of the hepatic differentiation process induced at the site of liver injury. Copyright

A case of ruptured segmental arterial mediolysis of the hepatic artery: report of a case.

This article reports a patient with intra-abdominal hemorrhage secondary to a rare vascular disease, segmental arterial mediolysis (SAM). The patient was a 68-year-old male who presented with chilling and severe abdominal pain. Abdominal computed tomography results suggested the presence of an intra-abdominal hemorrhage. Although visceral angiography illustrated multiple aneurysms in the branches of the hepatic artery, active bleeding was not evident. Conservative therapy including transfusion was performed, and re-angiography revealed the disappearance of multiple hepatic arterial aneurysms 8 months later. This is the first case of intra-abdominal hemorrhage related to SAM of the hepatic artery in which natural history of SAM was seen.

Curcumin improves the survival rate after a massive hepatectomy in rats.

BACKGROUND/AIMS Curcumin possesses anti-inflammatory and antioxidant effects. Curcumin pretreatment provided a hepatoprotective effect in rat models of chemically-induced hepatotoxicities and ischemia/reperfusion injuries. In this study, we examined whether curcumin could improve the survival rate of rats undergoing a 90% hepatectomy. METHODOLOGY Rats were administered 340 mg/kg oral curcumin formulated with phosphatidylcholine (curcumin group) or vehicle (control group) for 7 consecutive days and 2 hours prior to the massive hepatectomy. RESULTS Six of the 13 rats pretreated with curcumin survived, whereas all 13 rats pretreated with vehicle died within day 2 following a massive hepatectomy. A histological examination showed the lobular structure to be disturbed in the rats pretreated with vehicle, whereas the hepatic lobular structure remained relatively stable without necrosis in the rats pretreated with curcumin. The contents of heme oxygenase-1 (HO-1) protein in the control group were low in the preoperative phase. In contrast, the levels of HO-1 protein in the curcumin group were high at the preoperative phase, and thereafter remained at high levels until day 7 following surgery. CONCLUSIONS Our results suggest that curcumin improves the survival rate by increasing the antioxidant activity in rats after a massive hepatectomy.

Tumor thrombectomy via a surgically reopened umbilical vein combined with right hemihepatectomy in a patient with hepatocellular carcinoma.

This report presents a case of a patient with a huge hepatocellular carcinoma in the right lobe of the liver with an extensive portal venous tumor thrombus extending into the main portal trunk and left portal branch. The patient underwent extended right hemihepatectomy with tumor thrombectomy with direct extraction from an opening of the ventral wall of the right portal vein and using a balloon catheter to push the tumor thrombus via the surgically reopened umbilical vein. This technique seems useful in cases of tumor thrombus that extend deep into the umbilical portion of the left portal vein. In addition, this technique may have minimized the intraoperative migration of the tumor thrombus into the future remnant liver by occluding portal flow with the balloon catheter during the thrombectomy.

Are there any similarities in the hepatic vascular anatomy among blood relatives

BACKGROUND/AIMS The existence of similarities in the hepatic vascular anatomy among blood relatives (BR) have never been studied before. Since in living donor liver transplantation (LDLT), the donor may be a BR, an opportunity is available to assess whether there are similarities in the hepatic vascular anatomy among BR. METHODOLOGY We conducted an analysis of 61 LDLT during the period from January 2004 to August 2008. Based on preoperative multi-detector computed tomography data, the hepatic arteries (HA) were classified into 4 groups, the portal vein (PV) was classified into 2 groups and the right hepatic vein (RHV) was classified into 2 groups. The data of each group were then compared between BR (n=47) and NBR (n=14). RESULTS With regard to the HA anatomy, 30 cases (68%) of the BR donor matched that of the recipient and 9 cases (69%) in the NBR donor. The PV anatomy was matched in 41 cases (87%) of BR donor and 11 cases (79%) in the NBR donor. The anatomy of the RHV was matched in 25 cases (53%) in the BR donor and 9 cases (64%) in NBR donor. There was no significant difference in all contexts. CONCLUSIONS No similarities were therefore observed in the hepatic vascular anatomy among BR.