Hirofumi Kanemura

Expression of hypoxia-inducible factor-1 alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma : correlation with poor prognosis with possible regulation

Objectives: Hypoxia-inducible factor 1&agr; (HIF-1&agr;) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1&agr; expression; however, the association between HIF-1&agr; and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. Methods: Hypoxia-inducible factor 1&agr;, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1&agr;, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. Results: Hypoxia-inducible factor 1&agr;, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1&agr;, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1&agr; and HDAC1-positive stainings were significantly lower than for patients with HIF-1&agr; and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. Conclusions: These results suggest that HIF-1&agr; expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1&agr; and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment.

Current Concept of Small-for-Size Grafts in Living Donor Liver Transplantation

The extended application of living donor liver transplantation (LDLT) has revealed the problem of graft size mismatching called “small-for-size (SFS) graft syndrome.” The initial trials to resolve this problem involved increasing the procured graft size, from left to right, and even extension to include a right lobe graft. Clinical cases of living right lobe donations have been reported since then, drawing attention to the risks of increasing the liver volume procured from a living donor. However, not only other modes of increasing graft volume such as auxiliary or dual liver transplantation, but also control of the increased portal pressure caused by an SFS graft, such as a portosystemic shunt or splenectomy, have been trialed with some positive results. To establish an effective strategy for transplanting SFS grafts and preventing SFS graft syndrome, it is essential to have precise knowledge and tactics to evaluate graft quality and graft volume, when performing these LDLTs with portal pressure control. We reviewed the updated literature on the pathogenesis of and strategies for using SFS grafts.

Real time elastography for noninvasive diagnosis of liver fibrosis

BACKGROUND/PURPOSE The accurate preoperative evaluation of liver fibrosis stage is important in determining surgical procedures. Although percutaneous liver biopsy is the gold standard, it may cause undesirable complications, such as bleeding. This study aimed to evaluate the usefulness of real-time tissue elastography for the preoperative assessment of liver fibrosis stage. METHODS We focused on a new mode of sonogram, real-time elastography, which can show tissue elasticity on images, and express the elasticity numerically. The elastic ratio of the liver for the intercostal muscle for each patient was calculated preoperatively, using the sonography device. The liver fibrosis stages were finally determined in the operative specimens from 41 patients. We examined the correlation between the elastic ratio and the histological fibrosis stage. RESULTS The lower the elastic ratio, the more advanced was the liver fibrosis stage. There was a significant correlation between the elastic ratio and the histological fibrosis stage. The area under the receiver-operating characteristics curve for the diagnosis of significant liver fibrosis using this device was superior to those conventionally determined by blood parameters. CONCLUSIONS Real-time elastography is a promising sonography-based noninvasive method for the preoperative assessment of liver fibrosis.

Strategies for improving the outcomes of small-for-size grafts in adult-to-adult living-donor liver transplantation

Living-donor liver transplantation (LDLT) has been refined and accepted as a valuable treatment for patients with end-stage liver disease in order to overcome the shortage of organs and mortality on the waiting list. However, graft size problems, especially small-for-size (SFS) grafts, remain the greatest limiting factor for the expansion of LDLT, especially in adult-to-adult transplantation. Various attempts have been made to overcome the problems regarding SFS grafts, such as increasing the graft liver volume and/or controlling excessive portal inflow to a small graft, with considerable positive outcomes. Recent innovations in basic studies have also contributed to the treatment of SFS syndrome. Herein, we review the literature and assess our current knowledge of the pathogenesis and treatment strategies for the use of SFS grafts in adult-to-adult LDLT.

Argon gas embolism in the application of laparoscopic microwave coagulation therapy

BACKGROUND A major concern in the use of the argon beam coagulator system is the potential risk of argon gas embolism. METHODS Seven cases with argon gas embolism in the English literature were reviewed along with the current case. The latter case was a 77-year-old female having laparoscopic hepatectomy after application of the microwave coagulation system on the cutting planes. RESULTS Immediately following shots of an argon beam to control local bleeding at the needle hole in the liver caused by microwave coagulation, the end-tidal carbon disappeared, followed by cardiovascular collapse. After 18 min of cardiovascular resuscitation, the tumors were resected under laparotomy. CONCLUSIONS After reviewing the cases, pneumoperitoneum (57.1%), hepatic needle punctures (42.8%) and direct application of the argon beam to the liver (28.6%) can be considered as risky processes in such events. Caution is necessary in the use of an argon beam in liver surgery to avoid life-threatening gas embolism.

Beneficial effects of hyperbaric oxygen pretreatment on massive hepatectomy model in rats.

Background. The purpose of this study was to investigate the impact of hyperbaric oxygen (HBO) pretreatment in massive hepatectomy model, a surrogate model of small-for-size graft, using rats. Methods. (Experiment I) Rats were divided into the following four groups: HBO (−), HBO-1D (day), HBO-3D, and HBO-5D. Samples were taken after the completion of HBO pretreatment, and the following parameters were evaluated: reverse transcription polymerase chain reaction and immunohistochemical staining for HSP 70 and HO-1; biochemical parameters; and liver weight to body weight ratio (Lw/Bw ratio). (Experiment II) Rats were divided into four groups as follows; 70% hepatectomy (Hx), 70% Hx-HBO, 90% Hx, and 90% Hx-HBO group. Samples were taken 12, 24, 48, and 72 hr after hepatectomy and the following parameters were investigated: biochemical analysis; Lw/Bw ratio; PCNA labeling index; and survival. Results. (Experiment I) The expression of HSP70 mRNA was significantly increased in the HBO-3D group compared with the HBO (−) group (P<0.05). HSP70- and HO-1-positive hepatocytes were significantly increased in the HBO-3D group compared with the HBO (−) group (P<0.05). (Experiment II) Transaminases were significantly decreased in both 70% and 90% Hx-HBO groups compared with Hx alone group (P<0.05). The Lw/Bw ratio and PCNA labeling index of the 90% Hx-HBO group were significantly increased compared with the 90% Hx group, 24, 48 and 72 hr after hepatectomy (P<0.05). The survival rate in the 90% Hx-HBO group was significantly higher than that in the 90% Hx group (P=0.01). Conclusions. HBO pretreatment had beneficial effects in a massive hepatectomy model in rats via the induction of HSP70 and HO-1.

The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma: a special reference to recurrence pattern and Milan criteria.

Introduction. Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). Methods. Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. Results. (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. Conclusions. For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR.

Sclerosed hemangioma of the liver: Report of a case and review of the literature.

A sclerosed hemangioma of the liver is an extremely rare type of benign hepatic tumor. A 77‐year‐old female was referred to Tokushima University Hospital with fever, abnormal liver function tests and a large liver mass. The tumor, 10 × 5 cm in size and located in segment 5–6 of the liver, was depicted as a low density tumor with enhancement by computed tomography (CT). Magnetic resonance imaging (MRI) showed it to be a tumor with a low signal on T1‐weighted and a high signal on T2‐weighted images. The patient was negative for hepatitis B surface antigen and hepatitis C antibody. She underwent a right hepatectomy for possible malignant liver tumors, including intrahepatic cholangiocarcinoma or fibrolamellar hepatocellular carcinoma. The following histological examination of the surgical specimen revealed the tumor to be a hepatic sclerosed hemangioma with characteristic dense collagenous tissues. We report here on the case of this unusual tumor and review the relevant literature.

Mucoepidermoid carcinoma of the liver: report of a rare case and review of the literature.

Although a mucoepidermoid carcinoma is sometimes seen as a neoplasm originating from the salivary glands, its origination from the liver is rare. A review of the medical literature in the English language disclosed only 16 cases originating from the hepatic system. The case explored here is that of an 81‐year‐old female, without any significant medical history, who was referred to our hospital for elevated liver function tests. Computed tomography (CT) showed a huge tumor, 10 cm in diameter, in the right lobe of the liver. The central part of the tumor was consistently un‐enhanced, suggesting a large necrotic area. The liver tumor was diagnosed as mucoepidermoid carcinoma by a percutaneous biopsy. Despite chemotherapy with radiation therapy, the tumor showed very aggressive malignancy, resulting in early mortality. We herein report on a rare case of primary mucoepidermoid carcinoma of the liver with pulmonary and lymph node metastasis, confirmed by autopsy, and review the literature.

Beneficial use of the round ligament as a patch graft for vena cava reconstruction

BACKGROUND/PURPOSE The availability of an appropriate vascular graft is a significant concern in an extensive hepatic resection with part of the vena cava. METHODS/RESULTS The patient had multinodular hepatocellular carcinoma, occupying the whole posterior segment with a tumor thrombus bulging inside the vena cava. At laparotomy, a segment of the round ligament was procured for use as a patch graft. After the mobilization of the right-side liver without taking down the short hepatic veins, parenchymal resection was completed with the use of a hanging maneuver. The hepatic vena cava was semitotally side-clamped, followed by resection of the caval wall with the tumor thrombus, resulting in an en-bloc resection. The procured round ligament was opened, trimmed, and sutured to the vena cava as a patch graft, followed by smooth reperfusion. CONCLUSIONS The use of an opened round ligament as a venous patch graft is an easy and feasible technique in patch reconstruction of the vena cava.