Ken Takasaki

Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma

Background. In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. Methods. We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. Results. Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas-7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P=0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31 ; 95 percent confidence interval, 0.12 to 0.78). Conclusions. Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

We describe six patients with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). From 1990 to 2001, we treated 82 patients with NASH and observed six patients (three men and three women, aged 56-72 years) in this group who were referred with HCC or developed the complication during follow-up. In five of these six patients, NASH was associated with obesity (cases 3, 4 and 5), hyperlipidemia (case 5), or diabetes mellitus (cases 1, 3 and 6). We confirmed the presence of HCC by ultrasonography-guided tumor biopsy or surgery except in case 3 where we diagnosed the tumor by ultrasonography, computed tomography and selective hepatic arteriography. The carcinomas measured 1.5-6.0 cm in diameter and three were well differentiated. When HCC was diagnosed, cirrhosis was present in all instances. Four of the six tumor patients also had esophageal varices but only one patient had a history of variceal bleeding and ascites. Treatment of HCC consisted of surgery (cases 1 and 5), transcatheter arterial embolization or infusion and/or percutaneous ethanol injection (cases 2, 3, 4, and 6). In patients with NASH cirrhosis, the development of treatable HCC is sufficiently common to warrant regular screening for this grave complication.

Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma

Survival after surgery for intrahepatic cholangiocarcinoma (ICC) is usually poor. The objective of this study was to investigate whether the gross appearance of ICC indicates postoperative prognosis.

Differential diagnosis of polypoid lesions of the gallbladder by endoscopic ultrasonography

BACKGROUND Transabdominal ultrasonography (US) has made the detection of gallbladder polyps easier, but the differential diagnosis of polyps less than 20 mm remains difficult. Therefore, we evaluated the usefulness of endoscopic ultrasonography (EUS) for the differential diagnosis of gallbladder polyps. METHODS Among patients with gallbladder polyps less than 20 mm, we reviewed 89 patients who underwent US and EUS before surgery and assessed the results of differential diagnoses by them. RESULTS In all, 86.5% of these polyps were precisely diagnosed by EUS. However, only 51.7% were diagnosed by US. Sensitivity, specificity, and positive and negative predictive values of EUS at the diagnosis of carcinoma were 91.7%, 87.7%, 75.9%, and 96.6%, respectively. Those of US were 54.2%, 53.8%, 54.2%, and 94.6%, respectively. CONCLUSIONS EUS may markedly improve the accuracy of the differential diagnosis of gallbladder polyps. Therefore, EUS is thought to play an important role in determining the treatment strategy for gallbladder polyps.

Bleeding during hepatectomy can be reduced by clamping the inferior vena cava below the liver

BACKGROUND Control of blood loss is a crucial problem during hepatectomy. Bleeding from the inflow system can be controlled by the Pringle maneuver or selective vascular occlusion. Bleeding from the outflow system is closely related to central venous pressure (CVP). Therefore, in this study, we evaluated whether vascular outflow control by clamping the inferior vena cava (IVC) below the liver (IVC clamping) during hepatectomy is a safe and effective method to reduce blood loss and CVP. METHODS We reviewed the outcomes of 103 consecutive patients whose CVP values were >5 cm H(2)O and who had undergone right or left hemihepatectomy between 1995 and 2000. Forty-seven patients who underwent hepatectomy with IVC clamping (Group A) between 1998 and 2000 were compared with the previous 56 patients who underwent hepatectomy without IVC clamping between 1995 and 1997 (Group B). RESULTS The CVP decreased by 3.7 cm H(2)0 after IVC clamping. Estimated blood loss was 910 mL in Group A and 1177 mL in Group B. (P=.008) No severe renal or cardiovascular damage occurred after IVC clamping. CONCLUSIONS IVC clamping is very effective in reducing blood loss during hepatectomy when the CVP is elevated and cannot be reduced pharmacologically or by fluid restriction.

Clinicopathologic features of patients with hepatocellular carcinoma seropositive for α‐fetoprotein‐L3 and seronegative for des‐γ‐carboxy prothrombin in comparison with those seropositive for des‐γ‐carboxy prothrombin alone

Abstract Background : There has been no study of the clinicopathologic features of patients with hepatocellular carcinoma (HCC) who are seropositive for lectin‐reactive α‐fetoprotein (AFP‐L3) alone, or seropositive for AFP‐L3 and seronegative for des‐γ‐carboxy prothrombin (DCP) in comparison with those who are seropositive for DCP alone. Thus, the present comparative study was performed.

Favorable Surgical Outcomes in Patients With Early Hepatocellular Carcinoma

Background:Early hepatocellular carcinoma (HCC) is defined as well-differentiated HCC with an obscure tumor margin in the classification of the Liver Cancer Study Group of Japan. However, the surgical outcomes in patients with early HCC have not yet been clarified. Methods:From 1985 to 1994, 186 patients with HCC 2 cm or less in greatest dimension underwent curative hepatectomy. Of the 186 cases, 37 were early HCC and 149 were small advanced HCC. The relationship between clinicopathological findings and surgical outcomes was examined. Results:The rate of hepatitis C antibody or number of tumors was significantly higher in patients with early HCC than in patients with small advanced HCC. Liver function test showed no differences between patients with early HCC and patients with small advanced HCC. The 5-and 10-year survival rates were 85% and 61%, respectively, in patients with early HCC, which was significantly better than in patients with small advanced HCC (P = 0.0137). Univariate and multivariate analysis showed Child-Pugh class, intrahepatic metastasis, and early HCC to be significant prognostic factors. Conclusions:Patients with early HCC had a different clinical background and good surgical outcomes; therefore, it should be recognized that early HCC is a distinct clinicopathological entity.

Should the Extrahepatic Bile Duct be Resected or Preserved in R0 Radical Surgery for Advanced Gallbladder Carcinoma? Results of a Japanese Society of Biliary Surgery Survey: A Multicenter Study

PurposeWe assessed the significance of an extra bile duct resection by comparing the survival of patients with advanced gallbladder carcinoma who had resected bile ducts with those who had preserved bile ducts. A radical cholecystectomy that includes extra bile duct resections has been performed without any clear evidence of whether an extra bile duct resection is preventive or curative.MethodsWe conducted a questionnaire survey among clinicians who belonged to the 114 member institutions of the Japanese Society of Biliary Surgery. The questionnaires included questions on the preoperative diagnosis, complications, treatment, and surgical treatment, resection procedures, surgical results, pathological and histological findings, mode and site of recurrence, and the need for additional postoperative treatment. A total of 4243 patients who had gallbladder carcinoma and were treated from January 1, 1994 to December 31, 2003 were identified. The 838 R0 patients with pT2, pT3, and pT4 advanced carcinoma of the gallbladder for which there was no cancer invasion to the hepatoduodenal ligament or cystic duct in the final analysis.ResultsThe 5-year cumulative survival, postoperative complications, postoperative lymph node metastasis, and local recurrence along the hepatoduodenal ligament were not substantially different between the resected bile duct and the preserved bile duct groups.ConclusionsOur retrospective questionnaire survey showed that an extrahepatic bile duct resection had no preventive value in some patients with advanced gallbladder carcinoma in comparison to similar patients who had no such bile duct resection. An extrahepatic bile duct resection may therefore be unnecessary in advanced gallbladder carcinoma without a direct infiltration of the hepatoduodenal ligament and the cystic duct.

Hepatic resection in 485 R0 pT2 and pT3 cases of advanced carcinoma of the gallbladder: results of a Japanese Society of Biliary Surgery survey—a multicenter study

PURPOSE We conducted this study to evaluate the optimal hepatic resection for pT2 and pT3 advanced carcinoma of the gallbladder without invasion of the hepatoduodenal ligament. METHODS We conducted a questionnaire survey regarding 4,243 cases of carcinoma of the gallbladder treated during the recent 10-year period at 112 institutions belonging to the Japanese Society of Biliary Surgery. The questionnaires included questions on preoperative-diagnosis, complications, treatment, and surgical treatment, procedures of resection, surgical result, path histological findings, mode, and site of recurrence, additional post-operative treatment. They included 293 pT2 and 192 pT3 R0 cases, which were negative for hepatoduodenal ligament invasion, and the cumulative survival rates and sites of postoperative recurrence in the form of liver metastasis, were retrospectively analyzed in these 485 cases. RESULT There were no significant differences in survival rate or recurrence rates in the form of liver metastasis between the groups that underwent resection of the gallbladder bed, the group that underwent segmentectomy 4a+5, and the group that underwent hepatectomy in patients with of both pT2 or pT3 gallbladder cancers. Our results also did not show that liver metastasis to segment 4a5 alone was particularly common. CONCLUSION For gallbladder cancer, neither with hepatoduodenal ligament invasion nor hepatic invasion, resection of the gallbladder bed is more preferable for surgical hepatic procedure. For gallbladder cancer that invades any hepatic sites, a hepatic surgical procedure that could eliminate surgical margins would be desirable.

Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for α-fetoprotein alone and those seropositive for des-γ-carboxy prothrombin alone1

There has been no comparative study of the clinicopathological features of HCC patients who are seropositive for α‐fetoprotein (AFP) alone and those who are seropositive for des‐γ‐carboxy prothrombin (DCP) alone. The authors, thus, performed this comparative study.