Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system.

AIMS: We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group, which had the same size liver but no PL. METHODS: The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays and the hepatic ATP level was measured. RESULTS: The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, P < 0.05). Gene expression of cyclin D1, proliferating cell nuclear antigen, cyclin A and B was upregulated, and the cyclin-dependent kinase inhibitor was downregulated. Increases were observed in: (i) pyruvate dehydrogenase, the tricarboxylic acid cycle cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48 +/- 0.01 micromol/ml vs. 0.33 +/- 0.01 micromol/ml, P < 0.05). CONCLUSION: The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism.

Diaphragmatic hernia resulting from injury during microwave-assisted laparoscopic hepatectomy.

A 31-year-old woman underwent microwave-assisted laparoscopic hepatectomy of the left lateral segment for focal nodular hyperplasia on January 14, 1998. On September 9, 1998, she felt continuous left abdominal pain and was admitted to our hospital for further examination. An upper gastrointestinal series showed converging folds of the greater curvature of the upper third of the stomach and craniad displacement of this portion. Thoracic magnetic resonance imaging showed herniation of the stomach into the pleural cavity. The patient was referred to our department, where she underwent surgery for a diaphragmatic hernia. The fundus of the stomach had escaped into the left pleural cavity through a defect in the diaphragm near where laparoscopic hepatectomy had been performed. The stomach was returned to the peritoneal cavity and the defect sutured. The patients postoperative course was uneventful. Although diaphragmatic hernia after laparoscopic surgery is a rare complication, with the performance of more advanced laparoscopic procedures and the use of higher-technology tissue-destruction/hemostatic devices such as the microwave coagulator, more caution should be observed to prevent injury to adjacent organs such as the diaphragm.

Adjuvant therapies using biliary stenting for malignant biliary obstruction.

The aim of this study was to analyze the patency of expandable metallic stents in malignant biliary obstruction and to evaluate the efficacy of adjuvant therapy accompanied by biliary stenting. We analyzed 29 patients in whom bile duct stenting was performed for malignant biliary obstruction. Their types of disease were: hilar ductal carcinoma (n = 8), gallbladder carcinoma (n = 11), and pancreatic carcinoma (n = 10). Initially, 46 expandable metallic stents were placed in 29 patients. In 23 of the 29 patients, adjuvant therapy was administered. Seventeen patients underwent radiotherapy, and 16 patients received various systemic chemotherapies. In principle, hyperthermia was performed twice a week, simultaneously with radiotherapy. Patient survival and the probability of stent patency were calculated using actuarial life table analysis. There was no significant difference in stent patency among the patients according to type of disease. Hyperthermia did not influence the stent patency rate. The median stent patency time was significantly greater in the chemo-radiation group than in the no-adjuvant therapy group: 182 days versus 68 days, respectively (P = 0.017). Moreover, a significant increase was seen in the median survival time in the chemo-radiation group: 261 days versus 109 days (P = 0.0337). Complications occurred in 9 patients (31.0%). Stent occlusion occurred in 6 patients (20.7%), with all of these patients managed successfully using a transhepatically placed new expandable metallic stent, employing the stent-in-stent method. Stent migration occurred in 2 patients after radiotherapy. Adjuvant therapies such as radiotherapy and systemic chemotherapy, in combination with stent insertion, resulted in an increase in the patency period of expandable metallic stents and in increased patient survival time.

Two-step selective clamping of IVC for removal of hepatocellular carcinoma with intracaval extension.

Hepatocellular carcinoma (HCC) with retrohepatic intracaval extensions are difficult to treat. HCC may sometimes extend into the inferior vena cava (IVC) through two routes: via the right hepatic vein and via the inferior right hepatic vein. In such cases, in which tumor emboli are located both above and below the confluence of the hepatic vein with the IVC, we first remove the upper embolus during THVE, and then remove the lower one while the IVC is clamped obliquely in order to preserve the residual liver circulation.

Liver transplantation for primary sclerosing cholangitis.

Although the development of interventional radiology and biliary surgical techniques has prolonged the survival time of patients with primary sclerosing cholangitis, liver transplantation remains the only effective treatment for patients with primary sclerosing cholangitis with liver cirrhosis. Several prognostic survival models have been establised for this disease, and the efficacy of actual liver transplantations has been reported in comparison with these survival models. One- and 5-year actuarial patient survivals after liver transplantation for primary sclerosing cholangitis were shown to be greater than and approximately equal to 90%, respectively. An association with cholangiocarcinoma is the most adverse factor affecting survival after liver transplantation for primary sclerosing cholangitis, while the association of inflammatory bowel disease or previous bili-ary surgery does not adversely affect the outcome of the liver transplantation. Recurrent sclerosing cholangitis is an important issue for posttransplant patients with primary sclerosing cholangitis, and occurs in 10%-20% of such patients. Although our understanding of recurrent sclerosing cholangitis is still in the early stages, its potential occurrence indicates the need for a longer follow-up period after liver transplantation.

Reconsideration of the lymph node metastasis pattern (N factor) from intrahepatic cholangiocarcinoma using the International Union Against Cancer TNM staging system for primary liver carcinoma.

BACKGROUND: In cholangiocarcinoma, no established method of analysis of lymph node metastasis has been reported with respect to the surgical outcome. METHODS: The authors retrospectively examined the pattern of lymph node metastasis and the surgical outcome with reference to the International Union Against Cancer (UICC) TNM stage in 47 patients with cholangiocarcinoma who underwent complete tumor resection followed by a period of observation of >2 years. RESULTS: The tumors were located in the left lobe of the liver in 32 patients, in the right lobe in 12 patients, and in both lobes in 3 patients. Lymph node metastasis was found in 15 patients (12 with left lobe tumors and 3 with right lobe tumors). Among those patients with the left lobe tumors, six had no metastasis in the hepatoduodenal ligament (regional lymph nodes), but did display metastasis to lymph nodes around the cardiac portion of the stomach or along the common hepatic artery (distant lymph nodes), whereas no such skip metastasis was found in those patients with right lobe tumors. The patients with lymph node metastasis showed a tendency toward a lower survival rate than those without metastasis (difference not statistically significant), but the patients with only regional lymph node metastasis showed no difference in survival rate compared with those with distant lymph node metastasis. Patients with mass-forming type tumors without bile duct invasion had less lymph node metastasis and a better survival than those with bile duct invasion. CONCLUSIONS: The lymph node metastasis pattern of the UICC TNM classification, at least with respect to the regional lymph nodes, should be reconsidered.

[Microwave tissue coagulation therapy compared to hepatectomy for whole-liver multinodular hepatocellular carcinoma].

We compared the effectiveness of microwave tissue coagulation therapy (MTC) with the effectiveness of hepatectomy for patients with whole-liver multinodular hepatocellular carcinoma (HCC). The comparison was made using two sub-groups of 67 patients treated for multinodular HCC in the whole liver. One subgroup (group M, 17 patients) underwent MTC while another group (group H, 33 patients) underwent hepatectomy. The clinical stage of the liver in group M was significantly worse than in group H (p < 0.05), and the maximum diameter of HCC nodules in group M was significantly smaller than group H (p < 0.05). Survival rates of both groups were similar, but the group H disease-free survival rate was significantly better than that of group M (p < 0.05). Furthermore, the interval between treatment and tumor recurrence in group H was significantly longer than for group M (p < 0.05). We believe the more frequent incidence of local recurrence in group M may have been due to incomplete coagulation. Thus, MTC provides a possible new option for local treatment of HCC, but it is important to ensure complete coagulation of the tumors.

A Case of Ductal Carcinoma In Situ (DCIS:noncomedo type)Detected by Ultrasonography: Demonstration of Occult Multiple Foci.

We report a case of ductal carcinoma in situ (DCIS) of the breast detected by ultrasonographic mass screening in a 51-year-old woman. In a mass screening program for breast cancer, physical examination with inspection and palpation, and ultrasonography (US) were performed. A hypoechoic mass with a slightly irregular margin was detected by US in the lateral upper quadrant of the right breast, at a distance 2 cm from the edge of the nipple. The mass was not detected by physical examinations or by mammography (MMG). The mass, which measured 0.8 x 0.5 cm and was examined by fine needle aspiration biopsy (FNAB) under US guidance, was cytologically diagnosed as class X. Modified radical mastectomy (Auchincloss method) was performed with the patient's consent. Pathological examination of the resected specimen revealed DCIS (noncomedo type) and occult multiple foci of malignancy which was considered tracking centripetally underneath the nipple. This case suggests that US and FNAB performed under US guidance are useful in the detection and diagnosis, respectively, of a breast mass. We should take multifocality into consideration, particularly with tendency tracking to the nipple, in the treatment of small breast cancers such as DCIS.

Usefulness of ultrasonography combined with conventional physical examination in mass screening for breast cancer: a retrospective study of Yamanashi Health Care Center results from 1989 to 1994.

We retrospectively analyzed the records for 34,474 women who participated in mass screening for breast cancer by physical examination with or without ultrasonography (US) at Yamanashi Health Care Center between April, 1989 and March, 1994 to evaluate the usefulness of US in mass screening. In one group (15,935 women) conventional physical examination with inspection and palpation alone had been performed, and in another (18,539 women) both conventional physical and US examinations were performed. Breast cancer was detected in 27 of the women (0.08% of the total group screened), 22 of whom were in the group examined by US; moreover, 16 of these 22 women had early breast cancer, which was a non-palpable tumor in 13. Half of the 22 women were examinees under the age of 50 years. Of the 22 tumors detected in the groups examined by US, 16 (73%) were early breast cancer. The overall detection of early breast cancer (0.09%) in the US group was significantly higher than that (0.01%) in the group examined by conventional methods (P < 0.05). Of the tumors detected in the US group, 59.1% were non-palpable. These results suggest that early and non-palpable breast cancer can be detected using US, and the incidence of detection of such tumors in women under the age 50 years is increased in mass screening including US examination. This examination is effective in mass screening for breast cancer, especially for early and non-palpable breast cancer tumors.

Two Cases of Choroidal Metastasis from Breast Cancer.

We report two cases of choroidal metastasis from breast cancer. The first case was a 41-year-old woman with loss of her right upper visual area in whom right breast cancer accompained by lung and choroidal metastases were detected simultaneousyl. She died without having received radiation therapy for the affected eye 6 months after mastectomy and oophorectomy. The second case was a 34-year-old woman in whom choroidal metastasis causing right visual disturbance was diagnosed 3 years after mastectomy for breast cancer. She received radiation therapy following oophorectomy and her visual acuity completely recovered. She dies 7 months later. Radiation therapy improved her quality of life despite her short survival, because her visual acuity was maintained until death. In general, the life span of patients with choroidal metastases is short because of multiple organ metastases, but to obtain a better quality of life, active treatment of the affected eye is necessary.

A case of hepatocellular carcinoma consisting of two solitary poorly differentiated polyclonal intrahepatic tumor nodules.

Two intrahepatic solitary tumors consisting of poorly differentiated hepatocellular carcinoma (HCC) were identified as polyclonal HCC nodules by analysis of the pattern of integration of hepatitis B viral DNA into nuclear DNA. After the removal of each nodule by partial liver resection, recurrent multiple tumors appeared within 10 months postoperatively. The findings in this case suggest that the effectiveness of reduction surgery for intrahepatic multiple tumors is limited in solitary multicentric HCC that consists of poorly differentiated HCC.

Intrahepatic distant metastasis and metachronous multicentric occurrence in solitary hepatocellular carcinoma of less than five centimeters in diameter.

During the 7 years from 1984 to 1990, 36 patients underwent liver resection for solitary hepatocellular carcinoma (HCC) measuring less than 5 cm in diameter, with no intrahepatic vascular invasion on imaging diagnoses and no macroscopic infiltration into the tumor capsule or surrounding tissues. Although HCC is less likely to cause intrahepatic adjacent metastasis to the cut liver surface, an analysis revealed the possibility of intrahepatic distant metastasis and metachronous multicentric occurrences, even after complete removal of the primary tumor. The 5-year cumulative survival rate was 53%, while the 5-year cumulative recurrence-free survival rate was 19%. Of the 36 patients, 18 (50%) had suffered a recurrence by April, 1992, one with extrahepatic metastasis. Recurrence of intrahepatic metastasis was multifocal in 5 patients, single and adjacent in 1, and single (or a few) and distant in 11. Multifocal recurrence was observed within 1 year after liver resection. The sole single and adjacent metastatic case occurred in one of eight patients in the recurrent group in whom distance of the surgical margin was less than 1 cm [TW(+)]. Multicentric occurrence was found in 6 of 13 patients (46%) whose recurrent tumors were examined histologically, and all belonged to the "single (or a few) and distant" type of recurrence. In this report, we also present two typical cases of metastasis, one being multifocal metastasis occurring within 3 months after liver resection and the other being intrahepatic metastasis occurring after a 4-year-dormant state, to demonstrate the complicated nature of the intrahepatic metastatic pattern.

The indications for tumor mass reduction surgery and subsequent multidisciplinary treatments in stage IV hepatocellular carcinoma.

The indications for tumor-mass reduction surgery and subsequent immunotherapy in patients with stage IV hepatocellular carcinoma (HCC) were elucidated in this study. About 42% of the resected specimens from stage IV-A patients (n = 26) contained well-differentiated multicentrically occurring HCC, which was not found in any of the stage IV-B patients (n = 9). The 2-year survival rate after reduction surgery was 49% for the stage IV-A patients and only 13% for the stage IV-B patients, while 6 of the stage IV-A patients who survived for more than 2 years had no vascular invasion or distant organ metastases. Some of the stage IV patients maintained normal peripheral natural killer (NK) activity and were also able to tolerate surgical insults immunologically, provided that appropriate postoperative immunotherapy was given. Thus, stage IV-A HCC has a greater possibility of containing slow-growing intrahepatic tumor clusters, and the removal of any rapidly growing tumors from among these should be undertaken by reduction surgery followed by subsequent multidisciplinary treatment for residual tumor cells, including appropriate immunotherapy.

[Analysis of human mitochondrial DNA in hepatocellular carcinomas].

Based on the following 3 points: 1) tumor proliferation is energy-dependent, 2) mitochondrial energy-production system is dominant for cell growth, and 3) liver mitochondria (mt) possess their own DNA and RNA synthesizing some of their own proteins including respiratory enzymes such as cytochrome oxidases, a possible relationship between mutations of mt-DNA and clinical status of cell proliferation was examined in 10 HCC patients who underwent liver resection. Mt-DNA at the cancerous and the noncancerous portions of 1g resected liver specimens were separated from the nuclear DNA, and then digested with Hinf I endonuclease. DNA filters were made of the digested mt-DNA fragments on the agarose and polyacrylamide gel. The filters were hybridized with a nick-translated 32P-labeled DNA fragments. In two cases, abnormal mt-DNA were detected. In the first case, the tumor was the massive type and grew rapidly invading the bile duct. One restriction fragment of 3.0 Kb of the cancerous and non cancerous portion became larger by 60 bp. In the second case, regarded as metachronous multicentric HCC, the second largest band of the 3.4 Kb fragment of the cancerous portion showed a wider range but not of the noncancerous portion. The former change may indicate polymorphism but the latter indicates an occurrence of the mutation of mt-DNA. Further studies are required, including examinations on the rest of mitochondrial fragments.

[Ultrastructural changes in the hepatocytes following massive hepatectomy in rats].

This study was carried out to investigate the ultrastructural changes of the hepatocytes of the remnant liver after 70% hepatectomy in rats. The remnant liver regained the preoperative weight one week after hepatectomy. During this early posthepatectomy period, the volume of the each hepatocytes increased to a peak 48 hours after hepatectomy, then returned to normal within one week. Electronmicroscopically mitochondria of the hepatocytes became swollen and the cristae were shortened until 3 hours after hepatectomy. Dividing mitochondria were also observed in the initial 2 hours. The volume density of the mitochondria measured as a percentage of the mitochondrial volume per the cytoplasmic volume of hepatocytes. It increased and reached a peak 3 hours after hepatectomy (p less than 0.05) and thereafter returned to the same value as the control within 6 hours. Then it gradually decreased until 7th day (p less than 0.001). The volume density of lipid droplets increased to a peak 48 hours after hepatectomy (p less than 0.01). These significant ultrastructural changes of the hepatocytes indicate an important roles of mitochondria especially in the energy metabolism in the early posthepatectomy period.