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Biomedical subjects

S Yogita

Publications and source records attributed to S Yogita.

17 recordsLinked to original sources

Hepatocellular carcinoma effectively treated by intravenous infusion of cisplatin.

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48-year-old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum alpha-fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist-II (PIVKA-II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA-II decreased markedly, to 26 ng/ml and <0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.

Antineoplastic Agents↗

Intraoperative microwave coagulation therapy for large hepatic tumors.

We report new surgical techniques for intraoperative microwave coagulation therapy (IMCT), conducted in three patients with large liver neoplasms with poor liver function or difficult tumor location. Anterolateral thoracotomy was performed for tumors in the right lobe to obtain a good operative field. Four electrode needles were inserted for microwave irradiation, with settings of 60 W, 45 s for coagulation and 1 s for dissociation. Clamping of the hepatoduodenal ligament was performed during IMCT. We began the coagulation at the bottom of the tumor, irradiating the tumor and the surrounding parenchyma to create regional necrosis with a safe margin. With these methods, we treated two women diagnosed with large hepatocellular carcinoma with liver cirrhosis and a man with liver metastasis from rectal cancer. The postoperative course of these patients was uneventful. A marked low-density area was seen in the region of therapy and no enhanced findings were observed on enhanced computed tomography postoperatively. However, in one patient, transcatheter embolization (TAE) was performed 1 month postoperatively because recurrence was noted on the bottom of the tumor. Thus, IMCT destroys the peripheral part of the tumor that may remain viable after TAE, but combination therapy with TAE is preferable, especially when a viable part exists within tumors. IMCT is an active, safe, and nontoxic therapeutic modality for large hepatic tumors, and is particularly applicable in patients with large hepatocellular carcinomas and poor liver function.

Aged↗

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma.

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.

Aged↗

Current status of surgical treatment for hepatocellular carcinoma.

The therapeutic modalities for hepatocellular carcinoma (HCC) have diversified during the past decades, and in particular, the treatment has mainly been concentrated on small HCC of 3 cm or less. Therefore, it has become very important for surgeons to be able to identify the clinical indications for liver resection in HCC. We reviewed data on liver resection for HCC using the National Primary Hepatic Cancer follow-up survey report of the Liver Cancer Study Group of Japan, indicating problem associated with liver resection for HCC. As a result, the indications of surgical treatment for HCC are as follows: (1) In patients with HCC of 3 cm or less in diameter, a solitary HCC indicates liver resection. However, priority should be given to medical treatment such as percutaneous transhepatic ethanol injection therapy, microwave coagulative necrosis therapy for multiple HCC and patients with clinical states II or III. (2) HCC between 3 cm and 5 cm in diameter is a good indicator for liver resection. Solitary HCC indicates liver resection as a first choice. (3) HCC greater than 5 cm diameter eter and cases with tumor stages II or III indicate liver resection. (4) There are limits to treating HCC with tumor thrombus in the second branch of the portal vein (Vp2) and tumor thrombus in the first branch, the trunk of the portal vein or in a branch on the opposite side (Vp3) only by liver resection. (5) HCC with tumor thrombus in the right, middle or left hepatic vein trunk, posterior inferior hepatic vein trunk or short hepatic vein (Vv2) and with tumor thrombus in the inferior vena cava (Vv3) are indicators for liver resection. A limited resection according to Glissons structure and with a negative surgical margin can be performed in HCC of 5 cm or less, however an extended resection is required for HCC greater than 5 cm. Furthermore, the extent of liver resection should be considered according to the hepatitis virus. Finally, it was emphasized that effective measures against the postoperative recurrence was essential in order to improve the outcome of HCC.

Carcinoma, Hepatocellular↗

Hepatocellular carcinoma with extension into the right atrium: report of a successful liver resection by hepatic vascular exclusion using cardiopulmonary bypass.

We report a successful liver resection using cardiopulmonary bypass with, total hepatic vascular exclusion (THVE) for hepatocellular carcinoma (HCC), with extension into the right atrium. A 61-year-old man with a cirrhotic liver was referred to our department with HCC in the medial segment of the left lobe of the liver, and tumor thrombus extending into the right atrium. During surgery, a left lobe and caudate lobe of the liver were transected leaving the left lobe of the liver connected to the inferior vena cava (IVC) by only the left and middle hepatic trunks, and then the intracaval tumor thrombus and the left lobe of the liver were removed en bloc using cardiopulmonary bypass with total hepatic vascular exclusion (THVE). Cardiac arrest was not performed during THVE, and the patient had an uneventful postoperative course and was discharged from the hospital 2 months following surgery. He died of multiple pulmonary metastases 4 years and 8 months after surgery; however, imaging showed no evidence of recurrence in the remnant liver during that period. In conclusion, by performing dissection of the hepatic parenchyma to the hepatic vein prior to removal of the tumor thrombus, the period of extracorporeal circulation, duration of warm ischemic time to the liver, and intraoperative blood loss were all reduced and a radical operation could be performed safely without scattering tumor cells during extirpation of the tumor.

Carcinoma, Hepatocellular↗

Hepatopulmonary syndrome-discussion of cardiopulmonary parameters.

We report a 70-year-old man with hepatopulmonary syndrome (HPS) in C liver cirrhosis. Hypoxemia worsened markedly, especially on exertion, while the hepatic function was clinically stable. Contrast echocardiography, 99mTc macroaggregated albumin (99mTcMAA) lung scan, and pulmonary angiography were performed. The findings suggested the presence of both intrapulmonary vascular dilatation and substantial right-to-left shunt. The contribution of intrapulmonary vascular abnormalities in patients with severe liver cirrhosis without abnormal chest radiography and spirometry tests when marked hypoxemia is present should be investigated.

Aged↗

Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection.

It has been proved that antibiotics binding to penicillin-binding protein 3 (PBP3) are associated with the greater release of endotoxin than those that bind to PBP2 in both in vitro and animal models. The aim of this study is to evaluate the potential clinical implications of antibiotic-induced endotoxin release after hepatic resection. Forty-five patients who underwent hepatic resection in our clinic were enrolled. The patients were divided into two groups. Group A (n = 26): antibiotics that bind primarily to PBP3, including cefmetazole (CMZ), latamoxef (LMOX), flomoxef (FMOX), were used. Group B (n = 19); antibiotics that bind to both PBP2 and PBP3, including cefazolin (CEZ), cefoperazone (CPZ), cefotiam (CTM). Postoperative complications, liver functional tests, and chemical mediators [endotoxin, interleukins (IL-6, IL-8), tumor necrosis factor alpha (TNFalpha), granulocyte colony-stimulating factor (G-CSF), hepatotrophic growth factor (HGF) were examined after hepatic resection. There were no significant differences in the backgrounds of the two groups. Eight patients in each group developed postoperative complications; in particular, 9 of 13 patients with biliary tract carcinoma developed postoperative complications. No significant elevation of peripheral blood endotoxin was noted by the endospecy method, in any of the patients, although six died following sepsis. Pre- and postoperative levels of cytokines showed no significant difference between the two groups. Our data suggest that clinical antibiotic-induced endotoxin release would not occur after hepatic resection regardless of the antibiotic, probably owing to continuous scavenging of endotoxin from peripheral blood.

Analysis of Variance↗

Effect of intermittent liver ischemia on outcome in patients with hepatocellular carcinoma on liver cirrhosis.

The influence on postoperative liver function of intermittent normothermic hepatic ischemia in cirrhotic patients was studied retrospectively. The mean total ischemia time was 88 (range 30-140) minutes in the hemi-hepatic occlusion group, and 68 (range 10-187) minutes in the total occlusion group. There were no operative deaths due to hepatic failure. Postoperative liver function improved within 1 week of the operation. There was no significant difference in the incidence of postoperative complications between the groups. Thus normothermic hepatic ischemia is tolerated for up to 180 minutes in the cirrhotic liver when an intermittent technique (15 minutes clamped and 5 minutes unclamped) is used.

Carcinoma, Hepatocellular↗

Can the liver with Gilbert's syndrome be used as graft of living-related liver transplantation?

Gilbert's syndrome is the common cause of non hemolytic unconjugated hyperbilirubinemia with a prevalance of 3-7%. Gilbert's syndrome may introduce a selection of potential liver donors from brain death patients. We present a case of living-related liver transplantation (LRLT) from a donor with Gilbert's syndrome. A 22-year-old woman had been diagnosed as having liver cirrhosis at the age of 5. She underwent liver transplantation with the donor's left lobe as the graft. The donor, who was the father of the patient, had been diagnosed with Gilbert's syndrome. Although the recipient was well until 11 months after surgery, she died of subacute fulminant hepatitis 16 months after surgery. However, it was clear that the liver with Gilbert's syndrome could be used as a graft of living-related liver transplantation for adult recipients.

Adult↗

Assessment of the biological malignancy of hepatocellular carcinoma: relationship to clinicopathological factors and prognosis.

It is difficult to determine the prognosis of patients with hepatocellular carcinoma (HCC). Assessment of the clinicopathological and biological malignancy of HCC may help in determining treatment strategies and predicting outcome. The tumor DNA content, p53 protein expression, proliferating cell nuclear antigen labeling index, and argyrophilic proteins of nuclear organizer regions were used as markers of biological malignancy. A correlation between these biological parameters and clinicopathological factors was sought. DNA aneuploidy was observed in 31 of 80 tumors (38.8%). Aneuploidy increased as differentiation decreased. The overall survival rate of patients with aneuploid tumors was significantly poorer than that of patients with diploid tumors. p53 overexpression was observed in 18 of 80 tumors (22.5%). The incidence of p53 positivity increased significantly with increasing tumor size and poorer differentiation. The overall survival rate of p53-positive patients was significantly worse than that of p53-negative patients. The proliferating cell nuclear antigen labeling index and the mean number of argyrophilic proteins of nuclear organizer regions were higher in more poorly differentiated lesions. We conclude that DNA ploidy and p53 expression are useful prognostic indicators in HCC. Cell proliferation increases as HCC progresses. With progression, tumors tend to become more poorly differentiated.

Adult↗

[Secondary hepatic resections in a case of sigmoid colon cancer with multiple liver metastasis (H3) after successful continuous hepatic artery infusion chemotherapy oriented by in vitro chemosensitivity test].

A 43-year-old woman was admitted to our hospital for sigmoid colon cancer with multiple liver metastasis (H3). As preoperative CTAP (CT during arterial portography) examination showed 23 metastatic nodules in the whole liver, hepatic resections were not indicated. Angiographic findings showed that right and left hepatic arteries branched separately from the celiac artery. Sigmoid colon resection with D3 lymph node dissection and catheterization to the right hepatic artery via gastroduodenal artery were undertaken as a first operation. Continuous hepatic artery infusion chemotherapy with MMC, 5-FU oriented by in vitro chemosensitivity test (SDI test: Succinic Dehydrogenase Inhibition test) of primary tumor was performed 7 days after the first operation. After administration of MMC (40 mg) and 5-FU (16,500 mg), metastatic nodules in the right lobe almost disappeared except for the one tumor of S7, but the size and number of the nodules in the left lobes increased. At 10 months after the first operation, the left hepatic lobectomy and extirpation of only one tumor in the right lobe (S7) underwent. This case showed the usefulness of continuous hepatic artery infusion chemotherapy oriented by in vitro chemosensitivity test for multiple liver metastasis from colon cancer.

Adenocarcinoma↗

Detection of different quasispecies of hepatitis C virus core region in cancerous and noncancerous lesions.

The quasispecies of hepatitis C virus (HCV) core region in non-cancerous and cancerous hepatocellular carcinoma (HCC) lesions, respectively, of 7 patients with hepatocellular carcinoma were studied. Multiple fluorescence based-polymerase chain reaction (PCR)-single strand conformation polymorphism exhibited a different set and a larger number of quasispecies in cancerous portions than those in non-cancerous portions. DNA sequencing of PCR-amplified core region substantiated an accumulation of nucleotide substitutions, and a greater number of quasispecies in cancerous portions than those in non-cancerous portions. The deduced amino acid sequences disclosed that at the peptide position 45, Ser is dominant in non-cancerous lesions, and Gly in cancerous lesions, respectively. Thus, HCV in hepatocellular carcinoma includes a large number of specific quasispecies presumably due to their vigorous proliferation. A different set of quasispecies with the amino acid change is presumed to be related to the hepatocarcinogenesis.

Aged↗

[Problems of living-related partial liver transplantation to adult patients].

Here, we describe the clinical course of an adult patient who had living-related liver transplantation (LRLT) from a donor with Gilbert's syndrome and problems of living-related liver transplantation to adult patients. A 22-year-old woman had been diagnosed as having liver cirrhosis at the age of 5. She had undergone devascularization and transsection of the esophagus, and splenectomy for esophageal varices at the age of 8. Complications such as spontaneous bacterial peritonitis and nonspecific colitis sometimes appeared from 17 years old, and icterus and ascites had appeared on all such occasions. Such complications had frequently occurred from 21 years old. Total bilirubin was 5.5 mg/dl and direct bil. was 4.2 mg/dl. The patient and her family members were informed that LRLT might be possible, and they indicated that the patient's 57-year old father was willing to act as the donor. His liver function was examined. His hepatic function was normal except for hyperbilirubinemia (T. Bil. 2.3 mg/dl, D. Bil. 0.3 mg/dl). He was diagnosed with Gilbert's Syndrome because of an increase of unconjugated bilirubin levels during low caloric intake and nicotinic acid test. The standard liver volume for the patient was calculated to be 900 ml on the basis of body weight. Volumetric analysis with computed tomography revealed that the left lobe volume of the donor's liver was 512 ml, corresponding to 56% of the recipient standard liver volume. This proposal was submitted to the ethical committee of Tokushima University School of Medicine and was accepted. In March 28, 1995, the patient underwent LRLT with the donor's left lobe as the graft. The graft weight was 440 g and the graft corresponded to 49% of the recipient's standard liver volume. Volumetric analysis showed rapid enlargement of graft to 683 ml as early as one week after the operation. The donor has returned to work after discharge from the hospital. The recipient is well 11 months after surgery. Total bilirubin was 1.8 mg/dl and D. Bil 0.5 mg/dl. LRLT may become an option for adult recipients, if graft of more than 30% of the recipient standard liver volume is transplanted even from a donor with Gilbert's syndrome.

Adult↗

A new method for determining cellular ATP content in hepatocytes.

We have developed a new ATP assay for hepatocytes which is simple, rapid and highly sensitive. ATP determination using luciferin-luciferase was performed on hepatocytes separated by perfusion of the liver with collagenase. There was a close correlation between the ATP content of hepatocytes and viable cell numbers. The ATP content of dead cells which were determined by trypan blue dye exclusion test had less than one per cent of levels of viable cells. ATP contents of isolated hepatocytes in Minimum Essential Medium was 6.8 +/- 0.6 x 10(-15) mol/cell at 2 hours after excision of the liver and showed no significant difference compared with that determined at 6 hours. This method was performed to evaluate changes in the cellular ATP content of hepatocytes after partial hepatectomy in rats and transcatheter portal embolization (TPE) in dogs. The ATP content in rat hepatocytes showed a remarkable increase after hepatectomy, with a peak value of 19.1 +/- 1.7 x 10(-15) mol/cell at 24 hours post-surgery. On the other hand, marked atrophy in the embolized lobes and compensatory hypertrophy in the non-embolized lobes were found following TPE in dogs. Cellular ATP content in the non-embolized lobes showed its highest level of 8.7 +/- 2.9 x 10(-15) mol/cell on the third day after TPE, but in the embolized lobes decreased immediately after TPE with significant differences compared with the non-embolized lobes (p < 0.05). Our method may also be applicable to the evaluation of other adenosine phosphate by use of converting enzymes for ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Experimental and clinical studies on liver regeneration following transcatheter portal embolization.

BACKGROUND/AIMS: We studied compensatory hypertrophy following transcatheter portal embolization experimentally in dogs and clinically under the condition of cholestasis. METHODOLOGY: Experimental study: Sixteen dogs were used for this study. Transcatheter portal embolization was performed in the left lobes (70% of the total liver) using Gelfoam powder in dogs with 2-week obstructive jaundice. Liver weight, liver blood flow and the intracellular adenosine triphosphate content of isolated hepatocytes were measured after transcatheter portal embolization. Clinical Study: transcatheter portal embolization of the right portal branch was performed in 13 patients with cancer of the biliary tract and 3 patients with hepatocellular carcinoma before (extended) right lobectomy, using Gelfoam powder and thrombin. Six patients who had a total bilirubin level > 5 mg/dLunderwent a percutaneous transhepatic biliary drainage before transcatheter portal embolization. Liver function tests, a volumetric study with computed tomography and immunohistochemical staining for profilerating cell nuclear antigen and apoptosis in the resected livers were performed. RESULTS: Experimental study: The weight ratio of the non-embolized lobes to the total liver, 2 weeks after transcatheter portal embolization in the dogs with jaundice, was significantly lower than that of the normal dogs with transcatheter portal embolization (40.5 +/- 4.5% vs. 47.6 +/- 3.2%), but significantly larger than that of the dogs without transcatheter portal embolization. The cellular adenosine triphosphate content and tissue blood flow in the embolized lobes were significantly lower than those in the nonembolized lobes in the normal and cholestatic livers. Clinical study: The postoperative course in all patients was uneventful, with no serious complication or liver dysfunction. Extended right lobectomy with caudate lobectomy was equivalent to 65% before transcatheter portal embolization and to 56% after, transcatheter portal embolization owing to compensatory hypertrophy of the left lobe. However, there was no significant difference in liver volume in the patients with or without obstructive jaundice. Apoptosis was observed in the embolized lobe. CONCLUSIONS: Preoperative transcatheter portal embolization with percutaneous transhepatic biliary drainage for the purpose of liver regeneration would be useful for treating extended hepatectomy with obstructive jaundice.

Animals↗

Differential diagnosis of small hepatocellular carcinoma and borderline lesions and therapeutic strategy.

BACKGROUND/AIMS: To investigate imaging characteristics and surgical results of adenomatous hyperplasia and early-stage hepatocellular carcinoma. METHODOLOGY: A retrospective study set in the First Department of Surgery, University of Tokushima, Japan. From 1994 to 1997, 33 patients with 55 small hepatocellular carcinomas (< or = 3 cm) and 10 borderline lesions (3 adenomatous hyperplasia, 5 atypical adenomatous hyperplasia, 2 atypical adenomatous hyperplasia with focal malignancy) were enrolled for this study. The detectability of these lesions on imaging was evaluated. Cumulative survival and disease-free survival rates were also calculated. RESULTS: Twenty-eight patients were incidentally diagnosed on ultrasonography during follow-up study for chronic disease. In the conventional studies, detection rates of ultrasonography, computed tomography and angiography for small hepatocellular carcinomas and borderline lesions were 76% 80%, 33% 10% and 36% 20%, respectively. Magnetic resonance imaging, intraoperative ultrasonography, helical computed tomography and portal angiographic computed tomography showed better results of 67% 20%, 100% 90%, 70% 50% and 74% 56%, respectively. On differential diagnosis, the ratio of echo level in small hepatocellular carcinomas was significantly higher than that in borderline lesions. The 3-year and 5-year survival rates for all patients were 61% and 41%, while disease-free survival rates at the corresponding times were 15% and 7%, respectively. A total of 25 patients (76%) developed intrahepatic recurrence during a mean follow-up of 33.8 months, although there was no recurrent lesion in 4 adenomatous hyperplasia patients treated with microwave coagulation therapy and ethanol injection intraoperatively. CONCLUSIONS: For tumors larger than 1 cm in diameter, the detection rates with various diagnostic modalities were rather high. However, the differential diagnosis of borderline lesions from small hepatocellular carcinomas could be based on pathologic studies only. Early detection of small hepatic lesions and treatment by methods such as resection or ethanol injection are of critical importance in improving long-term survival.

Carcinoma, Hepatocellular↗

Clarification of risk factors for hepatectomy in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatic resection is still associated with a higher morbidity than other major abdominal surgery. The aim of this study was to define risk factors for postoperative morbidity, and to evaluate the plasma cytokine pattern to detect early postoperative infection in patients with hepatocellular carcinoma. METHODOLOGY: One hundred and thirty-nine hepatic resections for hepatocellular carcinoma over a 10-year period from 1987 to 1997 were performed. Preoperative and intraoperative predictors of morbid outcomes were analyzed using multiple regression in a stepwise, logistic model. The postoperative concentrations of interleukin-6, interleukin-8, granulocytecolony stimulating factor, endotoxin and hepatocyte growth factor were measured in 32 patients following hepatic resection. RESULTS: Mortality rate within 30 postoperative days was 2.2%, with morbidity occurring in 40.2%. Significant pre- and intraoperative predictors for morbidity were ICGR15 and the presence of liver cirrhosis. Changes of interleukin-6, interleukin-8, granulocytecolony stimulating factor and endotoxin levels were not consistent with the occurrence of postoperative complications. However, the postoperative peak hepatocyte growth factor levels were positively correlated with morbidity. CONCLUSIONS: ICGR15 and presence of liver cirrhosis had a marked effect on the incidence of postoperative complications after hepatectomy for hepatocellular carcinoma. An increase of serum hepatocyte growth factor level could be used to detect complications in the early postoperative period, but the inflammatory cytokine response after hepatectomy did not relate to an increased complication rate.

Adult↗