Surgery for hepatocellular carcinoma with tumor thrombus in the right atrium

Three cases of tumor thrombus that originated from a hepatocellular carcinoma in the liver and extended into the right atrium are described. All patients had received both resection of the tumor thrombus and lobectomy of the liver either simultaneously or independently within a short interval. Surgical order and extracorporeal circulation system were varied depending on the thrombus extension. Two of the patients died within 4 months of surgery due to different reasons and the other is doing well at 24 months after surgery.     

Surgical therapy for hepatocellular carcinoma with liver cirrhosis

Approximately 80% of hepatocellular carcinoma (HCC) patients in Japan have associated liver cirrhosis, which increases the difficulty of surgical treatment. Liver dysfunction associated with liver cirrhosis is one of the most important predictive prognostic factors for HCC patients. Percutaneous ethanol injection therapy (PEIT) is useful for patients with small HCC or with poor hepatic functional reserve. Transcatheter arterial chemoembolization (TACE) is also useful both for patients with unresectable HCC and patients with multiple intrahepatic recurrence. Liver resection, however, lead to better outcome than other treatments when liver function is maintained after surgery. To determine operative procedures, it is important to evaluate the exact function of remnant liver, based on the preoperative liver function test and the evaluation of tumor character. For advanced HCC patients with vascular invasion, non-surgical treatments such as PEIT or TACE are not indicated, and surgical intervention can be an effective modality to improve their survival. Improvements of surgical technique and perioperative management have decreased fatal complications at a major liver resection and allowed us to carry out liver resection on patients with advanced HCC.     

Inferior vena cava filter used for unresectable renal cell carcinoma with tumor thrombi

A titanium Greenfield inferior vena cava filter was used for the treatment of 2 patients with unresectable renal cell carcinomas with tumor thrombi to prevent a fatal pulmonary embolism induced by tumor clots released during systemic interferon therapy and embolization of the primary tumor. After treatment, the size of the renal cell carcinomas at the primary site and the tumor thrombi decreased by 50%. There were no fatal pulmonary embolisms or complications related to the filter during the observation period (24 and 25 months) after therapy. This method may be useful in the prevention of a fatal pulmonary embolism induced by embolization and systemic interferon therapy in these patients.     

Topical cooling-assisted hepatic segmentectomy for cirrhotic liver with hepatocellular carcinoma

BACKGROUND: A safe limit for normothermic consecutive portal triad occlusion in hepatectomy for the cirrhotic liver was believed to be around 30 minutes. Possibly, the occlusion time can be prolonged by cooling the ischemic liver in vivo. We describe the technique of segmentectomy assisted by topical cooling and its usefulness in prolonging the hepatic inflow occlusion time for cirrhotic livers without causing further ischemic injury. STUDY DESIGN: Fifty patients with hepatocellular carcinoma and chronic hepatic disease who underwent right-sided segmentectomy under hemihepatic inflow occlusion were divided into two groups: normothermic (n = 27), and hypothermic with hemihepatic topical cooling using ice slush (n = 23). Segmentectomies were carried out in the same way in both groups, guided by initial enbloc ligation of the corresponding portal pedicles. RESULTS: The mean right hepatic inflow occlusion time was significantly longer in the hypothermic group than in the normothermic group (53 +/- 22 minutes compared with 17 +/- 9.3 minutes). Despite the significant difference in occlusion time, no differences were found in the recovery of hepatic functions and the incidence of postoperative complications between the groups. Intraoperative blood loss was significantly less in the hypothermic group. CONCLUSIONS: The hepatic right-sided partial inflow occlusion time can safely be prolonged to 60 to 90 minutes in the presence of cirrhosis without causing another injury from ischemia and intermittent reperfusion.     

Anesthetic management for renal tumor extending to the inferior vena cava

A 58 year-old woman underwent radical nephrectomy, thrombectomy and ileo-cecal resection for renal tumor with thrombus involving the inferior vena cava and ascending colon cancer. In a patient having tumor thrombus extending to the vena cava, recognition of the position of the thrombus is important for surgical and anesthetic management in pre- and intra-operative periods. Transesophageal echocardiography (TEE) enabled us to visualize the real-time movement and deformity of thrombus by surgical manipulation and compression during operation. TEE seemed also very useful not only in understanding the hemodynamics during operation but also in detecting the residual tumor and the blood flow in liver and the inferior vena cava after operation.     

Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation

PURPOSE: To review the treatment of cirrhotic patients with hepatocellular carcinoma in the era of liver transplantation and to determine the most appropriate approach to the treatment of patients at different stages of disease. DATA SOURCES: A MEDLINE search of English-language articles published between 1981 and 1997 and the clinical experience of the Mount Sinai Liver Transplant Program. STUDY SELECTION: Selected studies were 1) original articles reporting results of resection and transplantation in the treatment of hepatocellular carcinoma in cirrhotic patients and 2) initial reports from major transplantation centers of multimethod therapies combining chemotherapy with transplantation. DATA EXTRACTION: Study designs were assessed with careful attention to methods and aims. Relevant data on patient population, tumor stage distribution, treatment, survival, and rate of recurrent disease were extracted and analyzed. DATA SYNTHESIS: Options for the treatment of hepatocellular carcinoma in cirrhotic patients vary according to tumor stage and severity of underlying liver disease. Resection remains an important method primarily in eastern countries, where the screening of high-risk populations has been associated with early detection of small asymptomatic lesions. Long-term survival after resection, however, is low. In western countries, liver transplantation is becoming the treatment of choice in patients with advanced cirrhosis and small, unresectable lesions; resection is reserved for cirrhotic patients with small, peripheral lesions and preserved hepatic function. Minimally invasive procedures (such as percutaneous ethanol injection and transarterial chemoembolization) have been developed to treat unresectable tumors. Transarterial chemoembolization may also be effective in patients with advanced cirrhosis and unresectable lesions who are awaiting transplantation. CONCLUSIONS: The efficacy of liver transplantation for hepatocellular carcinoma has been proven mainly in patients with advanced cirrhosis and small lesions. Future studies may clarify the role of approaches combining neoadjuvant chemotherapy with transplantation for large (stage III) tumors.     

Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary gastric cancer

BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric cancer, it is usually presumed to be metastatic. However, this may not be true in a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This study was conducted to examine the clinicopathological factors of both conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a synchronous hepatectomy in combination with radical gastrectomy over the past 15 years was performed. RESULTS: Seven patients had metastatic gastric cancer, and seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node metastasis were the major features in the patients with metastatic gastric cancer. Early gastric cancer was found in three of the patients with the coexisting primary cancers. No patient with solitary metastatic cancer survived more than one year, but long-term survival of more than two years was achieved in two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the stomach and liver should be kept in mind in patients with gastric cancer concomitant with a solitary hepatic tumor, in order to provide optimal treatment.     

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Maltitol is a disaccharide alcohol that is produced by hydrogenation of maltose and exhibits resistance to intestinal disaccharidases. We demonstrated previously that maltitol stimulated transepithelial diffusional calcium transfer in the ileum, accompanied by an elevation of intestinal calcium absorption as well as calcium retention in the body. In this study we examined whether the maltitol-induced increase in the diffusional transfer of intestinal calcium absorption leads to an alteration of the physical properties of bones in the weanling rats which exhibit the maximal level of intestinal active calcium absorption. Rat pups were removed from dams at 24 d of age and were fed the diets containing either maltose (control) or maltitol and a requisite amount of calcium (0.52%) for 21 d. Balance studies performed during the final 5-d period showed that maltitol-fed rats had greater calcium retention and calcium absorption. The breaking force of femoral bones was 13% greater in the rats fed the maltitol diet than in controls. The calcium content and dry weight of both femurs and tibias, as well as the bone mineral density of tibias, were elevated in the rats fed the maltitol diet. In a separate experiment, gastric intubation of maltitol-containing diet increased the serum calcium concentration in the portal vein at 2 and 4 h compared to controls. These results indicate that the maltitol-induced increase in the intestinal calcium absorption through paracellular pathway leads to enhancement of the calcium content and the breaking strength in the bone of weanling rats.     

Fibrolamellar carcinoma of the liver with a mixture of ordinary hepatocellular carcinoma: a case report

Fibrolamellar carcinoma (FLC) of the liver is a rare variant of hepatocellular carcinoma (HCC), and only 13 cases have been reported in Japan up to 1997. We described a histologically unusual case of FLC. A 52-yr-old man was admitted to our hospital for work-up of hepatic mass. Laboratory examinations revealed no abnormalities except elevated serum alpha-fetoprotein (AFP) (2098 ng/ml). A diagnosis of HCC was made by imaging findings, and left lobectomy of the liver was performed. Histologically, the tumor was composed of areas of FLC mixed with ordinary HCC and those of pure ordinary HCC. Staining for AFP was positive in the HCC component and negative in the FLC component. Some cases of such mixed tumors have been reported in Europe and the United States, but not in Japan. We regarded our case as the first of the mixed tumor in Japan.     

Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma

The aim of the study was to assess the incidence of both types of liver cell dysplasia and concomitance with cirrhosis, hepatocellular carcinoma (HCC) and positive reaction for HBsAg in the autopsy material and an attempt to determine a relationship between these two types of liver cell dysplasia and hepatocellular carcinoma. Autopsy material included 102 cases of hepatocellular carcinoma, 101 cases of hepatocirrhosis without accompanying cancer and 106 control cases. Histological specimens stained with HE were analyzed for the presence of large liver cell dysplasia (LLCD) according to Anthony et al., small liver cell dysplasia (SLCD) according to Watanabe et al., the presence of macroregenerative nodules (< 8 mm) and antigen HBs (stained with orcein according to Shikata). The detected LLCD were also assessed semiquantitatively taking into account the number of dysplastic areas in a given case. Statistical significance of the results was tested with the chi square test. LLCD was most frequently detected in HCC with concomitant cirrhosis (55.3%), then in cirrhosis without HCC (40.6%), and in HCC without cirrhosis only in 12.5%. LLCD was found significantly more frequently (p < 0.05) in cirrhosis with HCC than in cirrhosis without HCC. Antigen HBs was found in 25.6% of cirrhoses and/or HCC. No significant differences in the presence of HBsAg were seen between the analyzed groups. The incidence of LLCD and HBsAg in controls was significantly lower than in other groups. A mean age at death in case of cirrhosis with HCC subdivided into that with or without LLCD was not significantly different, whereas in case with cirrhosis with LLCD age at death was 10.8 years higher (the difference statistically significant). Analysis of material with respect to gender revealed a high proportion of men in case of HCC with concomitant cirrhosis but without LLCD (13:1). A strong relationship was seen between the presence of positive reaction for HBsAg and LLCD (p < 0.001). Also the intensity of LLCD positively correlated with the presence of HBsAg. Furthermore, a positive correlation was seen between the presence of LLCD and macronodular cirrhosis (posthepatitic). The present findings suggest a closer relation between HBV infection and LLCD than between cirrhosis or HCC and LLCD. Also morphological patterns of LLCD foci do not confirm the hypothesis of some investigators about the precancerous character of these lesions. In the whole current material only seven cases of SLCD were detected. They were all present in cirrhotic livers with concomitant HCC. Both the morphological pattern of these lesions and their sometimes discerned close spatial relation with HCC foci indicate that SLCD is an alternative way of HCC development.     

Surgical treatment for advanced carcinoma of the gastric remnant

BACKGROUND/AIMS: Carcinoma of the gastric remnant has increased in recent years, but a therapeutic strategy for this disease has not been established. This retrospective study was performed to determine the most appropriate surgical procedure for carcinoma of the gastric remnant. METHODOLOGY: A total of 25 patients who underwent operation for advanced carcinoma of the gastric remnant that had developed after distal gastrectomy (13 for benign gastric diseases, B group; 12 for gastric carcinoma, M group) were studied. Clinicopathological features, as well as the status of lymph node metastasis, were investigated in the B and M groups. RESULTS: There were more patients with carcinoma invading other organs, stage IV disease, and with N2 or more lymph node metastasis (especially, with a high metastatic rate to lymph nodes along the splenic artery) in the M group than in the B group. Forty percent of patients in the M group were treated by left upper abdominal evisceration (LUAE), but only 8% in the B group. The survival rate (5-year, 46.0%) of the B group was significantly higher than that (5-year, 11.9%) of the M group. When we compared the survival rate of carcinoma of the gastric remnant with that of primary carcinoma of the upper third of the stomach, there was no difference between the two groups in the curative resection cases. CONCLUSIONS: Almost the same surgical strategy can be adopted for the B group as for primary gastric carcinoma. On the other hand, for the M group, a radical surgical procedure, LUAE, should be recommended.     

Serial changes in serum alpha-fetoprotein prior to detection of hepatocellular carcinoma in liver cirrhosis

In 49 liver cirrhosis patients with hepatocellular carcinoma in which the hepatocellular carcinoma nodule was smaller than 30 mm in size, serial changes in serum alpha-fetoprotein levels prior to the detection of the hepatocellular carcinoma were studied retrospectively, and compared with those of 70 cirrhotic patients with no hepatocellular carcinoma. The changes in alpha-fetoprotein levels were classified into the 4 types normal, low plateau, high plateau and spiky type. The spiky type (spiky elevation during a short period) was more frequently noted in the patients with hepatocellular carcinoma than in those with liver cirrhosis. In a prospective analysis of 39 patients with liver cirrhosis, hepatocellular carcinoma was detected in 6, and was also more frequently noted in the spiky type than the other types. Moreover, in the hepatocellular carcinoma patients with the spiky type of alpha-fetoprotein, hepatocellular carcinoma was suspected, on the basis of the tumor doubling time, to exist at the time of the first elevation of alpha-fetoprotein. These results suggest that the liver cirrhotics with the spiky type of alpha-fetoprotein may be considered to be a high-risk group of hepatocellular carcinoma.     

Successful preoperative interferon-alpha therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--case report

We report a case of renal cell carcinoma in whom preoperative interferon-alpha therapy was successful in reducing the primary lesion and the tumor thrombus extending into the inferior vena cava. A 67-year-old man was referred to our hospital because of his right renal mass. We made a diagnosis of a right renal tumor with tumor thrombus by imaging examinations. Because his performance status was 3, a radical operation was considered risky. So we started interferon-alpha therapy. Four months after the start of interferon-alpha therapy, the primary lesion and the tumor thrombus reduced in their size, and the clinical response was evaluated as partial response by the response criteria for urological cancer treatment. Because of improving the performance status and reducing the tumor size, radical nephrectomy and tumor thrombectomy could be performed. Pathological examinations revealed that viable renal cell carcinomas were found only in some small parts of the primary lesion, but not in the tumor thrombus. Postoperatively, no recurrence and metastasis of renal cell carcinoma of the patient have been detected in these two and a half years.     

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P < 0.001), habitual heavy drinking (P < 0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc, P < 0.05), and age greater than 60 years (P < 0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80-9.78) in male patients, 3.27 (95% CI, 1.46-7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01-3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00-4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively, P < 0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4 +/- 4.4 years vs 28.4 +/- 3.9 years; P < 0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis.     

Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma

In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.     

Surgical significance of telomerase activity in noncancerous liver tissue from patients with hepatocellular carcinoma

Telomerase activity has been detected in tissue from noncancerous liver of patients with chronic liver disease, but its functional significance remains to be elucidated. We therefore evaluated the telomerase activity in surgically obtained noncancerous liver tissue from 20 hepatocellular carcinoma (HCC) patients. Two samples of noncancerous liver tissue were obtained from each patient: one from the parenchyma adjacent to the HCC nodules of the resected specimen; the other from the parenchyma distant from the HCC nodules of the remnant liver. Telomerase activity was assayed by a non-radioisotope quantitative system based on "TRAP-eze." Five samples from the noncancerous liver tissue adjacent to the HCC nodules (25.0%) were telomerase-positive; all such cases showed high-grade malignant potential, such as intrahepatic metastasis and/or portal vascular invasion and infiltration of the fibrous capsule in the corresponding HCC nodules, and telomerase positivity showed neither a relationship with the histological activity index scores nor a correlation with liver function. Interestingly, no telomerase activity was detected in any of the 20 samples obtained from the parenchyma of the remnant liver. These results indicate that telomerase in noncancerous liver tissue is associated not with the hepatic condition accompanying HCC, but with the biological characteristics of the tumor itself, and may derive from infiltrating cancer cells. Determination of telomerase status may aid in designing more effective surgical procedures.     

Pancreatic carcinoma in remnant pancreas after pancreatectomy for mucinous cystadenoma

We report an unusual case of laryngomucocele occurring after subtotal laryngectomy. Laryngoceles generally have a congenital origin in a long-preexisting saccule, and their association with laryngeal carcinoma is well known. Laryngocele is usually favored by the increase of intraglottic pressure caused by the laryngeal carcinoma. However, an iatrogenic secondary laryngomucocele occurring after a surgical procedure is uncommon. We report in detail the physiopathologic conditions leading to the creation of this lesion.     

Positive correlation of plasma transforming growth factor-beta 1 levels with tumor vascularity in hepatocellular carcinoma

The initial somatosensory evoked magnetic fields following painful heat stimulation by CO2 laser beam applied to the upper and lower limb were investigated in normal subjects. The main deflections, 'Pain MA' and 'Pain ML' following the arm and leg stimulation, respectively, were identified in the bilateral second sensory cortices (SII). The onset latencies of Pain MA and Pain ML were approximately 150 and 200 ms, respectively. No consistent equivalent current dipole was found in other areas including the primary sensory cortex in each hemisphere. Therefore, we consider that neurons in the bilateral SII are initially activated following painful heat stimulation.