Background. The current study was undertaken to investigate whether or not tumor cells are dislodged into the portal venous stream during hepatic resection for hepatocellular carcinomas. Methods. A catheter was placed using echo guidance into the portal branch through the mesenteric vein in 31 patients. Cytologic examinations were done on multiple blood samples at various operative stages. Results. Tumor cells were recovered in 7 of 31 patients in whom the tumor sizes were more than 5 cm and portal invasions were found microscopically and/or macroscopically. By contrast, the remaining 24 tumors were less than 5 cm in size and showed negative portal invasions. Recovery of the tumor cells was found, not during the earlier operative stage of mobilization or rotation of the hepatic lobe, but during the later stages of hilar dissection or hepatic parenchymal dissection. Conclusions. The portal pedicles should be divided before hepatic dissection in segmentectomy and lobec‐tomy to lessen the chance of dissemination of intravasated tumor cells. Cancer 1992; 70:2263‐2267.
The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. Two hundred and thirty one tumors (< or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected at random from the 231 tumors. The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and the frequency of vascular invasion (correlation coefficient = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in six tumors. In all eight patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.
The prognostic value of nuclear DNA content was studied retrospectively using flow cytometry in 203 cases of resected hepatocellular carcinoma. The occurrence of DNA aneuploidy, which was detected in 50% of patients, correlated significantly with tumor size and the presence of vascular invasion or intrahepatic metastasis. Overall, patients with DNA aneuploid tumors had a significantly worse prognosis than those with DNA diploid tumors (P < 0.001) and, also in subdivided groups by tumor size (P < 0.01). Among DNA aneuploid patients, the survival times were significantly shorter for patients with a low DNA index (4.5) than for those with a high DNA index (21.5) (P < 0.05). In a Cox multivariate analysis, nuclear DNA content provided significant prognostic value (P = 0.008), as did vascular invasion (P = 0.001) and intrahepatic metastasis (P = 0.005). These results indicated that nuclear DNA content has an important prognostic value in hepatocellular carcinoma. Cancer 67:939-944,1991.EPATOCELLULAR CARCINOMA (HCC) iS one Of the H most frequent fatal tumors in Asia and Africa.' In Japan it is the third major cause of cancer death in males and the fifth among females.2 The 1-year survival rate is 55% even in resected Despite the argument that clinicopathologic factors affect the long-term survival rate,'y6 we often experienced an unsuspected clinical course or prognosis. The biological behavior of HCC is still unknown.Our goal was to develop a flow cytometric method for measuring the nuclear DNA content of HCC and to evaluate whether or not it had prognostic value as an independent factor. The relationship ofthe nuclear DNA content and other conventional prognostic variables was examined, and the survival data were analyzed using the Cox step-wise multivariate analysis' in a computerized program.From the First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.The authors thank Masahiro Kaji, Tomio Nakajima, and Hirotsugu Kubo for technical assistance.Address for reprints: Jiro Fujimoto, MD, First Department of Surgery, Hyogo College of Medicine, 1-1, Mukogawa-Cho, Nishinomiya 663, Japan.Accepted for publication August 20, 1990 Materials and Methods PatientsThe DNA ploidy analysis was done by flow cytometry from 203 patients receiving hepatectomy for hepatocellular carcinoma during the period from July 1973 to September 1987. The mean age of the patients was 57 years (range, 22-75), 88% of whom were male. These 203 patients received hepatectomy but did not undergo a palliative operation, such as hepatic artery ligation or cannulation. Chronic liver disease was noted as follows: cirrhosis, 168 (83%); and chronic hepatitis, fibrosis, or both, 20 (9.8%). Two samples taken from different places in the tumor were analyzed in 52 patients, whereas single samples were analyzed in 15 1 patients. The medical records of each patient were reviewed to confirm the sex, age, serum hepatitis B antigen (HBsAg), and serum alpha-fetoprotein (AFP). Pathologic examinationTumor size was the largest diameter recorded in...
Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.
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