Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses.

The purpose of this study was to clarify the factors linked to recurrence of small hepatocellular carcinomas, up to 3 cm in diameter, after hepatectomy. Fifty patients with small hepatocellular carcinomas who underwent hepatectomy between 1976 and 1988 were observed for possible recurrence for at least 2 yr. These patients were divided into two groups: 20 patients who had recurrence within 2 yr and 30 patients who had no recurrence within 2 yr. The recurrence pattern was analyzed by hepatic angiography. Statistical analysis by the chi 2 test and stepwise logistic regression showed that the risk factors linked to recurrence were (a) tumor diameter greater than 2.2 cm, (b) intracapsular infiltration of tumor cells, (c) tumor location deep in the liver, (d) macroscopical and microscopical tumor invasion into the portal vein and (e) tumor invasion into the portal vein or intrahepatic metastasis. When patients diagnosed with small hepatocellular carcinomas have any of these risk factors, postoperative adjuvant therapy and follow-up should be particularly carefully considered, since these patients are at high risk for early recurrence.     

Diagnostic significance of angiography for small hepatocellular carcinoma--comparison with other examinations]

The diagnostic value of angiography for small hepatocellular carcinoma was evaluated in comparison with histology, contrast-enhanced computed tomography, and ultrasonography. A total of 120 patients with small hepatocellular carcinoma (less than 3 cm in size) were examined. The definitive detection rate for primary tumors less than 2 cm in size was 44.9% by angiography, while it was 68.6% for primary tumors between 2 cm and 3 cm in size. When the primary tumor was less than 2 cm in size and without tumor vessels on angiography, it tended to be of Edmondson's grade 1 and to show fatty change. When the primary tumor was less than 2 cm in size and without tumor stain while non-cancerous parenchyma showed irregular stain, it tended to be of Edmondson's grade 1 and normotrabecular type. Angiography was found to be of particular value in detecting satellite tumors with a nodular parenchymal echo pattern in non-cancerous areas, because ultrasonography often fails to differentiate these satellite tumors from non-affected parenchyma.     

ras基因联合血清APF水平与肝癌转移关系的研究

目的 探讨ras基因及AFP水平与肝癌病程的关系。方法 测定50例病理检查确诊的肝癌患者血清AFP水平,并检测其手术切除肝癌组织中ras的表达,分析ras基因及血清AFP联合检测与肝癌有无远处转移及术后复发的关系。结果（1）ras在肝癌组织中阳性表达率为64．0％,ras表达与肿瘤大小、有无肝内转移密切相关（P〈0．05）。ras阳性、阴性表达病例3年复发率分别为65．6％、33．3％。（2）高血清AFP水平且ras阳性病例组3年复发率为76．2％,而低血清AFP且ras阳性病例组3年复发率45．5％,差异显著（P〈0．05）。结论 联合ras基因及血清AFP检测可作为判断肝癌术后复发的有效指标,多因素分析更有价值。     

Hepatic function immediately after hepatectomy as a significant risk factor for early recurrence in hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to clarify the significant risk factors as they relate to early recurrence after hepatectomy in cirrhotic patients with hepatocellular carcinoma (HCC). METHODOLOGY: We retrospectively investigated 42 cirrhotic patients undergoing hepatectomy for a single HCC. We compared the clinicopathologic features of 14 patients with early intrahepatic recurrence (recurrence was detected within 1 year after hepatic resection; Group 1) with 28 patients without recurrence or with late intrahepatic recurrence (recurrence was confirmed more than 1 year after hepatic resection; Group 2). RESULTS: There were no significant differences in the pre-operative and intra-operative clinical background data or pathological data between the 2 groups. Regarding recurrence pattern, although not significant, the incidence of intrahepatic metastasis in Group 1 (85.7%) was higher than in Group 2 (50.0%). Maximum values of total bilirubin and albumin within 7 days after hepatectomy for patients in Group 2 were significantly better than those in Group 1. Aspatate aminotransferase (AST) and alanine aminotransferase (ALT) immediately after hepatectomy in Group 1 were also higher than in Group 2, although statistically insignificant. The overall 1-year and 3-year survival rates between Group 1 versus Group 2 were 85.7% versus 100% (p < 0.01) and 57.2% versus 90.0% (p < 0.01), respectively. CONCLUSIONS: Hepatic functional damage immediately after hepatectomy is as significant risk factor for early intrahepatic recurrence in cirrhotic HCC. Careful perioperative management of hepatic function may therefore be important in preventing early recurrence and prolonging survival.     

Usefulness of Ultrasonography for Diagnosis of Small Bowel Tumors: A Comparison Between Ultrasonography and Endoscopic Modalities

Ultrasonography is a standard, noninvasive modality used to evaluate patients with gastrointestinal diseases. This study assessed the usefulness of ultrasonography in the detection of small bowel tumors.This study enrolled 558 consecutive patients (295 males, 263 females; mean age 71.1 years) who underwent ultrasonography before capsule endoscopy and/or balloon-assisted endoscopy. Ultrasonographic detection of small bowel tumors was compared with detection by capsule endoscopy and/or balloon-assisted endoscopy. In addition, factors affecting small bowel tumor detection by ultrasonography and clinical characteristics of patients with small bowel tumors undetected by ultrasonography were evaluated.Ninety-seven tumors (52 benign, 45 malignant) detected by capsule endoscopy and/or balloon-assisted endoscopy were retrospectively analyzed. The sensitivity and specificity of ultrasonography in the detection of small bowel tumors were 50.5% (47/93) and 100% (465/465), respectively. If we restricted patients to those with a tumor >20 mm in size, its detection ratio would become higher (91.7%): the ratio of submucosal tumor >20 mm in size was 85.7% (6/7) and that of partial and circumferential ulcerative tumors >20 mm in size was 96.9% (31/32), respectively. Small bowel tumors detected by ultrasonography (mean 33.2 mm) were significantly larger than those undetected by ultrasonography (mean 8.7 mm). The percentage of small bowel tumors located in the ileum detected by ultrasonography (70.6%) was significantly higher than those undetected by ultrasonography (29.4%). Of the 46 small bowel tumors undetected by ultrasonography, 42 (91.3%) were benign tumors with good clinical prognosis.Ultrasonography is a useful modality for detecting larger small bowel tumors and ulcerative lesions. Ultrasonography should be considered a first-line modality for patients suspected of having small bowel tumors, because most small bowel tumors undetected by ultrasonography were benign tumors with good clinical prognosis.     

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.     

Diagnosis and clinical features of small hepatocellular carcinoma with emphasis on the utility of real-time ultrasonography. A study in 51 patients

The clinical features and usefulness of various methods for diagnosis of small hepatocellular carcinoma, no greater than 5 cm in diameter, were studied in 51 patients. The diagnosis was verified in 28 patients by hepatic resection and in 4 patients at autopsy. The tumor was less than 3 cm in diameter in 23 patients. In 37 patients (72.5%), the tumor was first discovered by real-time linear scan ultrasonography, generally during a routine periodic follow-up examination of patients with chronic liver disease, mostly cirrhosis. Clinically, 62.7% of the patients were asymptomatic, and symptoms in the remainder were not suggestive of carcinoma. Most patients showed only mildly abnormal liver function tests that did not suggest the diagnosis. Serum alpha-fetoprotein level was normal in 25.5%, and it was elevated above 200 ng/ml in only 33.3%. Among the various imaging modalities, ultrasonography had the highest detection rate (92.2%) for these small hepatocellular carcinomas compared with computed tomography (73.2%), scintigraphy (50.0%), and angiography (86.0%). False-positive lesions, however, were also found frequently by ultrasonography, requiring ultrasonography-guided biopsy for differential diagnosis in some of the patients. Routine examination at regular intervals of patients with chronic liver disease using a combination of real-time ultrasonography and alpha-fetoprotein measurement is currently the most effective approach to detecting small hepatocellular carcinoma.     

Caution for Diagnosis and Surgical Treatment of Recurrent Cholangitis: Lessons From 5 Cases of Bile Duct Tumor Thrombus Without a Detectable Intrahepatic Tumor

The hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT) usually have no specific clinical symptoms at early stages. HCC with BDTT was usually misdiagnosed when the intrahepatic tumor was small, even undetectable.In this study, 5 cases of HCC with BDTT misdiagnosed as choledocholithiasis and cholangitis in the local hospital are described. We analyzed retrospectively and summarized our experiences of these 5 HCC patients with BDTT misdiagnosed in the local hospital during the past 5 years. The diagnosis, treatment, and outcome of the patients are discussed.Three patients underwent hepatectomy with thrombectomy and T-tube drainage. One patient underwent hepatectomy with the resection of the common bile duct and hepatojejunostomy, and palliative surgery was performed in 1 patient with portal vein tumor thrombus and intrahepatic metastasis. The patients were followed for 6–22 months; 4 patients died of tumor recurrence and metastasis or hepatic failure, despite 3 of these patients having received transhepatic arterial chemotherapy and embolization or radiofrequency ablation therapy.Early and accurate diagnosis of HCC with BDTT is very important. When patients have a history of abnormal recurrent cholangitis, HCC with BDTT should be highly suspected. Intraductal ultrasonography (US), intraoperative US, and histopathological examination are very valuable for the diagnosis. The prognosis of HCC patients with BDTT is dismal. Identification of this type of patient is clinically important, because surgical treatment may be beneficial.     

Limitations of current preoperative liver imaging techniques for intrahepatic metastatic nodules of hepatocellular carcinoma.

To determine the limitations of the latest techniques in preoperative liver imaging for hepatocellular carcinoma, 20 patients with histologically proven intrahepatic metastatic tumors were studied. In 32 masses, we were able to assess the relationship between these intrahepatic metastatic tumors and the findings of preoperative imaging individually. Six intrahepatic metastatic tumors not exceeding 5 mm in diameter were missed in all the imaging examinations. The detection rate was 60% in 13 intrahepatic metastatic tumors of 5 to 10 mm, 77% in 10 intrahepatic metastatic tumors of 10 to 20 mm and 100% in 3 intrahepatic metastatic tumors exceeding 20 mm. In total, computed tomographic imaging during arterial portography demonstrated the highest rate of detection (40%) of all the studies performed. Magnetic resonance imaging, which was recently introduced, was rather disappointing (31%) in this series. In two patients, intrahepatic metastatic tumors were only histologically confirmed. Our study suggests a low rate of detection of intrahepatic metastatic tumors with current preoperative imaging modalities. For improvement of prognosis after hepatectomy for hepatocellular carcinoma adjuvant therapy and extended hepatectomy seem necessary if the functional capacity of the remaining liver permits.     

Hepatic resection for hepatocellular carcinoma based on tumor hemodynamics

Survival or disease‐free survival is not considered an appropriate surrogate outcome for the locoregional curability (i.e. surgical margin) of hepatectomy for hepatocellular carcinoma because these are greatly influenced by non‐metastatic factors like multicentric carcinogenesis (MC) or liver function. Hepatocellular carcinoma metastasizes by hematogenous seeding; therefore, the tumor blood flow (TBF) drainage area is a high‐risk area for intrahepatic metastasis, and can be identified by computed tomography under hepatic arteriography and completely resected as part of the surgical margin. The TBF pattern is classified into marginal, portal vein or hypovascular types. Partial hepatectomies were mostly performed in patients with marginal or hypovascular type, whereas anatomical surgery was frequently performed in those with portal vein type. Pathologically, nodules inside the TBF drainage area were moderately or poorly differentiated carcinomas, suggesting intrahepatic metastasis. In contrast, those outside the drainage area were frequently solitary and contained well‐differentiated carcinoma, which is consistent with MC. The pattern of tumor recurrences after TBF‐based hepatectomy is divided into two distinct groups – “a few nodules” and “many nodules in multiple segments or extrahepatic” – indicating that intrahepatic recurrences develop from MC and from circulating tumor cells in peripheral blood, respectively. Anatomical resection has not shown a survival benefit over that of TBF‐based partial hepatectomy. TBF‐based hepatectomy enables us to preserve liver function without compromising locoregional curability.     

几种不同治疗手段对原发性肝癌的疗效比较研究

目的对原发性肝癌儿种不同治疗手段疗效进行比较分析,为临床合理化治疗方案的确定提供参考与帮助.方法我院1999年6月至2003年6月收治原发性肝癌病例中80例分为A组:单纯手术组;B组:手术切除 植入式肝动脉化疗泵化疗组;C组:单纯肿瘤内注射无水酒精组;D组:股动脉穿刺介入治疗组.对不同治疗手段疗效进行比较分析.结果治疗后A、B、C、D四组1年生存率分别为60.13%、71.26%、43.15%、42.78%,2年生存率分别为46.52%、51.38%,26.64%,25.83%.A、B组术后1年复发率分别为60.33%,49.28%,术后2年复发率分别为76.59%,61.24%.结论对原发性肝癌的治疗以手术切除病灶加化疗的综合治疗效果最佳,单纯手术切除较荷瘤的其他治疗手段效果好,但对无法手术切除的病例肿瘤局部用药的治疗手段仍具有一定的控制效果.     

Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma

BACKGROUND/AIMS: None of the previous studies have compared the prognosis or clinicopathological factors between the patients with extrahepatic recurrence and those with intrahepatic recurrence of hepatocellular carcinoma after a hepatic resection. METHODOLOGY: The clinicopathological features and prognoses of patients with extrahepatic recurrence after a curative hepatectomy for hepatocellular carcinoma were investigated. RESULTS: Twenty-three patients with extrahepatic recurrence had more advanced-stage hepatocellular carcinoma at the primary operation compared to 186 patients with intrahepatic recurrence. After adjusting for tumor size, the prognosis of the 2 groups were comparable. However, among the patients with hepatocellular carcinoma exceeding 5 cm in diameter, the number of patients whose plasma levels of des-gamma-carboxy prothrombin was higher than 2.0 AU/mL in the patients with extrahepatic recurrence (62.5%) was significantly more (P < 0.05) than that in the patients with intrahepatic recurrence (20.0%). On the other hand, the prognosis of the 13 patients with extrahepatic recurrence alone was significantly better than in the 10 patients with both intrahepatic and extrahepatic recurrences. The prognoses of the 3 patients who underwent a surgical resection for isolated extrahepatic recurrence were markedly better than that of the remaining 10 patients only treated palliatively. CONCLUSIONS: If patients have tumors exceeding 5 cm in diameter and their plasma levels of des-gamma-carboxy prothrombin are higher than 2.0 AU/mL, more careful follow-up examinations than usual may thus be necessary in order to detect extrahepatic recurrence as early as possible. Furthermore, a surgical resection for the isolated extrahepatic recurrence of hepatocellular carcinoma is also recommended to produce long-term survivors.     

Treatment for extrahepatic metastasis of hepatocellular carcinoma following successful hepatic resection

BACKGROUND/AIMS: Recent advances in both the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved its prognosis. Intrahepatic recurrence after hepatectomy can be treated with repeated hepatectomy, transhepatic arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), or microwave coagulo-necrotic therapy. However, treatment for extrahepatic recurrence is also important in prolonging survival in some patients. METHODOLOGY: After radical hepatectomy in 155 patients, extrahepatic recurrences were found in 15 patients that underwent subsequent treatment. The interval between completing treatment for the primary tumor and the discovery of metastasis, the location and mode of treatment of the metastasis, and the outcomes were analyzed. RESULTS: Distant metastasis was detected at a mean of 7 months after radical resection of the primary tumor. Location of the metastasis included lung, bone, and adrenal gland. Four patients had no intrahepatic recurrence and 11 patients had simultaneous intrahepatic recurrence. Six patients with intrahepatic and extrahepatic recurrence that underwent systemic chemotherapy had poor prognoses, and all died within 12 months as a result of progression of the intrahepatic tumor. Five patients with intra- and extrahepatic recurrence that underwent systemic chemotherapy combined with hepatic arterial infusion chemotherapy had relatively good outcomes; all survived for more than 12 months. CONCLUSIONS: These results suggest that to obtain a good prognosis for extrahepatic metastasis coexisting with intrahepatic recurrence, intrahepatic recurrence should be controlled by locoregional therapy, and extrahepatic metastasis should be controlled by systemic chemotherapy and/or irradiation therapy.     

Combination therapy of percutaneous mitoxantrone injection, percutaneous ethanol injection, and transcatheter arterial embolization for intrahepatic hepatocellular carcinoma and adrenal metastasis

We treated a 63-year-old man who had recurrent large hepatocellular carcinomas (> 5 cm in diameter) and left adrenal metastasis with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization. He received repeated transcatheter arterial embolization and percutaneous ethanol injection combination therapy for intrahepatic hepatocellular carcinomas, which controlled his disease for 6 months from the first treatment. After that, left adrenal metastasis was detected by biopsy specimen. Therefore, we repeated more transcatheter arterial embolization and percutaneous ethanol injection to the liver and left adrenal gland, but this combination therapy could not control the hepatocellular carcinomas in these organs. With the patient's consent, he was treated with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization for hepatocellular carcinomas of the liver and left adrenal gland. After this combination therapy, we followed-up the viable lesions by color Doppler ultrasonography and computed tomography examination. However, we could not detect these viable lesions of hepatocellular carcinomas in his body until one month before he died. When the degree of hepatic failure worsened due to the natural course of cirrhosis, this combination therapy was stopped 7 months before he died. He died of pulmonary tumor emboli from metastasis of inferior vena cava 24 months after the combination therapy started. However, on autopsy there was almost no remaining hepatocellular carcinoma found in the main lesions of liver and left adrenal gland. We suggest that a combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization may be indicated in elderly cases of intrahepatic large hepatocellular carcinoma and adrenal metastasis, which are not under control only by transcatheter arterial embolization and percutaneous ethanol injection.     

Poor prognostic factors of hepatectomy in patients with resectable small hepatocellular carcinoma and cirrhosis

Purpose Some patients with hepatocellular carcinoma (HCC) at an early stage cannot attain long-term survival after hepatectomy. The aim of the present study was to investigate the poor prognostic factors for hepatectomy in patients with resectable small HCC with cirrhosis.Methods We studied 95 patients with cirrhosis with HCC, which consisted of a single tumor 5 cm or smaller or two or three tumor nodules each 3 cm or less; an absence of extrahepatic metastasis; and an absence of radiological evidence of macroscopic portal vein or hepatic vein invasion. We used Coxs proportional hazard model to identify risk factors associated with prognosis to determine the contra-indications for hepatectomy in patients with resectable small HCC.Results Preoperative risk factors were: (1) serum AFP concentration of more than 400 ng/ml; (2) infiltrative-, massive-, or multinodular-type (multiple) HCC; and (3) the presence of intrahepatic metastasis. Patients who had had more than one of the three preoperative risk factors were poor candidates for hepatic resection, with a 4-year survival of 16.3%.Conclusion If patients with resectable small HCC are diagnosed as having more than one of three preoperative risk factors, they should not receive hepatectomy or should be considered for primary liver transplantation as a therapeutic option for HCC.     

Clonality and clonal evolution of hepatocellular carcinoma with multiple nodules.

To determine the clonal evolution of hepatocellular carcinoma, the integrated hepatitis B virus DNA patterns of the main tumor, satellites and/or metastatic lesions were analyzed by Southern-blot hybridization in 28 hepatocellular carcinomas, including three HBsAg-seronegative cases. Unicentric or multicentric hepatocellular carcinoma was confirmed by histopathological criteria in 89% of the cases. Among 17 unicentric hepatocellular carcinomas, minor changes of the integration pattern--including partial loss or addition of the integration sites or both--were detected in the metastatic lesions in 29% of the cases. Furthermore, none of five cases with free-form hepatitis B virus DNA in the primary tumor had detectable free hepatitis B virus DNA in the metastatic lesions. These results suggest that the alteration of integrated hepatitis B virus DNA pattern during the course of tumor growth and metastasis may occur more often than previously perceived and that the switch-off of virus replication may be related to tumor metastatic potential. In eight cases with unilateral, multicentric hepatocellular carcinoma, two clones were detected in six cases, three were seen in another and four were seen in one. One case of note was a 9-yr-old boy with two histological types and two different integration patterns, one associated with vascular invasion and lung metastasis. Three patients with bilateral hepatocellular carcinoma were confirmed to have bicentric or tricentric hepatocellular carcinoma rather than intrahepatic dissemination and had survival rates similar to those in unicentric hepatocellular carcinoma. Three invasive HBsAg-seronegative hepatocellular carcinomas were found to have hepatitis B virus DNA integration and were of unicentric origin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas

BACKGROUND/AIMS: The multistep development of overt hepatocellular carcinoma from very well-differentiated early hepatocellular carcinoma, and of early hepatocellular carcinoma from adenomatous hyperplasia has been strongly suggested. The clinicopathologic and immunohistochemical characteristics of solitary minute hepatocellular carcinomas smaller than 1 cm in size have yet to be clarified. METHODOLOGY: Fourteen minute hepatocellular carcinomas were divided into 2 groups consisting of: 1) hepatocellular carcinoma of hepatitis B surface antigen positive patients (B-HCC) (n = 5), and 2) hepatocellular carcinoma of hepatitis C virus antibody positive patients (C-HCC) (n = 9), then they were all analyzed histopathologically and clinicopathologically. Immunohistochemical studies were also performed using the antibodies against p53 protein. RESULTS: Six of the 14 minute hepatocellular carcinoma were demonstrated to be moderately or poorly differentiated tumors. Among the 8 well-differentiated minute hepatocellular carcinomas, 2 tumors already contained less differentiated components. B-HCC tended to be less differentiated than C-HCC (P < 0.05). Adenomatous hyperplasia was detected in only 2 cases of C-HCC. Small cell liver dysplasia was detected significantly more frequently in C-HCC than in B-HCC (P < 0.05). The prognosis of the 14 minute hepatocellular carcinomas varied considerably. Immunohistochemically, some tumor cells were positive for p53 in 3 cases. CONCLUSIONS: Our study suggests that 1) the multistep carcinogenesis through adenomatous hyperplasia may not be so frequent, 2) De novo carcinogenesis from not only well-differentiated hepatocellular carcinoma, but also from less differentiated hepatocellular carcinoma, especially B-HCC, may be present, 3) the carcinogenesis in the B-HCC cases may behave differently from that in C-HCC cases, and 4) minute hepatocellular carcinomas demonstrate varying prognoses after hepatectomy.     

Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection. METHODOLOGY: We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model). RESULTS: Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005). CONCLUSIONS: Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.     

The expression of p53 antigen in primary malignant epithelial tumors of the liver: an immunohistochemical study

ABSTRACT— We examined the expression of mutant p53 gene products in primary malignant epithelial tumors of the liver. Fourteen of 68 hepatocellular carcinomas, one of seven hepatoblastomas and one of nine intrahepatic cholangiocarcinomas showed nuclear staining for p53 proteins. None of the surrounding non-tumorous tissues expressed nuclear staining. The detection of p53 proteins in tumor cells was significantly higher in hepatocellular carcinomas of Oriental patients (31.6%) compared to non-Orientals (6.7%, p<0.015). No significant differences were seen in p53 antigen expression between hepatitis B and non-hepatitis B associated hepatocellular carcinomas in Oriental patients. These results suggest a role for other environmental factors, such as aflatoxin, in the etiology of p53 mutation in hepatocellular carcinoma in Oriental patients.     

Small hepatocellular carcinoma with minute satellite nodules

BACKGROUND/AIMS: To investigate the clinicopathologic characteristics of small hepatocellular carcinoma with minute satellite nodules. METHODOLOGY: We investigated the clinicopathologic characteristics of 131 solitary small (< or = 2.0 cm in diameter) hepatocellular carcinomas including 105 hepatocellular carcinomas without minute satellite nodules and 17 hepatocellular carcinomas with minute satellite nodules smaller than 5 mm, and also discuss the clinical significance. RESULTS: None of the clinical backgrounds of the patients and pathologic features of the main tumor, except for the average of preoperative serum alpha-fetoprotein, were significantly different between the two groups. Firstly, minute satellite nodules demonstrated that the maximum diameter of all minute satellite nodules was 1.5-4.0 mm, secondly, the moderately to poorly differentiated hepatocellular carcinomas had 4 or more minute satellite nodules within 1 cm from the main tumor, while well differentiated hepatocellular carcinomas may have 1 or 2 minute satellite nodules 6 cm or more away, and thirdly, 4 or more minute satellite nodules may present within 1 cm in intrahepatic metastasis cases, while 1 or 2 minute satellite nodules may be present 6 cm or more away from the main tumor in multicentric occurrence cases. CONCLUSIONS: At least 13% of solitary small hepatocellular carcinomas had preoperatively undetectable minute satellite nodules. In case of moderately to poorly differentiated hepatocellular carcinomas, hepatic resection as well as percutaneous ethanol injection should be performed including the surrounding liver tissue at least 1.0 cm from the main nodule. On the other hand, in well-differentiated hepatocellular carcinomas, which may indicate multicentric occurrence, closer observation and careful follow-up after therapy are recommended.