A total of 850 patients with hepatocellular carcinoma seen during the last 8 years were analyzed retrospectively for survival in relation to treatment and disease stage. A new staging scheme based on tumor size, ascites, jaundice and serum albumin was used. Clearly, the prognosis depended on disease stage. The median survival of 229 patients who received no specific treatment was 1.6 months, 0.7 month for Stage III patients, 2.0 months for Stage II, and 8.3 months for Stage I. The median survival of Stage I patients who had hepatic resection (n = 115) was 25.6 months and Stage II patients with resection (n = 42) was 12.2 months. In patients who had a small cancer (less than or equal to 25% of liver area in size) the median survival was 29.0 months. Survival of the surgically treated patients, which represented a highly selected group, was better than that of medically treated patients of a comparable stage. Median survival of Stage I medically treated patients (n = 124) was 9.4 months, for Stage II (n = 290) 3.5 months, and for Stage III (n = 50) 1.6 months. Medical treatment prolonged survival in Stage II and III patients, but not in Stage I. Transcatheter arterial embolization gave a better survival compared with chemotherapy, whether intra-arterial bolus administration of mitomycin C, systemic mitomycin C, or oral/rectal tegafur, in Stage II. Among various chemotherapeutic modalities, intra-arterial bolus injection was superior to systemic chemotherapy in survival in Stage II. In Stage III, chemotherapy improved survival as compared with no specific treatment. The major causes of death were hepatic failure and gastrointestinal bleeding, probably due to the coexistent advanced cirrhosis. These results in survival are much improved over the past reports, and the differences are probably a result of earlier diagnosis and frequent hepatic resections.

Natural history of hepatocellular carcinoma and prognosis in relation to treatment study of 850 patients

Clinical and pathologic features of 23 patients with a distinctive histologic and clinical variant of hepatocellular carcinoma are summarized. The variant pattern of hepatocellular carcinoma is most common in the age group 5--35 years and occurs equally in either sex. The distinctive histologic features include 1) deeply eosinophilic neoplastic hepatocytes, many of which contain intracytoplasmic hyaline globules and distinct pale bodies and 2) fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes. The histologic and gross features of the tumor have been confused both with focal nodular hyperplasia and with hepatocellular adenoma. The average survival of 32 months and the high operability rate of 48% far exceed the survival or operability for ordinary hepatocellular carcinoma. Thus, this tumor type must be recognized and considered separately when evaluating therapeutic results in large series of patients with hepatocellular carcinoma.

Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features.

Hepatocellular carcinoma, even when treated with operative resection, is generally regarded as uniformly fatal. Isolated reports of an unusual histologic variant characterized by polyglonal cells with a fibrous stroma (PCFS) suggest a more favorable outcome. Twelve cases of PCFS, representing the largest reported group, are presented. The mean age of the patients at the time of onset was 23.1 years and the male to female ratio was 1:2. Successful operative resection of the primary neoplasm and metastatic foci has resulted in a significant percentage of long-term survivors with a mean survival time of 68 months and two- and five-year survival rates of 82% and 63%, respectively. The variant shows cytologic similarity to differentiated hepatocellular carcinoma with a unique stromal appearance suggesting a pattern of fibrosis associated with focal nodular hyperplasia. Focal nodular hyperplasia is noted occasionally in the liver adjacent to PCFS. The possibility that PCFS represents an intermediate stage between focal nodular hyperplasia and the more malignant variants of hepatocellular carcinoma is discussed.

Hepatocellular carcinoma. Polygonal cell type with fibrous stroma—an atypical variant with a favorable prognosis

The clinical features of 57 autopsied cases of intrahepatic bile duct carcinoma including 28 cases of the peripheral type (cholangiocarcinoma in the narrow sense) and 29 cases of the hilar type are described in comparison with those of hepatocellular carcinoma, with a review of the literature on the clinicopathological aspects of intrahepatic bile duct carcinoma. As compared with hepatocellular carcinoma, the average age of the patients was older; the male predominance was not obvious, chronic parenchymal liver disease was infrequent in the past history, association of primary cirrhosis was seldom, cholestatic features were frequently the early signs and more pronounced during the course, the liver was enlarged to a lesser extent, ascites was less common, signs of portal hypertension were absent or minimal, and extrahepatic metastases were less frequent. In many respects, the hilar type resembled extrahepatic bile duct carcinoma, and the peripheral type was somewhat between it and hepatocellular carcinoma. Although the overall survival was not much different from that for hepatocellular carcinoma, early diagnosis is emphasized; this would make surgical management possible. Differential diagnosis from hepatocellular carcinoma may be possible in the majority with direct cholangiography, liver scan, celiac angiography, determination of alpha-fetoprotein and hepatitis B antigen, and blood chemistry such as SGOT, SLDH, serum bilirubin and alkaline phosphatase. Illustrative cases are given including one patient with a hilar carcinoma who survived for more than 2 years after transhepatic biliary drainage.

Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases.

Purpose: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. Experimental Design: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. Results: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. Conclusions: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.

https://clincancerres.aacrjournals.org/content/clincanres/11/10/3799.full.pdf

Proton Beam Therapy for Hepatocellular Carcinoma: A Retrospective Review of 162 Patients

Over a span of 20 years, 137 patients with primary malignant tumors of the liver received treatment at the Memorial Cancer Center. Seventy‐one percent of the patients had hepatocellular carcinoma. Various modalities of therapy were applied in the treatment of these patients. Early diagnosis is mandatory to increase the resectability rate. Thirty‐two patients had some form of hepatic resection of whom 5 survived more than 5 years. Good palliation and prolongation of life occurred in 2 out of 6 patients who had hepatic artery infusion by chemotherapeutic agents. The role of hepatic transplantation and re‐vascularization of segments of the liver in extending the scope of hepatic resection remains in the experimental phase.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197101%2927%3A1%3C7%3A%3AAID-CNCR2820270103%3E3.0.CO%3B2-Q

Primary malignant tumors of the liver.

Of 449 patients with carcinoma of the stomach seen at Memorial Hospital over a span of 10 years, 80 had palliative gastric resection. Forty-six had residual gross disease and thirty-four had microscopic cancer at the margins of the specimen. The postoperative mortality rate was 17.5%. The duration of palliation averaged two thirds of the survival time with 91% of the patients developing late complications.



The outcome of any palliative reaction in patients with gastric cancer depends on the location and extent of the disease. Distal subtotal gastrectomy should be performed only in the absence of extensive intra-abdominal spread or ascites. The high mortality and the poor results of total gastrectomy and esophagogastrectomy preclude their application.

Ali A. El-Domeiri

Papers

Primary malignant tumors of the liver.

A comparative study of palliative resections for gastric carcinoma