The relationship between prognostic and predictive factors in the management of breast cancer.

The discovery of new prognostic factors proceeds at a much more rapid pace than our knowledge of how to properly utilize this information in the management of patients with breast cancer, especially those with early breast cancer that has not metastasized to regional lymph nodes. Prognostic factors provide information on how the patient is likely to do regardless of treatment. Predictive factors provide information on whether a patient is likely to benefit from therapy. Most factors identified to date provide prognostic information, but relatively few provide information that is truly helpful in making a therapeutic decision in the management of individual patients. In large part this is because there has been insufficient study of the factor, especially prospective evaluations of the factor. Unfortunately this has resulted in the premature use of this information under the general rubric that patients with a poor prognosis deserve more treatment in spite of the fact that there may be no benefit from that therapy in the poor prognostic group.

Predicting clinical recovery from alcoholic liver disease.

We postulated that three tests could be used to advantage in the prognosis of patients with alcoholic liver disease. Ninety-eight patients who entered the hospital in hepatic failure, and who survived that illness, were observed for an average of 3.5 years after discharge. At the time of entry, most had jaundice, ascites, edema, and hepatosplenomegaly. Biopsy of the liver disclosed both cirrhosis and hepatitis in 75-80%. Neither clinical features nor laboratory tests could differentiate these patients at the time of entry. However, as early as 3 months after hospitalization, the clinical course and laboratory tests served to distinguish two groups: group 1 comprised 46 patients in whom the serum bilirubin was less than 2 mg/dl; the aspartate aminotransferase less than 55 mU/ml; and the alkaline phosphatase less than 125 mU/ml. In 40 (87%) of these 46 patients, clinical findings improved concomitantly with laboratory tests. Group 2 comprised 52 patients in whom one or more of these three tests showed persistent abnormality; only 12 (23%) of the 52 patients in this group improved clinically and three subsequently died. Although the majority of patients (76%) in group 1 reported abstinence on follow-up, 44% of group 2 patients also claimed abstinence. Complications of liver disease, shunt surgery, and continuing alcoholism contributed to liver failure. Early identification of such patients should aid in the management of alcoholic liver disease.

Recovery from alcoholism in cirrhotic patients: a study of 45 cases.

In order to determine factors that influenced their recovery from alcoholism, 45 men who attended a liver clinic were studied, employing a detailed questionnaire. All had shown classic signs of cirrhosis, and 84 percent were in frank hepatic failure at the time of hospitalization. In general, they were married, blue-collar workers who drank, on average, for 27 years and either abstained or sharply curtailed their alcohol intake for 3.7 years (range one to 11 yrs) following which their hepatic function improved steadily. They reported that severe medical illness was a critical factor in the decision to stop drinking (87 percent) and that continued medical care was very helpful in their recovery from alcoholism (73 percent). Formal alcoholism treatment seldom was employed. Most stated that they "did it on their own." Improvement in health, in psychologic state, in marital and social relations reinforced sobriety. The results indicate the potential impact of medical illness on the decision to stop drinking and the need to study further the factors that promote recovery from alcoholism in medical settings.

Alcohol, malnutrition, and alcoholic cirrhosis.

The relative importance of malnutrition and alcohol toxicity in the pathogenesis of cirrhosis has been controversial. In epidemiological studies the incidence of cirrhosis can be correlated with the duration and amount of alcohol imbibed. The importance of nutrition has been discounted. In these studies few analyses of dietary intake were included. Diets of patients with alcoholic cirrhosis characteristically are poor. Furthermore, alcohol toxicity impairs nutrition by interfering with absorption, transport, and utilization of essential nutrients. Patients with cirrhosis respond favorably to nutritious diets despite the concurrent intake of alcohol, although in lesser amount than their usual intakes. In long-term studies highly nutritious diets have protected rats against cirrhosis from alcohol. However, in acute experiments with "loading" doses there was evidence of direct hepatotoxicity in animals and man. Recently, cirrhosis has been produced in baboons with alcohol and a diet considered adequate. The findings are important, but there is some question whether dietary factors (imbalance) may have played a role. Also of recent interest has been the occurrence of lesions simulating alcoholic hepatitis and cirrhosis after jejunoileal bypass surgery. The evidence suggests that malnutrition may have been a major factor in this disease. The roles of alcohol toxicity and of malnutrition in the pathogenesis of cirrhosis are not fully understood. Further studies are needed to clarify these relationships.

Serum lipids in alcoholic patients with and without cirrhosis of the liver, with particular reference to endogenous familial hypertriglyceridemia.

The purpose of this study was to determine the frequency of hypertriglyceridemia in alcoholic patients with and without cirrhosis of the liver. It had been observed by others that subjects with endogenous familial hypertriglyceridemia (type IV hyperlipoproteinemia) showed an exaggerated lipidemic response to ingestion of alcohol, and, therefore, might be predisposed to hepatic cirrhosis. Comparison of 40 alcoholic cirrhotics with 40 noncirrhotic alcoholic patients showed no increased incidence of hypertriglyceridemia in either group. The findings suggest that the frequency of cirrhosis in the general population is not materially affected by subjects with this metabolic defect.

Minimal hepatic changes in rats fed alcohol and a high casein diet.

This study was designed to determine whether prolonged ingestion of alcohol in combination with a nutritious diet can produce hepatic cirrhosis in the rat. Male Wistar-strain rats were fed a high protein liquid diet in which alcohol comprised 35.5% of total calories. Rats maintained on this diet for 19 months had normal growth. There was no evidence of cirrhosis after 19 months. Histological examination showed no hepatocellular necrosis, inflammation, or increased connective tissue. Ultrastructural study showed no substantial changes, except for occasional mitochondrial enlargement in cells containing increased lipid. Biochemical analyses at 19 months showed moderate increase in hepatic triglyceride levels and slight increase in hepatic collagen content in the experimental groups.

Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients.

Alcohol intakes and dietary habits of 304 alcoholic, hospitalized patients were evaluated. There were 195 patients with hepatic cirrhosis, 40 precirrhotics, and 69 noncirrhotics. Alcohol contributed 50% to 58% of total calories. Two thirds of the patients drank excessively for more than 20 years. There were no statistically significant differences between the three groups in the duration or degree of alcohol excess. Dietary intakes were assessed for a period of at least two years before the presenting illness. Noncirrhotics had higher food caloric intakes and higher protein intakes than the cirrhotics (P less than .05). The findings suggest that dietary factors may be involved in the pathogenesis of the disease.

Cirrhosis of choline deficiency in the Rhesus Monkey. Possible role of dietary cholesterol (38541).

One of five rhesus monkeys fed a diet deficient in choline and protein for 31 mo developed signs of cirrhosis at 26 mo. Five other monkeys were fed the same diet for 14 mo, at which time cholesterol comprising 2% of the diet was added. Three followed a sharp rise in hepatic lipids. One monkey developed marked hypercholesterolemia and showed signs of cirrhosis 2 mo after cholesterol supplementation. The findings indicate that the rhesus monkey is susceptible to choline-deficiency cirrhosis. They suggest that cholestrol supplementation accelerates this process.

Management of umbilical hernias associated with hepatic cirrhosis and ascites.

A series of 35 umbilical herniorraphies in patients with cirrhosis of the liver is reported. In this group there were eight significant complications (22%) and six deaths (16%). There was no evidence in this study of increased likelihood of esophageal variceal bleeding secondary to the interruption of portosystemic collaterals in the umbilical region. An aggressive surgical approach is indicated in cirrhotic patients, with umbilical herniae complicated by incarceration, strangulation, rupture, ulceration, and leakage of ascitic fluid. On the other hand it is recommended, that repair of non-complicated umbilical herniae be delayed until the cirrhosis is stabilized, ascites has diminished and nutrition has been improved. In many instances herniorrhaphy may not be necessary after disappearance of ascites.