Hepatocellular carcinoma complicating chronic granulomatous hepatitis.

The development of hepatocellular carcinoma, is reported in a patient with chronic granulomatous hepatitis after a seven year interval in which clinical and biochemical improvement had occurred on corticosteroid therapy and in whom, the development of cirrhosis was excluded by liver biopsy.

Ultrasound in hepatoma-can specific diagnosis be made?

The ultrasound appearances of primary hepatocellular carcinoma in 32 patients are described. Attempts to correlate the appearances with serological, histological, and arteriographic findings revealed no consistent pattern. There appears to be no great difference in the range of ultrasound appearances in primary hepatocellular carcinoma when compared with that reported for metastatic disease. The findings suggest that in patients with cirrhosis, ultrasound is a sensitive method for the detection and accurate location of hepatocellular carcinoma, but that in these patients the echo pattern provides little help in the differentiation of primary from secondary carcinoma. Our study has revealed four different echo patterns in patients with hepatocellular carcinoma: echofree (47%), echogenic (23%), mixed (175) and diffuse infiltration 13%).

Serum alpha-foetoprotein in hepatocellular carcinoma--value in diagnosis, and prognosis.

The value of serum alpha-foetoprotein (AFP) estimation using radioimmunoassay in patients with hepatocellular carcinoma (HCC) has been investigated. Serum AFP concentration was raised in 97% of patients with cirrhosis complicated by tumour, while only one of 100 patients with uncomplicated cirrhosis had increased concentrations. Serial serum AFP estimation was therefore a valuable screening test in this high-risk group. Raised serum AFP was found to be an additional adverse prognostic factor in HCC patients: 81% of a group of HCC patients with normal serum AFP survived one year while only 12% of patients with raised AFP levels did so. However, this mainly reflects underlying cirrhosis in those HCC patients with raised AFP. Serum AFP doubling time was determined in 28 HCC patients with raised serum AFP and showed a significant correlation with survival, those slowest doubling times surviving longest. Serial AFP determinations were useful in predicting the outcome of chemotherapy: an exponential rise in AFP occurred in those who failed to respond to treatment, but serum AFP fell in those who achieved clinical remission, with a sustained fall in those with complete remission.

The use of therapeutic embolisation at the time of hepatic arteriography in the management of primary tumours of the liver.

In 10 of 14 patients with primary hepatic tumours the technique of selective arterial embolisation with gelatin foam was successful in inducing necrosis of the tumour tissue. In the patients with histologically proven hepatocellular carcinoma there was ultrasonographic evidence that this was produced, as was also shown by a rapid initial fall in serum alpha-foetoprotein concentration. Treatment was continued with a course of doxorubicin (Adriamycin) and the patients remained well and symptom-free for a median of 10 months, the longest survival being 19 months. In two patients with localised and highly vascular contraceptive pill-associated hepatic tumours, embolisation was followed by complete disappearance of the tumour mass in one and resolution of obstructive jaundice in the other. In one other the response was equivocal.

A case of factitious fever and 'epilepsy'.

We describe the case of a 23 year old male who presented with a history of intermittent pyrexia associated with apparent episodic loss of consciousness. During these events, thermometers placed in the rectum and axillae supported the elevated oral temperature readings. After numerous investigations including electroencephalography had excluded organic disease, the patient was observed applying a hot douche to his rectum prior to his temperature being recorded.

Heat illness. A report of 45 cases from Hong Kong.

During the summer of 1985, 45 soldiers with heat illness were admitted to the British Military Hospital, Hong Kong. Twelve had severe heat stroke, the remainder heat exhaustion. This paper discusses the management and prevention of heat illness in the military context.

Chronic pancreatitis in the British Army 1978-1989.

A retrospective study was made of all 28 soldiers with chronic pancreatitis first diagnosed between 1978 and 1989. All patients were male, alcohol was the aetiological factor in 90%, the mean age at diagnosis was 30 and the commonest mode of presentation was with recurrent painful episodes of pancreatitis. Endocrine and exocrine pancreatic insufficiency occurred in a quarter and a third of patients respectively and one third required surgical intervention.

Controlled clinical trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma.

Following reports that specific estrogen receptors could be detected in samples of hepatocellular carcinoma tissue, a prospective randomized controlled trial was undertaken in 59 patients, half of whom received doxorubicin (60 mg/m2 at 3-week intervals) and half doxorubicin and tamoxifen (10 mg twice per day). Response occurred in three (11%) of those patients receiving doxorubicin alone and in four (16%) of those given both drugs. This difference was not statistically significant nor was the difference in survival when compared by life-table analysis. One patient treated with both drugs achieved complete remission for 30 months which was maintained (on tamoxifen alone) for 18 months before death from a non-tumor-related condition. Tamoxifen may have a role in maintenance of doxorubicin-induced remissions.

Polyneuropathy: an unreported non-metastatic complication of primary hepatocellular carcinoma.

A patient with hepatic cirrhosis is described, who presented with a sensorimotor polyneuritis at the time of the development of a primary hepatocellular carcinoma. Typical clinical and electrodiagnostic features of a paraneoplastic peripheral neuropathy, not previously reported in hepatocellular carcinoma, were found on investigation.

Induction of remission in hepatocellular carcinoma. A comparison of VP 16 with adriamycin.

Following a pilot study of VP-16.213 (180 mg/m2 on 3 consecutive days at 2 weekly intervals) in the treatment of patients with hepatocellular carcinoma, the efficacy of the drug was compared with that of adriamycin in another 35 patients in a randomized crossover trial. Each drug gave a similar response rate (18 and 28%, respectively) but the duration of response was significantly longer in those receiving Adriamycin. Some patients who had not responded to treatment with Adriamycin had worthwhile remission with VP 16.

Hepatocellular carcinoma in HBsAg-negative chronic active hepatitis.

The occurrence of hepatocellular carcinoma in HBsAg-negative chronic active hepatitis is described in two patients. signs of the tumour appeared 18 years and nine years after the first clinical signs of chronic active hepatitis, although in one patients analysis of stored sera showed the serum alpha-fetoprotein levels had been rising over the previous 33 months. Female preponderance in HBsAg-negative chronic active hepatitis may partly account for the rarity of this complication, and the occurrence of hepatocellular carcinoma may also be a reflection of the better survival now being obtained in HBsAg-negative chronic hepatitis.

Plasma carcinoembryonic antigen in the diagnosis and management of patients with hepatocellular carcinoma.

The value of serial carcinoembryonic antigen (CEA) measurements as a marker of disease progression or in monitoring treatment was investigated in patients with hepatocellular carcinoma. Of 40 patients, including 16 with normal serum alpha-fetoprotein (AFP) concentrations, 29 (72.5%) had abnormal plasma CEA at presentation. Although this was more common in patients with pre-existing cirrhosis, the mean and range of plasma CEA were similar in patients with and without pre-existing hepatic disease. There was no correlation between plasma CEA and any biochemical parameter of hepatic function, although plasma CEA concentrations were significantly lower in patients with well-differentiated tumors. CEA concentrations increased in 71% of patients who had no response to cytotoxic drugs, but CEA also increased in 62.5% of those patients who did respond. Plasma CEA concentrations were elevated in 62.5% of patients with normal and 79% of patients with raised serum AFP on admission to the hospital. There was no correlation between individual AFP and CEA concentrations. Although elevated plasma CEA levels may be of diagnostic value in patients with hepatocellular carcinoma in the absence of pre-existing hepatic disease, and in those with normal serum AFP, our findings indicate that it does not behave as a true tumor marker.

Relationship between serum alpha-foetoprotein, cirrhosis and survival in hepatocellular carcinoma.

An analysis of survival time of 57 West European patients with hepatocellular carcinoma was carried out to define which of several possible factors (age, sex, cirrhosis and raised serum alpha-foetoprotein (AFP)) influenced survival. Although survival was significantly longer in younger patients (P less than 0.02) and in patients with normal serum AFP (P less than 0.01), multivariate analysis showed that significant variation in survival time is better explained by the single factor, the presence of cirrhosis, than by AFP level. This does not seem to apply for patients with this tumour in Africa and the Far East, and there may be a fundamental difference in the natural history of the tumour between high- and low-incidence areas.

Serum ferritin in hepatocellular carcinoma. A comparison with alphafetoprotein.

The serum ferritin level was raised in 34 of 35 (97%) patients with hepatocellular carcinoma and in 20 of 23 (87%) with uncomplicated cirrhosis. Levels rose following therapeutic embolisation in 14 of 15 patients and continued to rise in 85% of all tumor patients who showed no clinical response to chemotherapy (intravenous Adriamycin) whereas in those who did respond the serum ferritin level fell. By contrast, there was a fall in serum alphafetoprotein immediately after embolisation but like serum ferritin, alphafetoprotein levels rose with disease progression and only fell in those achieving clinical remission. Serum ferritin has no role in the differential diagnosis of hepatocellular carcinoma but may be a useful marker in monitoring response to chemotherapy particularly in the alphafetoprotein-negative patient.

Use of arterial devascularization and cytotoxic drugs in 30 patients with the carcinoid syndrome.

Thirty patients with symptoms of the carcinoid syndrome and other symptoms not controlled by pharmacological agents were analysed with respect to the value of various treatment measures used. Tumour devascularization was carried out in 11 patients, either by surgical ligation of the main hepatic artery (6) or by percutaneous arterial embolization (5). The latter was shown to be the safer technique, both with respect to initial morbidity/mortality and other side effects. Control of flushing and diarrhoea was achieved in 80% and the technique was also repeated on one occasion with success when symptoms recurred. The use of cytotoxic drugs alone, including 5-fluorouracil, cyclophosphamide and Adriamycin produced symptomatic relief in only 4 of the 22 patients treated. They should only be considered if devascularization by arterial embolization proves impossible or cannot be repeated when symptoms recur.

Hepatocellular carcinoma in the non-cirrhotic liver: a comparison with that complicating cirrhosis.

The clinicopathological features of 50 patients with hepatocellular carcinoma arising in a non-cirrhotic liver are described and compared with those of 100 patients in whom the tumour arose as a complication of cirrhosis. The non-cirrhotic patients were significantly younger, more often female and had a less strong association with serum markers of hepatitis B virus infection. Liver function tests and serum AFP were less often abnormal and survival was significantly better than in the cirrhotic group. The different aetiological factors, clinical features and prognosis of hepatocellular carcinoma arising in the non-cirrhotic liver compared to the more common form of hepatocellular carcinoma which complicates cirrhosis justifies detailed investigation by liver biopsy and other techniques.

PIP: The clinicopathological features of 50 patients with hepatocellular carcinoma arising in a noncirrhotic liver are described and compared with those of 100 patients in whom tumors arose as a complication of cirrhosis. The noncirrhotic patients were significantly younger, more often female, and had a less strong association with serum markers of hepatitis B virus infection. Liver function tests and serum alpha fetoproteins were less often abnormal and survival was significantly better than in the cirrhotic group. The different etiological factors, clinical features, and prognosis of hepatocellular carcinoma arising in the noncirrhotic liver compared to the more common form of hepatocellular carcinoma which complicates cirrhosis justifies detailed investigation by liver biopsy and other techniques.

Injection sclerotherapy for oesophageal varices: a prospective randomised trial of different treatment schedules.

A prospective randomised study to compare the efficacy and complications of injection sclerotherapy carried out at intervals of one week and three weeks up to the time obliteration of varices was achieved, was undertaken in 55 patients (48 cirrhosis, six portal vein thrombosis, one nodular regenerative hyperplasia). The number of courses of injection required for obliteration of the varices was not different in the two groups and despite a shorter time scale for obliteration in the weekly treated patients the frequency with which further episodes of bleeding occurred before that was not significantly less. Mucosal ulceration during the period required for obliteration was observed at endoscopy more frequently in the weekly treated patients but was not associated with a greater frequency of postinjection pain, dysphagia or of long term stricture formation.

B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis.

Oral metoprolol, in a dose sufficient to reduce resting pulse rate by 25%, was compared with repeated injection sclerotherapy for the long term management of variceal bleeding. The prospective, randomised study was undertaken in 32 patients with biopsy proven cirrhosis and variceal bleeding who were Grade A or B on a modified Child's classification. In the 15 patients receiving metoprolol, portal pressure showed a mean fall of 3.7 mmHg (17.3 +/- 1.2 to 13.6 +/- 1.2 mmHg, p less than 0.01) after four weeks of continuous therapy, as compared with pretreatment levels. Nine of the 15 patients taking metoprolol had further bleeding (total of 21 episodes) compared with six of 17 in the sclerotherapy group (nine episodes). The risk of bleeding per patient/month of follow up was three times higher in the metoprolol group compared with those treated by sclerotherapy (0.14 and 0.04 respectively, p less than 0.025). Rebleeding in the metoprolol group occurred in six of the patients who had a fall in portal pressure of 10% or more.