Intra-arterial chemotherapy followed by chemo-embolisation in unresectable hepatocellular carcinoma.

Unresectable hepatocellular carcinoma is related to a poor prognosis. Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemo-embolisation, but limited data are available on the association of the two treatment modalities. We therefore started a new programme combining i.a. chemotherapy with chemo-embolisation. The treatment regimen consisted of L-leucovorin (100 mg/m2 i.v.), 5-fluorouracil (800 mg/m2 i.a.), and carboplatin (250 mg/m2 i.a.). Chemo-embolisation with mitoxantrone (10 mg/m2) plus ethiodized oil followed immediately. The same treatment plus gelatin sponge was given after 28 days. 26 patients entered the study and were evaluable for response and side-effects. Main patient characteristics were: males 21, females 5: median age 68 years (range 42-76 years); stage TNM II-III 17, IVA 9; Child's A 12, Child's B 14; elevated baseline alpha-fetoprotein 17; cirrhosis 25. 14 patients had a partial response (54%; 95% confidence interval 33-73%), 3 had stabilisation and 9 had progressive disease. Median survival was 11 months (range 2-20+). 16 patients had grade I-II pain and 15 grade I-II fever. Our results indicate that the regimen is safe, well tolerated and capable of inducing objective remissions in a high percentage of patients with hepatocellular carcinoma.

Prognostic factors in patients with hepatocellular carcinoma submitted to chemoembolization.

The prognosis of unresectable hepatocellular carcinoma is poor. Encouraging response rates have been reported with chemoembolization, but no survival advantage has been demonstrated. Assessment of the impact of the treatment modality on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 16 variables in 63 patients submitted to chemoembolization. Patients were treated with epirubicin (50 mg) plus ethiodized oil and gelatin sponge (22 cases) or with a new program combining i.a, chemotherapy with chemoembolization (41 cases) as follows: L-leucovorin, 100 mg/m(2) i.v.; fluorouracil, 800 mg/m(2) i.a.; carboplatin, 250 mg/m(2) i.a. Chemoembolization with mitoxantrone, 10 mg/m(2), plus ethiodized oil and gelatine sponge was performed immediately after. Median survival for the whole group of patients was 294 days. A multivariate analysis showed a highly significant influence on survival for Child's status (p=0.002) and for TNM stage (p=0.01). Median survival for patients with Child's A disease was 13.9 months and for patients with TNM stage I-II disease 19 months. In conclusion, our data suggest that patients with limited disease and adequate liver function have a longer survival after chemoembolization.

Prognostic value of proliferating cell nuclear antigen (PCNA) expression in unresectable hepatocellular carcinoma.

Recent studies indicate that evaluation of cell proliferation in mallignant tumors may have prognostic value, but limited data are available on its expression in hepatocellular carcinoma. We therefore evaluated the prognostic tool of PCNA antigen expression on paraffin-embedded sections of 54 patients with hepatocellular carcinoma and concomitant cirrhosis. According to the number of positive cells, the PCNA expression ranged between 0.8 and 47%, and was divided into two groups (Group A, PCNA less than or equal to 5.5%; Group B, PCNA >5.5%). The two groups of patients were numerically well balanced. Median survival was 16 months for group A and 12 months for group B. According to the Cox multivariate analysis, PCNA expression (P=0.002),TNM stage (P=0.009) and ECOG performance status (P<0.001) significantly correlated with survival. In conclusion, PCNA antigen expression was found to be a significant prognostic faeature in unresectable hepatocellular carcinoma and may be a useful tool for future trials.

Feasibility of intra-arterial chemotherapy followed by chemoembolization, every 28 days, in unresectable hepatocellular carcinoma.

Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemoembolization, but limited data are available on the association of the two treatment modalities. We therefore started a feasibility study of i.a. chemotherapy plus chemoembolization, performed every 28 days for 3 cycles, according to the following schedule: L-leucovorin (100 mg/m(2) i.v.), fluorouracil (800 mg/m(2) i.a.), and carboplatin (250 mg/m(2) i.a.). Chemoembolization with mitoxantrone (10 mg/m(2)) plus ethiodized oil was performed immediately after this treatment, followed by gelatin powder. Fourteen patients entered the study and were evaluable for side effects. Main patient characteristics were: males 13, females 1; median age 65 yr (range 45-75); stage TNM II-III 10, IVA 4; Childs' A 8, Childs' B 6; elevated baseline alpha-fetoprotein, 11; cirrhosis 14. No drug-related deaths have been observed. Ten patients were able to complete the program. The reasons for discontinuing treatment were worsening of liver functions in 3 cases and grade IV neutropenia in 1 patient. Eight patients had grade I-II pain and 10 patients had grade I-II fever. In conclusion the study demonstrated that chemoembolization plus i.a. chemotherapy is feasible in patients with hepatocellular carcinoma in cirrhosis and deserves further investigation.

[Ischemic hepatitis. Description of 4 cases and review of the literature]. / L'epatite ischemia. Descrizione di 4 casi e revisione della letteratura.

We studied four patients who presented a striking elevation of blood transaminases suggesting acute hepatitis. The post mortem histological examination of the liver revealed centrolobular necrosis that is commonly diagnosed as ischaemic hepatitis. The liver necrosis arose from heart failure which was worsened by an acute anaemia in one patient and by a severe hypoxemia, due to respiratory failure, in another. In three subjects there was evidence of disseminated intravascular coagulation that may be responsible for aggravating the condition of liver hypoxia. The authors also review the literature on the various aspects of ischaemic hepatitis.

[Pharmacologic effects and safety profile of bethanechol in the differential diagnosis of pseudo-anginal thoracic pain]. / Effetti farmacologici e profilo di sicurezza del betanecolo cloruro nella diagnosi differenziale del dolore toracico pseudo-anginoso.

The use of bethanecol has recently been proposed to improve the diagnostic accuracy of esophageal manometry in identifying the origin of symptoms in patients with non cardiac chest pain. In this study we report our experience in 30 patients who underwent esophageal functional studies. Despite its low diagnostic value, bethanecol test (two subsequential doses of 50 micrograms/kg) demonstrated an excellent safety profile, there were few side effects, and patients tolerance was good. The Holter electrocardiographic study showed an isolated case of transient atrioventricular block.

[Chemical and cytologic tests in the differential diagnosis of ascites]. / L'esame chimico e citologico nella diagnosi differenziale dell'ascite.

The value of chemical (protein, LDH, glucose, total and differential cell count) and cytological examination of the ascitic fluid in the differential diagnosis of peritoneal ascites was assessed in a prospective study of 98 patients. The ascites caused by hepatic metastases and primary carcinoma were of the transudative type and could not be distinguished from the type caused by cirrhosis on the basis of the parameters examined. In contrast the ascites caused by peritoneal carcinosis was exudative presenting a highly significant (p less than 0.001 for all parameters) difference from the three preceding groups. However there was no clear-cut distinction between the groups: in fact cirrhosis patients may present exudative ascites (8% in the present series, 12-19% in the literature). There was a substantial decrease in ascitic fluid glucose (less than 60 mg/dl) only in peritonitis and its measurement is therefore of secondary importance. In contrast with reports by other authors the ratio between LDH and protein concentrations in the effusion and the serum was found to be insignificant. The cytological examination revealed a significantly higher total cell count in bacterial peritonitis with a prevalence of polymorphonuclear cells and in peritoneal carcinoma where mononuclear cells predominate. Finally cytology revealed malignant tumour cells in the ascitic fluid and neoplastic peritoneal effusions in 28% of the patients examined.

[Oro-pharyngeal oesophagus papillomatosis. Description of one case (author's transl)]. / Oropharyngeale Osophagus-Papillomatosis. Darstellung eines Falles.

A case of oro-pharyngeal oesophagus papillomatosis is described. It was associated with an adeno-carcinoma of the stomach. A brief, critical review of the literature with consideration of the aetiology and pathology is given.