Nuclear p53 protein expression in resected hepatic metastases from colorectal cancer: an independent prognostic factor of survival.

An association has been reported between nuclear p53 protein expression in tumour cells and a poor outcome in patients with colorectal cancer (CRC). In this study we investigated the prognostic significance of nuclear p53 protein expression in CRC liver metastases after curative hepatic resection. The study population consisted of 69 consecutive patients who underwent curative hepatic resection for metastases from CRC at our Institution between February 1987 and October 1993. Immunohistochemical expression of p53 protein was evaluated in formalin-fixed paraffin-embedded sections of CRC liver metastases using the monoclonal antibodies (MAbs) D01 and Pab 1801. The Cox proportional hazards model was used in forward stepwise regression to assess the relative influence of different prognostic factors. Forty-four (63.8%) CRC liver metastases were p53-positive. Kaplan-Meier survival curves demonstrated that patients with p53-positive metastases had a median survival of 27 months versus 93 months for patients with p53-negative metastases (P < 0.01). The 3 and 5 years survival rates were 31.5 and 21.0% in patients with p53-positive metastases and 71.8 and 53.1% in patients with p53-negative metastases. At multivariate analysis p53 protein status was the single best predictor of survival (P = 0.0079); the odds ratio of death among patients with p53-positive tumours was 2.53. Nuclear p53 protein expression in hepatic metastases from CRC is an independent prognostic factor of survival following liver resection. These findings may be of clinical importance in the selection of patients more likely to benefit from liver resection and could be used as criteria for stratification in trials on adjuvant therapy.

Bolus vs. continuous hepatic arterial infusion of cisplatin plus intravenous 5-fluorouracil chemotherapy for unresectable colorectal metastases.

UNLABELLED: A multicenter, randomized Phase 2 study that compared patients, affected by colorectal liver metastases, who received intrahepatic arterial infusion with two different schedules of cisplatin, bolus vs. continuous infusion, and systemic 5-fluorouracil. PURPOSE: The aim of this study was to validate results of a previous Phase 2 trial on bolus cisplatin intrahepatic arterial infusion, which reported a 47 percent response rate and a 32 percent 4-year survival rate for Gennari's Stage 2 patients, with a high rate of neurologic, gastrointestinal, and hematologic toxicity. METHODS: One hundred nine patients were randomized in a Phase 2 study to receive cisplatin intrahepatic arterial infusion (24 mg/m2/day, 1-->5, bolus vs. continuous infusion) and systemic intravenous 5-fluorouracil (250, 375, or 500 mg/m2/day, 1-->5; escalating doses, respectively, at cycles I, II, III, and VI). To avoid neurotoxicity a maximum of six cycles was administered. RESULTS: Preliminary results for the 78 evaluable patients are similar to those of the previous study: response rate 46 percent and at a median follow-up of 16.5 months, the overall survival was 16.5 months, with 45 percent of the patients who received more than 3 cycles alive at 3 years. Toxicity, evaluable in 99 patients, showed a decreased incidence of neurotoxicity and a tolerable gastrointestinal and hematologic toxicity, lower in the cisplatin continuous infusion arm. CONCLUSION: This study clearly shows that cisplatin intrahepatic arterial infusion is able to provide a good palliative effect with a tolerable toxicity.

Giant cavernous hemangiomas: diagnosis and surgical strategies.

From January, 1972 to June, 1989, 51 patients with liver hemangiomas (32 females and 19 males, mean age 35 years) were evaluated for surgical treatment. Diameters of the masses were 5 cm to 20 cm (median 8.5 cm). Nine of the patients had already been treated for cancer. Twenty-two (43.1%) of the 51 patients were symptomatic and 29 (56.9%) patients were asymptomatic. In 34 patients (66.7%) a definite diagnosis of hemangioma was made by scintiscan and/or ultrasound and/or computed tomography and/or angiography while in the remaining 17 (33.3%) patients the diagnosis was uncertain. The most common indications for resection were the presence of a symptomatic angioma, a symptomatic mass with an uncertain diagnosis, and/or lack of a definite pre-operative diagnosis. Surgery was performed on 25 patients. Ten anatomic and 15 atypical resections or enucleations were performed. There were no postoperative deaths. Two further patients, operated for probable hemangioma, were found to have primary hepatic malignancies. In the 26 unresected patients, no complications were observed during follow-up. In 3 patients, hemangioma enlargement was detected by ultrasound, but there were no symptoms. As cavernous liver hemangiomas are now more reliably diagnosed and their natural history is usually uneventful, surgery can be avoided in most cases. However, when a non-resection policy is adopted, an exact diagnosis is essential in order to rule out primary or metastatic cancer. Surgical exploration and treatment should be limited to symptomatic or complicated cases as well as to patients with an uncertain diagnosis.

Adriamycin in hyperthermic perfusion for advanced limb sarcomas.

From February 1989 to April 1991, 12 hyperthermic limb perfusions (HLP) with adriamycin (ADR) were performed in 12 patients with high grade soft tissue sarcomas (9 in the leg and 3 in the arm); two were at A.J.C. stage IIb, eight stage IIIb and two stage IV. ADR (0.7-1.5 mg/kg) was administered in bolus at a mean temperature of 41.5 degrees C and perfused for 60 min. No systemic toxicity was reported; seven patients had grade II locoregional toxicity, another four grade III and one grade IV. Tumor necrosis (radiological evaluation) was less than 25% in two patients, 25% to 50% in two, 50% to 75% in five and greater than 75% in three. Limb sparing surgery was feasible in ten patients. At present eight patients are alive; three had local recurrence and four distant metastases.

Colorectal metastases to the liver: present results and future strategies.

In recent years, wide agreement has been expressed on the value of surgical resection for liver metastases from colorectal cancer, while for unresectable patients different types of locoregional treatment have been attempted. One hundred seventy-one patients with hepatic metastases from colorectal cancer were treated by us over a period of 15 years. Sixty-four underwent hepatic resection, and 107 underwent various forms of locoregional treatment. Our experience confirms the opinion that hepatic resection can be performed with a "curative" aim in patients with colorectal liver metastases: a 5-year survival rate can be achieved in about 30% of resectable cases. Adjuvant chemotherapy after hepatic resection should be tested in prospective randomized trials. Patients with diffuse liver metastases can benefit from locoregional infusion chemotherapy. Symptoms improve in most patients and objective responses are higher than those reported for systemic chemotherapy. Survival benefit with respect to untreated patients, has not yet been demonstrated by prospective randomized studies. Future improvements may be achieved by using new treatment modalities, such as new drug combinations, repeat arterial ischemia, and local tumor destruction. As these types of treatment are still experimental they should be employed only in prospective clinical trials.

Colorectal metastases to the liver: present status of management.

The management of patients with hepatic metastases from colorectal carcinoma is controversial. While a "no treatment" attitude still persists, other patients undergo systemic chemotherapy with very limited results. Other possible options are hepatic resection and locoregional treatments. One hundred twenty-three patients with hepatic metastases from colorectal cancer were treated at the authors' institution over a period of 15 years. Thirty-nine patients underwent hepatic resection while 84 underwent various forms of locoregional treatment. Several patients in the latter group were registered in one national (RNSI) Phase 2 study and one international (EORTC) Phase 3 trial. The authors' experience confirms the opinion that hepatic resection can be performed with the aim of curing in patients with isolated metastases. A five-year survival rate can be achieved in 25 to 30 percent of the resectable patients. Patients with unresectable extrahepatic disease or multiple bilateral metastases are usually excluded from resection. In other cases, hepatic resection should be carried out when technically possible. The value of adjuvant chemotherapy to the remaining liver has to be tested in prospective randomized trials. Patients with diffuse metastases can benefit from locoregional infusion of chemotherapeutic agents. Symptoms improve in most patients; objective responses vary from 53 to 83 percent of the cases, which is a higher rate than that reported for systemic chemotherapy. Survival may be prolonged in respect to untreated patients but this has not been demonstrated yet by prospective randomized studies. Current trends are continuous infusion of chemotherapeutic agents and experimentation of new drugs or drug combinations. Future improvements may be achieved by adding hepatic arterial ischemia, hyperthermia, or radiation therapy. As these kinds of treatments are still experimental, they should be applied to the patients only in the context of prospective clinical trials.

[Hemobilia caused by an intrahepatic aneurysm]. / Emobilia da aneurisma intraepatico.

The authors describe one case of hemobilia for intrahepatic aneurysm treated successfully with the placement of Gianturco's stainless steel coil during hepatic arteriography.

Variations in transmucosal gastric potential difference during hemorrhagic shock in the rat.

Transmucosal gastric potential difference (TGPD) was measured in the antrum and fundus of the stomach in two groups of rats submitted to hemorrhagic shock. In the first group the stomach contained 2 cm3 of 0.1 N HCl and in the second 2 cm3 of physiological saline. After the hemorrhage both antral and fundal TGPD diminished significantly in both groups. Antral TGPD dropped from -20 to -6 mV (p less than 0.001) in the first group and from -22 to -12 mV (p less than 0.01) in the second group; fundal TGPD dropped from -41 to -16 mV (p less than 0.001) in the first group and from -40 to -17 mV (p less than 0.05) in the second group. 20 min after reinfusion of blood extracted during the hemorrhage, both antral and fundal TGPD returned to normal values in the rats instilled with physiological saline, while in those treated with HCl TGPD values remained at levels significantly lower than the baseline values (in the antrum -10 mV, p less than 0.001; in the fundus -25 mV, p less than 0.02). Only those rats whose stomachs contained HCl developed ulcers, mainly located in the fundus of the stomach. These results suggest that the energy metabolism of the cells of the gastric mucosa undergoes constant alteration from the earliest stages of hemorrhagic shock. These alterations are greater in the fundus than in the antrum, a fact compatible with the greater incidence of ulcers in the fundus.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow of experimental liver metastases in rat as evaluated by the locally injected 133-Xenon washout.

The investigations on blood flow in liver metastases are interesting from both a pathophysiological and a therapeutic point of view. Available data, however, are few and not definitive, as these studies are complex and difficult to perform. In a group of 25 Sprague-Dawley rats, in which liver metastases of Walker-256 carcinoma had been implanted, the blood flows in a metastasis and in the normal liver surrounding it were determined by means of the locally injected 133-Xenon washout. Thirteen sham-operated rats were a control group. Blood flow in the metastases was decreased as a group compared to that in the normal liver surrounding metastases and to that in liver of sham-operated rats. Small metastases showed normal or increased blood flow, large ones decreased or stagnant blood flow. Moreover, a significant inverse correlation was found between blood flow and diameter of metastasis. It is concluded that liver metastases of Walker-256 carcinoma show a decrease in blood flow which is related to the size of metastasis.