Carboplatin/gemcitabine alternating with carboplatin/pegylated liposomal doxorubicin and carboplatin/cyclophosphamide in platinum-refractory/resistant paclitaxel - pretreated ovarian carcinoma.

OBJECTIVE: In this phase II study the efficacy and toxicity of an alternating chemotherapy regimen was examined in platinum-resistant relapsed epithelial ovarian cancer (EOC) patients. METHODS: Forty-five patients with platinum-refractory/resistant relapsed EOC, previously treated with carboplatin+paclitaxel+/-epirubicin were included. The regimen was consisted of gemcitabine 800 mg/m(2) (days 1+8) and carboplatin AUC 5, alternating with pegylated liposomal doxorubicin 30 mg/m(2) and carboplatin AUC 5, alternating with carboplatin AUC 5 and cyclophosphamide 600 mg/m(2), every 3 weeks for a total of 9 cycles. RESULTS: Among 38 patients with measurable disease, 39.4% (95% CI: 23.2-55.7) responded (five complete response and 10 partial response), while 30 out of 40 (75%) patients assessable by CA125 criteria had a serological response. Responses were more frequent in patients with platinum-free interval (PFI) 3-6 months than in those with PFI 0-3 months, but this was not statistically-significant. After a median follow-up of 19.5 months (range, 1.0-37+ months) the median progression-free survival was 7.1 months (95% CI: 3.4-10.8) and the median survival (OS) was 18.8 months (95% CI: 15.6-22.0). For patients with PFI 0-3 months PFS was 4.3 (95% CI: 0.8-7.8) months, while for those with PFI 3-6 months PFS was 8.9 (95% CI: 5.3-12.4) months (p=0.062). The regimen was well-tolerated and the main grade 3-4 toxicity was myelosuppression, palmar-plantar erythrodysesthesia, allergy and fatigue. CONCLUSION: This alternating regimen, including carboplatin, gemcitabine, liposomal doxorubicin and cyclophosphamide, is an active and well-tolerated treatment in platinum relapsed/refractory EOC patients.

Gastric metastases originating from breast cancer: report of 8 cases and review of the literature.

BACKGROUND: Breast cancer metastasis to the stomach is rare. It is very important to distinguish a breast cancer metastasis to the stomach from a primary gastric cancer on the basis of clinical, endoscopic, radiological and histopathological features, in order to administer the appropriate treatment. PATIENTS AND METHODS: Eight patients with breast cancer metastasis to the stomach were identified in our database between 1995 and 2008. The clinicopathological data and outcome from the medical records of these patients were then reviewed. RESULTS: The median age at initial breast cancer diagnosis was 59.5 years (range 44-75 years), while the median interval between the primary breast cancer and the gastric involvement was 41 months (range 2-82 months). The primary breast cancer histological subtype was mostly lobular carcinoma. All the biopsy specimens were estrogen receptor (ER), cytokeratin (CK) 7 and gross cystic disease fluid protein-15 (GCDFP-15) positive and CK-20 negative, while two of them (25%) were HER-2-neu positive. All the patients received chemotherapy and two of them were also treated with hormonal treatment. Two patients underwent surgical intervention, while one patient who had gastric involvement as the only metastatic site will proceed to surgical resection of the stomach. All these three patients were alive after 9, 39 and 44 months of follow-up, respectively. The response rate to chemotherapy was 50% (1 complete response [CR], 3 partial responses [PR]), and the median survival was 11 months (range, 1-44+ months). CONCLUSION: Breast cancer metastasis to the stomach can be differentiated from primary gastric cancer by comparing the biopsies from the gastric metastasis with the original histological slides from the primary breast tumor. Appropriate systemic treatment for metastatic breast carcinoma is the preferred treatment, whereas surgical intervention should be reserved for palliation or may be indicated in cases of solitary resectable gastrointestinal tract metastases.

Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance.

BACKGROUND: The objective of this study was to evaluate the expression of bcl-2 in UICC stage I and stage III (Dukes's stage B and C) colorectal adenocarcinoma and to examine its association with clinicopathological features, c-erbB-2, p53, ki-67, CD44, laminin and collagen IV and long term outcome. METHODS: Paraffin embedded specimens from 61 patients with UICC stage I (Dukes's stage B) and 39 patients with UICC stage III (Dukes's stage C) colorectal adenocarcinoma who were treated with surgery were assessed. We determined by immunohistochemistry the expression of bcl-2, c-erB-2, p53, ki-67, CD44, laminin and collagen IV with 5 year follow up. RESULTS: Cytoplasmic staining of the bcl-2 gene product was seen in the tumour cells of 27 cases (27%). Expression of bcl-2 protein was unrelated to patient sex, age, tumour site or tumour grade, but was related to tumour stage (p = 0.012). No significant association was demonstrated between bcl-2 and c-erbB-2, p53 or CD44. However, there was very strong evidence of correlation between bcl-2 staining and ki-67, laminin and collagen IV. There was a trend towards increased survival in patients whose tumours expressed bcl-2 protein. When a correlation between bcl-2 and the other markers had been made the positive expression of bcl-2 was beneficial. CONCLUSIONS: The results from this study would suggest that expression of bcl-2 appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer.

To investigate the expression of CD44 in colorectal cancer and examine its association with clinicopathological features, bcl-2, p53 and long-term outcome, paraffin-embedded tumour specimens from 61 patients with Dukes stage B (AJCC/UICC stage I) and 39 patients with Dukes stage C (AJCC/UICC stage III) colorectal adenocarcinoma were assessed by immunohistochemistry. The expression of CD44, bcl-2 and p53 were correlated with 5-year follow-up. Low CD44 expression was present in 30%, moderate in 30% and extensive in 40% of cases. It was not related to patient sex and age but was related to tumour differentiation, stage and tumour site. No association was demonstrated between CD44 and bcl-2. However, there was significant evidence of an association between CD44 and p53 in 66 cases in which p53 was previously assessed. There was a trend towards increased survival in patients whose tumours expressed lower levels of CD44 protein. When entered into multivariate analysis model, which also included bcl-2 and p53, CD44 staining emerged as an indicator of poor prognosis in colorectal cancer patients.

Partial enterectomy in the rat does not diminish muscle glutamine production.

The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production.

Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs.

1. After operation, changes in nitrogen metabolism occur. Although increased flux of amino acids from peripheral to splanchnic organs after operation has been described, substrate utilization by the individual organs in the splanchnic area is less well characterized. We were specifically interested in substrate flux across the spleen as it is an organ with important immunological functions. 2. Therefore, hindquarter, gut, spleen and liver fluxes of amino acids, ammonia, glucose, lactate and blood gases were measured for 4 days after a standard operation in pigs. In a separate control group, fluxes were measured 2-3 weeks after this operation and these values were assumed to represent the normal situation. 3. One day after operation, the hindquarter effluxes of glutamine, alanine and several essential amino acids were increased (P > 0.001), but these normalized at the end of the observation period. In the same period, liver glutamine uptake increased (P < 0.01), concomitantly with increased HCO3-, glucose and urea production, which also normalized. Portal drained viscera ammonia production decreased, concomitant with decreased glutamine uptake (P < 0.001). After operation, the splenic release of ammonia increased sevenfold (P < 0.05) and that of lactate increased from -158 +/- 544 to 3294 +/- 642 nmol min-1 kg-1 body weight (P < 0.001). Glucose uptake increased from -964 +/- 632 to -3933 +/- 1524 nmol min-1 kg-1 body weight and glutamine efflux (391 +/- 143) reversed to uptake (-752 +/- 169 nmol min-1 kg-1 body weight) (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)