Validity of shape memory NiTi colon ring BioDynamix ColonRing™ (or NiTi CAR 27™) to prevent anastomotic colorectal strictures. Preliminary results.

PURPOSE: Anastomotic strictures occur in 3-30% of colorectal anastomosis and one of the main causes may be a reaction to the presence of the metal staples used for suturing. The aim of this study was to evaluate the efficacy of a compression anastomosis ring using the memory shaped device in initial, i.e. nickel-titanium alloy (NiTi) for the prevention of colorectal anastomotic strictures. PATIENTS AND METHODS: A compression anastomosis ring device (NiTi CAR 27™) was used to perform compression anastomosis in 20 patients underwent left hemicolectomy and anterior resection of the rectum for carcinoma. An endoscopic check of the anastomosis was carried out at one month and at six months after surgery. RESULTS: In 2 patients (10%) a dehiscence of the anastomosis occurred on the fifth and the eighth postoperative day. No anastomotic strictures were observed in any of the other 18 patients at six months follow-up after surgery. CONCLUSION: Our preliminary results suggest that the use of a compression anastomosis ring might well be a valid method of preventing anastomotic strictures in colorectal surgery. Further studies involving a larger number of patients are needed in order to confirm these preliminary results.

[Hemostatic effectiveness of TachoSil® patches in radiofrequency assisted minor hepatic resection]. / Efficacia emostatica del TachoSil® nelle resezioni epatiche minori eseguite con device bipolare a radiofrequenza.

AIM: Intra- and postoperative bleeding represents an extremely serious and frequent complication of hepatic surgery. The aim of this study was to evaluate the effectiveness of TachoSil® to improve hemostasis in radiofrequency assisted minor hepatic resection. METHODS: Between July 2008 and June 2010, 31 patients underwent radiofrequency assisted minor hepatic resection. At the end of the liver resection a sponge of TachoSil® was applied on the liver. RESULTS: The mean intraoperative bleeding from the liver was 56.1 mL (range 0-300 mL). No patients received intra- and postoperative blood transfusion. Surgical drains were removed between the first and the sixth-eight postoperative day. CONCLUSION: According to the authors Tacho-sil® is helpful to improve hemostasis and biliary leakage in patients undergoing radiofrequency assisted minor hepatic resection.

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems.

BACKGROUND: A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. AIM: To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. METHODS: We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. RESULTS: One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients. CONCLUSIONS: Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.

Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis: a prospective study.

BACKGROUND: Neoplastic seeding of hepatocellular carcinoma may arise after radiofrequency ablation. AIMS: In order to clarify the real risk of seeding, we observed a prospective cohort of patients undergoing radiofrequency ablation. METHODS: Ninety-three (22.9%) out of 406 consecutive patients with hepatocellular carcinoma superimposed to cirrhosis diagnosed at our Liver Unit (2000-2005) were selected for radiofrequency ablation according to the Barcelona 2000 EASL guidelines. Seventy-one patients were treated by a percutaneous approach and 22 at laparotomy. After radiofrequency ablation ultrasound scan was repeated every 3 months and spiral-computed tomography every 6 months. RESULTS: Overall 145 sessions were performed in 93 patients: 113 (77.9%) by a percutaneous approach and 32 (22.1%) at laparotomy. The median follow-up was 23 months (range 1-60). Only 1 of the 71 patients (1.4%; 95% C.I. 0.25-7.56) treated percutaneously and none of the 22 (0%; 95% C.I. 0-14.8) treated at laparotomy showed neoplastic seeding. CONCLUSION: In our experience the risk of seeding of hepatocellular carcinoma after radiofrequency ablation was small (1.1% per patient, 95% C.I. 0.19-5.84; 0.7% per procedure, 95% C.I. 0.12-3.80). A stringent selection of patients for radiofrequency ablation and retraction of the needle with a hot tip may have been instrumental in obtaining this low frequency.

Gastrointestinal stromal tumors (GISTs): focus on histopathological diagnosis and biomolecular features.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index, anatomic location, tumor rupture and disease-free interval are the classic characteristics used to predict the clinical course of patients who undergo complete gross resection. Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib mesylate is a rationally designed, molecularly specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer and which has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant GISTs. More recently Sunitinib, a new KIT/PDGFRA kinase inhibitor, has been tested in patients with GIST resistant to imatinib, with promising results.

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.

Radio-frequency thermal ablation (RFTA) of small hepatocellular carcinoma in patients with cirrhosis. Experience at a single tertiary referral center.

AIM: Radio-frequency thermal ablation (RFTA) may prolong the survival of patients with small hepatocellular carcinoma (HCC) associated with cirrhosis. The aim of this study was to evaluate efficacy and safety of RFTA. METHODS: We performed the Kaplan-Meier analysis to estimate the survival rate in 69 consecutive patients with HCC (mean age 66+/-6.5 years; 44/25 male/female; 56 Child-Pugh class A and 13 Child-Pugh class B) treated by RFTA. A single lesion was observed in 60/69 (87%), two lesions in 8/69 (11.6 %), and 3 lesions in 1/69 (1.4 %) of patients. The tumor size was = or <3 cm in 60/69 (87%). RESULTS: Twenty-two patients died during follow-up. Overall survival rates were 81%, 66%, and 46% at 1-, 2-, and 3-years, respectively. Cancer-free survival rates were 64% at 1 year, 30% at 2 years and 25% at 3 years. The 3-years rate of appearance of separate new lesions and local recurrence were 27.5% (19/69) and 26 % (18/69). CONCLUSIONS: Our study shows that patients with HCC and compensated cirrhosis may benefit from RFTA treatment, especially for tumors = or <3 cm. Nevertheless, the high rate of recurrence (both local and distant) points out the palliative role of this therapy.

Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study.

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype.

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Metabolic syndrome and breast cancer risk.

States of hyperinsulinemia with insulin resistance are frequently associated with proliferative tissue abnormalities, via stimulation of DNA synthesis and cell proliferation through the IGF-1 receptor. Such elements of metabolic syndrome (hyperinsulinemia/insulin-resistance, obesity, type 2 diabetes mellitus, hypertension, dyslipidemia) are explored in a population of 125 women (n. 50 with histologically confirmed diagnosis of breast cancer, Group A; n. 50 with benign breast pathology, Group B; n. 25 with no breast pathology, Group C, controls), affering to a Center for the prevention of breast cancer, in order to investigate for an eventual relationship between these pathologies. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, was higher in group of women affected by breast cancer vs. benign breast pathology and controls. This finding is in agreement with the hypothesis of the interrelationship of hyperinsulinism/insulin resistance with the growth-related abnormalities of breast cancer.

Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age

DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: results of a 5-year Gruppo Oncologico dell'Italia Meridonale (GDIM) prospective study.

BACKGROUND: The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS: Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were followed up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality. Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC] staging system) and node status. Moreover, DNA aneuploidy was significantly related to high SPF. K-ras-2 mutations were not associated with clinicopathologic variables or flow cytometric indicators. At univariate analysis, advanced TNM stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy, and high SPF proved to be significantly related to quicker tumor relapse and to shorter overall patient survival. With multivariate analysis, DNA aneuploidy, high SPF, and depth of invasion were related to risk of tumor relapse and patient death, whereas diffuse histotype was independently related to patient risk of tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with clinicopathologic staging, might be useful for the identification of GC patients who have different risks for death or relapse of disease.

Hereditary common cancers: molecular and clinical genetics.

This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.

[The use of stereotaxic cytology in the diagnosis of nonpalpable breast lesions. Our experience]. / L'impiego della citologia stereotassica nella diagnostica delle lesioni non palpabili della mammella. Nostra esperienza.

BACKGROUND AND AIMS: The increasingly frequent use of mammography for the early diagnosis of breast cancer and the consequent identification of mammary lesions at a preclinical stage raises the fundamental problem of the differential diagnosis between non-suspected non-palpable lesions (NPL) which can therefore be monitored over time and suspected NPL or definite carcinoma requiring histological confirmation and surgical biopsy. The diagnostic accuracy of mammography alone is not sufficiently high to differentiate benign lesions from malignant or strongly suspected ones. The use of surgical biopsy in the event of suspected NPL could be significantly reduced by the use of stereotaxic cytology which would improve the diagnostic accuracy of mammography. METHODS: The study refers to 72 suspected NPL undergoing surgical biopsy after having performed stereotaxic cytology on a sample taken with a dedicated mammographic device (Mammotest-TRC). RESULTS: The rate of inadequate samples for correct cytological evaluation was 16.1%. Of the 72 NPL undergoing surgical biopsy, 40 (55.5%) were found to be carcinomas and 32 (44.5%) were benign lesions. The sensitivities of mammography alone and cytology alone in identifying infraclinical breast carcinoma were respectively 0.85 and 0.95. If the results of the two methods were evaluated together, the level of sensitivity was 0.98. CONCLUSIONS: The use of stereotaxic cytology enables a marked improvement to be achieved in the diagnostic accuracy of mammography for the identification of suspected NPL to undergo surgical biopsy, notably reducing the cost of biopsy (number of benign lesions for each carcinoma diagnosed) and consequent discomfort for patients.

Cisplatin and epirubicin plus oral lonidamine as first-line treatment for metastatic breast cancer: a phase II study of the Southern Italy Oncology Group (GOIM).

Lonidamine (LND) is a unique antineoplastic drug derived from indazole-3-carboxylic acid which inhibits oxygen consumption and aerobic glycolysis, interfering with energy metabolism of neoplastic cells. LND has been experimentally shown to potentiate the cytotoxic effects of epirubicin (EPI) in human breast cancer cell lines, cisplatin activity in both platinum-sensitive and -resistant human ovarian carcinoma cell lines, and EPI antineoplastic activity in some recent phase III trials carried out in advanced breast cancer. A multicenter phase II trial was carried out with the combination of cisplatin 60 mg/m2, EPI 100 mg/m2 and LND 450 mg/day p.o. in three refracted doses/day starting 2 days before cisplatin and EPI (day -2 and -1), stopping 2 days after chemotherapy (day 0, +1 and +2). Thirty patients with metastatic breast cancer were enrolled into the study. Twenty-nine patients were evaluable for objective response. The overall response rate accordingly to an intent-to-treat analysis was 73% (95% CL 54-88%). Four patients achieved complete response (13%; 95% CL 4-31%) with a median duration of 9.5 months (range 4-16) and 18 patients had partial response (60%; 95% CL 41-77%) with a median duration of 9.8 months. Stable disease was obtained in five cases (17%) and progressive disease was recorded in three patients. One patient died of progressive cancer before restaging. The overall median survival of the whole series of patients was 14+ months. The most frequent toxicities were represented by gastrointestinal and hematological side effects. The combination of cisplatin + EPI plus oral LND is active against metastatic breast carcinoma. The antineoplastic activity of the cisplatin + EPI + LND regimen is as high as that reported for more aggressive regimens such as the fluorouracil + doxorubicin + cyclophosphamide combinations without an increase in toxic effects.

Primary extranodal non-Hodgkin lymphomas of the uterus and the breast: report of three cases.

The authors describe one case of a rare primitive non-Hodgkin lymphoma of the uterus, and two cases of primary non-Hodgkin lymphoma of the breast. Histologically, the uterine lymphoma, although clinically confined to the uterus, was a diffuse large cell lymphoma, group G according to the Working formulation for Clinical Usage. The two cases of breast lymphoma were a centrocytic-centroblastic and a lymphoplasmocytoid non-Hodgkin lymphoma, respectively. All cases were initially treated with radical surgery plus radiotherapy, but the first patient showed an early recurrence at distant sites, which required systemic cytotoxic chemotherapy. The patient with uterine non-Hodgkin lymphoma received a very intense regimen--i.e. the ProMACE-Cytabom--because of the unfavourable histology, while the two patients with primary breast non-Hodgkin lymphoma received less aggressive CHOP and CVP chemotherapy. All patients are still alive and free of disease 3 to 6 years after initial diagnosis. These cases stress the systemic nature of non-Hodgkin lymphomas even if apparently localized to a single extranodal organ. Thus, although a definitive therapeutic strategy cannot be drawn from the rare and occasional reports in the medical literature, primary extranodal lymphomas require integrated multimodality therapy with radiotherapy and/or chemotherapy.

Ondansetron versus granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial.

BACKGROUND: A single-institution, prospective, randomized open trial was performed to compare ondansetron and granisetron in the prevention of chemotherapy-related nausea and vomiting. The effect of antemetic drugs was analyzed indipendently for patients treated with highly emetogenic chemotherapy (Study 1), and those treated with moderately emetogenic regimens (Study 2). METHODS: In Study 1, 182 patients treated with chemotherapeutic regimens containing high dose cisplatin (more than 70 mg/m2) were randomized to receive 24 mg of ondasentron intravenously (i.v.) or 3 mg of granisetron i.v. for the control of acute emesis. Patients treated with fractionated chemotherapy and those followed-up for delayed emesis also received 8 mg of ondansetron orally twice a day or 3 mg of granisetron i.v. on the days after Day 1. In Study 2, 164 patients were randomized to receive either 16 mg of ondansetron i.v. or 3 mg of granisetron i.v. to prevent emesis in the first 24 hours. RESULTS: In the ondansetron group in Study 1, a complete response (CR) (i.e., no vomiting, nausea possible) from acute emesis was achieved in 52% of cases, a major response (MR) in 29%, and a minor response (MiR) in 14%. In the granisetron group in Study 1, a CR was seen in 49% of patients, an MR in 24%, and an MiR in 12%. Failure was recorded in 5% and 15% of cases in the ondansetron and granisetron groups, respectively. No statistically significant difference in any response category was seen between the two groups. In the ondansetron group, a complete protection from delayed emesis was recorded in 39% of cases, an MR in 32%, an MiR in 21%, and failure in 16%. In the granisetron arm, 36% of the patients had a CR, 22% had an MR, 14% had an MiR, and 14% experienced treatment failure. Again, these differences did not reach statistical significance. In Study 2, no statistical significant difference was observed between the ondansetron arm and the granisetron arm, both for acute and delayed emesis. Both ondansetron and granisetron were tolerated very well by most patients, with no severe side effects. In the group of patients treated with ondansetron, however, the incidence of headache (9%) was higher than in the group treated with granisetron (4%). CONCLUSIONS: These data suggest that although both ondansetron and granisetron are very effective drugs for the control of acute emesis, their efficacy against delayed emesis is still not entirely satisfactory.

A phase I-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5-fluorouracil and recombinant human granulocyte colony stimulating factor in metastatic breast carcinoma.

Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40 mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent patients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 35 mg/m2/day the overall response rate was 78%, with 22% CR and 56% PR. Four patients did not respond. Objective responses were seen at all tumor sites including bone and viscera, which usually are rather chemotherapy insensitive. Toxicity was generally acceptable. Although the response rate was quite high, the duration of objective tumor regression and patients' survival were not impressive. In conclusion, we do not recommend routine use of such an aggressive regimen for palliation of advanced breast cancer. Results of the present and similar studies may, however, be useful for planning of neoadjuvant or adjuvant trials with curative intent.

Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy.

Forty patients with chemotherapy-related diarrhea were randomized to receive (i) octreotide 0.5 mg three times per day s.c. or (ii) loperamide 4 mg three times per day p.o. until complete remission of diarrhea was achieved. In the octreotide group 80% of patients showed complete resolution of loose bowel movements within 4 days of therapy, while in the loperamide group this goal was obtained in only 30% of cases (p < 0.001). If after 4 days no benefit was seen, patients were considered to have failed antidiarrheal therapy. Failure was recorded in only one case (5%) treated with s.c. octreotide and in five patients (25%) who received loperamide. The mean duration of antidiarrheal therapy necessary to achieve remission was 3.4 days in the octreotide group and 6.1 days in the loperamide group (p < 0.001). Treatment with octreotide was very well tolerated with mild abdominal pain in 15% of cases and pain in the injection site in 15% of patients. Subcutaneous octreotide is highly effective in the management of chemotherapy-related diarrhea in cancer patients.

Renal cell (Grawitz) carcinoma: an immunohistochemical study in correlation with nuclear grade, histological pattern and proliferative activity of tumor cells.

Since morphological features of renal cell carcinomas may not always predict their clinical behaviour, other biological parameters are more and more searched for, as prognostic indicators. Among those, the Authors evaluate the cytokeratin-vimentin intermediate-sized filaments co-expression in a series of 32 renal carcinomas and analyze this feature in correlation with both traditional criteria and proliferative activity of tumor cells, studied by means of the proliferation cellular nuclear antigen (PCNA) expression as well as of the nucleolar organizer regions (NORs) count, within tumor cells. From this study, nuclear grade stands out as the best parameter which, furthermore, shows a significant relationship with the cytokeratin-vimentin co-expression and the mean NORs count in tumor cell populations. Further investigations about relationships between these parameters and survival of the patients, who, at present, are almost all alive, will be performed afterwards.