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.

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.

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.

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.

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.

Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease.

OBJECTIVE: To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS: 58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (29 patients). METHODS: Patients were treated with oral doses of cyclosporin microemulsion ranging from 200 to 400 mg daily. Blood samples were collected after 7 days of treatment; blood was drawn at 0, 0.5, 1, 2, 3, 5, 7 and 12 hours after the morning dose. In 23 patients out of 29 with ulcerative colitis and 23 out of 29 with Crohn's disease, these profiles were repeated immediately before hospital discharge, which took place an average of 18 days after admission. Blood specimens were assayed for cyclosporin immunoreactivity on the day of blood withdrawal by a radioimmunoassay technique. MAIN OUTCOME MEASURES AND RESULTS: In the range of doses employed, the average peak plasma drug concentration (Cmax) and area under the concentration-time curve to 12 hours tended to increase linearly with the dose (from 782.35 to 1,607.98 microg/L and from 3,612 to 7,221 microg x h/L for doses of 200 mg and 400 mg, respectively), whereas the time to Cmax (tmax) and elimination half-life (t 1/2beta) ranged between 78 and 95.2 min and 85.5 and 162 min, respectively, and did not appear to change with the dose. After dose-normalisation by transformation of data into percentage increase over baseline (trough) concentration for each patient, single kinetic parameters for the whole study population (n = 58) could be calculated (Cmax 620% vs baseline. tmax 86.5 min, t 1/2 115 min). Comparison between patients with Crohn's disease and ulcerative colitis showed that the latter had higher Cmax values (702% compared with 543% vs baseline, p < 0.05) whereas tmax and t 1/2beta values overlapped. CONCLUSIONS: The pharmacokinetic parameters of cyclosporin microemulsion in patients with inflammatory bowel disease are broadly similar to those previously measured in healthy volunteers and in other disorders requiring cyclosporin treatment.

Subcutaneous recombinant-human-erythropoietin prevents chemotherapy-related anemia in patients with advanced cancer.

Nineteen patients with advanced cancer were randomly allocated to receive: (i) rhEpo 150 UI/kg subcutanously three times/week starting 24 hours after the completion of cisplatin- or carboplatin-based chemotherapy; or (ii) normal saline. There were 17 patients with advanced head and neck carcinoma and 2 patients with small cell lung cancer. Patients were monitored for hemoglobin level, hematocrit, WBC, PLT and reticulocytes. Patients who received rhEpo overall showed a 7.2 +/- 6.3% mean increase in Hb level over their pretreatment values, while control patients had a 26.4 +/- 12% decrease. This difference was statistically significant (p<0.001). No patients in the rhEpo group required transfusion, while 4 patients in the control group received packed red cell transfusion. No significant side-effects attributable to rhEpo were recorded, but 1 patient showed a transitory increase in PLT count. In conclusion, subcutaneous rhEpo may be safely administered to patients with advanced cancer and effectively prevents cisplatin- or carboplatin-related anemia.

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

Etoposide, doxorubicin (Adriamycin) and cisplatin regimen in advanced gastric adenocarcinoma: experience with a lower dose schedule.

A phase II trial of etoposide (100 mg/m2) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m2) on days 1, 7, and cisplatin (30 mg/m2) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients, 2 (10%) had a complete response (CR), 7 (33%) had a partial response (PR), 4 (20%) showed no change and 8 progressed (38%). The mean duration of response (CR+PR) was 8.4+ months. Survival of the whole group was 7.5+ months. Treatment was quite well tolerated by most patients on an outpatient basis. Grade 3 vomiting and leukopenia were seen in 30% and 35% of cases respectively. One patient had grade 3 esophagitis, and 1 patient was hospitalized for severe grade 4 febrile leukopenia. Although the EAP regimen cannot be considered a standard therapy for gastric cancer, the EAP schedule employed in this study seems to be better tolerated than those reported by other authors, and can safely be given on an outpatient basis.

Malignant myoepithelioma of the breast - a case-history and review of literature.

A malignant myoepithelioma, mainly intraductally growing, of the breast was studied, emphasizing the immunohistological features of such tumors, in comparison with the more common, architecturally similar, infiltrating ductal carcinoma with intraductal component. Immunohistochemically, cell population of the tumor studied expressed intense reaction to alpha-SM-actin, cytokeratin 14, vimentin, S-100 protein and collagen IV antibodies, confirming myoepithelial differentiation. Since myoepitheliomas of the breast are very rare, complete knowledge of these neoplasms has not been attained. Nevertheless, histogenetic investigations may be useful in differentiating this type of tumor, from the above one, which is known to be characterized by severe clinical and prognostic implications.

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.

Levo folinic acid and 5-fluorouracil plus high dose epidoxorubicin as first line treatment for metastatic breast carcinoma.

Twenty-two women affected by metastatic breast carcinoma have been treated with a combination of levo folinic acid 100 mg/m2 plus 5-fluorouracil 450 mg/m2 i.v. on day 1-2, and epidoxorubicin 75-90 mg/m2 on day 2. This treatment cycle was repeated every 21-28 days. No patients had previously received chemotherapy for metastatic disease. Fourteen patients (64%) showed a major objective response with 3 complete (14%) and 11 partial responses (50%). Three patients showed a stabilization of disease and 5 (23%) progressed. All patients received ondansetron as antiemetic treatment which led to complete protection from vomiting in 68% of cases. Grade 1-2 diarrhea was recorded in 27% of the patients. Ten patients received recombinant human granulocyte-colony stimulating factor (rhG-CSF) as leukopenia-preventive treatment. In this group of patients the interval between chemotherapeutic cycles was shorter than in the group of 12 patients who did not receive rhG-CSF.

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.

Weekly levofolinic acid and 5-fluorouracil plus hydroxyurea in metastatic gastrointestinal adenocarcinomas.

There were 42 patients with advanced gastrointestinal carcinomas (GA) enrolled in the study. In the Phase I part of the study we identified the MTD of 5-fluorouracil (5FU) in combination with levofolinic acid 100 mg/m2 per week intravenously plus hydroxyurea 1 g/m2 per week given by mouth in 3 refracted doses starting 6 hours after 5FU was administered. This treatment was given weekly for 6 consecutive weeks followed by a 15-day rest period. We were not able to increase 5FU weekly dosage above 700 mg/m2 due to the occurrence of grade 3-4 gastrointestinal toxicity. Thus 5FU was employed at 600 mg/m2 per week for the Phase II part of the study. Among 20 evaluable patients with measurable metastatic colorectal cancer, 1 patient had CR of 6.0+ months and 7 patients had PR with a mean duration of 6.2+ months, for an overall response rate of 40%. Four patients (20%) showed stable disease, and 8 patients progressed. The mean survival of the whole group was 5+ months (range: 3.0-12.8). This treatment was very well tolerated by most patients, with grade 3 diarrhea in 10% of cases and grade 3 vomiting in 20% of patients. Hydroxyurea (HU), employed at this dosage, seems not to increase 5FU/FA-related toxicity. This regimen is quite active in the management of advanced colorectal carcinoma, and may be safely given on an out-patient basis. A Phase III randomized trial may be established if HU improves results achievable with the 5FU-FA combination.

A prospective evaluation of the activity of human granulocyte-colony stimulating factor on the prevention of chemotherapy-related neutropenia in patients with advanced carcinoma.

After informed consent, 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were randomized to receive placebo or subcutaneous granulocyte-colony stimulating factor (G-CSF) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity. The incidence of neutropenia (absolute neutrophil count < 1,000/mm3) was significantly reduced in patients receiving G-CSF than in controls (18% versus 42%; P < 0.05). The duration of neutropenia was also shortened by the administration of G-CSF (4.8 versus 8.2 days; P < 0.05). Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens. Patients treated with G-CSF showed oral fungal disease in 9% of cases, while control patients had a 21% incidence (NS). Patients treated with G-CSF received 91% of the programmed dose-intensity as compared to 71% of control patients (P < 0.05). These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia, infections, and reduction in dose-intensity. Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients.

Combination chemotherapy of 5-fluorouracil, epidoxorubicin and mitomycin C in the palliative treatment of locally advanced and/or metastatic adenocarcinoma of the stomach.

Thirty-seven consecutive patients with advanced and/or metastatic gastric adenocarcinoma received a combination of 5-fluorouracil 600 mg/m2 on days 1, 8, 29, 36; epidoxorubicin 75 mg/m2 i.v. on days 1, 29; mitomycin C 10 mg/m2 i.v. on day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response with an overall median duration of 40 weeks (range 20-128). The median survival of responding patients was not reached after a mean follow-up of 76 weeks, while that of patients with no change and progressive disease was reached at 36 and 13 weeks respectively. Treatment was generally well tolerated with hematological and gastrointestinal toxicities being the major side-effects. Despite the use of epidoxorubicin 75 mg/m2, the 26.4% (95% confidence limits 16-36%) objective response rate is not satisfactory. Evaluation of more aggressive protocols is strongly recommended within the limits of controlled trials.

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.

[Prolactin in pathology of the breast. Clinical study ]. / La prolattina nella patologia della mammella. Contributo clinico.

In the last years many Authors on the grounds of clinical and experimental studies have assumed the possibility of a connection between the prolactin and the breast pathology especially the carcionoma. In the present work the Authors give the results of the doses of the prolactin plasmatic basal levels, performed on 122 subjects belonging to 4 different groups: 1) patients with carcinoma of the breast; 2) patients with benign tumors of the breast; 3) patients with fibrocystic breast disease; 4) subjects of control. In patients who have undergone an operation further doses of blood prolactin have been carried out on 5th, 10th, 30th day after operation. On the grounds of such results the Authors propose new hypothesis of work wich will help to clear this problem.

[Dosimetry in hepato-biliary "in vivo" with thermoluminescent detectors. 3. Results of the use of I 131-rose bengal radioisotope diagnosis]. / Dosimetria "in vivo" con rivelatori a termoluminescenza Nota 3. Risultati per implego di [3]I-rosa bengala nella radioisotopodiagnostica epato-biliare.

Absorbed dose values measured in certain dog organs by in vivo application of RTL minidosimeters followed by i.v. adminstration of rose begal 131I in doses employed on a routine basis in hepatobiliary isotopodiagnosis are reported. The results are compared with those reported in the literature, obtained with a mathematical method.