Hypomethylation of the human HLA-DRα gene in breast carcinomas and autologous metastases

The methylation pattern of the human HLA-DR gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5 portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR gene could be proposed as a molecular marker of malignant breast tumors.     

Partial liberalization of visiting policies and ICU staff: a before-and-after study

Purpose

To investigate possible psychological distress among staff after partial liberalization of visiting policies in intensive care units (ICUs).

Methods

We surveyed eight Italian ICUs planning to increase daily visiting to at least 8 h. Participants completed the Maslach–Jackson Burnout Inventory and the State-Trait Anxiety Inventory before policy change (T0), after 6 months (T1) and 12 months (T2). At T0 and T2, their opinions on the new policy were solicited. Analyses were adjusted for main known confounders (age, gender, centre, educational and marital status, experience in ICU, baseline level of burnout or anxiety, and mortality rate).

Results

Baseline response rate was 89 % (230/258); 198 subjects (77 %) responded at T0 and T2, whereas 184 (71 %) participated in all three phases. High burnout levels were identified in 34.5 % of participants at T0 and 42.6 % at T2 (adjusted p = 0.001). All three phases showed a predominance of high burnout among nurses (adjusted p = 0.002). State and trait anxiety scores remained stable (adjusted p = 0.100 and 0.288, respectively). Most participants viewed the change positively at T0 (doctors 81.7 %; nurses 67.7 %) and T2 (doctors 87.0 %; nurses 62.7 %). At T2, 129 participants made comments (180 positive, 136 negative). Subjects with high burnout were more likely to comment negatively (p = 0.011).

Conclusions

Partial liberalization of ICU visiting policies was associated over the course of a year with a small but significant increase in staff members’ burnout levels. Nonetheless, doctors and nurses viewed the policy positively, maintaining this opinion after 1 year. Negative views were strongly correlated with burnout.     

Disentangling the Roles of Mammographic Screening and HRT in Recent Breast Cancer Incidence Trends in Italy by Analyses Based on Calendar Time and Time Since Screening Activation

Abstract: The aim of the study was to evaluate the roles of screening activation and hormone replacement therapy discontinuation on the recent declining breast cancer incidence trends in Italy. We analyzed 41,358 invasive female breast cancers incident during 1991–2004 in six Italian population‐based cancer registries. Overall and age‐specific incidence trends were evaluated using Joinpoint analysis. In addition to calendar years, data were analyzed on a years‐since‐screening‐activation basis. Annual percentage change of standardized rates was computed. There were statistically significant increasing trends for women 40–44 and 45–49 years that did not change after screening activation. On the contrary, for women 50–69 years old and for those 70+ years, the increasing trends flattened around 2 years after screening activation. The prevalence of hormone replacement therapy use in Italy is and was rather low. In conclusion, the recent tendency toward stabilization observed in Italy for female breast cancer incidence rates in women aged 50 years or more follows the introduction of mammographic screening.     

Does intraperitoneal insemination in the absence of prior sensitization carry with it a risk of subsequent immunity to sperm?

To evaluate the occurrence of antisperm antibodies in women, with no prior sensitization, 112 couples undergoing intraperitoneal insemination were tested for serum antisperm antibodies with the sperm immobilization test (SIT) and the immunobead test (IBT). A serum sample was taken from each of the 112 patients immediately before the first intraperitoneal insemination. Another sample was taken from 58 patients who underwent a second insemination procedure. In 16 of the 58 patients the IBT results were positive for one or more immunoglobulin classes. Five patients showed positive SITs. In 7 out of these 16 subjects (12%) the antibodies were bound to the head and to the shaft of the sperm tail. Five of the six patients submitted to a third intraperitoneal insemination procedure showed unchanged SIT values and IBT binding percentages. In one subject, SIT (6 months after the third insemination) became negative. Antibody production may be either a transient response to massive antigen stimulation or the first step toward systemic immunity.     

Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women.

PURPOSE: To evaluate the safety and efficacy of capecitabine in older women with advanced breast cancer. PATIENTS AND METHODS: Seventy-three eligible patients (median age, 73 years; range, 65 to 89 years) were enrolled. The first 30 patients received oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 every 21 days. Due to the occurrence of two toxic deaths, capecitabine 1,000 mg/m(2) twice daily was given to the subsequent 43 patients. RESULTS: All patients were assessable for safety and efficacy. A total of 351 treatment cycles were administered (median, six per patient; range, one to eight cycles). Dose reductions due to toxicities were required in 30% of patients in the standard-dose group, but capecitabine was given without a dose reduction to 95% of patients in the low-dose group. Capecitabine demonstrated a favorable safety profile. The overall incidence of grade 3/4 toxicities was low: the most common events reported in /= 24 weeks. In the low-dose group, the response rate was 34.9% (95% CI, 21% to 50.9%). An additional 15 patients had prolonged stabilization. The median time to disease progression was 4 months in either group. CONCLUSION: This study shows that capecitabine is safe and effective in the elderly breast cancer patient. Based on the overall results, the capecitabine dose of 1,000 mg/m(2) twice daily merits consideration as "standard" for older patients who do not have severely impaired renal function.     

Advances in diagnosis and therapy of neuroendocrine tumors

Neuroendocrine tumors represent a group of neoplasias characterized by significant histopathologic and biological heterogeneity. Diagnosis of neuroendocrine tumors relies upon histological examination augmented by newer techniques such as position emission tomography, meta-iodobenzylguanidine scintigraphy or octreoscan. Surgery represents the definite and curative therapeutic approach in early phase tumors. In metastatic or advanced disease, medical treatment is the best choice. Somatostatin analogs allow adequate control of the carcinoid syndrome, without a significant effect on tumor cell growth. Interferon-alpha may represent an alternative, alone or in association with somatostatin analogs. Chemotherapy is the best choice in the treatment of neuroendocrine tumors characterized by a poor differentiation grade and a high proliferation rate.     

Treatment of advanced malignant melanoma with vinblastine, bleomycin, and cisplatin

Thirty-two consecutive patients with metastatic malignant melanoma were treated with vinblastine, bleomycin, and cisplatin (VBD) chemotherapy. There were 29 evaluable patients; complete remission was observed in three and partial remission in five. No patient with visceral metastasis showed objective response. The 10-month survival rate of responders was significantly higher than that of nonresponders (57.1% vs 18.2%, P = 0.01); however, present results do not confirm that VBD is superior to other drug combinations for malignant melanoma.     

Merkel cell carcinoma after liver transplantation: a case report

BACKGROUND: Merkel cell carcinoma is a rare and aggressive neuroendocrine skin cancer with a very low incidence in the general population. MCC seems to be common in transplant recipients and 52 cases have been reported in the literature. METHODS AND RESULTS: This report describes a Merkel cell carcinoma which developed in a liver transplant recipient. To our knowledge, this is the second such case reported, as Merkel cell carcinoma most commonly occurs after kidney and heart transplants. The treatment approach is described and the literature on the subject is reviewed. CONCLUSION: There is currently no consensus regarding the optimal therapeutic approach to Merkel cell carcinoma. In transplant recipients, such tumors are more common and more aggressive but their treatment does not differ from the treatment of Merkel cell carcinomas in the general population.     

Methylation and expression of c-myc and c-abl oncogenes in human leukemic K562 cells before and after treatment with 5-azacytidine

The correlation between expression and extent of DNA methylation of c-myc and c-abl oncogenes has been investigated in the human leukemic K-562 cell line before and after 5-azacytidine-mediated erythroid induction. RNA accumulation was analyzed by cytoplasmic dot hybridization and DNA methylation by using HpaII and MspI endonucleases, which differently cleave the CCGG sequence depending on cytosine methylation. Both the oncogenes are expressed in uninduced cells; however, whereas the c-myc expression does not change following 5-azacytidine treatment, the c-abl expression sharply decreases. The HpaII pattern shows that the c-myc DNA region is undermethylated and that the c-abl gene is hypermethylated both before and after the erythroid induction. Nevertheless, in both the genes 5-azacytidine produces variations in the MspI pattern compatible with mCmCGG to CmCGG demethylations.     

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study.

PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR). RESULTS: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases. CONCLUSIONS: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.