Mode of delivery and threshold retinopathy of prematurity in pre-term ELBW neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationship with perinatal risk factors. We tested the hypothesis that the mode of delivery may be associated with threshold ROP as defined by CRYO-ROP. METHODS: We conducted a prospective, cohort analysis of a database of all extremely low birth weight (ELBW) neonates (= birth weight < 1000 g) admitted over a 8-year period from 1997 to 2004 to a large tertiary neonatal intensive care unit in a urban area of northern Italy and screened for ROP. Incidence of threshold ROP was calculated for the whole studied population. The definition of threshold ROP was as defined by the CRYO-ROP study. Univariate analysis was performed to look for significant associations between threshold ROP and several possible associated factors, and among them, the mode of delivery (vaginal delivery or caesarean section). When an association was indicated by p < 0.05, multiple logistic regression was used to determine the factors significantly associated with ROP. RESULTS: Enrolled ELBW neonates were 174, and 46 of them (26.4%) displayed threshold ROP. Threshold ROP occurred in 40.9% (27 of 66) of the neonates vaginally delivered and in 17.5% (19 of 108) of those born via caesarean section (R.R. 3.35; 95% CI 1.230-4.855; p = 0.008 at univariate analysis, and = 0.04 at multivariate logistic regression after controlling for birth weight, gestational age, intraventricular haemorrhage grade 2 or more, days on supplemental oxygen, systemic fungal infection). Birth by vaginal delivery was not significantly associated with other major sequelae of prematurity (intraventricular haemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis). CONCLUSIONS: In our Institution birth by vaginal delivery is a significant and independent predictor of threshold ROP in ELBW infants. We suggest to consider closely ophthalmological surveillance for pre-term ELBW infants born this mode.

Fungal and bacterial sepsis and threshold ROP in preterm very low birth weight neonates.

OBJECTIVE: To determine whether an association exists between either fungal or bacterial sepsis and retinopathy of prematurity (ROP). STUDY DESIGN: Retrospective cohort study on all neonates with birth weight <1500 g admitted to a large Italian third Level Neonatal Intensive Care Unit in the years 1997-2001 and screened for ROP. Univariate analysis and multiple logistic regression were used to detect significant associations with ROP (all grades and threshold) in neonates with birth weight<1000 g (extremely low birth weight (ELBW)) and 1000-1500 g. RESULTS: Among 301 enrolled neonates, ROP (all grades), threshold ROP, fungal and bacterial sepsis occurred in 31.9, 12.9, 11.6 and 40.5% of the infants, respectively. At multivariate analysis, only gestational age (P=0.03), colonization by Candida non-albicans spp (P=0.03) and fungal sepsis (P=0.03) were independent predictors of threshold ROP, and only in ELBW neonates. CONCLUSIONS: Fungal (but not bacterial) sepsis is significantly and independently associated with ROP, but only in ELBW neonates and only with threshold ROP.

Cost-minimisation analysis comparing gemcitabine/cisplatin, paclitaxel/carboplatin and vinorelbine/cisplatin in the treatment of advanced non-small cell lung cancer in Italy.

A retrospective cost-minimisation analysis was conducted comparing novel chemotherapies for the treatment of chemo-naive patients with locally advanced, recurrent, and/or metastatic non-small cell lung cancer (NSCLC). Resource use information was obtained from a Phase III randomised trial investigating the efficacy and toxicity of gemcitabine/cisplatin (Gem/Cis), paclitaxel/carboplatin (Pac/Carbo) and vinorelbine/cisplatin (Vin/Cis) combination regimens in 612 patients with advanced NSCLC. Since there were no statistically significant differences between the three treatments in terms of progression-free or overall survival in this trial, a cost-minimisation analysis was considered to be the appropriate type of economic evaluation. The perspective was that of the national healthcare provider in Italy. Medical resource use was obtained from the clinical trial database, from which mean cost streams were calculated for each treatment group. The mean total treatment costs per patient were 8094 euros, 11,203 euros and 9320 euros for the Gem/Cis, Pac/Carbo and Vin/Cis regimens, respectively. Based on resource consumption in a clinical trial, Gem/Cis had the lowest overall mean costs of the three chemotherapy regimens. Gem/Cis therefore has the potential to save costs in the treatment of advanced NSCLC in Italy.

Gemcitabine-associated CD8+ CD30+ pseudolymphoma.

We describe a 69-year-old man with a non-small cell carcinoma of the lung, stage III B, who developed bilateral multiple erythematous lesions in the abdominal-inguinal area following treatment with gemcitabine. Histologically, the lesion was characterized by a heavy lymphocytic infiltrate with large CD30+ cells. The lesion was highly suggestive of cutaneous involvement by malignant lymphoma, but complete regression was observed after cessation of gemcitabine. Although rarely reported, gemcitabine therapy can induce skin lesions. Pathologists should be aware of this possibility in order to avoid a misdiagnosis.

Gemcitabine and cisplatin combination in early-stage non-small-cell lung cancer.

A number of randomized clinical trials now support the conclusion that the combined-modality regimen that includes gemcitabine (Gemzar) and cisplatin (Platinol) may improve survival in disseminated non-small-cell lung cancer. Cisplatin is considered to be the "backbone" of this combination chemotherapy due to its proven activity. The regimen of gemcitabine and cisplatin has been tested and is now considered among the most active combinations in the treatment of disseminated non-small-cell lung cancer.

Medical treatment of brain metastases from solid tumours.

Brain metastases (BrM) are estimated to occur in 20% to 40% of cancer patients, and two-thirds of them become symptomatic during their lifetime. Although every solid tumour may spread to the brain, the risk of developing BrM is higher in lung cancer, breast cancer and melanoma patients. Several findings suggest that the incidence of BrM is rising as a result of advances in imaging procedures and improvements in therapy, which leaves more cancer patients at risk as survival increases. The prognosis of patients with BrM is dependent on the type of the primary tumour. Breast cancer patients have better prognosis than those with BrM from lung, melanoma or colorectal cancer. Patients with BrM from renal cell carcinoma tend to have a poor prognosis. The optimal treatment of patients with BrM continues to evolve. Several factors interfere with the therapeutic strategy, such as histology of primary tumour, patient compliance, localisation, size and number of BrM, and outcome of extracranial disease. Generally, surgery or stereotactic radiotherapy followed by whole brain radiotherapy (WBRT) are indicated in patients with controlled extracranial disease and good performance status presenting an isolated BrM. Adding chemotherapy in this subset of patients is controversial. Supportive care associated with WBRT remains the standard treatment for all patients with multiple symptomatic BrM or with isolated symptomatic BrM in the presence of uncontrolled extracranial disease. For potentially chemosensitive patients with asymptomatic multiple or isolated BrM with disseminated disease, chemotherapy represents the optimal starting therapy.

Depression, psychosocial variables and occurrence of life events among patients with cancer.

Depressive disorders and psychosocial related factors were investigated in 113 patients one year after the diagnosis of cancer. Patients with an ICD-10 diagnosis of depression (31% of the sample) showed higher external locus of control, poorer social support, higher incidence of undesirable and/or uncontrollable events than non-depressed patients. They also differed in reporting more frequently a life-time history of emotional disorders, inability to adjust to the diagnosis of cancer and in having a lower score on the performance status. Of these factors, past psychiatric history, early maladjustment to cancer, poor social support and low performance status were predictors of depressive symptoms. However, because of the cross-sectional nature of the study, no conclusion regarding a causal relationship between depression and psychosocial variables is possible.

The use of granulocyte colony-stimulating factors following peripheral blood progenitor cell rescue after high-dose chemotherapy for advanced breast cancer: a prospective study.

The use of high-dose chemotherapy followed by hematopoietic rescue is increasing worldwide for solid tumors. Several studies have suggested that the period of absolute neutrophil count (ANC, < 500/ml) may be shortened in patients who receive peripheral blood progenitor cells (PBPC). To estimate the clinical value of granulocyte-colony-stimulating factor, we examined a cohort of 26 consecutive patients with advanced breast cancer who received one or two cycles of high-dose chemotherapy with PBPC rescue with or without filgrastim. Thirty-five courses of high-dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy were administered and evaluated. All patients received PBPC rescue. Sixteen patients (21 courses) received subcutaneous filgrastim (5 mg/kg) following PBPC infusion. Recovery to > or = 500 ANC occurred at a median time of 7 days post PBPC infusion among patients who received filgrastim versus 10 days among patients who received standard support care only (P < 0.01). The administration of filgrastim was not associated with a reduction in the duration of hospitalization, in the total number of days on nonprophylactic antibiotics, number of red blood cell transfusions, time to platelet engraftment, or number of febrile days. This could be the consequence of the high hematopoietic cell dose administered in the study. Therefore, any effect of filgrastim was probably masked by the use of a large number of PBPC. Larger prospective randomized studies, specifically focused on the utility of the administration of growth factors following high-dose chemotherapy and PBPC rescue, may be warranted to know whether the administration of filgrastim after PBPC transplantation is really necessary.

Depressive symptoms and quality of life in home-care-assisted cancer patients.

To examine the prevalence of depressive symptoms and its relationship with quality-of-life domains in home-care cancer patients at an advanced stage of illness, 86 patients were given psychological tests for depression (Hospital Anxiety Depression Scale) (HAD) and quality of life (EORTC-QLQ-C30) 1 week after admission to the home-care program. Using a proper cut-off score on the HAD-Depression subscale, depressive symptoms were reported by 45% of the patients. The quality of life of depressed patients was more affected than non-depressed patients in the social, emotional, cognitive, and physical domains. Significant correlations were found between depression scores and impairment in most quality-of-life areas. These findings support the importance of depression and quality-of-life evaluation in patients with advanced cancer who are followed in a home-care setting. This evaluation is needed to provide patients, their families, and caregivers with appropriate psychosocial interventions.

Response of brain metastases from lung cancer to systemic chemotherapy with carboplatin and etoposide.

30 consecutive patients suffering from cerebral metastases from lung cancer [12 small cell lung cancer (SCLC), 18 non-small cell lung cancer (NSCLC)] were given systemic chemotherapy with carboplatin (300 mg/m2/day 1 every 4 weeks) associated with etoposide (120 mg/m2 days 1-3 every 4 weeks). 21 patient were untreated; 9 patients had had previous chemotherapy, 8 with platinum derivatives. Altogether 98 cycles of chemotherapy were administered. The results were as follows: 3 complete response (3 SCLC; 10%), 7 partial response (4 SCLC, 3 NSCLC; 23.3%), 5 stable disease (1 SCLC, 4 NSCLC; 16.7%), 15 progressive disease (4 SCLC, 11 NSCLC; 50%). The overall response was 33.3%. Of the 10 patients who responded to treatment, 4 had had previous chemotherapy with platinum derivatives. Treatment was generally well tolerated; 5 patients experienced grade 4 bone marrow toxicity; in 4 treatment was suspended because of progression, and 1 patient died after the 4th cycle due to pneumonia with bone marrow aplasia. Mean survival of patients responsive to treatment was 38.6 weeks (range 15-99); overall survival was 24.8 weeks (range 2-99), in SCLC 23 weeks (range 6-52) and in NSCLC 29.8 weeks (range 2-99). The combination of carboplatin and etoposide is highly successful in the treatment of cerebral metastases from lung cancer and it could be a valid alternative to the traditional radiotherapy.

Cost analysis of long-term feeding by percutaneous endoscopic gastrostomy in cancer patients in an Italian health district.

The aim of this study was to evaluate prospectively the cost of long-term feeding by percutaneous endoscopic gastrostomy (PEG). Cost analysis was carried out in 34 head and neck cancer patients, followed from the time of PEG placement to the death or the end of the study. Three main items were considered: (a) PEG placement (on an inpatient basis), subdivided into five subitems: the Freka FK-07 gastrostomy kit, materials and anaesthetic drugs used, antibiotics and antisecretory drugs, gastroscope amortization expenses and staff; (b) nutrition, considering the costs of enteral-feeding products, nutrition container and flexible tube connecting the container to the PEG; (c) patient care, dividing the patients into three groups: outpatients, home-care patients and outpatients shifting to home care during the follow-up. All patients had one medical and two nursing visits/month, and, if necessary, immediate additional access to a physician or nurse. The mean daily cost per patient of long-term feeding via PEG was obtained by adding up the mean daily costs per patient of the three items, and was compared with that of feeding via nasogastric tube, calculated in 11 patients using the same criteria. No procedure-related death nor periprocedural major or minor complications were observed. The 60-day mortality was 3/34. Seventeen patients were always seen on an outpatient basis and 8 were followed by our home-care unit: 9 outpatients shifted to home care during the follow-up. The mean duration of PEG use was 180.5 days (range 47-639). Two wound infections, treated with antibiotics, occurred during the follow-up. The mean daily costs of placement, nutrition and patient care were (Italian Iiras) L 2500, 24 510 and 1880 respectively (Deutschemarks: DM 2.08, 20.42 and 1.56), for a total mean daily cost of L 28,890 (DM 24.06), slightly higher than that of feeding via a nasogastric tube (L 27,340; DM 22.78). On the basis of the improved quality of life, as well as from the economic point of view, PEG can be considered the procedure of choice for enteral feeding of cancer patients, provided that a reasonably long survival can be expected.

A comparison of the antiemetic efficacy and safety of intramuscular and intravenous formulations of granisetron in patients receiving moderately emetogenic chemotherapy.

A total of 120 patients were treated with granisetron either intramuscular (i.m.) or intravenous (i.v.) in a crossover design, over two successive cycles of moderately emetogenic chemotherapy. Of the 117 patients evaluable for efficacy, 74.4% receiving i.m. and 76.9% receiving i.v. treatment experienced a complete response (no vomiting, no more than mild nausea, no need for rescue medication and no study withdrawal in the 24 h following the onset of chemotherapy). Only a small proportion of the patients experienced any vomiting, either during the first 24 h or in the follow-up period of 4-10 days. There were no statistically significant differences in any of the efficacy parameters between the two routes administration of granisetron. Both formulations of granisetron were also equally well tolerated. The main treatment-related adverse effects were headache and constipation (experienced by 13-15% of patients); local reactions to i.m. injection of granisetron were experienced by 2.6% of patients.

Henoch-Schönlein syndrome associated with breast cancer. A case report.

The association of the Henoch-Schönlein syndrome with leukemias and lymphomas, though rare, is well known, but this type of pathology appears to be exceptional in the case of solid tumors. The authors report a case of malignant breast tumor wherein cutaneous vasculitis appeared at the moment of the disease's progression.

[Primary lymphoma of the breast. Clinico-pathologic description of a case]. / Linfoma primitivo della mammella. Descrizione clinico-patologica di un caso.

Primary malignant lymphomas of the breast are extremely rare, accounting for only 0.04% to 0.53% of all breast malignancies. Recently a connection between some primary breast lymphomas and mucosa-associated lymphoid tissue (MALT) has been reported identifying an extranodal lymphoma as MALT-type bears some biologic relevance, especially in terms of its spread to other mucosal sites, which sometimes occurs before disseminating into peripheral lymphoid tissue. The Authors report a case of primary breast lymphoma associated with a possible connective disease. Nevertheless the case reported cannot confirm a precise time relationship between malignant lymphomas and autoimmunity, we think that it can be possible.

Haematological profile in cancer patients: analysis of circadian pattern.

This study was intended to evaluate whether unusual circadian patterns in blood cells exist in cancer patients. Ten patients (five men and five women) suffering from advanced malignancy were compared with a control group of apparently healthy volunteers, of comparable age and sex. After synchronization of daily activities, meals and rest of the two groups, blood samples were taken four times (at 8.00 a.m., 12.00 a.m., 4.00 p.m. and 8.00 p.m.) in a single day. The total red and white cell counts, haemoglobin, platelet count, and neutrophil, lymphocyte, eosinophil, monocyte and basophil differential white cell counts were analysed by both conventional (Student's t-test; multifactorial analysis of variance) and inferential statistics (single and mean cosinor). The average values for platelets (P = 0.04), white blood cells (P = 0.004) and lymphocytes (P << 0.001) showed significant changes with time, independently of disease state. Cosinor analysis indicated a circadian rhythmicity for haemoglobin (P = 0.02), eosinophils (P = 0.014), and lymphocytes (P = 0.001) in healthy subjects, and for eosinophils only (P = 0.024) in cancer patients.

Acute gastroduodenal mucosal injury after cisplatin plus etoposide chemotherapy. Clinical and endoscopic study.

The effects on gastric and duodenal mucosa induced by cisplatin plus etoposide (PE) chemotherapy were investigated in 32 patients with lung cancer. They were submitted to gastroduodenoscopy before receiving cisplatin 100 mg/m2 (day 1) plus etoposide at a mean dose of 107 mg/m2 (days 1, 3 and 5). Endoscopic examination was repeated on day 8. Before chemotherapy, 22 patients showed normal endoscopic appearance and 10 minimal lesions (3 or fewer erosions). After chemotherapy, 16 remained normal, 1 had minimal lesions and 15 developed major lesions: 11 gastric or duodenal multiple erosions, 1 diffuse erosive gastritis, 2 gastric and 1 duodenal ulcer (p less than 0.001). No difference was observed in the number of vomiting episodes nor in severity of upper gastrointestinal symptoms between the patients who remained normal and those who developed mucosal injury. We conclude that PE chemotherapy can have a properly called gastroduodenal toxicity, leaving nausea and vomiting out which are rather due to central than peripheral mechanisms. Some trials are necessary to investigate which kind of drugs (H2-receptor blockers, sucralfate, prostaglandin E analogues) may be useful in preventing acute gastroduodenal mucosal injury induced by PE chemotherapy.