ProMECE-CytaBOM vs MACOP-B in Advanced Aggressive Non-Hodgkin's Lymphoma: Long Term Results of a Multicenter Study of the Italian Lymphoma Study Group (GISL)

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m² of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure.

Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11). We observed an eventual total of 120 treatment failures, 64 (61%) in the group treated with P-C and 56 (54%) among those treated with M-B (P = 0.29). Patients alive without disease at four years were estimated to be 42% in the P-C arm and 49% in the M-B arm (P = 0.27). The estimated 4-year overall survival was 54% for P-C and 61 % for M-B, and the differences were also not significant (P = 0.29). Patients treated with M-B experienced more and more severe side effects, including mucositis, infections, neurologic, pulmonary and cardiac abnormalities. Patients treated with P-C had a 1.3 g mean decrease of hemoglobin over the induction therapy, while patients treated with M-B experienced a 2.2 g mean decrease (P = 0.01).

In conclusion, both P-C and M-B resulted in effective treatment for patients with aggressive NHL, and provided similar activity. However P-C was more manageable in an outpatient setting and produced less acute toxic effects.     

Menstrual and reproductive factors and pancreatic cancer risk in women

To investigate possible correlates of the systematically higher pancreatic cancer rates in males than in females, the role of menstrual, reproductive and hormonal factors in females have been assessed using data from a case-control study conducted in Northern Italy. Cases were 133 women with histologically confirmed incident cancer of the pancreas, and controls were 377 women in hospital for acute, non-neoplastic, non-digestive-tract disorders. After allowance for age, education, area of residence and smoking habit, an increased risk of pancreatic cancer was observed in women with early menarche (? 13 years) (OR = 1.9; 95% Cl; 1.0–3.6), but no significant association was observed with age at menopause or length of fertile life. Parous women were at reduced risk as compared to nulliparous women (OR = 0.7), although the trend in risk with number of births was not significant. No association with spontaneous or induced abortions was observed. Pancreatic cancer risk was inversely related to early age at first birth (first birth < 25 versus nulliparae: OR = 0.5; 95% C1: 0.3–0.9; p-value for trend < 0.01) and to age at last birth (last birth < 25 versus nulliparae: OR = 0.3; 95% C1: 0.1–0.8; p-value for trend < 0.05). Ever-users of estrogen replacement therapy showed a non-significantly increased risk (OR = 2.2). Although no clear pattern of association is evident, the present results are in agreement with previous epidemiological observations and experimental research indicating that hormonal (menstrual and reproductive) factors could explain part of the male-to-female differential in incidence and mortality from pancreatic cancer. © 1995 Wiley-Liss Inc.     

Prostate specific antigen in breast cancer,benign breast disease and normal breast tissue

Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (≥ 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III–IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.     

Randomized Multicentric Italian Study on two Treatment Regimens for Marrow Relapse in Childhood Acute Lymphoblastic Leukemia

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluahle patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.     

Bronchoscopic findings in infants treated with high-frequency jet ventilation versus conventional ventilation

To identify tracheobronchial abnormalities associated with assisted ventilation, 40 infants with respiratory distress syndrome randomized to receive either short-term (48 hours) conventional or high-frequency jet ventilation were studied. Flexible fiberoptic bronchoscopy (n = 13) was performed and/or clinical and radiographic assessments were used to evaluate for laryngeal, tracheal, and bronchial lesions. There was no bronchoscopic evidence of necrotizing tracheobronchitis after either high-frequency jet ventilation (n = 8) or conventional ventilation (n = 5). Laryngotracheomalacia and nodular vocal cords were the most common abnormalities noted, and they occurred with equal frequency in both groups. Study infants who were not bronchoscoped had no clinical or radiographic evidence of tracheal or mainstem bronchial obstruction. One patient did have microscopic evidence of necrotizing tracheobronchitis at autopsy, however. It is concluded that short-term treatment of respiratory distress syndrome with high-frequency jet ventilation may be performed without undue risk of tracheobronchial injury.     

Decreased ventilation in preterm infants during oral feeding

As respiratory difficulty may accompany nipple feeding in preterm neonates, we studied the effect of oral feeding on ventilation in 23 preterm infants. The infants composed two groups based on their postconceptional age at the time of study: Group A comprised 12 infants 34 to 35.9 weeks of age, and group B, 11 infants 36 to 38 weeks. Ventilation was measured via a nasal mask pneumotachometer, and sucking pressure via a nipple that also permitted milk delivery; transcutaneous PO2 and PCO2 were continuously monitored. The feeding pattern comprised an initial period of continuous sucking of at least 30 seconds, followed by intermittent sucking bursts for the remainder of the feed. When compared with an initial semi-upright control period, minute ventilation (V1) during continuous sucking fell by 52 +/- 6% (P less than 0.001) and 40 +/- 2% (P less than 0.001) in groups A and B, respectively. This was the result of a decrease in respiratory frequency and tidal volume and was associated with a fall in TcPO2 of 13 +/- 4 mm Hg (P less than 0.01) in group A and 10 +/- 2 mm Hg (P less than 0.01) in group B. During intermittent sucking, V1 and TcPO2 recovered partially only in the more mature infants (group B). At the end of the feed, TcPCO2 have risen by 3 +/- 1 mm Hg (P less than 0.001) in group A and by 2 +/- 2 mm Hg (P less than 0.05) in group B. Thus oral feeding results in an impairment of ventilation during continuous sucking and the subsequent recovery during intermittent sucking is dependent on postconceptional age.     

AMIL survey (anemia in Internal Medicine in Liguria)

The aim of the present study was to evaluate the epidemiology of anemias in Internal Medicine Departments. The study involved all patients discharged between May 1 and June 15, 2001 who, at the time of admission, had presented with hemoglobin levels < 12 g%. One thousand and nineteen data collection forms were deemed suitable for analysis and were divided according to the etiology and severity of the anemia. We discovered that simple diagnostic tests (reticulocyte count) were underused, that the majority of anemias were not corrected during hospitalization and that most inpatients of Internal Medicine wards in our Region are elderly (mean age 75 years) and suffer from polypathologies. We believe that further observational studies should be carried out in order to evaluate the progress of patients with anemia and to establish guidelines for the diagnosis and treatment.     

Role of venous drainage in cerebral arteriovenous malformation surgery,as related to the development of postoperative hyperperfusion injury

OBJECTIVE: To elucidate the role of venous drainage in cerebral arteriovenous malformation (AVM) surgery, with respect to the development of postoperative hyperperfusion injury. METHODS: For 52 patients with supratentorial AVMs, cortical capillary oxygenation (SaO(2)) was assessed intraoperatively, before and after resection, in the vicinity of the AVMs, by using a microspectrophotometric method. Assessed areas were defined as being related to feeding arteries or draining veins or as distant areas. Patients were divided into three groups on the basis of postoperative angiographic findings, as follows: Group 1, all former draining veins preserved (8 patients); Group 2, > or =1 former draining vein visible (12 patients); Group 3, no former draining veins visible (32 patients). Patients and SaO(2) values were pooled and compared by using paired and unpaired t tests (P < 0.05). Venous circulation times were calculated from digital subtraction angiography films. RESULTS: The postresectional relative increases in SaO(2) values were highest in draining vein areas (+40.8%, compared with +25% in feeder areas and +25.5% in distant areas). Five postoperative hyperemic complications occurred (9.6%), none in Group 1 (with all draining veins preserved), two (16.7%) in Group 2, and three (9.4%) in Group 3 (with all draining veins occluded). The lowest preresectional SaO(2) values (31.7 +/- 6.2%) were measured in the drainer areas of the five patients who subsequently developed hyperperfusion injuries. Among those patients, postresectional increases in SaO(2) values were significantly greater in drainer areas (+167.8%) than in feeder areas (+28.3%) or distant areas (+25.8%). Postoperative venous circulation times in former draining veins in Group 2 were significantly greater than those in Group 1 (8.9 +/- 1.5 s versus 6.3 +/- 0.6 s). Circulation times in normal veins in the five patients with hyperperfusion injury increased from 5.6 +/- 1.0 seconds (preoperatively) to 8.4 +/- 1.9 seconds (postoperatively). CONCLUSION: Postoperative hyperperfusion injury after resection of cerebral AVMs can be explained on the basis of unconstrained arterial inflow into cortical areas, which are rendered hypoxic/ischemic by longstanding preoperative venous hypertension. The risk for postoperative breakthrough complications seems higher in the presence of multiple draining veins, which also participate in the physiological venous drainage system of the ipsilateral hemisphere.