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Background: This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy. Methods: Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and FISH for ERG rearrangement and overexpression, PTEN deletion, and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR). Results: Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status, and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared with those with ERG or PTEN wild type (P < 0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR = 2.6; P = 0.02). Conclusions: Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Future studies are needed to validate prostate cancer molecular subtyping for risk stratification. Impact: Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization. Cancer Epidemiol Biomarkers Prev; 23(4); 594–600. ©2014 AACR.

Background To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). Materials and methods We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. Results QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. Conclusions The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.

This paper describes the development and testing of a European version of the Appropriateness Evaulation Protocol (AEP). It stemmed from the original U.S. version and the multiple adaptations and modifications made previously and separately by researchers in European countries. The group was particularly concerned with developing a common list of reasons for inappropriate admissions and days of stay, since the principal goal was to enable an understanding of inappropriate hospital use and potential solutions within local health and social care systems. Developing a common EU-AEP included several steps. First, each national instrument was translated from the national language to English. These back translations were compared with each other and with the US-AEP. A working group analyzed the content of the lists of reasons published in the literature and proposed a novel conceptual approach. On the basis of workshop discussions, a draft of a common European version was circulated to each participant for agreement. In the EU-AEP, the clinical criteria for the appropriateness of admission include 10 related to patient condition and five to clinical services. The criteria for the appropriateness of days of care include 10 covering medical services, six for life support/nursing services, and eight related to patient condition. The proposed core list of reasons of inappropriateness distinguish clearly between two concepts: a) the level of care required by the patient; and b) the reason why this level of care was not used. The first list would thus refer to the nature of resources and facilities required, while the second would focus more on the efficient organization of those resources. A validated European tool to assess inappropriate hospital admissions and hospital days of stay and their causes might be used to assess the need for resources for inpatient care as well as for outpatient care. Assessing the reasons for inadequacies might lead also to the examination of organizational questions. Finally, a common tool allows comparisons between countries concerning the frequency of inappropriate admissions and days of stay and their reasons in relation to the different organizations of health care across Europe.

The data on 256 non-diabetic patients entering renal replacement therapy (RRT) in Manchester between 1 January 1983 and 31 December 1986 were compared with those on 84 non-diabetic patients entering RRT in Milan between 1 January 1983 and 31 December 1988. In each unit, patients had been studied prospectively and the findings were entered on the same database for this report. At the end of the study, 68% of patients were alive in each centre and in each 16% had died from cardiovascular disease. 11% of Manchester and 18% of the Milan patients developed angina. The data do not support the view that there is a differential risk for cardiovascular disease in the Northern and Southern parts of Europe and it may be advisable to study the matter prospectively in a larger patient cohort.

This paper reports on the general features and findings of 11 studies conducted in Italy on appropriateness of hospital admission and days of stay using the Appropriateness Evaluation Protocol (AEP). Studies have been grouped for presentation in two categories. The first comprises six heterogeneous studies illustrating different ways of targeting the use of the AEP: two used it to assess appropriateness of admission in an emergency room setting, two measured appropriateness of days of stay in patients with AIDS and nosocomial infections and finally two others evaluated hospital days in a group of elderly patients and “before and after” the institution of a domiciliary nursing service, respectively. The second group comprises five more homogeneous utilization review studies aimed at assessing inappropriateness of admissions and days of stay in medical/surgical departments of large hospitals in northern Italy. Besides detecting a substantial amount of inappropriateness in admission (range = 25–38%) and days of stay (range = 28–49%) this latter group of studies suggests that delays in execution and reporting of laboratory investigations, unavailability of operating rooms and delays due to difficulties in transferring patients to long-term care facilities are the most common causes of inappropriate days of stay. Despite the differences in their objectives, design and methods of sampling, these studies indicate that an explicit, diagnosis-independent and standardized instrument such as the AEP can help to uncover a substantial amount of the potentially avoidable use of hospital resources in the Italian context.

In the corporate planning of clinical risk management, we performed an observational retrospective study based on random sampling of admission in General Hospital of Sassari, in 2005. We examined 400 patient clinical documentations in order to find the most frequent adverse events (AE), according to the international literature. We looked for 9 different adverse events; for each of these we elaborated a form personal data and detailed information for each event. During the analysis of the clinical documentations we have found also adverse events not previously classified: they were recorded and classified. We classified the events as explicit, if declared in clinical documentation, and implicit if not declared but clearly present in the records. 47 EA included in the initial 9 categories were found; while other 26 were not included the defined categories, global frequency of AE in our sample resulted: 18.3%. The study is an initial approach to the survey of AE and needs to be refined by determination of liability, severity, predictability, preventability.

Undifferentiated small cell carcinoma of the bladder is a rare but aggressive subset of urinary tract neoplasms. Analogous to small-cell carcinoma of the lung, this tumor frequently exhibits neuroendocrine differentiation. We report the 92nd and 93rd case of small cell carcinoma of the bladder reported in the literature with characteristic cytologic, histologic, histochemical, and ultrastructural features. The patients were treated initially with chemotherapy, but after a brief clinical course died for progression of disease and for myocardial infarction, respectively. The pathologic and clinical features and therapeutic options of the cases described in the literature are reviewed.

Nephrotic patients with persistent proteinuria also have various lipid abnormalities that may promote atherosclerosis and more rapid progression of renal disease. We aimed to find out whether dietary manipulation can correct the hyperlipidaemia found in these patients. After a baseline control period of 8 weeks on their usual diets, 20 untreated patients with chronic glomerular diseases, stable long-lasting severe proteinuria (5·9 [SD 3·4] g/24 h) and hyperlipidaemia (mean serum cholesterol 8·69 [3·34] mmol/l) ate a vegetarian soy diet for 8 weeks. The diet was low in fat (28% of total calories) and protein (0·71 [0·36] g/kg ideal body weight daily), cholesterol free, and rich in monounsaturated and polyunsaturated fatty acids (polyunsaturated/ saturated ratio 2·5) and in fibre (40 g/day). After the diet period the patients resumed their usual diets for 8 weeks (washout period). During the soy-diet period there were significant falls in serum cholesterol (total, low-density lipoprotein, and high-density lipoprotein) and apolipoproteins A and B, but serum triglyceride concentrations did not change. Urinary protein excretion fell significantly. The concentrations of all lipid fractions and the amount of proteinuria tended to return towards baseline values during the washout period. We do not know whether the favourable effect of this dietary manipulation on proteinuria was due to the qualitative or quantitative modifications of dietary protein intake or was a direct consequence of the manipulation of dietary lipid intake.

Pancreatic cancer is a highly lethal disease either for the high incidence of distant metastases or for the frequent local recidive also after potentially curative resection. For this reason new multimodality approaches have to be investigated. Intraoperative radiotherapy (IORT) permits to administer a high dose to the tumor or to the retropancreatic tissues and to the regional lymphnodes. Literature data suggest it is possible a better local control and pheraps a better survival than the surgery alone or the palliative treatments by the use of schedules with IORT. Anyway they are retrospective data and IORT is an investigational method which has to be indagate in the combined modality approaches to this disease.

From 1986 to 1994, 61 patients with oral tongue epidermoid carcinoma were treated using low dose rate iridium brachytherapy. Eleven patients treated with combined external beam and brachytherapy and 8 with nodal metastases at presentation were excluded from the study. The results in 42 fully evaluable and regularly followed patients here retrospectively reviewed. In 22 cases clinical stage was T1 greater than 1 cm and in the remaining 20 T2, N0 M0; all were cases of epidermoid carcinoma. The patients received definitive brachytherapy to the primary site using plastic tube technique at a dose of 5067 Gy (median 60 Gy) at reference isodose. The dose rate ranged from 35 cGy/h to 80 cGy/h (median 53 cGy/h). Elective neck dissection was performed in 24 patients, whereas a surveillance protocol was adopted in the remaining 18 cases. After an average follow-up of 40 months, 5 year absolute and disease specific survival (Kaplan Meier) was 61% and 88% respectively. Two patients failed at the primary site (local control probability 96%). Nodal metastases were found in 6 of 24 electively dissected patients and developed subsequently in 3 of 18 pN0 cases and in 4 of 18 non dissected patients. Four patients died of uncontrolled neck disease (regional control probability 76%). A severe necrosis developed in 9 patients (soft tissue in 4 and bone in 5 patients), but only 3 cases required surgery. This study confirms brachytherapy as an effective treatment modality for the early stage of oral tongue carcinoma.

This paper describes the development and testing of a European version of the Appropriateness Evaluation Protocol (AEP). It stemmed from the original U.S. version and the multiple adaptations and modifications made previously and separately by researchers in European countries. The group was particularly concerned with developing a common list of reasons for inappropriate admissions and days of stay, since the principal goal was to enable an understanding of inappropriate hospital use and potential solutions within local health and social care systems. Developing a common EU-AEP included several steps. First, each national instrument was translated from the national language to English. These back translations were compared with each other and with the US-AEP. A working group analyzed the content of the lists of reasons published in the literature and proposed a novel conceptual approach. On the basis of workshop discussions, a draft of a common European version was circulated to each participant for agreement. In the EU-AEP, the clinical criteria for the appropriateness of admission include 10 related to patient condition and five to clinical services. The criteria for the appropriateness of days of care include 10 covering medical services, six for life support/nursing services, and eight related to patient condition. The proposed core list of reasons of inappropriateness distinguish clearly between two concepts: a) the level of care required by the patient; and b) the reason why this level of care was not used. The first list would thus refer to the nature of resources and facilities required, while the second would focus more on the efficient organization of those resources. A validated European tool to assess inappropriate hospital admissions and hospital days of stay and their causes might be used to assess the need for resources for inpatient care as well as for outpatient care. Assessing the reasons for inadequacies might lead also to the examination of organizational questions. Finally, a common tool allows comparisons between countries concerning the frequency of inappropriate admissions and days of stay and their reasons in relation to the different organizations of health care across Europe.

Pancreatic cancer is a highly lethal disease either for the high incidence of distant metastases or for the frequent local recidive also after potentially curative resection. For this reason new multimodality approaches have to be investigated. Intraoperative radiotherapy (IORT) permits to administer a high dose to the tumor or to the retropancreatic tissues and to the regional lymph nodes. Literature data suggest it is possible a better local control and perhaps a better survival than the surgery alone or the palliative treatments by the use of schedules with IORT. Anyway they are retrospective data and IORT is an investigational method which has to be indagate in the combined modality approaches to this disease.

Objective To assess in a phase II trial the effectiveness and toxicity of combined chemotherapy and radiation with selective bladder preservation by response in the treatment of muscle-invasive bladder carcinoma. Patients and methods Fifty-six eligible patients with T2-4 MO transitional cell bladder cancer suitable for radical surgery and multi-agent chemotherapy received two courses of methotrexate, cisplatin and vinblastine, followed by 40 Gy of pelvic radiotherapy in 1.8Gy fractions with concomitant cisplatin. Tumour response was evaluated by cystoscopy and biopsy. Those responding completely were given a 24Gy bladder boost plus cisplatin; patients with residual tumour were assigned to immediate cystectomy. Results After induction therapy, 28 patients (50%) responded completely; 22 operable patients with residual tumour underwent immediate cystectomy, while 34 patients were consolidated with cisplatin and radiation. Bladder relapses developed in 16 patients; seven had successful endovesical therapy for superficial disease and salvage cystectomy was possible in four of nine cases with invasive recurrence. Distant metastases occurred in 22 cases (39%). After a median follow-up of 46 months, the 5-year actuarial disease-specific survival was 59%, disease-free survival 54% and local control without cystectomy (bladder preservation) 41%. There were no treatment-related deaths; grade 3 late complications occurred in two patients. Conclusion This combined chemotherapy-radiotherapy regimen with selective organ preservation should be considered as an option for muscle-invasive bladder carcinoma. The initial results suggest the possibility of retaining a functioning bladder in many patients, without compromising survival, compared with elective cystectomy approaches. A longer follow-up and quality-of-life assessment remain essential for a better definition of selection criteria and long-term results of this combined modality.

Objective To assess the quality of life (QoL) of patients with localized prostate cancer (LPC) after treatment by radical radiotherapy (RR). Patients and methods An ‘ad hoc’ self-administered questionnaire was developed, which comprised a series of 41 items grouped into seven subscales reflecting the main QoL domains, and the questionnaire's psychometric properties were assessed. A consecutive series of 118 patients treated with RR for LPC from 1981 to 1994 were then selected for a retrospective study and asked to complete the questionnaire. Results Ninety patients (76%) completed the questionnaire; because 20 of them were also treated with hormonal therapy, QoL was assessed only in the remaining 70 patients, to avoid confusion. The assessment of the psychometric properties showed that the questionnaire was valid and reliable (Cronbach's a coefficient >0.8 for each subscale). The main side-effects of RR were urinary symptoms and sexual impairment, while physical, psychological and relational well-being were good. The degree of information available about the therapy and the disease seemed to play a major role in the patients' QoL adjustment after RR. Conclusion The study assessed a sample of patients with LPC treated with RR and showed that QoL was acceptable after RR. Prospective studies are needed to improve knowledge of the factors involved in the restoration of the QoL after therapy for LPC.

The current treatment of bone and soft tissue sarcomas consists of a multimodality approach based on the combination of surgery, radiotherapy and, more rarely, chemotherapy. Since local recurrence is an important cause of failure and morbidity, new treatment modalities such as hyperthermia, have been proposed to try to overcome this problem. July, 1982, to June, 1993, twelve patients (15 lesions) with recurrent or locally advanced sarcoma, were treated at the Department of Radiation Oncology, S. Chiara Hospital-Trento (Italy) with irradiation and hyperthermia. Radiation therapy was delivered with different techniques using palliative or radical doses (24-70 Gy) and different fractionation schedules. Local microwave hyperthermia was given in 2-9 sessions (mean 4.7). Eight (53.3%) complete responses and 4 (26.6%) partial responses were observed. Three lesions recurred at 11, 13, and 30 months; 5-year actuarial local control was 25.4 +/- 13.4%. Actuarial 5-year overall survival was 49.5 +/- 16.4%. Toxicity was mild: two superficial necroses, spontaneously healed after few months, were observed; local pain during hyperthermic treatment was recorded in 15% of sessions. Lesion volume and total radiation dose appeared to be correlated with the response. In our experience, the combination of radiotherapy and hyperthermia seems to be a valuable therapeutic approach in the treatment of locally advanced or recurrent sarcomas.

Treatment and tumor-related parameters were reviewed in 176 patients with T1N0 carcinoma of the glottic larynx submitted to primary radiation therapy from 1980 to 1992. Our aim was to analyze local control and treatment-related toxicity. Over-all local control rates at 10 years were 88.3% with irradiation alone and 94.5% after salvage surgery (larynx preservation: 91%). Verrucous histology was a negative factor affecting local control and anterior commissure involvement exhibited only a negative trend but had no statistical significance. Among treatment-related factors, local control was 76.5% after split-course and 91.1% after continuous-course irradiation (p0.05). With continuous-course irradiation, the total dose influenced local control only for single of 2 Gy (local control rates were 69% with 60 Gy and 93% ator = 64 Gy; p0.05), but not for single doses of 2.25 Gy and total doses ranging 56.25-65.25 Gy (local control failed in 55 patients). Early and late complications did not increase with single dosesor = 2.25 Gy. Our current policy in T1N0 nonverrucous glottic carcinoma is to use a single fraction of 2.25 Gy and a total dose ranging 56.25-63 Gy according to tumor size, with a continuous course.

Amplification of the mdm-2 gene and overexpression of the mdm-2 protein might inactivate p53 function, and may have prognostic relevance. The present paper investigated the immunohistochemical overexpression of the mdm-2 and p53 proteins in 25 biopsy specimens of transitional cell bladder carcinomas (10 pT1 and 15 pT2 or higher stages). Five cases (20%) showed strong mdm-2 protein immunoreactivity in more than 5% of the tumor cells; 14 cases (56%) showed p53 immunoreactivity in more than 20% of the cells, and were considered as overexpressing p53 protein. Four of the five cases with strong mdm-2 immunoreactivity did not show p53 overexpression, and 13 of the 14 cases with p53 overexpression did not show mdm-2 immunoreactivity. Our data are consistent with the hypothesis that p53 overaccumulation (and hence possible p53 gene mutation) or mdm-2 overexpression (and hence possible mdm-2 gene amplification) may mirror two different and possibly complementary gene alterations, which might finally interfere with the control of cell proliferation and apoptosis. In this perspective, evaluation of the combined mdm-2/p53 protein phenotype in human bladder carcinomas could have prognostic relevance and give us better prognostic information than evaluation of the p53 protein alone.

One hundred twenty-eight patients with different renal diseases and chronic renal failure, stratified according to the underlying disease, were enrolled in a randomized controlled trial to investigate the effects on the rate of decline of renal function of two diets, a controlled protein diet (CPD) of 1 g protein/kg ideal body-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6 g protein/kg i.b.w./day, given for 27.1 +/- 21.8 months. Dietary compliance was assessed by a dietary questionnaire, dietary interviews and measurement of 24-h urinary urea excretion. At the end of 6 months, actual mean protein intake was higher than expected (1.06 +/- 0.25 g/kg i.b.w./day) in CPD patients, and (0.80 +/- 0.21 g/kg i.b.w./day) in LPD patients: values were similar at 12 and 18 months after the time of enrollment. The end-point, defined as halving of creatinine clearance, was reached in 40% of patients on CPD, and in 28.6% of those on LPD (P = 0.038 by comparative life-table analysis). Multivariate regression analysis confirmed that CPD was associated with a higher risk of progression than LPD, and that two additional parameters (creatinine clearance at the time of randomization and average proteinuria during the follow-up) were significant independent risk factors, even more important than protein intake.

Despite the availability of different classifications for rapidly progressive glomerulonephritis (RPGN), patients with 'idiopathic crescentic GN' have not been yet inserted as a precisely defined subgroup, pointing to their probable heterogenicity. Trying to better define their characteristic, we retrospectively analyzed the clinical, histological and immunopathological features of 41 patients diagnostically labelled 'idiopathic RPGN' because they had no evidence of systemic disease (including systemic vasculitis), no anti-GBM mediated glomerulonephritis and no clearly defined primary glomerulopathy. Starting by a thorough morphological review, 2 subgroups were defined: group I (25 patients) with variable degrees of intraglomerular necrosis, and group II (16 patients) with no intracapillary necrotizing lesions. Group I showed no or minimal endocapillary proliferation, intense interstitial infiltrates with periglomerular localization, frequent ruptures of Bowman's capsule and mild degree of glomerular and/or interstitial sclerosis. 16 patients in this group (64%) had irregular deposits of complement C3 at immunofluorescence while the remaining 9 (36%) had no immune deposits. Clinically they had no previous history of preceeding urinary abnormalities, had a mean of 1.8 g/day proteinuria and a positivity for ANCA in 92% (12/13). In group II there was frequently marked mesangial proliferation, scarce interstitial infiltrates, no ruptures of Bowman's capsule and marked degrees of glomerulosclerosis and interstitial fibrosis. All patients in this group had clearly defined immune deposits of C3 and/or IgG. Clinically 50% of these patients had a history of recurrent microhematuria and/or proteinuria, a mean of 4.5 g/day proteinuria and negativity for ANCA in all 8 patients tested. Despite having a comparable mean percentage of crescents and S. creatinine at the time of renal biopsy, both groups differed significantly in their response to almost the same therapy, with 18 patients (72%) in group I showing remarkable improvement (> 50% decrease in their S. creatinine), while 9 patients (57%) in group II showed no response to therapy and progressed to end-stage renal disease. We conclude that, 'idiopathic' RPGN can be in fact the outcome of one of two pathogenetic mechanisms: the first is an acute necrotizing inflammation, with many features in common with the systemic vasculitides and actually represents a form of 'renal-limited' vasculitis, while the other is the result of extracapillary proliferation acutely complicating an underlaying primary chronic glomerulopathy

Our aim was to determine whether a longer period of treatment with a vegetarian soy diet with addition of fish oil supplements would accentuate the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients we found in a previous study. After an 8-week baseline period on free diet, patients were randomly allocated either on soy diet alone (SD) or to SD plus 5 g/day of fish oil (SD + FO) orally for two months. Then they crossed over to the other treatment for two additional months. They finally resumed eating the free diet for 3 months. We selected 20 outpatients with chronic glomerulonephritis, proteinuria in the nephrotic range, fasting serum cholesterol250 mg/dl, mean serum creatinine concentrations 1.75 +/- 0.23 mg/dl. Serum lipid profile, urinary protein loss and nutritional parameters were monitored. With the soy diet, we obtained a significant decrease both of hyperlipidemia and of proteinuria. The effect of the soy diet on proteinuria increased over the 4 months. The addition of a moderate amount (5 g/day) of fish oil in a randomized cross-over design had no further beneficial effect. Stability of serum albumin, transferrin and the body mass index documented good nutritional status. In conclusion, the dietary manipulation with our vegetarian soy diet confirmed the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients. Such effects persisted and even ameliorated after 4 months of diet. The addition of moderate oral supplements of fish oil did not potentiate the beneficial effect.

Cigarette and alcohol use before and during pregnancy were studied in 4966 Italian women who delivered single liveborn infants. Using a standardized questionnaire mothers were interviewed in the early postpartum period about pregnancy-related events. Data are part of the Drug Use in Pregnancy (DUP) Study, an international epidemiological co-operative survey conducted under the auspices of the World Health Organization, in 22 countries during 1989-1990. Italian pregnant smokers were women under 30 years of age with a middle-school education or less, and drinkers were 30 years of age and more with more than a middle-school education. When pregnancy was confirmed, most of them cut down smoking and drinking but more so for smoking than drinking: 12% stopped smoking and 6% stopped drinking. Less than 1% gave up both. The more the mother smoked during pregnancy the lower was the infant's birthweight and the association between reduced fetal growth and higher smoking level persisted after controlling for confounding variables. Only smoking habits were associated with delivery of small-for-gestational age babies. A large proportion of Italian women use alcohol and cigarettes before and during pregnancy. Smoking during pregnancy is an important preventable risk factor for the delivery of a small-for-gestational-age child. Thus it may be worth campaigning more vigorously to encourage women to give up smoking during pregnancy.

A rectrospective analysis was performed of the results of 104 consecutive patients with carcinoma of the pyriform sinus, who underwent radiation therapy. Thirty-four patients underwent radical surgery and postoperative radiation therapy (group 1); 36 patients received radical radiation therapy alone (group 2); neoadjuvant chemotherapy was administered prior to full-dose radiation to 20 patients (group 3); 14 patients received palliative radiation therapy (group 4). Loco-regional control and survival rates at 5 years were 60.4% and 34.3% in group 1, 23.8% and 23.8% in group 2, 17.5% and 23.8% in group 3; no patients in group 4 survived at 5 years. Patients in group 1 experienced significantly better survival and local control than those in groups 2 and 3. No differences were observed between groups 2 and 3. Loco-regional recurrence was the main cause of failure in group 2 (69.4%) and 3 (70.0%). In group 1, 20.3% of cases developed distant metastases. Overall 5-year survival rate was 23.7%, confirming the poor prognosis of this disease. These results provide further support to the need of improving prevention and early diagnosis to improve both results and outcome in patients with carcinoma of the pyriform sinus.

In this retrospective study we report the outcome of 59 adults with idiopathic focal-segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) treated with corticosteroids and/or immunosuppressive drugs. Twenty-seven patients were initially treated with corticosteroids alone for 9.3 +/- 8 months; nineteen patients received corticosteroids and immunosuppressive agents associated or every other month for 5.5 +/- 4 months; thirteen patients received either azathioprine or cyclophosphamide alone for 25 +/- 27 months. At the end of a mean follow-up of 75 +/- 51 months, 35 patients (60%) were in complete (CR) or partial (PR) remission, 6 (10%) were stable and 18 (30%) had either chronic renal failure (CRF) or end-stage renal failure (ESRF). Out of 36 patients (61%) initially responsive to therapy, 30 (83%) obtained CR, 4 (11%) PR, one (2.7%) developed CRF and one (2.7%) ESRF. Only 10 of the responders (28%) attained remission within 8 weeks of treatment. Out of the 23 (39%) patients originally resistant to therapy, only one (4%) had CR, 6 (26%) remained unchanged, 6 (26%) developed CRF and 10 (43%) ESRF. The presence at initial renal biopsy of interstitial fibrosis was the only feature which could predict a poor renal outcome. These data show that prolonged treatment of FSGS can obtain sustained remission of the disease and improved renal survival in a consistent proportion of adult patients which would be considered refractory to a two-month course with corticosteroids.

Twenty neurophysiological parameters were employed to evaluate the presence and the degree of peripheral neuropathy (PNP) in a cohort of 135 patients (pts) on regular dialysis treatment (RDT) for 2 to 184 months. The 135 pts were divided into 3 groups according to the duration of RDT (group I: 52 pts with less than 5 yrs; group II: 46 pts 5 to 10 yrs; group III: 37 pts 10 to 15 yrs). Each group was then divided into two subgroups according to age (less or more than 47 yrs) to evaluate the influence of age on PNP. Correlations of electrophysiological parameters with some biochemical parameters (urea, creatinine, PTH) were looked for. The presence of clinical PNP was evaluated according to the Bolton classification: in group I, 50% of pts have mild PNP; in group II, 45.7% of pts have mild PNP; in group III, 81.1% have mild, 10.8% have moderate and 2.7% of pts have severe PNP. In as many as 84.4% of the 135 pts at least one of the 20 parameters studied had abnormal values and in 63% two or more parameters were abnormal. Of 20 parameters evaluated separately in the 3 groups only three showed abnormal mean values: sural nerve latency in all 3 groups; sural nerve Sensory Conduction Velocity (SCV) and peroneal nerve Max. Motor Conduction Velocity (MCV) in group III. Five parameters referring to ulnar nerves and two referring to the sural nerve were significantly more impaired in the group of pts with the longest duration of RDT and in this group the impairment was more severe in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

External beam radiotherapy (RT) is an effective treatment modality for selected patients with invasive bladder cancer. Patients who achieve a complete clinical response (cCR) after full dose RT enjoy a 45–69 Wo probability of surviving 5 years.

From 1976 to 1987, 98 patients affected with nasopharyngeal carcinoma were observed at the Oncology Center, Trento, Italy. Eighty of them were treated with radical radiation therapy (average total dose: 6432 Gy, range: 5500-7400 Gy) on primary tumor and positive neck nodes. The clinically negative neck received 5000 Gy. Each dose ranged from 180 to 250 Gy. Fifty-nine patients were treated with the split-course technique with an interval of about 15 days after receiving 4000 cGy. The patients were 60 males and 20 females, their age ranging 17-81 years (mean: 57 years). Histology diagnosed squamous cell carcinoma in 15 cases and undifferentiated carcinoma in 65 cases. All patients were staged according to TNM (UICC, 1978) criteria. Ten patients were stage I/II. Complete local control was obtained in 81.3% of cases. Actuarial global survival at 10 years was 52%, actuarial relapse-free survival was 49%. Mean follow-up is 33 months (range: 4-122 months). Squamous cell carcinoma at histology and advanced nodal involvement (N2-N3) were negative prognostic factors. Six patients had a relapse in the nasopharynx and 5 in the neck; the incidence of distant failures was 20%. The most frequent mid-/long-term side-effect was xerostomia.

The technical complexity of intraoperative radiotherapy (IORT) requires modification of the standard physical and dosimetric methods used in external electron beam therapy. At the Radiotherapy Department of Ospedale S. Chiara in Trento a number of technical innovations have been developed, including an electron beam applicators system and related devices. Ionometric and film dosimetry have been used to obtain relative dose distributions of clinical electron beams in phantoms.

Histological features and data on the natural history after 1 to 45 years (mean 6.56 +/- 8.55) of total apparent duration and 1 to 13 years (mean 3.48 +/- 5.04) of post-biopsy follow-up, are reported in 374 patients (mean age, 33.9 +/- 11.9 yrs) with idiopathic mesangial IgA nephropathy, who presented with a history of macroscopic hematuria (56%), recurrent in two-thirds of the patients, or with persistent microscopic hematuria and no previous episodes of gross hematuria (44%). Mesangial cell proliferation ranged from minimal to diffuse. Associated varying degrees of extracapillary proliferation, segmental and global glomerular sclerosis, tubulo-interstitial damage and arteriolar hyalinosis usually correlated with each other and with the extent of mesangial proliferation (P less than 0.05). The actuarial curve of progression to renal death showed a 75% survival after 20 years from apparent onset. Progression to renal failure was more rapid in patients with: an older age at onset (P = 0.0582); male sex (P = 0.0730); no history of recurrent gross hematuria (P = 0.0406); high blood pressure (P = 0.0011); more marked global (P = 0.0007) and segmental (P = 0.0026) glomerular sclerosis; more severe interstitial sclerosis (P = 0.0147); more diffuse and global mesangial proliferation (P = 0.0820); mesangio-parietal pattern at immunofluorescence (P = 0.0778). However, all these parameters showed a poor predictive value if applied to any single patient.

An unusual feeding behavior of the western spruce budworm (Choristoneuraoccidentalis Freeman) reduced height growth and deformed young western larch (Larixoccidentalis Nutt.). On western larch, budworm larvae did not confine their feeding to foliage, their usual diet on other conifers; they also fed on and severed stems of current-year terminal and lateral shoots. A 5-year study in young larch stands showed that: (1) amount and severity of budworm damage increased annually, (2) all trees were damaged sometime during the study, (3) severance of the terminal shoot was the most serious type of budworm damage to larch, (4) severances reduced net height growth at least one-fourth and resulted in forked, bushy-topped trees, and (5) specific forks in the tree did not persist more than 5 years because of the strong apical dominance characteristic of larch.

Unseasonal temperatures, as low as −6°C, were recorded in western Montana in mid-June 1969, a period when western spruce budworm (Choristoneura occidentalis Freeman) larvae were actively feeding on newly developing foliage of coniferous host trees. Studies in progress at that time provided circumstantial evidence that the freeze reduced: (1) budworm populations on Douglas-fir (Pseudotsuga menziesii var. glauca (Beissn.) Franco), western larch (Larix occidentalis Nutt.), and ponderosa pine (Pinus ponderosa Laws.) over 90%; and (2) budworm damage to young larch 54–71%.

Objective:To assess the predictivity of predefined variables with respect to long-term mortality in a cohort of patients with chronic critical leg ischaemia (CLI).Design:Prospective observational study.Methods:Census offices were asked to release information on survival or death status of 574 patients with CLI 2 years after their recruitment in the study.Results:Of 522 patients with available information, 165 (31.6%) died within 2 years of hospital admission, mostly from vascular causes as expected. Among the variables considered, male sex, current smoking, arterial hypertension, diabetes mellitus, hypercholesterolaemia, obesity, history of myocardial infarction and low ankle systolic pressure showed no univariate association with mortality. The multivariate analysis also excluded revascularisation procedures and the Fontaine stage as prognostic factors in terms of mortality. Besides age ≥ 70 years (relative risk, RR 1.94; 95% confidence interval (CI) 1.37–2.70), only a history of stroke (RR 1.82; 95% CI 1.19–2.79) and major amputation (RR 1.90; 95% CI 1.30–2.80) were significantly associated with mortality.Conclusions:CLI is a clinical condition of such severity that most of the recognised cardiovascular risk factors cannot further influence the fate of the patients, one-third of whom die within 2 years.

Objective:To draw a picture of the different practices adopted for the diagnosis, specific treatment and general care of critical leg ischaemia (CLI) in the light of the recommendations of the recent Consensus Document.Design:Prospective observational study.Setting:A representative sample of vascular and general surgery, angiology, general medicine departments of the Italian National Health Service.Subjects:Patients with leg ischaemia considered as chronic and critical according to the definition and diagnostic criteria adopted in each centre.Chief outcome measures:Epidemiological profile of the standard population; prevalence of definition criteria and of diagnostic and therapeutic procedures; short and medium-term clinical outcome as well as of the general vascular morbidity and mortality.Main results:Over a 3 month period, 574 patients were recruited in 69 centres mainly on the basis of clinical findings of CLI (rest pain and/or trophic lesions). They had an adequate diagnostic assessment of their vascular lesions and a high cardiovascular risk in terms of prior morbidity and presence of risk factors. Over half of the patients underwent revascularisation and three quarters were given pharmacological treatments. At the end of the observation period, 50 patients had died (8.7%), three had had a myocardial infarction (0.5%), six a stroke (1.0%), 70 a major amputation (12.2%) and 103 had persistent CLI (17.9%).Conclusions:This survey confirms the dramatic prognosis of patients with CLI and provides an appropriate background and setting to conduct experimental clinical studies in this field.

The role of infiltrating blood-borne cells in the pathogenesis of renal damage in human glomerulonephritis is under active investigation. We have evaluated leukocyte infiltrates (number of cells/mm 2 ) in the renal interstitium of 21 patients with Berger's disease and eight normal kidneys with monoclonal antibodies and a four-layer immunoperoxidase technique. In our population of patients, the number of infiltrating T-lymphocytes (OKT 8 + cells) was significantly higher (median, 132) than in the normal kidneys (median, 60). This increase was mainly due to T-suppressorlcytotoxic lymphocytes (OKT 8 + cells; median, 68), while T-helperlinducer lymphocytes (Leu 3A+ cells) and monocytes were in the normal range. T-lymphocyte infiltration was more marked in ten patients with impaired glomerular filtration rate (GFR) at the time of biopsy (median, 167) than in patients with normal GFR (median, 88). In addition, ten patients who showed deterioration of renal function during the subsequent followup, whatever their serum creatinine levels at the time of biopsy, had significantly more total T cells (median, 269), OKT 8 + cells (median, 143), and Leu 3A + cells (median, 105) than 11 patients with persistently stable GFR and normal controls. More data are necessary to establish whether this T-lymphocyte infiltration is the consequence of a cell-mediated mechanism acting in the interstitium, concomitant with the immune-complex-mediated mechanism acting in the glomerulus, or is a nonspecific consequence of the tubulointerstitial damage induced by the immunologically mediated glomerular disease.