Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population.

AIM: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model.

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

[Observational study of adverse events in admissions in general hospital of Sassari about corporate planning of clinical risk management]. / Studio osservazionale degli eventi avversi relativi ai ricoveri del 2005, nell'ambito di un programma di gestione del rischio clinico della ASL di Sassari.

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.

Fitting late rectal bleeding data using different NTCP models: results from an Italian multi-centric study (AIROPROS0101).

BACKGROUND AND PURPOSE: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer. PATIENTS AND METHODS: Rectal dose-volume histograms of the rectum (DVH) and clinical records of 547 prostate cancer patients (pts) pooled from five institutions previously collected and analyzed were considered. All patients were treated in supine position with 3 or 4-field techniques: 123 patients received an ICRU dose between 64 and 70 Gy, 255 patients between 70 and 74 Gy and 169 patients between 74 and 79.2 Gy; 457/547 patients were treated with conformal RT and 203/547 underwent radical prostatectomy before RT. Minimum follow-up was 18 months. Patients were considered as bleeders if showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system) within 18 months after the end of RT. Four NTCP models were considered: (a) the Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident with the classical Lyman-Kutcher-Burman, LKB, model), (b) logistic with DVH reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d) relative seriality (RS). The parameters for the different models were fit to the patient data using a maximum likelihood analysis. The 68% confidence intervals (CI) of each parameter were also derived. RESULTS: Forty six out of five hundred and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed rectal bleeding within 18 months and were then considered as bleeders The risk of rectal bleeding can be well calculated with a 'smooth' function of EUD (with a seriality parameter n equal to 0.23 (CI 0.05), best fit result). Using LEUD the relationship between EUD and NTCP can be described with a TD50 of 81.9 Gy (CI 1.8 Gy) and a steepness parameter m of 0.19 (CI 0.01); when using LOGEUD, TD50 is 82.2 Gy and k is 7.85. Best fit parameters for RS are s=0.49, gamma=1.69, TD50=83.1 Gy. Qualitative as well as quantitative comparisons (chi-squared statistics, P=0.005) show that the models fit the observed complication rates very well. The results found in the overall population were substantially confirmed in the subgroup of radically treated patients (LEUD: n=0.24 m=0.14 TD50=75.8 Gy). If considering just the grade 3 bleeders (n=9) the best fit is found in correspondence of a n-value around 0.06, suggesting that for severe bleeding the rectum is more serial. CONCLUSIONS: Different NTCP models fit quite accurately the considered clinical data. The results are consistent with a rectum 'less serial' than previously reported investigations when considering grade 2 bleeding while a more serial behaviour was found for severe bleeding. EUD may be considered as a robust and simple parameter correlated with the risk of late rectal bleeding.

[Brachytherapy in the management of the initial stage of the mobile tongue carcinoma]. / Il trattamento con curieterapia del carcinoma della lingua mobile in stadio iniziale.

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.

A European version of the Appropriateness Evaluation Protocol. Goals and presentation. The BIOMED I Group on Appropriateness of Hospital Use.

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.

[Intraoperative radiotherapy in the combined treatment of pancreatic cancers]. / La radioterapia intraoperatoria nel trattamento integrato del carcinoma pancreatico.

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.

Comparison between two prospective studies of cardiovascular disease carried out amongst renal replacement patients in UK and Italy.

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.

Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single-institution phase II study.

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 M0 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 1.8 Gy fractions with concomitant cisplatin. Tumour response was evaluated by cystoscopy and biopsy. Those responding completely were given a 24 Gy 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.

Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study.

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 +/- 19% and 5-year actuarial survival was 24 +/- 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile.

Assessment of quality of life after radical radiotherapy for prostate cancer.

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 alpha 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.

Assessment of quality of life after cystectomy or conservative therapy for patients with infiltrating bladder carcinoma. A survey by a self-administered questionnaire.

BACKGROUND: Quality of life (QOL) has rarely been assessed in nonmetastatic bladder cancer patients (NMBC). Therefore, very little information is available for comparing the impact of different treatments on QOL for patients affected by NMBC. METHODS: We developed an "ad hoc" self-administered questionnaire and evaluated its psychometric properties. We then carried out a retrospective study by mailing the questionnaire to a consecutive series of 93 patients treated for NMBC between 1981 and 1994. The patients were treated either with a conservative approach (CT), based on radiotherapy with or without chemotherapy, or with cystectomy followed by urostomy (US). RESULTS: Twenty-nine questionnaires (66%) mailed to conservatively treated patients and 30 (61%) mailed to cystectomized patients were returned. The questionnaire used in the study showed sufficient psychometric properties: an alpha-Cronbach coefficient > 0.8 was reached and validity was established in all of its aspects. The items were grouped into seven subscales reflecting different QOL domains. The two treatment groups reported differences in QOL adjustment. QOL after cystectomy, marked by stoma presence, was reduced by a lack of sexual activity and a worsened physical condition, but social and recreational life were little affected. Conversely, a low incidence of urinary symptoms and an acceptable sexual adjustment were found in the CT sample; the physical, psychologic, and sociorelational adjustments were also good. QOL in the CT group was consistently better than in the US group. All subscale scores were higher in the CT group than in the US group, with a statistically significant difference in four of six subscales. CONCLUSIONS: QOL is better after conservative therapy than after cystectomy, as expected. Prospective studies with repeated measurements covering all fields of interest in QOL would offer an accurate assessment of QOL in NMBC patients.

[Hyperthermia and palliative radiotherapy for sarcoma]. / Ipertermia e radioterapia palliative dei sarcomi.

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.

[Radiotherapy of T1N0 neoplasms of the glottis. Analysis of the parameters that influence local control]. / La radioterapia nelle neoplasie T1N0 della glottide. Analisi di alcuni parametri che influenzano il controllo locale.

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 (p < 0.05). 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% at > or = 64 Gy; p < 0.05), 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 doses > or = 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.

Appropriateness of hospital use: an overview of Italian studies.

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.

Expression of mdm-2 and p53 protein in transitional cell carcinoma.

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.

Stage I seminoma of the testis: long term results and toxicity with adjuvant radiotherapy.

AIMS AND BACKGROUND: Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento, METHODS: From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. RESULTS: The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespread metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. CONCLUSIONS: In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.

Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial.

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.

Critical re-evaluation of 41 cases of "idiopathic" crescentic glomerulonephritis.

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 preceding 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of proteinuric patients with a vegetarian soy diet and fish oil.

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 cholesterol > 250 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.