Chiara Mazzetta

The prevalence of lower urinary tract symptoms in men and women in four centres. The UrEpik study.

The topics covered in this section relate to areas of considerable interest for urologists everywhere. The UrEpik study is introduced in the ‘Comments’ section and the results of the study will appear in a series of papers published over the next few months. They will give a new insight into many aspects of LUTS.

The association between lower urinary tract symptoms and erectile dysfunction in four centres: the UrEpik study.

To report a large‐scale multinational investigation of lower urinary tract symptoms (LUTS) and sexual function, designed to investigate the independent association between them, as recent small‐scale epidemiological studies suggest an association between benign prostatic hyperplasia and sexual dysfunction; both conditions are strongly associated with age and no study has been able to exclude age as a confounding factor in this relationship.

The impact of lower urinary tract symptoms and comorbidities on quality of life: the BACH and UREPIK studies.

In a large epidemiological study, authors investigated the effect of LUTS on quality of life among various cultures. They showed a close association between the two, and that the effect of having moderate symptoms has a similar effect on quality of life as diabetes, hypertension or cancer, and that having severe symptoms had a similar effect as a heart attack or stroke.

Receptor radionuclide therapy with 90Y-DOTATOC in patients with medullary thyroid carcinomas.

UNLABELLED Metastatic medullary thyroid cancer (MTC) shows a progressive course. Surgery is the only curative treatment. In advanced disease, chemo- and radiotherapy show poor results. Newly developed somatostatin analogue [DOTA0,Tyr3]octreotide (DOTATOC) labeled to 90Y is administered in patients with endocrine tumors expressing somatostatin receptors, like MTC. Preliminary studies demonstrated that 90Y-DOTATOC could be safely administered, resulting in objective responses in 27% of patients. AIMS To evaluate the efficacy of 90Y-DOTATOC therapy in metastatic MTC patients with positive OctreoScan, progressing after conventional treatments. Twenty-one patients were retrospectively evaluated after therapy, receiving 7.5-19.2 GBq in 2-8 cycles. RESULTS Two patients (10%) obtained a complete response (CR), as evaluated by CT, MRI and/or ultrasound, while a stabilization of disease (SD) was observed in 12 patients (57%); seven patients (33%) did not respond to therapy. The duration of the response ranged between 3-40 months. Using biochemical parameters (calcitonin and CEA), a complete response was observed in one patient (5%), while partial response in five patients (24%) and stabilization in three patients (14%). Twelve patients had progression (57%). Complete responses were observed in patients with lower tumor burden and calcitonin values at the time of the enrollment. CONCLUSIONS This retrospective analysis is consistent with the literature, regarding a low response rate in medullary thyroid cancers treated with 90Y-DOTATOC. Patients with smaller tumors and higher uptake of the radiopeptide tended to respond better. Studies with 90Y-DOTATOC administered in earlier phases of the disease will help to evaluate the ability of this treatment to enhance survival. New more specific peptides and new isotopes will also represent the key of a better treatment of MTC.

The prevalence of male urinary incontinence in four centres: the UREPIK study.

To report the results of the prevalence and health status associated with male urinary incontinence (UI) in a population‐based, multicentre study in four countries, and to assess the epidemiology of this condition.

The relationship between lower urinary tract symptoms and health status: the UREPIK study

Is it justifiable to treat men in chronic retention conservatively? Urologists from the UK assess the outcome of men presenting with LUTS associated with large postvoid residual urine volumes. They found that complications such as renal failure and UTIs were uncommon in these patients. It was felt that conservative management for such patients was reasonable, but careful follow‐up was advisable.

The prevalence of urinary incontinence in community‐dwelling married women: a matter of definition

To determine the prevalence of female urinary incontinence (UI) and its impact on quality of life.

Mammaglobin Expression in Leukapheresis Products Is a Predictive Marker of Poor Prognosis in Women with High-Risk Breast Cancer

Purpose: The purpose of this study was to investigate the incidence and prognostic relevance of tumor cell detection in granulocyte colony-stimulating factor–mobilized peripheral blood progenitor cell collections (PBPCCs) using cytokeratin (CK), maspin (MAS), and mammaglobin (MAM) genes as epithelial cell markers. The population on which the study was conducted was drawn from stage III breast cancer patients undergoing high-dose chemotherapy and autologous transplantation with PBPCCs. Experimental Design: One hundred and ninety-four patients were enrolled in the study and analyzed for tumor cell detection on the basis of 481 PBPCCs gathered before administration of chemotherapy. CK, MAS, and MAM gene expressions were investigated by means of the reverse transcription nested polymerase chain reaction, and those samples expressing CK were further hybridized with a radiolabeled internal probe to reduce false-positive results. Sensitivity and specificity were assessed on 37 controls (12 cell lines, 12 healthy donors, and 13 nonepithelial malignancies). Each of the known prognostic variables (age, stage, lymph node status, receptor status, c-ErbB2 status, and Ki67 status) was then analyzed (both individually and together with CK, MAS, and MAM expression on PBPCCs) in relation to patient overall survival (OS) and relapse-free survival (RFS). Results: After a 3-year follow-up, an estimated 83% (95% confidence interval, 77.1–88.8%) of the patients were alive and an estimated 67% (95% confidence interval, 60.1–74.6%) were free of relapse. One hundred and seventy-six of the 194 patients (91%) had contaminated PBPCCs evidenced by at least one positive sample for any of the markers evaluated. The PBPCC frequency of CK, MAS, and MAM positivity (+) was 71%, 36%, and 16%, respectively. MAM expression on PBPCC was associated with an increased risk of relapse (P = 0.003), whereas CK and MAS expressions were not associated with changes in either RFS or OS. Conclusions: MAM gene expression on leukapheresis products of high-risk breast cancer patients is an indicator of poor prognosis. The method of evaluation is simple and reproducible and provides new tools for evaluating the role played by tumor cells in apheresis products and their potential in causing metastasis.

ChlVPP/ABVVP, a first line ‘hybrid’ combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis

We retrospectively analysed toxicities and clinical results of 61 Hodgkins lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III–IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6–8 cycles. Involved field radiotherapy (IFRT) (30–35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow‐up of 60 months, 5‐year overall survival, relapse‐ and event‐free survival were 78·8% (95% CI 68·2–91·1%), 81% (95% CI 70·6–92·2%) and 71·9% (95% CI 68·2–82·2%) respectively. Grades 3–4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non‐haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non‐haematological toxicity. Long‐term results of the ongoing randomized trial, comparing ABVD versus high‐dose intensity weekly regimens will be useful to confirm our results.

Hyperfractionated Radiotherapy in Locally Advanced Nasopharyngeal Cancer

Background:Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity.Patients and Methods:43 patients with nasopharyngeal cancer (stage II–IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week.Results:Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively.Conclusion:Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.Hintergrund:Obwohl zahlreiche randomisierte Studien zugunsten unkonventioneller Fraktionierungsschemata bei lokal fortgeschrittenenen Kopf-Hals-Tumoren sprechen, ist der Stellenwert dieses Vorgehens beim Nasopharynxkarzinom umstritten. Auf der Basis gängiger klinischer Erfahrung führten die Autoren die hyperfraktionierte Bestrahlung in die Therapie lokal fortgeschrittener Kopf-Hals-Tumoren, einschließlich Nasopharynxkarzinome, ein. Erste Ergebnisse dieses Therapieansatzes bei Patienten mit Nasopharynxkarzinom werden vorgestellt und insbesondere Grenzen des Verfahrens und seine Toxizität diskutiert.Patienten und Methodik:43 Patienten mit Nasopharynxkarzinom (Stadium II–IV, TNM 1997) erhielten eine hyperfraktionierte Strahlentherapie. In 34 Fällen gingen der Bestrahlung im Mittel drei Zyklen einer Cisplatin-basierten Induktionschemotherapie voraus. Die Strahlentherapie wurde im Rahmen einer „Shrinking-Field-Technik“ bis zu einer Gesamtdosis von 74,4 Gy in 62 Fraktionen mit 2× täglich 1,2 Gy (Minimum 6-h-Interval) an 5 Tagen pro Woche durchgeführt.Ergebnisse:Die Akuttoxizität der hyperfraktionierten Strahlentherapie war bedeutend, aber tolerabel. Häufigste Nebenwirkung war die Mukositis (Grad 3: 24 Patienten, Grad 4: drei Patienten). Schwerwiegende Spättoxizitäten wurden nicht festgestellt. 30 von 34 Patienten (88%) sprachen auf die Induktionschemotherapie an. 6 Wochen nach Abschluss der Strahlentherapie, wurde eine komplette Remission bei 35 Patienten (81%) beobachtet, partielles Ansprechen bei fünf (12%), Krankheitsstillstand bei einem und Fortschreiten der Erkrankung bei zwei Patienten. Nach im Median 32 Monaten Follow-up zeigte sich bei 18 Patienten (41%) eine Progression der Erkrankung. Fortschreiten des Primärtumors wurde bei drei Patienten beobachtet, und sieben Patienten wiesen entweder Befall der regionalen Lymphknoten oder Fernmetastasen auf. In einem Fall wurden sowohl Befall der regionalen Lymphknoten als auch Fernmetastasen diagnostiziert. Das progressionsfreie Überleben und Gesamtüberleben nach 2 Jahren waren 58% bzw. 84%.Schlussfolgerung:Die hyperfraktionierte Strahlentherapie scheint bei lokal fortgeschrittenem Nasopharynxarzinom praktikabel und wirksam zu sein. Die auftretende Akut- und Spättoxizität ist akzeptabel und gefährdet die Verabreichung der geplanten Strahlungsdosis nicht. Dieses Vorgehen führt zu einer hohen lokalen Kontrolle; allerdings verlangt das relativ hohe regionale und systemische Therapieversagen weitere Modifikationen, z. B. die Optimierung der Bestrahlungstechnik und/oder Dosisekalation sowie verbesserte systemische Therapien.