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Background Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. Patients and methods Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. Results From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51–86] in the minimal surveillance group and 62 months (IQR 50–85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. Conclusion Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. ClinicalTrials.gov NCT02409472.

De nos jours, les jeux d’argent sont souvent critiqués par les médias, les intellectuels, les observateurs… L’État croupier et les opérateurs ludiques sont accusés d’exploiter la passion ancestrale des hommes pour les jeux de hasard. À partir du cas français, ce texte montre que l’histoire des jeux d’argent est celle de leur prohibition, et qu’il existe en réalité une complicité entre les joueurs et les faiseurs de jeux. Les pouvoirs publics doivent s’interroger sur l’offre de jeux d’argent car le développement spectaculaire de cette industrie (loteries, machines à sous, cartes à gratter…) a des conséquences économiques et sociales négatives. La France – qui a pris beaucoup de retard en matière de politique de jeux – est actuellement à la croisée des chemins. Elle doit mettre en place avant toute chose une structure indépendante et pluridisciplinaire (observatoire) qui se prononce sur les aspects médicaux, sociaux et culturels du jeu. In our times, gambling is mostly frowned upon by the medias, the intellectuals, the observers… The Dealer State and the game industry are accused of taking advantage through money of the ancestral passion of men for gambling.Through the study of the French case, this article shows that telling the history of gambling is also telling the history of a prohibition, and that, in fact, there is a connection between the players and the game makers. Nonetheless, the offer concerning gambling must be questioned because the extraordinary increase of the game industry (lottery, slots machines…) has economic and social negative consequences about which the government must apply a right of legislative and regulatory interference. France – who is behind in the field of game policies – is at a crossroad. The country has to build a independent and multidisciplinary structure (Observatory) that will have to rule on medical, social and cultural aspects of gambling.

Although the incidence of gastric cancer has gradually decreased in many Western Countries, it remains one of the leading causes of cancer-related deaths worldwide, and it now ranks second only to lung cancer with about 755 000 new cases per year (Karpeh et al, 2001). Since screening for early detection is not performed in Western Countries, in approximately 50% of newly diagnosed cases, the tumour is beyond its local–regional margins (Kelsen, 1996; Karpeh et al, 2001). Surgery remains the mainstay of any curative treatment, but only when a radical resection is feasible (removal of all gross cancer cells at the resection margins as determined by histopathological examination). Those patients who are considered not amenable of curative resection generally receive chemotherapy in order to obtain palliation of symptoms and improved survival. Since there is no evidence that a more aggressive treatment could result in a better survival, most of the patients receive a combination of 5-fluorouracil (5-FU), mitomycin C or cisplatin (Karpeh et al, 2001). Only a few studies have focused on the role of preoperative chemotherapy in unresectable gastric cancer. Comprehensively, these trials suggested that chemotherapy could allow radical surgery in approximately 40% of all cases not amenable of curative resection at presentation, but at the cost of severe toxicity (Kelsen, 1996). In a pilot trial, we observed that a preoperative chemotherapy with weekly cisplatin (CDDP), epidoxorubicin (epi-ADR), 5-FU, 6S-leucovorin, glutathione and bone marrow support (filgastrim) could allow a radical resection in 13 out of 32 (41%) patients previously considered unresectable (Cascinu et al, 1998). These encouraging findings followed our demonstration of activity (62% overall response rate in 105 patients) of this chemotherapy regimen in patients with advanced gastric cancer. In this latter trial, five of 11 (45%) patients with exclusively locally advanced unresectable disease could undergo a curative resection after chemotherapy (Cascinu et al, 1997). In order to test whether the hypothesis of a more aggressive and expensive approach in this subset of gastric cancer patients could be justifiable, we prospectively analysed the effects of this intensive weekly treatment in a larger group of gastric cancer patients not amenable of curative resection.

The “Misura” project is a retrospective survey, with the aim to evaluate how 5FU is used in the treatment of colorectal cancer in clinical practice in Italian oncology departments. Twenty-four centers participated. Patients seen in the second half of 1998 with colorectal cancer and treated with 5FU were analyzed. Observed patients were 664, 45.9% of patients presented metastatic disease. Biochemical modulation with folinic acid and bolus 5FU was the most used schedule (59%). The De Gramont (LV 5FU2) regimen, alone or with other cytotoxic drugs, was the second most chosen schedule (14%). The most frequent side effect observed was gastrointestinal toxicity. No hematological toxicity was demonstrated in 68.8% of patients. Cutaneous toxicity occurred in 21.1% of patients. 5FU is widely used independently by the stage of disease. In palliative treatment a variety of schedules were administered by the Italian centers, lacking a standard therapy. There are very few surveys investigating oncology clinical practice. A larger survey on this issue is auspicable.

Progress in medical science, technology and the multidisciplinary approach over the last half century has made it possible for people to live longer and to remain in good physical condition [1]. However, these benefits are sometimes only physical. Many studies have demonstrated that although patients are grateful for restored physical health, they have suffered psychologically from the lack of direct contact with their doctor which has been replaced by an anonymous team of specialists and machines. The old style doctor-patient relationship has been discarded; the patient is no longer a whole person but has become a list of scan and test results. Is it any wonder that patients feel that their doctor is not really interested in them as people [2–4]. In general, medical training does not include or barely touches on the importance of communication in the doctorpatient relationship focusing instead on the physical illness and not the patient [5, 6]. The communicative relationship between doctor and patient is inevitably conditioned by numerous variables such as the time and space available, the ability and psychological willingness of the doctor to face bad news for the patient and the patient’s ability to take part in a psychologically intense meeting. The relationship is further conditioned by the medical discipline involved, for example intensive care, paediatrics, oncology, ophthalmology, surgery, dermatology, palliative care, to name just a few of the specialist disciplines which all represent different experiences for the patient, different diagnostic and therapeutic interventions which often are diametrically opposed and which have a notable influence on the doctor-patient relationship and the method of communication. Unfortunately, the so called spending review has and will further reduce human resources which translates into the doctor having less time to dedicate to the fundamental moments of treatment such as listening, understanding and having a dialogue with the patient.

Aims and background The phase II trial was designed to evaluate the activity of combined oxaliplatin (L-OHP), continuous infusion (CI) ± bolus 5-fluorouracil (5FU) and levo-folinic acid (IFA) in patients with metastatic colorectal cancer progressing after one or more lines of 5FU-based chemotherapy. Patients and methods We designed two contemporary studies: in the former we enrolled patients previously treated with 1 line of chemotherapy, and in the latter, patients previously treated with 2, 3 and 4 lines. Seventy-six consecutive patients were enrolled: 45 received L-OHP (85 mg/m2 iv 2 h on day 1) + I-FA (100 mg/m2 iv 2 h on days 1 and 2) + 5FU iv bolus (400 mg/m2 days 1 and 2) + 5FU (600 mg/m2 CI 22 h days 1 and 2 (FOLFOX 4); 31 received L-OHP (100 mg/m2 iv 2 h on day 1) + I-FA (250 mg/m2 iv 2 h on days 1 and 2), followed by 5FU (1500 mg/m2 CI 24 h days 1 and 2 (FOLFOX 2). The treatment was recycled every 2 weeks and continued until progression and/or unacceptable toxicity or patient preference. The primary end point was activity (tumor growth control [TGC]: partial response [PR] + stable disease [SD]); the secondary end points were time to progression (TTP), overall survival (OS) and toxicity. Results Forty-five patients in 2nd line (22 FOLFOX 4, 23 FOLFOX 2), 23 (17 FOLFOX 4, 6 FOLFOX 2) in 3rd, 4 in 4th and 1 in 5th line were assessable; 3 were lost to follow-up. In 15 patients (11 FOLFOX 4, 4 FOLFOX 2), disease involved the liver only. A total of 533 courses were administered with a range of 1-14 in FOLFOX4 and 1-12 in FOLFOX2; dose intensity was 92.85%, and the total dose of the administered L-OHP was 98.29%. As a 2nd line treatment, FOLFOX 4 achieved TGC in 72.8% of the patients (PR, 18.2%; SD, 54.6%), with a median TTP of 6 months and a median OS of 7 months, whereas in the FOLFOX 2 group these figures were 78.3% (PR 21.8%, SD 56.5%), and 5 and 9 months. As a 3rd line treatment, FOLFOX 4 produced TGC in 41.1% of patients (PR 23.5%, SD 17.6%), with a median TTP of 5 months and median OS of 7+ months, whereas FOLFOX 2 obtained respective values of 50% (PR 16.7%, SD 33.3%), 7 and 9 months. As a 4th line of treatment, TGC was achieved in 2 patients (1 PR, 1 SD); the patient in 5th line therapy obtained a SD. With “de Gramont” as the first-line regimen, patients assessable were 24 in FOLFOX 4 and 18 in FOLFOX 2. In the former population, TGC was 70.8% (PR 37.5%, SD 33.3%), with a TTP of 6 months and OS of 10 months, whereas with FOLFOX2 these values were 61.1% (PR 5.6%, SD 55.5), 5 and 7 months. In patients with liver involvement only, FOLFOX 4 obtained TGC in 63.6% of cases (with a TTP of 7 months and OS of 6+ months), FOLFOX 2 in 100% (with a TTP of 9.5 months and OS of 13.5+ months). Both schedules exhibited an acceptable toxicity: neurologic, hematologic and hepatic grade 3 side effects occurred in a limited number of patients, with a higher frequency in the FOLFOX 2 group. Conclusions Treatment with L-OHP, CI ± bolus 5FU and I-FA was well tolerated. The activity in terms of TGC was interesting and comparable with results reported in the literature for the standard treatment for 2nd line, i.e. irinotecan alone. Treatment was effective in 2nd line and in patients previously treated with more than two chemotherapy lines; in particular, treatment was active in patients with hepatic disease only. Although the two schedules seemed to achieve the same benefit with the same tolerance, we could not define from the study the better regime.

PURPOSE A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.

HMB-45 is an anti-melanoma monoclonal antibody widely used in diagnostic pathology owing to its great specificity in identifying poorly differentiated melanomas. In this study, by a series of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblots with the enhanced chemiluminescent (ECL) detection method on the HU-214 melanoma cell line, we identified the antigen of HMB-45 in a protein or proteins of 30-35 kDa. Although this result is in discrepancy with the previous literature which identified the antigen as a protein of 7 or 10 kDa, a family of proteins of 25-70 kDa of as a protein of 100 kDa (gp100), the present data indicate that the antigen signal we found might be specific. Furthermore, immunoblots on neuraminidase-treated cell lysates show, in agreement with already published data, that the antigen might be a sialated glycoprotein with the sialic acid involved in the epitope. Immunoblots on partially purified melanosomes confirmed the presence of the antigen in these organelles.

The immunoperoxidase staining of normal and hyperplastic prostatic epithelium for Prostate Specific Antigen (PSA) is, with few exceptions, uniform and strong. In contrast to the benign tissue, most reports of prostatic adenocarcinoma demonstrated an apparent correlation between staining-variability and increasing tumour grades. Decreased PAP staining may be related to incorrect manipulation of prostatic tissue. Finally there are many tumours and pseudotumours of the prostate in which the PSA stain is regularly negative. In the differential diagnosis of prostate tumour, both PSA and PAP (Prostatic Acid Phosphatase) stains should be performed. It is mandatory that the stains be interpreted in the appropriate histologic and clinicopathologic setting with due consideration of positive and negative staining.

— We report the results of a retrospective study of two groups of patients affected by locally advanced bladder cancer: the first group was submitted to adjuvant chemotherapy with Cisplatin and Methotrexate after cystectomy and the second group was submitted to neoadjuvant chemotherapy with the same scheme following radical cystectomy. The validity of the study is given by the homogeneity of the two groups for period of recruitment, number of patients, patient's age, stage of disease and treatment. The overall survival of 5 years in the first group was 30%, while the 5-year survival rate of the second group was 38%, 63% and 17% for all the patients, the responders and the nonresponders respectively. No significant difference in terms of survival was found between the two groups, but the results of the neoadjuvant approach may be influenced by clinical staging errors. The chemosensitivity, that can be assessed only with the neoadjuvant treatment, is the main prognostic factor.

Resume L'observateur qui s'interesse aux jeux d'argent est d'abord gene par les discours sur le joueur qui vont de la condamnation moralisante a l'apologie, en passant par la complaisance et l'exotisme esthetico-litteraire. Le present article fournira l'occasion de montrer que l'on peut traiter le jeu, le joueur sans devenir visionnaire et sans proceder par anatheme moralisateur ou discours apologetique. Il donnera au sujet qui se lance dans l'aventure ludique toute sa place, sans s'identifier a ses experiences. Si le sujet est au centre de cette investigation, c'est cependant comme sujet social donnant sens a des pratiques dont la pratique sociologique doit rendre raison, a condition de la mettre en oeuvre dans toute sa diversite. Par consequent, les «je ne sais quoi» ou les «presque rien» que nous avons observes dans les espaces de jeu, entendus en interrogeant les joueurs ou en analysant le materiel ludique, sont a la genese de notre reflexion sur le jeu.

Summary Purpose: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of tomudex with methotrexate (MTX)/5-fluorouracil (5-FU)/leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer. Patients and methods: Patients with histologically proven metastatic colorectal cancer and at least one bidimensionally measurable lesion, aged 18-70, with performance status =S 2, normal baseline biological values, and no prior chemotherapy, were selected. Treatment was tomudex 3 mg/m 2 and, after two weeks, MTX, 200 mg/m 2 by 30' infusion after hydration with 1500 ml saline solution, followed on day 2 by 5-FU, 600 mg/m 2 and leucovorin, orally, 15 mg for six times every 6 hours, beginning 24 hours after MTX. Cycles were repeated every four weeks. Tumor response assessment was performed after three cycles. Results: Thirty-four patients were enrolled in this study, of whom twenty-four had liver metastases, nine local relapse, five lymph node involvement, four lung metastases, and three peritoneal carcinomatosis. Four patients achieved objective responses (one complete and three partial), for an overall response rate of 12% (95% CI: 0%-22%). Twelve patients had stable disease and 18 progressed on therapy. Median survival for all patients was 13 months. Two patients experienced grade 3 WHO neutropenia while hepatotoxicity was reported in 13 patients (6 grade 1, 3 grade 2, 3 grade 3, 1 grade 4), suggesting that this combination could increase hepatic toxicity in comparison to tomudex or MTX/5-FU alone. Conclusions: Our results suggest that this regimen does not warrant further investigation in advanced colorectal cancer patients, at least not with this schedule and doses.

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

Testis pure teratoma accounts for 2.7% to 3% of all germ cell tumors in adult where it behaves as a malignant neoplasm. Pure teratoma of the testis presents in clinical stage I disease in 44% of the patients whose risk of having pathological stage II disease is 16.7% to 19.2%. Herein we report on 5 cases of adult pure teratoma of the testis presenting itself in clinical stage I disease.From September 1976 to February 2000, 75 patients underwent orchidectomy for clinical stage I nonseminomatous germ cell cancer of the testis. Testis pure teratoma was detected in 5 patients (7%). Testis tumor markers were evaluated in all cases. Patients underwent imaging examination to detect the clinical stage of the disease. Treatment options after orchidectomy included retroperitoneal lymph node dissection (RPLND) in 4 patients and surveillance in 1.The average age of the patients was 31 years (range 24-45). The tumor was on the left sided in 3 cases (60%) and right in 2 (40%). Tumor average size was 3.2 cm (rang 1-6). Histopathology detected the following subtypes: mature teratoma in 3 cases (60%), immature teratoma in 1 (20%) and teratoma with malignant transformation in (20%). All patients were at clinical stage I disease. Germ cell cancer microscopic metastatic disease including embryonal carcinoma was detected in I dissected lymph node of 1/4 patients (25%). Average follow up was 166 months (range 93-249). All patients were alive and disease free and no relapses were detected during the follow up period.Primary pure teratoma of the testis does not respond to chemotherapy nor does it to radiation therapy. The disease treatment options after orchidectomy for patients with clinical stage I disease include RPLND or surveillance with their relative risks and benefits. RPLND is the chosen treatment because it is both staging and treating. A close a long term follow up is required since pure teratoma metastatic disease may clinically develop after more than 10 years.

The authors report on a rare pediatric case of adrenal extramedullary hematopoiesis in a patient with beta-thalassemia disease. The lesion was clinically discovered as incidentaloma of the right adrenal gland and treated by surgery. Adrenal extramedullary hematopoiesis may clinically be detected as incidentaloma. Adrenal incidentalomas presenting with hematologic disorders, such as agnogenic myeloid aplasia and beta-thalassemia, need careful imaging as well as adrenal hormonal investigation in order to exclude malignancy and subclinical hypersecretory syndromes. Ultrasound or CT-FNA of the lesion are effective in finding out the disease.

This retrospective study was performed to evaluate histopathologic prognostic risk factors in 75 patients on clinical stage 1 nonseminomatous germ cell cancer of the testis (NSGCTT).From September 1976 to February 2000 we operated on 75 patients for NSGCTT on clinical stage 1 disease. Average age was 29.5 years (range 16-71). After orchiectomy, therapeutic options included retroperitoneal lymph node dissection (RLND) for 44 patients (58.6%), surveillance for 26 (34.6%) and neoadjuvant chemotherapy for 5 (6.6%). Testis primary tumor samples were assessed for studying prognostic risk factors that included vascular and/or lymphatic invasion (IV/IL+), percentage of embryonal carcinoma (%EC) and absence of yolk sac tumor (YS-).All patients were alive and disease-free. The average age follow-up was 84.5 months (range 1-254). Relapses occurred in 11 (14.6%) patients after an average follow-up of 9.09 months (range 3-24). Prognostic risk factors were detected as follows: IV/IL+ in 17 cases (22.7%), (50-80%) EC in 23 (30.6%), CE%80 in 23 (30.6%), YS- in 55 (72%). In 8 (10.6%) patients there was not any prognostic risk factor. Disease relapse related to prognostic risk factors was detected as follows: 18.1% for VI/LI, 90.9% for EC%50 (27.2% for 50-80% EC and 63.6% for CE%80) and 90.9% for YS-. Relapsing rates between patients with EC%80 and 50-80% EC resulted statistically significant (p = 0.02, odds ratio = 12.25). Relapsing rates between patients on surveillance and those who underwent RLND was next to be significant (p = 0.05, odds ratio 3.68).EC%80 is a prognostic risk factor for disease relapse in patients with clinical stage 1 NSGCT who are selected in a high risk group requiring RPLND or neoadjuvant chemotherapy as therapeutical option.

Aims and background Combined 5-fluorouracil (5FU) and folinic acid (FA) is the first-line treatment of metastatic colorectal cancer. The aims of this study were to individualize the dose of 5FU in a weekly schedule in which the maximum tolerated dose of 5FU is administered to each patient, and to evaluate the impact of increasing 5FU doses on response and survival. Methods Thirty-two patients (30 evaluable for response) with metastatic colorectal cancer were treated with weekly intravenous doses of FA 150 mg/m2 and a fast infusion of 5FU, at an initial dose of 600 mg/m2 which was increased by 60 mg/m2 every week until the appearance of a side effect, in order to determine the maximum tolerated dose for the patient. Results We obtained 11 objective responses (36.7%, median survival 22 months) and 15 disease stabilizations (50%, median survival 15 months); there were four cases of progressive disease (13.3%, median survival 4 months). The overall survival was 15 months. Twenty-eight patients (87.5%) tolerated 5FU doses of 720 mg/m2 or more. Conclusions Weekly 5FU with high-dose FA modulation can be individualized by dose escalation. A 5FU dose of 720 mg/m2 per week seems to be critical, as higher doses are no more effective and lead to severe side effects. This schedule gives good results in terms of response, even though the complete response rate remains low.

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

GISCAD was established in July 1990, following the positive experience of the Medical Therapy Group of FONCAD (Italian Task Force against Digestive Tract Cancer).

Caring for a patient implies performing technical interventions and caring for the whole person, recognising his/her personal life, habits, family, wills. The working experience of an intensive care unit of Bellinzona is described: the theoretical framework that led the health team to start this new approach to intensive care patients and its translation in everyday practice. Verbal and non verbal communication skills (with the patient and the team) are pivotal in this approach; relatives are considered partners in the care of the patient and an essential element of the caring environment. Nurses identified meaningful data (soft data) related to living experience of the patient, to the interaction with the healing environment, his/her patterns of communication, and their use in the intensive care unit is described.

We report and immunohistochemically document the first (to the best of our knowledge) case of malignancy in which an intraductal carcinoma resembling apocrine breast cancer arose within a papillary hidradenoma of the vulva. Papillary hidradenoma is generally thought to originate from apocrine sweat glands, but a derivation from milk line remnants of the vulva should also be considered. Immunoreactivities for low- and high-molecular-weight cytokeratins, alpha-smooth-muscle-specific actin, carcinoembryonic antigen, S100 protein, and gross cytic disease fluid protein 15, an antigen of apocrine differentiation, show features that resemble those of an intraductal apocrine breast cancer. Positivity for gross cystic disease fluid protein 15 as well as the presence of estrogen and progesterone receptors suggest that tumor cells are controlled by ovarian steroid hormones. To our knowledge, no cases of malignancy arising from a papillary hidradenoma have been proved to date. Therefore, we also discuss previously reported cases of putative cancers that have developed in papillary hidradenomas. In the case presented herein, a local excision with a narrow rim of surrounding tissue was performed, and the patient was alive and well, without signs of recurrence, after 2 years of follow-up.

Summary In a multicentre Phase III trial, 182 patients were randomized to either folinic acid (FA) (200 mg/sqm i.v. × 5 days) + 5-fluorouracil (5-FU) (400 mg/sqm i.v. in 15' × 5 days) every 4 weeks (Arm A), or to 5-FU one at the same dosage (Arm B). Response rates were 20.6% (Arm A) and 10% (Arm B) with a significant (p = 0.046) advantage for FA + 5-FU. Median time to progression (6 and 6 months) and overall survival (11.5 and 11 months) were similar in the 2 groups of patients, while neither treatment was effective in reducing pain or improving performance status. Univariate analysis showed that no prognostic factors other than treatment influenced response, although survival was affected by the number and site of metastases, performance status, and the presence and degree of pain. Toxicity was acceptable and lower in comparison with other Phase II-III trials, with no significant difference between the 2 arms. However, in individual patients, grade 3-4 side effects (mainly stomatitis and diafrrhoea) were observed, particularly in patients receiving FA: this led to interruption of the treatment in 7 cases. The superiority, in terms of objective response, of FA + 5-FU over 5-FU alone would seem to justify a large-scale evaluation of this combination in the adjuvant setting. Further improvements in relation to advanced disease (i.e, modifications to the schedule and/or introduction of other modulators) are warranted.