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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.

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.

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.

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.

The increased incidence of malignancies associated with AIDS has been the subject of several reports in the North American literature: besides Kaposi’s sarcoma and other tumours, such as squamous carcinoma of the tongue and cloacogenic carcinoma of the anorectum [1–22], malignant lymphomas have been demonstrated to be one of the major problems among the neoplastic complications of AIDS [12–24]. According to the North American experience, non-Hodgkin’s lymphomas in patients with AIDS or AIDS-related clinical conditions present at an advanced stage in which lesions are concentrated in extranodal and often unusual locations, notably the CNS. Disease confined to the lymph nodes is uncommon. These lymphomas are predominantly high-grade B-cell neoplasms classified as immunoblastic and Burkitt’s-like lymphomas. A variety of severe opportunistic infections and Kaposi’s sarcoma affect these patients. At the same time, the association with AIDS is strengthened by the regular demonstration of reversed ratios of helper (T4+) and suppressor (T8+) lymphocytes in the peripheral blood and by the presence of antibodies to human immune deficiency virus (HIV) [22]. The prognosis is dismal: response to chemotherapy does not positively affect median survival. Mortality rates analysed by histological grade are higher than the currently reported rates for comparable patient populations [18].

14572 Background: FOLFOX4 schedule represents the standard treatment for metastatic colorectal cancer in EU, but is characterized by relevant adverse effects like G3–4 neutropenia in 42 % of patients (data from MOSAIC study). Adjustment of chemotherapy delivery schedule to the circadian timing system allows a significative improvement of tolerability. Objective of this multicentric observational study is the evaluation of therapeutic index of a OHP and 5-FU + AF based schedule at the same doses of FOLFOX 4, but administered according to a chronomodulated schedule (FLOX-1). Methods: From November 2005 to December 2006, we treated 41 metastatic colorectal cancer patients (19 male and 22 female, average age 65) with OHP 85 mg/m2/d1q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 PM; 5-FU 1000 mg and AF 100 mg/m2/d1–2q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 AM: a total of 258 cycles (5.5 average for patient) were administered using Melodie infusional programmable system (138 cycles) and CIP preprogrammed disposable system (128 cycles), all in homecare regimen. These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. Results: Overall average dose intensity was 39.1 mg/m2/w for OHP and 907.5 mg/m2/w for 5-FU respectively. No G3-G4 haematological, hepatic and neurological toxicity were observed. ORR (CR+PR) was 41%. No patient has been treated with G-CSF. Conclusions: These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. No significant financial relationships to disclose.

13557 Chronotherapy studies in pretreated CRC cancer pts showed that 6 hrs chronomodulated CPT11 infusion from 2 to 8 a.m., alone or combined with 5FU+AF±OHP, is less toxic than the standard 90 min. infusion, and CPT11-SN38 convertion efficency is improved with an higer objective response rate. Objective of this study was evaluation of CPT11 pharmacokinetics after hepatic i.a. perfusion according to infusion time and circadian patient pattern. To evaluate patient circadian pattern, serum levels of prolactin and cortisol were detected at 2–6, 4 pm and 2–6, 4 -8 pm respectively. CPT11 and SN38 serum levels were detected, according to two different time schedules, following the HPLC method. Every pt received 240 mg/mq i.a. CPT11 perfusion alternating daily with nightly schedule: from NOV04 to FEB05 5 metastatic CRC patients were treated. All pts concluded all programmed cycles. No cycle was delayed due to toxicity. Haematological, hepatic and g.i. G 3–4 (NCI) toxicity were not observed (only neutropenia G1 in the female subject). Circadian organization seems to be progressively lost according to cycle number. At 3rd cycle, cyrcadian levels of cortisol and prolactin are lost in all pts. Kinetic data suggests for a progressive reduction of liver enzymatic capability; this is probably due to cumulative liver drug toxicity: this phenomenon is clearly evidenced in female subject but is also signicative in the male subjects (see Table). These preliminary data show enormous PK/PD interpatient variability and a significative AUC reduction 2nd cycle vs 1st and 3rd vs 2nd; due to this unespected observation we are not able to evaluate cyrcadian oscillation of enzymatic systems: in order to fully understand these data we decided to perform polimorphism assesment for UGT1A1,Carboxil Esterase isoform2 and ABC transporters genes.This analysis will be performed on paraffin included samples for the first 5 pts and on fresh tissue for the next pt set. [Table: see text] No significant financial relationships to disclose.

Attacks of laryngeal edema in patients with hereditary angioedema (HAE) have been successfully treated with the infusion of C1-inhibitor (C1-INH) concentrate. No side effects were observed.

Serum C1 esterase inhibitor was determined in 138 members of 18 italian families with hereditary angioedema by immunochemical and enzymatic assays. On the basis of quantitative and functional findings, the type A of hereditary angioedema was diagnosed in 44 subjects, and the type B in 15. Some technical devices concerning serum sample handling were identified. The influence of heparin, EDTA, and citrate on C1 esterase inhibitor activity of normal plasma was also investigated.

Background: A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b ( 10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. Objective: Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. Design, setting, and participants: Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. Intervention: Patients underwent either radical or partial nephrectomy. Measurements: Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. Results and limitations: In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend < 0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. Conclusions: The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

OBJECTIVES To compare the prognostic accuracy of the Solsona and European Association of Urology (EAU) risk groups in the identification of lymph node involvement in a cohort of patients with squamous cell carcinoma of the penis. METHODS The clinical and pathologic data of 175 patients who had undergone surgery for squamous cell carcinoma of the penis from 1980 to 2002 at 11 urologic centers of northeastern Italy were retrospectively collected. RESULTS According to the EAU risk group, 25 patients were categorized as at low (15.1%), 23 (13.9%) as intermediate, and 118 (71.1%) as high risk of lymph node metastasis. Similarly, using the criteria of the Solsona risk group stratification, 25 (15.1%), 55 (33.1%), and 86 patients (51.8%) were categorized as at low, intermediate, and high risk. At the median follow-up of 26 months, lymph node involvement was observed in 71 (40.6%) of 175 patients. Receiver operating characteristic curve analysis showed that both the EAU risk group (area under the curve = 0.632) and Solsona risk group (area under the curve = 0.697) had a low accuracy for predicting lymph node involvement. Both risk groups were independent predictors of lymph node involvement, as well as the clinical stage of lymph node involvement and the presence of vascular and/or lymphatic embolization. CONCLUSIONS The Solsona and EAU risk groups were both independent predictors of lymph node involvement, although the receiver operating characteristic curve analysis showed that both risk groups had low predictive accuracy.