Juvenile idiopathic arthritis-associated uveitis: a retrospective analysis from a centre of South Italy.

PURPOSE: To investigate the clinical and laboratory characteristics of the children affected by juvenile idiopathic arthritis (JIA) who developed uveitis. METHODS: In this retrospective study, we have examined data of 109 patients aged from 3 to 16 years, affected by JIA and followed at Paediatrics Rheumatology Clinic and Ophthalmology Clinic of University Hospital of Messina in the period from 2007 to 2017. The main outcome measures were clinical and laboratory findings related to JIA and ocular involvement. The prevalence of ocular signs and symptoms was determined and correlated with age. RESULTS: Twenty-one (19.3%) subjects developed uveitis. Two different peaks of age with ocular involvement were registered. The first occurred between 4 and 6 years and the second between 10 and 12 years. All subjects in the first group resulted to be female, presented oligoarticular arthritis and chronic anterior uveitis. In the second group, the 84% of patients were male with different types of JIA and acute anterior uveitis. The prevalence of ocular complications was higher in the first group. CONCLUSIONS: Two peaks of age emerged and were characterized by different clinical outcomes of arthritis and ocular involvement. The first occurred between 4 and 6 years and interested females affected by oligoarticular JIA who develop chronic anterior uveitis. The second appeared at 10-12 years and interested older males affected by different types of JIA with acute anterior uveitis. Early diagnosis and cooperation between paediatric rheumatologist and ophthalmologist are of great importance in the proper management of JIA children with uveitis.

A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

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. CLINICALTRIALSGOV: NCT02409472.

Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly patients.

This study involved 25 elderly (> 65 years old) patients (pts) with unresectable non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy. The diagnosis of NSCLC was histologically or cytologically documented, and all of them had measurable or evaluable disease. The median age of the patients was 71 (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine weekly or bi-weekly depending on the results of blood tests. The treatment continued until disease progression or tolerance. No complete response was achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%) stable disease (SD) with an improvement in symptoms, such as cough and/or pain, and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients. The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment in 1 patient. The median survival time was 10 months (lower quartile 5 months, upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be considered a rational choice in elderly pts with advanced NSCLC who are not suitable for aggressive polychemotherapy, with the aim of improving their quality of life in terms of symptoms and outpatient treatment.

Paclitaxel efficacy and tolerability in second-line treatment of refractory and relapsed ovarian cancer patients.

Nineteen patients with recurrent or refractory ovarian carcinoma after a first-line platinum-based chemotherapy were treated with a 3-hour i.v. infusion of paclitaxel 175 mg/m2 every 3 weeks from November 1992 to October 1996. The major hematologic toxicity was neutropenia (63.2%). No febrile neutropenia was observed. Other hematologic effects were leukopenia (47.4%) and anemia (47.4%). The main non-hematologic toxicities were as follows: neuropathy (52.6%), nausea and vomiting (36.8%), myalgia (36.8%), cardiac toxicity (15.8%) and mucositis (10.5%). Alopecia was observed in the majority of cases. The overall response rate was 47.4%, with 5 (26.3%) complete responses (CRs) and 4 (21.1%) partial responses (PRs). The median duration of response was 7 months (range: 3-19), with a median follow-up of 17 months (range: 3-61). Quality of life of responding patients was good. Our results confirm that paclitaxel as second-line therapy in relapsed and refractory ovarian cancer patients is an acceptable treatment with a good safety profile, and can be safely administered at the dose of 175 mg/m2. In our study paclitaxel was more active in relapsed than in refractory patients. Consequently, further studies are needed to identify more effective drugs for the refractory subset.

Etoposide, doxorubicin and cisplatin (EAP regimen) in advanced gastric cancer.

The treatment of advanced gastric cancer is unsatisfactory. The response rates for single chemotherapy agents: 5-fluorouracil, mitomycin-c, methotrexate, cisplatin, adriamycin, nitrosoureas and etoposide are approximately 10-25% and response duration ranges from 3 to 6 months. Complete responses with single agents are rare. Combination chemotherapy produces higher response rates, but these responses are short. Recently the combination of etoposide, adriamycin and cisplatin (EAP regimen) has been reported to produce results superior to what have been previously reported with other regimens. Twenty-four consecutive patients with locally advanced or metastatic gastric cancer (stage III-IV) were treated between June 1990 and December 1992 with the EAP regimen at our Department. Twenty-two patients were evaluable for response and toxicity. Objective responses were observed in 8 of 22 patients (response rate 36%; 95% confidence interval 17% to 59%). No clinical complete response was found. The median duration of the response was 7 months (range 2 to 22). Myelosuppression represented the primary toxicity associated with the EAP regimen. Grade 4 leukopenia was observed in 4 patients (18%). Grade 3-4 thrombocytopenia was registered in two patients, and grade 3 anemia was detected in 4 patients (18%). The median survival for all patients was 8 months and 12 months for the 8 responding patients. The EAP regimen seems to be an effective chemotherapeutic regimen, but cannot be considered the standard therapy for patients with locally advanced or metastatic gastric cancer, because of the high incidence of moderate to severe myelotoxicity and a response rate and duration of survival similar, but not superior, to those obtained using a less toxic schedule.

[Role of colposcopy in high-grade CIN (CIN II-III)]. / Il ruolo della colposcopia nelle CIN di grado elevato (CIN II-III).

We have considered the colpo-cytologic characteristic of 83 patients with CIN II-III histologic lesions over 900 colposcopic biopsies carried out at our Department from 1990-1992. In particular 38 cases were classified as CIN II of which 23 associated with HPV cytopathic feature, while 45 cases were, classified as CIN III, of which 13 associated with HPV c.f. 29% of CIN II were evident in women under 30 years of age; in this group the age decreased with the presence of HPV. 31% of CIN III were present in women under 35. A good correlation between cytologic and histological analysis on the same patient was observed particularly in CIN with the higher grade. Also a good correlation between colposcopy grading and CIN was observed. In CIN II, grade I images were present, while in CIN III, punctuation and white epithelium were the most common features. Our study shows also the impossibility of distinguishing between the images of simple viral infection and their related CIN morphologic patterns. Colposcopy represents a basic test for the definition of CIN, particularly for those with higher grade, and a complementary test for the definition of the topography of the lesions with the correct choice of the therapeutic treatment.

Combination chemotherapy of carboplatin and gemcitabine against solid tumors: a phase I trial.

BACKGROUND: Some trials have suggested that the combination of gemcitabine and platinum compounds can have a synergistic effect on several solid tumors, but, at present, the data concerning carboplatin-gemcitabine combinations are not sufficient to allow the planning of phase II trials. The present phase I trial was planned to define the maximum tolerated dose and the dose-limiting toxicity of a carboplatin-gemcitabine combination. METHODS: Thirty-two patients with advanced, pretreated solid tumors were treated with carboplatin on day 1 and gemcitabine on days 1, 8, and 15 every 28 days. The starting doses of carboplatin and gemcitabine were 3.5 mg/ml per min (area under the curve; AUC), and 600 mg/m2, respectively. The doses of the two agents were alternately increased to 4, 4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose level, three patients were initially enrolled. If one of them experienced grade IV hematological toxicity or grade III-IV nonhematological toxicity (with the exception of alopecia), an additional three patients were enrolled at the same dose level. If two or more patients experienced grade IV hematological toxicity or grade III-IV non-hematological toxicity (with the exception of alopecia), the maximum tolerated dose was considered to have been reached, and the dose below this was recommended for further studies. All patients were evaluated weekly for toxicity and after every two courses of chemotherapy for response. RESULTS: Dose-limiting toxicity was hematological, and the maximum tolerated doses were 4.5 mg/ml per min for carboplatin and 800 mg/m2 for gemcitabine. The activity of the carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate (7/32), three complete disease regressions, and a median time to progression of 30 weeks. The gemcitabine doses of day 15 or days 8 and 15 were omitted for hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while no courses of chemotherapy were delayed for grade III-IV hematological or nonhematological toxicity. CONCLUSION: The maximum tolerated doses suggested by this trial are lower than those in other similar phase I trials, but they are consistent with those reported by most of the trials investigating gemcitabine either in combination with cisplatin or in heavily pretreated patients. Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8, and 15 every 28 days may represent a promising schedule for further phase II trials.

Role of biological markers in the clinical outcome of colon cancer.

We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease.