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.

Biologic therapies for plaque type psoriasis in patients with previous malignant cancer: long-term safety in a single- center real-life population.

INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.

Increasing doses of 5-fluorouracil and high-dose folinic acid in the treatment of metastatic colorectal cancer.

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.

Follow-up after mastectomy for breast cancer. Observations in 96 patients.

From 1978 to 1982 at the Oncology Unit of the Rho Hospital, we followed 96 women who had been operated for breast cancer. In 22 cases (23%) the first signs of recurrence were changes in the following: physical examination (9), symptoms (7), ESR (3), bone scan (2), alkaline phosphatase (1), chest X-ray (1). An adequate follow-up schedule is based on the following: a) limited examinations causing little disturbance to the patient, easily feasible, sensitive, specific, and of limited cost; b) lead-intervals of various tests set according to the risk of relapse; c) critical periodic review of the series, with constant updating of information in the literature.

Rhabdomyosarcoma presenting as acute hematologic malignancy: case report and review of the literature.

The authors describe a case of undifferentiated rhabdomyosarcoma from unknown primary site, presenting as an acute hematologic malignancy with generalized lymphadenopathy, extensive bone marrow involvement and clinical and laboratory features of disseminated intravascular coagulation. Such a peculiar behaviour is known for rhabdomyosarcoma but is rare and can be a serious diagnostic problem for the clinician and the pathologist. The importance of a large spectrum immunohistochemistry as first diagnostic approach to any undifferentiated small-cell malignant tumor is stressed, together with the knowledge of the different immunoreactivity patterns. Desmin, MS-actin and myoglobin are the most reliable markers of this type of myogenic sarcoma.

Cisplatin-vinorelbine combination chemotherapy in locally advanced non-small cell lung cancer.

AIM: The North Milan Group presents the results of a phase II study on a cisplatin-vinorelbine combination schedule in the treatment of locally advanced non-small cell lung cancer to evaluate its activity and tolerability. METHODS: Seventy-six consecutive patients entered the study. Patients' characteristics were the following: males/females 69/7; median age, 61.4 years (range, 40-73); ECOG performance status, 0-1; 17 stage IIIa and 59 stage IIIb. There were 49 squamous cell carcinomas, 20 adenocarcinomas, and 7 large cell carcinomas. All patients had not been previously treated and showed measureable disease. Treatment consisted of vinorelbine, 25 mg/m2 on days 1 and 8, plus cisplatin, 80 mg/m2 on day 1, administered intravenously every 21 days for three standard courses. RESULTS: Seventy-four patients were evaluable for response. Objective responses were documented in 42/74 patients with an overall response rate (CR+PR) of 56.7%; 18/74 patients (24.3%) showed stable disease and the remaining 14/74 (18.9%) went into progression. Twelve patients (16.2%) were suitable for a subsequent surgery. The median duration of response was 13.3 months. Survival time ranged from 4 to 36 months; it was 14.6 months for PR patients, 8.6 months for NC and 5 months for PD. Mean survival time is presently 12.85 months (SE, 1.2 months). Toxicity evaluated on 222 cycles administered was acceptable, and it was necessary to use G-CSF or delay the treatment because of severe leukopenia in only a few cases. CONCLUSIONS: The regimen is active and safe: the slight survival increase is likely due to the small amenability to surgery achieved (16.2%). However, our results are fully comparable to others obtained with vinorelbine in two/three drug combination chemotherapy regimens.

Diagnosis and follow-up of minor cervical trauma.

In order to evaluate sensitivity, specificity and accuracy of radiographic findings, 1347 patients with minor cervical injury underwent clinical, orthopaedic, neurosurgical examination, and were classified as monosymptomatic (only cervical pain) or polysymptomatic (cervical pain plus additional symptoms). X-rays were taken in anteroposterior, lateral and open-mouth views; additional views if necessary. X-ray outcome was normal in 69.8% of monosymptomatic patients and there were no fractures. In 45.1% of polysymptomatic patients, outcome was normal, but there were seven fractures. Computed tomography/magnetic resonance (CT/MR) was performed in patients with documented injury and/or strong persistent symptoms. X-ray follow-up at 4-6 weeks included flexion-extension examination. Elevated statistical radiographic values were reached. All patients with minor cervical trauma should undergo clinical, neurosurgical and three-view radiographic follow-up. A simplified algorithm could lead to substantial savings and decrease patients' exposure to radiation.

[Stage classification of chronic lymphatic leukemia. A retrospective analysis of 263 cases]. / La classificazione in stadi della leucemia linfatica cronica. Analisi retrospettiva di 263 casi.

We have analyzed 263 consecutive patients with chronic-lymphocytic leukemia. They all have been studied according to five different staging systems respectively proposed by Rai (1975), Binet (1977), Binet again (1981), Baccarini (1982) and Rozman (1984). All these procedures proved to be effective, because they divided our cases in groups with significant differences in survival time. The paper displays features and usefulness of each staging system.

[Report of a case of allergic granulomatous vasculitis (Churg-Strauss syndrome)]. / Osservazioni su di un caso di vasculite granulomatosa allergica (sindrome di Churg-Strauss).

A 35 year female with a previous history of asthma came to our observation about 10 months ago. She was dyspneic, showed small nodules (2 to 5 mm) in arms, hands and legs and had radiological evidence of pulmonary granulomatosis and pleural effusion. Diagnosis was made by means of cutaneous biopsy showing a necrotic granulomatous vasculitic lesions with eosinophilic infiltration and giant cells, consistent with allergic granulomatosis of Churg-Strauss syndrome. Steroid therapy alone (prednisone 1 mg/kg/die) led to a rapid and complete clinical and humoral remission. The patient is still doing an alternate day prednisone therapy (15 mg) and is well after a 10 months follow-up.

In search of superior hospital management: a comparative analysis.

In post-socialist Europe, the emergence of a consumer-oriented change in health care management will take time, given the outdated framework in which centralized systems stagnated over the years. Based on personal interviews in two European countries, this study compares the experience of hospital unit general managers (HUGMs) in England and hospital medical superintendents (HMSs) in post-socialist Malta.

Determinant of hospital marketing effectiveness: the importance of conflict.

As hospitals and health organizations become more marketing oriented, and more interwoven into the environment, the more they face internal resistance. The careful handling of conflict not only helps the health care marketer to overcome hostility and antagonism, but also rewards the health care institution with the "productivity of confrontation."

Clinical experience with covered wallstents for biliary malignancies: 23-month follow-Up.

PURPOSE: To evaluate the effectiveness of partially covered metallic Wallstents to prevent tumoral ingrowth in patients with neoplastic obstruction of the biliary tract. METHODS: Twenty-one patients with malignant obstructive jaundice have been treated with Wallstents partially covered with a polyurethane polymer. In total, 36 covered stents (8 and 10 mm in diameter, 70 and 90 mm long) were deployed. All the stents were free from covering at both ends. RESULTS: Jaundice was successfully treated in 100% of cases. There were no problems related to the releasing system during stent positioning, no major complications, and no incompatibility reactions to the materials composing the endoprostheses. At 23-month follow-up, 6 patients are still alive and 15 are dead; of these 15 patients, 11 died in the first 6 months and the last 4 died between 6 and 23 months. Seven patients had an obstructed stent; in four of these, cholangioscopy showed the presence of tumoral ingrowth and in one it showed necrotic tissue with biliary pigments and inflammatory cells. No biopsy specimen was obtained in the remaining two patients with stent obstruction. The follow-up, ranging from 7 to 23 months, showed a primary patency of 46.8% and 24.6% and an assisted patency of 66.3% and 59% at 6 months and 23 months, respectively. CONCLUSIONS: Covered metallic stents are effective and may produce improved survival in patients with malignant biliary obstruction (27. 8% at 23 months). Stent patency, however, is similar to that of uncovered stents. Modifications in the design of the covering membrane may reduce stent obstruction resulting from disruption of the plastic covering.

A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma.

BACKGROUND: The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS: Between September 1986 and July 1992, 218 patients from 12 Centers in Lombardy entered this study. The inclusion criteria were: a histological diagnosis of intermediate or diffuse large cell (DLC) NHL and no previous radio-chemotherapy. The patients in stages IA and IIA (both intermediate and DLC) received four CEOP courses followed by local/regional radiotherapy; those with intermediate NHL in stages IB, IIB, III A and B and IV A and B received six CEOP courses and, if they achieved CR, three further courses as consolidation. RESULTS: Among the 160 evaluable patients, CR was observed in 90% of the subjects with DLC-NHL (stages IA and IIA) and in 59% of those with intermediate-grade NHL (all clinical stages). If the clinical stages are considered separately, the CR rates were 92% for stages IA, IIA and 53% for stages IB, IIB, III A and B, IV A and B. Relapses occurred in 20% of the patients treated with four CEOP courses plus radiotherapy and in 31% of those who received nine CEOP courses because of the advanced stage of their disease. As of May 1994, the median follow-up was 42 months. If all of the patients are considered together, the 7-year overall survival (OS) probability was 64% and the 7-year disease-free survival (DFS) probability 67%. In comparison with stages III/IV, the patients in stages I-II had better DFS (7-year chance 77% vs 56%, p < 0.03). Hematological toxicity was acceptable, and a delay in the administration of CEOP chemotherapy was required in only three patients. No life-threatening infections were recorded. CONCLUSIONS: Our cooperative study of the use of the CEOP combination in NHL patients shows that response rates and the length of DFS are equal to the best results obtained with CHOP and more intensive programs, although further confirmation must be provided by means of a longer follow-up and a more careful analysis of prognostic factors according to the recently proposed international index. In our experience, an EPI dose of 90 mg/m2 has negligible toxicity (particularly on bone marrow), even in elderly patients. These findings are interesting since it is well known that myelotoxicity is the principal limiting factor for the majority of anthracycline-containing regimens used in the treatment of potentially curable NHL.

TEM/CBED determination of strain in silicon-based submicrometric electronic devices

The convergent beam electron diffraction technique (CBED) of the transmission electron microscopy (TEM) has been employed to determine the strain distribution along a cutline parallel to the padoxide/Si interface in a 0.80 micron wide recessed-LOCOS structure. The values of the components of the strain tensor so obtained have been compared with those computed by two simulator codes. It has been found that both the LOCOS morphology and the strain distribution deduced from TEM images and TEM/CBED patterns, respectively, were in agreement with the simulation results, if some oxidation-related parameters were modified.

EBVD and alternating MOPP/EBVD with or without localized field radiotherapy in advanced or unfavorably presenting Hodgkin's disease.

PATIENTS AND METHODS: Ninety-five patients with previously untreated, advanced or unfavorably presenting Hodgkin's disease were recruited in ten centers. Twenty-five patients with stage II-A-bulky disease received four courses of EBVD (epirubicin, bleomycin, vinblastine, dacarbazine) plus involved field radiotherapy (Group 1); 24 patients in stage I-B, II-B and III-A received 6 courses of EBVD (11 of them also received radiotherapy on bulky localizations (Group 2); 46 patients in stage III-AS > or = 3 nodes, III-B and IV received MOPP/EBVD 4 + 4 courses (Group 3). RESULTS: Eighty patients (84%) achieved CR, eight patients (8%) a PR, five patients did not respond and two progressed during therapy. CRs were achieved by 23/25 patients (92%) in Group 1, 21/24 (87%) in Group 2 and 36/46 (78%) in Group 3. The mean duration of follow-up was 33.3 months (range 5-69). There were three deaths from directly treatment-related causes. Twelve patients suffered chronic toxicity, including six who suffered lung toxicity and two who developed secondary myelodysplasia. CONCLUSIONS: The results achieved in this co-operative study are similar to those reported by most single-Institution trials and those with adriamycin-containing regimens. Long-term toxicity deserves careful consideration.