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Tubular carcinoma of the breast: association with multicentricity, bilaterality, and family history of mammary carcinoma.

Seventeen tubular carcinomas occurred among 211 consecutive mastectomies (7.6%). The relative frequencies of multicentric involvement in the ipsilateral breast (56%), history of bilateral mammary cancer (38%) (P less than .01), and family history of mammary cancer in a first-degree relative (40%) (P less than .05) were all significantly greater in patients with tubular carcinomas than among patients with other carcinomas studied in a review of serial subgross examined mastectomy specimens. Patients with tubular carcinomas also tended to be somewhat younger (56 vs. 59 years) than those with other forms of mammary cancer. These features suggest that tubular carcinoma may be a histologic marker for a subpopulation of patients with mammary carcinomas strongly associated with multicentricity, bilaterality, and familial history of mammary carcinoma.

Adult↗

The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for pre- and post-menopausal node-positive breast cancer patients in a Belgian multicentric trial: a study of consistency in relative dose intensity (RDI) and cumulative doses across institutions.

BACKGROUND: Classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) including oral cyclophosphamide is still considered an important adjuvant chemotherapy regimen in patients with early breast cancer (BC). Concern has been raised regarding the feasibility of this regimen, especially in postmenopausal patients. PATIENTS AND METHODS: 254 pre- and post-menopausal node-positive BC patients aged < or = 70 years received six cycles of CMF in the context of a Belgian multicentric phase III trial of adjuvant chemotherapy. CMF dose and schedule were as follows: cyclophosphamide 100 mg/m2 p.o. on days 1 to 14, methotrexate 40 mg/m2 intravenously (i.v.) on days 1 and 8, 5-fluorouracil 600 mg/ml i.v. on days 1 and 8; cycles q. 28 days. The relative dose intensity (RDI) was calculated as the ratio between the delivered DI and the planned DI. We also analysed the RDI in two subgroups of patients with age > or = 50 years or < 50 years. RESULTS: Overall, the percentage of patients ending the six cycles of the planned CMF regimen was 90%. The mean RDI achieved in the population of 254 patients was 90% (range 8% to 129%). The subgroup analysis of patients aged > or = 50 years and < 50 years showed that 81% and 76% of patients, respectively, received > or = 80% of the planned chemotherapy dose intensity (P = 0.33). No statistically significant difference was found between the percentage of patients who received a RDI < 80% and the participating institutions (P = 0.50). CONCLUSIONS: The classical CMF regimen was a feasible regimen in the context of a multicentric trial, in which academic institutions as well as community hospitals participated. No substantial differences in RDI and cumulative doses were found in relation to a patient's age and the participating institution.

Adult↗

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

Activities of Daily Living↗

Retrospective multicentre study on mechanical and enzymatic preparation of fresh and cryopreserved testicular biopsies.

BACKGROUND: Isolation of sperm suitable for ICSI from fresh or frozen-thawed testicular sperm extraction (TESE) can be facilitated by mechanical or enzymatic processing of the samples. METHODS: A retrospective multicentre study was initiated to compare these two approaches. Eleven German centres provided data on their TESE cycles performed during the period 1996/1997. Quality of retrieved sperm, fertilization rates of injected oocytes, embryo quality, resulting pregnancy rates and evolution of pregnancies were evaluated. RESULTS: The percentage of cycles with at least some motile sperm available for injection was higher after mechanical preparation. Independent of the preparation method, fertilization rates were higher for motile compared with immotile sperm or elongated spermatids in all groups and in general higher for cryopreserved versus fresh samples. Embryo quality was significantly better after injection of motile sperm for all treatments and in particular after enzymatic versus mechanical processing of biopsies. Pregnancy rates were identical for embryos derived from sperm prepared mechanically or enzymatically from fresh or cryopreserved testicular samples. The abortion rate (32/172, 18.6%) and the rate of multiple implantations (32/140, 22.9%) were not different from results reported in the literature for ICSI using ejaculated sperm. CONCLUSION: In this retrospective multicentre study, no unequivocal advantage of one over the other preparation method could be identified in 839 ICSI cycles using testicular sperm from 549 patients.

Abortion, Spontaneous↗

Conservative treatment in epithelial ovarian cancer: results of a multicentre study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer) and SFOG (Société Francaise d'Oncologie Gynécologique).

BACKGROUND: Results of conservative management of epithelial ovarian cancer (EOC) remain controversial in the literature. The aim of this study was to assess the clinical outcomes and fertility following fertility-sparing surgical management of EOC in a retrospective multicentre study. METHODS: A multicentre retrospective study was performed by members of two French groups. Six inclusion criteria were defined: (i) Histological review by the same pathologist; (ii) age < or =40 years; (iii) conservative management; (iv) complete peritoneal staging; (v) delivery of a platinum-based chemotherapy in stage > or = IC; and (vi) follow-up >1 year. RESULTS: Thirty-four patients fulfilled the inclusion criteria: 30 had stage IA disease; three had stage IC and one had stage IIA. Eleven patients had recurrence: 10 patients had invasive disease and one had borderline recurrence. Among 10 patients with invasive recurrence, initial stage and grade were: stage IA G1, n = 1; stage IA G2, n = 4; stage IA G3, n = 1; and stage> or = IC, n = 4. All patients with stage > IA had recurrence. Ten pregnancies were observed in nine patients. CONCLUSION: Conservative surgery for patients with EOC could be considered in young patients with stage IA G1 disease. This procedure should not be performed in patients with FIGO stage > IA.

Adolescent↗

Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council.

The 1948 report of the British Medical Research Council's randomized trial of streptomycin for pulmonary tuberculosis is widely regarded as marking the beginning of the modern history of controlled clinical trials. Four years earlier, however, a methodologically sophisticated multicentre trial conducted under the aegis of the Medical Research Council was reported, which assessed the effects of the antibiotic patulin on the course of common colds. Philip D'Arcy Hart and Joan Faulkner (later Joan Doll) were the secretary and assistant secretary, respectively, to the committee overseeing the trial, and they clearly recognized the importance of preventing foreknowledge of allocations from those admitting patients to the study. To do this and to 'muddle people up', they and Ruth D'Arcy Hart devised a scheme involving the use of two patulin groups and two placebo groups, allocating patients to one of these four groups using strict rotation. Philip D'Arcy Hart believes that this study has been overshadowed by the celebrated streptomycin trial (for which he was also secretary to the oversight committee) because no beneficial effect of patulin was detected, and because the report of the streptomycin trial referred to the use of random sampling numbers to generate the allocation schedule. This article makes clear why we agree with Philip D'Arcy Hart that the 1944 patulin trial deserves wider recognition as the first well controlled, multicentre clinical trial to have been conducted under the aegis of the British Medical Research Council. This status is reflected in the International Journal of Epidemiology's reproduction of the full text of the trial report in this issue of the journal.

Common Cold↗

Re-evaluation and modification of the Stuivenberg Hospital Acute Renal Failure (SHARF) scoring system for the prognosis of acute renal failure: an independent multicentre, prospective study.

BACKGROUND: A prognostic scoring system for hospital mortality in acute renal failure (Stuivenberg Hospital Acute Renal Failure, SHARF score) was developed in a single-centre study. The scoring system consists of two scores, for the time of diagnosis of acute renal failure (ARF) and for 48 h later, each originally based on four parameters (age, serum albumin, prothrombin time and heart failure). The scoring system was now tested and adapted in a prospective study. METHODS: The study involved eight intensive care units. We studied 293 consecutive patients with ARF in 6 months. Their mortality was 50.5%. The causes of ARF were medical in 184 (63%) patients and surgical in 108 (37%). In the latter group, 74 (69%) patients underwent cardiac and 19 (18%) vascular surgery. RESULTS: As the performance of the original SHARF scores was much lower in the multicentre study than in the original single-centre study, we re-analysed the multicentre data to customize the original model for the population studied. The independent variables were the score developed in the original study plus all additonal parameters that were significant on univariate analysis. The new multivariate analysis revealed an additional subset of three parameters for inclusion in the model (serum bilirubin, sepsis and hypotension). For the modified SHARF II score, r(2) was 0.27 at 0 and 0.33 at 48 h, respectively, the receiver operating characteristic (ROC) values were 0.82 and 0.83, and the Hosmer-Lemeshow goodness-of-fit P values were 0.19 and 0.05. CONCLUSION: After customizing and by using two scoring moments, this prediction model for hospital mortality in ARF is useful in different settings for comparing groups of patients and centres, quality assessment and clinical trials. We do not recommend its use for individual patient prognosis.

Acute Kidney Injury↗

A case of glomeruloid hemangioma associated with multicentric Castleman's disease.

Glomeruloid hemangioma is a term that was coined J.K.C. Chan and colleagues in 1990 because the condition is histopathologically similar to renal glomeruli. In the three cases described to date, there have been signs of POEMS syndrome of multicentric Castleman's disease. We present the case of a 44-year-old Korean woman who developed glomeruloid hemangioma in association with multicentric Castleman's disease and some features of POEMS syndrome. It is interesting that in this patient, the first biopsy specimen revealed an immature vascular tumor that could not be precisely classified and the second indicated glomeruloid hemangioma. The present case may lend support to the suggestion that in POEMS disease, some types of vascular proliferations develop in response to angiogenic stimuli that show a spectrum of histopathologic features, and glomeruloid hemangioma is one of the reactive vascular proliferations. We believe that the primitive vascular tumor seen in the first biopsy specimen may be the most immature stage of this spectrum.

Adult↗

Multicentric Castleman's disease and Kaposi's sarcoma.

This report describes two cases of multicentric Castleman's disease associated with Kaposi's sarcoma, and reviews the literature. With the recent delineation of a multicentric variant, Castleman's disease has evolved as a disease entity with a wide clinical spectrum ranging from localized, reversible disease as originally described by Castleman et al., to a generalized disease that is rapidly progressive and fatal. The latter represents the most severe form of the disease in which the associated immune derangement predisposes the patients to infections and Kaposi's sarcoma.

Aged↗

Musculoskeletal features of disorders of lipid metabolism and multicentric reticulohistiocytosis.

PURPOSE OF REVIEW: Musculoskeletal features of hyperlipidemia are well known, although rarely encountered by rheumatologists. New data have been collected on the beneficial and adverse effects of lipid-lowering drugs, which are of interest to rheumatologists. Multicentric reticulohistiocytosis is a rare systemic disorder of which joint involvement is an important and frequent feature. Recent advances in its pathophysiology and management have been made. RECENT FINDINGS: Little has been added to the knowledge about the musculoskeletal features of hyperlipidemia in the recent literature. In contrast, the interest in fenofibrate for treating hyperuricemia in patients with lipid disorders or in those intolerant of allopurinol has been further supported. Muscle toxicity of statins continue to retain attention, and the ability of these drugs to induce low-grade myopathy, without increasing serum creatine kinase, has been defended. Multicentric reticulohistiocytosis has been the subject of a number of articles, including reports on the efficacy of cyclosporine and of etanercept in one patient each. SUMMARY: Several issues of therapeutic importance are discussed in this brief review.

Fenofibrate↗

Multicentric chondrosarcomas.

Multicentric chondrosarcomas, other than those from mesenchymal chondroma, are rare and difficult to differentiate from metastatic disease. Eight new patients with multicentric chondrosarcomas are reported. Five patients had chondrosarcomas that were monomelic, 3 had disseminated chondrosarcomas, 3 had synchronous involvement, and 5 had metachronous involvement; 1 patient had Ollier's disease. A bimodal age distribution was apparent: 4 patients were between 62 and 76 years old, and the remaining 4 were between 16 and 33 years old. Average duration of followup was 6 years, 4 months. Each of the patients with synchronous chondrosarcomas had single bone lower extremity involvement and presented with symptoms occurring at only 1 of the 2 sites of tumor. Each of the 5 patients with metachronous chondrosarcomas experienced involvement of a different bone when the second tumor presented. Only 1 of these metachronous chondrosarcomas was limited to the lower extremity. The second tumor occurred in all patients after excellent control of the primary tumor by wide excision. The average duration between diagnosis of the 2 tumors was 4 years, 4 months (range, 8 months-12 years, 9 months). Patients who had nonmonomelic malignancies must be viewed with a considerably more guarded prognosis than those who had monomelic chondrosarcoma because each of the 2 deaths resulting from progressive disease occurred among the 3 patients with nonmonomelic chondrosarcoma. The nonmonomelic malignancies may represent metastatic chondrosarcoma with a rare predilection to bony involvement. Monomelic chondrosarcoma simply may represent lesions analogous to the skip lesions observed in osteosarcoma.

Adolescent↗

Human papillomavirus infection of the lower female genital tract: association with multicentric neoplasia.

Fifty-four patients with multiple condylomatous lesions and/or multicentric neoplasia were identified in a consecutive series of 2,627 colposcopic examinations (2%). Forty-one percent presented with condylomata only and 57% exhibited associated intraepithelial or invasive neoplasia in at least one site. Only one patient was found to have multicentric neoplasia with no condylomatous features. There was a significant increase in mean age between patients presenting with multiple condylomatous lesions and those who had intraepithelial neoplasia as well. An association with pregnancy was found in 17% of the cases, and with renal transplant in 5%. Virus particles compatible with human papillomavirus were found in 62% of the cases examined. Evidence for a causative role in the development of neoplasia of the lower female genital tract is considered.

Adolescent↗

Synchronous multicentric development of hepatocellular carcinoma.

Recently, the multicentric origin of hepatocellular carcinoma (HCC) has been recognized, but its clinical importance has still not yet been clarified. The histological characteristics of small hyperechoic HCCs coexisting in 44 consecutively resected Japanese patients whose main HCCs were < 5.0 cm in size were studied. Twelve small hyperechoic HCCs were found and classified into the following two groups: eight nodules in seven patients (15.9%) were early-stage HCC, and four nodules in four patients (9.1%) were more advanced HCC. Thus, early-stage HCC comprised 66.7% of the small echogenic HCCs. Eight HCCs detected as small hyperechoic lesions (found in 15.9% of the patients) showed varying degrees of fatty change yet proved to be well differentiated and retained the preexisting liver structure of either associated liver cirrhosis or chronic hepatitis. Moreover, the histologic characteristics of the eight early-stage HCCs were different from those of the main HCCs. In conclusion, approximately 15% of HCCs in Japanese patients may have a synchronous multicentric origin, and small hyperechoic lesions should be carefully evaluated. However, in the United States or other areas where the occurrence of fatty liver is common, that advice for small hyperechoic lesions may be overly cautious.

Adult↗

Multicentric pleomorphic xanthoastrocytomas: case report.

We report the case of a 22-year-old woman who developed multicentric pleomorphic xanthoastrocytomas (PXAs) in the cerebral hemisphere. She underwent a first operation for a PXA in the right parietal lobe at the age of 7 years and a second operation at the age of 15 years in the right frontal lobe, remote from the previous tumor site. At age 22 years, she was found to have a tumor, which was a newly formed PXA, in the left occipital lobe. There was no recurrent tumor in the right frontal lobe. Clinical and pathological aspects of multicentric PXAs are reviewed and discussed.

Adolescent↗

Multicentric Castleman's disease: imaging findings.

Multicentric Castleman's disease is an unusual lymphoproliferative lesion typically associated with systemic manifestations and specific histopathology. We describe two cases of pathologically proven multicentric Castleman's disease along with radiographic and ultrasonographic findings.

Adult↗

Evaluation of a commercial serological kit for detection of salivary immunoglobulin G to Helicobacter pylori: a multicentre study.

OBJECTIVE: To evaluate the usefulness of a commercial serological enzyme immunoassay (EIA) for detecting salivary immunoglobulin (Ig) G to Helicobacter pylori. DESIGN: Prospective, multicentre study. SETTING: The study was conducted at 11 gastroenterology hospital centres throughout Italy. PARTICIPANTS AND INTERVENTIONS: Two hundred and thirteen dyspeptic patients underwent gastroscopy with antral biopsies. At each centre, two of the following three tests for H. pylori diagnosis were performed: urease quick test, histology, and 13C-urea breath test. Samples of unstimulated saliva and venous blood were collected from each patient. Salivary and serum H. pylori IgG were determined with the EIA Helori-test IgG (Eurospital, Trieste, Italy). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and accuracy of the salivary and serum EIAs. RESULTS: By using a receiver operating characteristic curve, salivary EIA yielded 81% (95% confidence interval 73-87%) sensitivity, 73% (62-83%) specificity, 84% (76-90%) positive predictive value, 69% (58-79%) negative predictive value, and 78% (72-84%) accuracy. At the cut-off suggested by the manufacturer, serum EIA had 90% (84-95%) sensitivity, 78% (67-86%) specificity, 88% (81-93%) positive predictive value, 82% (71-90%) negative predictive value, and 86% (81-91%) accuracy. CONCLUSION: In this large multicentre study, detection of salivary H. pylori IgG with a commercial serological EIA was a fairly accurate diagnostic method. Data confirm that saliva testing does not compare favourably with serology in the assessment of H. pylori status.

Adolescent↗

Metachronous multicentric giant cell tumor: a case report and literature review.

Metachronous multicentric giant cell tumors of bone are rare. The case of a 47-year-old woman who had a giant cell tumor of the ilium develop 24 years after resection of a giant cell tumor of the proximal tibia is reported. The initial and current surgical approaches for this patient are described. A literature review is presented to show that this patient had the longest disease-free interval documented for a patient with metachronous multicentric giant cell tumors.

Adult↗

Detecting postsurgical recurrent hepatocellular carcinoma with multiphasic helical computed tomography: intrahepatic metastasis or multicentric occurrence?

OBJECTIVE: The aim of this study was to assess the computed tomography (CT) patterns of postoperative recurrent hepatocellular carcinoma (HCC). METHODS: Of 84 patients with histologically proven HCC by hepatectomies, multiphasic helical CT demonstrated 54 HCC lesions of intrahepatic recurrence in 31 (37%) patients. The initial and final appearances of HCC on hepatic arterial phase images were retrospectively determined by the serial CT scans, which were compared with appearances of primary HCC. RESULTS: The initial appearances of 54 recurrent HCCs were identical to the appearances of primary HCC in 41 (76%) lesions. Serial changes from the initial appearance to the final appearance of recurrent HCC were observed in 10 (42%) of 24 lesions. The 13 discordant lesions and the 10 lesions with altered lesion vascularity in our series implied that at least 43% were of multicentric occurrence. CONCLUSION: More than 40% of postoperative recurrent HCCs show intranodular hemodynamic changes. The incompatibility between CT findings of primary and recurrent HCCs implies that these tumors contain nodules of multicentric occurrence.

Adult↗