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PubMed1993

Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma.

It has been reported that multicentricity of pancreatic carcinomas extending beyond the pancreatic duct occur in 15% to 40% of patients. This has been difficult to confirm, however, with currently available histologic techniques. Mutations in the Kirsten (Ki)-ras oncogene, which can be detected frequently in pancreatic carcinomas using the polymerase chain reaction (PCR), may serve as a potential clonal marker of the cancer cells. Fifty-three patients with a histopathologic diagnosis of pancreatic carcinoma were selected for the determination of certain Ki-ras mutations through PCR. The authors identified mutations in the Ki-ras codon 12 in 46 of 53 tumors. Two of these 46 tumors had two different mutations to aspartic acid (GAT) and to valine (GTT) in Ki-ras codon 12. Another isolate had an additional mutation in Ki-ras codon 13. The detection of different mutations in the same tumor suggests that there may be multicentricity in pancreatic carcinomas and that its frequency may be as low as 6% of the carcinomas. These results imply that total pancreatectomy for eliminating tumor recurrence due to multicentricity may not be warranted.

Adenocarcinoma↗
PubMed2001

Interpreting sexual behaviour data: validity issues in the multicentre study on factors determining the differential spread of HIV in four African cities.

BACKGROUND: The main conclusion of the multicentre study on factors determining the differential spread of HIV in four African cities was that differences in sexual behaviour could not, by themselves, explain the differences in HIV prevalence between the four cities. The present paper examines three potential sources of bias that could invalidate this conclusion: (1) changes in sexual behaviour since the start of the HIV epidemics; (2) bias due to the low response rates of men; and (3) bias in reported sexual behaviour. METHODS: To assess whether there have been any changes in sexual behaviour over time, selected parameters of sexual behaviour were compared between different age groups in the four cities. The maximum likely extent of bias due to non-participation of men in Yaoundé, Kisumu and Ndola was assessed with a simulation exercise, in which records of non-participants were replaced with records of 'low activity men' in Yaoundé and 'high activity men' in Kisumu and Ndola. To assess the validity of the sexual behaviour data, internal validity checks were carried out: comparing biological data on sexually transmitted infections with reports; comparing reports of spouses; and comparing numbers of sex partners reported by men and women. A fourth method consisted of comparing the findings of the multicentre study with an external source, Demographic and Health Surveys (DHS). RESULTS: There were differences in sexual behaviour between the younger and the older age groups in all four cities but there was no evidence of a shift towards safer sexual behaviour in the high HIV prevalence cities. After simulating results for male non-participants in Yaoundé, Kisumu and Ndola, the median lifetime number of sex partners was similar in Yaoundé, Kisumu and Ndola. By testing for various sexually transmitted infections among men and women aged 15-24 years who reported that they had never had sexual intercourse, we could establish that, in all four cities, at least 1-9% of men and 6-18% of women had misreported their sexual activity. The number of non-spousal partners in the past 12 months reported by men was two to three times higher than the number reported by women, as has been found in other studies. The most consistent differences between our survey and the DHS were found in the numbers of non-spousal partners in the past 12 months reported by never-married men and women. In all four cities, participants reported more non-spousal partners in the DHS than in our survey. CONCLUSIONS: In all four cities, we found evidence that men as well as women misreported their sexual behaviour, but overall it seems that under-reporting of sexual activity was not more common or more serious in the two high HIV prevalence cities than in the two low HIV prevalence cities. We believe that the main conclusions of the multicentre study still hold.

Adolescent↗
PubMed2004

Conservative management of hyperplastic and multicentric nephroblastomatosis.

PURPOSE: The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT). MATERIALS AND METHODS: During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions. Children with multiple solid renal masses on imaging were treated with 2-drug chemotherapy until disappearance of the lesions. Stabilization or progression of the lesions despite chemotherapy, as well as heterogeneity of the lesions on imaging, prompted nephron sparing surgery (NSS). RESULTS: Three female infants (12, 13 and 20 months old, respectively) presented with multiple solid renal tumors at imaging. Despite chemotherapy, small and unilateral WT developed in 2 cases of hyperplastic nephroblastomatosis, which was excised. One of these infants subsequently presented with a small contralateral metachronous WT, which was excised. Both infants are disease-free with 2 normal kidneys at followup of 6 and 2 years, respectively. The third infant, who presented with unilateral multicentric WT and unilateral hyperplastic nephroblastomatosis nodules, was successfully treated with preoperative chemotherapy and enucleation of 5 tumors. Subsequently, nephrectomy was performed at another institution because the abnormal kidney outline due to NSS was misinterpreted as a recurrence of WT. She was lost to followup. CONCLUSIONS: Hyperplastic and multicentric nephroblastomatosis is not a rare lesion and is most often associated, either initially or subsequently, with WT. In some infants with multiple solid renal masses on imaging chemotherapy and for developing WT NSS may safely allow maximum sparing of the parenchyma of both kidneys.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Multicentric Castleman's disease in association with a solitary plasmacytoma: a case report.

Multicentric Castleman's disease with aggressive systemic symptomatology is usually associated with the plasma cell variant. We report a case in which the clinical presentation was typical of multicentric Castleman's disease but which was associated with the hyaline vascular subtype histologically. Plasma cells were absent from all biopsies until, at autopsy, a solitary plasmacytoma was found in the vertebral column. This case supports the view that plasma cells are of primary importance in the clinical and pathological manifestations of multicentric Castleman's disease.

Adult↗
PubMed1998

Effect of learning during an anaesthesiological multicentre trial.

BACKGROUND: After the completion of a multicentre study, it was disputed whether becoming acquainted with a novel drug would affect dosing, and how many consecutive patients would be sufficient for this phenomenon. METHODS: A post hoc analysis of the data on 408 patients from a multicentre study on propofol was performed to reveal a possible learning effect. For study purposes, the patients were given consecutive anaesthetic serial numbers per anaesthesiologist. Patients eligible for the study with serial numbers 3-8 (113) were included in the initial group, and numbers 12-17 (89) in the end group. RESULTS: The patients in the end group opened their eyes (4.1 vs. 5.5 min, P < 0.05), gave their date of birth (4.5 vs. 6.3 min, P < 0.005) and walked sooner (27.1 vs. 49.8 min, P < 0.05) than the patients in the initial group. They received a higher dose of propofol at induction (2.37 vs. 2.26 mg kg-1, P < 0.05) and the last additional dose of propofol earlier (3.3 vs. 2.7 min, P < 0.05). CONCLUSION: This study shows that the learning effect can influence the results in a multicentre study. Learning contamination may occur if a novel drug is dosed by clinical judgement, and if the allocation of patients into groups is markedly uneven during the different stages of the study.

Adult↗
PubMed1993

Musculoaponeurotic fibromatosis (extraabdominal desmoid tumor) in a child with idiopathic multicentric osteolysis.

The fibromatoses are a group of benign proliferations of fibrous tissue with clinical behavior ranging from that of truly malignant tumors to that of benign reactive fibrous proliferations. Some of the superficial fibromatoses are fairly common, but the deep ones, also known as desmoid tumors or musculoaponeurotic fibromatoses, are rare. Idiopathic multicentric osteolysis is a rare skeletal disorder of childhood that causes progressive destruction of bones and renal failure. We recently saw a young girl with both extraabdominal musculoaponeurotic fibromatosis and idiopathic multicentric osteolysis. The classification, diagnosis, and treatment of the deep fibromatoses are reviewed, and the possible association between the minor bone changes occasionally reported in musculoaponeurotic fibromatosis and idiopathic multicentric osteolysis is discussed.

Biopsy↗
PubMed1978

Multicentric primary malignant melanomas of the choroid: two separate malignant melanomas of the choroid and two uveal naevi in one eye.

Two completely separate malignant melanomas of the choroid occurred in 1 eye containing 2 additional uveal naevi. Review of the literature disclosed 7 further patients with unilateral multicentric malignant melanomas of the choroid and 11 bilateral multicentric malignant melanomas of the uvea. General aspects of multicentric primary neoplasia are discussed and an interpretation is attempted.

Choroid Neoplasms↗
PubMed1998

Intrathoracic multicentric Castleman disease: CT findings in 12 patients.

PURPOSE: To assess the computed tomographic (CT) findings of intrathoracic involvement in multicentric Castleman disease. MATERIALS AND METHODS: The study comprised 12 patients with lymph node biopsy-proved Castleman disease and multicentric involvement. The patients were aged 23-58 years (mean age, 42.9 years; five men, seven women). Seven patients underwent open lung biopsy (n = 3) or transbronchial lung biopsy (n = 4), which demonstrated lymphocytic interstitial pneumonitis. RESULTS: All patients had systemic symptoms, polyclonal hypergammaglobulinemia, and bilateral hilar and mediastinal lymph node enlargement. The nodes showed mild to moderate enhancement after intravenous administration of contrast material. At thin-section CT, all 12 patients showed poorly defined centrilobular nodules. Thin-walled cysts were present in 10 patients, thickening of the bronchovascular bundles in 10, and interlobular septal thickening in nine. Less common findings were subpleural nodules, ground-glass attenuation, air-space consolidation, and bronchiectasis. CONCLUSION: Multicentric Castleman disease is characterized by the presence of systemic symptoms, bilateral hilar and mediastinal lymphadenopathy, and centrilobular nodular opacities. The pulmonary parenchymal findings are due to the associated lymphocytic interstitial pneumonitis.

Adult↗
PubMed1993

Multicentric squamous cell carcinoma in situ resembling Bowen's disease in cats.

Multicentric squamous cell carcinoma in situ was studied in 12 cats (eight castrated males and four spayed females). The neoplasms occurred in middle-aged to old (mean age = 12 years) mixed-breed cats with a variety of hair-coat colors. The lesions were found in haired pigmented regions of the skin, including the trunk, limbs, feet, head, and neck, and were unrelated to exposure to sunlight. Lesions occurred at multiple sites in nine cats and at solitary sites in three cats and were from 0.5 cm to 3.0 cm in diameter, irregular, slightly elevated, plaque-like or papillated, and partially alopecic. Histologically, the lesions consisted of sharply demarcated regions of neoplastic, keratinocytic infiltration of the epidermal and follicular infundibular epithelium. Neoplastic cells were confined to the epithelium without frank invasion of the dermis. Two histologic subclasses of multicentric squamous cell carcinoma in situ were identified, the irregular nonhyperkeratotic type and the verrucous hyperkeratotic type. Three cats also had invasive squamous cell carcinoma adjacent to lesions characteristic of multicentric squamous cell carcinoma in situ. Grossly, these were solitary 2.0-4.0 cm-diameter firm, crusted, crateriform cutaneous masses. During follow-up periods of 4 to 20 months (mean follow-up period = 11 months), neoplasms did not recur locally after surgical excision; however, similar lesions developed at new sites in four cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Methodology of neuropsychological research in multicentre randomized clinical trials: a model derived from the International Subarachnoid Aneurysm Trial.

As advances in medicine and surgery lead to reductions in mortality rates for life-threatening conditions, it has become increasingly important to refine the methodology of auditing long-term morbidity. The inclusion of appropriate neuropsychological outcomes in a large multicentre randomized clinical trial poses considerable methodological and logistical difficulties. This paper presents a model developed to implement such a multicentre neuropsychological and quality of life audit for a subset of patients within the International Subarachnoid Aneurysm Trial (ISAT), the largest ever randomized trial in the treatment of subarachnoid haemorrhage. Based on our experience of collecting quality of life and neuropsychological outcomes from more than 550 patients, data are presented on the relative cost and efficacy of different organizational strategies, methods of canvassing patients and associated response rates. On the basis of this experience, we estimate a potential recruitment pool of 135 cases would be required to obtain some neuropsychological data on 100 cases. The design of any similar trial would therefore need to accommodate a loss to follow-up of approximately one third of the sample. In addition, our experience suggests that for a trial of this size and complexity, the deployment of centrally-based co-ordinators travelling to satellite centres is more cost-effective than employing co-ordinators based at those centres. Extrapolations from the observations and calculations reported here can be employed as an evidence base to inform the design of neuropsychological outcome studies in large multicentre trials.

Humans↗
PubMed2005

Synchronous multicentric pleomorphic xanthoastrocytoma: case report.

OBJECTIVE AND IMPORTANCE: Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytoma of adolescence. Relatively favorable outcomes have been achieved with complete surgical resection. However, few data exist regarding the treatment of recurrent, deep-seated, or multicentric lesions. We report the first case to our knowledge of synchronous multicentric PXA and discuss the related therapeutic challenges. CLINICAL PRESENTATION: A 13-year-old Hispanic girl presented with a 1-year history of progressive headaches, polyuria, and generalized fatigue. Findings from the neurological examination were notable only for the presence of papilledema. Results of laboratory studies revealed diabetes insipidus and hypothyroidism. The magnetic resonance imaging study revealed numerous nodular, homogeneously enhancing lesions, approximately 1 cm in size, scattered throughout both cerebral hemispheres. INTERVENTION: A right frontal craniotomy was performed for excisional biopsy of a superficial lesion beneath the coronal suture. Results of the histological examination were consistent with a diagnosis of PXA. The patient was treated with whole-brain radiation of 3600 cGy, with additional intensity-modulated boosts to the enhancing lesions of 1440 cGy. Three years after treatment, the patient remains neurologically nonfocal and shows no evidence of disease progression. Surgical intervention will be considered if accessible lesions progress in size on later imaging studies. CONCLUSION: Synchronous multicentric PXA presents unique challenges in that gross total resection would impose significant surgical morbidity; histological homogeneity among the lesions cannot be confirmed; and the well-described potential for anaplastic transformation may be increased with multiple lesions. The optimal treatment for patients with this rare and challenging diagnosis awaits further study.

Adolescent↗
PubMed2003

Magnetic resonance imaging in patients diagnosed with ductal carcinoma-in-situ: value in the diagnosis of residual disease, occult invasion, and multicentricity.

BACKGROUND: Although magnetic resonance imaging (MRI) has been shown to be a sensitive imaging tool for invasive breast cancers, its utility in ductal carcinoma-in-situ (DCIS) of the breast remains controversial. We studied the performance of MRI in patients with known DCIS for assessment of residual disease, occult invasion, and multicentricity to determine the clinical role of MRI in this setting. METHODS: Fifty-one patients with biopsy-proven DCIS underwent contrast-enhanced MRI before surgical treatment. Pre-, early post-, and late postcontrast three-dimensional gradient echo images were obtained and MRI findings were correlated with histopathology. When possible, the performance of MRI and mammography was compared. RESULTS: The accuracy of MRI was 88% in predicting residual disease, 82% in predicting invasive disease, and 90% in predicting multicentricity. The performance of MRI was equivalent in the core biopsy group when compared with the surgical biopsy group. For occult invasion only, MRI and mammography were equivalent. However, overall, MRI was more sensitive and had a higher negative predictive value than mammography. CONCLUSIONS: MRI of DCIS can serve as a useful adjunct to mammography by providing a more accurate assessment of the extent of residual or multicentric disease. The performance of MRI is not significantly affected by antecedent surgical excision. MRI may be particularly valuable if preoperatively negative.

Adult↗
PubMed1999

Hospital selection for unit cost estimates in multicentre economic evaluations. Does the choice of hospitals make a difference?

OBJECTIVE: The objectives of this study were (i) to develop a conceptual framework for selecting hospitals for unit cost estimates in national and international multicentre trials and (ii) to test the impact of alternative hospital selection on the cost results. DESIGN AND SETTING: Within the conceptual framework, the following considerations which can be used when selecting a sample of hospitals for unit cost estimates in multicentre trials were identified: the number of hospitals; the sampling method; and the desired level of geographical subanalysis. Results from a recently completed international multicentre trial were used to explore changes in cost results obtained by using alternative methods of selecting and stratifying hospitals for unit cost estimates. PATIENTS AND PARTICIPANTS: The study included 5041 women from 72 hospitals in 6 countries with prelabour rupture of the membranes at term. INTERVENTIONS: The women were randomly assigned to induction of labour with intravenous oxytocin, induction of labour with prostaglandin E2 gel, or expectant management for up to 4 days with labour induced if complications developed. MAIN OUTCOME MEASURES AND RESULTS: Across each of the 4 management strategies of the study, the method of selecting and stratifying hospitals resulted in a 30 to 55% difference between the lowest and highest median unit cost estimates. In some cases, the relative ranking of the least to most expensive strategy varied across methods of hospital selection. The statistical comparisons across strategies found that the method used had a substantial impact on the conclusions of the economic evaluation. CONCLUSIONS: Unit cost information should be collected from as many hospitals as possible. Multivariate hospital cost studies are needed to identify important cost drivers that will assist with hospital selection in the future.

Costs and Cost Analysis↗
PubMed1976

Idiopathic multicentric osteolysis.

A 59 year old while female with striking carpal and tarsal osteolysis is reported. The process primarily involves the carpals and tarsals but includes other sites. The pertinent literature is reviewed and a simplified classification of idiopathic multicentric osteolysis is presented. Idiopathic multicentric osteolysis may be sporadic but can demonstrate either dominant or recessive inheritance. There may or may not be associated nephropathy. The underlying mechanism appears similar in all variations of this condition. Gorham's disease, the Winchester syndrome, and other osteolytic conditions which may predominantly affect the tarsal and carpal bones most likely are totally different processes, unrelated to idiopathic multicentric osteolysis.

Arthritis, Juvenile↗
PubMed1985

Diffuse, multicentric neurogenic tumors in two macerated fetuses: a possible intrauterine form of neurofibromatosis.

Two tiny macerated fetuses with a remarkably similar pattern of multicentric neurogenic neoplasms of both paravertebral autonomic structures and peripheral nerves are described. Maceration precluded further histologic classification of the neoplasms in either fetus. The first fetus had a Meckel's diverticulum, short attachment of the small bowel mesentery, pulmonary hypoplasia, and intrauterine growth retardation. The second had the sympus bipus variant of sirenomelia sequence. The multicentric neoplasms in these two fetuses are very similar to those previously described in a few neonates and one stillborn with well-documented or suspected neurofibromatosis. It is reasonable to hypothesize that these two fetuses may represent an early intrauterine expression of neurofibromatosis characterized by multicentric neurogenic neoplasms of autonomic structures and peripheral nerves. Detailed examination of early abortuses, especially those from families with neurofibromatosis, may help to confirm or disprove the hypothesis.

Autonomic Nervous System Diseases↗
PubMed2006

Evaluation of web-based annotation of ophthalmic images for multicentric clinical trials.

An Internet browser-based annotation system can be used to identify and describe features in digitalized retinal images, in multicentric clinical trials, in real time. In this web-based annotation system, the user employs a mouse to draw and create annotations on a transparent layer, that encapsulates the observations and interpretations of a specific image. Multiple annotation layers may be overlaid on a single image. These layers may correspond to annotations by different users on the same image or annotations of a temporal sequence of images of a disease process, over a period of time. In addition, geometrical properties of annotated figures may be computed and measured. The annotations are stored in a central repository database on a server, which can be retrieved by multiple users in real time. This system facilitates objective evaluation of digital images and comparison of double-blind readings of digital photographs, with an identifiable audit trail. Annotation of ophthalmic images allowed clinically feasible and useful interpretation to track properties of an area of fundus pathology. This provided an objective method to monitor properties of pathologies over time, an essential component of multicentric clinical trials. The annotation system also allowed users to view stereoscopic images that are stereo pairs. This web-based annotation system is useful and valuable in monitoring patient care, in multicentric clinical trials, telemedicine, teaching and routine clinical settings.

Humans↗
PubMed2005

Multicentre research: lessons from the field.

Multicentre research can be used to explore and generate significant data in aspects of care that affect small numbers of children. This article describes the problems and benefits encountered by a group of nurses from 11 hospitals undertaking a multicentre study of pressure ulcers in children and young people in England and Wales. Multicentre research can generate a large amount of useful data contributing to high quality evidence-based care and can provide nurses with a valuable learning and networking experience.

Adolescent↗
PubMed1988

[A case of a small hepatoma with multicentric development in precirrhotic fibrosis].

Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one.

Carcinoma, Hepatocellular↗