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PubMed2006

Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria.

BACKGROUND: Inactivation of p16(INK4A) promotes G1/S progression of cell cycle. Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker, is known to better correlate with clinical outcomes than Ki-67 in many carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains challenging in prognostication, we analyzed the utility of these three markers in GISTs. METHODS: Immunohistochemistry was performed in tissue microarrays of 277 primary GISTs and correlated with NIH consensus criteria and clinical outcomes. RESULTS: The increment of NIH risk levels significantly correlated with increasing labeling indices (LI) of both Ki-67 (P <.001) and Mcm2 (P <.001) and loss of p16(INK4A) expression (P <.035). However, the latter aberration did occur in 23% of very low/low-risk GISTs. The relationship between Mcm2 and Ki-67 LIs could be modeled as linear (P <.001, r = 0.697), while Mcm2 LI was considerably higher (P <.001) with a stepwise escalation related to risk levels. Ki-67 LI >5% (P <.0001) and Mcm2 LI >10% (P <.0001) were strongly predictive of inferior disease-specific survival (DSS), while aberrant loss of p16(INK4A) only reached a trend (P = .0954). In multivariate analyses, independent adverse factors of DSS were high-risk category (RR = 16.93, P <.0001), metastatic disease (RR = 4.12, P = .0015), Ki-67 LI >5% (RR = 3.55, P = .001), and presence of epithelioid histology (RR = 2.17, P = .0308). CONCLUSIONS: Prognostic efficacy of NIH consensus criteria is substantiated. P16(INK4A) deregulation can occur early in GIST tumorigenesis and marginally correlates with patient survival. Despite Ki-67 LI being an independent prognosticator, simultaneous detection of Mcm2 is recommended as a prognostic adjunct of GISTs, given its better sensitivity and stepwise escalation with increasing risk levels.

Adult↗
PubMed1995

Health Services Technology/Assessment Text (HSTAT).

Health Services Technology/Assessment Text (HSTAT), an online collection of documents pertaining to clinical practice guidelines, HIV/AIDS treatment information, and health care decision making, was recently introduced by the National Library of Medicine. Access to HSTAT is available through the NLM Full-Text Retrieval System (FTRS), a document search and retrieval system developed by the Information Technology Branch of NLM. Internet FTP, Gopher, and World Wide Web clients may also be used to obtain documents from the HSTAT collection.

Acquired Immunodeficiency Syndrome↗
PubMed2001

US-Japan workshops in medical mycology: past, present and future.

The Extramural Mycology Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) has organized and implemented a five workshop series in medical mycology during a critical period in the evolution of contemporary medical mycology (1992 to 2000; http://www.niaid.nih.gov/research/dmid.htm). The goals of the workshop series were to: initiate interactions; build collaborations; identify research needs; turn needs into opportunities; stimulate molecular research in medical mycology; and summarize recommendations emerging from the workshop proceedings. A recurring recommendation in the series was to foster communications within and beyond the field of medical mycology. US-Japan interactions were noted as one specific example of potential information exchange for mutual benefit. The first formal action directed at this recommendation was the workshop Emergence and Recognition of Fungal Diseases convened under the auspices of the US-Japan Cooperative Medical Science Program (USJCMSP; http://www.niaid. nih.gov/dmid/us%5Fjapan/default.htm) in Bethesda, Maryland USA on 30 June 1999 (D.M. Dixon & T. Matsumoto, co-chairs). A major goal of the workshop was to present contemporary medical mycology to the Joint Committee of the USJCMSP through representative research presentations in order to make the Committee aware of current status in the field, and the potential for scientific interactions. The second formal action is the workshop, under the auspices of the Japanese Society for Medical Mycology Medical Perspectives of Fungal Genome Studies scheduled for 28 November 2000 in Tokyo, Japan (T. Matsumoto & D.M. Dixon, co-chairs). The NIAID Mycology Workshop series recommended interactions between the following groups: academic and pharmaceutical; medical and molecular (model systems); medical and plant pathogens; basic and clinical; mycologists and immunologists. The first two US-Japan workshops can be viewed as consistent with these recommendations, and serve as a Western/Eastern gateway for exchange. The focus of the second US-Japan workshop on genome projects for the medically important fungi provides an excellent model for international communications. Given the tsunami of information that is flowing from genomics and bioinformatics, it is clear that global interactions will be essential in managing and interpreting the data.

Consensus Development Conferences, NIH as Topic↗
PubMedDate not supplied

Breast cancer screening among women younger than age 50: a current assessment of the issues.

In the hope of resolving underlying policy questions related to the value of breast cancer screening with mammography for women younger than 50 years of age, the National Institutes of Health and the National Cancer Institute in 1997 jointly sponsored a consensus conference on the subject. While the panel concluded that the data were insufficient to endorse mammography for this age group apart from individual choice, the conclusion was not the "consensus" sought by many of those with strong opinions on both sides of this issue, and the debate raged on. Prior to the 1997 conference, and since, meta-analyses of trial data and assessments of service screening programs have indicated that breast cancer screening with mammography for women between 40 and 49 meets recommended levels of performance compared with performance in women 50 years and older, especially if programs achieve high quality and screen at 12-to-18 month intervals. Because the detectable preclinical phase is shorter in younger women who develop breast cancer compared with that in women 50 years of age or older, a key component of any screening program for those younger than 50 is an appropriate screening interval. Many of the screening programs that had historically been developed for women in their forties--and whose disappointing results contributed to the confusion and controversy about the efficacy of mammography in younger women--had a 24-month screening interval, which was not found to be of significant benefit for early detection of breast cancer in this age group. While a new emphasis of this controversy has focused on the balance of benefits and harms in women ages 40 to 49, women of all ages need to be fully informed about the benefits and limitations of breast cancer screening--more specifically, what to expect at the time of screening, and what to expect from screening. There are differences in the performance and effectiveness of mammography in different age groups of women aged 40 and older, but these differences are not so great to question the value of screening in any one group. While some questions remain unresolved, the efficacy of mammography in women ages 40 to 49 should no longer be considered controversial.

Adult↗
PubMedDate not supplied

Clinical management of primary hyperparathyroidism and thresholds for surgical referral: a national study examining concordance between practice patterns and consensus panel recommendations.

OBJECTIVE: To determine whether 1990 guidelines established by the National Institutes of Health (NIH) for the optimal management (surgical versus nonsurgical) of patients with asymptomatic primary hyperparathyroidism (PHPT) are known and followed by endocrinologists. METHODS: We surveyed endocrinologists in the United States who were randomly selected in 1998 from two endocrine societies. Endocrinologists were asked about management of asymptomatic patients with PHPT, awareness of NIH recommendations, practice demographics, and annual PHPT case volume. We classified endocrinologists into either low-volume (<12 cases of PHPT per year) or high-volume (> or = 12 cases per year) physicians. RESULTS: Of 374 eligible physicians, 146 (39%) responded to our survey. In comparison with nonrespondents, respondents were of similar age, sex, years in practice, and geographic location profiles; this finding suggested minimal nonresponse bias. More high-volume physicians than low-volume physicians were aware of the NIH guidelines (75% versus 50%; P<0.01). Management of asymptomatic patients was similar between volume groups; overall, 39% of patients were referred for surgical treatment. Nevertheless, considerable variation in management existed; 7% of all physicians referred > or = 90% of their asymptomatic patients for surgical treatment, whereas 31% referred < or = 10%. Adherence to monitoring guidelines for nonsurgically managed patients ranged widely, depending on the specific recommendation (from 6% of physicians obtaining creatinine clearance assessments every 6 months to 78% of physicians ordering serum calcium measurements every 6 months). Surgical referral practices also varied substantially, with 25% of all physicians referring a 40-year-old patient with PHPT when hypercalcemia was mild (< or = 1 mg/dL above normal), 39% when hypercalcemia was moderate, and 31% when hypercalcemia was severe (>1.5 mg/dL above normal). Of the responding physicians, 4% reported that hypercalcemia alone was not sufficient justification to refer a patient for surgical intervention. Higher PHPT case volume was not associated with differences in surgical referral. CONCLUSION: Suboptimal awareness of the 1990 NIH panel recommendations and the substantial variation in clinical management of PHPT indicate that newer NIH guidelines developed in 2002 must be more widely disseminated and strongly recommended if practice patterns are to be influenced and clinical outcomes improved.

Adult↗
PubMed1998

Treating histologically mild chronic hepatitis C: monotherapy, combination therapy, or tincture of time?

The recent National Institutes of Health Consensus Conference on hepatitis C solidified the justification for a selective approach to treatment. Nevertheless, the high profile of chronic hepatitis C has led to a sense of urgency about treating "all-comers" and thus has caused the variable natural history of this disease to be overlooked. The debate about whom to treat has failed to focus attention on the alternative approach of waiting for better emerging therapies for the subset of patients with histologically mild chronic hepatitis C. Practitioners should be more confident about postponing treatment in less symptomatic patients if liver biopsy specimens show no more than grade 1 necroinflammatory activity or stage 1 fibrosis. Patients with these lesions, in the absence of clinical signs of advancing disease, are much less likely than patients with higher grades or stages to progress to cirrhosis. A "cure" for chronic hepatitis C remains elusive. End points of treatment depend on the achievement of sustained clearance of serum hepatitis C virus RNA, which is influenced, in turn, by the patient's viral replication and immune balance. Treatment of histologically mild chronic hepatitis C may ultimately mimic that of HIV infection.

Alanine Transaminase↗