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PubMed1987

Pathological findings in mine workers: II. Quality of the PATHAUT data.

To assess the feasibility of using the pathology automation system (PATHAUT) for research, the quality of the data was explored by examining who comes to autopsy, the quality of the autopsy material, interobserver variability, and repeatability of diagnoses. The data indicated that autopsy rates in the gold mining industry, especially for whites, are high and that even among blacks, gold miners are represented in proportions exceeding the relative size of the working population. Because of the perception of the autopsy service as a means of obtaining compensation, miners with occupational diseases fully compensated in life are probably underrepresented. The autopsy material submitted for full autopsy is generally better preserved than cardiorespiratory organs that are sent for examination. The gold mining industry has a high proportion of full autopsies as does the Iron and Steel Corporation of South Africa. Full autopsies are more commonly performed on older deceased miners. This was true for both blacks and whites. The allocation of material to pathologists for full autopsies and examinations of the cardiorespiratory organs were clearly not random, and this may affect comparisons among pathologists. Active tuberculosis, silicosis, and emphysema prevalences appeared fairly comparable across pathologists; however, there was wide variability in the prevalence of bronchiolitis as determined by the pathologists. Agreement between the diagnoses on PATHAUT and reclassifications by single pathologists was very good for the severity of emphysema and the histological type of bronchogenic carcinoma.

Autopsy↗
PubMed1979

Mutational mosaicism and genetic counseling in retinoblastoma.

Mutations may arise throughout an organism's life cycle. Typically, sporadic meiotic mutations give rise to individuals with all their germinal and somatic cells bearing the mutant gene. These mutations may be amorphs (with full penetrance and expressivity) or hypomorphs (with reduced penetrance and expressivity). Mutational mosaicism, however, involves the origin of mutations occurring during mitosis, whether in the parent at some stage prior to reproductive maturity or in the offspring at some time following fertilization. The phenotypic expression and transmission of these new mutations are dependent on the proportion of cells bearing the mutant gene as well as the location of these cells in somatic and/or germinal tissues. Mutational mosaicism was used as a developmental model to analyze 1,500 sporadic and 179 familial cases of retinoblastoma from the world literature. This model provided an interpretation for the origin, onset, and transmissibility of the sporadic unilateral retinoblastoma cases, which represent over 60% of all retinoblastoma patients. The model also permits a reclassification of all transmissible types of retinoblastoma; based on this classification, more accurate risk figures for genetic counseling can be offered. In addition, mutational mosaicism can be extended as a model to other autosomal dominant and X-linked mutations.

Animals↗
PubMed2004

Ectodermal dysplasias.

Ectodermal dysplasias are a large group of heritable conditions characterized by congenital defects of one or more ectodermal structures and their appendages: hair (hypotrichosis, partial, or total alopecia), nails (dystrophic, hypertrophic, abnormally keratinized), teeth (enamel defect or absent), and sweat glands (hypoplastic or aplastic). The ectodermal dysplasias, as a rule, are not pure "one-layer diseases." Mesodermal and, rarely, endodermal dysplasias coexist. Embryogenesis exhibits distinct tissue organizational fields and specific interactions among the germ layers that may lead to a wide range of ectodermal dysplasias when genes important for development are mutated or otherwise altered in expression. Of the approximately 200 different ectodermal dysplasias, about 30 have been studied at the molecular level with identification of the causative gene. Freire-Maia and Pinheiro used the clinical aspects for their classification, and Priolo integrated molecular genetic and clinical aspects for her scheme. Those two more historical classification schemes have the difficulty that, when applied strictly, several additional groups of diseases should be integrated within the term "ectodermal dysplasias," e.g. keratodermas with skin or hair alterations or the ichthyoses with associated features. Such consequent classification would lead to an endless list of diseases and would be useless for the practical work. Recent evidence implicates a genetic defect in different pathways orchestrating ectodermal organogenesis. Modern molecular genetics will increasingly elucidate the basic defects of the different syndromes and yield more insight into the regulatory mechanisms of embryology. In this way, a reclassification of ectodermal dysplasias will be possible according to the function of their involved mutated genes. Lamartine recently proposed a helpful classification according to the functions of the genes discovered in different types of ectodermal dysplasias. Accordingly, the present overview categorizes the various ectodermal dysplasias into four major functional subgroups: cell-cell communication and signaling, adhesion, transcription regulation, and development.

Cell Adhesion↗
PubMed1989

Infarcts of undetermined cause: the NINCDS Stroke Data Bank.

In a prospective study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, the 1,273 with infarction were classified into diagnostic subtypes. Diagnosis was based on the clinical history, examination, and laboratory tests including computed tomography, noninvasive vascular imaging, and where safe and relevant, angiography. Five hundred and eight cases (fully 40%) were labeled as infarcts of undetermined cause (IUC), of which 138 (27%) were evaluated with both computed tomography and angiography. The clinical syndrome and computed tomographic and angiographic findings in 91 (65.9%) of these 138 IUC cases were clearly not attributable to large-artery thrombosis and could permit reclassification of the infarct as due to some form of embolism. Failure to define a source of embolus kept them in the category of IUC. Thirty-one cases (22.5%) could be reclassified as due to stenosis or thrombosis of a large artery, and 16 (11.6%) as lacunar infarction. To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses, a stepwise multiple logistic model was used. The most important characteristics were young age, presence of a superficial infarct, prior transient ischemic attack, low weakness score, and presentation with a nonlacunar syndrome. The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis. Continued use of the category IUC may help clarify risk factors and stroke subtypes, allow new mechanisms of ischemic stroke to be uncovered, and prevent classification categories of stroke used in clinical trials from becoming too broad.

Cerebral Angiography↗
PubMed1988

The incidence of rheumatoid arthritis is predicted by rheumatoid factor titer in a longitudinal population study.

Rheumatoid factor (RF) is often detected in subjects who do not have rheumatoid arthritis (RA). To determine if the presence of RF is predictive of the development of RA, 2,712 Pima Indians of Arizona, 20 years of age or older, initially without RA, have been observed for up to 19 years with biennial examinations. These included a medical history, physical examination of the joints, radiographs, and RF determination by sheep cell agglutination test. During the study period, 70 new cases of RA developed. When the population at risk was stratified by RF titer, with reclassification at subsequent examinations if the RF titer changed, the age- and sex-adjusted incidence of RA increased with higher titers of RF. The incidence of RA (in cases per 1,000 person-years) according to RF titer was 2.4 (RF titer less than 1:2); 6.7 (titer 1:2-1:16); 11.0 (titer 1:32-1:256); and 48.3 (titer greater than 1:256) (P less than 0.001). The same trend was also found within each age and sex group, and within groups defined by the number of American Rheumatism Association criteria present before the definite diagnosis. We conclude that the presence of RF, in subjects without RA, is a risk factor for the development of RA, and that this risk is related to the RF titer. It is also suggested that RF may represent a marker of the earliest phases of the pathogenetic process of RA, that may be detectable before the appearance of other features that permit a clinical diagnosis.

Adult↗
PubMed1996

Glutamine.

Glutamine is the most abundant free amino acid in the circulation. It is a primary fuel for rapidly dividing cells and plays a key role in the transport of nitrogen between organs. Although glutamine is absent from conventional regimens aimed at nutritional support, glutamine deficiency can occur during periods of metabolic stress; this has led to the reclassification of glutamine as a conditionally essential amino acid. Experiments with various animal models have demonstrated that the provision of glutamine can result in better nitrogen homoeostasis, with conservation of skeletal muscle. There is also considerable evidence that glutamine can enhance the barrier function of the gut. This review concludes by discussing the clinical evidence that supports the inclusion of stable forms of glutamine in solutions of nutrients.

Enteral Nutrition↗
PubMed2003

Decline in admission rates for acute appendicitis in England.

BACKGROUND: The incidence of acute appendicitis declined in western countries between the 1930s and the early 1990s. The aim of this study was to determine time trends in hospital admissions for acute appendicitis in England between 1989-1990 and 1999-2000, and in population mortality rates for appendicitis from 1979 to 1999. METHODS: : Hospital Episode Statistics for admissions were obtained from the Department of Health and mortality data from the Office for National Statistics. RESULTS: Between 1989-1990 and 1999-2000, age-standardized hospital admission rates for acute appendicitis decreased by 12.5 per cent in male patients and by 18.8 per cent in female patients. The proportions of admissions that resulted in operation remained stable. Admission rates for non-specific mesenteric lymphadenitis fell. Admission rates for abdominal pain increased between 1989-1990 and 1995-1996, at which time the International Classification of Diseases codes changed. Between 1995-1996 and 1999-2000, admission rates for abdominal pain declined. Analysis of age-specific admission rates for acute appendicitis and abdominal pain from 1989-1990 to 1995-1996 showed that the decline in acute appendicitis could not be accounted for by a change in diagnostic practice. Mortality rates for acute appendicitis remained stable over the study period. CONCLUSION: Admission rates for acute appendicitis declined over the study period. This decline cannot be explained by reclassification.

Acute Disease↗
PubMed1985

Hemodynamic evaluation of stenotic cardiac valves: I. Effect of ventriculography and atropine on mitral stenosis.

Mitral area is the parameter used for quantitating mitral stenosis (MS) severity. When mitral gradient (MG) is low and reduction of mitral valve area (MVA) might be critical, interventions presumably increasing mitral valve flow (MVF), such as stress or atrial pacing, have been carried out. The purpose of this study was to analyze in 28 patients the combined effect of left ventriculography (LVG) and intravenous atropine (ATR) in the hemodynamic evaluation of MS. The rationale for combining these two interventions is to add up the ATR-positive chronotropic effect to the LVG potentiation of cardiac output. The LVG plus ATR markedly accelerated heart rate (from 80 +/- 14 to 104 +/- 18 bts/min, P less than 0.001), mildly increased cardiac index (from 2.6 +/- 0.6 to 2.9 +/- 0.6 1/min/m2, P less than 0.05), and importantly increased MVF (from 136 +/- 30 to 172 +/- 46 ml/bt, P less than 0.001). Pulmonary wedge pressure increased (from 14 +/- 5 to 21 +/- 5 mmHg, P less than 0.001) because of an important increment of MG (from 12 +/- 6 to 18 +/- 7 mmHg, P less than 0.001). None of six cases with mild MS (MVA greater than 1.5 cm2) and nine of ten cases with severe MS (MVA less than or equal to 1.0 cm2) had MG after LVG plus ATR greater than 12 mmHg. The remaining case with severe MS and the two cases (out of 12) with moderate MS having MG after LVG plus ATR less than or equal to 12 mmHg had, at surgical evaluation, noncritically reduced MVA. This study shows that LVG plus ATR is a valid and easy intervention for increasing MVF during cardiac catheterization. It also allows the reclassification of patients with low baseline MG and reduced MVA into two subgroups: Cases with critically reduced MVA at surgery achieve a postintervention MG greater than 12 mmHg and those cases with noncritically reduced MVA achieve a postintervention MG less than or equal to 12 mmHg.

Adult↗
PubMed2004

Vascular age: integrating carotid intima-media thickness measurements with global coronary risk assessment.

BACKGROUND: An imaging test that quantifies atherosclerotic burden and that can be integrated with existing risk stratification paradigms would be a very useful clinical tool. HYPOTHESIS: Measurement of carotid intima-media thickness (CIMT) is feasible in a clinical setting. Such measurements can be integrated into coronary risk assessment models. METHODS: Carotid intima-media thickness was measured by B-mode ultrasound in 82 consecutive patients without manifest atherosclerotic vascular disease. The values were used to determine "vascular age" (VA) based on nomograms from the Atherosclerosis Risk in Communities study. Vascular age was substituted for chronological age and standard and vascular age-adjusted 10-year coronary heart disease (CHD) risk estimates were compared. RESULTS: The mean chronological age was 55.8 +/- 9.0 years. The mean VA using CIMT was 65.5 +/- 18.9 years (p < 0.001). The Framingham 10-year hard CHD risk estimate was 6.5 +/- 4.9%. Substituting CIMT-derived VA for chronological age increased the 10-year CHD risk estimate to 8.0 +/- 6.8% (p < 0.001). Of 14 subjects initially at intermediate risk, 5 (35.7%) were reclassified as higher risk and 2 (14.3%) were reclassified as lower risk. Significant predictors of reclassification were tobacco use, high-density lipoprotein cholesterol, systolic blood pressure, and low-density lipoprotein cholesterol. CONCLUSIONS: Measurement of CIMT, a noninvasive estimate of current atherosclerotic burden, is feasible in a clinical setting and can be integrated into CHD risk assessment models. Determining VA using CIMT values may help individualize the age component of population-based CHD risk estimates. This strategy should be tested in a large trial with hard clinical endpoints.

Adult↗
PubMed2002

The effects of the current World Health Organization/International Society of Urologic Pathologists bladder neoplasm classification system on urine cytology results.

BACKGROUND: Historically, the diagnostic accuracy of urine cytology for the detection of urothelial carcinoma has been low, particularly for low-grade lesions. In 1998, the World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) established a new classification system for urothelial neoplasms. It has been postulated that the accuracy of urine cytology for the detection of low-grade carcinomas should improve, because the current WHO/ISUP system classifies bladder lesions that lack any significant cytologic atypia as papillary urothelial neoplasms of low malignant potential (PUNLMP). Also, the accuracy of urinary cytology for the detection of high-grade lesions is expected to decrease, because the criteria for high-grade lesions is lowered, placing most of the previous WHO Grade 2 tumors into the current high-grade carcinoma category. METHODS: One hundred bladder biopsies that were classified according to the previous WHO classification system were examined by one pathologist and were reclassified according to the new WHO/ISUP scheme. All biopsies had corresponding urine specimens that had been diagnosed previously by a different cytopathologists. The patients' previous WHO and current WHO/ISUP surgical diagnoses were compared with the corresponding urine cytology. In addition, cytospins obtained from 40 patients with a histologic diagnosis of low-grade urothelial carcinoma (n = 20 patients) and high-grade urothelial carcinoma (n = 20 patients) according to the WHO/ISUP classification system were reviewed to identify any outstanding cytologic features. RESULTS: According to the original WHO classification system, there were 26 patients with Grade 1 transitional cell carcinoma (TCC), 61 patients with Grade 2 TCC, and 13 patients with Grade 3 TCC. The corresponding cytology was positive in 11 of 26 Grade 1 tumors, 28 of 61 Grade 2 tumors, and 12 of 13 Grade 3 tumors. After the reclassification, there was 1 papilloma, 12 PUNLMP lesions, 50 low-grade urothelial carcinomas, and 37 high-grade carcinomas. The cytology was positive in 0 of 1 papillomas, 5 of 7 PUNLMP lesions, 18 of 50 low-grade carcinomas, and 28 of 37 high-grade carcinomas. In addition, morphologic uniformity and cytoplasmic homogeneity (50.0% and 45.0%, respectively) were seen more commonly in low-grade bladder tumors. CONCLUSIONS: The diagnostic accuracy of urine cytology for high-grade lesions decreased, as expected; however, cytologic detection of low-grade urothelial carcinomas was remarkably lower than expected. In addition, no outstanding cytologic features could be identified to make a definitive diagnosis.

Aged↗
PubMed2003

Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial.

BACKGROUND: Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system. METHODS: From October 1987 to April 1992, 304 patients with advanced-stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty-six patients were eligible and fully evaluable. With a median follow-up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression-free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms. RESULTS: With a longer follow-up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor-risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic toxicity, occurred on the VIP arm. CONCLUSIONS: With a median follow-up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide-containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate-risk germ cell tumors, four cycles of BEP remain the standard therapy.

Adult↗
PubMed2003

Progress in the chemotherapy of metastatic cancer of the urinary tract.

Cytotoxic chemotherapy has an evolving role in the management of metastatic cancer of the bladder and urinary tract. The most responsive of these tumors are transitional cell carcinomas. Standard single agents (e.g., methotrexate, doxorubicin, mitomycin, ifosfamide, vinblastine, and cisplatin) have produced objective response rates of 15-25% and combination chemotherapy has resulted in objective regression in 40-75% of cases. The taxanes and gemcitabine are now being incorporated into combination regimens because they have activity against this disease, both in previously treated and untreated patients. In previously untreated patients, regimens incorporating gemcitabine and paclitaxel and a platinum complex, with or without ifosfamide or doxorubicin, produce median survival periods of 15-20 months. Contemporary experience with the methotrexate/vinblastine/doxorubicin/cisplatin regimen yields a median survival period of 18 months. Traditional cytotoxic regimens have been ineffective in the management of adenocarcinoma and squamous cell carcinoma of the bladder. However, regimens predicated on the taxanes and gemcitabine yield response rates of 30-40%, which may translate into improved survival. Nevertheless, stage migration may produce the semblance of improved survival, which may reflect reduced tumor burden (via reclassification) and case selection. Because historically controlled comparisons may introduce errors from case selection bias, stage migration, differences in duration of follow-up, and the evolution of supportive care, it is essential to validate the role of new agents in well structured, randomized clinical trials.

Adenocarcinoma↗
PubMed2003

Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945.

BACKGROUND: The objectives of the current study were to determine the outcome of children who were treated with chemotherapy and radiotherapy on the Children's Cancer Group (CCG) high-grade glioma protocol (CCG-945) who were diagnosed with low-grade gliomas on post hoc central pathologic review and to identify clinical and biologic features associated with prognosis. METHODS: Between 1985 and 1991, 250 children with institutionally classified high-grade gliomas were enrolled on CCG-945. Patients older than 24 months with intracranial lesions were assigned randomly to receive either lomustine, vincristine, and prednisone (control regimen) or the 8-drugs-in-1-day regimen (experimental regimen); younger patients and those with primary spinal cord tumors were assigned nonrandomly to the experimental regimen. Central independent review by 5 neuropathologists led to a reclassification of low-grade glioma in 70 patients, who were the focus of the current study. RESULTS: The study involved 42 males and 28 females (median age, 7.7 years) with a median follow-up of 10.4 years. At 5 years, the progression-free survival (PFS) rate was 63% +/- 6%, and the overall survival (OS) rate was 79% +/- 5%, compared with a PFS rate of 19% +/- 3% (P < 0.0001) and an OS rate of 22% +/- 3% (P < 0.0001) in the remainder of the cohort. Significantly poorer 5-year PFS was seen in children younger than 24 months, those with fibrillary astrocytoma, and those with posterior fossa tumors. Patients demonstrated a modest improvement in PFS but no improvement in OS compared with children with low-grade gliomas who were treated with contemporary chemotherapy-alone approaches. CONCLUSIONS: The current report calls attention to the importance of central pathologic review in large multiinstitutional trials of children with gliomas and suggests that aggressive front-line combined chemoradiotherapy does not confer a survival advantage in this highly selected population of patients.

Adolescent↗
PubMed2004

Noninflammatory breast carcinoma with skin involvement.

BACKGROUND: According to the TNM Supplement, only breast carcinoma with macroscopic 'classic' skin changes (e.g., edema, peau d'orange, ulceration) should be placed in the T4 category; the classification of tumors with histologically proven skin involvement but no clinical skin changes or only discreet changes should be based on the size of the tumor (T1-3). To the authors' knowledge, no data supporting these recommendations have been reported to date. METHODS: Seventy-six patients with noninflammatory breast carcinoma and histologically proven skin involvement were classified based on the degree of their skin involvement. Fifty patients (66%) presented with clinically obvious skin involvement (Group A), and 26 patients (34%) had breast carcinoma with histologically proven skin involvement but without clinical skin changes (Group B). Reclassification was undertaken to assess the malignant potential of tumors independent of the morphologic parameter 'skin involvement'. RESULTS: Patients in Group A presented significantly more frequently with extensive disease at regional or distant sites (Stages IIIC and IV; P=0.009). The clinical outcome of patients in Group B was significantly more favorable (P=0.0003). The adjusted 3-year survival rates in Group A and Group B were 46.7% and 92.3%, respectively, and the 5-year rates were 38.1% and 83.7%, respectively. Patients in Group B were found to have significantly better (P=0.036) distant recurrence-free survival (DRFS) rates. The DRFS rate at 3 years was 63.6% in Group A, compared with 91.7% in Group B, and the DRFS rate at 5 years was 56.9% in Group A, compared with 82.0% in Group B. Using a cutoff point of tumor size=3 cm, similar findings were made. CONCLUSIONS: Both study groups exhibited distinct clinical entities with significant differences in clinical course and prognosis. Cases with histologic skin involvement, relative to those with classic skin involvement, were found to have much less malignant potential. This corroborates the recommendation that cases with only histologic skin involvement should not be placed in the T4 category of the TNM classification.

Adult↗
PubMed2005

The clinical use of staging bone scan in patients with breast carcinoma: reevaluation by the 2003 American Joint Committee on Cancer staging system.

BACKGROUND: Using the new 2003 American Joint Committee on Cancer (AJCC) staging system, the authors evaluated the usefulness of the staging bone scan in patients with primary breast carcinoma. METHODS: The authors examined 1939 patients with primary breast carcinoma for staging bone scan who were treated at a single institution. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging systems. RESULTS: Bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of 154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with Stage IIIB disease according to the 1988 AJCC staging system. The authors found a significant difference in the bone metastasis rate between patients with Stages IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the patients by the 2003 system resulted in significant upstaging, especially for patients with Stage II/III disease. According to the 2003 staging system, bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4 of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2 of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients with Stage IIIC disease. It was noteworthy that there was a significant difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010). CONCLUSIONS: Stage reclassification using the new AJCC staging system resulted in upstaging of high-risk patients, as well as a significant decrease in the bone metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost-effectiveness of staging bone scan, the data suggested that it was of little value for patients with Stage I and II breast carcinoma, but was highly recommended for patients with worse than Stage III disease by the new 2003 staging system.

Adult↗
PubMed2006

T4 category revision enhances the accuracy and significance of stage III breast cancer.

BACKGROUND: Because of the considerable heterogeneity in breast carcinoma with noninflammatory skin involvement (T4b/Stage IIIB), a revision was proposed of the TNM staging system that would classify these tumors exclusively based on their tumor size and lymph node status. In the current study, the authors evaluated how implementation of this proposal will affect Stage III noninflammatory breast cancer. METHODS: Two hundred seven patients who were classified with noninflammatory Stage III breast cancer were treated consecutively between 1990 and 1999 at the University Hospital Basel, Switzerland. To assess the extent of T4b/Stage IIIB tumors independent of the clinicopathologic feature of skin involvement, the reclassification was undertaken. RESULTS: Of 68 patients who had nonmetastatic T4b breast cancer, 37 patients (54.4%) had a tumor extent in accordance with Stage I/II and had improved disease-specific survival (DSS) compared with patients who had Stage III breast cancer (P = .008). Excluding those patients from Stage III led to a 17.9% reduction of the number of patients in this group (n = 170 patients). The 10-year DSS declined from 48.5% to 42.9%. CONCLUSIONS: Considerable numbers of patients who are classified with noninflammatory Stage IIIB breast cancer show only a limited disease extent. Through a revision of the T4 category, these low-risk patients were excluded from the highest nonmetastatic TNM stage, and overstaging could be avoided. This procedure decreased the degree of heterogeneity of the entire Stage III group and may result in a more precise assessment of this disease entity.

Breast Neoplasms↗
PubMed1999

Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma.

Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC-IP) and mass forming type (ICC-M). The survival of patients with BDCC or ICC-IP is significantly better than that of patients with ICC-M. We examined these subtypes (ICC-IP and ICC-M) and BDCC for their expression of MUC1 mucins of different glycoforms. ICC-M showed significantly higher MUC1 expression rates (90%, 95%, and 85% positive rates as measured with the DF3, MY.1E12, and MUC1-Glycoprotein antibodies, respectively) than BDCC and ICC-IP (14% and 33%, 58% and 58%, and 0% and 50% positive respectively, as measured by the same antibodies). In contrast, BDCC (86% positive) and ICC-IP (67% positive) showed significantly higher MUC2 expression rates than ICC-M (25% positive) as measured with the anti-MRP antibody. Thus, the immunohistochemical staining pattern of ICC-IP resembled the pattern of BDCC more than they resembled ICC-M. In general, MUC1 expression is associated with poor patient outcome, irrespective of the glycosylation status. In particular, high expression of more sialylated forms of MUC1 mucins was correlated with poor survival. In contrast, expression of non-sialylated MUC2 mucin is a favorable prognostic indicator. These results suggest that ICC-IP is a different entity from ICC-M. This reclassification may have value in determining prognosis and treatment method.

Antigens, Neoplasm↗
PubMed2007

Impact of interobserver disagreement on phenotype-genotype associations in Crohn's disease.

BACKGROUND: Nonvalidated definitions of disease-related parameters in inflammatory bowel disease cause variations in diagnosis and disease classification. We determined interobserver agreement on applications of definitions of the Vienna Classification variables and computed the potential influence of misclassification on genotype/phenotype associations. METHODS: Ten records of patients with Crohn's disease (CD) were independently evaluated by 19 observers using a standardized inflammatory bowel disease documentation system, which included the Vienna Classification. Interobserver agreement (IOA) was calculated as a percentage of the observers' agreement with a predetermined reference observer and by Cohen's kappa. Randomized reclassifications were then computed with 10,000 simulation runs using the IOA results and published NOD2/CARD15 gene status. A chi-square independence test was calculated for each simulation run. RESULTS: IOA for location and behavior was 70% (K = 0.57) and 95% (K = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and for behavior from 91% to 97%. By including the results of histopathology into the evaluation of location, the overall IOA increased significantly, to 80% (P = 0.019). Assuming a true genotype/phenotype association, the proportion of studies with nonsignificant findings (P > 0.05) because of the observed misclassification of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%, depending on a study sample size of 500 or 150 patients respectively. CONCLUSIONS: We concluded that there is appreciable interobserver disagreement on the location of CD according to the original Vienna Classification that may obscure true genotype/phenotype associations. Definitions of disease parameters have to be validated before being used as the bases for classifications.

Adult↗