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PubMed1993

Ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive irradiation. Correlation of pathologic parameters with outcome of treatment.

BACKGROUND: To evaluate the pathologic characteristics of the primary tumor relative to local control, survival, and freedom from distant metastases, an analysis was performed of 172 patients with ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive breast irradiation. METHODS: The clinical records and pathology slides were reviewed from 172 women with ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation at multiple institutions in Europe and the United States. Central pathology review was performed by one pathologist without knowledge of the clinical outcome. The clinical outcome was measured in terms of local control, overall survival, cause-specific survival, and freedom from distant metastases. The median follow-up time was 84 months (range, 17-177 months). RESULTS: The pathologic parameters evaluated were histologic subtype, nuclear grade, amount of necrosis, and final pathology margin. The only pathologic parameter that correlated with the rate of local recurrence was the presence versus the absence of the combination of the histologic subtype of comedo carcinoma plus nuclear grade 3 (8-year actuarial rate of local recurrence of 20% versus 5%, respectively; P = 0.009 on univariate analysis; P = 0.017 on multivariate analysis). None of the pathologic parameters evaluated correlated with overall survival (all P > or = 0.16), cause-specific survival (all P > or = 0.13), or freedom from distant metastases (all P > or = 0.13). CONCLUSIONS: These results have demonstrated that there are important differences in the rate of local recurrence based on the pathologic characteristics of the primary tumor for women with ductal carcinoma in situ treated with breast-conserving surgery and definitive irradiation. However, the differences in local recurrence have not been associated with differences in survival or freedom from distant metastases. Careful follow-up for patients at increased risk for local recurrence is warranted because of the potential ability to salvage patients with local recurrence.

Adult↗
PubMed2003

Disparity in pathologic and clinical lymph node staging in oral tongue carcinoma. Implication for therapeutic decision making.

BACKGROUND: Regional lymph node metastasis is the most reliable predictor of treatment outcomes for patients with squamous cell carcinoma of the oral tongue (SCCOT). A recent American Joint Committee on Cancer staging update of malignant melanoma has incorporated pathologic lymph node staging. The authors hypothesized that pathologic lymph node staging (pN) would be a more reliable predictor of treatment outcomes than clinical lymph node staging (cN). METHODS: The authors retrospectively reviewed 266 patients who received primary surgical treatment for SCCOT, including a neck dissection, from January 1980 to December 1995. Overall and disease-specific survival and disease-free interval were compared with respect to clinical and pathologic lymph node stages. RESULTS: Statistically significant survival differences were identified for both clinical (cN0-cN2) and pathologic lymph node stages (pN0-pN2). However, survival and disease-free interval differences for pathologic lymph node staging reached higher statistical significance (P < 0.0001) than for clinical lymph node staging (P < 0.002). This disparity can be explained by stage migration (i.e., patients with cN0-1 disease have a more advanced lymph node stage at the time of pathologic review compared with patients without cN0-1 disease). The authors found a 34% rate of occult lymph node disease in the cN0 group (19% of occult lymph nodes had extracapsular spread [ECS]). Similarly, 43% of cN1 patients had a higher stage than pN2b disease and 50% had ECS. CONCLUSIONS: Pathologic lymph node staging, based on a staging or therapeutic neck dissection, should be considered for patients treated for SCCOT to identify high-risk patients who may benefit from additional adjuvant therapy. Prospective studies are essential to validate these findings before pathologic lymph node staging is included in standard staging criteria.

Carcinoma, Squamous Cell↗
PubMed2004

Pathologic evaluation of radical cystectomy specimens: a cooperative group report.

BACKGROUND: The authors evaluated the pathology of radical cystectomy and pelvic lymph node specimens from patients with bladder carcinoma who were enrolled in a cooperative group trial. Their objective was to determine whether current practices conform to suggested pathology practice guidelines for reporting on radical cystectomy and pelvic lymph node specimens. METHODS: Overall, 268 patients underwent radical cystectomy with pelvic lymph node dissection over 11 years in a total of 109 diverse geographic locations and types of institutions. Institutions included 50 community hospitals, 36 academic hospitals, and 23 Veterans Administration (VA)/military hospitals, which evaluated 84, 137, and 47 patients, respectively. The quality of pathology examination was assessed based on the original pathology reports of specimens that were submitted according to published practice guidelines. RESULTS: Among all types of institutions, pathologic evaluation of radical cystectomy specimens generally was complete for tumor histology, grade, size, location, pathologic stage, lymph node status, prostate involvement, and associated mucosal abnormalities, including ureters and urethra. Perivesical fat (soft tissue) margins were not recorded in 10% of specimens, and 18% of patients did not mention either the presence or the number of lymph nodes. These deficiencies were observed primarily at community and VA hospitals. CONCLUSIONS: The overall quality of pathologic examination of radical cystectomy specimens is high. Better reporting of soft tissue margin status and pelvic lymph node counts is needed to achieve compliance with the standards published by evolving practice protocols. Standardized pathologic evaluation and reporting of radical cystectomy specimens will optimize important prognostic information and foster better communication between the pathologist, surgeon, and interested oncologists to benefit patients.

Aged↗
PubMed2002

Changes in breast cancer therapy because of pathology second opinions.

BACKGROUND: Examination of pathology slides is a routine part of a breast cancer second opinion. The purpose of this study was to determine how often the pathologic second opinion (1) altered the diagnosis and (2) resulted in a change in the surgical procedure. METHODS: Patients presenting between 1997 and 2001 for a second opinion after a biopsy diagnosis of breast cancer (invasive or noninvasive) were included in this study. RESULTS: There were 340 patients presenting for second opinions regarding 346 breast cancers. Sixty-eight pathologic second opinions (20%) did not result in any change in pathology or prognostic factors, whereas in the remaining 80%, some change occurred. Major changes that altered surgical therapy occurred in 7.8% of cases, and pathology review provided additional prognostic information in 40%. Changes were more common in in situ carcinoma than invasive carcinoma (P =.004), but biopsy type (core vs. excisional biopsy) was not a significant predictor of change in pathologic information. CONCLUSIONS: This study confirms the benefit of a pathology second opinion to improve preoperative estimates of prognosis and to determine the appropriate surgical procedure. Missing information on grade and histological subtype was responsible for a large number of cases, suggesting a need for widespread application of standardization and quality improvement in pathology reporting.

Biopsy↗
PubMed2005

Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy.

PURPOSE: To prospectively compare the ability of clinical examination, mammography, vascularity-sensitive ultrasound, and magnetic resonance imaging (MRI) to determine pathologic complete response (CR) in breast cancer patients undergoing neoadjuvant chemotherapy. PATIENTS AND METHODS: Participants were women with primary measurable, operable invasive breast cancer (Stages I-III) who presented to the University of Michigan Breast Care Center. Eligibility criteria were based on clinical need for chemotherapy as part of the overall treatment plan. The chemotherapy consisted of doxorubicin and docetaxel administered every 3 weeks for four cycles. Tumor size measurements by physical examination and by the three imaging modalities were performed before chemotherapy was initiated and after its completion, prior to definitive surgery. Response criteria were pre-specified in this prospective design, and study radiologists analyzed the mammographic, sonographic and MRI image sets blinded to information from the other modalities and blinded to final histological diagnosis. The pathologic CR rate obtained by the clinical and imaging modalities was compared to pathologic CR as determined pathologically. RESULTS: 41 of 43 enrolled patients had a determination of pathologic response, and 4 patients had a pathologic CR to this chemotherapy (9.8%). The accuracy of physical examination, mammography, ultrasound, and MRI in determining pathologic CR was 75, 89, 82, and 89% respectively (NS). CONCLUSION: Biopsy after neoadjuvant chemotherapy remains absolutely necessary to determine pathologic CR to neoadjuvant chemotherapy, as the accuracy of current imaging modalities is insufficient to make this determination. The accuracy of mammography, vascularity-sensitive ultrasound, and MRI were not observed to be significantly different.

Adult↗
PubMed2006

Stroop performance in pathological gamblers.

Pathological gambling is a relatively prevalent psychiatric disorder that typically leads to severe family, social, legal, and occupational problems and is associated with a high rate of suicide attempts. Understanding the neurobiological basis of pathological gambling is a current focus of research, and emerging data have demonstrated that pathological gamblers may have impaired decision-making because of an inability to inhibit irrelevant information. In this study, we examined pathological gamblers by using the Stroop Color-Word Test, a neurocognitive task used to assess interference control. The "reverse" variant of the Stroop Color-Word Test was administered to a cohort of medication-free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In the reverse variant of the Stroop task, subjects are asked to read the meaning of the word rather than name the ink color. The reverse Stroop task was chosen because it highly discriminates ability to inhibit interference in a population of psychiatric patients. In our study, performance on the reverse Stroop task in the pathological gamblers was significantly slower and less accurate than in the healthy subjects. A new finding in our study was that for pathological gamblers, the average reaction time in the neutral condition (where the color names are displayed in black letters) was slower than the average reaction time in the incongruent condition (where the meaning of the color name and the color of the printed letters are different). This controlled study extends previous findings by showing that performance on the Stroop task is impaired in a sample of medication-free pathological gamblers.

Adult↗
PubMed2006

Impact of discordant radiologic and pathologic tumor size on renal cancer staging.

OBJECTIVES: To determine whether the discrepancy in the radiologic and pathologic size of renal cell carcinoma influences the final cancer stage. METHODS: Renal masses resected from December 1999 to September 2004 were identified using a pathologic database and compared by surgical accession number to an existing clinical renal tumor database to identify those T1 and T2 tumors for which radiologic and pathologic data were available. The tumor histologic features, maximal pathologic diameter, and maximal radiologic diameter were recorded. The percentage of tumor size reduction was then calculated using these data. RESULTS: Of the 236 renal cancers evaluated, 52% had regressed in size when comparing the pathologic and radiologic sizes. When stratified by histologic subtype, clear cell tumors regressed more often and to a greater degree than those that were chromophobe or papillary. Also, 15 organ-confined tumors were downstaged when comparing the maximal radiologic diameter and the maximal pathologic diameter, and 13 of these were clear cell tumors. CONCLUSIONS: A reduction in kidney tumor size is commonly observed at surgical resection because of a loss of blood flow to the tumor. This tumor size reduction has an impact on the final pathologic stage in organ-confined tumors for which size is the only criterion. The greatest tumor size reduction, and most frequent downstaging, was observed for conventional (clear cell) tumors. We believe this may explain, in part, the worse stage-stratified outcomes for clear cell tumors compared with other tumor types. We propose that renal cancer staging should be determined from accurate measurement of the radiologic size, rather than the pathologic size.

Adult↗
PubMed2000

Echocardiographic predictors of coronary artery pathology in pulmonary atresia with intact ventricular septum.

Coronary artery pathology is a major determinant of treatment strategy and outcome in patients with pulmonary atresia and intact ventricular septum (PA/IVS). For this reason, infants with PA/IVS routinely undergo preoperative cardiac catheterization. The goal of this study was to identify echocardiographic predictors of coronary artery pathology in infants with PA/IVS. The initial preoperative echocardiograms of 30 consecutive infants with PA/IVS (median age at diagnosis 1 day) were reviewed for indexes predicting the degree of coronary pathology. The tricuspid valve (TV) annulus diameter Z- score was determined and evidence of abnormal flow in the coronary arteries by Doppler was evaluated. Coronary pathology was defined by angiography and graded as: 0 = no fistulae; 1 = fistulae/no right ventricular (RV)-dependent coronary arteries; 2 = fistulae with 1 RV-dependent coronary; 3 = fistulae with >/=2- vessel RV-dependent coronary arteries. Outcome was classified as: 2 ventricles, "1.5" ventricles, and 1 ventricle. By angiography, 30% of the patients had grade 0 coronary pathology, 30% had grade 1, 20% had grade 2, and 20% had grade 3. There was 1 death in a patient with grade 3 coronary pathology. Among the survivors (median age at follow-up 28. 6 months), biventricular circulation existed in 12 patients (41%), 7 patients (24%) were 1.5, and 10 (34%) were 1 ventricle. All patients with TV Z-score </=-2 had coronary fistulae by angiography and 35% had grade 3 coronary pathology. None of the patients with grade 2 or 3 coronary artery pathology had a TV Z-score >-2.5. The sensitivity, specificity, positive, and negative predictive values of TV Z-score </=-2.5 in predicting RV dependent coronary arteries were 100%, 83%, 80%, and 100%, respectively. Thus, in newborns with PA/IVS the echocardiographically derived TV Z-score predicts the likelihood of coronary artery fistulae and RV-dependent coronary arteries and can be used to rationalize the need for preoperative diagnostic catheterization.

Cardiac Catheterization↗
PubMed2006

[Contribution of the pathology examination in the operating theatre in patients with skin cancer: retrospective analysis of 388 patients].

INTRODUCTION: Pathological examination in the operating theatre in patients undergoing resection of a skin cancer is one of the most adapted therapeutic approaches. We present our experience with 388 patients, comparing the rate of recurrence with or without operating-theatre pathological examination. MATERIAL AND METHOD: The study population included 388 patients, mean age 69.5 years (28-98 years) who underwent resection of 544 skin tumors (520 primary and 36 recurrent), 76.6% unique tumors. The pathological examination of the surgical specimen was performed immediately after removal. This method was systematic procedure for spinocellular carcinomas, was not performed for basocellular carcinomas measuring less than 1 cm when well circumscribed and not peri-orifice, and when reconstruction was not planned. RESULTS: The pathological examination was not performed in the operative theatre for 76 tumors; for 470 examinations performed in the operative theatre, at least one surgical margin was positive in 93 (19.8%). Anatomic regions concerned most were the tip of the nose and the eyelids. Recurrent tumors (5.0% of resections) accounted for 27% of the positive pathological results. Thirty-one patients had to have revision surgery, four after a false negative on the pathological examination performed in the operative theatre, four patients for a healing problem and 23 because of tumor recurrence (4%). DISCUSSION: Pathological examination in the operative theatre can help decrease the rate of recurrence in comparison with classical surgery using empiric margins. This method is reliable if performed by an experienced pathologist so that reconstruction can be undertaken before the definitive pathological results are obtained, improving patient comfort. These therapeutic options have a cost however in terms of equipment and personnel. Indications should be well chosen and balanced against the advantages of a two-phase classical procedure.

Adult↗
PubMed1997

Interstitial cystitis: a critique of current concepts with a new proposal for pathologic diagnosis and pathogenesis.

Interstitial cystitis (IC) has continued to be an unresolved problem in clinical urology despite intense investigation over the past 16 or more years. Its etiology and pathogenesis are still undetermined, and its pathologic diagnosis is essentially one of exclusion, with no specific or clear criteria. In this review, current concepts of the etiology/pathogenesis and pathology are critically analyzed, new pathologic observations summarized, and a proposal of neurogenic inflammation as the primary pathogenetic factor is presented in the context of all currently available information. The popular postulate attributing IC to a deficient or defective glycosaminoglycan urothelial surface layer is not substantiated by morphologic, experimental, clinical, or therapeutic observations. Although the consensus seems to discount an infectious etiology, there is sufficient evidence that a microbial factor-short of a bona fide clinical infection-may have a role. Both autoimmunity and mast cell infiltration also appear to have a role, despite the lack of evidence that either is involved as the primary etiologic factor. Claims that the so-called feline urologic syndrome may represent a natural animal model of IC are shaky. As it now stands, there is no natural or induced animal model that duplicates IC as it occurs in humans. No specific or diagnostic light microscopic pathologic features are provided by either routine histopathology or immunohistochemistry. Increasingly, it has been recognized that detrusor mast cell count has little or no diagnostic value. On the other hand, electron microscopy has provided important new observations: (a) presence of mast cells, activated by piecemeal degranulation, in close proximity to intrinsic nerves-particularly in suburothelium: (b) distinctive pathologic changes in urothelium, suburothelium, and muscularis in biopsy samples obtained after diagnostic bladder hydrodistension; (c) constant associated changes in venules, capillaries, and neural elements in the same biopsy samples; and (d) diffuse involvement of bladder wall, with the most evident and profound pathologic changes in posthydrodistension biopsy samples obtained from cystoscopically obvious lesions (glomerulations). These features are sufficiently distinctive to allow definitive pathologic diagnosis of IC, and provide a firm basis for primary involvement of neurogenic inflammation in its pathogenesis. A proposal is presented regarding the mechanisms invoked by neurogenic inflammation. This proposal revolves around sensory nerve excitation, the release of neuropeptides, and activated differential secretion of potent mast cell mediators. This proposal can account for the heterogeneity and variability of observed pathologic features, and upholds the tacit acceptance of IC as a disease of pluricausal etiology and multifactorial pathogenesis.

Animals↗
PubMed2001

Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

BACKGROUND: We have undertaken a large unselected, community-based neuropathology study in an elderly (70-103 years) UK population in relation to prospectively evaluated dementia status. The study tests the assumption that dementing disorders as defined by current diagnostic protocols underlie this syndrome in the community at large. METHODS: Respondents in the Medical Research Council Cognitive Function and Ageing Study were approached for consent to examine the brain at necropsy. Dementia status was assigned by use of the automated geriatric examination for computer-assisted taxonomy algorithm. Neuropathological features were standardised by use of the protocol of the Consortium to Establish a Registry of Alzheimer's Disease, which assesses the severity and distribution of Alzheimer-type pathology, vascular lesions, and other potential causes of dementia. A statistical model of dementia risk related predominantly to Alzheimer-type and vascular pathology was developed by multivariate logistic regression. FINDINGS: We report on the first 209 individuals who have come to necropsy. The median age at death was 85 years for men, and 86 years for women. Cerebrovascular (78%) and Alzheimer-type (70%) pathology were common. Dementia was present in 100 (48%), of whom 64% had features indicating probable or definite Alzheimer's disease. However, 33% of the 109 non-demented people had equivalent densities of neocortical neuritic plaques. Some degree of neocortical neurofibrillary pathology was found in 61% of demented and 34% of non-demented individuals. Vascular lesions were equally common in both groups, although the proportion with multiple vascular pathology was higher in the demented group (46% vs 33%). INTERPRETATION: Alzheimer-type and vascular pathology were the major pathological correlates of cognitive decline in this elderly sample, as expected, but most patients had mixed disease. There were no clear thresholds of these features that predicted dementia status. The findings therefore challenge conventional dementia diagnostic criteria in this setting. Additional factors must determine whether moderate burdens of cerebral Alzheimer-type pathology and vascular lesions are associated with cognitive failure.

Aged↗
PubMed1999

Effect of total androgen ablation on pathologic stage and resection limit status of prostate cancer. Initial results of the Italian PROSIT study.

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%, respectively). The initial results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens. These two effects are more pronounced after six months of NHT than after three months of therapy. The same degree of beneficial effects are not observed in clinical C tumours.

Adenocarcinoma↗
PubMed2006

The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study.

BACKGROUND: Few data are available about how social networks reduce the risk of cognitive impairment in old age. We aimed to measure this effect using data from a large, longitudinal, epidemiological clinicopathological study. METHODS: 89 elderly people without known dementia participating in the Rush Memory and Aging Project underwent annual clinical evaluation. Brain autopsy was done at the time of death. Social network data were obtained by structured interview. Cognitive function tests were Z scored and averaged to yield a global and specific measure of cognitive function. Alzheimer's disease pathology was quantified as a global measure based on modified Bielschowsky silver stain. Amyloid load and the density of paired helical filament tau tangles were also quantified with antibody-specific immunostains. We used linear regression to examine the relation of disease pathology scores and social networks to level of cognitive function. FINDINGS: Cognitive function was inversely related to all measures of disease pathology, indicating lower function at more severe levels of pathology. Social network size modified the association between pathology and cognitive function (parameter estimate 0.097, SE 0.039, p=0.016, R(2)=0.295). Even at more severe levels of global disease pathology, cognitive function remained higher for participants with larger network sizes. A similar modifying association was observed with tangles (parameter estimate 0.011, SE 0.003, p=0.001, R(2)=0.454). These modifying effects were most pronounced for semantic memory and working memory. Amyloid load did not modify the relation between pathology and network size. The results were unchanged after controlling for cognitive, physical, and social activities, depressive symptoms, or number of chronic diseases. INTERPRETATION: These findings suggest that social networks modify the relation of some measures of Alzheimer's disease pathology to level of cognitive function.

Aged↗
PubMed2003

The prevalence of DSM-IV personality pathology among individuals with bulimia nervosa, binge eating disorder and obesity.

BACKGROUND: There are numerous reports of personality disorder pathology in different eating disorders. However, few studies have directly compared personality pathology in bulimia nervosa, binge eating disorder and obesity. The present study examines group differences in DSM-IV personality pathology, considering the potential utility of understanding personality disorders in terms of diagnosis and dimensional scores. METHOD: Eating disorder diagnoses were established using the Eating Disorder Examination interview. Thirty-five bulimia nervosa patients, 15 binge eating disorder patients and 37 obese patients were assessed and compared on the International Personality Disorder Examination using categorical and dimensional personality disorder scores. RESULTS: For most personality disorders, there was a dichotomy of binge eaters versus non-binge eaters. In contrast, there was a continuum of severity in borderline personality disorder pathology between the groups. The dimensional system of measurement of personality pathology allowed for clearer differentiation between the groups. CONCLUSION: The study strongly indicates that personality disorder difficulties are present in patients who binge eat, while obese patients who do not binge eat display significantly less personality disorder pathology. Assessment of bulimia nervosa, binge eating disorder and obesity needs to address personality disorders and pathology. Dimensional markers of personality pathology can be used to supplement categorical diagnoses, providing information about the traits that underlie diagnosis.

Adult↗
PubMed2003

The role of natural recovery in alcoholism and pathological gambling.

While most pathological gamblers, like most alcohol abusers, recover on their own, it seems likely that they are at greater risk for relapse than those who have been through successful treatment. Accordingly, a substantial increase in treatment resources for pathological gamblers, along with greater efforts to establish the effectiveness of these treatments, ought to receive national priority. If the data on alcohol-abusing self-changers are generalizable to self-changing pathological gamblers, the prognosis for gamblers who stop gambling all together is better than for those who aspire to controlled or nonproblem gambling. While pathological gamblers with comorbid substance abuse are more difficult to treat than those without it, the impact of comorbid substance abuse on the decision by pathological gamblers to change has not yet been explored, although it should be. Similarly, the impact of other Axis I pathology on pathological gambling self-change, especially depression and anxiety, should be thoroughly explored. The most pressing problem in this field appears to be definitional. As a consequence, until consensus is reached on a reliable, valid, and useful classification scheme for pathological gambling, both research and clinical efforts will continue to suffer.

Alcoholism↗
PubMed2002

The free-to-total serum prostatic specific antigen ratio as a predictor of the pathological features of prostate cancer.

OBJECTIVES: Curative therapy and extended period of disease free survival for patients with prostate cancer is possible only if the radical prostatectomy is performed when the disease is organ confined. It has been shown that combined use of local clinical stage, Gleason score of transrectal needle biopsy and serum PSA can accurately predict the final pathological stage in men undergoing radical prostatectomy. Recently the free/total PSA (F/T PSA) has been shown to improve the specificity of serum PSA level in early detection prostate cancer. In this study the utility of F/T PSA ratio in prediction the final pathological features of the prostate cancer was investigated. METHODS: 52 patients who had undergone radical prostatectomy were included in this study with mean age of 63 (ranging from 49 to 73). According to the pathologic features of the tumors, patients were classified as organ confined in 37 (%71), specimen-confined in 39 (%75) and as with favorable pathology which was defined as organ confined or specimen confined with Gleason score lower than 7, 39 (%75) patients. RESULTS: Neither total PSA levels nor F/T PSA values correlate significantly with the pathological characteristics of the tumor. The logistic regression analysis showed that the biopsy Gleason score was the only variable that was able to predict the pathology of the tumor (p < 0,05). CONCLUSION: As a conclusion Gleason score of the needle biopsy specimen is the most predictive factor of the final pathological outcome. F/T PSA ratio did not provide additional information about predicting pathological stage.

Biopsy, Needle↗
PubMed2006

Restriction of the CD4+ T-cell receptor repertoire prevents immune pathology in TGF-beta1 knockout mice.

Mice with a targeted deletion in TGF-beta1 spontaneously develop CD4+ T-cell-dependent multifocal inflammatory disease and autoimmune pathology. T cells from TGF-beta1-/- mice are strongly activated, but the mechanisms that lead to T-cell activation and organ pathology are not well understood. Recent work shows that TGF-beta1 raises the threshold for signaling through the TCR, suppressing the response of T cells to mitogenic stimuli. This suggests the possibility that CD4+ T cells in TGF-beta1-/- mice become aberrantly activated and cause damage in response to physiologic inputs that ordinarily are not sufficient for cell activation, such as homeostatic MHC-TCR interactions, cytokines, or adhesion molecules. This model predicts that pathology is largely antigen-independent, and that CD4+ T cells, regardless of antigen specificity, will become activated in TGF-beta1-/- mice, with subsequent organ pathology. To test this model, we crossed BALB/c-TGF-beta1-/- mice with the DO11.10 TCR transgenic mouse. To obviate the possible development of nonclonotypic TCRs, we also bred in a deficiency in RAG-1. Cohorts of highly inbred BALB/c background TGF-beta1-/- mice with an increasingly restricted CD4+ T-cell repertoire (TGF-beta1-/- mice; DO11.10-TGF-beta1-/- mice; DO11.10-RAG-1-/-TGF-beta1-/- mice) were then analyzed for inflammatory organ pathology and T-cell activation. The data show that progressively restricting the CD4+ T-cell repertoire improved survival, ameliorated target organ pathology, and reduced T-cell activation to control levels. Therefore, these results find no support for the involvement of atypical T-cell activation pathways in disease in TGF-beta1-/- mice. Rather, T-cell activation and pathology in TGF-beta1-/- mice appear to be functions of typical TCR activation pathways. This supports the hypothesis that immune pathology in TGF-beta1-/- mice is self-antigen triggered.

Animals↗
PubMed1993

Preoperative CA-125 levels predict poor prognostic pathologic features in early stage, FIGO grade 1 and 2 endometrial adenocarcinoma.

Preoperative CA-125 levels were studied in patients with favorable histology and early clinical stage endometrial adenocarcinoma to determine its ability to predict the presence of poor pathologic prognostic features on final pathology. One hundred and one patients with clinical stage I (N = 65) or II (N = 19) or diagnosed by endometrial curettage (EMC) only (N-17) with grade 1 or 2 endometrial adenocarcinoma without gross cervical involvement underwent preoperative CA-125 levels. Final pathology was reviewed for five poor prognostic pathologic features: FIGO grade 3 histology, unfavorable histologic type (sarcoma, clear cell, or papillary serous), invasion into the outer third of the myometrium, extension to the cervix, and extra-uterine metastases. Fifteen patients (14.9%) had CA-125 levels greater than 30 IU ml-1. Of these 15 patients, 12 had one or more of the five poor prognostic pathologic features (positive predictive value 80.0%, specificity 95.8%, P < 0.0001). However, since 30 of the 101 patients were found to have one or more of these poor prognostic pathologic features the sensitivity was only 40.0%. When clinical stage I patients were analyzed separately three patients (4.6%) had CA-125 levels greater than 30 IU ml -1 (positive predictive value 100%, specificity of 100%, sensitivity of 21.4%, P = 0.008). For patients with clinical stage II carcinoma, CA-125 was not predictive of pathologic findings except as a negative predictor of disease in a subgroup of patients whose endocervical curettage (ECC) demonstrated carcinoma unattached to endocervical tissue. In patients diagnosed by EMC only, an elevated CA-125 level was associated with poor prognostic pathologic features (P = 0.001). An elevated preoperative CA-125 reliably predicts advanced disease even in patients with apparently favorable histology and clinical stage, however the sensitivity of this method remains low.

Journal Article↗