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PubMed1996

Extraneous tissue in surgical pathology: a College of American Pathologists Q-Probes study of 275 laboratories.

OBJECTIVE: To develop a multi-institutional reference database of extraneous tissue (contaminants) in surgical pathology. DESIGN: In 1994, participants in the College of American Pathologists Q-Probes quality improvement program performed prospective and retrospective evaluations of extraneous tissue found in surgical pathology microscopic sections for a period of 4 weeks or until 1000 slides were reviewed in each participating laboratory. PARTICIPANTS: Two hundred seventy-five surgical pathology laboratories institutions, predominantly from North America. MAIN OUTCOME MEASURES: Extraneous tissue contamination rate for slides in prospective and retrospective reviews; staffing and practice procedures; location of extraneous tissue on slides; type of extraneous tissue (normal, abnormal, nonneoplastic, neoplasm, microorganisms, etc); class of extraneous tissue (slide or block contaminants); source of extraneous tissue (different or same case); origin of extraneous tissue (pathology laboratory, physician's office or operating room); and degree of diagnostic difficulty caused by extraneous tissue. RESULTS: Three hundred twenty-one thousand seven hundred fifty-seven slides were reviewed in the prospective study and 57083 slides in the retrospective study. There was an overall extraneous tissue rate of 0.6% of slides (2074/321757) in the prospective study and 2.9% of slides (1653/57083) in the retrospective study. Of those slides with extraneous tissue, the extraneous tissue was located near diagnostic tissue sections in 59.5% of the slides reviewed prospectively and in 25.3% of slides reviewed retrospectively; deeper sections were performed to evaluate extraneous tissue in 12.2% of prospective cases and in 3.1% of retrospective cases. Of the laboratories, 98% had written guidelines for changing solution in tissue processors, and 64.9% had guidelines for maintaining water baths free of extraneous tissue. A total of 98.9% used lens paper, filter bags, or sponges for processing fragmented and small specimens. Written protocols for documentation of extraneous tissue in surgical pathology reports were established in 6.1% of laboratories, for removal of extraneous tissue from blocks in 5.7%, and for removal of extraneous tissue from microscopic slides in 4.7%. In 24% of laboratories no comment or record was kept to document extraneous tissue. Extraneous tissue consisted of neoplasm in 12.7% of the prospectively reviewed slides and in 6.0% of the retrospectively reviewed slides. For the prospective study, 59.4% of extraneous tissue was classified as slide contaminants, and 28.4% was found to be contaminants within the paraffin block; for the retrospective study, 72.9% was classified as slide contaminants and 15.9% as block contaminants. For the prospective study, 63.2% of extraneous tissue was presumed to be from a different case, and in the retrospective study, 48.5% was presumed to be from a different case. Over 90% of extraneous tissue was thought to originate from the pathology laboratory. The degree of diagnostic difficulty caused by extraneous tissue was judged to be severe in 0.4% of slides in the prospective study and 0.1% of slides in the retrospective study. In the prospective study, it could not be determined whether the tissue in the diagnostic sections was extraneous in 0.6% of slides, and in the retrospective study, it could not be determined whether tissue in the diagnostic sections was extraneous in 0.1%. CONCLUSIONS: This study has documented the frequency, type, origin, source, and diagnostic difficulty of extraneous tissue and presents benchmarks of extraneous tissue experienced in the general practice of surgical pathology.

Databases, Factual↗
PubMed1992

Interinstitutional assessment of colorectal carcinoma surgical pathology report adequacy. A College of American Pathologists Q-Probes study of practice patterns from 532 laboratories and 15,940 reports.

In 1991, the College of American Pathologist's Q-Probes Quality Improvement Program evaluated practices in 532 institutions for pathologic information provided in surgical pathology reports of 15,940 resected primary colorectal carcinomas. Participating institutions studied their last 30 completed cases and were from the United States (98%), Canada (1.5%), and Australia (0.4%). The influence of various institutional differences and other practice patterns were analyzed to determine factors associated with an increased institutional likelihood of providing information on pathology reports. The one practice significantly associated with increased likelihood of providing complete oncologic pathology information on eight of 11 gross and microscopic information items surveyed was the use of a standard report form or checklist. Other institutional differences bearing inconsistent associations included teaching institution status, presence of pathology residency, use of microscopic descriptions, institution bedsize category, and performance of DNA ploidy analysis. The development and adoption of a standardized report form or checklist for each case is a simple but effective means to assure report adequacy and consistent communication of oncologic pathology information. In conjunction with accompanying criteria for its accurate use, this process can be considered a practice guideline or practice parameter that can be extended to the surgical pathology examination of all resected malignant neoplasms.

Colorectal Neoplasms↗
PubMed2005

The early years of pathology as a specialty in Singapore.

During the first 86 years of Singapore's medical history (1819 to 1905), nobody was officially designated a "pathologist" although pathology was practised. All pathological work (purely medical or forensic) was done by non-specialist doctors. Representative cases are quoted so that conclusions can be drawn regarding what pathological practice was like and the problems faced. In 1905, the Governor, concerned about the high death rate in Singapore, consulted the Principal Civil Medical Officer, who advised that the most effective means to reduce the death rate was the establishment of a Department of Pathology with a full-time specialist pathologist in charge. Dr GA Finlayson was appointed the first Government Pathologist, responsible for all the hospitals in Singapore. He was also appointed Lecturer in Pathology in the Medical School. Work in the Pathology Department increased by leaps and bounds, and no research was possible. The first Annual Report of the Department (1907) is quoted in some detail to show the scope of the work done, reflecting the public health conditions of Singapore a hundred years ago. The Department gradually expanded and more staff were recruited. The new position of Government Bacteriologist was created. This officer served under the Government Pathologist in the Pathology Department.

History, 19th Century↗
PubMed2004

[Pathology in Rostock].

The name of Rostock was first mentioned in 1161 by the Danish historian Saxo Grammaticus. As the oldest university in Northern Europe, the Alma mater rostochiensis was inaugurated in 1419 and is proudely called Light of the North ("Leuchte des Nordens"). Its Medical Faculty belonged to the three founding faculties. As elsewhere, the roots of Rostock pathology hark back to anatomy. A Theatrum anatomicum existed since 1790. First lectures on pathology were read by Johann Wilhelm Josephi (1763-1845) who was Head of Anatomy in the so-called Dissection House ("Zergliederungshaus") situated at the Old Market of Rostock. In 1844, anatomy together with its pathology rooms moved into the Garden House ("Gartenhaus") on the university yard. From 1878 to 1930, the Pathology represented one section of the downtown Medical Studies Building. From 1930 up to now, the Pathology Institute is situated in the Strempel Street at the corner of the clinical center. The Rostock Pathology Chair was established in 1865. Since that time, the institute had ten directors. Inter alios, Ernst Schwalbe (1871-1920) was a famous teratologist at the beginning of the 20th century. Walther Fischer (1882-1969) was Head of Institute for 24 years and became well-known as oncopathologist. After World War II, Alexander Bienengräber (1911-1990) reconstructed the institute in all ist compartments to a modern standard. At present, about 40 persons, with eight pathologists among them, represent the staff of the institute. 150 medical students are taught in each semester. Scientific topics concern oral, colorectal and thyroid carcinoma, pancreatitis as well as renal and transplant pathology. Nearly 15,000 histology, 20,000 cytology, and 150 autopsy cases are presently examined per year.

Faculty, Medical↗
PubMedDate not supplied

[Anatomical pathology and molecular diagnosis].

150 years ago, R. Virchow proposed a "cellular pathology" theory that forced one to revise many concepts of the mechanisms responsible for the development of disease and marked the beginning and further development of anatomical pathology as an independent discipline. Rapid progress in immunology, genetics, biotechnology, and cellular and molecular biology in the late 1980s to the early 1990s gave rise to a new field, namely molecular medicine. Damage changes the profile of expression some genes, activates various signal systems, and, due to of intercellular and cellular-matrix interactions, then spreads first at the level of organs, then at that of the whole body if a pathological process cannot localize. By involving some cells, the pathological process cannot cause characteristic morphological changes and therefore traditional studies yield a negative result. Molecular pathology became a necessary additional tool in the work of a pathologist, by allowing him to obtain the information that had been earlier beyond the reach, which increased the validity of diagnosis. Some points of the Virchow "cellular pathology" theory are supported by molecular pathology.

Humans↗
PubMed2006

The history of the Laboratory of Pathology of the Cluj-Napoca Oncological Institute.

The Laboratory of Pathology of the actual "Professor Ion Chiricută" Oncological Institute of Cluj-Napoca, former "Iuliu Maniu" Institute for Cancer Study and Prophylaxis, had the privilege that in its framework carry on an important part of their activity professors Titu Vasiliu and Rubin Popa, who are forming, beside Victor Babeş, the golden trinity of the Romanian pathology. The Cancer Institute of Cluj, one of the first in the World, was founded in 1929, especially by the clear-sightedness and the efforts of Professor Iuliu Moldovan, the master of the modern Romanian school of hygiene. The clinic division was assisted by a Laboratory of Pathology, whose chief was appointed the young pathologist of high competence, Rubin Popa, associate Professor of this department of the Cluj School of Medicine. In 1942' he became director of the Institute, function accomplished until his premature disappearance in 1958. Titu Vasiliu worked in the Oncological Institute from 1949, a year after his forced retreat from the chair of pathology, up to 1958. Fortunately, his premature disappearance did not interrupt the activity of the laboratory, because the management of the Oncological Institute was committed to Ion Chiricută, an experimented and modern surgeon of Bucharest. From 1960, the Laboratory of Pathology has been led by Professor Augustin Mureşan, an experimented, rigorous and prudent pathologist, who has imprinted these indispensable qualities to his disciples learning under his leadership. The activity of the laboratory has been very favorably influenced by the presence of Professor Gheorghe Badenski from the Department of Microbiology. The collaboration with Professor Eugen Pora from Babeş-Bolyai Department of Animal Physiology and his disciples, Virgil Toma, Draga Nestor, Sena Roşculet, Carmen Stugren and Georgette Buga has carried on the performance of interesting works concerning the thymus involution in tumor-bearing hosts and its signification for the depressed immunity in the advanced stages of cancer. In the same direction, the behavior of mast cells has been studied in collaboration with Professor George Csaba from the Budapest Medical University, Department of Biology. The observations brought about were remarked by the Canadian scientist Hans Selye. Most of these works have been included in the book "Immunity and cancer", distinguished with "Victor Babeş" Prize of the Romanian Academy. The arrival in the Institute of Professor Ion Macavei, disciple of Iuliu Hatieganu and founder of the Clinical Hematology in Cluj, expert in blood and bone marrow cytology, has given a strong impulse to the studies of malignant hemopoietic diseases. The current use of cytologic and histopathologic examinations in this field of pathology and, especially, the introduction by him, for the first time in Romania, of the osteomedullary biopsy has permitted the elaboration of an appreciated work about the cytologic and histologic diagnosis of lymphadenopathies. In the histochemical-histoenzymatic period of the microscopic diagnosis, between the years 1960-1990, the laboratory has enjoyed by the advices and the material help of Professor Raymond Wegmann from the Paris University, Institute of Histochemistry, the founder-editor of the International Review of Histochemistry, from 1976, of Cellular and Molecular Biology, who visited our laboratory in 1992. From 1965, in an adjacent Laboratory of Cytogenetics, Corneliu D. Olinici has performed the first karyotypes in Cluj and has teached the method to several other specialists. Despite the technical difficulties, the works performed in the Laboratory of Pathology have succeeded sometimes to reach the quality required by Professor Chiricută to a valuable scientific work in cancerology. This performance has been obtained by a study concerning Crabtree effect variations in tumoral metastases or about lactic-dehydrogenase behavior in breast carcinomas.

Cancer Care Facilities↗
PubMed1987

From Osler to Olafson. The evolution of veterinary pathology in North America.

Most branches of biological science in North America developed first in the United States, and later were taught and practiced in Canada. An exception was veterinary pathology, which as a discipline taught in veterinary colleges and as a field of research, developed first in Canada, and from there crossed the border to the United States. Pathology was first taught at the Montreal Veterinary College, founded in 1866 by Duncan McEachran, a graduate of the Edinburgh Veterinary College. From the outset, he formed a close association with the medical faculty of McGill University, permitting his students to attend the same classes in the basic subjects with the medical students. Eventually, the Montreal Veterinary College became formally affiliated with McGill University, as the Faculty of Comparative Medicine and Veterinary Science. The McGill veterinary faculty was forced to close for economic reasons in 1903, but it left an enduring legacy, particularly in the field of veterinary pathology. The legacy, a novel concept in the 1870's, was that pathology was the cornerstone of a veterinary education; the place where anatomy, physiology, chemistry and botany met with the clinical subjects, and gave the latter meaning. This tradition was formed at the Montreal Veterinary College by the world renowned physician William Osler, North America's leading medical teacher, whom McEachran had invited to teach at the College in 1876 in addition to his duties in the faculty of medicine. Osler had studied with Virchow in Berlin and applied his methods of autopsy technique and of scientific inquiry to his teaching of both human and veterinary pathology at McGill. Osler also undertook investigations into various diseases of domestic animals, at the request of McEachran, who doubled as Chief Veterinary Inspector for the Dominion Department of Agriculture. Osler left McGill University in 1884. Only after that year did other North American veterinary schools adopt pathology as a discipline of instruction. However, by 1884, Osler had already left his indelible imprint on the students (both medical and veterinary) he had taught in Montreal, one of whom took over the teaching of pathology in the veterinary college. Another, who followed Osler's example and also studied in Berlin with Virchow, wrote the first book in the English language on veterinary post mortem technique in 1889.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

[Substance and intellectual roots of pathologic anatomy in Leipzig].

A survey is given on the development of pathologic anatomy in Leipzig since its establishment in the academic sense in 1869. Special interest was focussed on the scientific role of the directors of the institute and their influence on pathologic anatomy in Germany. It is obvious that research work was concentrated on problems of clinical pathology. But questions of experimental pathology as well as of etiology and pathogenesis of diseases were also of great interest. The principal cause for the high level of pathologic anatomy in Leipzig depends on the intellectual exchange with other schools of pathologic anatomy in Germany. 15 coworkers of the institute were called to a chair in other universities of Germany. Most directors came from other medical schools or worked several years out of Leipzig, resp. Personalities of special influence were Julius Cohnheim and Felix Marchand. Their scientific heritage is of great importance for the present time, too. In contrast to their scientific significance the important social changes of the last century found no reflection in the intellectual position of the leading exponents of academic pathology at Leipzig. In this sense a more conservative or reactionary position was characteristic.

Germany↗
PubMed1995

Pathology and emerging infections--quo vadimus?

There have been dramatic changes in the occurrence of infectious diseases throughout the world in the previous two decades. The emergence of new microbial agents, and the reemergence of infections previously believed to be controlled, threatens the health of all populations. The emergence of these infectious diseases has occurred during a period of breakdown in the capabilities of the public health surveillance systems, prevention programs, and disease control efforts. Expertise in pathology is critical to provide a strong national control program for emerging and reemerging infectious diseases. Despite the many significant achievements made by pathologists in improving understanding of the pathogenesis and diagnosis of infectious diseases, the field of pathology remains largely oriented toward neoplastic diseases, and has not yet identified infectious disease diagnosis as an important component of anatomic pathology training and research, even in the face of the current threats posed by microbial agents. In addition, there is currently a dearth of infectious disease pathologists in the United States and elsewhere in the world, and the use of the autopsy, a prime pathological tool for diagnosis of emerging infections, is on the wane. The most serious problem is that no formal training program for infectious disease pathology currently exists in the United States or elsewhere in the world. As a consequence of this lack of training opportunities, there is a severe deficiency of young, well-educated pathologists with infectious disease expertise. This article explores the historical linkages between the disciplines of infectious diseases and pathology, and suggests that infectious disease pathology as a subspecialty be strengthened and training programs be initiated.

Autopsy↗
PubMed1998

Evolution of pathology practice in the United States: current status and future trends.

This article traces the development of pathology practice from its origins in autopsy pathology to its current practice in the United States. The American model of practice differs markedly from that in continental European countries because of the extensive incorporation of "Clinical Pathology" with the traditional disciplines of anatomic pathology under the auspices of the Pathology Department. "Clinical Pathology" as it is now defined includes the laboratory testing disciplines of Chemistry, Hematology, Immunology, Medical Microbiology, and Transfusion Medicine. The increasing importance of computers and information management, DNA diagnostic techniques, and the multiple roles of the pathologist as a researcher and consultant in pathology practice in the United States is discussed.

Forecasting↗
PubMed2001

The genetic and pathological classification of familial frontotemporal dementia.

BACKGROUND: Frontotemporal dementia (FTD) is an important cause of neurodegenerative dementia, particularly in younger patients. TAU has been identified as the gene responsible for FTD linked to chromosome 17, but it is likely that there is pathological and genetic heterogeneity among families with FTD. OBJECTIVE: To explore the genetic and pathological basis of familial FTD. DESIGN: Clinical case series with genetic analysis of each family, and pathological confirmation of diagnosis where possible. SETTING: Specialist dementia research group, particularly recruiting patients with young-onset dementia. PATIENTS: Twenty-two families with an index member with FTD, meeting Lund-Manchester criteria, and a family history of other affected members with dementia were ascertained. RESULTS: Half of the families had mutations in the TAU gene (TAU exon 10 +14, +16, and P301S), and pathological diagnoses were available in 17 of 22 families. Three main pathological diagnoses were made: FTD with neuronal and glial tau deposition, FTD with ubiquitin inclusions, and FTD with neuronal loss and spongiosis but without intracellular inclusions. No cases of familial Pick disease were identified. With the use of the pathological diagnoses, each family with FTD with neuronal and glial tau deposition had a TAU mutation, whereas TAU mutations were not identified in families in the other 2 diagnostic groups. CONCLUSIONS: This study illustrates the value of TAU sequencing in FTD and suggests that around one half of individuals with familial FTD have TAU mutations and dementia with tau pathological findings. Furthermore, these data suggest that there are at least 2 additional genes to be identified among families with autosomal dominant FTD.

Adult↗
PubMed2005

Pathological gambling caused by drugs used to treat Parkinson disease.

BACKGROUND: Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood. OBJECTIVE: To examine the relationship between medical therapy for PD and pathological gambling. METHODS: In our routine movement disorders practice (2002-2004), we encountered 11 patients with idiopathic PD who had recently developed pathological gambling. We assessed the relationship to their medical therapy and compared them with cases identified by systematic review of the existing literature on pathological gambling and PD. RESULTS: All 11 patients with PD and pathological gambling were taking therapeutic doses of a dopamine agonist; 3 of these patients were not treated with levodopa. In 7 patients, pathological gambling developed within 3 months of starting to take or escalating the dose of the agonist; in the other 4 with a longer latency, gambling resolved after the agonist use was discontinued. Pramipexole dihydrochloride was the agonist in 9 of 11 cases in our series and 10 of 17 in the literature (68% in total). CONCLUSIONS: Dopamine agonist therapy was associated with potentially reversible pathological gambling, and pramipexole was the medication predominantly implicated. This may relate to disproportionate stimulation of dopamine D(3) receptors, which are primarily localized to the limbic system.

Adult↗
PubMed1999

Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses.

BACKGROUND: A number of prognostic factors have been reported for resected nonsmall cell lung carcinoma. None of them, however, has been reported to have greater prognostic impact than the pathologic TNM staging system. The authors evaluated 18 conventional clinicopathologic prognostic factors in each pathologic stage. METHODS: A retrospective study was conducted on surgically resected 836 lung carcinoma patients, and the following conventional prognostic factors were evaluated in multivariate analyses: age, gender, pack-year smoking, serum carcinoembryonic antigen and squamous cell carcinoma antigen levels, laterality of tumor, clinical N status, histologic type of tumor, greatest tumor dimension, grade of differentiation, pleural involvement, lymphatic invasion, vascular invasion, degree of fibrosing scarring, nuclear atypia, mitotic activity, and curativity of resection. RESULTS: The overall 5-year survival rate was 63.8%. In 430 cases of pathologic Stage I disease, multivariate analyses revealed 3 significant prognostic factors: clinical N status (P < 0.001), vascular invasion (P = 0.001), and curativity of resection (P < 0.001). In 406 cases of more advanced disease, i.e., pathologic Stage II, IIIA, IIIB, or IV, multivariate analyses revealed 4 factors as significant: histology (P = 0.001), pathologic N status (P < 0.001), tumor size (P < 0.001), and curativity of resection (P = 0.002). CONCLUSIONS: Conventional clinicopathologic prognostic factors had a different impact on prognosis in each pathologic TNM stage among patients who underwent surgical resection of nonsmall cell lung carcinoma. These factors should be analyzed separately in each pathologic TNM stage.

Adult↗
PubMed2001

Evaluation of artificial neural networks for the prediction of pathologic stage in prostate carcinoma.

BACKGROUND: Currently, the standard for predicting pathologic stage from information available at the time of prostate biopsy is the "Partin nomograms" that were derived using logistic regression analysis. The authors retrospectively reviewed a large series of men with clinically localized prostate carcinoma who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy. They then utilized pathologic and clinical data at the time of prostate biopsy to develop and test an artificial neural network (ANN) to predict the final pathologic stage for this group of men. They then compared the results of ANN with the previous nomograms. METHODS: Five thousand seven hundred forty-four men were treated at the authors' institution from 1985 to 1998. An ANN was developed using two randomly selected training and validation sets for predicting pathologic stage. Input variables included age, preoperative serum prostate specific antigen level, clinical TNM (tumor, lymph node, and metastasis) classification, and Gleason score from the biopsy specimen. Outcomes included organ confinement and lymph node involvement status. RESULTS: The ANN was slightly superior to the nomograms in predicting pathologic stage, such as organ confinement and lymph node involvement status. CONCLUSIONS: In predicting organ confinement and lymph node involvement status, ANN was more accurate and had a larger area under ROC than the nomograms based on the logistic regression method. Artificial neural network models can be developed and used to better predict final pathologic stage when preoperative pathologic and clinical features are known.

Adult↗
PubMed2000

Interventions for pathological gambling.

BACKGROUND: With the legalization of new forms of gambling there are increasing numbers of individuals who appear to have gambling related problems and who are seeking help. The individual and societal consequences are significant. Pathological gambling can result in the gambler jeopardizing or losing a significant relationship or job and committing criminal offences. Pathological gamblers may develop general medical conditions associated with stress. Increased rates have been reported for mood disorders, attention-deficit/hyperactivity disorder, substance abuse or dependence. There is a high risk of suicide and a high correlation with antisocial, narcissistic and borderline personality disorders and alcohol addiction. With increasing public awareness of gambling related problems health funders and practitioners are asking questions about the efficacy of treatments. Consequently quality research into gambling treatment is crucial. OBJECTIVES: The objective of this review was to complete a systematic review and meta-analysis of all randomised controlled trials (RCTs) of psychological and pharmacological treatments for pathological gambling, from both published and unpublished scientific reports. SEARCH STRATEGY: Published and unpublished RCTs of treatments of pathological gambling were identified by searches of electronic databases and hand searching journals likely to contain RCTs of gambling treatments. Researchers and gambling treatment centres were contacted by letter. Bibliographies of all identified research studies were scanned to identify other relevant references. SELECTION CRITERIA: All RCTs of treatments for pathological gambling were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The data was entered into the Cochrane Review Manager software (REVMAN). The component RCTs were quality rated, with special emphasis on the concealment of treatment allocation and blinding. Relative risk analyses were conducted for the dichotomous outcome of controlled vs. uncontrolled gambling. The relative risks were aggregated using both fixed and random effects models. Tests for heterogeneity were undertaken. Both short-term (1 month or less) and long-term (6 months or longer) outcomes were considered. MAIN RESULTS: Only four RCTs of psychological treatments were identified. These RCTs were heterogeneous in terms of design, interventions, outcome measurement and follow-up periods. All had small numbers of participants. The studies had poor methodological quality features. The experimental interventions, behavioural or cognitive-behavioural therapy (BT/CBT), were more efficacious than the control interventions in the short-term (relative risk 0.44, 95% confidence interval (CI) 0.24-0. 81). There was a trend for long-term treatment with BT/CBT to be more efficacious than the control treatments, but the statistical significance of this was sensitive to the statistical model used for meta-analysis. With a fixed effect model the relative risk was 0.56 (95% CI 0.33-0.95); the relative risk with a random effects model was 0.61 (95% CI 0.25-1.47). REVIEWER'S CONCLUSIONS: This systematic review revealed a paucity of evidence for effective treatment of pathological gambling. As gambling is becoming more accessible in many countries and there is epidemiological evidence of increasing rates of pathological gambling, more rigorous RCTs are required.

Behavior Therapy↗
PubMed1992

Molecular characterization and measurement of Alzheimer's disease pathology: implications for genetic and environmental aetiology.

The neuropathological changes seen in Alzheimer's disease represent an interaction between the ageing process in which normal intellectual function is retained, and changes which are specifically associated with severe cognitive deterioration. Molecular analysis of these changes has tended to emphasize the distinction between neurofibrillary pathology, which is intracellular and highly correlated with cognitive deterioration, and the changes associated with the deposition of extracellular amyloid, which appears to be widespread in normal ageing. Extracellular amyloid deposits consist of fibrils composed of a short 42 amino acid peptide (beta/A4) derived by abnormal proteolysis from a much larger precursor molecule (APP). The recent demonstration of a mutation associated with APP in rare cases with familial dementia, neurofibrillary pathology in the hippocampus and atypical cortical Lewy body pathology raises the possibility that abnormal processing of APP could be linked directly with neurofibrillary pathology. Neurofibrillary tangles and neuritic plaques are sites of dense accumulation of pathological paired helical filaments (PHFs) which are composed in part of an antigenically modified form of the microtubule-associated protein tau. The average brain tissue content of PHFs measured biochemically does not increase in the course of normal ageing but increases 10-fold relative to age-matched controls in patients with Alzheimer's disease. There is also a substantial (three-fold) disease-related decline in normal soluble tau protein relative to age-matched controls. This intracellular redistribution of a protein essential for microtubule stability in cortico-cortical association circuits may play an important part in the molecular pathogenesis of dementia in Alzheimer's disease. The role of abnormal proteolysis of APP in this process remains to be elucidated. Immunohistochemical studies on renal dialysis cases have failed to detect evidence of neurofibrillary pathology related to aluminium accumulation in brain tissue. Nevertheless it needs to be seen whether more sensitive biochemical assays of neurofibrillary pathology can demonstrate evidence of an association with aluminium.

Alzheimer Disease↗
PubMed2004

Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response.

BACKGROUND: Complete pathologic response of breast carcinoma to neoadjuvant chemotherapy is a well defined outcome that correlates with prolonged survival. Categorization of incomplete response depends on accurate measurement of residual tumor size but is complicated by the variable histopathologic changes that occur within the tumor bed. In the current study, the authors investigated the contribution of assessing tumor cellularity in the pathologic evaluation of response to chemotherapy. METHODS: The slides from diagnostic core needle biopsy and the subsequent matched resection specimens were examined in 240 patients with breast carcinoma: 120 "treated" patients who received neoadjuvant chemotherapy and 120 "control" patients who received primary surgical management within a few weeks of diagnosis. Clinical response and residual tumor size were evaluated in 108 treated patients who completed a clinical trial with paclitaxel and then received combined 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Tumor cellularity was assessed from hematoxylin and eosin-stained tissue sections as the percentage of tumor area that contained invasive carcinoma. RESULTS: After neoadjuvant chemotherapy, tumor cellularity decreased from a median of 40% in core needle biopsy to 10% in resection specimens (P<0.01; Wilcoxon signed rank test). The cellularity of core needle biopsy (median, 30%) tended to underestimate the cellularity of resection specimens (median, 40%) in the control group (P<0.01). Changes in cellularity varied within each clinical response category, particularly partial response and minor response. The greatest reduction was observed in the cellularity of residual primary tumors that measured < or =1 cm (pathologic T1a [pT1a] and pT1b tumors), but changes in cellularity varied in the pT1, pT2, and pT3 residual tumor categories. The shape of the distribution of tumor size, expressed as the greatest dimension in cm, was similar in the control group and the treatment group (excluding complete pathologic response); however, when residual tumor size and cellularity were combined, the distribution of pathologic response shifted left (toward complete response) with a steep decline, suggesting that many tumors had a large reduction in cellularity but little change in the tumor size. CONCLUSIONS: Cellularity of the tumor mass was reduced significantly by neoadjuvant chemotherapy, and the change varied widely in different categories of clinical response. Although residual tumors measuring < or =1 cm in greatest dimension had the most reduction in tumor cellularity, there was broad variability for all residual tumor groups (pT1-pT3). The frequency distribution of residual tumor size was altered markedly by the inclusion of tumor cellularity, indicating that the product of pathologic size and tumor cellularity may provide more accurate pathologic response information than tumor size alone.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.

Aged↗