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PubMed2006

Somatostatin receptor profiling in hepatic metastases from small intestinal and pancreatic neuroendocrine neoplasms: immunohistochemical approach with potential clinical utility.

BACKGROUND: The expression of somatostatin receptors (SSTRs) on endocrine tumor (ET) cells forms the basis for somatostatin analog treatment of patients with SSTR-positive, hormonally active ETs. In patients with SSTR-negative ETs, the clinical response is generally absent or suboptimal, while nonfunctioning ETs with SSTR positivity show a variable response to such therapy. METHODS: We retrospectively studied SSTR subtype expression in hepatic metastases from 14 adult patients with primary endocrine carcinomas (ECAs) of the small intestine and pancreas and compared SSTR subtype expression among the primary and metastatic ECAs. Polyclonal antibodies against the 5 SSTR subtypes were used on formalin-fixed, paraffin sections from each primary and metastatic ECA. Both qualitative and semiquantitative evaluation of the stained ECA sections was carried out. RESULTS: Eleven (61%) of 18 hepatic metastases from small intestinal and pancreatic ECAs were positive for SSTR-1, 15 (83%) for SSTR-2, 13 (72%) for SSTR-3, 10 (56%) for SSTR-4, and 15 (83%) for SSTR-5. Among 11 hepatic ECA metastases from small intestinal ECAs (carcinoids), 7 (63%) expressed SSTR-1, 9 (81%) expressed SSTR-2, 8 (72%) expressed SSTR-3, 6 (54%) expressed SSTR-4, and 10 (91%) expressed SSTR-5. Of 7 hepatic ECA metastases from pancreatic ECAs, 4 expressed SSTR-1, 6 expressed SSTR-2, and 5 expressed SSTR-3 and SSTR-5 each. We also observed the immunohistochemical evidence of heterogeneity of expression of various SSTR subtypes in the primary enteropancreatic ECAs and their hepatic metastases. CONCLUSIONS: SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.

Adult↗

PubMed2006

Classification of multiple sclerosis patients by latent class analysis of magnetic resonance imaging characteristics.

BACKGROUND: Disease heterogeneity is a major issue in multiple sclerosis (MS). Classification of MS patients is usually based on clinical characteristics. More recently, a pathological classification has been presented. While clinical subtypes differ by magnetic resonance imaging (MRI) signature on a group level, a classification of individual MS patients based purely on MRI characteristics has not been presented so far. OBJECTIVES: To investigate whether a restricted classification of MS patients can be made based on a combination of quantitative and qualitative MRI characteristics and to test whether the resulting subgroups are associated with clinical and laboratory characteristics. METHODS: MRI examinations of the brain and spinal cord of 50 patients were scored for 21 quantitative and qualitative characteristics. Using latent class analysis, subgroups were identified, for whom disease characteristics and laboratory measures were compared. RESULTS: Latent class analysis revealed two subgroups that mainly differed in the extent of lesion confluency and MRI correlates of neuronal loss in the brain. Demographics and disease characteristics were comparable except for cognitive deficits. No correlations with laboratory measures were found. CONCLUSIONS: Latent class analysis offers a feasible approach for classifying subgroups of MS patients based on the presence of MRI characteristics. The reproducibility, longitudinal evolution and further clinical or prognostic relevance of the observed classification will have to be explored in a larger and independent sample of patients.

Adult↗

PubMed2001

The role of endothelin receptor antagonists in cardiovascular pharmacotherapy.

Endothelin (ET) is a hormone produced predominantly by endothelial cells which has been recognised to play a significant role in the development of several cardiovascular disease states. In order to combat the deleterious effects of ET, several ET-receptor antagonists (ETRA) are currently in clinical development. The agents developed thus far inhibit the actions of ET through either selective inhibition of the ET(A) receptors or non-selective inhibition of both ET(A) and ET(B) receptors. However, due to the differing proportions of the two receptor subtypes in various tissues, animal models and pathologies, it remains a matter of debate whether receptor selective agents impart significant clinical benefits over non-selective agents. This paper seeks to briefly summarise the important preclinical and clinical effects that have been reported in the literature and will attempt to provide a rationale for the use of both types of ETRAs in the treatment of both systemic and pulmonary hypertension as well as chronic heart failure (CHF).

Journal Article↗

PubMed1998

Predictive factors for local recurrence in osteosarcoma: 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy.

We investigated predictive factors for local recurrence in 540 patients with non-metastatic osteosarcoma of the extremity treated with surgery and neoadjuvant chemotherapy, between March 1983 and October 1994. The median follow-up was 7.5 (2.5-15) years. Local recurrences developed in 31 (6%) patients after a median time of 2 (0.5-7) years. Local recurrence did not correlate with patients' age and sex, histologic subtype, site and tumor volume, presence of pathologic fracture, chemotherapy regimen and type of surgery. Local recurrence-free survival (LRFS) correlated with the quality of surgical margins and response to chemotherapy: the 7-year LRFS was 97% after adequate surgical margins and 71% after inadequate surgical margins (p < 0.0001), and was 95% in good responders and 90% in poor responders (p = 0.001). Only 1 of 31 patients with local recurrence was free of disease 15 months after the last treatment, 3 were alive with uncontrolled disease and 27 died. This post-relapse outcome is significantly worse than in patients who relapsed with metastases only (25% free of disease, 0.5-9 years after the last treatment). We conclude that, in osteosarcoma of the extremity, limb-salvage procedures should be planned only when the preoperative staging indicates that it is possible to achieve adequate surgical margins. If the pathologic examination of the surgical specimen shows inadequate surgical margins, an immediate amputation should be considered, especially if the histologic response to preoperative chemotherapy was poor.

Adolescent↗

PubMed2001

Chordoid meningioma with polyclonal gammopathy. Case report.

The authors present a case of chordoid meningioma in a 55-year-old woman who manifested headache and personality change. Magnetic resonance imaging of the brain and cerebral angiography demonstrated a mass in the right frontal lobe that resembled a typical convexity meningioma. However, the pathological diagnosis was chordoid meningioma, a rare subtype of this tumor that usually occurs in adolescence and is known to be associated with Castleman syndrome. A meningothelial meningiomatous pattern suggestive of a meningothelial origin was focally present, and cytokeratin-positive squamoid cells were noted in the tumor. The lesion lacked dense infiltration of lymphocytes and plasma cells. Polyclonal gammopathy was the only sign of Castleman syndrome and hypochromic microcytic anemia was absent in this case. Polyclonal gammopathy resolved completely 6 months after total removal of the mass.

Castleman Disease↗

PubMed2002

Proteomics for cancer biomarker discovery.

The emergence of novel technologies allows researchers to facilitate the comprehensive analyses of genomes, transcriptomes, and proteomes in health and disease. The information that is expected from such technologies may soon exert a dramatic change in the pace of cancer research and impact dramatically on the care of cancer patients. These approaches have already demonstrated the power of molecular medicine in discriminating among disease subtypes that are not recognizable by traditional pathologic criteria and in identifying specific genetic events involved in cancer progression. This review covers a selection of advances in the realm of proteomics and its promise for cancer biomarker discovery. It also addresses issues regarding sample preparation and specificity and discusses current challenges that need to be overcome. Finally, the review touches on the efforts of the Early Detection Research Network at the National Cancer Institute in promoting biomarker discovery for translation at the clinical level.

Affinity Labels↗

PubMed2003

[Male breast cancer].

As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.

Aged↗

PubMedDate not supplied

Comparative analysis of clinical features and prognostic factors in resected bronchioloalveolar carcinoma and adenocarcinoma of the lung.

BACKGROUND: Over the past few years, clinical, radiological and pathological classification of lung adenocarcinoma and its subtypes, particularly bronchioloalveolar carcinoma (BAC), has radically changed. PATIENTS AND METHODS: Out of a series of 384 non-small cell lung cancer (NSCLC) patients, submitted to surgical resection and followed-up in our Department from 1981 to 1999, the data of 151 adenocarcinomas (35 BAC and 116 non-BAC) were reviewed and analyzed for prognosis. RESULTS: BAC and non-BAC series were similar in clinical and radiographic findings, type of resection and stage. Stage I was a dominant favorable prognostic factor (10-year survival: 58% of BAC, 41.2% of non-BAC), albeit associated with a significant risk of second primary metachronous lung tumor (10-year risk: 25% of BAC, 32% of non-BAC). Other independent prognostic factors were: absence of lymph node involvement for BAC and stage III-IV for non-BAC. In term of prognosis, advantages of BAC over non-BAC were fewer cases with lymph node involvement, increased presence of "well-differentiated" cells (p = 0.016) and lower incidence of a second primary metachronous tumor. Moreover BAC patients with a single nodule or mass also had a higher survival expectancy (mean survival: 77 months versus 56 for non-BAC). An unfavorable feature was the higher incidence of diffuse or multicentric radiological forms (p = 0.012). For both groups the presence of multiple or satellite nodules remain a diagnostic and surgical challenge: in BAC cases the evaluation of clonality is recommended.

Adenocarcinoma↗

PubMed2005

[Discovery of a new species of the pentastomid genus Porocephalus (Humboldt, 1811) from Taiwan, China and its pathogenic features].

OBJECTIVE: To describe the morphological characteristics of Porocephalus taiwana sp. nov., discuss its pathogenic features and the method of etiological diagnosis of the new disease. METHODS: Fecal sedimentation concentration was used to collect nymphs from the patient's watery stool for species identification. Clinical information was collected for determining the pathogenic features of the new infection. RESULTS: A new pathogenic pentastomid Porocephalus taiwana sp. nov. is discovered and a new disease, porocephaliasis taiwana, is nominated. With the findings from this case it is proposed that the traditional visceral pentastomiasis should be divided into two subtypes, Encystic and Excystic. According to the pathological features, this case belongs to the excystic visceral pentastomiasis. CONCLUSION: Porocephalus taiwana sp. nov. is a new pathogenic pentastomid infecting humans. Porocephaliais taiwana belongs to a novel type (excystic) of visceral pentastomiasis.

Animals↗

PubMed1988

The dystonias.

Both the pharmacological and pathological data suggest that the dystonias may be a group of disorders with multiple etiologies. Knowledge in this field would be immeasurably advanced if a genetic linkage or a consistent regional or chemical brain pathology could be identified for any single subtype. Both kinds of advance are required before the specific etiology can be identified. The problem in trying to identify disturbances in a disease where no obvious neuronal degeneration can be found is rendered extremely complex by the large numbers of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain. The problem is well exemplified by the relatively little progress that has been made in understanding the etiologies of the psychoses despite the many years of intense research effort. An additional difficulty in the dystonia field is the relative scarcity of postmortem tissue available for examination. It thus seems incumbent upon researchers in the field to garner whatever clues they may from the available literature. Each reader of the literature will probably form his own opinion as to the most fruitful brain regions and chemical avenues for research. This review seems to suggest, however, that the following brain regions may deserve the closest scrutiny for possible detection of a lesion: basal ganglia--including the zona incerta--with particular emphasis on the putamen red nucleus and surround vestibular nuclei nucleus of Cajal nucleus fastigii parabrachial area sensorimotor cortex Other regions worth attention are the spinal cord, premotor area, motor cortex and thalamus. It is even more difficult to decide on the types of chemical or histochemical assays that should receive priority. Recent work indicating that immunohistochemical staining for the immune complex glycoprotein HLA-DR can readily reveal areas of active neuronal degeneration, not detected by the usual histological methods, in a number of progressive neurological diseases suggests that such staining should be tried in dystonic brains. The hints in the literature that dystonic symptoms may be provoked or exacerbated by autoimmune processes would be further reason to undertake such staining. It is this literature which has already led Sandyk et al. to suggest that hypothalamic dysregulation of immune responses might be of fundamental importance in focal dystonia.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Diseases↗

PubMed1984

Perspectives on borderline subtypes--overview of current research.

This paper has reviewed recent efforts to subtype patients within the borderline group. An overview of current definitions of the borderline syndrome was followed by a critical evaluation of recent empirical investigations designed to subtype within the larger domain of borderline pathology. Studies of borderline patients have, in large part, been based on the descriptive-phenomenological approach. It has been argued that while establishing a reliable diagnosis based on signs and symptoms provides internal validation for current theories of the borderline syndromes, studies providing external validating criteria are sorely needed.

Borderline Personality Disorder↗

PubMed1994

[Clinical importance of karyotype in hematology].

Cytogenic analysis of leukemic cells has proven to be a mandatory part of the diagnosis of malignant hemopathies. Recurring clonal cytogenetic abnormalities may be divided into those exclusively associated with myeloid disorders, those uniquely observed in lymphoid diseases, and those detected in both myeloid and lymphoid hemopathies. Several of the common defects are characteristic of specific FAB types or subtypes and are associated with specific clinico pathologic syndromes and clinical complications. Cytogenetic abnormalities have served to define relatively homogeneous subsets of malignant hemopathies which are not evident from morphological and other available markers. Cytogenetic findings have been demonstrated to be powerful indicators in predicting clinical course and outcome in patients and in guiding their management. Given the significant progress made in the treatment of malignant hemopathies, it is very important to identify parameters which may be used to predict whether patients will respond favorably to standard therapies or if they are unlikely to do so and require alternative strategies, such as bone marrow transplantation. Cytogenetic studies have also provided important insights into the understanding of malignant transformation processes. In a number of recurring chromosome translocations characteristic of leukemias and lymphomas the genes that are located at the breakpoints have been identified. Molecular analysis has revealed that alteration in expression of these genes or in the properties of the encoded proteins resulting from the rearrangements plays an integral part in malignant transformation. Studies of clonality have suggested that several chromosome abnormalities may arise in pluripotent hemopoietic stem cells, whereas others may originate in cells of more restricted lineage. The author focuses first on the implications of the karyotype in the diagnosis and the prognosis of myeloproliferative syndromes, acute leukemias and myelodysplastic syndromes, then on the interest of describing new clinical-cytogenetic associations. Finally, some of the recent results obtained in a cytogenetic study of myelodysplastic syndromes are discussed.

Acute Disease↗

PubMed1998

[Renal cell carcinoma detected by metastasis to the frontal sinus: a case report].

A 58-year-old man was admitted with a swelling in the frontal region. Computerized tomography scan, magnetic resonance imaging and angiography revealed a tumor in the right frontal sinus. The surgically extirpated specimen showed clear cell carcinoma which was suspected to be a metastasis from renal cell carcinoma. Subsequent urologic examination disclosed the right renal tumor. Since there were no other systemic metastases, right nephrectomy was performed. Pathologically, the renal tumor was clear cell subtype renal cell carcinoma and had the same histology as the frontal sinus tumor.

Carcinoma, Renal Cell↗

PubMed1998

Altered expression of glutamate transporter GLAST mRNA in rat brain after photochemically induced focal ischemia.

BACKGROUND: The neurotransmitter glutamate is involved in fast excitatory synaptic transmission in the mammalian brain. Glutamate released from presynaptic terminals must be removed rapidly from the synaptic cleft by high affinity, sodium-dependent glutamate transporters to keep the extracellular glutamate concentration low to protect neuron from glutamate excitotoxicity, which is the major pathological mechanism of brain ischemia. GLAST is one of the identified four subtypes of the glutamate transporter system and has been suggested to play an important role in some pathological conditions. But until recently, very little information existed the concerning relationship between GLAST expression and cerebral ischemia. METHODS: Nonradioactive in situ hybridization was employed to evaluate the changes of glutamate transporter GLAST mRNA expression in rat cerebral cortex and hippocampus following photochemically induced focal cortical ischemia. RESULTS: GLAST mRNA expression in cerebral pyramid cells below the infarcted area did not change at 3 h, significantly decreased at 12 h, recovered to the control level at 24 h, and significantly increased at 72 h following the ischemic lesion. No changes in GLAST mRNA expression were observed in all subfields of the hippocampal complex. CONCLUSIONS: The present findings suggest that the time-course changes of GLAST mRNA expression after ischemia may be correlated with the pathogenesis of photosensitive ischemic brain damage.

ATP-Binding Cassette Transporters↗

PubMed2021

Automated Extraction of Tumor Staging and Diagnosis Information From Surgical Pathology Reports.

PURPOSE: Typically stored as unstructured notes, surgical pathology reports contain data elements valuable to cancer research that require labor-intensive manual extraction. Although studies have described natural language processing (NLP) of surgical pathology reports to automate information extraction, efforts have focused on specific cancer subtypes rather than across multiple oncologic domains. To address this gap, we developed and evaluated an NLP method to extract tumor staging and diagnosis information across multiple cancer subtypes. METHODS: The NLP pipeline was implemented on an open-source framework called Leo. We used a total of 555,681 surgical pathology reports of 329,076 patients to develop the pipeline and evaluated our approach on subsets of reports from patients with breast, prostate, colorectal, and randomly selected cancer subtypes. RESULTS: Averaged across all four cancer subtypes, the NLP pipeline achieved an accuracy of 1.00 for International Classification of Diseases, Tenth Revision codes, 0.89 for T staging, 0.90 for N staging, and 0.97 for M staging. It achieved an F1 score of 1.00 for International Classification of Diseases, Tenth Revision codes, 0.88 for T staging, 0.90 for N staging, and 0.24 for M staging. CONCLUSION: The NLP pipeline was developed to extract tumor staging and diagnosis information across multiple cancer subtypes to support the research enterprise in our institution. Although it was not possible to demonstrate generalizability of our NLP pipeline to other institutions, other institutions may find value in adopting a similar NLP approach-and reusing code available at GitHub-to support the oncology research enterprise with elements extracted from surgical pathology reports.

Humans↗

PubMed1998

Intra-axial tumors of the medullocervical junction: diagnosis and microsurgical treatment.

OBJECTIVE: To describe the clinical features, operative methods and postoperative management of the intra-axial tumors of medullocervical junction, and to make differential diagnosis for different subtypes. METHODS: Fifteen patients with intra-axial tumors of medullocervical junction were treated from August 1988 to June 1997. The diagnoses were confirmed by MRI and histological examinations. The tumors were divided into two subtypes according to the clinical features and the main body of the tumor. The distinctive points of the two subtypes and the appropriate surgical methods of different pathological type tumors were expounded. RESULTS: Tumors were totally removed in 10 patients and subtotally in 5. There was no death caused by operation. Postoperative complications included respiratory disturbance in six cases, upper digestive tract bleeding in one, depressed cough reflex in two, most of which recovered after proper treatment. On discharge, the nervous system status was improved in 11 cases, stable in 2 and worsened in 2. CONCLUSIONS: The intra-axial tumors of medullocervical junction can be divided into cervicomedullary and medullocervical subtypes. The MRI examination is decisive in the distinction of the diagnosis, and is important in the determination of the nature of the medullar cystic lesions and the guidance of the resection of tumor extent. The cervicomedullary tumors are more amenable to an aggressive surgical treatment, during which the surgeon should remove the tumors first in the cervical spinal cord area, then in the medullar area with the tumor resection expanding rostrally. It can make the operation safer to remove the tumors using appropriate techniques varied with pathological types of the tumors. Managing postoperative respiratory disturbances without delay is one of the important points in improving the therapeutic effect.

Adolescent↗

PubMed2002

Synapse loss is greater in presenile than senile onset Alzheimer disease: implications for the cognitive reserve hypothesis.

In the past, 'Alzheimer disease' (AD) referred to pathologic AD with clinical onset of dementia in the presenium, while 'senile dementia of the Alzheimer type' (SDAT) referred to senile onset AD. Because AD appears clinically homogeneous regardless of age of onset, the two subtypes in more recent years have not been distinguished. Pathologic differences have been noted, but synapse loss has not previously been compared between the two groups. Hypothesizing that synapse loss would be greater in presenile onset than senile onset AD, we compared synapse loss, as well as Alzheimer pathology in presenile and senile onset AD, using an ELISA method to quantify synaptophysin. Synaptophysin was significantly lower in presenile than senile AD in right frontal and bilateral parietal lobes. Neuritic plaque counts were significantly higher in presenile than senile AD in bilateral frontal and parietal lobes. Semi-quantitative evaluation of neurofibrillary tangles revealed significantly more tangles in bilateral frontal and parietal lobes in presenile than senile AD. Brain weight was significantly lower in presenile than senile AD. The differences in synapse loss and Alzheimer-type pathology in presenile and senile onset AD support the hypothesis that 'cognitive reserve' protects the human brain from neurodegenerative disease.

Aged↗

PubMed2006

Prognostic value of the International Neuroblastoma Pathology Classification in Neuroblastoma (Schwannian stroma-poor) and comparison with other prognostic factors: a study of 182 cases from the Spanish Neuroblastoma Registry.

In addition to clinical and biological factors, further valuable prognostic information in neuroblastoma (Schwannian stroma-poor) (NB) patients is provided by the histopathologic analysis and the application of the International Neuroblastoma Pathology Classification (INPC) system. The objective of this study was to assess the prognostic impact of the INPC classification in a series of NB (Schwannian stroma-poor) and its relation with other prognostic factors. One hundred eighty-two cases of NB were collected from the files of the Spanish Neuroblastoma Registry. Slides were reviewed, and NB cases were grouped into favorable and unfavorable categories according to INPC criteria, taking into account morphological features (mitosis-karyorrhexis index, histological subtype) and patient's age at diagnosis. Other pathological [presence of calcifications, tissular components, and number of mitotic cells per 10 high-power field (HPF)], immunohistochemical (P-glycoprotein and Ki-67 protein expression) and genetic (MYCN amplification and chromosome 1p deletion) features were also studied. Statistical analyses of overall survival with Kaplan-Meier curves and a multivariate study using Cox regression were performed (40.3% of NBs were considered favorable and 59.7% unfavorable). Unfavorable NB showed a mean survival time of 57 months compared with 89 months in favorable cases. Advanced stage, more than ten mitoses per 10 HPF, Ki-67 expression in more than 30% of tumor cells, MYCN oncogene amplification and chromosome 1p deletion were observed more frequently in unfavorable NB. The Cox regression analysis demonstrated that clinical stage (International Neuroblastoma Staging System stage 4) and histological subtype (undifferentiated NB) were the most important factors that influence the overall survival (p<0.001). INPC classification results are major prognostic indicators in NB and should be considered in the therapeutic stratification of NB patients.

Child↗