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Worse Prognosis (bad + prognosis)
Selected AbstractsDoes Proximal Location of Culprit Lesion Confer Worse Prognosis in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction?JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2006KISHORE J. HARJAI M.D. ST segment elevation myocardial infarction (STEMI) from proximally located culprit lesion is associated with greater myocardium at jeopardy. In STEMI patients treated with thrombolytics, proximal culprit lesions are known to have worse prognosis. This relation has not been studied in patients undergoing primary percutaneous coronary intervention (PCI). In 3,535 STEMI patients with native coronary artery occlusion pooled from the primary angioplasty in myocardial infarction database, we compared in-hospital and 1-year outcomes between those with proximal (n = 1,606) versus nonproximal (n = 1,929) culprit lesions. Patients with proximal culprits were more likely to die and suffer major adverse cardiovascular events (MACE) during the index hospital stay (3.8% vs 2.2%, P = 0.006; 8.2% vs 5.8%, P = 0.0066, respectively) as well as during 1-year follow-up (6.9% vs 4.5%, P = 0.0013; 22% vs 17%, P = 0.003, respectively) compared to those with nonproximal culprits. After adjustment for baseline differences, proximal culprit was independently predictive of in-hospital death (adjusted odds ratio% 1.58, 95% confidence intervals, CI 1.05,2.40) and MACE (OR 1.41, CI 1.06,1.86), but not 1-year death or MACE. In addition, proximal culprit was independently associated with higher incidence of ventricular arrhythmias and sustained hypotension during the index hospitalization. The univariate impact of proximal culprit lesion on in-hospital death and MACE was comparable to other adverse angiographic characteristics, such as multivessel disease and poor initial thrombolysis in myocardial infarction flow, and greater than that of anterior wall STEMI. In conclusion, proximal location of the culprit lesion is a strong independent predictor of worse in-hospital outcomes in patients with STEMI undergoing primary PCI. [source] Inactivation of O6 -Methylguanine-DNA Methyltransferase in Human Lung Adenocarcinoma Relates to High-grade Histology and Worse Prognosis among SmokersCANCER SCIENCE, Issue 2 2002Hiroyuki Hayashi To evaluate the significance of O6 -methylguanine-DNA methyltransferase (MGMT) activity in the development of human lung adenocarcinoma (AC), we investigated promoter hypermethylation of the MGMTx gene by methylation-specific PCR, and the expression of MGMT protein by immuno-histochemistry in relation to smoking history of the patients. In total, 31 of 87 AC patients (35.5%) showed hypermethylation of the MGMT gene, and no significant difference was observed between smokers (37.3%) and non-smokers (33.3%). However, hypermethylation of the MGMT gene increased in parallel with lesser differentiation grade of tumors among smokers (well, 16.7%; moderately, 42.1%; poorly, 57.1%; P=0.022), although this trend was not observed among non-smokers. Almost all the tumors with promoter hypermethylation of the MGMT gene showed consistently negative MGMT staining by immunohistochemistry. When the prognosis of stage-I patients was compared among smokers, it was apparent that the prognosis of patients with inactivated MGMT was worse than that of MGMT-positive patients (P=0.036). Such differences in the prognoses were not observed among non-smokers. In conclusion, MGMT inactivation is related to the differentiation grade and the prognosis of lung AC patients among smokers. Although further studies are required, we speculate that smoking may induce hypermethylation, not only of the MGMT gene, but also of other important tumor suppressor genes. [source] Prognosis of dermal lymphatic invasion with or without clinical signs of inflammatory breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Guenther Gruber Abstract It is still an open debate whether tumor emboli in dermal lymphatics without inflammatory signs represent a similar bad prognosis like inflammatory breast cancer. We evaluated the prognostic role of dermal lymphatic invasion (DLI) in breast cancer with (DLI + ID) or without (DLI w/o ID) inflammatory disease (ID). From August 1988 to January 2000, 42 patients with DLI were irradiated. Twenty-five were classified as pT4, 13 out of them as pT4d (inflammatory disease); the 17 remaining patients had 1 T1c, 12 T2 and 4 T3 cancers with DLI. Axillary dissection revealed node-positive disease in 39/41 patients (median, 9 positive nodes). Thirty-eight out of 42 patients received adjuvant systemic treatment(s). After a mean follow-up of 33 months, 22/42 patients (52%) are disease-free. The actuarial 3-year disease-free survival is 50% (DLI w/o ID, 61%; DLI + ID, 31%; p < 0.03); the corresponding overall survival was 69% (DLI w/o ID, 87%; DLI + ID, 37%; p = 0.005). The presence or absence of ID was the only significant parameter for all endpoints in multivariate analyses. Dissemination occurred in 19 (45%), local relapse in 7 (n = 17%) and regional failure in 4 (10%). Nine patients (21%) had contralateral breast cancer/relapse. Despite the same histopathologic presentation, DLI w/o ID offered a significantly better disease-free survival and overall survival than ID. The finding of dermal lymphatic tumor invasion predicts a high probability for node-positive disease. © 2003 Wiley-Liss, Inc. [source] Significance of cell kinetic parameters in the prognosis of malignant melanoma: a reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2007Pierre Vereecken The maximum tumor thickness as measured by Breslow's method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB-1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings. [source] Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2009Adi Broyde Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki-67 proliferation index (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268 patients, the Ki-67 PI was correlated with clinical course and outcome. The mean Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse large B-cell lymphoma (n = 141), a Ki-67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three-year survival was 75% ± 5.6% in patients with a low Ki-67 index compared with 55.9% ± 6% in patients with a high index (P = 0.015). In patients with a low IPI (,2), 3-year survival was 94% ± 4% in those with a Ki-67 index ,70% and 64% ± 8.1% in those with a higher index (P = 0.002); in patients with bulky disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and 25% ± 12% (P = 0.012). Our results suggest that the mean Ki-67 PI differs by type of lymphoma. A cut-off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] ABH and Lewis histo-blood group antigens in cancerAPMIS, Issue 1 2001JACQUES LE PENDU Antigens of the ABH and Lewis histo-blood group family can be found on many normal cells, mainly of epithelial type. In carcinomas, altered expression of the various carbohydrate epitopes of this family occur, and are often strongly associated with either a good or bad prognosis. A review of the available data on these tumor-associated markers, their biosynthesis and their prognostic value is proposed here. For a long time it has been unclear whether their presence could affect the behavior of carcinoma cells. Recent data, however, indicate that they play biological roles in the course of tumor progression. The presence of sialyl-Lea or sialyl-Lex, which are ligands for selectins, promotes the metastatic process by facilitating interaction with the endothelium of distant organs. The loss of A and B antigens increases cellular motility, while the presence of H epitopes increases resistance to apoptosis by mechanisms that remain to be defined. The Ley antigen has procoagulant and angiogenic activities. All these observations are used to present a model that may account for the described associations between the presence or loss of these markers and the outcome of disease. Finally, their potential clinical applicaitons as tumor-associated markers or as targets of immunotherapy are reviewed. [source] Surgical Monotherapy Versus Surgery Plus Adjuvant Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma: A Systematic Review of OutcomesDERMATOLOGIC SURGERY, Issue 4 2009ANOKHI Jambusaria-PAHLAJANI MD BACKGROUND Adjuvant radiotherapy (ART) has been recommended for squamous cell carcinoma (SCC) with a high risk of recurrence, particularly perineurally invasive disease. The utility of ART is unknown. This study compares reported outcomes of high-risk SCC treated with surgical monotherapy (SM) with those of surgery plus ART (S+ART). METHODS The Medline database was searched for reports of high-risk SCC treated with SM or S+ART that reported outcomes of interest: local recurrence, regional or distant metastasis, or disease-specific death. RESULTS There were no controlled trials. Of the 2,449 cases of high-risk SCC included, 91 were treated with S+ART. Tumor stage and surgical margin status before ART were generally unreported. In 74 cases of perineural invasion (PNI), outcomes were statistically similar between SM and S+ART. In 943 high-risk SCC cases in which clear surgical margins were explicitly documented, risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death were 5%, 5%, 1%, and 1%, respectively. CONCLUSIONS High cure rates are achieved in high-risk cutaneous SCC when clear surgical margins are obtained. Current data are insufficient to identify high-risk features in which ART may be beneficial. In cases of PNI, the extent of nerve involvement appears to affect outcomes, with involvement of larger nerves imparting a worse prognosis. [source] PNET-like features of synovial sarcoma of the lung: A pitfall in the cytologic diagnosis of soft-tissue tumorsDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2001Pascale Hummel M.D. Abstract Fine-needle aspiration (FNA) cytology of soft-tissue tumors is evolving. As more experience is gained, we are becoming aware of potential pitfalls. We describe 2 cases of synovial sarcoma of the lung, primary and metastatic, in patients who had FNA biopsy performed on a lung mass. The cytologic smears showed extremely cellular groups of malignant small round cells, intersected by small blood vessels, with numerous loose single cells, in a background of macrophages and mature lymphocytes. The tumors displayed monomorphic cells forming rosettes and displaying occasional mitoses. A diagnosis of neuroendocrine tumor/primitive neuroepithelial tumor (PNET) was suspected. Furthermore, this suspicion was supported by immunohistochemical stains, which showed positivity for a neuroendocrine marker, Leu 7 (case 1), and for a neural marker, CD 99 (O 13 or HBA 71) (both cases); and negativity for cytokeratins (case 1). The resection specimen of case 1 had mostly tightly packed small round cells, with occasional rosettes, similar to the FNA biopsy, and focal areas composed of spindle cells, organized in a focal fibrosarcoma-like and hemangiopericytoma-like pattern. A balanced translocation between chromosomes X and 18, demonstrated by both karyotyping and fluorescent in situ hybridization (FISH), enabled us to make a diagnosis of synovial sarcoma, which was histologically classified as poorly differentiated. Case 2 was a metastatic biphasic synovial sarcoma of the arm, with a prominent epithelial component. Synovial sarcoma, when composed mainly of small round cells on cytologic smears, is a great mimicker of neuroendocrine/PNET tumors, with light microscopic and immunohistochemical overlap. Awareness of this potential pitfall may aid in preventing a misdiagnosis. Its recognition is of major concern, especially for the poorly differentiated variant, because it is associated with a worse prognosis. Diagn. Cytopathol. 24:283,288, 2001. © 2001 Wiley-Liss, Inc. [source] An infantile-onset, severe, yet sporadic seizure pattern is common in Sturge-Weber syndromeEPILEPSIA, Issue 9 2009Eric H. Kossoff Summary The young age of onset and frequently intractable nature of seizures associated with Sturge-Weber syndrome (SWS) have been well-reported in large studies. However, many clinicians also anecdotally describe prolonged but sporadic seizure clusters. Over a 5-year period, 77 children and adults with SWS and at least one reported seizure were referred to and evaluated at the Hunter Nelson Sturge-Weber Center at the Kennedy Krieger Institute. The median age of seizure onset was 6 months with 43 (56%) presenting <1 year of age. Age at seizure onset ,6 months was associated with increased hemiparesis, but not seizures. A characteristic pattern of clustering, intense seizures followed by prolonged seizure-free periods was reported in 30 (39%), but was not associated with worse prognosis. This seizure pattern appears to be common with SWS and leads to difficult treatment decisions, especially in regard to the timing of potential surgical resection. [source] Status Epilepticus in Children with Epilepsy: Dutch Study of Epilepsy in ChildhoodEPILEPSIA, Issue 9 2007Hans Stroink Summary:,Purpose: To study course and outcome of epilepsy in children having had a status epilepticus (SE) as the presenting sign or after the diagnosis. Methods: A total of 494 children with newly diagnosed epilepsy, aged 1 month through 15 years, were followed prospectively for 5 years. Results: A total of 47 Children had SE. Forty-one of them had SE when epilepsy was diagnosed. For 32 (78%), SE was the first seizure. SE recurred in 13 out of 41 (32%). Terminal remission at 5 years (TR5) was not significantly worse for these 41 children: 31.7% had a TR5 <1 year versus 21.2% of 447 children without SE. They were not more often intractable. Five out of six children with first SE after diagnosis had a TR5 <1 year. Mortality was not significantly increased for children with SE. Independent factors associated with SE at presentation were remote symptomatic and cryptogenic etiology, and a history of febrile convulsions. Children with first SE after inclusion more often had symptomatic etiology. Conclusions: Although we find a trend for shorter TR5 in children with SE at presentation, outcome and mortality are not significantly worse. Etiology is an important factor for prognosis. Children with SE during the course of their epilepsy have a worse prognosis and a high recurrence rate of SE. This outcome is not due to the SE itself, but related to the etiology and type of epilepsy. The occurrence of SE is just an indicator of the severity of the disease. [source] Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2004Krzysztof Jamroziak Abstract: The significance of genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Polymorphisms of genes encoding for xenobiotics and drug transporters are potential factors, which can influence the risk of developing ALL and its clinical outcome. P-glycoprotein (P-gp) is an adenosine triphosphate-binding cassette (ABC)-family transporter involved in protection against xenobiotics and multi-drug resistance. Recently, the single-nucleotide polymorphism C3435T of MDR1 gene has been found to be associated with altered tissue expression and function of P-gp. To evaluate whether C3435T MDR1 polymorphism is associated with the occurrence and outcome of ALL, 113 children with ALL (median age 5.1 yr) and 175 healthy individuals of Polish Caucasian origin were studied by polymerase chain reaction-restriction fragment-length polymorhism (PCR-RFLP) assay. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (OR, 95% CI; 1.8, 1.1,3.1; P = 0.037). Besides, the analysis of factors influencing clinical outcome of our ALL patient cohort showed that CC genotype carriers had significantly lower event-free survival probability (pEFS) (0.62 vs. 0.87; P = 0.007) and overall survival probability (pOS) (0.72 vs. 0.91; P = 0.006). The Cox proportional hazards model-based analysis revealed that the hazard ratios for lower pEFS and lower pOS among CC homozygous subjects were 3.9 (P = 0.008) and 3.3 (P = 0.02), respectively. In conclusion, the results of the present study provide evidence that C3435T MDR1 polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL. Carriers of the TT genotype are more at risk of developing ALL than other individuals, whereas CC genotype carriers are supposed to have worse prognosis. [source] Outcome of sinonasal melanoma: Clinical experience and review of the literature,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2010Thomas N. Roth MD Abstract Background. Primary sinonasal malignant melanoma (SNMM) is a rare clinical entity. There is neither a classification nor a staging system nor an evidence-based treatment concept established. Our objective was to find potential risk factors predicting the outcome. Methods. Twenty-five patients with histologically confirmed SNMM were consecutively included and retrospectively analyzed. Staging methods were nasal endoscopy, CT, MRI, and positron emission tomography (PET) scan. Patients were selected for a curative or palliative concept. All patients had postoperative follow-up with control-MRI at 3 and 6 months. Restaging was performed when local recurrence occurred. Results. Nineteen patients underwent primary surgery with curative intention; in 16 cases with tumor free margins. Thirteen patients (68%) had transnasal endoscopic surgery, 4 lateral rhinotomy, and 2 transfacial approach with orbital exenteration. Six patients (32%) had palliative therapy and 7 patients (37%) had adjuvant radiotherapy. Despite radical operations, 6 patients (37%) showed local recurrence and 8 patients (50%) developed distant metastasis. In 2 patients with incomplete surgery, regional metastasis was noted. The median disease-free interval was 18 months, and the median overall survival rate was 23 months. Conclusion. SNMMs of the ethmoid and maxillary sinuses have a worse prognosis than other localizations in the nasal cavity; infiltration into the skull base, orbit, or facial soft tissue correlates with a very poor outcome corresponding to the palliative situations. Furthermore, local recurrence insinuates aggressive disease with short survival rate. A main difference from its cutaneous counterpart seems to be a primary tendency to hematogenic spread. Further research is needed to confirm these findings. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [source] Primary cancer of the sphenoid sinus,A GETTEC study,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2009Pierre Olivier Vedrine MD Abstract Background. Primary involvement of the sphenoid sinus occurs in 2% of all paranasal sinus tumors and is associated with dismal prognosis. Optimal management remains debatable. Methods. A total of 23 patients were treated for a primary cancer of the sphenoid sinus from 1988 to 2004. Charts were reviewed for patient-, tumor-, and treatment-related parameters. Univariate and multivariate analyses were conducted to identify prognostic factors for locoregional control and survival. Results. Cranial neuropathies were present in 12 patients. Pathologic findings included adenoid cystic carcinoma, adenocarcinoma, lymphoma, squamous cell carcinoma, sarcoma, neuroendocrine carcinoma, melanoma, and malignant hemangiopericytoma. All but 2 patients had stages III to IV cancer. Radiotherapy was performed in 18 patients and chemotherapy in 12. Of 10 patients undergoing surgery, total excision with grossly negative margins was achieved in 4 patients and subtotal resection in 6. Median locoregional control and overall survival were 12 and 41 months, respectively. On multivariate analysis, cranial neuropathy was associated with worse locoregional control and survival. Surgery was rarely complete because of advanced stages at presentation, but it yielded better outcomes than other treatments without surgery in non lymphoma-cases. Conclusion. Early CT and MRI should be performed when facing aspecific, rhinological, or neuro-ophtalmological symptoms. Cranial neuropathies indicate a worse prognosis. Surgery, including debulking surgery, may be preferred to combined modality treatments without surgery. Its apparently favorable impact on prognosis would need to be tested in homogenous histological groups of patients, which is impossible because of the rarity of the disease. Highly conformal radiotherapy (adjuvant or definitive) should be encouraged and optimized with concurrent chemotherapy in advanced stages. Aggressive multidisciplinary management including surgery, chemotherapy, and radiotherapy should be encouraged and adapted on histology and tumor extensions. Progress is still warranted to improve outcomes. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Impact of young age on prognosis for head and neck cancer: A matched-pair analysisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2005Jeffrey S. Gilroy MD Abstract Background. The purpose of this study was to review outcomes of young patients (age <40 years) treated with definitive radiotherapy alone for squamous cell carcinoma of the oropharynx, and larynx, and to compare these results with an older matched patient cohort. Methods. Since 1983, 30 previously untreated young patients underwent definitive radiotherapy at the University of Florida and were matched with an older group of patients (age >45 years) with respect to primary site, stage of disease, and sex. Results. There was no difference in cause-specific survival, locoregional control, or long-term complications between the two groups; however, there was a significant difference in overall survival favoring young patients (p = .0174). Older patients had twice as many second malignancies. Conclusion. Young age does not confer a worse prognosis in patients treated with definitive radiotherapy for squamous cell carcinoma of the oropharynx and larynx. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2002Christopher J. O'Brien MS, FRACS Abstract Background Metastatic cutaneous cancer is the most common parotid malignancy in Australia, with metastatic squamous carcinoma (SCC) occurring most frequently. There are limitations in the current TNM staging system for metastatic cutaneous malignancy, because all patients with nodal metastases are simply designated N1, irrespective of the extent of disease. The aim of this study was to analyze the influence of clinical stage, extent of surgery, and pathologic findings on outcome after parotidectomy for metastatic SCC by applying a new staging system that separates metastatic disease in the parotid from metastatic disease in the neck. Methods A prospectively documented series of 87 patients treated by one of the authors (COB) over 12 years for clinical metastatic cutaneous SCC involving the parotid gland and a minimum of 2 years follow-up was analyzed. These patients were all previously untreated and were restaged according to the clinical extent of disease in the parotid gland in the following manner. P1, metastatic SCC of the parotid up to 3 cm in diameter; P2, tumor greater than 3 cm up to 6 cm in diameter or multiple metastatic parotid nodes; P3, tumor greater than 6 cm in diameter, VII nerve palsy, or skull base invasion. Neck disease was staged in the following manner: N0, no clinical metastatic disease in the neck; N1, a single ipsilateral metastatic neck node less than 3 cm in diameter; N2, multiple metastatic nodes or any node greater than 3 cm in diameter. Results Clinical P stages were P1, 43 patients; P2, 35 patients; and P3, 9 patients. A total of 21 patients (24%) had clinically positive neck nodes. Among these, 11 were N1, and 10 were N2. Conservative parotidectomies were carried out in 71 of 87 patients (82%), and 8 of these had involved surgical margins (11%). Radical parotidectomy sacrificing the facial nerve was performed in 16 patients, and 6 (38%) had positive margins, (p < .01 compared with conservative resections). Margins were positive in 12% of patients staged P1, 14% of those staged P2, and 44% of those staged P3 (p < .05). Multivariate analysis demonstrated that increasing P stage, positive margins, and a failure to have postoperative radiotherapy independently predicted for decreased control in the parotid region. Survival did not correlate with P stage; however, many patients staged P1 and P2 also had metastatic disease in the neck. Clinical and pathologic N stage both significantly influenced survival, and patients with N2 disease had a much worse prognosis than patients with negative necks or only a single positive node. Independent risk factors for survival by multivariate analysis were positive surgical margins and the presence of advanced (N2) clinical and pathologic neck disease. Conclusions The results of this study demonstrate that patients with metastatic cutaneous SCC in both the parotid gland and neck have a significantly worse prognosis than those with disease in the parotid gland alone. Furthermore, patients with cervical nodes larger than 3 cm in diameter or with multiple positive neck nodes have a significantly worse prognosis than those with only a single positive node. Also, the extent of metastatic disease in the parotid gland correlated with the local control rate. The authors recommend that the clinical staging system for cutaneous SCC of the head and neck should separate parotid (P) and neck disease (N) and that the proposed staging system should be tested in a larger study population. © 2002 Wiley Periodicals, Inc. [source] Histological grading of invasive breast carcinoma , a simplification of existing methods in a large conservation series with long-term follow-upHISTOPATHOLOGY, Issue 6 2009Jeremy St J Thomas Aims:, To assess the validity of grading in the Edinburgh Breast Conservation Series; a consecutive cohort of 1812 early breast cancer patients treated by breast conservation and radiotherapy between 1981 and 1998 in a single specialist centre with ,9 years' follow-up and full staging data. Methods and results:, A single pathologist (J.St.J.T) graded 1650 cases using the Elston and Ellis method (EE) with particular reference to the component data: acinar differentiation, nuclear pleomorphism and mitotic counts. The original method was then compared with binary scoring of the same components and the relationship to prognosis reassessed. EE grades and individual grade components were prognostic (P < 0.0001) with 10-year cause-specific survival of 95.6%, 86.4% and 74.7% for EE grades 1, 2 and 3, respectively. A binary scoring of grade components produces four groups, splitting EE grade 2 tumours into two groups with different outcomes , 10-year survival rates for the four revised grades were 96.0%, 89.0%, 79.7% and 75.4%, respectively. Conclusions:, Existing grading methodology is fully applicable in the narrower context of a conservation series but can be simplified. Subdivision of EE grade 2 into a true intermediate prognosis group and a second group with a worse prognosis also adds benefit. [source] Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes,HUMAN MUTATION, Issue 5 2010Katherine V. Towns Abstract PRPF8 -retinitis pigmentosa is said to be severe but there has been no overview of phenotype across different mutations. We screened RP patients for PRPF8 mutations and identified three new missense mutations, including the first documented mutation outside exon 42 and the first de novo mutation. This brings the known RP-causing mutations in PRPF8 to nineteen. We then collated clinical data from new and published cases to determine an accurate prognosis for PRPF8 -RP. Clinical data for 75 PRPF8 -RP patients were compared, revealing that while the effect on peripheral retinal function is severe, patients generally retain good visual acuity in at least one eye until the fifth or sixth decade. We also noted that prognosis for PRPF8 -RP differs with different mutations, with p.H2309P or p.H2309R having a worse prognosis than p.R2310K. This correlates with the observed difference in growth defect severity in yeast lines carrying the equivalent mutations, though such correlation remains tentative given the limited number of mutations for which information is available. The yeast phenotype is caused by lack of mature spliceosomes in the nucleus, leading to reduced RNA splicing function. Correlation between yeast and human phenotypes suggests that splicing factor RP may also result from an underlying splicing deficit. © 2010 Wiley-Liss, Inc. [source] Studies of scleroderma at The Alfred Hospital, MelbourneINTERNAL MEDICINE JOURNAL, Issue 8 2006A. J. Barnett Abstract Scleroderma had been virtually unrecognized in this country before this study. Our interest in this condition was raised by the discovery that certain patients being investigated for ischaemic disease of the hand had scleroderma. Although uncommon, it is not excessively rare and we have been able to study an increasingly large number of patients, eventually resulting in 177 patients over a period of 35 years. The clinical features in these patients have been delineated. At first, the patients were subdivided into types: type 1, skin changes obvious only in the hands; type 2, skin changes extending beyond the hands but excluding the trunk; type 3, skin changes diffuse and involving the trunk. All types have similar visceral changes, but these are more severe and there is a worse prognosis in type 3 patients. Types 1 and 2 can conveniently be combined as acrosclerosis. Types 1 and 2 have a similar and good prognosis with survival at 30 years of 40%. Type 3 patients have a much worse prognosis, with no type 3 patients living more than 20 years. All types have a high incidence of autoantibodies, but these are generally not related to the severity of the disease and do not occur in relatives or spouses, this being the evidence of the absence of hereditary and environmental factors in their presence. Although patients may receive much relief from symptomatic measures, no treatment had lessened the skin stiffness and there is no specific treatment for the visceral lesions. The cause of the condition remains unknown. [source] Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Dipok Kumar Dhar Abstract KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1 -expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley-Liss, Inc. [source] Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 5 2003Marina Pollán Abstract The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis. © 2003 Wiley-Liss, Inc. [source] Prognostic significance of thrombocytosis in renal cell carcinoma patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2004KATSUKI INOUE Abstract Background: Thrombocytosis has been reported in many types of malignancies and has been studied as a prognostic factor. In the present study, we examined the incidence of thrombocytosis in patients with renal cell carcinoma (RCC) in order to evaluate the prognostic value of thrombocytosis. Methods: One hundred and ninety-six patients treated by radical nephrectomy for RCC were enrolled in this study. We divided the patients into a normal platelet count group and a thrombocytosis group according to the presurgical platelet count. The two groups were compared pathologically and clinically, including prognosis. Results: Thrombocytosis was present in 16 patients (8.2%). Platelet counts had normalized after nephrectomy in all patients with thrombocytosis. There was no correlation between histological type or grade and thrombocytosis. However, there were correlations between thrombocytosis and tumor size and tumor stage. Patients with thrombocytosis had a worse prognosis than patients without thrombocytosis (P = 0.0028). When adjusted for stage or tumor size, the correlation was limited to low stage (stage 1 + 2: P = 0.0041, stage 3 + 4: P = 0.2983) or small tumors (tumor size: ,4 cm, P = 0.0021; 4,7 cm, P = 0.0142; >7 cm, P = 0.8158). Conclusion: Thrombocytosis is an inexpensive and easy tool with which to evaluate the prognosis of RCC patients in daily medical practice. [source] Multiple primary malignancies in Spanish patients with hepatocellular carcinoma: Analysis of a hospital-based tumor registryJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2009Mario Fernández-Ruiz Abstract Background and Aim:, Little is known about the etiological associations and clinical features of extrahepatic primary malignant (EHPM) neoplasms in subjects with hepatocellular carcinoma (HCC). The aim of this study was to characterize this phenomenon in a consecutive series of Spanish patients in order to define its natural history and influence on survival. Methods:, A retrospective analysis of 245 patients with HCC during the period 1999,2003 was performed. Subjects identified with a second primary malignancy elsewhere constituted the EHPM group and were compared to patients with HCC alone. Results:, Eighteen patients (7.3%) had one or two associated extrahepatic malignancies (mean age 67.7 ± 9.7 years); of these, 17 had double cancer and one patient, triple. Nine of the 19 EHPM occurred before HCC diagnosis. The associated cancers included five cases of colorectal carcinoma, four cases of head and neck carcinoma, three cases of genitourinary cancer, two cases of lymphoproliferative disorder, one lung carcinoma, one skin melanoma, one breast carcinoma, and two cancers of unknown origin. Age and sex distribution, etiology of underlying hepatopathy, and liver function tests did not differ significantly between both groups. There was no difference between the overall survival rates. Conclusions:, EHPM is not rare among Spanish patients with HCC, although no specific clinicopathological features were detected in this population. Our results suggest that the association of another primary tumor with HCC does not imply a worse prognosis. The possibility of development of EHPM should be kept in mind when deciding on therapy and follow-up of HCC. [source] Does Proximal Location of Culprit Lesion Confer Worse Prognosis in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction?JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2006KISHORE J. HARJAI M.D. ST segment elevation myocardial infarction (STEMI) from proximally located culprit lesion is associated with greater myocardium at jeopardy. In STEMI patients treated with thrombolytics, proximal culprit lesions are known to have worse prognosis. This relation has not been studied in patients undergoing primary percutaneous coronary intervention (PCI). In 3,535 STEMI patients with native coronary artery occlusion pooled from the primary angioplasty in myocardial infarction database, we compared in-hospital and 1-year outcomes between those with proximal (n = 1,606) versus nonproximal (n = 1,929) culprit lesions. Patients with proximal culprits were more likely to die and suffer major adverse cardiovascular events (MACE) during the index hospital stay (3.8% vs 2.2%, P = 0.006; 8.2% vs 5.8%, P = 0.0066, respectively) as well as during 1-year follow-up (6.9% vs 4.5%, P = 0.0013; 22% vs 17%, P = 0.003, respectively) compared to those with nonproximal culprits. After adjustment for baseline differences, proximal culprit was independently predictive of in-hospital death (adjusted odds ratio% 1.58, 95% confidence intervals, CI 1.05,2.40) and MACE (OR 1.41, CI 1.06,1.86), but not 1-year death or MACE. In addition, proximal culprit was independently associated with higher incidence of ventricular arrhythmias and sustained hypotension during the index hospitalization. The univariate impact of proximal culprit lesion on in-hospital death and MACE was comparable to other adverse angiographic characteristics, such as multivessel disease and poor initial thrombolysis in myocardial infarction flow, and greater than that of anterior wall STEMI. In conclusion, proximal location of the culprit lesion is a strong independent predictor of worse in-hospital outcomes in patients with STEMI undergoing primary PCI. [source] Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2010Shinichi Ohba J Oral Pathol Med (2010) 39: 74,78 Object:, Malignant cells show increased uptake, which is considered to be facilitated by glucose transporters (GLUTs). Increased GLUT-1 expression has been reported in many human cancers. We hypothesized that a oral squamous cell carcinoma, characterized by high frequency of lymph node metastasis, distant metastasis or local recurrences, was associated with GLUT-1 overexpression in invasion front. Methods:, GLUT-1 immunostaining in invasion front was studied on 24 oral squamous cell carcinomas, and revealed the correlation with the clinical characteristics. Result:, The analysis showed that all oral squamous cell carcinoma patients and GLUT-1 expression correlated the depth of the tumors (P = 0.023 < 0.05). Furthermore the survival of patients who had overexpression of invasion front was significant shorter than that of patients with GLUT-1 weakly positive (P = 0.046 < 0.05). No significant association was noted between GLUT-1 immunostaining and either age, gender, subsites, tumor size, or lymph node status. Conclusion:, The present study shows that GLUT-1 served as a marker indicating that tumors with deep invasion tended to result in a worse prognosis in patients due to either lymph node metastasis, a recurrence of the primary lesion or distant metastasis. [source] Differential expression of E-cadherin in metastatic lesionscomparing to primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006K.-F. Hung Background:, The main cause of treatment failure in resectable oral squamous cell carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell adhesion and motility, and is associated with OSCC progression. The aim of this study was to investigate the clinical significance of E-cad expression in OSCC with lymph node metastasis which had radical neck dissection done. Method:, Immunohistochemistry was used to detect E-cad expression in normal oral mucosa (NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45), and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated with the clinicopathologic features. Results:, E-cadherin immunoreactivity was progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It decreased significantly in the advanced stages of OSCC. However, the increase in E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions in relation to primary OSCC. Patients with such increased or positive immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis. Conclusion:, The findings suggested a dynamic change in E-cad immunoreactivity during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15,14.67; P = 0.040) implied the potential role of mortality predictors for OSCC cases with nodal involvement. [source] Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Hee Eun Lee MD Abstract Background and Objectives We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Methods Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. Results Low Ki-67 PI was correlated with poorly differentiated histology (P,=,0.034), an advanced T stage (P,<,0.001), and lymph node metastasis (P,=,0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P,=,0.003, log-rank test). Multivariate analysis revealed that Ki-67 PI remained as an independent prognostic factor (hazard ratio (95% CI),=,0.670 (0.450,0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P,=,0.025). Conclusions These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. J. Surg. Oncol. 2010;102:201,206. © 2010 Wiley-Liss, Inc. [source] Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006Koviljka Matusan MD Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. © 2006 Wiley-Liss, Inc. [source] Venous thromboembolism in malignant gliomasJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2010E. O. JENKINS Summary., Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas. [source] Cross-Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988,2006)JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010Rachel E. Pollard Background: Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas. Hypothesis/Objective: To identify differentiating features on cross-sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas. Animals: Thirty-three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma (n= 20), invasive adenoma (n= 11), or adenocarcinoma (n= 2). Methods: Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors. Results: Mean (± standard deviation) age for dogs with pituitary adenomas (10.6 ± 2.9 years) was greater than that of those with invasive adenomas (8.3 ± 2.7 years, P= .04). Eighteen out of 20 (90%) dogs with adenomas had contrast-enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 ± 0.7 cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast-enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 ± 0.7 cm, which was significantly greater than adenomas (P= .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas. Conclusions and Clinical Relevance: Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass >1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging. [source] Cardiovascular Involvement in 8 Dogs with Blastomyces dermatitidis InfectionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2006Chad Schmiedt Background:Blastomycosis is a common systemic fungal infection in dogs. Hypothesis:Dogs with cardiovascular involvement may have abnormalities in electrical conduction and valvular function, and may have a worse prognosis. Animals:Eight client-owned animals. Methods:Dogs with cardiovascular lesions caused by blastomycosis were identified from retrospective evaluation of medical records. Results:Five dogs had de novo infections and 3 had recurrences of previously treated infections. Harsh labored breathing, lethargy, and anorexia were the most common historic complaints. Three dogs had syncope. Physical examination and clinicopathologic data were typical of blastomycosis and included dyspnea, increased lung sounds, and lethargy. In addition, 3 dogs had heart murmurs and 1 had a third-degree atrioventricular block. Four dogs had myocarditis and 2 had pericarditis or epicarditis. Two dogs had cardiac signs attributed to extracardiac compression by fungal granulomas and clinical signs were relieved by treatment. Half of the remaining 6 dogs were euthanized; 2 of these were not treated. Of the remaining 3 dogs, 1 dog died acutely while sleeping; the second died intraoperatively during an attempt to place an epicardial pacemaker; and the third had Blastomyces -induced endocarditis and died of heart failure. Conclusions and Clinical Importance: Blastomycosis should be considered in the differential diagnosis of dogs from endemic areas with inflammatory myocarditis, heart block, heart base or intracardiac mass lesions, syncope, or endocarditis. 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