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High Grade (high + grade)
Terms modified by High Grade Selected AbstractsClinicopathological analysis of osteosarcoma of jaw bonesORAL DISEASES, Issue 1 2007EH Nissanka Objectives:, To identify clinicopathological characteristics and prognosis of osteosarcoma of the jaw bones (JOS) and to compare the data with results of similar studies. To study the effectiveness of different treatment modalities currently available for this malignancy. Subjects and methods:, Nineteen cases of JOS diagnosed from 1993 to 2003 were retrieved from the departmental archives. These were categorized into histopathological subtypes and graded according to the severity of the malignancies and the data analyzed. Fourteen cases were followed up and the success rate with different treatment modalities assessed. Results:, The mean age for JOS was 34.1 years. There were 11 mandibular lesions and eight maxillary lesions. Osteoblastic variant (53%) was the commonest histopathological subtype. High grade (grades III and IV) was more prevalent. All 14 followed up patients underwent surgical excision , five with adjuvant radiotherapy and six with adjuvant chemotherapy. Local recurrence was the commonest complication. Nine of the 14 were surviving with a survival rate of 64.2% for a median follow-up period of 5.25 years. Conclusions:, JOS is a distinct group of lesions with a better prognosis if diagnosed and treated early. It does not show any ethnic variability. Existing histopathological typing and grading may not indicate the prognosis of JOS. Adjuvant chemotherapy is a better treatment modality than adjuvant radiotherapy. [source] Comparison of the sensitivity of conventional cytology and the ThinPrep Imaging System for 1,083 biopsy confirmed high-grade squamous lesions,DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2010C.T. (A.S.C.), C.T. (I.A.C.), J. A. Halford B.App.Sc. Abstract Liquid-based cytology continues to be utilized as an adjunct to conventional cytology in most Australian laboratories, even though a direct-to-vial ThinPrep protocol has been introduced in many countries with established cervical screening programs. Manual screening of ThinPrep slides has been widely practiced for more than 10 years and the recent introduction of the ThinPrep Imaging System (TPI) has been reported as being more sensitive than the conventional smear (CS) in the identification of high-grade cervical disease. We report our experience with ThinPrep Imaging since its introduction into our routine gynecological cytology service. 87,284 split sample pairs reported using the Imaging System demonstrated a decrease in unsatisfactory reports (3.65% for CS and 0.87% for TPI) and an increase in possible high grade and definite high-grade squamous reports (1.57% for CS and 1.62% for TPI). For 1,083 biopsy confirmed high-grade lesions, the correct diagnosis of high grade or possible high-grade squamous disease was made on the ThinPrep imaged slide in 61.0% (661/1,083) of cases and on the CS in 59.4% (643/1,083). This was not statistically significant. When all abnormalities identified on cytology were considered, including possible low grade and definite low-grade abnormalities, the difference in sensitivity for Thinprep imaged slides of 96.0% (1,040/1,083) and CSs of 91.6% (992/1,083) was statistically significant. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis,HEPATOLOGY, Issue 3 2007Luca Di Tommaso Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725,734.) [source] Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosisHISTOPATHOLOGY, Issue 2 2010Lin Yu Yu L, Yang W, Cai X, Shi D, Fan Y & Lu H (2010) Histopathology,57, 193,201 Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosis Aims:, To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal-like phenotype and its prognosis. Methods and results:, The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohis-tochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high-molecular-weight CK (34,E12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring-like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal-like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal-like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal-like markers. Follow-up data of 19 patients were available. Median progression-free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months). Conclusions:, CNC has distinctive morphological features, which mostly exhibit a basal-like immunophenotype and poor prognosis. CNC is a typical representative of basal-like breast cancer. [source] The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in ,pure' ductal carcinoma in situ of the breastHISTOPATHOLOGY, Issue 2 2007M A J De Roos Aims:, To classify MUC1 according to five predefined expression patterns in ductal carcinoma in situ (DCIS) and related clinicopathological parameters, coexpression of other biological markers and prognosis. Methods and results:, With a manual tissue arrayer, 92% (n = 80) of the 87 DCIS samples were successfully targeted. Immunohistochemistry was carried out for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/Neu, p53 and cyclin D1. Entire membrane expression was related to Her2/neu negativity (P =0.042). Apical membrane expression was associated with low grade (P = 0.027), Her2/neu negativity (P = 0.014) and PR positivity (P = 0.005). Focal cytoplasmic expression was related to high grade (P = 0.006). Diffuse cytoplasmic expression was associated with high grade (P = 0.004), large tumour size (P = 0.046), Her2/neu positivity (P =0.042) and cyclin D1 positivity (P = 0.002). On the basis of these analyses the four patterns were reclassified as membranous or cytoplasmic expression. On multivariate analysis, cytoplasmic MUC1 expression (hazard ratio 8.5, 95% confidence interval 1.0, 73.0; P = 0.04) was the only independent predictor of local recurrence. Conclusions:, Four patterns of MUC1 expression are recognized in DCIS that suggest a relationship to functional differentiation and can be simplified into two types that are clinically relevant and could therefore be helpful in the distinction between different subgroups of DCIS. [source] Uncommon skin lesion in a patient with ataxia-telangiectasiaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2008Chinedu Ivonye MD A 20-year-old African-American man, with a history of ataxia-telangiectasia diagnosed at the age of one year, presented to the hospital with fever, cough, and headache of 2 days' duration. The fever was of high grade, associated with chills and rigors. The headache was frontal in location, constant, pounding in nature, and associated with photophobia and phonophobia; there was no neck pain, no neck stiffness, and no blurring of vision. The patient complained of facial pain. There were no relieving or aggravating factors. The family denied any change in mental status. ,The cough was productive of yellowish sputum. There was associated rhinorrhea. The patient complained of nausea and vomiting with the headache. A review of other systems was negative. ,On presentation in the emergency room, the patient was tachypneic, febrile, and tachycardic. He was oriented to time, place, and person. His neck was supple and meningeal signs were negative. He had maxillary sinus tenderness. Neurologic examination revealed nystagmus, ocular telangiectasia (Fig. 1), ataxia, and globally decreased muscle strength. Skin examination showed hypopigmented areas on all four extremities, the face, and neck (Figs 1,4), without involvement of the trunk. The rest of the physical examination was unremarkable. Figure 1. Area of vitiligo on the neck with premature graying of the hair Figure 2. Vitiligo on the hands Figure 3. Vitiligo involving the legs Figure 4. Ocular telangiectasia ,The leukocyte count was elevated at 19,600/mcL, with a differential of neutrophils (84%), monocytes (11%), and lymphocytes (5%). Hemoglobin and hematocrit were normal. Chemistry and chest X-ray were normal. ,Computed tomography scan of the head showed acute sinusitis and cerebellar atrophy consistent with ataxia-telangiectasia. ,A lumbar puncture was performed, and cerebrospinal fluid findings were suggestive of aseptic meningitis. ,The patient was treated for aseptic meningitis and acute sinusitis with acyclovir and ceftriaxone. The leukocyte count normalized, the patient remained afebrile, and was asymptomatic after 2 days of treatment with antimicrobials. The rest of the hospital stay was uneventful. [source] Serum calcitonin gene-related peptide levels in untreated prostate cancer patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006KAZUMI SUZUKI Background:, The role of calcitonin gene-related peptide (CGRP) in prostate cancer has not been fully understood. Moreover, the serum CGRP level in prostate cancer patients has never been reported. We measured the serum CGRP levels in untreated prostate cancer patients to elucidate its clinical significance. Materials and methods:, We used 36 serum samples from prostate cancer patients. All patients had never received any treatment. Serum CGRP was measured by immunoradiometric assay, and we analysed the association between serum CGRP level and clinicopathological factors. Results:, Serum CGRP levels in the patients with higher clinical stages and histological grade were significantly higher than in those with lower stages and grade, respectively. But the levels did not correlate with the patient's age, liver or renal functions, serum prostate-specific antigen levels. Conclusion:, Serum CGRP levels were significantly elevated in the patients with high grade or high stage untreated prostate cancer patients. Measurement of the serum CGRP may be a useful predictor of staging or grading of prostate cancer in the untreated prostate cancer patients. [source] Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004TETSUYA IMAO Abstract Background: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival. Methods: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34. Results: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 ± 67 and 58 ± 35 per ×400 field (mean ± SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 ± 22 and 142 ± 54 per ×400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors. Conclusion: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor. [source] Clinicopathological factors predicting recurrence of N0M0 renal cell carcinoma: A case series analysis of one facilityINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2003AIICHIRO MASUDA Abstract Background: Although many factors have been reported as predictors of the recurrence of renal cell carcinoma (RCC), none of the factors are consistent among different studies. In the study presented here, the potential clinicopathological predictors of the recurrence of N0M0 RCC were examined. Methods: A total of 201 patients who underwent nephrectomy for N0M0 RCC were examined to determine the pathological tumor stage (pT stage), pathological tumor grade of malignancy (tumor grade), symptoms, and tumor size. Results RCC recurred in 29 patients (14.4%), 50% of whom developed new tumors within 24 months after nephrectomy. The disease-free 3- and 10-year survival rates declined as the pT stage and tumor grade increased: these rates were, respectively, 98.6% and 86.5% for pT1a; 93.7% and 87.9% for pT1b; 100% and 100% for pT2; 78.6% and 58.0% for pT3a; and 88.9% and 16.7% for pT3b. Significant differences in the recurrence rate were noted between pT3 and pT1 or pT2, as well as between grade 3 disease and grade 1 or grade 2 tumors. Multivariate analysis showed that a combination of the pT stage, grade, and presence of symptoms was useful for predicting the recurrence of RCC. Conclusion: The present study showed that patients undergoing nephrectomy for N0M0 RCC should be followed-up carefully for 2 years postoperatively with special attention to high pT stage, high grade, and the development of symptoms. [source] Superficial leiomyosarcoma: a clinicopathologic review and updateJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Clarissa T. Fauth Fauth CT, Bruecks AK, Temple W, Arlette JP, DiFrancesco LM. Superficial leiomyosarcoma: a clinicopathologic review and update. Background: Superficial leiomyosarcomas (SLMSs) are rare soft tissue malignancies. A clinicopathologic review of 25 cases was undertaken. Methods: Twenty-five cases diagnosed between 1990 and 2007 were reviewed. Clinical information was obtained from patient charts. Histologic slides were reviewed, and immunohistochemical stains were performed. Results: All patients presented with a nodule. Fourteen tumors were confined to the dermis and 11 involved subcutaneous tissue. Smooth muscle markers were positive in all cases. CD117 was consistently negative. Novel histological features included epidermal hyperplasia, sclerotic collagen bands and increasing tumor grade with the depth of the lesion. Poor outcome was associated with size > 2 cm, high grade and depth of the lesion. Conclusions: SLMSs are rare but important smooth muscle tumors of the skin. The clinical presentation may be non-specific. The histologic appearance is that of a smooth muscle lesion, but epidermal hyperplasia and thickened collagen bands are previously underrecognized features. Immunohistochemical stains are useful in confirming smooth muscle differentiation, but CD117 is of limited utility. SLMS can appear low grade or even benign on superficial biopsies, leading to undergrading or a delay in the correct diagnosis. Clinicians and pathologists alike should therefore be aware of these pitfalls and must approach these cases with caution. [source] Consensus statement on the loco-regional treatment of appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei),JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2008Brendan Moran MD Abstract Pseudomyxoma peritonei (PMP) is a rare condition mostly originating from low malignant potential mucinous tumours of the appendix. Although this disease process is minimally invasive and rarely causes haematogenous or lymphatic metastases, expectation of long-term survival are limited with no prospect of cure. Recently, the combined approach of cytoreductive surgery (CRS) and perioperative loco-regional chemotherapy (PLC) has been proposed as the standard of treatment for the disease. The present paper summarizes the available literature data and the main features of the comprehensive loco-regional treatment of PMP. The controversial issues concerning the indications and technical methodology in PMP management were discussed through a web-based voting system by internationally known experts. Results were presented for further evaluation during a dedicated session of "The Fifth International Workshop on Peritoneal Surface Malignancy (Milan, Italy, December 4,6, 2006)". The experts agreed that multiple prospective trials support a benefit of the procedure in terms of improved survival, as compared with historical controls. Concerning the main controversial methodological questions, there was an high grade of consistency among the experts and agreement with the findings of the literature. J. Surg. Oncol. 2008;98:277,282. © 2008 Wiley-Liss, Inc. [source] Extraction of pure lycopene from industrial tomato by-products in water using a new high-pressure processJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 14 2008Daniele Naviglio Abstract BACKGROUND: Lycopene, a precursor of ,-carotene with a well-known antioxidant activity, contained in many natural products such as tomato (Lycopersicon esculentum Mill.), watermelon, red pepper and papaya, is usually recovered from natural vegetal sources using organic solvents and a purification step. In this paper an innovative process for the extraction of pure lycopene from tomato waste in water that uses the Naviglio® extractor and water as extracting phase is presented. RESULTS: Lycopene was obtained in the all- trans form at a very high grade of purity, not less than 98% (w/w), with an average recovery of 14% (w/w). The availability of high-purity trans -lycopene allowed measurement of the molar absorption coefficient. An alternative procedure for high-performance liquid chromatographic analysis using a phenyl-hexyl silicone phase as inverse phase and a linear gradient in water and acetonitrile is also described. CONCLUSIONS: The use of water as extracting phase considerably reduces the cost of the entire process when compared with the commonly used solvent-based procedure or with the newer supercritical extraction process of lycopene from tomato waste. Lycopene, not soluble in water, was recovered in a quasi-crystalline solid form and purified by solid-phase extraction using a small amount of organic solvent. Copyright © 2008 Society of Chemical Industry This article was published online on September 15, 2008. Errors in Figures 2 - 4 were subsequently identified. The publishers wish to apologise for these errors. This notice is included in the online and print versions to indicate that both have been corrected [September 19, 2008] [source] The value of postoperative radiotherapy in childhood nonrhabdomyosarcoma soft tissue sarcoma,PEDIATRIC BLOOD & CANCER, Issue 5 2004Arnold C. Paulino MD Abstract Objective To determine the value of postoperative radiotherapy (RT) in the management of nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) of childhood. Procedure From 1964 to 2000, 62 children with a median age of 14 years were seen at the University of Iowa and underwent a wide local excision for non-metastatic NRSTS. Tumors were high grade in 36 (58%) and >5 cm in 24 (39%). Margins of resection were negative (Group I) in 37 (60%) and positive (Group II) in 25 (40%). Postoperative RT was delivered to 20 patients (32%); eight of 37 (22%) Group I and 12 of 25 (48%) Group II children received postoperative RT. Chemotherapy was employed in 19 patients (31%). Median follow-up was 9.6 years. Results The 5- and 10-year overall survival rates for Group I were 69 and 63% and for Group II were 66 and 60%. The 5- and 10-year local control rate was 66%. On multivariate analysis, size of tumor (P,<,0.001) and postoperative RT (P,=,0.017) were prognostic factors for local control. All 13 Group I children with low grade, ,5 cm tumors were locally controlled without RT. For Group II patients, 2- and 5-year local control rates were 92 and 82% with postoperative RT and 51 and 43% for no RT (P,=,0.0426). Conclusions Local control was improved by the addition of postoperative RT in tumors with positive margins of resection. © 2004 Wiley-Liss, Inc. [source] Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies,THE JOURNAL OF PATHOLOGY, Issue 2 2008RT Bryan Abstract Bladder cancer is the fifth most common malignancy in the UK. Clinically, the most important process in determining prognosis is the development of invasion, initially of the lamina propria and then beyond as these transitional cell carcinomas (TCCs) progress from stage pT1 to stages T2+. Cadherins and catenins are the main mediators of cell,cell interactions in epithelial tissues, and loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade, advanced stage and poor prognosis in bladder cancer and other malignancies. However, the role of P-cadherin is yet to be fully elucidated in bladder TCC. The objectives of this study were to establish how the expression of cadherins and catenins determines clinical and in vitro behaviour in bladder TCC. Utilizing immunohistochemistry, immunofluorescence and western blotting, we demonstrated a significant reduction in the expression of E-cadherin and ,-catenin as grade and stage of bladder TCC progress, accompanied by a significant increase in P-cadherin expression (all p < 0.05, Pearson's ,2 test). Increased P-cadherin expression was also associated with a significantly worse bladder cancer-specific survival (log rank p = 0.008), with Cox regression showing P-cadherin to be an independent prognostic factor. Utilizing a variety of tissue culture models in a range of functional studies, we demonstrated that P-cadherin mediates defective cell,cell adhesion and enhances anchorage-independent growth. The results provide evidence that increased P-cadherin expression promotes a more malignant and invasive phenotype of bladder cancer, and appears to have a novel role late in the disease. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancerTHE JOURNAL OF PATHOLOGY, Issue 4 2003Boriana M Zaharieva Abstract Gene amplification is a common mechanism for oncogene overexpression. High-level amplifications at 11q13 have been repeatedly found in bladder cancer by comparative genomic hybridization (CGH) and other techniques. Putitative candidate oncogenes located in this region are CCND1 (PRAD1, bcl-1), EMS1, FGF3 (Int-2), and FGF4 (hst1, hstf1). To evaluate the involvement of these genes in bladder cancer, a tissue microarray (TMA) containing 2317 samples was screened by fluorescence in situ hybridization (FISH). The frequency of gains and amplifications of all genes increased significantly from stage pTa to pT1,4 and from low to high grade. In addition, amplification was associated with patient survival and progression of pT1 tumours. Among 123 tumours with amplifications, 68.3% showed amplification of all four genes; 19.5% amplification of CCND1, FGF4, and FGF3; and 0.8% co-amplification of FGF4, FGF3, and EMS1. Amplification of CCND1 alone was found in 9% of the tumours, while EMS1 alone was amplified in 1.6% and FGF4 in 0.8%. Overall, the amplification frequency decreased with increasing genomic distance from CCND1, suggesting that, among the genes examined, CCND1 is the major target gene in the 11q13 amplicon in bladder cancer. Copyright © 2003 John Wiley & Sons, Ltd. [source] Loss of CD59 expression in breast tumours correlates with poor survivalTHE JOURNAL OF PATHOLOGY, Issue 5 2003Z Madjd Abstract CD59 (protectin), a phosphatidylinositol-anchored glycoprotein, is a member of the cell membrane-bound complement regulatory proteins that inhibits the formation of the terminal membrane attack complex (MAC) of complement. In this study, the expression of CD59 was evaluated in 520 breast carcinomas from patients with a mean follow-up of 87 months. This expression was correlated with clinicopathological features and patient survival. Marked variation in the intensity of CD59 expression, which correlated with histological grade and Nottingham prognostic index (NPI), was found, with higher expression of CD59 found more often in well and moderately differentiated tumours and those of good prognosis (NPI , 3.4). In contrast, high grade and poor prognosis (NPI > 5.4) carcinomas significantly demonstrated lack of CD59 expression (p < 0.001). Moreover, it was found that the percentage of CD59-positive cells correlated significantly with patient survival, ie patients with a high percentage of positive cells (>50%) had a better overall survival (p = 0.006). A correlation was also found between the percentage of CD59-positive cells and tumour type and also the development of distant metastases. No association was found between either the intensity or the percentage of cells expressing CD59 and vascular invasion, lymph node stage, tumour size, patient age or menopausal status. In multivariate analysis, CD59 percentage positivity was of independent prognostic significance with grade and lymph node stage. These findings indicate that loss of CD59 may offer a selective advantage for breast cancers, resulting in more aggressive tumours and conferring a poor prognosis for patients. Copyright © 2003 John Wiley & Sons, Ltd. [source] Adjuvant chemotherapy for stage C colonic cancer in a multidisciplinary settingANZ JOURNAL OF SURGERY, Issue 10 2009Pierre H. Chapuis Abstract Background:, In this study of patients undergoing adjuvant chemotherapy for clinicopathological stage C colonic cancer after optimal surgery, the aims were: to describe their immediate experience of chemotherapy, to assess disease-free survival, to compare overall survival with that of a matched untreated historical control group, and to evaluate the associations between previously identified adverse risk factors and survival. Methods:, Data were drawn from a comprehensive, prospective hospital registry of resections for colorectal cancer between 1971 and 2004, with retrospective data on adjuvant chemotherapy. The main end point was overall survival. Statistical analysis employed the chi-squared test, Kaplan,Meier estimation and proportional hazards regression. Results:, From May 1992 to December 2004, there were 104 patients who received adjuvant chemotherapy. Duration of treatment, withdrawal from treatment, toxicity and other immediate treatment outcomes were similar to those in other equivalent studies. There were no toxicity-associated deaths. Overall survival was significantly longer in the treated patients than in the control group (3-year rates 81% and 66%, respectively, P = 0.009). A significant protective effect of adjuvant therapy was found (hazard ratio 0.5, 95% confidence interval 0.3,0.8, P = 0.001) after adjustment for histopathology features previously shown to be negatively associated with survival (high grade, venous invasion, apical node metastasis, free serosal surface involvement). Conclusions:, For patients who have had a curative resection for lymph node positive colonic cancer in a specialist colorectal surgical unit and been managed by a multidisciplinary team, post-operative adjuvant chemotherapy is safe and provides the same survival advantage as seen in randomized trials. [source] A cellular model system of differentiated human myotubes,APMIS, Issue 11 2001M. GASTER The aim of this study was to select an effective and stable protocol for the differentiation of human satellite cells (Sc) and to identify the optimal time period for the experimental use of differentiated human Sc-cultures. In order to identify the differentiation conditions which give a good survival of myotubes and a high grade of differentiation, Sc-cultures were induced to differentiate in media supplemented with either 2% fetal calf serum (FCS) 2% horse serum (HS) or 10% HS. Based on higher CK-activities in cultures differentiating in FCS-supplemented media compared to horse sera, fetal calf serum was chosen to induce differentiation. The ATP, DNA and protein content increased during the first 4 days after induction of differentiation and was followed by a period with minor changes. The maximal differences of ATP, DNA and protein between days 4,10 were evaluated and the differences in the three components were found to be less than 20% of the average value with a certainity of more than 0.9. Day 8-myotubes were investigated morphologically and were found immunoreactive for fast myosin, and expressed areas with clear cross striation. We recommend the use of differentiated Sc-cultures in the period from day 4 to 8 after induction of differentiation as only minor differentation-related changes will take place in the cells during this period of time. [source] HuR expression in the nucleus correlates with high histological grade and poor disease-free survival in ovarian cancerAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009Xiaofang YI Background: HuR, a nucleo-cytoplasmic shuttling protein, plays an important role in mRNA stability as well as cellular differentiation. Recently, HuR expression, particularly in the cytoplasm, was thought to be associated with the prognosis of several cancers including ovarian cancer. Aims: To study the clinical significance of nuclear HuR expression in ovarian cancer. Methods: Primary epithelial ovarian carcinomas (102) and ovarian low malignant potential tumours (11) were assessed for HuR protein expression by immunohistochemistry. HuR scoring accounted for both intensity and percentage of cells stained, and ranged from 0 to 300. Results: HuR was found to be present predominantly in the nucleus, where it was expressed in 85.8% of cases. Nuclear HuR was associated with the invasive cancers (P = 0.004), high grade (P < 0.0001), large residual disease (P = 0.045) and poor disease-free survival (P = 0.0009). Among those 91 specimens with high grade, 76.9% had a high nuclear HuR score, while in those 22 cases with low grade, only 31.8% had a high HuR score (P < 0.0001). Multivariate analysis showed that nuclear HuR intensity was an independent prognostic factor for poor disease-free survival (P = 0.0484). When the invasive cancers were analysed separately, only the association between nuclear HuR and high grade remained (P = 0.0089). Conclusions: Our results support the clinical significance of nuclear HuR in ovarian carcinoma and suggest that nuclear HuR may also play a role in the biology of ovarian cancer. These data suggest a more complex model for HuR in ovarian cancer than one limited to cytoplasmic localisation. [source] Chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinomaCANCER, Issue 20 2010Jeffrey La Rochelle MD Abstract BACKGROUND: The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses. METHODS: In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status. RESULTS: Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p-deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3-T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ,4 cm in greatest dimension, 9p-deleted tumors were more likely to recur (19% vs 2%; P = .01). CONCLUSIONS: Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment. Cancer 2010. © 2010 American Cancer Society. [source] Influence of compartmental involvement on the patterns of morbidity in soft tissue sarcoma of the thighCANCER, Issue 1 2009Andreas Rimner MD Abstract BACKGROUD: The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb-sparing surgery and postoperative radiation therapy (RT). METHODS: A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982,2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins. Adjuvant RT consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%), or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58 medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor grade, size, depth, margin status, and RT type. RESULTS: Overall local control (LC) was 89%, distant metastases-free survival (DMFS) was 61%, and overall survival (OS) was 66% at 5 years (median follow-up, 71 months). Overall rates for complications at 5 years were wound reoperation (10%), edema (13%), joint stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation and edema were significantly higher for medial-compartment tumors (P = .01 and .005, respectively), whereas nerve damage occurred more frequently in posterior-compartment tumors (P < .001). There were no differences among bone fracture, joint stiffness, DMFS, or OS rates between compartments. CONCLUSIONS: Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These results may help guide decisions concerning current patients and improve the design of future treatments tailored to compartments. Cancer 2009. © 2008 American Cancer Society. [source] DNA ploidy compared with human papilloma virus testing (Hybrid Capture II) and conventional cervical cytology as a primary screening test for cervical high-grade lesions and cancer in 1555 patients with biopsy confirmationCANCER, Issue 2 2006Martial Guillaud PhD Abstract BACKGROUND. Because 80% of cervical cancers arise in low-resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large-scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy. METHODS. Patients entered either a screening or diagnostic study of several optical technologies: quantitative cytology, quantitative histopathology, and fluorescence and reflectance spectroscopy using a point probe, a multispectral digital colposcope, or a combination of the two. We calculated sensitivities, specificities, positive and negative predictive values, and their confidence interval testing conventional cytology, Hybrid Capture (HC) II testing, and DNA ploidy measured on the Feulgen-stained quantitative Pap smear. RESULTS. The current investigation reports on 1555 patients for whom colposcopically directed biopsies were read 3 times by study pathologists. The final histopathologic diagnosis was high grade (cervical intraepithelial neoplasia [CIN] 2, CIN 3, carcinoma in situ [CIS], and cancer) in 16% of patients. Using high-grade squamous intraepithelial lesions (SILs) histopathology as the threshold and gold standard, the sensitivity and specificity, respectively, were: 0.47 and 0.96 for conventional cytology, 0.91 and 0.80 for HC II, and 0.59 and 0.93 for DNA ploidy. The positive and negative predictive values (PPV, NPV) for conventional cytology were 0.70 and 0.90, 0.46 and 0.98 for HC II, and 0.63 and 0.92 for DNA ploidy. CONCLUSIONS. DNA ploidy shows comparable sensitivity, specificity, PPV, and NPV values to conventional cytology and HC II. Unlike conventional cytology, DNA ploidy is semiautomated and can be performed in less than 8 hours. Cost effectiveness studies are under way, but in the authors' laboratory DNA ploidy is inexpensive. Cancer 2006. © 2006 American Cancer Society. [source] Breast carcinoma in pregnant womenCANCER, Issue 5 2003Assessment of clinicopathologic, immunohistochemical features Abstract BACKGROUND Breast carcinoma is one of the most common carcinomas in pregnant women. The incidence of breast carcinoma may increase in the future because of the trend toward delayed childbearing and increased screening. However, very few contemporary studies have attempted to identify the combined histopathologic and immunohistochemical features of breast carcinoma in these patients. METHODS The authors evaluated 39 patients with breast carcinoma occurring coincident with pregnancy. This was comprised of a critical histologic review and immunohistochemical evaluation to determine the status of prognostic and predictive markers including estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Ki-67, and p53. RESULTS The mean age at presentation was 33 years (range, 24,44 years). Densities and/or masses were noted on mammograms in 14 of 16 patients with available radiographic information. The primary tumors were a mean of 4.5 cm in greatest dimension (range, 0.1,13.5 cm). Two of the 39 patients had clinical (American Joint Committee on Cancer) Stage I disease, 19 patients had Stage II disease, 16 had Stage III disease, and 2 patients had Stage IV disease at the time of presentation. Histologically, high-grade invasive ductal carcinomas were found in 32 of 38 patients. The primary tumor was not available for review in one patient. A predominantly solid pattern of growth was observed in nine patients. Lymphovascular invasion was identified in 61% of cases. Ductal carcinoma in situ was identified in 72% of tumors and was high grade in all cases. Of the 25 patients tested, ER positivity was found in 7 patients, PR positivity was found in 6 patients, HER-2/neu positivity was found in 7 patients, and p53 positivity was found in 12 patients. The proliferation rate as shown by Ki-67 staining was high in 60% of the cases. Follow-up information was available for 35 patients and the mean follow-up period was 43 months (range, 2,163 months). Distant metastasis occurred in seven patients. The mean time to disease recurrence was 20.4 months (range, 10,33 months). Of 35 patients, 4 have died, 22 were alive with no evidence of disease, and 9 were alive with disease at the last follow-up. The remaining four patients died of unknown causes. CONCLUSIONS Pregnant women with breast carcinomas generally present with advanced-stage disease and the tumors have poor histologic and prognostic features. The findings from the follow-up indicated that these tumors do not follow a very aggressive clinical course as was proposed in earlier reports. Breast carcinomas occurring during pregnancy share many histologic and prognostic similarities with breast carcinoma occurring in other young women. Cancer 2003;98:1055,60. © 2003 American Cancer Society. DOI 10.1002/cncr.11614 [source] Microsatellite Instability and k- ras, p53 Mutations in Thyroid LymphomaCANCER SCIENCE, Issue 3 2000Tetsuya Takakuwa Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type. Sixteen distinct microsatellite repeats were analyzed. Mutations of p53 and k- ras genes were also examined. When alterations at 2 or more microsatellite loci were judged as positive, only 5 DLBL cases exhibited MSI. The frequency of MSI in DLBL was significantly higher than that in other types of TL and CLTH (P < 0.05). Four of 19 cases (21.1%) showed point mutation of the k- ras gene. The k- ras mutations occurred in the cases with DLBL with RER, and four of five cases with RER had a k- ras mutation, indicating a close association between RER and k- ras mutation. p53 mutations were not found in the CLTH. Two of 19 TL cases showed mutations of p53 gene. There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contributes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions. [source] Psychosocial, Motivational, and Contextual Profiles of Youth Reporting Different Patterns of Substance Use During AdolescenceJOURNAL OF RESEARCH ON ADOLESCENCE, Issue 1 2007Alison Bryant Ludden This research examined patterns of substance use and academic factors among a sample of 733 African-American and European-American adolescents from a metropolitan area. First, youth were classified into 11th grade high, moderate, or no substance use groups and classified as users, initiators, desistors, and nonusers based on eighth and 11th grade use. Nonusers did not differ in eighth grade from 11th grade moderate users and initiators over time. Eighth graders who reported misbehavior and having low-achieving friends were more likely to be high 11th grade users and users at both grades. Direct achievement effects were not found; however, interactions indicated achievement was protective when paired with having fun at school, high task value, and low levels of socioeconomic status (SES); and was a risk factor when paired with positive self regard, low fun at school and high SES. Cluster analyses indicated the most prevalent group of substance users reported high grades, social reasons for going to school, and having friends who do well in school. [source] Histologic classification of ductal carcinoma in situMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2002Shabnam Jaffer Abstract Prior to the current mammographic era, ductal carcinoma in situ (DCIS) usually presented as a large mass, was classified morphologically by architecture, and treated by mastectomy. The introduction of screening mammography led to an increase in the incidence of DCIS, a decrease in the average size of DCIS, and an increased emphasis on its heterogeneous nature. Thus, a reproducible and prognostically relevant classification system for DCIS is necessary. The ultimate goal of this classification is proper selection of patients for whom lumpectomy would suffice rather than mastectomy. Features to evaluate include: extent and size of disease, adequacy of resection margins, and histology. While none of the proposed histological classification systems were endorsed at the recent Consensus Conference on the Classification of DCIS, nuclear grade was the most important feature common to most of them. Architecture was given secondary importance. By definition, DCIS is a non-invasive clonal proliferation of epithelial cells originating in the terminal duct lobular unit, which would be expected to be monomorphic; however, it is the degree of nuclear pleomorphism that is primarily used to separate DCIS into low, intermediate, and high grades. Architecturally, DCIS has been divided into the following types: comedo, solid, cribriform, micropapillary, and papillary. Different architectural patterns and grades may be present in a given particular case; however, some combinations of patterns occur more frequently than others. Interobserver studies have shown nuclear grading to be interpreted with greater consistency than architecture, and nuclear grading methods have correlated with biological and molecular marker studies. Microsc. Res. Tech. 59:92,101, 2002. © 2002 Wiley-Liss, Inc. [source] The value and correlation between PRL-3 expression and matrix metalloproteinase activity and expression in human gliomasNEUROPATHOLOGY, Issue 6 2007Lingfei Kong Local invasion of tumor cells is characteristic of most human glioma invasions. It is associated with increased motility and a potential to degrade the extracellular matrix. Matrix metalloproteinases (MMPs) have been proved to be a main process in local invasion of brain tumor. PRL-3 is a new protein tyrosine phosphatase which would also degrade the extracellular matrix and has been proved to be expressed in liver metastases derived from colorectal cancer. In this study, we sought to investigate the expression of PRL-3 in glioma tissues and investigate the relationship between MMPs (MMP2, MMP9, membrane-type matrix metalloproteinase 1 [MT1-MMP]) activity and expression in gliomas. The modifications of in situ hybridization of mRNA phosphatase of regenerating liver-3 (PRL-3) methods are preformed in the study of paraffin-embedded slides. The immunohistochemistry and gelatin zymography are used to detect the expression of PRL-3 and activity of MMPs. The results show that PRL-3 mRNA and antibody of PRL-3 are detected in glioma tissues mainly in grades IV and III, only a little in grade II, but not in normal brain tissue and glioma grade I. MMP2 and MMP9 are observed mainly in glioma tissues of grades IV and III in activity and expression. MT1-MMP protein is located in glioma tissues and vessel endothelial cells. This is the first report of detecting PRL-3 expression in gliomas, especially in grades III and IV, which may play an important role in progression of gliomas. PRL-3, MMP2 and MT1-MMP cooperatively contribute to gliomas invasion. Intermediate MMP2 (MT1-MMP, TIMP-2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas. [source] | |||||||||||||||||||||||||||||||