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Aggressive Disease (aggressive + disease)
Selected AbstractsIn-Transit Metastasis From Primary Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Nonimmunosuppressed Patients: Clinical Characteristics, Management, and Outcome in a Series of 21 PatientsDERMATOLOGIC SURGERY, Issue 4p2 2004John A. Carucci MD Background. In-transit metastases from cutaneous squamous cell carcinoma (SCC) may occur in organ transplant recipients and may indicate aggressive disease and poor prognosis. Objective. The objective of this study was to describe in-transit metastases from cutaneous SCC and to identify factors associated with this phenomenon in a series of 21 patients. We also attempted to evaluate outcome with respect to status as an organ transplant recipient or nonorgan transplant recipient. Methods. A multicenter case series of patients was reviewed; factors included clinical presentation, management, and outcome. Results. Twenty-one patients, 15 organ transplant recipients, and 6 nontransplant recipients with in-transit metastases were reviewed. In-transit metastases presented most commonly as discrete, dermal papules distinct from but in the vicinity of the primary tumor site. Histologic differentiation was variable. At a mean follow up of 24 months, 33% the transplant patients had no evidence of disease compared with 80% of nontransplant patients. Thirty-three percent were dead from disease and 33% were alive with nodal or distant metastases. In contrast, 80% of nonimmunosuppressed patients had no evidence of disease and none had died at mean follow-up of 24 months. Conclusion. In-transit metastasis from cutaneous SCC is a unique presentation of metastatic SCC, more commonly described in organ transplant recipients, and is associated with poor prognosis in that group. This description represents the largest experience with in-transit metastases from cutaneous SCC in the literature. [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] Prognosis of follicular lymphomasHEMATOLOGICAL ONCOLOGY, Issue 2 2006Stefano Luminari Abstract Follicular lymphoma (FL) is as an indolent neoplasia with median survival measured in decades. Nevertheless, some patients have poor progression-free survival and overall survival. Several treatment approaches are proposed for patients with FL, however criteria to rationalize treatment decisions are lacking. Studies have been performed to build up prognostic indices that are useful for defining risk-adapted treatment recommendations. Available indices are based on parameters that have an independent role in predicting patient survival and that are variably correlated with the features of the disease, with the characteristics of the patient and with the effects of treatment. Two new prognostic indices have recently been proposed for FL: the Italian Lymphoma Intergroup (ILI) index and the Follicular Lymphoma International prognostic Index (FLIPI). Both indices are based on large series of patients and exhibit differences in their ability to discriminate between patients with different probabilities of survival. In recent years, with the advent of gene expression profile studies, our knowledge of the biology of FL is changing as novel data become available about the lymphoma cell and about the role of the microenvironment; these studies have already provided novel prognostic tools for identifying patients with more aggressive disease. Further data and large international cooperative studies are needed to translate into clinical practice the novel acquisitions of biology and therapeutics. Copyright © 2006 John Wiley & Sons, Ltd. [source] Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomasHISTOPATHOLOGY, Issue 1 2010Michael G A Norwood Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology,57, 101,111 Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:, ,-Catenin is an important molecule in cancer biology. Membranous ,-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results:, Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess ,-catenin expression. Increasing ,-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of ,-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions:, This is one of the largest prognostic studies of ,-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic ,-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic ,-catenin could be used as a prognostic marker for less aggressive disease. [source] ERG rearrangement in small cell prostatic and lung cancerHISTOPATHOLOGY, Issue 7 2010Veit J Scheble Scheble V J, Braun M, Wilbertz T, Stiedl A-C, Petersen K, Schilling D, Reischl M, Seitz G, Fend F, Kristiansen G & Perner S (2010) Histopathology,56, 937,943 ERG rearrangement in small cell prostatic and lung cancer Aims:, Small cell prostatic cancer is a rare but aggressive disease. Currently, its histogenetic origin is unclear and its distinction from metastatic small cell lung cancer is challenging. The aim of our study was to determine whether the ERG rearrangement commonly observed in acinar prostatic cancer can distinguish small cell prostatic cancer from small cell lung cancer samples. Methods and results:, We assessed 15 small cell prostatic cancers and 22 small cell lung cancers for ERG rearrangement using fluorescence in situ hybridization. Commonly used and novel immunohistochemical markers (i.e. androgen receptor, calcium activated nucleotidase 1, Golgi phosphoprotein 2, prostate-specific antigen, prostate-specific membrane antigen, CD56, epithelial membrane antigen, thyroid transcription factor 1, chromogranin A, synaptophysin and Ki67) were further studied. ERG rearrangement occured in 86% of small cell prostatic cancers but in none of the small cell lung cancers and was the best marker to differentiate between both tumours (P < 0.0001). Conclusions:, The ERG rearrangement is commonly observed in small cell prostatic cancer, supporting the hypothesis that ERG rearrangement occurs in aggressive prostatic cancers. Furthermore, the ERG rearrangement is the most significant marker to differentiate between small cell prostatic cancer and small cell lung cancer. Moreover, our data suggest that small cell prostatic cancer is not a tumour entity on its own, but a dedifferentiated variant of common acinar prostatic cancer. [source] Interaction of tumour biology and tumour burden in determining outcome after hepatic resection for colorectal metastasesHPB, Issue 2 2010Dhanny Gomez Abstract Aims:, To determine the outcome of colorectal liver metastasis (CRLM) patients based on tumour burden, represented by tumour number and size, and tumour biology as assessed by an inflammatory response to tumour (IRT) and margin positivity. Methods:, Data were collated from CRLM patients undergoing resection from January 1993 to March 2007. Patients were divided into: low (,3 metastases and/or ,3 cm); moderate (4,7 metastases and/or >3,,5 cm); and high (,8 metastases and/or >5 cm) tumour burden. Results:, Seven hundred and five patients underwent resection, of which 154 (21.8%), 262 (37.2%) and 289 (41.0%) patients were in the low, moderate and high tumour burden groups, respectively. The 5-year disease-free (P < 0.001) and overall (P < 0.001) survival were significantly different between the groups. IRT (P < 0.001), extent of resection (P < 0.001) and margin (P < 0.001) also differed between the groups. Sub-group analysis revealed that IRT was the only adverse predictor for disease-free and overall survival in the low group. In the moderate group, IRT predicted poorer disease-free survival on multi-variate analysis. In the high group, R1 resection and transfusion were predictors of poorer disease-free survival and age ,65 years, R1 resection and IRT were adverse predictors of overall survival. Conclusion:, Resection margin influenced the outcome of patients with high tumour burden, hence the importance of achieving clear margins. IRT influenced the outcome of patients with less aggressive disease. [source] State of the art: IBD therapy and clinical trials in IBDINFLAMMATORY BOWEL DISEASES, Issue S1 2005Kim L Isaacs MD Abstract Inflammatory bowel diseases (IBD) encompass Crohn's disease and ulcerative colitis, which are diseases characterized by chronic intestinal inflammation. IBD is believed to result from predisposing genetic and environmental factors (specific antigens and pathogen-associated molecular patterns) acting on the immunoregulatory system and causing inflammation of the gastrointestinal mucosa. IBD may be the result of an imbalance of effector (proinflammatory) and regulatory T-cell responses. Three scenarios indicative of the outcome of this balance exist in animal models: balanced effector and regulatory T cells resulting in a normal controlled inflammation; overactive effector T cells resulting in inflammation and disease; and an absence of regulatory T cells resulting in uncontrolled inflammation and severe, aggressive disease. The number of products under study for the treatment of IBD has increased from 3 products and 1 target in 1993 to more than 30 products and more than 10 targets in 2005. The number of products under development and continued investigations into the pathogenesis of IBD emphasize the need to expand clinical research efforts in IBD. [source] The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Melissa J. LaBonte Abstract Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER-2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN-38, the active metabolite of irinotecan (CPT-11), in colon and gastric cancer cell lines. Concentration-dependent antiproliferative effects of both lapatinib and SN-38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range 0.08,11.7 ,M; SN-38 range 3.6,256 nM). Lapatinib potently inhibited the growth of a HER-2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER-2 expression. The combination of lapatinib and SN-38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Cotreatment with lapatinib and SN-38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN-38 when compared to SN-38 treatment alone. Finally, the combination of lapatinib and CPT-11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT-11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas. © 2009 UICC [source] Large plaque parapsoriasis: clinical and genotypic correlationsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2000Martin Simon Twelve patients with large plaque parapsoriasis (LPP) were investigated for the presence of predominant T-cell clones, analyzing the T-cell receptor (TCR) ,-chain gene. The diagnostic and prognostic significance of TCR gene rearrangement status was assessed by a correlation with the long-term clinical follow-up. Six out of 12 patients showed a clonal T-cell population. Clinically, among the patients with clonal disease one developed clearcut mycosis fungoides (MF) after a follow-up of 8 years, in the other 5 patients no such diagnosis could be made after follow-up of 2,21 years (median: 9 years). In patients with polyclonal infiltrates the lesions remained virtually unchanged. These findings indicate that in LPP TCR gene rearrangement status has no prognostic significance and does not allow distinction of LPP and early MF. Both conditions show a clonal T-cell infiltrate with similar frequency, are very similar in clinical and histologic presentation and according to recent studies share the same low risk to develop overt MF. Therefore both terms refer to the identical clinical situation. This should be designated as early MF and efforts should concentrate on identifying those patients that are at risk to develop aggressive disease. [source] Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongueJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2010Ioulia Chatzistamou J Oral Pathol Med (2010) 39: 667,671 Background:, Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. Methods:, Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. Results:, Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. Conclusion:, Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue. [source] Delphian node metastasis in head and neck cancers,Oracle or myth?,JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010FRCS, N. Gopalakrishna Iyer MD Abstract Delphian node (DN) refers to the pre-laryngeal or pre-cricoid nodal tissue often identified during laryngeal or thyroid surgery. The original nomenclature is based on the assumption that metastasis to this node was predictive of aggressive disease and poor outcome for patients. In this article, we review the existing literature on the topic to determine the significance of DN metastasis in laryngeal, hypopharyngeal and thyroid cancers. J. Surg. Oncol. 2010;102:354,358. © 2010 Wiley-Liss, Inc. [source] Review article: smoking cessation as primary therapy to modify the course of Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2005G. J. Johnson Summary This article aims to offer an updated review of the effects of smoking on inflammatory bowel disease, and provide a review of the methods of achieving smoking cessation. A systematic review of Embase and Medline databases was conducted. Smoking causes opposing effects on ulcerative colitis and Crohn's disease. The odds ratio of developing ulcerative colitis for smokers compared with lifetime non-smokers is 0.41. Conversely, smokers with Crohn's disease have a more aggressive disease requiring more therapeutic intervention. Smoking cessation is associated with a 65% reduction in the risk of a relapse as compared with continued smokers, a similar magnitude to that obtained with immunosuppressive therapy. Although difficult to achieve smoking cessation can best be encouraged by accessing appropriate counselling services, nicotine replacement therapy and bupropion. Using a combination of these treatments there is an improved chance of success of up to 20% compared with an unassisted quit attempt. Smoking cessation unequivocally improves the course of Crohn's disease and should be a primary therapeutic aim in smokers with Crohn's disease. [source] Classifying the medulloblastoma: insights from morphology and molecular geneticsNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2002D. Ellison Significant advances in the treatment of the medulloblastoma (MB) have been made in the last 30 years, reducing mortality by 2-fold. Further improvements in the cure rate require an increased understanding of the biology of MBs, and this will translate into refinements in their classification. Scrutiny of the cytological variation found among MBs has recently led to the concept of the anaplastic MB, which overlaps the large-cell variant and appears to share its poor prognosis. In contrast, the MB with extensive nodularity, a distinctive nodular/desmoplastic variant occurring in infants, has a better outcome than most MBs in these young patients. Building on cytogenetic studies that have drawn attention to abnormalities on chromosome 17 in over a third of MBs, research shows non-random losses on chromosomes 8, 9, 10, 11 and 16, and gains on chromosomes 1, 7 and 9. Overexpression of ErbB2 receptors and losses on chromosome 17p have been proposed as independent indicators of aggressive behaviour, while high TrkC receptor expression indicates a favourable outcome. There is a strong association between anaplastic/large-cell tumours and MYC amplification, which has previously been linked with aggressive disease, but associations between abnormalities on chromosome 17 and anaplastic/large-cell MBs and between abnormalities in the shh/PTCH pathway and the desmoplastic variant are more controversial. Classification of the MB histopathologically and according to profiles of molecular abnormalities will help both to rationalize approaches to therapy, increasing the cure rate and reducing long-term side-effects, and to suggest novel treatments. [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] Successful cell-mediated cytokine-activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Benjamin Gesundheit Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell-mediated cytokine-activated immunotherapy in a high-risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft-versus-leukemia effect, presenting as a reversible episode of graft-versus-host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed. Am. J. Hematol., 2009. © 2008 Wiley-Liss, Inc. [source] Recurrent Respiratory Papillomatosis: A Longitudinal Study Comparing Severity Associated With Human Papilloma Viral Types 6 and 11 and Other Risk Factors in a Large Pediatric Population,THE LARYNGOSCOPE, Issue S104 2004Brian J. Wiatrak MD Abstract Objectives/Hypothesis: A database was developed for prospective, longitudinal study of recurrent respiratory papillomatosis (RRP) in a large population of pediatric patients. Data recorded for each patient included epidemiological factors, human papilloma virus (HPV) type, clinical course, staged severity of disease at each surgical intervention, and frequency of surgical intervention. The study hypothesizes that patients with HPV type 11 (HPV-11) and patients younger than 3 years of age at diagnosis are at risk for more aggressive and extensive disease. Study Design: The 10-year prospective epidemiological study used disease staging for each patient with an original scoring system. Severity scores were updated at each surgical procedure. Methods: Parents of children with RRP referred to the authors' hospital completed a detailed epidemiological questionnaire at the initial visit or at the first return visit after the study began. At the first endoscopic debridement after study enrollment, tissue was obtained and submitted for HPV typing using polymerase chain reaction techniques and in situ hybridization. Staging of disease severity was performed in real time at each endoscopic procedure using an RRP scoring system developed by one of the authors (B.J.W.). The frequency of endoscopic operative debridement was recorded for each patient. Information in the database was analyzed to identify statistically significant relationships between extent of disease and/or HPV type, patient age at diagnosis, and selected epidemiological factors. Results: The study may represent the first longitudinal prospective analysis of a large pediatric RRP population. Fifty-eight of the 73 patients in the study underwent HPV typing. Patients infected with HPV-11 were significantly more likely to have higher severity scores, require more frequent surgical intervention, and require adjuvant therapy to control disease progression. In addition, patients with HPV-11 RRP were significantly more likely to develop tracheal disease, to require tracheotomy, and to develop pulmonary disease. Patients receiving a diagnosis of RRP before 3 years of age had significantly higher severity scores, higher frequencies of surgical intervention, and greater likelihood of requiring adjuvant medical therapy. Patients with Medicaid insurance had significantly higher severity scores and required more frequent surgical debridement. Birth by cesarean section appeared to be a significant risk factor for more severe disease and necessity of more frequent surgical intervention. Conclusion: Statistical analysis of the relationships among epidemiological factors, HPV type, and clinical course revealed that patients with HPV-11 and patients younger than 3 years of age at RRP diagnosis are prone to develop more aggressive disease as represented by higher severity scores at endoscopic debridement, more frequent operative debridement procedures per year, a greater requirement for adjuvant therapy, and greater likelihood of tracheal disease with tracheotomy. [source] Methylation of the ASC gene promoter is associated with aggressive prostate cancerTHE PROSTATE, Issue 7 2006Rachael L. Collard Abstract Background The aim of this study was to investigate the methylation status of apoptosis-associated speck-like protein containing a CARD (ASC; TMS1; PYCARD) in prostate cancer cell lines and human tissues and to determine if those findings correlate with the clinicopathological features of prostate cancer. Methods Genomic DNA was isolated from prostate cell lines and microdissected tissues, bisulfite converted and analyzed by methylation specific polymerase chain reaction (MSP). Expression of ASC in prostate cancer cell lines treated with or without methylation inhibitors was determined by quantitative or qualitative RT-PCR. Results ASC gene expression was silenced or reduced in five prostate cancer cell lines and correlated with methylation status. Treatment of MDAPCa2b prostate cancer cells with the methylation inhibitors 5-aza-2-deoxycitidine and Zebularine reactivated expression of ASC. Of 58 prostate cancer specimens, methylation of the ASC promoter region was present in 65% of primary cancer tissue, 64% (7/11) of cancer-associated high grade-prostatic intraepithelial neoplasia (HG-PIN), and 28% of normal-appearing but adjacent to tumor prostate tissue. While ASC methylation was not related to Gleason score (P,=,0.46) or pathological stage (P,=,0.75), there was a significantly higher frequency of ASC methylation in the adjacent normal tissue for patients with biochemical recurrence (P,=,0.0383). Conclusions Methylation of the ASC gene promoter is both a frequent and early event in prostate cancer carcinogenesis. Surprisingly, methylation of the adjacent normal tissue occurs significantly more often in patients who later undergo biochemical recurrence, suggesting a role for inactivation of the ASC gene in the initial stages of aggressive disease. Prostate © 2006 Wiley-Liss, Inc. [source] The impact of volume on outcomes after oesophageal cancer surgeryANZ JOURNAL OF SURGERY, Issue 9 2010Ioannis Rouvelas Abstract Oesophageal cancer is an aggressive disease with a poor prognosis. Oesophagectomy is an established, potentially curative treatment, for patients with resectable oesophageal cancer. The anatomical location of the oesophagus explains why this type of operation is one of the most demanding and traumatic surgical procedures undertaken in general surgery. Unfortunately, the risk for severe post-operative complications is high and the chance for cure remains low. It is, however, encouraging that the post-operative morbidity has been decreasing and the survival has been improving during recent years. Several factors might have contributed to this improvement, including the centralization of oesophageal cancer surgery to high volume centres. This review focuses on the impact of hospital and surgeon volume on various outcomes after oesophagectomy for oesophageal cancer. Most available research indicates that, as far as post-operative complications, early post-operative mortality and health economics after oesophagectomy are concerned, high surgery volume is to be recommended, while the few studies evaluating long-term survival and health-related quality of life adjusted for tumour stage found no evidence of a role for volume. In conclusion, the available literature supports the centralization of oesophagectomy for cancer to dedicated centres with a multidisciplinary approach and a good track record of valid clinical research. [source] Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 7 2003Fiona M. McQueen Objective Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. Methods We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. Results At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78,18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R2 = 0.59, adjusted R2 = 0.44). Conclusion MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease. [source] Ductal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical managementBJU INTERNATIONAL, Issue 4 2010Hakan Aydin Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA). PATIENTS AND METHODS The presence of DCP in transrectal ultrasonography-guided prostate biopsy (TRUSB) is associated with adverse pathological findings at radical prostatectomy (RP) and clinical outcomes, and the significance of detecting DCP initially in transurethral biopsy (UB) or transurethral resection (TURP) in the present era of screening with prostate-specific antigen (PSA) is unclear. The study included 23 cases of pure DCP without acinar PA diagnosed on UB or TURP. Demographic information, serum PSA level, follow-up surgical procedures (RP, TURP or TRUSB) and outcome data were collected. RESULTS The mean age of the men was 67.5 years and the mean PSA level before the procedure was 12.5 ng/mL; 14 cases were detected on UB and nine were diagnosed on TURP. The mean (range) follow-up was 4 (1,23) months after the initial procedure. In all, 21 (89%) patients had DCP or PA in follow-up procedures. Two (11%) patients had no residual cancer, one on RP and the other on two repeat TURPs. DCP or PA was found in 12 RP cases; four patients had Gleason score 7 PA, three of which were organ-confined, and eight had Gleason score ,8 PA. Extraprostatic extension, seminal vesicle invasion and regional lymph node metastasis were present in seven, six and two cases, respectively. CONCLUSIONS Most DCP diagnosed on UB or TURP in this contemporary series was associated with aggressive PA, but a subset presented as a small periurethral tumour with no concomitant acinar PA, and was eradicated by the initial biopsy/TURP alone. We recommend that patients with a diagnosis of DCP on UB or TURP undergo follow-up TURP and TRUSB before radical surgery is offered. [source] Prognostic significance of HER-2 status in women with inflammatory breast cancerCANCER, Issue 9 2008Shaheenah Dawood MRCP(UK) Abstract BACKGROUND Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer with poorly understood prognostic variables. The purpose of this study was to define the prognostic impact of HER-2 status on survival outcomes of patients with IBC. METHODS In all, 179 patients with IBC, diagnosed between 1989 and 2005, with known HER-2 status, and treated with an anthracycline-based chemotherapy regimen without trastuzumab, were included in the analysis. Patients with HER-2-positive disease who received trastuzumab at the time of disease recurrence were included. Survival outcomes were estimated by the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. A Cox proportional hazards model was fitted to determine the association of survival outcomes with HER-2 status after adjusting for patient and tumor characteristics. RESULTS A total of 111 patients (62%) had HER-2-negative disease and 68 (38%) had HER-2-positive disease. The median follow-up among all patients was 35 months. At the time of the analysis, 62 patients (55.9%) with HER-2-negative disease and 42 patients (61.8%) with HER-2-positive disease had a recurrence. Thirty-one patients (73.8%) with HER-2-positive disease who had a disease recurrence went on to receive trastuzumab. On univariate analysis, no statistically significant difference was observed for either recurrence-free survival (P = .75) or overall survival (P = .24) between patients who had HER-2-positive disease and those who had HER-2-negative disease. In a multivariate model, HER-2 status did not appear to significantly affect recurrence-free survival (hazards ratio [HR] of 0.75; 95% confidence interval [95% CI], 0.46,1.22 [P = .241]). In the multivariate model, patients with HER-2-positive disease had a decreased hazard of death (HR of 0.56; 95% CI, 0.34,0.93 [P = .024]) compared with patients with HER-2-negative disease. CONCLUSIONS HER-2 status, in the absence of trastuzumab, did not appear to significantly affect recurrence-free survival. After adjusting for other characteristics, the addition of trastuzumab in the metastatic setting significantly improved survival in the HER-2-positive group above and beyond that of the HER-2-negative group. This gives us further insight into the biology of this aggressive disease and underlines the major effect of targeted intervention. Cancer 2008. © 2008 American Cancer Society. [source] Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray,CANCER, Issue 8 2006Gina G. Chung M.D. Abstract BACKGROUND Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA. METHODS TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4,,6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies used were VEGF, FLT-1, FLK-1, and cytokeratin. RESULTS Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan,Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044). CONCLUSIONS VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease. Cancer 2006. © 2006 American Cancer Society. [source] Body mass index is weakly associated with, and not a helpful predictor of, disease progression in men with clinically localized prostate carcinoma treated with radical prostatectomyCANCER, Issue 10 2005Kozhaya N. Mallah M.D. Abstract BACKGROUND Several studies have recently suggested an association between body mass index (BMI) and disease progression after radical prostatectomy. In the current study, the authors examined this association and that between the reciprocal of BMI (INVBMI, 1/BMI) and progression-free probability in men treated with radical retropubic prostatectomy (RRP) for clinically localized prostate carcinoma. METHODS The authors retrospectively studied 2210 patients who underwent RRP at Memorial Sloan-Kettering Cancer Center between September 1986 and May 2003. Clinicopathologic variables analyzed included BMI (kg/m2), preoperative serum prostate-specific antigen level (ng/mL), clinical T classification, year of surgery, race, biopsy-derived primary and secondary Gleason grades, and INVBMI, known to better correlate with percent body fat than BMI. Cox regression analysis was used to examine the possible association between BMI or its reciprocal with disease progression after controlling for the effects of common prognostic factors. The areas under the receiver operating curve (AUC) for models with and without INVBMI were calculated RESULTS Of the 2210 patients analyzed, 251 experienced disease progression in a median follow-up time of 25.9 months (range, 0,143 months). After adjusting for all clinical variables, both BMI (P = 0.071; hazards ratio [HR] = 1.027) and INVBMI (P = 0.041; HR < 0.001) were associated with disease progression. However, the areas under AUC for models with and without INVBMI were similar (range, 0.794,0.798). CONCLUSIONS Although conflicting evidence has been reported regarding the link between obesity and an increased risk of developing prostate carcinoma, as well as an increased risk of developing aggressive disease and prostate carcinoma-related mortality, the authors found weak associations with disease progression for both BMI and INVBMI. These variables were of negligible prognostic value in men who received surgery. Studies with longer follow-up, that examine alternative end points, and that follow treatment(s) besides surgery are needed. Cancer 2005. © 2005 American Cancer Society. [source] Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinomaCANCER, Issue 7 2004Riichiroh Maruyama M.D. Abstract BACKGROUND Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RAR,) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6 -methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. Cancer 2004;100:1472,7. © 2004 American Cancer Society. [source] Histopathology of breast cancer among African-American women,CANCER, Issue S1 2003Lavinia P. Middleton M.D. Abstract Although the overall incidence of breast cancer in African-American women is lower than in white women, African-American women younger than 50 years old have a higher incidence of breast cancer than white women. African-American women with breast cancer have a poorer survival rate than white women and are more likely to die of breast cancer in almost every age group. To explain this disparity, we studied a substantial body of literature that reported a biologic difference in the tumors found in African-American and white women. Specifically, more aggressive histopathologic patterns have been described among African-American patients with breast cancer when compared with white women. In addition, there are data that support an ethnicity-related variation in the expression of breast tumor hormonal markers. The objective of this study was to critically evaluate the existing published data on the histologic features of breast cancer to determine whether breast cancer in African-American women is a histologically more aggressive disease than in white women. We conclude that the aggressive tumor histology reported in African-American women has not been analyzed carefully with respect to the age of the patient at the time of diagnosis and the stage of disease at presentation. Furthermore, there is a need for central pathology review using accepted, published criteria for diagnosis of uncommon and controversial histologic subtypes of breast cancer. Cancer 2003;97(1 Suppl):253,7. Published 2003 by the American Cancer Society. DOI 10.1002/cncr.11021 [source] Treatment planning in cutaneous T-Cell lymphomaDERMATOLOGIC THERAPY, Issue 4 2003Eric C. Vonderheid ABSTRACT:, Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice. [source] | ||||||||||||||||||||||||||||