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Vascular Invasion (vascular + invasion)

Distribution by Scientific Domains

Medical Sciences	97%

Distribution within Medical Sciences

Transplantation	19%
Dermatology	16%
Surgery & Surgical Specialties	11%
Pathology	9%
Urology	7%
Hepatology	4%
5 Other Subdomains	18%

Selected Abstracts

Increased Expression of Laminin-5 and Its Prognostic Significance in Hypopharyngeal Cancer,

THE LARYNGOSCOPE, Issue 7 2004
Meijin Nakayama MD
Objectives: We investigated the clinicopathologic significance of laminin-5 ,2 chain (LN,2) expression in 26 surgically removed hypopharyngeal cancers and compared the results with conventional prognostic factors elicited from hematoxylin-eosin (H&E) stained whole-mount laryngeal sections. Study Design: Stainability of LN,2 was mainly evaluated at the invasive front of the cancer nests. Scoring was performed on the basis of a semiquantitative scale defined according to the number of immunopositive cancer cells (score 3, 2, 1, and 0). Stainability of LN,2 was also evaluated macroscopically at different tumor locations such as surface center, interstitial space, and invasive front. Status of cartilage and vascular invasion and patterns of tumor extension were evaluated from H&E stained sections. The results of LN,2 expression correlated with the tumor stages, neck node status, pathologic differentiation, and prognoses. Results: Among the 26 cases, 24 demonstrated positive LN,2 expression. Of these cases, 1, 14, 9, and 0 showed scores of 3, 2, 1, and 0, respectively. Positive expression of LN,2 at the invasive front was more prominent in the high-expression group, and surface center was often positive in the cases of low-expression group. Among the H&E stained prognostic factors, vascular invasion and infiltrative pattern demonstrated significant correlations with clinical outcome. Vascular invasion and infiltrative pattern were also closely related to positive LN,2 expression. Five-year survival rates of patients who showed high LN,2 expression were significantly poorer than in patients with low expression. Conclusion: Hypopharyngeal cancers positive for LN,2 indicate a considerable risk for cancer progression and are closely related to prognosis. Increased LN,2 expression might be a prognostic indicator for squamous cell carcinomas of the hypopharynx. [source]

18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant Patients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
A. Kornberg
Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased 18F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET,) pre-LT. PET, recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET,population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased 18F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria. [source]

A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma

CANCER, Issue 7 2004
Jennifer R. Bellon M.D.
Abstract BACKGROUND Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0,3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age < 40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (< 1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted. Cancer 2004;100:1358,64. © 2004 American Cancer Society. [source]

Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation and metastatic spread

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2001
Michael J. Veness MB
Abstract Background Pindborg tumors (calcifying epithelial odontogenic tumors) are uncommon neoplasms of odontogenic origin most often located in the posterior mandible. First described in detail in 1955 by Pindborg, these tumors are considered benign but can be locally aggressive in nature, with recurrence rates of 10% to 15% reported. The malignant form of this tumor is exceedingly rare. Methods We describe the case of a 64-year-old woman initially treated for a painful infected left mandibular third molar. The patient underwent extraction of the tooth and excision of an associated soft tissue component. Subsequent histologic review identified a Pindborg tumor of the left posterior mandible. Results After initial excision, this tumor recurred twice, with the recurrences exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma) with vascular invasion and spread to a cervical lymph node. Further treatment involved radical surgery and adjuvant radiotherapy. At last review 12 months after treatment, the patient was disease free. Conclusions This article describes only the second case of odontogenic carcinoma. The transformation from benign to malignant histologic findings has not previously been documented in this tumor. The salient clinical features of this case are presented along with supportive pathologic and radiologic evidence. © 2001 John Wiley & Sons, Inc. Head Neck 23: 692,696, 2001. [source]

Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis,,§

HEPATOLOGY, Issue 6 2006
Vincenzo Mazzaferro
Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA,positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc],negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc,positive) groups, then randomized to IFN-, (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09,0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment. (HEPATOLOGY 2006;44:1543,1554.) [source]

Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta-analysis

HEPATOLOGY RESEARCH, Issue 10 2010
Jian-Hong Zhong
Aim:, The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC. Methods:, Electronic and manual searches were conducted to identify randomized controlled trials (RCT) evaluating postoperative adjuvant TACE for participants with HCC. Results:, Six RCT totaling 659 participants, of whom almost all were of stage IIIA HCC, were included. For the 1-year tumor recurrence rate, hepatectomy plus TACE showed statistically significant less incidence of recurrence, with a pooled risk ratio (RR) of 0.68 (95% confidence interval [CI] = 0.55,0.84, P = 0.0003). For 1-year mortality, the trials were favorable for TACE with a pooled risk ratio of 0.48 (95% CI = 0.35,0.65, P < 0.00001). For 3-year mortality, the trials also revealed statistically significant less incidence, with a pooled risk ratio of 0.76 (95% CI = 0.64,0.90, P = 0.002). However, for 5-year mortality, TACE did not demonstrate statistically significant less incidence (RR = 0.94, 95% CI = 0.81,1.08, P = 0.36). Transient fever and nausea/vomiting were reported as side-effects of TACE but were well tolerated by most participants. Conclusion:, Postoperative adjuvant TACE seems promising for participants with HCC with risk factors (multiple nodules of >5 cm or vascular invasion) but requires further trial. [source]

Disseminated bony metastases following incidental gallbladder cancer detected after laparoscopic cholecystectomy

HPB, Issue 4 2003
F Youssef
Background In patients with gallbladder cancer bony metastases are usually a late feature. Case outline A 47-year-old woman presented with a 2-month history of right upper quadrant pain. Ultrasound scan showed gallstones and a thick-walled gallbladder. Laparoscopic cholecystectomy was performed. Histopathology showed poorly differentiated adenocarcinoma infiltrating the muscular layer and vascular invasion. She was referred for further surgery. Staging CT scan of the abdomen showed no local residual disease. However Tc-99 bone scan suggested disseminated bony metastases, which were confirmed by bone trephine biopsy. The cancer progressed rapidly and the patient died 4 months after the diagnosis. Discussion Bone metastases can occur with early gallbladder cancer and a radioisotope bone scan can avoid unnecessary extensive liver surgery. [source]

High ,-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and ,-catenin mutations

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
Shian-Yang Peng
Abstract ,-Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (, 55 years; p = 0.00001), hepatitis B surface antigen (HBsAg) in serum (p = 0.00001), p53 mutation (p = 0.008), large tumor (p = 0.00001), vascular invasion (p = 0.00001) and early tumor recurrence (p = 0.00001) were significant associates of high AFP, while anti-HCV in serum and ,- catenin mutation in HCC had less frequent high AFP (p = 0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10-year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p = 0.05), p53 mutation (p = 0.0004), liver cirrhosis (p = 0.0094), large tumor (p = 0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR = 1.2; CI = 1.0,1.4) after adjustment for the effect of tumor size and tumor stage (p = 0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA-positive HCC was associated with more frequent early recurrence (p = 0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy. © 2004 Wiley-Liss, Inc. [source]

Solitary embolic cutaneous aspergillosis in the immunocompromised patient with acute myelogenous leukemia , a propos another case caused by Aspergillus flavus

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2003
Aleksandar L. Krunic MD
A 68-year-old male with acute myelogenous leukemia was admitted for consolidation chemotherapy. The in-hospital course was complicated by neutropenia, fever and nodular pulmonary opacities suggestive of multifocal pneumonia. The patient subsequently developed a single, solitary necrotic crusted nodule on the right cheek. Skin biopsy demonstrated embolic vascular invasion with septate hyphae, dichotomous branching and minimal inflammation. Tissue culture revealed Aspergillus flavus. Despite systemic antifungal therapy with amphotericin B and granulocyte transfusions, the patient developed respiratory failure and died of disseminated aspergillosis, sepsis and renal failure. The clinical presentation of disseminated infection with Aspergillus flavus as a solitary embolic cutaneous lesion is extremely rare. We have reviewed other cases described in the literature and suggest this pattern of cutaneous involvement as more typical of disseminated infection with Aspergillus flavus. [source]

The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005
SHUICHI KAMIJIMA
Aim: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. Methods: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. Results: p53 over-expression was signi,cantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was signi,cantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a signi,cant prognostic factor in the univariate analysis (P < 0.05), but it did not have a signi,cant impact on survival in the multivariate analysis. Ki-67 labeling index was a signi,cant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. Conclusion: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value. [source]

Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2004
U. Ripamonti
Abstract Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the transforming growth factor-, (TGF-,) superfamily, are soluble mediators of tissue morphogenesis and induce de novo endochondral bone formation in heterotopic extraskeletal sites as a recapitulation of embryonic development. In the primate Papio ursinus, the induction of bone formation has been extended to the TGF-, isoforms per se. In the primate and in the primate only, the TGF-, isoforms are initiators of endochondral bone formation by induction and act in a species-, site- and tissue-specific mode with robust endochondral bone induction in heterotopic sites but with limited new bone formation in orthotopic bone defects. The limited inductive capacity orthotopically of TGF-, isoforms is associated with expression of the inhibitory Smads, Smad6 and Smad7. In primates, bone formation can also be induced using biomimetic crystalline hydroxyapatite matrices with a specific surface geometry and without the exogenous application of osteogenic proteins of the TGF-, superfamily, even when the biomimetic matrices are implanted heterotopically in the rectus abdominis muscle. The sequence of events that directs new bone formation upon the implantation of highly crystalline biomimetic matrices initiates with vascular invasion, mesenchymal cell migration, attachment and differentiation of osteoblast-like cells attached to the substratum, expression and synthesis of osteogenic proteins of the TGF-, superfamily resulting in the induction of bone as a secondary response. The above findings in the primate indicate enormous potential for the bioengineering industry. Of particular interest is that biomimetic matrices with intrinsic osteoinductivity would be an affordable option in the local context. [source]

Phosphate regulates embryonic endochondral bone development

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2009
Alena A. Zalutskaya
Abstract Phosphate is required for terminal differentiation of hypertrophic chondrocytes during postnatal growth plate maturation. In vitro models of chondrocyte differentiation demonstrate that 7,mM phosphate, a concentration analogous to that of the late gestational fetus, activates the mitochondrial apoptotic pathway in hypertrophic chondrocytes. This raises the question as to whether extracellular phosphate modulates chondrocyte differentiation and apoptosis during embryonic endochondral bone formation. To address this question, we performed investigations in the mouse metatarsal culture model that recapitulates in vivo bone development. Metatarsals were cultured for 4, 8, and 12 days with 1.25 and 7,mM phosphate. Metatarsals cultured with 7,mM phosphate showed a decrease in proliferation compared to those cultured in 1.25,mM phosphate. This decrease in proliferation was accompanied by an early enhancement in hypertrophic chondrocyte differentiation, associated with an increase in FGF18 expression. By 8 days in culture, an increase caspase-9 activation and apoptosis of hypertrophic chondrocytes was observed in the metatarsals cultured in 7,mM phosphate. Immunohistochemical analyses of embryonic bones demonstrated activation of caspase-9 in hypertrophic chondrocytes, associated with vascular invasion. Thus, these investigations demonstrate that phosphate promotes chondrocyte differentiation during embryonic development and implicate a physiological role for phosphate activation of the mitochondrial apoptotic pathway during embryonic endochondral bone formation. J. Cell. Biochem. 108: 668,674, 2009. © 2009 Wiley-Liss, Inc. [source]

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2006
L. Hammock
Objective:, To determine whether loss of melastatin (MLSN) is a universal phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma patients who experienced recurrence. Material and methods:, Paraffin blocks of primary melanomas (PMs) were retrieved from 30 patients who had a negative sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate the expression of MLSN mRNA. These results were correlated with clinicopathologic data. Results:, Variable, heterogeneous expression of MLSN mRNA was identified in normal, in situ and invasive melanocytes within and between cases. For the invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN mRNA. The remaining 20% had either regional or total partial downregulation of MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%), with mean relative tumor area of 38%, range 5,85%. Increasing loss of MLSN mRNA significantly correlated with increasing tumor depth and microsatellites (r = 0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%). Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, , 75 vs. >75% mRNA loss, p = 0.02). Decreased overall survival significantly correlated with increasing age and vascular invasion on multivariate analysis. Conclusion:, Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy. [source]

Merkel cell carcinoma: a clinicopathologic study with prognostic implications

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2004
Ryan T. Mott
Background:, Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome. Methods:, Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods. Results:, We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size ,5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome. Conclusions:, The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens. [source]

Proliferative drive and liver carcinogenesis: Too much of a good thing?

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2009
Narci C Teoh
Abstract There have been innumerable studies published in the attempt to identify gene expression signatures in hepatocellular carcinoma (HCC). When all the regulators and targets of the differentially expressed genes are analyzed from larger studies, the most striking theme is upregulation of mitosis-promoting and cell proliferation genes in HCC compared with ,liver-specific gene clusters' in non-tumorous tissue. A major limitation of expression profiling is that it only provides a ,snapshot' of what is an evolving process and thus cannot distinguish the differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream consequences. The development of HCC in a chronically diseased liver, often referred to as hepatocarcinogenesis, is a multistep process characterized by the progressive accumulation and interplay of genetic alterations causing aberrant growth, malignant transformation of liver parenchymal cells, followed by vascular invasion and metastasis. This review will discuss HCC precursor lesions, draw on the ,proliferation cluster' genes highlighted from HCC expression profiling studies, relate them to a selection of regulatory networks important in liver regeneration, cell cycle control and their potential significance in the pathogenesis of HCC or primary liver cancer. [source]

Predictive Factors and the Effect of Phenoxybenzamine on Outcome in Dogs Undergoing Adrenalectomy for Pheochromocytoma

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008
M.A. Herrera
Background: Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. Hypothesis: Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. Animals: Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. Methods: A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. Results: Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P= .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P= .028), lack of intraoperative arrhythmias (P= .0075), and decreased surgical time (P= .0089). Conclusions and Clinical Importance: Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs. [source]

Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation

LIVER TRANSPLANTATION, Issue 5 2010
Deniz Nart
Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail. Liver Transpl 16:621-630, 2010. © 2010 AASLD. [source]

Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma

LIVER TRANSPLANTATION, Issue 5 2008
Michael A. Zimmerman
Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy. Liver Transpl 2008. © 2008 AASLD. [source]

Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma

LIVER TRANSPLANTATION, Issue 4 2008
Igor Dvorchik
Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes. The fractional allelic imbalance (FAI) rate index was determined in each case and was used to compare the acquired mutational load between different tumors. The FAI was determined from the microdissected tissue site displaying the greatest amount of acquired allelic loss. FAI was found to be the strongest predictor of recurrence followed by vascular invasion and then by tumor number or hepatic lobar involvement. Based on these findings, 3 prognostic models were constructed for selection of candidates for LT in patients with concomitant HCC. Molecular markers of tumor progression are the strongest predictors of HCC recurrence currently available, surpassing all components of the tumor-node-metastasis classification system for staging of malignant tumors (TNM), including vascular invasion. Incorporation of these molecular markers of tumor progression could help resolve the ongoing conundrum of organ allocation for patients with HCC. Liver Transpl 2007. © 2007 AASLD. [source]

Transplantation for hepatocellular carcinoma: The Milan criteria and beyond

LIVER TRANSPLANTATION, Issue S2 2006
Richard B. Freeman Jr.
Key Concepts: 1Liver transplantation offers excellent results for selected candidates with hepatocellular carcinoma (HCC). 2Selection strategies have evolved but are mainly based on size and number of tumors, which are surrogates for vascular invasion. Newer techniques show promise for identifying patients at high risk for recurrence and selecting those with low risk, even though they may exceed currently established tumor size criteria. 3Evaluation of the effectiveness of liver transplantation for HCC requires an intent-to-treat approach that must include an accounting of the dropout rate of patients while waiting. 4Locoregional pretransplantation adjuvant treatments may have some role for downstaging and/or reducing the dropout rate before transplantation, but their posttransplantation effect on outcome remains undetermined. 5Liver allocation for HCC candidates in the context of increasing HCC prevalence requires better and evidence-based prioritization policies. Liver Transpl 12:S8,S13, 2006. © 2006 AASLD. [source]

Liver transplantation in association with hepatocellular carcinoma: An update of the international tumor registry

LIVER TRANSPLANTATION, Issue 9 2002
Ernesto P. Molmenti
Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor. [source]

Necrotizing sialometaplasia of the parotid gland associated with angiocentric T-cell lymphoma: A case report and review of the Literature

PATHOLOGY INTERNATIONAL, Issue 4 2010
Takako Yoshioka
A very rare case of necrotizing sialometaplasia of the parotid gland associated with angiocentric T-cell lymphoma was described. A 66-year-old male had left neck and pharyngeal masses and biopsy specimen showed a monotonous proliferation of atypical lymphoid cells with massive necrosis in the parotid gland. Angiocentric pattern or vascular invasion by the lymphoid cells was observed and the involved parotid gland exhibited squamous metaplasia of the ducts and acini; necrotizing sialometaplasia. Immunohistochemical analysis revealed a cytotoxic T-cell phenotype of the lymphoid cells (CD3+, CD4-, CD5+, CD8+, CD56-, Granzyme B+, TIA-1+, Perforin-) but in situ hybridization showed no relation to Epstein-Barr virus. Although necrotizing sialometaplasia is relatively rare in the parotid gland, angiocentric T-cell lymphoma should be considered for a causative condition of necrotizing sialometaplasia. [source]

Composite paraganglioma,ganglioneuroma of the urinary bladder

PATHOLOGY INTERNATIONAL, Issue 9 2005
Hiroyuki Usuda
Presented herein is the case of a 73-year-old man, complaining of dysuria, who had a composite paraganglioma,ganglioneuroma of the urinary bladder (CPGUB). At cystoscopy a submucosal tumor was found in the urinary bladder and resected after transurethral biopsy. The levels of serum catecholamine and 24 h urinary excretion of catecholamine and vanillylmandelic acid were elevated. Grossly, the resected tumor, measuring 4 × 3 × 2.5 cm, had a brownish cut surface with no necrosis and hemorrhage. Histologically, the tumor had alternating cellular and fibrous areas. The cellular areas consisted of polygonal cells, arranged in well-defined nests (Zellballen) and positive for Grimelius staining, with abundant amphophilic to acidophilic cytoplasm, occasionally containing eosinophilic hyaline globules and brown pigments. Although the nuclei of several polygonal cells were bizarre, mitoses and vascular invasion were not found. Fibrous areas consisted of spindle cells, resembling Schwann cell, admixed with ganglionic cells. To the authors' knowledge, only four cases of CPGUB have been reported in the English-language literature. Detailed reported cases and the present case showed no malignant features, such as extra-bladder infiltration and metastasis, and no recurrence in the short length of follow up. Accumulation of long-term follow-up cases may provide valuable prognostic information on this composite tumor. [source]

Activation of STAT3 in thymic epithelial tumours correlates with tumour type and clinical behaviour

THE JOURNAL OF PATHOLOGY, Issue 2 2006
K-C Chang
Abstract The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31%) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Loss of CD59 expression in breast tumours correlates with poor survival

THE JOURNAL OF PATHOLOGY, Issue 5 2003
Z 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]

Increased Expression of Laminin-5 and Its Prognostic Significance in Hypopharyngeal Cancer,

Case Report: Fatal Apophysomyces elegans Infection Transmitted by Deceased Donor Renal Allografts

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010
B. D. Alexander
Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near-drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant-related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near-drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near-drowning events. Attention to aseptic technique during organ recovery and processing is re-emphasized. [source]

Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical Factor

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
E. Vibert
Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ,progression' of AFP was defined by >15 ,g/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 ,g/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 ,g/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness. [source]

HURTHLE CELL NEOPLASM OF THE THYROID GLAND

ANZ JOURNAL OF SURGERY, Issue 3 2008
Mohammed Ahmed
Background: A clinicopathological analysis and long-term follow up of 32 patients with Hurthle cell neoplasm (HCN) was undertaken to contrast the clinical and histological features between benign versus malignant HCN of thyroid and to examine the effect of treatment on the outcome. Methods: This is a retrospective study of 32 patients with HCN who were identified out of an archival clinical/pathological/imaging database of 3752 thyroid cancer patients seen between 1976 and June 2006. All patients underwent thyroid surgery. Data for the non-surgical treatment along with follow up were also analysed. Results: Seventeen patients were classified as malignant HCN (MHCN) and 15 as benign HCN (BHCN). Among the MHCN, there were 11 women and 6 men, whereas among BHCN there were 14 women and 1 man. Three patients designated MHCN presented with metastases, one with pulmonary metastases and two others with skeletal metastases who developed lung metastases 9,19 months later. The mean tumour size was 4.43 ± 0.66 cm for MHCN, and 2.57 ± 0.32 cm for BHCN (P = 0.03). Multicentric tumour foci were evident in five cases (29%) of MHCN but none among the BHCN (P = 0.03). At neck exploration cervical lymph node dissection was carried out in nine MHCN patients with findings of tumour metastases in 33%. Postoperatively, three MHCN patients had no thyroid remnant on ultrasound and computed tomography of neck and undetectable serum thyroglobulin; these were considered to be in remission. Fourteen other MHCN patients with postoperative thyroid remnant and/or distant metastases received 131I treatment. Eight of these patients had negative whole-body scans after 131I treatment and undetectable thyroglobulin. Accordingly, 11 MHCN patients (64.7%) showed evidence of remission and 6 patients did not respond to 131I treatment. After a mean follow up of 35 months, all BHCN patients are alive with no evidence of disease. Of the MHCN, 11 (64.7%) were in remission and 35% had evidence of persistence/recurrence. One patient who had recurrence is dead. A lack of effectiveness of 131I therapy in two patients with distant metastases is an important finding. Conclusion: Features of MHCN consisted of a large tumour size, unequivocal capsular and vascular invasion, multicentric tumour foci, metastatic lymph node deposits in one-third of patients and presence of distant metastasis in a few. Findings of dominant Hurthle cell cytology in a fine-needle aspiration biopsy from a thyroid nodule should prompt surgical resection of the lesion to assess malignancy. [source]

Recurrent keratoacanthoma with vascular invasion: A diagnostic and management dilemma

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2009
Anil Kurien
ABSTRACT A 71-year-old man with chronic renal failure and on peritoneal dialysis presented with recurrence of multiple keratotic nodules along a surgical scar. This was 6 months after the excision of a recurrent keratotic nodule reported as squamous cell carcinoma from the same site. The lesions were initially reported as squamous cell carcinomas, but on review of histology were consistent with keratoacanthomas. One of the keratoacanthomas showed vascular invasion. These responded well to low-dose acitretin at 10 mg three times per week and the patient stayed in remission after 18 months of follow up. [source]