PubMed Health⌕ Search

Biomedical subjects

Alexander Stojadinovic

Publications and source records attributed to Alexander Stojadinovic.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of recurrence in patients with T2 and early T3, N0 adenocarcinoma of the rectum treated by surgery alone.

PURPOSE: Treatment of rectal cancer with neoadjuvant radiotherapy has been shown to reduce local recurrence and improve overall survival. The role of chemoradiotherapy in patients with T2, N0 and early T3, N0 rectal cancer, treated by radical surgery with total mesorectal excision, remains controversial. The aim of this study was to identify predictors of recurrence in this group of patients to enhance treatment selection. PATIENTS AND METHODS: One hundred patients with primary T2-3, N0 adenocarcinoma of the rectum, uniformly treated by surgery alone, were studied. The pathology slides available for 97 patients were rereviewed. Three patients with incomplete data sets were excluded. Clinical and survival data were obtained from a prospective computerized database and updated from hospital and office charts. The study end points were disease-free survival, disease-specific survival (DSS), time to pelvic recurrence (PR), and distant recurrence. RESULTS: Complete follow-up was available for all study patients. Median follow-up was 79.5 months (range, 57.7 to 105.9 months). During this time period 30 patients (31.9%) died as a result of disease and 64 patients (68.1%) remained alive and disease free. Five-year DSS was 73%. The cumulative risk for PR was 8% at 5 years and 10% at 8 years. Lymphovascular invasion, preoperative serum carcinoembryonic antigen (CEA > 5 ng/mL) level, and age older than 70 years were all associated with adverse outcome. CONCLUSION Patients with T2-3, N0 rectal cancers and either lymphovascular invasion or elevated CEA levels have reduced survival and a higher incidence of PR, and should be considered for future randomized trials.

Adenocarcinoma↗
PubMed2006

Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine.

We are conducting clinical trials of the E75 peptide as a vaccine in breast cancer (BrCa) patients. We assessed T cell subpopulations in BrCa patients before and after E75 vaccination and compared them to healthy controls. We obtained 17 samples of blood from ten healthy individuals and samples from 22 BrCa patients prior to vaccination. We also obtained pre- and post-vaccination samples of blood from seven BrCa patients who received the E75/GM-CSF vaccine. CD4, CD8, CD45RA, CD45RO, and CCR7 antibodies were used to analyze the CD4+ and CD8+ T cells by four-color flow cytometry. Compared to healthy individuals, BrCa patients have significantly more memory and less naïve T cells and more effector-memory CD8+ and less effector CD4+ T cells. Phenotypic differences in defined circulating CD4+ and CD8+ T cell subpopulations suggest remnants of an active immune response to tumor distinguished by a predominant memory T cell response and by untapped recruitment of naïve helper and cytotoxic T cells. E75 vaccination induced recruitment of both CD4+ and CD8+ naïve T cells while memory response remained stable. Additionally, vaccination induced global activation of all T cells, with specific enhancement of effector CD4+ T cells. E75 vaccination causes activation of both memory and naïve CD4+ and CD8+ T cells, while recruiting additional naïve CD4+ and CD8+ T cells to the overall immune response.

Antigens, CD↗
PubMed2006

Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine.

PURPOSE: We are conducting clinical trials in breast cancer (BrCa) patients to test the HER2/neu peptide vaccine (E75). We have investigated the impact of this vaccine on circulating levels of regulatory T cells (Treg) and the resulting effects on antitumor responses. EXPERIMENTAL DESIGN: Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2+ patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry. Cytotoxic activity against HER2/neu+ tumors was measured by 51Cr-release. Serum from BrCa patients and normal subjects were analyzed for TGF-beta levels. RESULTS: BrCa patients have a greater percentage of circulating Treg (CD4+CD25+, 4.45% versus 2.96%; p=0.007) than normal subjects. HLA-A2+ BrCa patients had more Treg compared to the HLA-A2- BrCa patients (CD4+CD25+, 5.63% versus 3.28%; p=0.001). E75 vaccination increased circulating activated CD4+ T cells post-vaccination (CD4+CD69+, 1.23 versus 3.81%; p=0.03). However, T(reg) were significantly reduced after vaccination (CD4+CD25+, 5.31-1.81%; p<0.0001). Furthermore, activated Treg also decreased (CD4+CD25+CD69+, 0.23% versus 0.08%; p=0.06). Importantly, post-vaccination decreases in Treg were temporally associated with increased E75 vaccine-specific CD8+ T cells and corresponding HER2/neu+ tumor cytotoxicity. Serum TGF-beta levels were significantly elevated in BrCa patients compared to normals (3548 pg/ml versus 1007 pg/ml; p=0.007). Four of seven vaccinated patients showed decreased serum TGF-beta levels post-vaccination. CONCLUSIONS: Treg, are increased in BrCa patients along with serum levels of TGF-beta. E75 vaccination resulted in CD4+ recruitment but was associated with a significant decrease in circulating Treg and TGF-beta levels in the majority of the vaccinated patients. Successful cancer vaccination strategies may require the alteration of complex immune interactions.

Antigens, CD↗
PubMed2006

Prospective study of electrical impedance scanning for identifying young women at risk for breast cancer.

BACKGROUND: One way to improve the cost-benefit ratio for breast cancer screening in younger women is to identify those at high-risk of breast cancer and manage them in an optimal manner. The purpose of this study is to evaluate the sensitivity and specificity of Electrical Impedance Scanning (EIS) for identifying young women who are at risk for having breast cancer and should be followed with directed imaging technologies. METHODS: A prospective, observational, two-arm, multi-site clinical trial was performed on women aged 30-45 years. The 'Sensitivity Arm' included Clinical Breast Examinations (CBE) and EIS (T-Scan 2000ED) on 189 women prior to scheduled breast biopsy. The 'Specificity Arm' included 1361 asymptomatic women visiting clinics for routine annual well-woman examination. Sensitivity and specificity were determined. Relative probability for a woman with a positive EIS examination was computed and compared with other approaches commonly used to define 'high-risk' in this population. RESULTS: Fifty of 189 women in the Sensitivity arm had verified cancers, 19 of whom had positive EIS examination resulting in sensitivity of 38% (19/50). Of the 1361 women in the Specificity arm, 67 had positive EIS examination resulting in a specificity of 95% (1294/1361). The relative probability of a woman with a positive EIS examination was 7.68, which compares favorably with other established risk identifiers (e.g. two first-degree relatives with breast cancer or atypical ductal hyperplasia). CONCLUSION: EIS may have an important role as a screening tool for identifying young women that should be followed more closely with advanced imaging technologies for early detection of breast cancer.

Adult↗
PubMed2006

The use of rapid parathyroid hormone assay in predicting postoperative hypocalcemia after total or completion thyroidectomy.

PURPOSE: To evaluate the rapid parathyroid hormone assay (rPTH) as a perioperative tool in predicting postoperative symptomatic hypocalcemia following thyroidectomy. METHODS: We conducted a prospective study of 69 patients undergoing total or completion thyroidectomy. Rapid PTH levels were obtained preoperatively, intraoperatively, and postoperatively upon arrival in the postanesthesia care unit (PACU). All patients were closely monitored postoperatively for the development of symptomatic or asymptomatic hypocalcemia. RESULTS: Of 60 patients (25%) undergoing thyroidectomy, 15 developed hypocalcemia, 7 (11.7%) were symptomatic, and 8 (13.3%) asymptomatic. An intraoperative rPTH level less than 12 pg/mL was 71% sensitive and 95% specific for predicting postoperative symptomatic hypocalcemia, whereas a PACU rPTH level less than 12 pg/mL was 100% sensitive and 92% specific. A greater than 75% decline in preoperative rPTH level when measured intraoperatively was 71% sensitive and 86% specific, whereas a greater than 75% decline in rPTH level in the PACU was 100% sensitive and 88% specific for predicting symptomatic hypocalcemia. CONCLUSIONS: The rPTH assay is a highly accurate and effective tool for predicting symptomatic hypocalcemia immediately after thyroidectomy. Routine utilization of this assay is recommended, because it will allow safe and timely discharge of normocalcemic patients and the early identification of patients requiring treatment of postthyroidectomy hypocalcemia.

Adult↗
PubMed2005

Electrical impedance scanning for the early detection of breast cancer in young women: preliminary results of a multicenter prospective clinical trial.

PURPOSE: To evaluate the feasibility and patient satisfaction with electrical impedance scanning (EIS) for early detection of breast cancer in young women. METHODS: Women undergoing screening clinical breast examination, imaging, or biopsy were eligible for EIS examination with T-Scan 2000ED (Mirabel Medical Systems, Austin, TX). Multiple logistic regression analysis evaluated the association between clinical variables and EIS performance. Patients completed a screening EIS satisfaction questionnaire (1 = least satisfied to 5 = most satisfied). RESULTS: Twenty-nine cancers were identified among 1,103 women. Sixty-six percent (19 of 29) of cancers were nonpalpable and 55% (16 of 29) were in women age < or = 50 years. EIS sensitivity and specificity in women younger than 40 years was 50% and 90%, respectively. Exogenous estrogen use (P < .001) and menopausal status (P = .007) correlated significantly with EIS performance. False-positive rates were increased in postmenopausal women and those taking exogenous hormones. No correlation was evident between EIS performance and family history, prior breast cancer, breast density, or palpability. EIS-positive women younger than age 40 were 4.5 times more likely to have breast carcinoma than were women randomly selected from the general population. Patients were highly satisfied with the comfort, speed, and reporting of EIS screening (mean score, 4.8). CONCLUSION: EIS seems promising for early detection of breast cancer, and identification of young women at increased risk for having the disease at time of screening. Positive EIS-associated breast cancer risk compares favorably with relative risks of conditions commonly used to justify early breast cancer screening. Patients are satisfied with a screening paradigm involving breast EIS.

Adult↗
PubMed2005

Electrical impedance scanning of thyroid nodules before thyroid surgery: a prospective study.

BACKGROUND: Electrical impedance scanning (EIS) is a novel imaging technique based on differential electrical conductivity and capacitance of malignant and normal human tissues. The aim of this study was to evaluate the accuracy of EIS in the detection of thyroid malignancies. METHODS: Patients with thyroid nodules scheduled for thyroid surgery were eligible for the study. Enrolled patients underwent EIS with a T-Scan 2000ED. Nodule location, size, and type (cystic vs. solid) measured by ultrasound, cytology results, thyroid conductivity, and capacitance calculated by EIS were recorded. EIS results were interpreted as positive or negative for malignancy and compared with final histopathology results. Study end points included EIS accuracy, sensitivity, specificity, negative and positive predictive values, and false-positive and false-negative rates. RESULTS: Sixty-four patients were enrolled onto the study, and all underwent either lobectomy-isthmusectomy (20%) or total thyroidectomy (80%). The mean tumor diameter was 2.64 +/- 14.8 mm. Thyroid cancers were identified by histology in 30 patients (46.9%). There were 11 false-positive and four false-negative cases. The overall diagnostic accuracy of EIS was 76.6% (49 of 64 correct diagnoses). The sensitivity and specificity of EIS were 86.7% (26 of 30 true positive) and 67.6% (23 of 34 true negative), respectively. The corresponding positive and negative predictive values were 70.3% and 85.2%. CONCLUSIONS: EIS is a potentially useful imaging modality for differentiating thyroid neoplasms. If these results are confirmed in large-scale trials, EIS may be an important part of the evaluation of thyroid nodules.

Adolescent↗
PubMed2005

Technical complications and durability of hepatic artery infusion pumps for unresectable colorectal liver metastases: an institutional experience of 544 consecutive cases.

BACKGROUND: Hepatic arterial infusion pump chemotherapy is an important component in the treatment of patients with hepatic metastases. Successful use of a hepatic arterial infusion pump requires a low technical complication rate. We evaluated the complications and longterm durability of these devices at our institution. STUDY DESIGN: Between April 1986 and March 2001, 544 patients underwent hepatic arterial infusion pump placement for treatment of unresectable colorectal liver metastases. Patient- and pump-related data were collected by chart review. Pump-related complications, duration of pump function, and overall patient survival were recorded. RESULTS: Median patient survival was 24 months after pump placement. The incidences of pump failure were 9% at 1 year and 16% at 2 years. Pump complications occurred in 120 (22%) of the patients. Complications that occurred early after operation (< 30 days) were more likely to be salvaged than those occurring late (70% versus 30%, p < 0.001). Increased pump complication rates occurred in the setting of variant arterial anatomy (28% versus 19%, p = 0.02), when the catheter was inserted into a vessel other than the gastroduodenal artery (42% versus 21%, p = 0.004), if the pump was placed during the first half of the study period (1986 to 1993, 25% versus 1994 to 2001, 18%; p = 0.05), and if the surgeon had performed fewer than 25 earlier procedures (< 25, 31% versus > or = 25, 19%; p < 0.002). CONCLUSIONS: In this large single institution experience, pump-related complications were low, the majority of early pump complications were salvaged, and pump complication rates improved as institutional experience accumulated. Longterm durability of pump function was excellent.

Catheterization↗
PubMed2004

Squamous cell carcinoma-related oncogene is highly expressed in developing, normal, and adenomatous adrenal tissue but not in aggressive adrenocortical carcinomas.

BACKGROUND: Our previous work has demonstrated squamous cell carcinoma-related oncogene (SCCRO) expression in adult murine adrenocortical tissue. The aim of this study was to assess patterns of SCCRO expression in the embryonic murine adrenal gland, and in normal and neoplastic human adrenocortical tissues in order to determine its role as a marker of differentiation in adrenocortical development and neoplastic progression. METHODS: Murine embryos were procured at developmental stages E8 to E18. A tissue microarray was constructed containing 38 normal, 39 adenomatous, and 87 carcinomatous human adrenocortical specimens. Immunohistochemistry for SCCRO was performed and its expression was graded in suitable tissues. RESULTS: SCCRO expression was detected in the murine adrenal cortex as early as E15 and persisted into the postnatal period. High-level SCCRO expression was identified in 94% of normal (32/34) and adenomatous (29/31) adrenocortical specimens but in only 63% (45/72) of adrenocortical carcinoma (ACC) specimens ( P = .001). Loss of SCCRO expression in primary ACC (13/34 (34%)) correlated with advanced stage ( P = .06), presence of M1 disease at presentation ( P = .03), and worse overall survival ( P = .006). CONCLUSIONS: SCCRO appears to be a marker of adrenocortical differentiation in both murine and human systems. SCCRO expression may be useful in distinguishing adrenocortical adenomas from ACC. Moreover, loss of SCCRO expression in primary ACC is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors.

Adrenal Cortex Neoplasms↗
PubMed2003

An evidence-based approach to the surgical management of resectable pancreatic adenocarcinoma.

BACKGROUND: Randomized prospective trials have addressed various treatment approaches to pancreatic adenocarcinoma in order to improve on the dismal prognosis associated with this disease. We conducted a comprehensive review of prospective randomized clinical trials and summarized the contemporary treatment of resectable pancreatic carcinoma. STUDY DESIGN: A literature search strategy identified prospective randomized clinical trials for pancreatic carcinoma using standard medical subject heading terms. The articles were critically reviewed and ranked according to a standardized three-tiered system (Ia, Ib, Ic) by a panel of experts. RESULTS: Surgical studies have demonstrated that morbidity and mortality are similar for pylorus-preserving and classic pancreaticoduodenectomy. Extended retroperitoneal lymphadenectomy can be performed with similar mortality but increased morbidity compared with standard pancreaticoduodenectomy but does not prolong survival. Pancreaticogastrostomy and pancreaticojejunostomy appear to be comparable techniques for pancreatic duct reconstruction. Pancreatic-enteric anastomosis is associated with lower rates of pancreatic fistula and endocrine insufficiency than duct occlusion without anastomosis. Intraperitoneal drainage after pancreatic resection is unwarranted and may contribute to intraabdominal complications. Routine use of prophylactic octreotide does not lower the rate of pancreatic fistula; it should be considered for reoperative pancreatic resection or for a soft gland. Early trials found that adjuvant chemoradiation therapy prolongs survival. But in more recent studies chemoradiation after resection has failed to show a survival advantage over surgery alone. CONCLUSIONS: Surgical resection remains the only potentially curative therapy for adenocarcinoma of the pancreas. There is no clear indication as to a single preferable resection approach.

Adenocarcinoma↗
PubMed2003

Prognostic indicators of outcomes in patients with distant metastases from differentiated thyroid carcinoma.

BACKGROUND: Distant metastasis is uncommon in differentiated thyroid cancer and the prognosis is unclear. This study aims to evaluate outcomes and to define independent variables that are associated with tumor-related mortality in patients with distant metastasis from thyroid carcinoma. STUDY DESIGN: A retrospective review of the thyroid cancer research database identified 336 patients with distant metastasis from differentiated thyroid carcinoma treated at a single institution between 1941 and 2000. After excluding patients with local or regional recurrence, distant disease was either the first site of recurrence or was detected at the time of diagnosis of the primary tumor in 242 patients (72%). Patient, tumor, and treatment-related factors were analyzed for their relation to disease-specific survival (DSS) using multivariate Cox regression and the log-rank test. RESULTS: Median survival was 4.1 years and 10-year DSS was 26%. Distant disease was synchronous with the primary diagnosis in 97 of 242 (40%) patients. The site of metastasis was lung only in 103 (43%) patients, bone only in 80 (33%), other sites in 14 (6%), and more than one organ system in 45 (19%). Multivariate analysis identified age 45 years or more, symptoms, site other than lung only or bone only, and no radioactive iodine treatment for the metastasis as predictors of poor outcome with 13%, 11%, 16%, and 12% 10-year DSS, respectively. This compares with age less than 45 years, asymptomatic presentation, metastasis only in the lung or bone, and radioactive iodine treatment with 10-year DSS rates of 58%, 45%, 32%, and 33%, respectively (all p < 0.0001). Radioactive iodine treatment was more often given in patients who were less than 45 years of age, asymptomatic, and with metastasis only in the lung or bone only (p = 0.03, 0.11, 0.01). CONCLUSIONS: Longterm survival is possible in patients with distant metastasis from differentiated thyroid cancer. This retrospective study found that age of 45 years or more, site other than lung only or bone only, and symptoms at the time of diagnosis are associated with poorer outcomes.

Adenocarcinoma, Follicular↗
PubMed2003

Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis.

We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.

Adenoma↗
PubMed2003

Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

Adolescent↗
PubMed2003

Effect of hyperglycemia and nitric oxide synthase inhibition on heat tolerance and induction of heat shock protein 72 kDa in vivo.

Diabetes and nitric oxide synthase (NOS) inhibition both exacerbate mesenteric ischemia/ reperfusion injury. Heat shock protein 72 (HSP-72) protects against KDa ischemia/reperfusion damage in vivo. The effect of diabetes on HSP-72 expression in vivo is unknown. The aim of this study was to determine the effects of diabetes and NOS inhibition on HSP-72 induction in vivo. Rats were assigned to four groups: control (C), streptozotocin-induced diabetic (D), acute hyperglycemia (A), and L-N(omega)-nitro-L-arginine treated (L). Rats were subjected to hyperthermia and allowed to recover for 4 hours. Intestine and liver samples from heated (H) and nonheated (NH) rats were analyzed for HSP-72 by Western blot. HSP-72 levels were increased significantly in CH compared to CNH rats. No deaths occurred in CH rats; however, death rates were significant in AH, DH, and LH rats. DH rats died earlier than LH and AH rats. HSP-72 in liver and intestine was reduced significantly in LH rats. When compared with CH rats the surviving AH and DH rats exhibited similar HSP-72 levels in the liver. Diabetes, acute hyperglycemia, and L-N(omega)-nitro-L-arginine treatment lower heat stress tolerance. NOS is required for HSP-72 expression, but not survival. Diabetics who survive heat stress moderately express HSP-72. Characterization of altered thermotolerance and HSP-72 may provide mechanisms for the deranged diabetic stress response.

Acute Disease↗
PubMed2002

Primary adult soft tissue sarcoma: time-dependent influence of prognostic variables.

PURPOSE: To define prognostic factors for postrelapse survival and their time-dependent influence for adult soft tissue sarcoma (STS). PATIENTS AND METHODS: We analyzed 2,123 patients with completely resected localized primary STS treated from 1982 to 1999. Variables studied included tumor site, size, depth, grade, and resection margin but not treatment other than resection. Landmark time frames were used to assess the influence of disease-free interval (DFI) on disease-specific survival (DSS). DSS was estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. Time-dependent stepwise regression analysis evaluated the time-dependent influence of each variable. RESULTS: Two thirds of recurrences developed within 2 years of initial resection. Tumor size (P <.001), grade (P <.001), and microscopic resection margin (P <.001) independently predicted DSS for all STS. Size and grade independently predicted early (DFI 3 years) DSS. Risk of tumor-related death was the same across all sites 3 years postresection and decreased significantly for extremity/trunk STS when DFI exceeded 3 years (P <.001). Influence of initial high-risk factors for tumor-related mortality in extremity/trunk STS decreased by 40% 3 years postresection, but their influence over DSS for non-extremity/trunk sites remained constant over time. Likelihood of complete resection after recurrence (all sites) increased with DFI (9% and 33% for DFI < 6 and > 36 months, respectively). CONCLUSION: Tumor size, grade, and resection margin predict outcome for completely resected STS, and their influence for DSS is time- and site-dependent. The influence of prognostic factors changes over the natural history of extremity/trunk STS. Time to recurrence exerts significant influence over complete resection rates for recurrent disease.

Adolescent↗
PubMed2002

Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

Adolescent↗
PubMed2002

Hürthle cell carcinoma: a 60-year experience.

BACKGROUND: The aim of this study was to define the clinical behavior and prognostic indicators of outcome in Hürthle cell cancer (HCC). METHODS: Diagnosis was confirmed for 56 patients with HCC treated between 1940 and 2000, who form the basis of this study. Primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Data were analyzed with the Kaplan-Meier method and by log-rank test. RESULTS: The extent of thyroid resection did not predict outcome. Recurrence was a significant predictor of tumor-related mortality. Significant adverse predictors of RFS and DSS were degree of invasion, size >4 cm, extrathyroidal extension, and initial nodal or distant metastases. The most significant predictor of outcome was extent of invasion. Eight-year RFS values for low- and high-risk groups were 100% and 24%. Corresponding rates of 8-year DSS were 100% and 58%. CONCLUSIONS: Widely invasive HCC is an aggressive malignancy that identifies patients who are at high risk for recurrence and tumor-related death. Patients with HCC have a prognosis that is reliably predicted by degree of invasion, tumor size, extrathyroidal disease extension, and initial nodal or distant metastasis. Recurrence portends a poor outcome. High-risk patients and those with recurrence should be considered for adjuvant therapy.

Adenoma, Oxyphilic↗