Biomedical subjects

Alexander Stojadinovic

Publications and source records attributed to Alexander Stojadinovic.

32 records · Page 2Linked to original sources

PubMed2002

The management of variant arterial anatomy during hepatic arterial infusion pump placement.

BACKGROUND: The success of hepatic arterial infusion pump (HAIP) placement in patients with variant arterial anatomy has not been well described. METHODS: Patients who underwent HAIP placement over a 5-year time period were evaluated. Arterial- and catheter-related pump complication rates and pump survival were compared between patients with normal and variant arterial anatomy. RESULTS: Pumps were placed in 265 patients. Variant anatomy was present in 98 (37%) patients. The presence of variant versus normal anatomy did not increase pump complication rates (8% vs. 4%; P =.18) or decrease pump survival (P =.12). In all patients with an isolated variant right or left hepatic artery (n = 56), ligation of the variant vessel and cannulation of the gastroduodenal artery (GDA) resulted in complete hepatic perfusion and no pump complications. Cannulation of vessels other than the GDA (n = 22) was associated with increased pump complication rates (27% vs. 4%; P =.0001) and decreased pump survival (P =.002). CONCLUSIONS: In this study, HAIP placement in patients with variant anatomy was not associated with increased pump complication rates or decreased pump survival. An optimal strategy for managing variant anatomy is to ligate isolated variant vessels and cannulate the GDA.

Catheterization, Peripheral↗

PubMed2002

Recurrent differentiated thyroid carcinoma: biological implications of age, method of detection, and site and extent of recurrence.

BACKGROUND: We identified factors predictive of outcome for recurrent differentiated thyroid carcinoma (DTC). METHODS: Fifty-seven patients with local (LR), regional (RRec), and/or distant recurrence (DR) of 431 recurrent DTCs were studied. Disease-specific survival (DSS) rate was estimated with the Kaplan-Meier method. Univariate and multivariate comparisons were conducted by log-rank and Cox regression analysis. RESULTS: The median follow-up was 13 years. Distribution of the first relapse was LR only (35%), LR and RRec (23%), LR and DR (30%), and LR, RRec, and DR (12%). Factors predictive of resectability were a long (>or=5-year) disease-free interval (DFI) and subclinical and thyroid remnant recurrence. Only 26% of symptomatic and 45% of thyroid bed LR, and 43% with DFI <5 years, could be resected completely. No isolated thyroid remnant and 75% of thyroid bed LR resulted in tumor-related mortality. Age <45 years, subclinical recurrence, isolated LR, and the ability to render the patient disease free independently predicted DSS. Fifteen-year DSS for LR only; LR and RRec; LR and DR; and LR, RRec, and DR were 49%, 28%, 15%, and 0%, respectively. CONCLUSIONS: Isolated thyroid remnant recurrence defines a benign phenotype. Age, method of detection, site and extent of recurrence, and the ability to render the patient disease free predict outcome for recurrent DTC. Multimodality long-term follow-up is warranted to detect recurrence at a subclinical potentially curative stage.

Adolescent↗

PubMed2002

Clinical significance of molecular expression profiles of Hürthle cell tumors of the thyroid gland analyzed via tissue microarrays.

Hürthle cell tumors are rare thyroid neoplasms for which disease biology is poorly understood and diagnosis of carcinoma can be challenging. The aim of the study was to characterize molecular expression profiles of Hürthle cell tumors and to determine the clinical significance of identified phenotypes. Paraffin-embedded tissue cores of normal thyroid (n = 18), and histopathologically well-defined Hürthle cell adenomas (n = 27), Hürthle cell tumors of unknown malignant behavior (n = 7), and minimally (n = 14) and widely (n = 21) invasive Hürthle cell carcinomas were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, and Ki-67 were detected by immunohistochemistry and correlated with clinicopathological data and patient outcome using standard statistical methodology. Median follow-up time was 8 years. High Ki-67 proliferative index was evident only in the clinically aggressive widely invasive Hürthle cell carcinomas and was associated with significantly reduced relapse-free (P = 0.001) and disease-specific (P < 0.001) survival. The molecular phenotype of Hürthle cell tumors, independent of histopathological subtype diagnosis, was characterized by p53(-), mdm-2(+), p21(+/-), cyclin D1(-), and Bcl-2(+/-). Normal thyroid tissue demonstrated a p53(-), mdm-2(-), p21(-), cyclin D1(-), and Bcl-2(+) phenotype. The Bcl-2(+) phenotype was associated with improved relapse-free survival (P = 0.04) and disease-specific survival (P = 0.01) in widely invasive carcinomas and the Ki-67(+)/Bcl-2(-) phenotype was associated with the diagnosis of widely invasive Hürthle cell carcinoma (P < 0.001). This study demonstrates that tissue microarray-based profiling allows identification of molecular markers that are associated with patient prognosis. High Ki-67 proliferative index was associated with adverse outcome in Hürthle cell neoplasms. Together with down-regulation of Bcl-2, high Ki-67 proliferative index may be useful for diagnosing widely invasive Hürthle cell carcinomas. Molecular alterations in the p53 pathway play a role in Hürthle cell tumorigenesis, but other unidentified molecular changes seem to be required to induce the malignant phenotype.

Adenoma, Oxyphilic↗

PubMed2002

Randomized clinical trials in pancreatic cancer.

The authors reviewed 59 prospective, randomized, controlled trials for pancreatic carcinoma that were published between 1977 and 2000. Of the 11 surgical trials, two each studied extent of resection (standard versus pylorus-preserving pancreaticoduodenectomy) and lymphadenectomy (standard versus extended lymph node dissection), five trials compared different types of pancreaticenteric reconstruction, and one each evaluated the role of prophylactic gastrojejunostomy and chemical splanchnicectomy in the setting of advanced disease.

Evidence-Based Medicine↗

PubMed2002

Completely resected recurrent soft tissue sarcoma: primary anatomic site governs outcomes.

BACKGROUND: We define the natural history and influence of primary anatomic site for completely resected locally recurrent soft tissue sarcoma (STS) without distant metastasis. STUDY DESIGN: We selected 290 patients having at least one local recurrence (LR) after complete resection of primary STS (all sites) between 1982 and 1999. Of these, 239 patients had complete resection of their first LR: 161 extremity-trunk and 78 retroperitoneal-head and neck-visceral-thoracic sarcomas. Study end points included second local recurrence-free survival, distant recurrence-free survival, and disease-specific survival, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and Cox's proportional hazards model for extremity-trunk and retroperitoneal (RP; n 39) tumor sites only. RESULTS: Median followup was 82 months. Complete gross resection rates declined with each subsequent recurrence. Primary tumor site (extremity-trunk: relative risk ERR] 0.74, confidence interval [CI] 0.57 to 0.96, p = 0.03) and microscopic resection margin (negative: RR 0.80, CI 0.62 to 0.99, p 0.04) independently predicted subsequent local control. Extremity-trunk sire and high tumor grade were significant independent predictors of distant disease relapse after complete resection of LR. Site also had a notable influence on disease-specific survival: RP recurrence was associated with 1.4 times increased risk of tumor-related mortality (p = 0.02; 5-year disease-specific survival: extremity-trunk 70% versus RP 57%). High tumor grade was the most marked predictor of tumor-related mortality (RR 1.66, CI 1.28 to 2.18, p<0.001. Nine percent of extremity-trunk and 77% of RP STS-related deaths were caused by advanced LR without synchronous metastasis. CONCLUSIONS: Site governs local control, distant recurrence-free and disease-specific survival for completely resected locally recurrent sarcoma without metastasis. Distant disease relapse determines outcomes for recurrent extremity-trunk STS, and local recurrence is the determinant of tumor-related death in the RP.

Disease-Free Survival↗

PubMed2002

The role of operations for distantly metastatic well-differentiated thyroid carcinoma.

BACKGROUND: The role of operations for distantly metastatic well-differentiated thyroid carcinoma (DTC) is poorly defined. We review the indications for operation for metastatic DTC. METHODS: This study consists of 260 patients treated between 1941 and 2000 for metastatic DTC, of which 59 (23%) underwent operations. Median follow-up was 7 years (range, 1 to 49 years). Metastases were identified clinically in 157 (60%) and radiologically in 103 (40%) patients. The disease-specific survival was estimated with the Kaplan-Meier method. RESULTS: Twenty-four patients (9%) were disease-free with resection. Palliative resection was indicated for painful bone metastasis, pathologic fracture, or symptomatic spinal cord involvement (35/260, 14%). Patients who could undergo complete metastasectomy survived longer than those having incomplete/palliative resection or nonoperative treatment for metastatic DTC (5-year disease-specific survival, 78% vs 43% vs 46%, P =.03). CONCLUSIONS: Solitary distant metastasis of DTC amenable to complete resection is infrequent. Complete metastasectomy may be associated with improved survival for localized distant disease. Palliative resection is indicated to improve quality of life for symptomatic distant metastasis.

Adolescent↗

PubMed2002

A phase II trial of preoperative combined-modality therapy for localized esophageal carcinoma: initial results.

OBJECTIVE: We sought to evaluate treatment response to a novel combined-modality treatment regimen for localized esophageal carcinoma. METHODS: Localized esophageal carcinoma was confirmed with endoscopic ultrasonography, computed tomography, and positron emission tomography before induction therapy. This therapy consisted of combined cisplatin/paclitaxel (cisplatin, 75 mg/m(2); paclitaxel, 175 mg/m(2); 2 cycles, 3-hour infusion) for weeks 1 and 4, combined cisplatin (30 mg. m(-2). wk(-1)) and paclitaxel (30-80 mg. m(-2). wk(-1), 96-hour infusion) with concurrent radiation (external beam, 1.8 Gy/d; total, 50.4 Gy) for weeks 7 to 12, and esophagectomy for week 16 after restaging confirmed resectability. RESULTS: Forty-one patients (36 men) with adenocarcinoma (n = 25) or squamous cell carcinoma (n = 16) were enrolled. Thirty-six patients completed treatment, of whom 34 (85%) had locally advanced disease of clinical stage T3-4 N0-1. Symptoms resolved or improved in 35 (92%) of 38 patients after induction chemotherapy. Fourteen (35%) and 10 (24%) patients experienced grade III/IV myelosuppression during induction chemotherapy and chemoradiation, respectively. Two (5%) had grade III and none had grade IV esophagitis during chemoradiation. Only 2 (5%) patients required enteral feeding-tube support during therapy. Of 33 R0 resections, 9 (26%) had complete pathologic disease, and 4 (12%) had microscopic residual disease. Major (eg, anastomotic response, delayed stricture, and respiratory failure) postoperative morbidity occurred in 13 (36%) of 36 patients. Operative mortality was 5.5% (2/36). CONCLUSION: This regimen of induction concurrent chemoradiation followed by surgical intervention for esophageal carcinoma produces rapid dysphagia relief with initial chemotherapy, has a high overall response rate, and has acceptable toxicity levels.

Adenocarcinoma↗

PubMed2002

Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy.

The presence of focal endocrine cells in colorectal adenocarcinoma is a relatively common phenomenon. However, endocrine differentiation in treated adenocarcinomas of the gastrointestinal tract has received little attention. We noted striking numbers of cells with endocrine morphology and phenotype in the residual tumor of six randomly encountered cases of rectal adenocarcinoma that were subjected to neoadjuvant therapy. All six cases had a substantial treatment response (> or =50%). To validate our initial observation and to explore its clinicopathologic significance, further morphologic and immunohistochemical studies were performed on 53 cases of rectal adenocarcinomas treated with preoperative radiation with (33 cases) or without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53 cases and 79 resection specimens of rectal adenocarcinoma that received no neoadjuvant therapy were used as controls. Chromogranin positivity was identified in the posttreatment resection specimens in 36 of the 53 study cases (67.9%). Twenty of the 36 showed positive staining in > or =20% of the residual tumor cells. The chromogranin-positive cells in these cases often formed cords or nests. On hematoxylin and eosin sections these cells had markedly eosinophilic cytoplasm and round and uniform or sometimes pleomorphic nuclei with an often dense chromatin pattern. The proportion of chromogranin-positive cells was significantly associated with the extent of treatment response (p = 0.0005). Tumors treated with both chemotherapy and radiotherapy were more likely to have abundant chromogranin-positive cells compared with tumors treated with radiotherapy alone (p = 0.0004). In contrast, only 30% of the pretreatment biopsies and 17.7% of the control resection specimens of untreated rectal carcinomas showed chromogranin-positive cells, predominantly arranged as scattered individual positive cells, constituting <10% of the tumor. No significant correlation was observed between pretreatment and posttreatment specimens with regard to chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose resection specimens showed positive chromogranin staining failed to demonstrate any chromogranin positivity in their pretreatment biopsy specimens. In addition, groups or nests of chromogranin-positive cells noted in posttreatment specimens showed a very low Ki67 labeling index (<5%) but showed a frequency of abnormal p53 protein expression comparable with that observed in tumor foci resembling conventional adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is an increased frequency and density of cells with an endocrine phenotype in rectal adenocarcinomas that were subjected to neoadjuvant therapy and that the extent of endocrine cells appears proportional to the degree of treatment response. The possible mechanism for the increased endocrine cells in treated rectal adenocarcinomas may be related to induction of endocrine differentiation in tumor cells by cytotoxic insult.

Adenocarcinoma↗

PubMed2002

Value of frozen-section analysis of sentinel lymph nodes for primary cutaneous malignant melanoma.

OBJECTIVE: To analyze a large, single-institution experience with routine frozen section (FS) of the sentinel lymph node (SLN) in patients with primary cutaneous melanoma. SUMMARY BACKGROUND DATA: Controversy exists over the utility of intraoperative FS analysis of the SLN in patients with primary cutaneous melanoma. METHODS: All patients with clinically node-negative cutaneous melanoma undergoing SLN biopsy from 1991 to 1999 were identified from a prospective database. All SLNs were examined by FS. Step-sectioning and immunohistochemistry of permanent section were performed for SLNs negative by FS. RESULTS: At least one SLN was identified in 98% (360/368) of patients. There were 74 (20%) SLNs positive on permanent section; FS was positive in 59% of these. The accuracy, sensitivity, and specificity of FS were 92%, 59%, and 100%. Because isolated recurrence developed in six patients in the nodal basin in which the SLN was negative, the failure rate was 1.7%. The false-negative rate for SLN biopsy was 7.5%. CONCLUSIONS: Because the prevalence of metastases within the SLN and sensitivity of FS analysis are low, routine use of FS for all patients undergoing SLN biopsy is not recommended.

Adolescent↗

PubMed2002

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

OBJECTIVE: To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. METHODS: The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. CONCLUSIONS: Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

Adolescent↗

PubMed2002

Prospective functional voice assessment in patients undergoing thyroid surgery.

OBJECTIVE: To analyze voice function before and after thyroidectomy for patients with normal preoperative voice using a standardized multidimensional voice assessment protocol. SUMMARY BACKGROUND DATA: The natural history of post-thyroidectomy voice disturbances for patients with preserved laryngeal nerve function has not been systematically studied and characterized with the intent of using the data for postoperative voice rehabilitation. METHODS: During a prospective single-arm study, patients with normal voice underwent functional voice testing using a standardized voice grading scale and a battery of acoustic, aerodynamic, glottographic, and videostroboscopic tests before, 1 week after, and 3 months after thyroidectomy. Differences in observed sample means were evaluated using analysis of covariance or t test; categorical data was analyzed using the Fisher exact or chi-square test. RESULTS: Fifty-four patients were enrolled; 50 and 46 were evaluable at 1 week and 3 months, respectively. No patient developed recurrent laryngeal nerve injury; one had superior laryngeal nerve injury. Fifteen (30%) patients reported early subjective voice change and seven (14%) reported late (3-month) subjective voice change. Forty-two (84%) patients had significant objective change in at least one voice parameter. Six (12%) had significant alterations in more than three voice measures, of which four (67%) were symptomatic, whereas 25% with three or fewer objective changes had symptoms. Patients with persistent voice change at 3 months had an increased likelihood of multiple (more than three) early objective changes (43% vs. 7%). Early maximum phonational frequency range and vocal jitter changes from baseline were significantly associated with voice symptoms at 3 months. CONCLUSIONS: Early vocal symptoms are common following thyroidectomy and persist in 14% of patients. Multiple (more than three) objective voice changes correlate with early and late postoperative symptoms. Alterations in maximum phonational frequency range and vocal jitter predict late perceived vocal changes. Factors other than laryngeal nerve injury appear to alter post-thyroidectomy voice. The variability of patient symptoms underscores the importance of understanding the physiology of dysphonia.

Adult↗

PubMed2002

Heat stress protection against mesenteric I/R-induced alterations in intestinal mucosa in rats.

Prior induction of heat shock protein 70 (HSP70) protects against ischemia-reperfusion (I/R) mucosal injury, but the ability of HSP70 to affect I/R-induced alterations in epithelial cell function is unknown. Rats subjected to whole body hyperthermia (41.5-42 degrees C for 6 min) increased HSP70 and heat shock factor 1 mRNA expression, reaching a maximum 2 h after heat stress and declining thereafter. HSP70 production was maximally elevated at 4 h after heat stress and remained elevated until after 12 h. Heat stress alone had no effect on mucosal function except to enhance secretion in response to ACh. Heat stress provided complete morphological protection against I/R-induced mucosal injury but did not confer a similar protection against I/R-induced decreases in mucosal resistance, sodium-linked glucose absorption, or tachykinin-mediated chloride secretion. Heat stress, however, attenuated the I/R-induced suppression of ACh response, and this effect was dependent on enteric nerves. Thus induction of heat shock protein 70 is associated with the preservation of mucosal architecture and attenuation of some specific functional alterations induced by I/R.

Absorption↗

PubMed2002

Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: a comprehensive analysis.

PURPOSE: Early-stage adenocarcinoma of the rectum treated with curative intent has a favorable overall prognosis; however, 20%-30% of the patients recur, and the majority ultimately die of disease. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors accounting for their more aggressive biological behavior. This study evaluates such molecular phenotypes with regard to cell cycle regulation and proliferation and determines their significance for patient outcome. EXPERIMENTAL DESIGN: One hundred patients with primary T(2-3), N(0) adenocarcinoma of the rectum uniformly treated by surgery alone were studied. Core biopsies of pathological specimens were assembled on tissue microarrays, and expression of p53, mdm-2, p21, Bcl-2, p27, cyclin D1, and Ki-67 was analyzed by immunohistochemistry. Molecular profiles were correlated with disease-free (DFS) and disease-specific survival (DSS). RESULTS: Despite previously described prognostic relevance of some of the investigated molecules in analyses where different stages of colorectal cancer were included, none of the cell cycle-regulatory or proliferation-related markers was associated with recurrence or survival. However, patients with tumors demonstrating down-regulation of p27, a cyclin-dependent kinase inhibitor and tumor suppressor gene associated with development of metastases, showed a trend toward reduced DFS and DSS (P = 0.06 and P = 0.07, respectively). CONCLUSIONS: In this homogeneous group of patients with early-stage, node-negative adenocarcinoma of the rectum uniformly treated by surgery alone, the investigated cell cycle-regulatory and proliferation-associated proteins appear to have no prognostic significance. However, down-regulation of p27 appears to be associated with a trend toward reduced DFS and DSS, which suggests further investigation of other p27-related pathways potentially relevant for metastatic disease.

Adenocarcinoma↗

PubMedDate not supplied

Responding to challenges in modern combat casualty care: innovative use of advanced regional anesthesia.

BACKGROUND: The war in Iraq has resulted in a high incidence of severe extremity injury requiring multiple surgical procedures and extensive rehabilitation. We describe the use of advanced regional anesthesia to meet this significant medical challenge. METHODS: From March 2003 to December 2004, 4,100 casualties have been evacuated to Walter Reed Army Medical Center (WRAMC). Of 1,400 inpatients, 750 have been battle-injured with 500 having extremity injuries. Of these, 287 (57%) received surgical care incorporating regional anesthesia including single-injection peripheral nerve blocks and continuous peripheral and epidural infusion catheters. Wounding, surgical, anesthetic, and outcomes data have been prospectively collected. RESULTS: Over 900 operations (mean 4+/-2/patient) were performed on 287 casualties prior to arrival at WRAMC, and 634 operations (mean 2+/-1/patient) were performed at WRAMC. Thirty-five percent of this cohort was amputees. In the study group, 646 advanced regional anesthesia procedures, including 361 continuous peripheral nerve blocks (CPNBs), were performed with a mean catheter infusion time of 9 days (1-34). Catheter-related complications occurred in 11.9% of casualties and were technical or minor in nature. Catheter-related infection rate was 1.9%. In 126 casualties with indwelling CPNB catheters, a significant decrease in pain score over 7 days was apparent (mean 3.7+/-0.2 to 2.2+/-0.2, P<0.001). CONCLUSION: Advanced regional anesthetic techniques allowed for safe perioperative surgical anesthesia and analgesia in the management of the modern combat casualty.

Adolescent↗