Biomedical subjects

Jonathan D'Cunha

Publications and source records attributed to Jonathan D'Cunha.

9 recordsLinked to original sources

PubMed2005

Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial.

PURPOSE: A major problem with the staging system for non-small cell lung cancer (NSCLC) is clinical underestimation of the extent of disease. Many patients with clinical stage 1 disease do not retain that designation following surgical resection. Herein, we present data from Cancer and Leukemia Group B (CALGB) protocol 9761 evaluating the correspondence between clinical and pathologic analysis in early stage NSCLC. METHODS: Five hundred and two patients with suspected or biopsy-proven NSCLC classified as clinical stage 1 (T1-2, N0) by computed tomography (CT) scan or cervical mediastinoscopy were prospectively enrolled in CALGB 9761. The purpose of CALGB 9761 was to prospectively evaluate molecular markers of micrometastatic disease in stage 1 NSCLC. Enrollment occurred at 11 selected institutions within the CALGB. Patients with clinically suspected resectable early stage lung cancer were eligible for enrollment if they had no evidence of mediastinal or hilar adenopathy on CT scan or if they had CT evidence of potential N2 or N3 disease (lymph node > or =1.0 cm) but with negative mediastinoscopy. No prior chemotherapy or radiotherapy was permitted. RESULTS: Of the 502 patients felt to have clinical stage 1 NSCLC enrolled in CALGB 9761, 489 underwent resection with complete surgical staging and routine histopathologic analysis. From these 489 patients, only 422 (86.3%) turned out to have pathologically documented NSCLC. Of these 422 patients, 302 (71.6%) had pathologic stage 1 disease (173 stage 1A and 129 stage 1B). Despite clinical assessment of stage 1 disease, 59 (14%) patients had pathologic stage 2 disease, 57 (13.5%) had stage 3 disease, and four (0.9%) patients had stage 4 disease. Of the patients undergoing resection for clinical stage 1 NSCLC, 65 patients did not have NSCLC (44 had benign disease and 21 had malignancies other than NSCLC) and two additional patients had dual synchronous primary NSCLC tumors and were not eligible for the study. Overall, only 61.7% (302 of 489) of patients with suspected stage 1 NSCLC disease retained that stage and diagnosis after complete surgical staging, while 38.3% had an inaccurate pre-operative clinical stage or diagnosis. CONCLUSIONS: The results from this prospective trial demonstrate the poor predictive value of current clinical staging techniques in early stage NSCLC. These findings will serve as a benchmark for comparison of future clinical imaging modalities and other tests evaluating early stage NSCLC.

Biopsy↗

PubMed2004

Expression profiling of non-small cell lung carcinoma identifies metastatic genotypes based on lymph node tumor burden.

OBJECTIVE: This study hypothesized that non-small cell lung carcinoma cells from primary tumors isolated by laser capture microdissection would exhibit gene expression profiles associated with graded lymph node metastatic cell burden. METHODS: Non-small cell lung carcinoma tumors (n = 15) were classified on the basis of nodal metastatic cell burden by 2 methods, obtaining 3 groups: no metastasis, micrometastasis, and overt metastasis. We then performed microarray analysis on microdissected primary tumor cells and identified gene expression profiles associated with graded nodal tumor burden using a correlation-based selection algorithm coupled with cross-validation analysis. Hierarchical clustering showed the regrouping of tumor specimens; the classification inference was assessed with Fisher's exact test. We verified data for certain genes by using another independent assay. RESULTS: The 15 specimens clustered into 3 groups: cluster A predominated in specimens with overt nodal metastasis; cluster B had more specimens with nodal micrometastases; and cluster C included only specimens without nodal metastases. Cluster assignment was based on a validated 75-gene discriminatory subset. Notably, genes not previously associated with positive non-small cell lung carcinoma lymph node status were encountered in the profiling analysis. CONCLUSIONS: Microdissection, combined with microarray analysis, is a potentially powerful method to characterize the molecular profile of tumor cells. The 75-gene expression profiles representative of clusters A and B may define genotypes prone to metastasize. Overall, the 3 groups of tumor specimens clustered separately, suggesting that this approach may identify graded metastatic propensity. Further, genes singled out in clustering may yield insights into underlying metastatic mechanisms and may represent new therapeutic targets.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Gene expression profiling identifies matriptase overexpression in malignant mesothelioma.

STUDY OBJECTIVE: We investigated the gene expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel genes that are potentially involved in the oncogenic transformation of human pleural cells. DESIGN: Complementary DNA (cDNA) microarray transcriptional profiling studies of 10 MPM cell lines and 4 MPM primary tumor specimens were performed using hierarchic clustering. To confirm microarray data, we used real-time polymerase chain reaction and immunoblotting. RESULTS: Cluster analysis differentiated among epithelial (E), sarcomatoid, and biphasic MPM variants. Expression profiling identified common overexpressed or underexpressed genes in MPM. Notably, matriptase messenger RNA was found to be overexpressed by 826-fold in E MPM, with protein expression subsequently confirmed by immunoblot analysis. This recently characterized trypsin-like serine protease has been implicated in tumor invasion and metastasis of E-derived cancers, but has not been described until now in MPM. We also identified other novel genes, such as insulin-like growth factor binding protein 5 and a cDNA clone similar to proteolipid MAL2. CONCLUSIONS: Thus, further large-scale profiling of MPM may elucidate previously unrecognized molecular mechanisms by identifying novel genes that are involved in malignant transformation. Our study has now found matriptase to be one of these mesothelioma-associated genes, with potential pathogenic and therapeutic significance.

Cell Line, Tumor↗

PubMed2003

Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.

PURPOSE: Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS: Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Surgical treatment of tracheal and carinal tumors.

Tracheal tumors are rare. The two most common histologic types (occurring in about equal numbers) are adenoid cystic carcinoma and squamous cell carcinoma. Current approaches for tracheal mobilization allow safe resection of up to 50% of the tracheal length and primary anastomosis in the vast majority of patients.

Anastomosis, Surgical↗

PubMed2003

An Internet-based evaluation system for a surgical residency program.

BACKGROUND: Efficient and meaningful evaluation of performance is critical to the professional development of trainees in surgical residency programs. Current paper-based evaluation instruments have numerous limitations. We developed an Internet-based evaluation system to more rapidly and efficiently assess the experience of residents, faculty, and rotations. STUDY DESIGN: An on-line evaluation system was designed and implemented in October 1999. Custom evaluations were created for residents, faculty, and rotations. Evaluations were completed via the Internet site from remote locations with standard computers and standard Web browser software. Completed evaluations were automatically available on-line for review and data analysis. Data were analyzed by chi-square analysis with a probability value of less than 0.05 considered statistically significant. RESULTS: Compliance in completion of evaluations improved from 50% to 80% in the initial 6 months of implementation (p < 0.01) with the Web-based system. There was no significant difference between faculty and resident compliance. In evaluation of "ease of use," a total of 612 responses were received over this period with a total average score of 3.5 (5 point scale, 5 = strongly agree). Residents' opinions (average score, 3.69) were slightly more positive than those of faculty (average score, 3.31). Confidentiality was improved over paper-based systems by a detailed security network. CONCLUSIONS: This Internet-based evaluation system is a potentially powerful instrument for evaluating our surgical residency program and making changes to improve the educational experience in a timely and efficient manner.

Attitude of Health Personnel↗

PubMed2002

Molecular staging of lung cancer: real-time polymerase chain reaction estimation of lymph node micrometastatic tumor cell burden in stage I non-small cell lung cancer--preliminary results of Cancer and Leukemia Group B Trial 9761.

OBJECTIVE: The 5-year survival for patients with surgically resected stage I non-small cell lung cancer is only 60% to 70%, probably because of undetected systemic occult micrometastases. Detection of occult micrometastases in lymph nodes by reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA in non-small cell lung cancer has not been reported. Detection of occult micrometastases by standard reverse-transcriptase polymerase chain reaction provides only yes or no answers about their presence, whereas quantitative real-time reverse-transcriptase polymerase chain reaction permits reproducible quantitation of target molecules. This study evaluated the ability of quantitative reverse-transcriptase polymerase chain reaction to quantitate lymph node occult metastases with carcinoembryonic antigen messenger RNA as a tumor marker. METHODS: Standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA were performed on 232 lymph nodes from 53 patients with stage I disease (node negative according to histologic examination). Quantitative reverse-transcriptase polymerase chain reaction determined carcinoembryonic antigen messenger RNA quantity by detecting fluorescence increase at a threshold polymerase chain reaction cycle. Threshold polymerase chain reaction cycle values were correlated with standard curves created from serially diluted carcinoembryonic antigen-positive HTB-174 tumor cells to estimate the number of micrometastatic tumor cells in a lymph node. RESULTS: Detection rates of occult metastases were similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 38 of 232 (16.4 %) and 59 of 232 (25.4 %), respectively. Upstaging rates among 53 cases of stage I non-small cell lung cancer were also similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 23 of 53 (43.4 %) and 30 of 53 (56.6%), respectively. Comparison of positive lymph node stations according to quantitative reverse-transcriptase polymerase chain reaction (threshold polymerase chain reaction cycle <45) with HTB-174 tumor cell standard curves yielded estimates of metastatic tumor cell burden of 1.07 x 10(3)to 3.24 x 10(5)cells per lymph node station (median 7190 tumor cells per lymph node station). CONCLUSIONS: Standard and quantitative real-time reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen detected occult metastases in patients with stage I non-small cell lung cancer at similar rates; both upstaged about 50% of cases. Quantitative reverse-transcriptase polymerase chain reaction allows estimation of the number of metastatic cells per lymph node, however, which potentially allows greater precision in predicting recurrence risk.

Adenocarcinoma↗

PubMed2002

Synovial sarcoma of the pleura: a clinical and pathologic study of three cases.

Synovial sarcomas are rare soft tissue malignancies that most commonly affect the extremities in the vicinity of large joints. These malignancies typically occur in adolescents and young adults between the ages of 15 and 40 years.(1,2) Historically they are believed to originate from primitive pluripotent mesenchyme capable of synovial differentiation. This belief is consistent with the malignancy's origin from sites devoid of normal synovium, such as the pleural cavity. A variety of pleural cavity sarcomas have been described, including liposarcoma,(3) chondrosarcoma,(4) osteosarcoma,(5) and malignant schwannoma.(6) Pleural synovial sarcoma, however, is a much rarer entity. In fact, pleural synovial sarcoma was first described only 6 years ago(7) and has not yet been reported in the surgical literature. Because of its rarity, pleural synovial sarcoma is often mistaken for the histologically similar malignant mesothelioma, the most common of the pleural neoplasms. This is a critical distinction, because synovial sarcoma may be extremely aggressive. Studies in the last 10 years have shown it to be extremely sensitive to ifosfamide-based chemotherapy, and survival of patients with synovial sarcoma has recently increased with chemotherapy, with 5-year survivals now as high as 57%.(8-10) In this report, we describe 3 cases of synovial sarcoma of the pleura. Clinical findings are correlated with pathologic features, including immunohistochemical stains and fluorescence in situ hybridization (FISH) for the identification of the diagnostic chromosomal translocation, t(X;18)(p11.2;q11.2). This delineation of the clinical and pathologic aspects of this rare, newly recognized tumor should increase awareness among the surgical community.

Adult↗

PubMedDate not supplied

Postoperative severe microangiopathic hemolytic anemia associated with a giant hepatic cavernous hemangioma.

Complications related to liver hemangioma are rare. We herein describe the case of a patient with three giant cavernous hemangiomas of the liver, of which two were resected for symptoms. A significant microangiopathic hemolytic anemia occurred in the early postoperative period, leading to acute renal failure and necessitating blood transfusions. The systematic evaluation of hemolytic processes in the postoperative patient is described. Surgeons should be aware of the potential for hemolytic complications after major surgery when giant hepatic hemangiomas are present.

Anemia, Hemolytic↗