Biomedical subjects

Hubert Stein

Publications and source records attributed to Hubert Stein.

7 recordsLinked to original sources

PubMed2006

The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas.

BACKGROUND: The objectives of this study were to investigate histomorphologic features as a response classification after neoadjuvant radiochemotherapy (RTx/CTx) and to correlate the results with clinical outcome parameters (e.g., postoperative morbidity and mortality, recurrence, and survival) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Three hundred eleven patients with histologically proven, locally advanced, intrathoracic ESCC (clinical T3 or T4, N0-N+, M0) located at or above the level of the tracheal bifurcation underwent preoperative, combined, simultaneous RTx/CTx followed by esophagectomy. Response to RTx/CTx was classified by the quantification of residual tumor cells. A histopathologic response was defined as <10% residual tumor cells found within the specimen compared with a histopathologic nonresponse, which was characterized by >10% residual tumor cells. RESULTS: A histopathologic response was correlated significantly with complete tumor resection status (R0 resection) (P .0001), histopathologic tumor (ypT) category (P <.0001), lymph node involvement (P <.0001), lymphatic vessel invasion (P <.001), and survival (P <.0001). A multivariate Cox regression analysis revealed that histopathologic response classification according to the percentage of residual tumor cells was an independent prognostic factor (P <.0001). Nonresponders had greater postoperative pulmonary morbidity (P = .01), a greater 30-day mortality rate (P = .02), and a dismal survival rate compared to histopathologic responders (P <.0001). CONCLUSIONS: Histopathologic response evaluation based on the quantification of residual tumor cells provided meaningful information for the assessment of outcomes among patients with ESCC who have underwent neoadjuvant RTx/CTx. The current results indicated that histopathologic responders may represent a subgroup of patients who benefit from neoadjuvant therapy followed by surgery.

Aged↗

PubMed2006

Target vessel detection and coronary anastomosis assessment by intraoperative 12-MHz ultrasound.

PURPOSE: Our aim was to assess whether the left internal mammary artery, left anterior descending artery, and anastomosis could be visualized by intraoperative ultrasound for safe graft harvesting, optimal anastomotic target selection, and quality control. DESCRIPTION: In 10 patients, the left internal mammary artery, the left anterior descending artery, and the constructed anastomosis were scanned with 12-MHz epicardial ultrasound. Anastomosis quality was assessed on ultrasound and compared with surgeon score. EVALUATION: All left internal mammary arteries and left anterior descending arteries could be identified, and pathways could be followed on the ultrasound. Plaque and calcifications were detectable. Deviation from initial coronary anastomotic target was necessary in 2 of 10 patients. None of the constructed anastomoses needed revision. On the anastomotic scans, six anastomoses scored satisfactory and four scored good. CONCLUSIONS: Epicardial ultrasound was able to evaluate vessel characteristics and coronary anastomosis patency. This can lead to correction of surgical technique related problems in the operating room, possibly improving graft patency. Further advancements could make epicardial ultrasound a cost effective standard for anastomotic quality control. Applying it during robotic-assisted bypass surgery could make this procedure appropriate for more patients.

Aged↗

PubMed2004

Coamplification and coexpression of GRB7 and ERBB2 is found in high grade intraepithelial neoplasia and in invasive Barrett's carcinoma.

The human growth factor receptor-bound protein 7 gene (GRB7), the founding member of a family of adaptor molecules has been shown to regulate cell migration and has been implicated in tumor progression. GRB7 is localized in close proximity to the ERBB2 gene within an amplicon previously identified in Barrett's adenocarcinoma (BCA). We evaluated gene amplification and mRNA expression of GRB7 and ERBB2 in Barrett's carcinoma and its associated precursor lesions to assess their possible role in Barrett's malignant transformation. Copy number and expression levels were analyzed by Q-PCR (GRB7, ERBB2) and QRT-PCR (GRB7, ERBB2) using TaqMan technology and fluorescence in situ hybridization (ERBB2) in a series of 24 laser-microdissected samples of Barrett's carcinomas and 32 samples of associated premalignant lesions. Parallel analysis of gene copy number changes and expression levels demonstrated that GRB7 and ERBB2 displayed concomitant elevated expression levels and increased copy numbers in 32% of Barrett's carcinomas. There was a correlation between GRB7 and ERBB2 in BCA at the DNA level (r(s) = 0.76, p < 0.001) and the mRNA level (r(s) = 0.89, p < 0.001). Moreover, coamplification (r(s) = 0.97, p < 0.001) and coexpression (r(s) = 0.81, p < 0.001) of GRB7 and ERBB2 are shown to be already present in a subset of BCA associated high-grade intraepithelial neoplasia (HGIN), possibly reflecting a role of a concerted expression of GRB7 and ERBB2. No alterations, neither gene amplification nor overexpression were detected in Barrett's carcinoma associated low grade intraepithelial neoplasia (LGIN), intestinal metaplasia (IM) and squamous epithelium, indicating that alterations of GRB7 and ERBB2 are late events in the carcinogenesis of Barrett's esophagus. These findings may be of particular interest because the transition from high grade intraepithelial neoplasia to invasive carcinoma is a crucial step in malignant transformation in Barrett's carcinogenesis and might underline the putative role of GRB7 and ERBB2 in cell migration and tumor invasion.

Adenocarcinoma↗

PubMed2004

Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma.

Array-based comparative genomic hybridization (aCGH) allows the identification of DNA sequence copy number changes at high resolution by co-hybridizing differentially labelled test and control DNAs to a micro-array of genomic clones. The present study has analysed a series of 23 formalin-fixed, paraffin wax-embedded tissue samples of Barrett's adenocarcinoma (BCA, n = 18) and non-neoplastic squamous oesophageal (n = 2) and gastric cardia mucosa (n = 3) by aCGH. The micro-arrays used contained 287 genomic targets covering oncogenes, tumour suppressor genes, and DNA sequences localized within chromosomal regions previously reported to be altered in BCA. DNA sequence copy number changes for a panel of approximately 50 genes were identified, most of which have not been previously described in BCA. DNA sequence copy number gains (mean 41 +/- 25/BCA) were more frequent than DNA sequence copy number losses (mean 20 +/- 15/BCA). The highest frequencies for DNA sequence copy number gains were detected for SNRPN (61%); GNLY (44%); NME1 (44%); DDX15, ABCB1 (MDR), ATM, LAMA3, MYBL2, ZNF217, and TNFRSF6B (39% each); and MSH2, TERC, SERPINE1, AFM137XA11, IGF1R, and PTPN1 (33% each). DNA sequence copy number losses were identified for PDGFB (44%); D17S125 (39%); AKT3 (28%); and RASSFI, FHIT, CDKN2A (p16), and SAS (CDK4) (28% each). In all non-neoplastic tissue samples of squamous oesophageal and gastric cardia mucosa, the measured mean ratios were 1.00 (squamous oesophageal mucosa) or 1.01 (gastric mucosa), indicating that no DNA sequence copy number chances were present. For validation, the DNA sequence copy number changes of selected clones (SNRPN, CMYC, HER2, ZNF217) detected by aCGH were confirmed by fluorescence in situ hybridization (FISH). These data show the sensitivity of aCGH for the identification of DNA sequence copy number changes at high resolution in BCA. The newly identified genes may include so far unknown biomarkers in BCA and are therefore a starting point for further studies elucidating their possible role in Barrett's carcinogenesis.

Adenocarcinoma↗

PubMed2003

Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial.

PURPOSE: We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy. PATIENTS AND METHODS: Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival. RESULTS: Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P =.002) CONCLUSION: This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Facilitated endoscopic beating heart coronary artery bypass grafting using a magnetic coupling device.

BACKGROUND: Suturing of a coronary anastomosis in totally endoscopic coronary artery bypass grafting on the beating heart is technically demanding. The potential benefits of the endoscopic Magnetic Vascular Positioner device (Ventrica, Inc, Fremont, Calif) to facilitate construction of a coronary anastomosis in a closed chest environment were evaluated. METHODS: Totally endoscopic coronary artery bypass grafting on the beating heart was performed in 8 foxhound-beagle inbred dogs with the da Vinci telemanipulation system (Intuitive Surgical, Mountain View, Calif). A prototype of the endoscopic Magnetic Vascular Positioner device was used to facilitate construction of the coronary anastomosis. One pair of magnets was inserted in the internal thoracic artery and left anterior descending artery using robotic instruments to guide and place the endoscopic delivery platform. All animals underwent angiography; gross inspection of the anastomotic site was performed after excision of the hearts. RESULTS: The procedure was accomplished in all animals in 169 minutes (155-190 minutes). Dissection of the left anterior descending coronary artery (6.5 minutes; 1-20 minutes), positioning of the stabilizer (8.5 minutes; 7-16 minutes), placement of occlusion tapes (6 minutes, 3-10 minutes), and arteriotomy 5.5 minutes (3-30 minutes) was achieved without problems. By use of the Magnetic Vascular Positioner device, the anastomosis at the graft site was performed with the graft still in situ. Except for 1 premature deployment, all other deployments were easily accomplished in 3 minutes (1-28 minutes). The following adverse events were encountered: bleeding from the right ventricle caused by occlusion tape (1), anastomotic leakage on reperfusion requiring repair stitches (2), and anastomotic occlusion as a result of thrombus (1). All except 1 animal with a patent graft and anastomosis survived the procedure. The overall patency was 7 of 8. DISCUSSION: The combination of robotic technology allowing for dexterous manipulation in a closed chest environment and a simple yet effective and timesaving technique for anastomotic coupling may facilitate beating heart totally endoscopic coronary artery bypass grafting.

Anastomosis, Surgical↗

PubMed2003

Totally endoscopic multivessel coronary artery bypass surgery using the da Vinci surgical system: a feasibility study on cadaveric models.

BACKGROUND: The aim of the study was to develop a totally endoscopic coronary artery bypass procedure for the treatment of multivessel disease (MVTECAB). METHODS: Procedure development was conducted on 6 human cadavers with the da Vinci Surgical System. For aortic clamping, a transthoracic aortic clamp was applied. The proximal anastomoses of vein grafts were created transthoracically with the Corlink automated anastomosis device. The target vessels on the heart were exposed with a modified endoscopically applicable Starfish vacuum device. In 1 cadaver, the endo-sling and endoscopic fan retractors were studied for exposure support. RESULTS: Harvesting of bilateral internal thoracic arteries was easily accomplished. Aortic clamping was easier from the right side. In the left-side approach, the proximal anastomoses were completed without leakage in all 3 cadavers. One incorrect deployment occurred, and the deployment needed to be redone. In the right-si d e approach, 1 proximal anastomosis was performed without leakage, and another needed to be repaired for incorrect deployment. The fan retractors either covered too much of the targeted area of the heart surface or did not provide good manipulation capabilities. The endo-sling enabled atraumatic exposure of the target vessels. The modified Starfish performed sufficiently for exposing target vessels. Problems were found with epicardial fat clogging the Starfish suction chamber and with bending of the suction tube neck, both of which resulted in a loss of tissue contact. Two of the cadavers approached from the left side were completely revascularized with 3 grafts, and 4 anastomoses were performed on the third cadaver. Triple-vessel revascularization was performed in the cadavers approached from the right side. CONCLUSION: This study demonstrates the feasibility of performing an MVTECAB on the arrested heart with the da Vinci Surgical System. Further procedure development is necessary to optimize the synergistic effects of the technologies used and to introduce this operation into clinical practice.

Cadaver↗