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James Kinross - One of the best experts on this subject based on the ideXlab platform.

  • mass spectrometry transanal minimally invasive surgery ms tamis to promote Organ Preservation in rectal cancer
    Surgical Endoscopy and Other Interventional Techniques, 2020
    Co-Authors: Sam E Mason, Eftychios Manoli, Liam Poynter, James L Alexander, Petra Paizs, Afeez Adebesin, R D Goldin, Ara Darzi, Zoltan Takats, James Kinross
    Abstract:

    Transanal minimally invasive surgery (TAMIS) is deployed for Organ Preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established. In this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers. Forty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS. REIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.

Marshall R. Posner - One of the best experts on this subject based on the ideXlab platform.

  • Organ Preservation for adenoid cystic carcinoma of the larynx
    Oncologist, 2013
    Co-Authors: Krzysztof Misiukiewicz, Robert I Haddad, Roy B Tishler, Nadia Camille, Sewanti Atul Limaye, Marshall R. Posner
    Abstract:

    Objectives. Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for Organ Preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an Organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC.

  • Organ Preservation for adenoid cystic carcinoma of the larynx
    Oncologist, 2013
    Co-Authors: Krzysztof Misiukiewicz, Robert I Haddad, Roy B Tishler, Nadia Camille, Sewanti Limaye, Marshall R. Posner
    Abstract:

    Objectives Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for Organ Preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an Organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC. Methods Two treatment-naive patients with laryngeal ACC treated at Dana-Farber Cancer Institute between 2002 and 2007 were identified. Both patients were offered standard laryngectomy followed by adjuvant radiotherapy or Organ-sparing treatment modality. Results Both patients were males, aged 57 and 73. The patients completed a course of combined chemoradiotherapy with weekly carboplatin and paclitaxel and 7-8 weeks of radiotherapy to a total dose of 6,600 and 7,000 cGy over 50 and 57 days, respectively. There were no treatment breaks or delays because of toxicity. The major toxicities reported by both patients, as anticipated, were Grade 3 mucositis, desquamative dermatitis, and severe dysphagia, all of which resolved. Both patients are alive with local regional control and functional larynx; one at 112+ months with pulmonary metastases at 54 months, and the other disease free at 60+ months. Conclusions Definitive chemoradiation with weekly carboplatin and paclitaxel may be a potential alternative to the current standard of surgery and radiation for patients with locally advanced laryngeal ACC who request an Organ-sparing approach. In this group of patients, salvage laryngectomy may be reserved for those who are locally recurrent or chemoradiotherapy resistant. Although CRT provided long-term local regional control in our two patients, there are evident limitations in obtaining evidence for a determination of treatment of rare diseases. This report provides support for following an Organ Preservation plan in selected patients.

  • sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in tax 324 survival surgery and Organ Preservation
    Annals of Oncology, 2009
    Co-Authors: Marshall R. Posner, C. M. Norris, Lori J. Wirth, Dong M Shin, Kevin J Cullen, Eric Winquist, Cesar R Blajman, E A Mickiewicz, Gary Frenette, L F Plinar
    Abstract:

    Abstract Background Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. Patients and methods These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. Results Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31–not reached] versus 24 months (95% CI: 13–42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41–0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12–59) versus 11 months (95% CI: 8–14) for PF (HR: 0.66; 95% CI: 0.45–0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37–0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). Conclusions In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for Organ Preservation or to improve survival in locally advanced LHC.

  • Organ Preservation and treatment toxicity with induction chemotherapy followed by radiation therapy or chemoradiation for advanced laryngeal cancer
    American Journal of Clinical Oncology, 2005
    Co-Authors: Beverly Ashleigh Guadagnolo, Marshall R. Posner, Lori J. Wirth, Robert I Haddad, Linda Weeks, Charles M Norris, Christopher A Sullivan, Laura A Goguen, Paul M Busse, Roy B Tishler
    Abstract:

    Objectives:The authors reviewed records of patients with advanced laryngeal cancer treated with induction chemotherapy (IC) and hyperfractionated radiation therapy (RT) or chemoradiation (CRT) to determine the rates of Organ Preservation and function.Methods:A total of 29 patients with stage III (45

Tamas Radovits - One of the best experts on this subject based on the ideXlab platform.

  • effects of custodiol n a novel Organ Preservation solution on ischemia reperfusion injury
    The Journal of Thoracic and Cardiovascular Surgery, 2010
    Co-Authors: Sivakkanan Loganathan, Tamas Radovits, Kristof Hirschberg, Sevil Korkmaz, Andrea Koch, Matthias Karck, Gabor Szabo
    Abstract:

    Objective Custodiol (histidine-tryptophan-ketoglutarate solution) is a leading Organ Preservation solution. On the basis of this solution, the novel Custodiol-N was developed. The present study investigated the effects of Custodiol-N in a rat model of heart transplantation. Methods Heterotopic heart transplantation was performed in Lewis rats. Four groups were assigned: 2 Custodiol-N–treated groups and 2 Custodiol-treated control groups with a reperfusion time of 1 hour and 24 hours, respectively. Coronary blood flow, left ventricular pressure, its first derivative, left ventricular end-diastolic pressure, endothelium-dependent vasodilatation to bradykinin and endothelium-independent vasodilatation to sodium nitroprusside, and adenosine triphosphate content were measured. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was performed to detect apoptotic cardiomyocytes. Results After 1 hour, coronary blood flow (3.99 ± 0.24 mL/min/g vs 2.86 ± 0.35 mL/min/g; P P P P P P Conclusion Custodiol-N improves myocardial and endothelial function during the critical phase of reperfusion after heart transplantation.

  • endothelial dysfunction after long term cold storage in htk Organ Preservation solutions effects of iron chelators and n α acetyl l histidine
    Journal of Heart and Lung Transplantation, 2008
    Co-Authors: Tamas Radovits, Matthias Karck, Li Ni Lin, Julia Zotkina, Achim Koch, Ursula Rauen, Gernot Kohler, Gabor Szabo
    Abstract:

    Background To improve the rate of successful heart transplantations, Organ Preservation should be optimized in cardiac transplantation surgery. Iron-dependent oxidative damage and iron-independent, chloride-dependent injury of the endothelium have been described after cold ischemic storage and reperfusion, leading to an enhanced rate of complications and unfavorable outcomes. This screening study tested the effects of iron chelator supplementation in different histidine–tryptophan–ketoglutarate (HTK) Organ Preservation solutions on endothelial function in a long-term storage model of the isolated rat aorta. Methods Isolated rat aortic rings underwent a 24-hour cold ischemic Preservation in different HTK solutions supplemented with iron chelators of low (deferoxamine) and high (LK-614) membrane permeability. In vascular reactivity measurements we investigated the phenyleprine-induced contraction and both endothelium-dependent and -independent vasorelaxation by using cumulative concentrations of acetylcholine and sodium nitroprusside with and without an additional external oxidant injury during re-oxygenation. Results Traditional HTK solution, Custodiol, failed to prevent endothelial dysfunction in our experiments. Use of chloride-poor HTK solutions containing N -α-acetyl-l-histidine with and without supplementation with LK-614, but not with deferoxamine, resulted in significant improvement of impaired endothelial function; moreover, complete protection of the endothelium was feasible after 24-hour cold storage. Endothelium-independent functions of vascular smooth muscle were not affected in any of the groups. Conclusions Our results demonstrate the important pathophysiologic role of iron-dependent oxidative injury in the development of endothelial dysfunction after cold storage, which can be prevented by cell-permeable iron chelators.

Sam E Mason - One of the best experts on this subject based on the ideXlab platform.

  • mass spectrometry transanal minimally invasive surgery ms tamis to promote Organ Preservation in rectal cancer
    Surgical Endoscopy and Other Interventional Techniques, 2020
    Co-Authors: Sam E Mason, Eftychios Manoli, Liam Poynter, James L Alexander, Petra Paizs, Afeez Adebesin, R D Goldin, Ara Darzi, Zoltan Takats, James Kinross
    Abstract:

    Transanal minimally invasive surgery (TAMIS) is deployed for Organ Preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established. In this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers. Forty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS. REIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.

Gabor Szabo - One of the best experts on this subject based on the ideXlab platform.

  • effects of custodiol n a novel Organ Preservation solution on ischemia reperfusion injury
    The Journal of Thoracic and Cardiovascular Surgery, 2010
    Co-Authors: Sivakkanan Loganathan, Tamas Radovits, Kristof Hirschberg, Sevil Korkmaz, Andrea Koch, Matthias Karck, Gabor Szabo
    Abstract:

    Objective Custodiol (histidine-tryptophan-ketoglutarate solution) is a leading Organ Preservation solution. On the basis of this solution, the novel Custodiol-N was developed. The present study investigated the effects of Custodiol-N in a rat model of heart transplantation. Methods Heterotopic heart transplantation was performed in Lewis rats. Four groups were assigned: 2 Custodiol-N–treated groups and 2 Custodiol-treated control groups with a reperfusion time of 1 hour and 24 hours, respectively. Coronary blood flow, left ventricular pressure, its first derivative, left ventricular end-diastolic pressure, endothelium-dependent vasodilatation to bradykinin and endothelium-independent vasodilatation to sodium nitroprusside, and adenosine triphosphate content were measured. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was performed to detect apoptotic cardiomyocytes. Results After 1 hour, coronary blood flow (3.99 ± 0.24 mL/min/g vs 2.86 ± 0.35 mL/min/g; P P P P P P Conclusion Custodiol-N improves myocardial and endothelial function during the critical phase of reperfusion after heart transplantation.

  • endothelial dysfunction after long term cold storage in htk Organ Preservation solutions effects of iron chelators and n α acetyl l histidine
    Journal of Heart and Lung Transplantation, 2008
    Co-Authors: Tamas Radovits, Matthias Karck, Li Ni Lin, Julia Zotkina, Achim Koch, Ursula Rauen, Gernot Kohler, Gabor Szabo
    Abstract:

    Background To improve the rate of successful heart transplantations, Organ Preservation should be optimized in cardiac transplantation surgery. Iron-dependent oxidative damage and iron-independent, chloride-dependent injury of the endothelium have been described after cold ischemic storage and reperfusion, leading to an enhanced rate of complications and unfavorable outcomes. This screening study tested the effects of iron chelator supplementation in different histidine–tryptophan–ketoglutarate (HTK) Organ Preservation solutions on endothelial function in a long-term storage model of the isolated rat aorta. Methods Isolated rat aortic rings underwent a 24-hour cold ischemic Preservation in different HTK solutions supplemented with iron chelators of low (deferoxamine) and high (LK-614) membrane permeability. In vascular reactivity measurements we investigated the phenyleprine-induced contraction and both endothelium-dependent and -independent vasorelaxation by using cumulative concentrations of acetylcholine and sodium nitroprusside with and without an additional external oxidant injury during re-oxygenation. Results Traditional HTK solution, Custodiol, failed to prevent endothelial dysfunction in our experiments. Use of chloride-poor HTK solutions containing N -α-acetyl-l-histidine with and without supplementation with LK-614, but not with deferoxamine, resulted in significant improvement of impaired endothelial function; moreover, complete protection of the endothelium was feasible after 24-hour cold storage. Endothelium-independent functions of vascular smooth muscle were not affected in any of the groups. Conclusions Our results demonstrate the important pathophysiologic role of iron-dependent oxidative injury in the development of endothelial dysfunction after cold storage, which can be prevented by cell-permeable iron chelators.