Organ Preservation Protocols Research Articles

Number to Treat Analysis for Planned Neck Dissection after Organ Preservation Therapy with Advanced Neck Disease

To perform a number to treat analysis for planned neck dissection after organ preservation protocols (OPPs) in N2-3 neck disease for head and neck cancer. We performed a literature review from 1993 to the present and collected aggregate data to produce the following four variables: (1) percentage of N2-3 necks still harbouring cancer after radiotherapy in OPPs (C); (2) percentage of regional recurrence after planned neck dissection (P); (3) unsuccessful salvage rate in patients in whom a watch and wait strategy for neck disease was employed (S); and (4) the mortality rate of planned neck dissection (M). The number to treat can be estimated as 1/((C x S + C x M) - (P + M)) RESULTS: The number to treat in this analysis was 4.4. In organ preservation therapy with N2-3 disease, one needs to perform 4.4 neck dissections to prevent one fatal regional recurrence. Although this calculation does have some inherent biases and errors, it may form the basis for an informed discussion with patients faced with the option of planned neck dissection.

Swallowing dysfunction—preventative and rehabilitation strategies in patients with head-and-neck cancers treated with surgery, radiotherapy, and chemotherapy: A critical review

BHARAT B. MITTAL, M.D.,* BARBARA R. PAULOSKI, PH.D., DANIEL J. HARAF, M.D., HAROLD J. PELZER, M.D., ATHANASSIOS ARGIRIS, M.D., EVERETT E. VOKES, M.D., ALFRED RADEMAKER, PH.D., AND JERILYN A. LOGEMANN, PH.D. Departments of *Radiology, Section of Radiation Oncology, Communication Sciences and Disorders, Head and Neck Surgery, Medical Oncology, and Biostatistics Core Facility, Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; Departments of Radiation and Cellular Oncology, and Medicine, Division of Hematology-Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL

Microvascular committee: organ preservation protocols: a panacea or a reconstructive nightmare

Microvascular committee: organ preservation protocols: a panacea or a reconstructive nightmare

Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation.

Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.

Use of the linear stapler for pharyngoesophageal closure after total laryngectomy.

Use of the linear stapler for pharyngoesophageal closure after total laryngectomy.

An algorithm for cadaver kidney allocation based on a multivariate analysis of factors impacting on cadaver kidney graft survival and function

Abstract The large imbalance between cadaver kidney supply and demand makes the implementation of equitable and effective organ allocation systems an urgent need. This has triggered a revision of the criteria used so far for cadaver kidney allocation within the North Italy Transplant program, not least in the light of the many changes that have occurred recently with respect to broader criteria for admission of patients to the waiting list, donor selection, tissue-typing methods, organ preservation and immunosuppressive protocols. We based the critical revision of our cadaver kidney allocation algorithm on univariate and multivariate analysis of a number of immunological, clinical, social and administrative factors that impacted on the transplant outcome in 2,917 patients transplanted in the 12 transplant centers operating within our organization from 1 January 1990 to 30 September 1997. This analysis indicated that younger donor age, absence of pretransplant transfusions, patient dialysis center and level of HLA match showed statistically significant positive associations with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. The results of this analysis were used to develop a new computer-assisted version of our adult kidney allocation algorithm. It works in two steps (local pool first, then the entire waiting list) and four levels (0-1 HLA MM, PRA +; 2 HLA MM, PRA +; 0-1 MM, PRA-; 2-4 HLA MM, PRA-); within each level, selection takes into account waiting time and age difference from donor age. The evaluation of 731 transplants allocated in 19 months with the new algorithm, as against 698 transplants allocated in the preceding 19 months according to the previous algorithm, showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.2% versus 22.6%). The use of the new algorithm was also associated with a significantly increased number of transplanted alloimmunized patients (18.8% versus 9.2% with the previous algorithm) and recipients with 0-1 HLA mismatches (22% versus 14.3%). Furthermore, the number of kidneys used locally has steadily increased. Differences in 6-month graft survival and percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with the new versus the previous algorithm. Survivals were 93.7% versus 91.8%. Percentages of patients with excellent renal function were 69.9% and 71.8%, respectively. These preliminary data suggest that the new algorithm improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

An algorithm for cadaver kidney allocation based on a multivariate analysis of factors impacting on cadaver kidney graft survival and function.

The large imbalance between cadaver kidney supply and demand makes the implementation of equitable and effective organ allocation systems an urgent need. This has triggered a revision of the criteria used so far for cadaver kidney allocation within the North Italy Transplant program, not least in the light of the many changes that have occurred recently with respect to broader criteria for admission of patients to the waiting list, donor selection, tissue-typing methods, organ preservation and immunosuppressive protocols. We based the critical revision of our cadaver kidney allocation algorithm on univariate and multivariate analysis of a number of immunological, clinical, social and administrative factors that impacted on the transplant outcome in 2,917 patients transplanted in the 12 transplant centers operating within our organization from 1 January 1990 to 30 September 1997. This analysis indicated that younger donor age, absence of pretransplant transfusions, patient dialysis center and level of HLA match showed statistically significant positive associations with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. The results of this analysis were used to develop a new computer-assisted version of our adult kidney allocation algorithm. It works in two steps (local pool first, then the entire waiting list) and four levels (0-1 HLA MM, PRA+; 2 HLA MM, PRA+; 0-1 MM, PRA-; 2-4 HLA MM, PRA-); within each level, selection takes into account waiting time and age difference from donor age. The evaluation of 731 transplants allocated in 19 months with the new algorithm, as against 698 transplants allocated in the preceding 19 months according to the previous algorithm, showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.2% versus 22.6%). The use of the new algorithm was also associated with a significantly increased number of transplanted alloimmunized patients (18.8% versus 9.2% with the previous algorithm) and recipients with 0-1 HLA mismatches (22% versus 14.3%). Furthermore, the number of kidneys used locally has steadily increased. Differences in 6-month graft survival and percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with the new versus the previous algorithm. Survivals were 93.7% versus 91.8%. Percentages of patients with excellent renal function were 69.9% and 71.8%, respectively. These preliminary data suggest that the new algorithm improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

Trace Amounts of Albumin Protect Against Ischemia and Reperfusion Injury in Isolated Rat Hearts

Albumin is used to provide colloid osmotic pressure in some resuscitation and organ preservation protocols. These solutions are expensive and carry the risks of using high concentrations of blood products. Used as a carrier of drugs and substrates, the concentration of albumin present in perfusates may be considerably lower in experimental ischemia. The present study examined if trace amounts of albumin (0.0004%) reduce injury from ischemia and reperfusion in isolated rat hearts. Hearts were perfused by the Langendorff technique (60 mmHg) with an intraventricular balloon. Zero-flow ischemia (20 min, 37°C) was followed by reperfusion (35 min, 37°C). Recovery of contractile function during reperfusion was significantly improved by the presence of fatty acid-free bovine serum albumin (BSA) (22 290±1280 mmHg/min, pressure–rate product) or rat serum albumin (RSA) (21 095±2836 mmHg/min) compared with Krebs–Henseleit buffer with no albumin (KHB) (9660±2324 mmHg/min). Release of lactate dehydrogenase activity, formation of tissue edema and accumulation of tissue malonyldialdehyde were significantly reduced in hearts receiving BSA or RSA compared with KHB alone. These parameters were not altered by the presence of albumin in non-ischemic control hearts or in the pre-ischemic values of the hearts subjected to ischemia and reperfusion. Development of ischemic contracture with an extended period of ischemia (27 min) was not altered by the presence of BSA, suggesting that protection observed with albumin occurred during reperfusion, rather than during ischemia. Reperfusion following 45 min of ischemia with bovine serum albumin resulted in similar myocardial injury to hearts that were reperfused following 20 min of ischemia without bovine serum albumin. Thus, trace amounts of albumin provide significant reduction in myocardial injury from ishemia and reperfusion, probably via antioxidant mechanisms.

SURGICAL RECONSTRUCTION AFTER CHEMOTHERAPY OR RADIATION: Problems and Solutions

This article summarizes the most common effects of organ-preservation protocols on head and neck tissues. These highly successful regimens create special problems, such as wound complications and mandibular ORN, that the surgeon must consider. The evolution of reconstructive techniques for the head and neck, culminating with micro-vascular free-tissue transfer, has provided solutions to many of the problems created by these innovative treatments. Continued refinement of these techniques will offer patients the benefits of organ-sparing protocols while assuring an excellent functional outcome should salvage surgery become necessary.

Audit in the management of T3 fixed-cord laryngeal cancer

Purpose: To determine results of various treatments for T3 fixed-cord lesions and the subset T3 glottic cancer in Auckland from 1979 to 1995. Patients and Methods: Data were collected retrospectively from a departmental database, and the notes were reviewed. Because of the difficulty in determining the subsite of some fixed-cord lesions, the entire group of T3 fixed-cord lesions was examined, and those tumors that were considered to be definitely arising from the glottis were then analyzed as a specific subset. Results: Fixed-cord lesions were diagnosed in 75 patients (21 supraglottic, 54 glottic). Primary surgery (total laryngectomy) was performed on 46 patients, primary radical dose radiotherapy was undertaken on 25 patients, and four patients were treated palliatively. For T3 fixed-cord lesions, disease-specific survival for radiotherapy and surgery was 36% and 66%, respectively, and 32% and 67%, respectively, for T3 glottic lesions. For both T3 fixed-cord and T3 glottic lesions, surgery produced significantly better survival than did radiotherapy (<60 Gy; P = .0157). With radiotherapy greater than 60 Gy, cancer of the larynx has been controlled in seven of 13 patients, although only five patients are alive, with a median follow-up of 24 months (range, 12–49 months). Conclusion: Radiotherapy less than 60 Gy produced markedly inferior results to surgery for T3 fixed-cord lesions and T3 glottis in Auckland. Radiotherapy at more than 60 Gy shows promise, but an ongoing audit is essential to ensure that survival is similar to surgery and to that reported by those promoting organ-preservation protocols.

Effects of dimethyl sulfoxide on the globally ischemic heart: Possible general relevance to hypothermic organ preservation

Isolated perfused rabbit hearts were made globally ischemic for 2 hr, then reperfused. For 5 min before and after ischemia hearts were perfused with hypothermic (20 or 27 °C), hypoxic, substrate-free cardioplegic solutions, some of which contained 70 m M dimethyl sulfoxide. Postischemic ventricular pressure development, spontaneous heart rate, coronary flow, lactate dehydrogenase release, tissue Ca 2+ content, and in vitro mitochondrial oxidative phosphorylation were used to evaluate the protective effects of the various solutions. Aside from the expected observations that cold cardioplegia lessens ischemic damage, we found that dimethyl sulfoxide gave no indication that it exacerbated ischemic damage or lessened the protection afforded by cardioplegia. We also found that, compared to values measured in comparable drug-free treated hearts, dimethyl sulfoxide significantly improved mitochondrial State 3 respiratory rates, respiratory control, and oxidative phosphorylation rates, and essentially prevented mitochondrial changes due to ischemia and reperfusion. We propose that dimethyl sulfoxide may act as a “scavenger” of cytotoxic free radicals, many of which are known to be generated by mitochondria during reoxygenation. Since hypoxia, ischemia, and reoxygenation are common accompaniments of most organ preservation protocols, we suggest that low concentrations of dimethyl sulfoxide might serve as a useful adjunct to organ preservation in the nonfrozen state, when cryoprotective concentrations are not needed.