Discipline MCP5774 The Importance of Pleural Sclerosis in the Treatment of Malignant Effusions

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1 Discipline MCP5774 The Importance of Pleural Sclerosis in the Treatment of Malignant Effusions Subject Area: 5150 Created: 17/10/2013 Active since: 17/10/2013 Number of credits: 1 Hours: Theoretical Practical Self-study Duration Total (per week) (per week) (per week) week 15 hours Faculty Member Responsible: Lisete Ribeiro Teixeira Objectives: To analyze the importance of pleural sclerosis in the treatment of malignant pleural effusions. To foster discussion among the used sclerosing agents (for example, chemotherapeutic agents, talc powder, doxycycline, silver nitrate, iodopovidone etc), as well as their different mechanisms of action and interaction with other drugs in order to produce an effective pleudoresis. To question, based in current knowledge, the possible mechanisms involved in the production of the respiratory distress syndrome produced by intrapleural talc administration. To critically analyze therapeutic modalities that make it possible to control clinical manifestations and prevent the relapse, and to research alternative methods to produce pleural symphysis. In summary, the course will allow students: 1) to analyze and compare the classical treatments and local therapeutic alternatives for the recurrent malignant pleural effusion; 2) to analyze the role of classical thoracoscopy, video assisted thoracoscopy, pleutoperitonial shunt and longterm pleural catheters in the approach of malignant effusion; 3) to analyze the pleudoresis, from techniques and indicated drugs to results obtained; 4) to have a prediction of the administration in human patients of the experimental techniques used in rabbits; 5) to study the pathophysiology of the pleudoresis with the different sclerosing agents. Background: Malignant or neoplastic pleural effusion affects patients with primary or metastatic thoracic neoplasms to the thorax, with an approximate incidence of 150 to 175 thousand cases per year in countries such as England and the United States, and more than 2 million worldwide. The damage of the pleural space, with buildup and accumulation of

2 fluid, results in clinical manifestations that determine rapid deterioration in quality of life of patients; the most important among these manifestations are dyspnea and pain. Survival is drastically reduced: it is believed that once the effusion occurs, death follows in a matter of months. The main reason for this is the lack of appropriate treatment. Once the effusion happens, treatment is palliative. Radiotherapy is not indicated and chemotherapy only exceptionally controls the relapse of the effusion. Thus, in order to soften symptoms, patients are offered a local treatment that softens the pain and the dyspnea. Several methods are recommended, and the discussion of such methods are the subject of the course. Content: It will be discussed: therapeutic proposals, including thoracentesis, drainage of the pleural space (discussion of different catheters), placement of pleuroperitoneal shunt and pleurectomy, either through assisted thoracoscopy or through thoracotomy. drugs that adequately induce the formation of effective pleurodesis, either as a result of the primary sclerosing effect or as a consequence of the antitumor effect. Antibiotics (tetracycline and its derivatives minocycline and doxycycline), chemotherapeutic agents (nitrogen mustard, bleomycin, mitoxantrone), immunomodulatory agents (Corynebacteriumparvum), the most widely accepted agent, talc and the use of other irritants as silver nitrate, sodium hydroxide iodopovidone. the method of producing pleurodesis, analyzing the drug interaction, the need to move the patient immediately after the introduction of the sclerosing agent into the pleural space to allow better distribution of the drug and the need for drainage of the pleural cavity with a tubular drain the Pathophysiology of pleurodesis, with emphasis on the dynamics of collagen deposition and the action of interleukins in the pleurodesis mechanism. the establishment of clinical and experimental protocols to compare the pleural sclerosing effects of various drugs. Assessment Methods: Students will present seminars that will be evaluated and graded by the faculty members responsible for the seminars. Observation: Bibliography: 1. Brour N, Amjadi K, Forster A, Aaron S. Management of malignant pleural effusions with indwelling pleural catheters or talc pleurodesis. Can Respir J Mar- Apr;20(2): Godazandeh G, Qasemi NH, Saghafi M, Mortazian M, Tayebi P. Pleurodesis with povidone-iodine, as an effective procedure in management of patients with malignant pleural effusion. J Thorac Dis Apr;5(2): Basso SM, Mazza F, Marzano B, Santeufemia DA, Chiara GB, Lumachi F. Improved quality of life in patients with malignant pleural effusion following videoassistedthoracoscopic talc pleurodesis. Preliminary results. Anticancer Res Nov;32(11): Matsubara N, Itoh K, Mukai H, Nagai S. Long-term outcome of pleurodesis with OK-432 in metastatic breast cancer: a new risk model for success from an analysis of 75

3 cases. Int J ClinOncol Oct;17(5): Leuzzi G, Vita ML, Porziella V, Congedo MT, Cesario A. Single center experience on talc poudrage morbidity: focus on high talc dosage. J Cardiothorac Surg Jun 27;6: Teixeira LR, Vargas FS, Acencio MM, Ribeiro SC, Sales RK, Antonangelo L, Marchi E. Blockageof vascular endothelialgrowthfactor (VEGF) reduces experimental pleurodesis. Lung Cancer Dec;74(3): Chee A, Tremblay A. The use of tunneled pleural catheters in the treatment of pleural effusions. CurrOpinPulm Med Jul;17(4): Dey A, Bhuniya S, DattaChaudhuri A, Pandit S, Saha-DuttaChowdhury M, Sengupta A, Saha I, De P. Iodopovidonepleurodesis: experience of a tertiary hospital in Kolkata. Singapore Med J Feb;51(2): Thornton RH, Miller Z, Covey AM, Brody L, Sofocleous CT, Solomon SB,Getrajdman GI. Tunneled pleural catheters for treatment of recurrent malignant pleural effusion following failed pleurodesis. J VascIntervRadiol May;21(5): Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ; Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline BTS Pleural Disease. Guideline Group Thorax Aug;65Suppl 2:ii Caglayan B, Torun E, Turan D, Fidan A, Gemici C, Sarac G, Salepci B, KiralN.Efficacy of iodopovidonepleurodesis and comparison of small-bore catheter versus large-bore chest tube. Ann SurgOncol Sep;15(9): Yildirim H, Metintas M, Ak G, Metintas S, Erginel S. Predictors of talc pleurodesis outcome in patients with malignant pleural effusions. Lung Cancer.2008 Oct;62(1): G Antunes, E Neville, J Duffy, N Ali BTS guidelines for the management of malignant pleural.effusion. Thorax 2003;58(Suppl II):ii29 ii Noppen M. Who's (still) afraid of talc? EurEurRespir J. 2007, 29: Stather DR, Tremblay A. Use of tunneled pleural catheters for outpatient treatment of malignant pleural effusions. CurrOpinPulm Med 2007; 13: Hsu LH, Soong TC, Feng AC, Liu MC.Intrapleuralurokinase for the treatment of loculated malignant pleural effusions and trapped lungs in medically inoperable cancer patients. J ThoracOncol. 2006;1: Janes SM, Rahman NM, Davies RJ, Lee YC. Catheter-tract metastases associated with chronic indwelling pleural catheters. Chest. 2007;131: Aelony Y. Talc pleurodesis and acute respiratory distress syndrome. Lancet. 2007, 5;369(: Janssen JP, Collier G, Astoul P, Tassi GF, Noppen M, Rodriguez-Panadero F, Loddenkemper R, Herth FJ, Gasparini S, Marquette CH, Becke B, Froudarakis ME, Driesen P, Bolliger CT, Tschopp JM. Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet. 2007, 5;369(: Stather DR, Tremblay A. Use of tunneled pleural catheters for outpatient treatment of malignant pleural effusions. CurrOpinPulm Med. 2007; 13: Acencio MM, Vargas FS, Marchi E, Carnevale GG, Teixeira LR, Antonangelo L, Broaddus VC. Pleural Mesothelial Cells Mediate Inflammatory and Profibrotic Responses in Talc-induced Pleurodesis. Lung 2007; 12, 1243=7 22. Teixeira LR, Vargas FS, Acencio MM, Bumlai RU, Antonangelo L, Marchi E.Experimentalpleurodesisinducedbyantibiotics (macrolidesorquinolones). Clinics. 2006;61): Liao H, Guo Y, Jun Na M, Lane KB, Light RW.The short-term administration of

4 Ketoprofen does not decrease the effect of Pleurodesis induced by talc or Doxycycline in rabbits Respir Med. 2007;101(5): Antonangelo L, Vargas FS, Teixeira LR, Acencio MM, Vaz MA, Filho MT, Marchi E. Pleurodesis induced by talc or silver nitrate: evaluation of collagen and elastic fibers in pleural remodeling. Lung. 2006;184(2): Agarwal R, Aggarwal AN, Gupta D.Efficacy and safety of iodopovidonepleurodesis through tube thoracostomy.respirology. 2006;11: Teixeira LR, Vargas FS, Acencio MM, Paz PF, Antonangelo L, Vaz MA, Marchi EInfluence of antiinflammatory drugs (methylprednisolone and diclofenac sodium) on experimental pleurodesis induced by silver nitrate or talc.. Chest. 2005; 128: Cetin B, Koçkaya EA, Atalay C, AkayMT.Polidocanol at different concentrations for pleurodesis in rats. Surg Today. 2005;35(12): Dikensoy O, Zhu Z, Donnelly E, Stathopoulos GT, Lane KB, Light RW. Combination therapy with intrapleural doxycycline and talc in reduced doses is effective in producing pleurodesis in rabbits.chest. 2005;128: Paschoalini MS, Vargas FS, Marchi E, Pereira JR, Jatene FB, Antonangelo L, Light RW.Prospective randomized trial of silver nitrate vs talc slurry in pleurodesis for symptomatic malignant pleural effusions. Chest. 2005; 128: Dikensoy O, Light RW. Alternative widely available, inexpensive agents for pleurodesis. CurrOpinPulm Med. 2005;11: Antonangelo L, Vargas FS, Teixeira LR, Acencio MM, Vaz MA, Filho MT, Marchi E.Pleurodesis induced by talc or silver nitrate: evaluation of collagen and elastic fibers in pleural remodeling. Lung. 2006;184: Antony VB, Loddenkemper R, Astoul P, Boutin C, Goldstraw P, Hott J, Rodriguez Panadero F, Sahn SA. Management of malignant pleural effusions. Eur Respir J ; 18): Ferrer J, Villarino MA, Tura JM, Traveria A, Light RW. Talc preparations used for pleurodesis vary markedly from one preparation to another. Chest. 2001; 119: Cardillo G, Facciolo F, Carbone L, Regal M, Corzani F, Ricci A, Di Martino M, Martelli M.Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent pleural effusions. Eur J Cardiothorac Surg. 2002; 21:: Schulze M, Boehle AS, Kurdow R, Dohrmann P, Henne-Bruns D. Effective treatment of malignant pleural effusion by minimal invasive thoracic surgery: thoracoscopic talc pleurodesis and pleuroperitoneal shunts in 101 patients. Ann Thorac Surg. 2001; 71: Campos JR, Vargas FS, de Campos Werebe E, Cardoso P, Teixeira LR, Jatene FB, Light RW. Thoracoscopy talc poudrage: a 15-year experience. Chest. 2001;119: Burrows CM, Mathews WC, Colt HG. Predicting survival in patients with recurrent symptomatic malignant pleural effusions: an assessment of the prognostic values of physiologic, morphologic, and quality of life measures of extent of disease. Chest. 2000;117: Vargas FS, Teixeira LR, Antonangelo L, Vaz MA, Carmo AO, Marchi E, Light RW. Experimental pleurodesis in rabbits induced by silver nitrate or talc: 1-year followup. Chest. 2001;119: Gary Lee YC, Teixeira LR, Devin CJ, Vaz MA, Vargas FS, Thompson PJ, Lane KB, Light RW. Transforming growth factor-beta2 induces pleurodesis significantly faster than talc. Am J RespirCritCare Med. 2001;163: Vargas FS, Teixeira LR, Vaz MA, Carmo AO, Marchi E, Cury PM, Light RW. Silver nitrate is superior to talc slurry in producing pleurodesis in rabbits. Chest. 2000;118:

5 41. Sahn SA. Management of malignant pleural effusions. Monaldi Arch Chest Dis. 2001; 56: Pollak JS. Malignant pleural effusions: treatment with tunneled long-term drainage catheters. Curr Opin Pulm Med. 2002; 8: Vaz MC, Marchi E, Vargas FS.Pleurodesis: techniqueandindications. J BrasPneumol. 2006;32:347-56