Trattamento chirurgico dell'esofago di Barrett - Gastrolearning®

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Gastrolearning II modulo/12a lezione
Trattamento chirurgico dell'esofago di Barrett
Dr. Carlo Castoro - Università di Padova

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Trattamento chirurgico dell'esofago di Barrett - Gastrolearning®

  1. 1. La Chirurgia nell’esofago di Barrett e nell’Adenocarcinoma Carlo Castoro USD Chirurgia Oncologica dell’Esofago Istituto Oncologico Veneto IOV-IRCCS Padova GASTRO-LEARNING 2014 Secondo Modulo: Oncologia Gastrointestinale Padova 16 giugno, 2014
  2. 2. The Natural History of Barrett’s Esophagus Starts here….. …..And ends here
  3. 3. Barrett’s esophagus Management The management of patients with Barrett's esophagus involves three major components: ● Treatment of the associated GERD ● Endoscopic surveillance to detect dysplasia ● Treatment of dysplasia The goal of therapy is to prevent cancer development
  4. 4. Meta-analysis of Incidence of AC in BE patients Overall Incidence: 6.3/1000 pts year (95%c.i. 4.7-8.4) Heterogeneity: χ2= 238.2, p<.001) Yousef F Am J Epidemiol 2008
  5. 5. Esofago di Barrett e Rischio di Adenocarcinoma E.B.R.A. Registry • Standard endoscopic definition • Standard pathologic report • Definition of follow- up and outcomes • Audit • Semestral meeting24 participant centers Prof G Zaninotto – Prof M Rugge
  6. 6. • Only index endoscopy: 439 pts (34%) • Incident lesion at index endoscopy – 4 invasive cancer – 7 HG IEN • Incident lesion (w/in 12 months) – 3 invasive cancer – 3 HG IEN BE enrolled patients : 1297 Considered for analysis: 841 E.B.R.A. Registry. Results .1. Median F-Up: 44.6 (24.7 – 60.5) months 3083 Patient/years 23pts
  7. 7. Progression to HG-IEN/AC Multivariate Analysis P-Value RR (95% CI) Age 0.12 - BE Length ( cm) 0.01 1.16 (1.03-1.30) Hiatus Hernia(cm) 0.25 - Nodularity/Ulcerati on (yes-no) 0.0002 7.60 (2.63- 21.98) LG –IEN (yes-no) 0.02 3.74 (1.22- 11.43)
  8. 8. Barrett’s esophagus Dysplasia as a marker of risk — Endoscopic surveillance is performed primarily to detect dysplasia in Barrett's esophagus - LGD ( LG NIN ) - HGD ( HG NIN ) The goal of therapy is to prevent cancer progression
  9. 9. Barrett’s esophagus Treatment of GERD ● Medical therapy: PPI Reduces, does not eliminate, acid secretion and reflux Eliminates symptoms ● Antireflux surgery The goal of therapy is to prevent cancer development
  10. 10. Intervento Antireflusso
  11. 11. Barrett’s Esophagus: Medical vs. Antireflux Surgery • 89 patients (71 M 18 F, median age 58 yrs) • 45 pts Laparoscopic Nissen • 44 PPI • Follow-up 34 months (minimum F-up 12 months) G Zaninotto JOGS, 2012
  12. 12. Symptoms: surgery vs medical therapy 0 5 10 15 20 25 Total Surgery Medical therapy * p<0.001 Before treatment After treatment * **
  13. 13. I.M. 1-30% I.M. 31-100% I.M. 1-30% I.M. 31-100% SSBE LSBE PRE POST I.M. Score before and after treatment p<0.001 No I.M. 27% 12/44 Zaninotto G JOGS 2011
  14. 14. I.M. 1-30% I.M. 31-100% I.M. 1-30% I.M. 31-100% SSBE PRE POST I.M. Score before and after treatment SSBE Surgery Medical Therapy No I.M. No I.M. p<0.04 42% 16%
  15. 15. Effect of Antireflux Surgery on Barrett’s epithelium (Short and Long Segment) Oelschlager 2001 30/54 (55%) 0/36 (0%) <0.001 Hofstetter 2001 8/20 (40%) 1/49 (2%) <0.001 Gurski 2003 11/32 (34%) 0/21 (0%) <0.001 Zaninotto 2005 6/11 (54%) 0/24 (0%) <0.001 Biertho 2006 23/59 (39%) 0/11 (0%) <0.001 Csendes* 2006 20/31 (64%) 26/42 (62%) Author Year Regression SSBE LSBE p * Vagotomy, Partial Gastrectomy & Duodenal Diversion
  16. 16. Regression of LG NiN in BE: Multivariate Analysis Medical 12/19 63.2 15.53 0.033 Surgery 15/16 93.8 < 60 13/16 77.2 1.02 0.407 > 60 14/19 76.9 Male 17/22 77.2 1.10 0.211 Female 10/13 76.9 SSBE 12/16 75 1.75 0.677 LSBE 15/19 78.9 Post-treatment regression (%) O.R. p Rossi, Ann Surg 2006
  17. 17. Metanalysis: Probability of regression to lower grades of dysplasia, nondysplastic or non metaplastic tissue between surgical and medical treated patients Chang, Ann Surg 2007
  18. 18. Metanalysis: Probability of progression to more advanced grades of dysplasia between surgical and medical treated patients Chang, Ann Surg 2007
  19. 19. Comparison of pooled incidence rates of esophageal adenocarcinoma betwen surgically and medically treated patients Chang EY, Ann Surg 2007
  20. 20. Onset of HGD/Ca after medical (43 pts) or surgical therapy (58 pts) : long-term results 5% 3% BE Onset of HGD/Ca Medical treatment Surgical treatment No patients had cancer when surgery was effective! Parrilla P et al. Ann Surg 2003
  21. 21. Participants 189 820 BMI 26.1 23.1 1. s/p A.R Surgery 7 (3.7) 8 (1) 1 pts on antireflux medications 4 (57%) 0 0.026 Mean duration (years) of post-op A/R medications 10 = = Esophageal Adenocarcinoma Controls p
  22. 22. Barrett’s esophagus Treatment of GERD Does aggressive treatment of reflux prevent progression to cancer? — The primary goal of anti-reflux therapy for patients with Barrett's esophagus is to control their reflux symptoms Available data suggest, but do not prove, that aggressive antireflux therapy might also prevent cancer in these patients. The goal of therapy is to prevent cancer development
  23. 23. Does antireflux surgery prevent cancer? Probably yes,....providing the dam can cope!
  24. 24. Barrett’s esophagus Treatment of LGD ENDOSCOPIC ABLATION / MUCOSECTOMY AND ANTIREFLUX SURGERY ? No Agreement
  25. 25. Barrett’s esophagus Treatment of LGD ● For most patients with verified low-grade dysplasia after extensive biopsy sampling, we suggest surveillance endoscopy at intervals of 6 to 12 months (Grade 2C). Extensive biopsy sampling involves taking four- quadrant biopsies at intervals of no more than 1 cm throughout the columnar-lined esophagus AGA guidelines
  26. 26. Barrett’s esophagus Treatment of LGD ● For most patients with verified low-grade dysplasia after extensive biopsy sampling, we suggest surveillance endoscopy at intervals of 6 to 12 months (Grade 2C). Extensive biopsy sampling involves taking four- quadrant biopsies at intervals of no more than 1 cm throughout the columnar-lined esophagus Radiofrequency ablation may be an appropriate therapy for verified low- grade dysplasia if an experienced provider is available Antireflux surgery?? AGA guidelines
  27. 27. No agreement Barrett’s esophagus Treatment of HGD TREATMENT OF HIGH-GRADE DYSPLASIA — For patients with verified high-grade dysplasia (also called intraepithelial neoplasia) in Barrett's esophagus, there are generally four proposed management options: ● Esophagectomy ● Endoscopic therapies that ablate the neoplastic tissue ● Endoscopic mucosal resection ● Intensive endoscopic surveillance in which invasive therapies are withheld until biopsy specimens reveal adenocarcinoma.???
  28. 28. No agreement Barrett’s esophagus Treatment of HGD TREATMENT OF HIGH-GRADE DYSPLASIA — For patients with verified high-grade dysplasia (also called intraepithelial neoplasia) in Barrett's esophagus, there are generally four proposed management options: ● Esophagectomy ● Endoscopic therapies that ablate the neoplastic tissue ● Endoscopic mucosal resection ● Intensive endoscopic surveillance in which invasive therapies are withheld until biopsy specimens reveal adenocarcinoma.???
  29. 29. No agreement Barrett’s esophagus Treatment of HGD TREATMENT OF HIGH-GRADE DYSPLASIA — For patients with verified high-grade dysplasia (also called intraepithelial neoplasia) in Barrett's esophagus, there are generally four proposed management options: ● Esophagectomy ● Endoscopic therapies that ablate the neoplastic tissue ● Endoscopic mucosal resection ● Intensive endoscopic surveillance in which invasive therapies are withheld until biopsy specimens reveal adenocarcinoma.???
  30. 30. Barrett’s esophagus Treatment of HGD ● For most patients with Barrett's esophagus and high-grade dysplasia who are fit to undergo endoscopy, we suggest endoscopic eradication therapy rather than esophagectomy or intensive endoscopic surveillance (Grade 2C). Endoscopic eradication therapy includes endoscopic mucosal resection for the removal and staging of visible lesions (if present), followed by radiofrequency ablation to ablate the remaining metaplastic epithelium. AGA guidelines
  31. 31. IS THE PRESENCE OF BURIED BE A CLINICALLY RELEVANT ISSUE ? Several cases of invasive adenocarcinoma developing from “buried” Barrett’s epithelium have already been reported after Barrett mucosal ablation (Bonavina, 1999 Van Laethem, 2000 Macey, 2001 Shand, 2001 Wolfsen, 2002 Overholt, 2003) Courtesy E Ancona
  32. 32. EUS Stadiazione
  33. 33. Prophylactic esophagectomy in Barrett’s esophagus with HGD • Incidence of occult invasive adenocarcinoma: Tseng, 2003 30% 1982-1994: 43% ( 61% pStage I ) 1994-2001: 17% ( 100% pStage I ) Fernando, 2002 39% Headrick, 2002 36% Zaninotto, 2000 33% Patti, 1999 36% Ferguson, 1997 53% Edwards, 1996 41% Peters, 1994 55% Rice, 1993 38% Pera, 1992 50% Altorki, 1991 45% range: 30-55% pT1a: 5% pN+ pT1b: 18-31% pN+ Courtesy E Ancona
  34. 34. No agreement Barrett’s esophagus Treatment of HGD TREATMENT OF HIGH-GRADE DYSPLASIA — For patients with verified high-grade dysplasia (also called intraepithelial neoplasia) in Barrett's esophagus, there are generally four proposed management options: ● Esophagectomy ● Endoscopic therapies that ablate the neoplastic tissue ● Endoscopic mucosal resection ● Intensive endoscopic surveillance in which invasive therapies are withheld until biopsy specimens reveal adenocarcinoma.???
  35. 35. Barrett’s esophagus Treatment of HGD ● Esophagectomy is the only therapy for high-grade dysplasia that clearly removes all of the neoplastic epithelium, ● rates of procedure-related mortality and long-term morbidity ● post-op quality of life impairment Endoscopic eradication therapy is available, has proven efficacy (although long-term data are not yet available), and is relatively safe
  36. 36. DIVERTICOLO FARINGO-ESOFAGEO? Attività 2010-2013 Chirurgia Oncologia dell’Esofago INTERVENTI RESEZIONE ESOFAGEA: 216 Mortalità Postoperatoria: 2/216 (0.9%) Fistole Anastomotiche: 6/216 (3.6%)
  37. 37. Open questions in surgical resection for HGD or Early Cancer in Barrett’s Esophagus • The role of minimal resection (idest Merendino jejunal interposition) Courtesy E Ancona
  38. 38. Merendino jejunal interposition
  39. 39. Barrett’s esophagus The case for esophagectomy Multifocal HGD, not amenable of eradication with endoscopic mucosectomies Confirmed diagnosis, 2 expert pathologists, repeated biopsies Surgical risks acceptable Lack of patient compliance to endoscopic follow up The goal of therapy is to prevent cancer progression
  40. 40. No agreement EGJ Adenocarcinoma Survival after R0 resection 0 20 40 60 80 100 0 6 12 18 24 30 36 42 48 54 60 mos. % pStage 0 - Ia pStage I b pStage II pStage III-IV
  41. 41. Barrett’s adenocarcinoma Influence of surveillance on survival 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 6 12 18 24 30 36 42 48 54 60 months Occasional finding Unsurveilled Barrett's Surveilled Barrett's N=10 pts N=49 pts N=14 pts G Zaninotto, E Ancona JOGS, 2012
  42. 42. Barrett’s esophagus Summary and Recommendations Barrett’s – IM no dysplasia - Treat GERD - Antireflux surgery in non responders to medical therapy LGD - Endoscopic ablation and antireflux surgery - Strict endoscopic followup HGD - Endoscopic mucosectomy and/or ablation and antireflux surgery - Esophagectomy if eradication fails or multifocal HGD
  43. 43. Oesophagectomy for cancer: techniques and results
  44. 44. K Esofago Toracico (n = 2992) K Esofago Cervicale (n = 717) K Cardias (n = 972) Periodo: 1980 / 1994 - Pazienti: 3020 13% 65% 22% Tecnica di esofagectomia per cancro Esophageal and EG Junction Carcinoma 1980-2011: 4179 pz
  45. 45. Tecnica di esofagectomia per cancro Esophageal and EG Junction Carcinoma 1980-2011: 4179 pz 0 20 40 60 80 100 SCC Adeno Altro
  46. 46. Achieving R0 resection should be the goal of surgery (it is the most significant independent prognostic factor) Key points • surgical approach • esophageal resection • gastric resection • extent of lymphadenectomy Tecnica di esofagectomia per cancro
  47. 47. Type II: Distal esophagectomy and proximal gastrectomy with paraesophageal and upper abdominal lymphadenectomy; resection extended to subtotal esophagectomy with proximal gastrectomy or total gastrectomy, or esophago-gastrectomy.
  48. 48. Adenocarcinoma of the esophagus & esophago-gastric junction • Type I Esophago-gastric resection & gastric pull-up • Type II Esophago-gastric resection & gastric pull-up Extended gastrectomy & esophago-jejunostomy Limited resection for early cancer : short esophageal resection + proximal gastrectomy & Merendino jejunal interposition • Type III Extended gastrectomy (D2) & esophago-jejunostomy ?
  49. 49. Tecnica di esofagectomia per cancro Trends in Management and Prognosis for Esophageal cancer Surgery Twenty-five Years of Experience at a Single Institution Objective: To investigate trends in results of esophagectomies for carcinoma at a single high-volume institution Ruol A, Castoro C, et al. Arch Surg 2009; 144(3):247-254
  50. 50. Tecnica di esofagectomia per cancro 1980-2004: 3493 carcinoma of the thoracic esophagus & EG-J type I-II  1978 consecutive surgical resections years 1980-1987 1988-1995 1996-2004 N. patients % resections p = 0.01 785/1438 54.6% 659/1178 55.9% 534/877 60.9% R0 complete resections p < 0.0001 585 74.5% 502 76% 481 90% Ruol, Castoro et al. Arch Surg 2009;144(3):247-54
  51. 51. 1978 esophagectomies for Cancer of the thoracic esophagus & EG-J - postoperative deaths 0 2 4 6 8 10 1980-1987 1988-1995 1996-2004 % 1.4% (7/495)after gastric pull-up 64/785 8.2% 42/659 6.4% 14/534 2.6% in-hospital deaths p < 0.0001 Ruol, Castoro et al. Arch Surg 2009;144(3):247-5 Tecnica di esofagectomia per cancro
  52. 52. 0 25 50 75 100 12 24 36 48 60 1980-1987 (n=785) 1988-1995 (n=659) 1996-2004 (n=534) Survival after resection surgery (R0-2), including postop. deaths months % p<0.0001 43% 19% 23% Ruol, Castoro et al. Arch Surg 2009;144(3):247-5 Tecnica di esofagectomia per cancro
  53. 53. Tecnica di esofagectomia per cancro New standards • Early cancer T1a: endoscopic mucosectomy • Neoadjuvant chemo-radiation (CROSS Trial) • Minimally invasive oesophagectomy • High volume centers multidisciplinary team
  54. 54. - Stadio potenzialmente operabile: CT, CT-RT, Chirurgia? - Terapia neoadiuvante: quando? quale ? - Terapia definitiva: quando? quale CT-RT? Carcinoma dell’esofago e del cardias: percorsi diagnostico-terapeutici Padova, 9 Maggio 2014
  55. 55. Courtesy H. van Laarhoven To treat or not to treat neoadjuvantly? That is not the question (anymore)
  56. 56. Courtesy H. van Laarhoven Ronellenfitch, Eur J Cancer 2013, 3149
  57. 57. Courtesy H. van Laarhoven Sjoquist Lancet Oncol 2011
  58. 58. BJS 2014; 101: 321
  59. 59. Courtesy H. van Laarhoven Surgery (n=188) N+ or T2/T3 oesophageal cancer 41.4Gy in 5 wks paclitaxel 50 mg/m2 q wk Carboplatin AUC 2 q wk Surgery (n=178) CROSS: randomized phase III study Van Hagen NEJM 2012
  60. 60. Courtesy H. van Laarhoven Van Hagen NEJM 2012
  61. 61. Courtesy H. van Laarhoven Van Hagen NEJM 2012
  62. 62. Courtesy H. van Laarhoven Neoadjuvant chemoradiation treatment of choice for oesphageal adenocarcinoma How to make another substantial step forward?
  63. 63. Courtesy H. van Laarhoven Target therapy

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