Presentation on theme: "Anastomotic leakage in rectal surgery after neoadjuvant therapy"— Presentation transcript:
1 Anastomotic leakage in rectal surgery after neoadjuvant therapy Montecatini Terme 28 maggio 2005Dario ScalaINT Napoli
2 Anastomotic leakage in rectal surgery: risk factors TMEAnastomosis heightProtective stomaNeoadjuvant therapyExtension and tumor-related obstructionGenderBowel preparationIntraoperative blood lossPelvic drainageCo-morbidities
3 Adjuvant therapy and rectal cancer Adjuvant Therapy for Patients with Colon and Rectum Cancer. NIH Consensus Statement 1990Is there effective adjuvant therapy for patients with rectal cancer?We recommend adjuvant therapy for stage II and III rectal cancerCombined post-operative chemotherapy and radiation therapy improves local control and survival in stage II and III rectal cancerJAMA 1990
4 Postoperative RT randomized trials GITSG GyFISHER GyDUTCH 50 GyDANISH 50 Gy SPLITMRC III 40 GyEORTC 46 GyLocal control in 2 trial (p<0.005)ToxicityNo influence on survival
5 only 50- 65% of patients completing the therapeutic plan. Post-operative combined radiotherapy and chemotherapyAdjuvant combined RT and CHT produce a benefit in termsof local control and overall survival.Compared to surgery alone RT decreases LRWith the addition of CHTdecreases local failure (-10%)increases 5-years survival (+10/15%).butincrease in acute toxicity 25 to 50%only % of patients completing the therapeutic plan.Guidelines on colorectal cancer, ASSR, Roma 2002
6 Preoperative vs postoperative RT Advantages:irradiating tissue not rendered hypoxic by previous surgeryEnhancing sphincter preservation by shrinking large distal tumors (standard RT only)Decreasing likelihood of radiation-induced injury to small bowel trapped in the pelvis by adhesionsLower acute and long-term toxicityShort Course25Gy in 5 daysRiderStockholm I e IIRCGICRFRotterdamSwedishStandard45-50 Gy in 5 weeksVASAG I e IIMSKCCMRC I e IIEORTCPUCCNorwayMRC
7 Pre-operative high-dose short-term radiotherapy The Dutch Trial1718 pts with T1-T3 operable rectal tumorsOptimal surgery alone vspre-operative radiotherapy and immediate optimal surgery.Local recurrenceSurgery alonePre-op. radiotherapy and surgeryUpper rectum3.5%1.5%Mid rectum10.0%1.0%Lower rectum5.8%The overall recurrence rate at 2 years fell from 8.4% to 2.4%.E Kapitaijn et al. N Engl J Med 2001; 345:
8 Pre-operative high-dose short-term radiotherapy The Dutch TrialPre-operative radiotherapy had no impact on survival:the distant recurrence rate was equivalent in the two arms (16% vs 15%) with 15% of patients dead in each arm by two years.E Kapitaijn et al. N Engl J Med 2001; 345:Pre-operative radiotherapy did not allow to achieve down-staging of the tumoral lesion. This treatment cannot be used to facilitate either sphincter preservation or secondary resection of initially unresectable tumors.CAM Marijen et al. J Clin Oncol 2001; 19:
9 Neo-adjuvant chemo-radiotherapy and surgery END POINTSChemotherapy is a radiation sensitizerDown-stagingLocal recurrence reductionImprovement of overall survivalIncrease in rates of sphincter-saving surgical proceduresImprovement of quality of life
11 Neoadjuvant therapy and anastomotic leakage Is neoadjuvant therapy in rectal cancera relevant risk factorfor anastomotic leakage?What is the EBM report?
12 Neoadjuvant therapy and anastomotic leakage: pathogenesis of the damage Fibrosis induced by radiotherapy is likelihood to provide hypoxic tissues and anastomosisPreoperative chemoradiotherapy for advanced rectal cancer results in a significant preoperative and postoperative immune dysfunction as indicated by depression of lymphocyte subpopulations, monocytes, granulocytes, and proinflammatory cytokine release Wichmann et al Dis Colon Rectum Jul;46(7):
13 Neoadjuvant radiotherapy morbidity randomized trials UKMRC 1b (1982)UKMRC 1a (1984)EORTC (1988)UKMRC 2 (1996)SRCT (1997)No increase in the dehiscence of colorectal anastomosis
14 Neoadjuvant therapy and anastomotic leakage Stevens KR Jr, et al. Cancer 1978 May;41(5):higher incidence of anastomotic leakage in preoperative irradiated patientsSimunovic M, Heald RJ Br J Surg 2003 (90):pre RT group ,4% anastomotic leakageno RT group ,8% anastomotic leakage
15 Neoadjuvant therapy and anastomotic leakage The Dutch trial N Engl J Med 2001; 345:1861 pts randomly assigned to short RT followed by TME or TME aloneno difference as concerns anastomotic leaksmore perineal wound infections after APR in the RT groupGerman Rectal Cancer study group. N Engl J Med 2004;351:823 pts randomly assigned to receive preop or post CT-RTno difference in anastomotic leaks between preop (11%) e postop (12%) treatment
16 Neoadjuvant therapy and anastomotic leakage Norwegian Rectal Cancer Group Colorectal Dis Jan;7(1):51-7.1958 pts undergoing rectal surgery with anterior resectionoverall rate of AL of 11,6%risk significantly higher in pts receiving preop RT (O.R. 2.2)Morino M, Parini U et al Ann Surg 237:100 pts undergoing laparoscopic anterior resectionoverall rate of AL of 17%higher incidence in pts with preop RT (21% vs 12,5%)
17 Neoadjuvant therapy and anastomotic leakage Delgado S, Lacy AM et al. Surg Endosc 2004, 18:220 pts undergoing laparoscopic assisted rectal surgery130 pts (59%) receiving preop CT-RToverall AL rate 7,3% (12/166)7/12 leaks in pts treated with preop CT-RT5/12 leaks in pts not treated before surgeryno difference between the two groups in AL rateHorie H et al. Surg Today 1999; 29(10):992-8.29 pts undergoing preop CT-RT48 pts undergoing surgery alone
18 Neoadjuvant therapy and anastomotic leakage …....I am so confused……….What is the literature EBM response about anastomotic leaks and neoadjuvant therapy of rectal cancer?
19 Istituto Nazionale dei Tumori – Napoli Colorectal Cancer Cooperative TeamSurgical Oncology “C”V. Parisi, F. Cremona, F. Ruffolo,R. Palaia, P. Delrio, D. Scala,V. Albino, M. Di Marzo, D.N. IdàRadiotherapyB. Morrica,C. Guida, V. Ravo,M. Elmo, B. PecoriMedical Oncology AG. Comella, P. ComellaR. Casaretti, A. AvallonePathologyG. BottiF. TatangeloExp.OncologyA. BudillonE. Di GennaroNuclear MedicineS. LastoriaG.M. CasciniEndoscopyA.TempestaG.B. Rossi, M. De Bellis,P. Marone, F. PetrulioRadiologyA. Siani, V. De Rosa,G. Burgazzi, A. PetrilloExp. OncologyUniv. Fed. IIS. Pepe
21 OXALIPLATIN Down-regulation of TS expression Influence over 5-FU clearanceIn preclinic studies: Sinergic action with 5-FU and Raltitrexed.Toxicity profile different from 5-FU and Raltitrexed.High response rate (~ 50%) with both 5-FU and Raltitrexed in pts with metastatic colorectal cancerImproves efficacy of 5-FU/FA in adjuvant therapy of colorectal cancerRadiation sensitizer as well as 5-FU e Raltitrexed.
22 Radiotherapy Tecnica personalizzata Generalmente, 3 campi isocentrici PA e 2 LL con cuneiLimiti Campi AP-PA: Sup. 2cm sopra il promontorio sacrale; Inf.: a 2cm dal margine inferiore della neoplasia (valutata endoscopicamente e/o radiologicamente); Lat.: 1,5cm oltre i limiti laterali della pelvi osseaCampi laterali: Sup.e Inf.come i campi AP-PA; Ant.: 2cm al davanti della neoplasia e/o linfonodi locoregionali; Post.: 2cm al di dietro della faccia anteriore del sacroFotoni X 6-20 MVDose tot.45 Gy (1.8 Gy/fr.)Istogrammi dose/volume (DVH)Fusione di immagini
23 CT-RT AccrualDiagnosis of rectal cancer below the peritoneal reflection - stage II/III (in the second group of phase I and in the whole phase II study only cT4; cT3 < 5cm anal verge; cN+; cMCR+) - age > 18 years. - ECOG performance status 2 or less - No previous chemotherapy, immunotherapy or radiotherapy granulocytes > 1500/ml; PLT > /ml; total bilirub < 1,5 mg/dl; creat < 1,5 mg/dl
24 Short term radiotherapy short-term RT (25 Gy in five days, surgery after 2 week) has been administered to patients with T3N0 CRM- disease or T2N0 CRM- with tumor at less than 5 cm from the anal verge.
25 Pretreatment staging of rectal cancer - clinical exam. - CEA - chest X-ray scan - abdomen and pelvis CT scan - abdomen and pelvis MRI - Flexible colonoscopy and biopsy - EUS - PET scanAll the procedures are ripeated before surgery
26 Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgeryBeets-Tan R.G.H., Beets G.L., Vliegen R.F.A., Kessels A.G.H., Van Boven H., De Bruine A., von Meyenfeldt M.F., Baeten C.G.M.I., van Engelshoven J.M.A.The Lancet 357; 2001:A mesorectal circumferential margin < 1mm can be accurately predicted by a 5 mm distance at MRI
27 Dynamic evaluation of response PET scan (before and during CHT-RT)DNA ploidy (before and during CHT-RT)
28 Surgery8 weeks after the end of radiochemotherapy Low or ultralow anterior resection or APR according to restaging loop ileostomy
30 The surgeon as prognostic factor Non colorectal surgeons > LR> APRSurgical training 50% reduction of LRSurgical volume recommendedAt least 4 rectal resection /monthHermanek EJSO 96Steele EJSO 96Harmon Ann Surg 99Temple DCR 99van de Velde 00Martling Lancet 00
32 OXATOM + FAFU + RT : phase II patients (n=30) ACCRUAL from 2002 July to 2004 MarchNo. Pts %GenderMFAgeaverage (range) (30 – 74)PS (ECOG)
33 Activity DOWNSIZING 30 100 Complete mesorectal excision 29 97 No.Pts %DOWNSIZINGComplete mesorectal excisionAlmost complete m. excisionRRpMRC > 1 mmpMRC < 1mmpN+ (32 average N retrieved) (1focal;4N1;1N2)TRG1/2-pN /
34 Activity TRG1 12 40 TRG2 9 30 TRG3 6 23 TRG4 2 7 TRG5 0 0 No.Patients %TRGTRGTRGTRGTRGAt a median follow up of 16 months (7-27)all the 30 pts of phase II study are alive and disease free.
35 Neoadjuvant therapy for rectal cancer: Naples NCI experience From December 2000 to May 200565 pts with LARC submitted to CT-RT23 pts with T3N0 CRM- and T2N0 CRM- below 5 cm submitted to short-term RT71 AR with TME (64 low or ultralow anastomosis, 7 Hartmann’s procedures)17 APR56 side to end anastomosis by triple stapler technique8 coloanal manual anastomosis (J pouch in 4)Pelvic suction drainage in all (removed on day 2 to 5)
36 Protective stoma59 protective stoma performed out of 64 colorectal or coloanal anastomosis5 pts refusing even a temporary stoma(being aware about the risk for anastomotic dehiscence)55 loop ileostomy with a skin bridge4 loop colostomy in elderly ptsStoma closure 1-2 months after primary surgery and after endoscopic control of anastomosis
37 Morbidity and mortality 1 death in the short RT group occurred the day after surgery for heart failure (1,1%)3 perineal wound infections out of 17 APR (17,6%)8 abdominal wound infections (9,1%)2 bowel obstructions requiring a reoperation (2,2%)4 delayed bladder catheter removal (4,4%)2 postoperative temporary anastomotic bleeding (2,2%)
38 Anastomotic leakageClinical evidence: fever, neutrophylia, perineal pain, anal discharge, pelvic infection at CT scan5/64 anastomotic leakage (7,8%)2 rectovaginal fistulas (1 radiological finding at 1st follow up, 1 in a patient reoperated on for small bowel obstruction due to ileostomy loop torsion, in which ileostomy was closed)1 pelvic abscess after Hartmann’s procedure, with dehiscence of rectal stump and anal discharge
39 Anastomotic leakage: treatment Conservative treatment by pelvic drainage and washing in 4 pts (the patient with Hartmann procedure and 3 pts with anastomotic dehiscence and protective stoma)Reoperation in 3 pts (1 rectovaginal fistula clinically evident treated by temporary colostomy, 2 temporary colostomy in pts with anastomotic leakage and no protective stoma)No treatment in the patient with rectovaginal fistula radiologically but not clinically evident
40 Crical data evaluation Gender: all the anastomotic leaks and the rectal stump dehiscence occurred in male patientsAnastomosis: all leaks occurred after mechanical side to end anastomosis by means of TA 30, EEA 31, TA 60Comorbidity: 3/8 pts were suffering from Chronical pulmonary disease; 3/8 were suffering from diabetes
41 Critical data evaluation Protective stoma: 2/5 pts (40%) without a protective stoma suffered from anastomotic leakage (3/6 if we consider also the female pt reoperated for loop ileostomy torsion with closure of the ileostomy and reoperated once more for rectovaginal fistula clinically evident)Short RT: 3/23 dehiscences (13%)CT-RT: 5/65 complications (7,7%)
42 ConclusionsOverall number of reoperations: 5 (2 for loop ileostomy torsion, 2 for anastomotic leakage in non protected pts, 1 for rectovaginal fistula after first closure of ileostomy)Average of hospital stay: 12 days for complicated pts vs 7 days for non complicated ptsTransanal or perineal drainage removed after 2 to 4 daysOutpatient care of the problem by transanal washing 2 to 3 time a week100% of spontaneous healing of anastomotic leakageDelay in stoma closure of 2 months
43 ConclusionsLiterature reports don’t show a clear likelihood of neoadjuvant therapy for anastomotic dehiscence in rectal cancer surgeryOur data show a correlation between anastomotic leakage and male gender, mechanical anastomosis, chronical co-morbiditiesShort RT more than CT-RT seems to have more likelihood with anastomotic complicationsWe strongly recommend to perform a protective stoma in all pts with LARCThe protective stoma avoids more important and life-threatening complications, allows a quick discharge of pts and a outpatient care of the problem.