The extent of Surgery in Lynch Syndrome. Gabriela Möslein

Transcription

1 The extent of Surgery in Lynch Syndrome Gabriela Möslein

2 5 % High rate of syn- and metachronous cancers Indexpersons underidentified Preoperative identification? Prophylactic surgery? Colon Rectum Endometrium Ovaries 2

3 Lifetime Cancer Risk With identified MMR mutation colorectum* 28-75% in males 24-52% in females With identified MMR mutation endometrium* 16 to 71% Annually approx. 30,000 new HNPCC - Lynch Syndrome) colorectal cancers (CRC) diagnosed in the world *Vasen HF, Moslein G, Alonso A, et al. (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44(6): *Bonadona V, Bonaiti B, Olschwang S, et al. (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305(22):

4 Surgery for HNPCC Lynch Syndrome Preventive or curative or extended Prophylactic palliative prophylactic 4

5 Surgical options in colon cancer Segmental resection Extended resection Right hemicolectomy Left hemicolectomy Sigmoid resection Subtotal Colectomy One anastomosis in each of the procedures Comparable surgical and perioperative risk overall complication-free rate 75.4 versus %, n.s. (You et al. Dis Colon Rectum 2008;51: ) 5

6 afap? MAP? Lynch Syndrom? Hyperplastic Polyposis? Synd. X? Others? Colon cancer 2 Adenomas Age 46 Sporadic Lynch S.? FAP 6

7 Ams + MSI + or IH + Lynch-S + Colorectal cancer Surgery Rationale for extended surgery? Efficacy of surveillance and polypectomies Rate of metachronous CRC despite surveillance? QOL? 7

8 Metachronous Colorectal Cancer Risk Estimated colorectal cancer risk at 60 y. despite surveillance: 22% (women) - 35% (men) (Mecklin et al. 2007;133: ) 10-year metachronous cancer risk: 16% after hemicolectomy versus 4% after subtotal colectomy (de Vos tot Nederveen Cappel et al. Gut 2003;52: ) 22% metachronous cancer after segmental resection versus 0% in extended surgery (Parry et al. Gut 2010; epub ahead of print) 20-year metachronous cancer risk: 23.7% after operation despite regular (yearly) colonoscopic surveillance (Engel et al. Clin Gastroenterol Hepatol. 2010;8:174-82) Significant shorter time to metachronous cancer after segmental resection (Natarajan et al. Dis Colon Rectum. 2010;53:77-82) 8

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10 Metachronous Colorectal Cancer Risk Estimated colorectal cancer risk at 60 y. despite surveillance: 22% (women) - 35% (men) (Mecklin et al. 2007;133: ) 10-year metachronous cancer risk: 16% after hemicolectomy versus 4% after subtotal colectomy (de Vos tot Nederveen Cappel et al. Gut 2003;52: ) 22% metachronous cancer after segmental resection versus 0% in extended surgery (Parry et al. Gut 2010; epub ahead of print) 20-year metachronous cancer risk: 23.7% after operation despite regular (yearly) colonoscopic surveillance (Engel et al. Clin Gastroenterol Hepatol. 2010;8:174-82) Significant shorter time to metachronous cancer after segmental resection (Natarajan et al. Dis Colon Rectum. 2010;53:77-82) 10

11 de Vos tot Nederveen, Cappel WH, Nagengast FM, Griffoen G Dis Colon Rectum 2002 Dec;45(12): The 10-year cumulative risk of developing colorectal cancer was 10.5 (95 percent confidence interval, ) percent in proven mutation carriers, 15.7 (95 percent confidence interval, ) percent after partial colectomy (n=110), and 3.4 percent after subtotal colectomy (n=29). 11

12 Metachronous Colorectal Cancer Risk Estimated colorectal cancer risk at 60 y. despite surveillance: 22% (women) - 35% (men) (Mecklin et al. 2007;133: ) 10-year metachronous cancer risk: 16% after hemicolectomy versus 4% after subtotal colectomy (de Vos tot Nederveen Cappel et al. Gut 2003;52: ) 22% metachronous cancer after segmental resection versus 0% in extended surgery (Parry et al. Gut 2010; epub ahead of print) 20-year metachronous cancer risk: 23.7% after operation despite regular (yearly) colonoscopic surveillance (Engel et al. Clin Gastroenterol Hepatol. 2010;8:174-82) Significant shorter time to metachronous cancer after segmental resection (Natarajan et al. Dis Colon Rectum. 2010;53:77-82) 12

13 Metachronous cancers in Lynch Syndrom S. Parry et al. Methods 13

14 Metachronous cancers in Lynch Syndrom S. Parry et al. MMR mutation carriers : incidence metachronous CRC after segmental versus extended resection 14

15 Metachronous cancers in Lynch Syndrom S. Parry et al. Conclusions 15

16 Metachronous Colorectal Cancer Risk Estimated colorectal cancer risk at 60 y. despite surveillance: 22% (women) - 35% (men) (Mecklin et al. 2007;133: ) 10-year metachronous cancer risk: 16% after hemicolectomy versus 4% after subtotal colectomy (de Vos tot Nederveen Cappel et al. Gut 2003;52: ) 22% metachronous cancer after segmental resection versus 0% in extended surgery (Parry et al. Gut 2010; epub ahead of print) 20-year metachronous cancer risk: 23.7% after operation despite regular (yearly) colonoscopic surveillance (Engel et al. Clin Gastroenterol Hepatol. 2010;8:174-82) Significant shorter time to metachronous cancer after segmental resection (Natarajan et al. Dis Colon Rectum. 2010;53:77-82) 16

17 German Consortium: yearly colonoscopy Prospektiv erhobene Daten 1126 Personen und 3474 Koloskopien 81% of all colonoscopies were performed within 15 months of the kolorektale 43 follow-up Karzinome colonoscopies bei 90 Patienten revealing a CRC had been preceded by a normal surveillance colonoscopy within the recommended interval of 12 months Clin Gastroenterol Hepatol Oct 14. [Epub ahead of print] 17

18 Effect of colonoscopy screening, German Consortium CRC-Incidence depending on risk group MSS: low CRC risk MUT+ und MSI have equal CRC risk Engel C, et al; Clin Gastroenterol Hepatol Feb;8(2):

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20 Rectal cancer Two small studies reported that the risk of metachronous cancer after proctectomy in Lynch syndrome patients was 15 and 18% respectively. [17, 20] In 33 patients reported from Cleveland Clinic, at a median follow up of months, the incidence of high-risk adenomas or metachronous cancers after proctectomy was 51%. [20] In the report by Lee et al, 3 of 18 patients developed metachronous colon cancers at a median of 203 months post proctectomy. [17] In another report from Germany and the Mayo Clinic 6 of 11 patients developed metachronous colon cancers at a median of 88 months after proctectomy. [21] 20

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22 What about extended colorectal surgery? Generally prefered worldwide (but not in Germany) No prospective randomized studies Mathematical models demonstrate survival benefit in young patients Increase in bowel movements with IRA and ileoanal Pouch Less invasive screening Difference between IRA and ISA? What about QOL? When are patients identified? 22

23 Significance of knowing MSI- status preoperatively (!) Option of risk reduction via extended primary colorectal surgery Also focus preoperatively on : endometrium, adnexes 23

24 Screening Recommendations Yearly surveillance Physical examination (dermatology?) Colonoscopy beginning age 25 Gyn examination beginning age 20 Endometrial biopsy! Abdominal sonography starting age 25 Gastroduodenoscopy starting age 35 24

25 Detection of MMR deficiency MLH1/PMS2 MSH2 MSH6 Sequence QMPSF/MLPA Splicing Assay 25

26 Henry Lynch 1977 Should a direct-line relative of a kindred manifesting the Cancer Family Syndrome develop carcinoma of the colon, we believe that it would be advisable to proceed with a total colectomy rather than hemicolectomy because of the enormous genetic risk of additional primary cancers occuring in any segment of the colon not removed. Lynch et al. Ann Surg 1977;185:

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34 Important wrap-up issues Probably extended surgery is better for colon cancer IRA versus ISA Probably prophylactic hysterectomy at the time of a colon cancer is reasonable Age-depending probably prophylactic salpingooophorectomy is beneficial Maybe in selected young patients with rectal cancer proctocolectomy and ilaoanal pouch is an option Education and awareness is a real issue! Aspirin might change the whole story 34