Colorectal Surgery in Lynch Syndrome Patients: When and How?

Líška, Dávid; Kalady, Matthew F.

doi:10.1007/s11888-015-0262-9

Cited by 5 publications

(7 citation statements)

References 66 publications

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“…It is the most common form of inherited predisposition to colorectal cancer (CRC) and endometrial cancer (EC), with 1‐3% of both tumor types attributable to LS, although the proportion may be higher . Diagnosis of LS in people with MMR‐deficient (dMMR) CRCs can potentially alter clinical care by influencing both the extent of colorectal resection and adjuvant chemotherapy treatment decisions . Identifying dMMR CRCs, regardless of germline or somatic causes, may become more important in future if programmed cell death ligand (PD‐L1) inhibitors live up to their initial promise in the treatment of tumors displaying dMMR .…”

Section: Introductionmentioning

confidence: 99%

Current mismatch repair deficiency tumor testing practices and capabilities: A survey of Australian pathology providers

Mascarenhas

Shanley

Spurdle

et al. 2018

Asia-Pac J Clncl Oncology

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Aim & Methods An electronic survey of the Royal College of Pathologists of Australasia accredited pathology services was conducted to assess Lynch syndrome tumor screening practices and to identify barriers and capabilities to screen newly diagnosed colorectal and endometrial tumors in Australia. Results Australia lacks a national policy for universal mismatch repair‐deficient (dMMR) testing of incident colorectal and endometrial tumors cases. Routine Lynch syndrome tumor screening program for colorectal and/or endometrial tumors was applied by 95% (37/39) of laboratories. Tumor dMMR screening methods varied; MMR protein immunohistochemistry (IHC) alone was undertaken by 77% of 39 laboratories, 18% performed both IHC and microsatellite instability testing, 5% did not have the capacity to perform in‐house testing. For colorectal tumors, 47% (17/36) reported following a universal approach without age limit, 30% (11/36) tested only “red flag” cases; 6% (3/36) on clinician request only. For endometrial tumors, 37% (12/33) reported clinician request generated testing, 27% (9/33) were screening only “red flag” cases, and 12% (4/33) carried out universal screening without an age criteria. BRAF V600E mutation testing of colorectal tumors demonstrating aberrant MLH1 protein expression by IHC was the most common secondary tumor test, with 53% of laboratories performing the test; 15% of laboratories also applied the BRAF V600E test to endometrial tumors with aberrant MLH1 expression despite no evidence for its utility. Tumor testing for MLH1 promoter methylation was performed by less than 15% laboratories. Conclusion Although use of tumor screening for evidence of dMMR is widely available, protocols for its use in Australia vary widely. This national survey provides a snapshot of the current availability and practice of tumor dMMR screening and identifies the need for a uniform national testing policy.

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Section: Introductionmentioning

confidence: 99%

Current mismatch repair deficiency tumor testing practices and capabilities: A survey of Australian pathology providers

Mascarenhas

Shanley

Spurdle

et al. 2018

Asia-Pac J Clncl Oncology

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“…As mentioned before, there are no randomized controlled trials comparing different surgical procedures for young patients with LS developing CRC (19). For colonic cancer, the surgical options include segmental resection (hemicolectomy) or total abdominal colectomy with ileorectal anastomosis (TAC-IRA) (21). Currently, although some authors support the former plus yearly colonoscopy, laparoscopic TAC-IRA is the recommended procedure, although causing significantly more frequent defecation, and the risk of metachronous cancer in the rectal remnant is still high (3-12% at 10-12 years); in both cases lifelong proctoscopy is strongly advised (21).…”

Section: Curative Surgery Of Patients With Ls With Young-onset Crcmentioning

confidence: 99%

“…For colonic cancer, the surgical options include segmental resection (hemicolectomy) or total abdominal colectomy with ileorectal anastomosis (TAC-IRA) (21). Currently, although some authors support the former plus yearly colonoscopy, laparoscopic TAC-IRA is the recommended procedure, although causing significantly more frequent defecation, and the risk of metachronous cancer in the rectal remnant is still high (3-12% at 10-12 years); in both cases lifelong proctoscopy is strongly advised (21). When performing an IRA, there is no recommendation favoring one anastomotic method over another (stapled vs. handsewn, end-to-end vs. end-to-side) (21).…”

Section: Curative Surgery Of Patients With Ls With Young-onset Crcmentioning

confidence: 99%

“…Currently, although some authors support the former plus yearly colonoscopy, laparoscopic TAC-IRA is the recommended procedure, although causing significantly more frequent defecation, and the risk of metachronous cancer in the rectal remnant is still high (3-12% at 10-12 years); in both cases lifelong proctoscopy is strongly advised (21). When performing an IRA, there is no recommendation favoring one anastomotic method over another (stapled vs. handsewn, end-to-end vs. end-to-side) (21). Rectal cancer in LS is common (20-30% of patients) and represents the index cancer in 15 to 24% of cases (21).…”

Section: Curative Surgery Of Patients With Ls With Young-onset Crcmentioning

confidence: 99%

“…When performing an IRA, there is no recommendation favoring one anastomotic method over another (stapled vs. handsewn, end-to-end vs. end-to-side) (21). Rectal cancer in LS is common (20-30% of patients) and represents the index cancer in 15 to 24% of cases (21). The optimal surgical treatment for rectal cancer is controversial including segmental (proctectomy alone with colorectal anastomosis, low anterior resection with colorectal or coloanal anastomosis or abdominoperineal resection) or extended resection [total proctocolectomy with end ileostomy (TPC) or restorative proctocolectomy with ileal pouch-anal anastomosis (RPC-IPAA) with or without temporary ileostomy (TI)] (6,21).…”

Section: Curative Surgery Of Patients With Ls With Young-onset Crcmentioning

confidence: 99%

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Curative and Prophylactic Surgery of Young-onset Colorectal Cancer in Inherited Syndromes: A 15-Year Monocentric Retrospective Experience

Virgilio¹,

Balducci²,

Mercantini³

et al. 2019

Anticancer Res

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Background/Aim: Although genoproteomic and clinicopathological knowledge on Lynch syndrome (LS) and familial adenomatous polyposis (FAP) has notably increased during the past two decades and even though surgery represents the mainstay of treatment for both conditions, as of 2019, the surgical choice in terms of timing and procedure still appears controversial in the absence of definitive guidelines. Materials and Methods: Data were retrospectively analyzed of patients with colorectal cancer (CRC) surgically treated at our Institution between 1st January 2003 and 31st December 2018. Particular attention was given to patients with LS and FAP ≤45 years of age (young-onset CRC); for this category of patients, the surgical procedures performed were compared in terms of benefits and disadvantages. Results: A total of 1,878 primary CRCs were submitted to major surgery; young-onset malignancies accounted for 3.8% of all CRCs. Thirteen youngonset inherited CRCs were surgically removed from 11 patients with LS and two with FAP. Segmental colectomy and restorative proctocolectomy were the procedures most frequently performed in young patients with LS and FAP, respectively. Conclusion: In the light of our retrospective results, we highlight the need for randomized controlled trials comparing the surgical options for LS-and FAP-related CRC developing in young patients. Defining the advantages and risks of each surgical option is of the utmost importance in order to improve prognosis of such patients and establish unanimous recommendations.With over 1.8 million new cases and 881,000 deaths, in 2018 colorectal cancer (CRC) ranked third in terms of worldwide incidence and second in terms of cancer-related mortality (1). Young-onset CRC, between the ages of 20 and 49 years, accounts for 2-8% of all CRC (2). Compared to late-onset CRC, young-onset CRC shows an increasing incidence and a more aggressive behavior (2). This is probably due to a different molecular profile: 15-20% of cases, in fact, have a strong hereditary component with well-recognized molecular alterations (3). Nevertheless, just like late-onset CRC, most cases are sporadic and the pathogenic mechanisms remain to be elucidated (2-5). The two most frequent and best-known syndromes of dominantly inherited CRC are Lynch syndrome (LS) and familial adenomatous polyposis (FAP) (6). LS (previously known as hereditary non-polyposis CRC syndrome, HNPCC) is the more common condition, accounting for approximately 2-4% of all CRC cases (6). In approximately 60% of families that meet the Amsterdam-I criteria, LS is associated with an identified germline defect (classical LS, 30%) or deficient expression (Lynch-like tumors, Lynch tumor or suspected LS, 70%) in at least one of the DNA mismatch repair (MMR) anti-oncogenes such as mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) (80-90% of cases), MSH6 and postmeiotic segregation increased 2 (PMS2) (10-20%), and epithelial cell adhesion molecule (EPCAM) (3%) (7-10). The remaining 40% of families, however, do not carry any altered pr...

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Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge

et al. 2017

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Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

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Colorectal Surgery in Lynch Syndrome Patients: When and How?

Cited by 5 publications

References 66 publications

Current mismatch repair deficiency tumor testing practices and capabilities: A survey of Australian pathology providers

Current mismatch repair deficiency tumor testing practices and capabilities: A survey of Australian pathology providers

Curative and Prophylactic Surgery of Young-onset Colorectal Cancer in Inherited Syndromes: A 15-Year Monocentric Retrospective Experience

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge

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