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Page 10 of 13 Ambe et al. Mini-invasive Surg 2018;2:37 I http://dx.doi.org/10.20517/2574-1225.2018.45

must be considered in each case. Thus an individualized decision-making and a personalized strategy with
the patient’s active involvement in terms of shared decision-making should represent a major aspect of
management.

Basically, the principles of oncologic surgery should be respected in call cases with CRC independent of
mutational status. The need for extended surgery beyond segmental colectomy for CRC can be made as a
“tailored approach” in selected cases based on mutational status, that is gene and gender. This is a moving
target and the challenge lies in the translational aspect of patient management. As an example: LS still may
be considered by most as a syndrome with a high risk for colorectal and other GI malignancies. However,
depending on the gene, endometrial cancer may be the sentinel cancer and not CRC (MSH6). Or, PMS2 is
a very low penetrant gene and mutations may not predispose to a substantial amount of cancers. Therefore
annual invasive screening or prophylactic surgery may not be warranted. MLH1- and MSH2-LS patients,
however, have a very high risk for metachronous CRC cancers, despite even yearly colonoscopies. There-
fore, patients might opt to have more extended surgery at the time of their primary surgery. Or, especially
for MSH6 mutation carriers, a simultaneous hysterectomy after completion of the family planning might
be the preferred option. In order to address these issues it is becoming pivotal to generate genetic tests and
a reliable risk assessment as timely as possible following the diagnosis of CRC and prior to cancer surgery.

Prophylactic colorectal resection (restorative proctocolectomy) with or without IPAA is currrently reserved
for hereditary syndroms with 100% penetrance for the development of CRC including FAP, aFAP and
MAP. The role of prophylactic colorectal surgery for hereditary syndromes without a 100% penetrance is
still to be defined and must include patient preference.

Patients with hereditary CRC are usually younger than those with sporadic CRC. Thus quality of life fol-
lowing surgery is of even greater importance to these patients. Therefore attention to technical details with
respect to surgery like minimizing surgical trauma and preservation of nerve function during pelvic dis-
section is a major aspect of surgical management. Furthermore, the postoperative follow-up should be in
accordance with syndrome-specific guidelines.

The role of effective chemoprevention for example with aspirin may influence decision-making regarding
prophylactic surgery and must be assessed prospectively. In the light of evolving evidence, it is mandatory
to involve patients in decision-making with the most recent knowledge available.

In conclusion, with increasing understanding of tumor genetics, the role of gene and gender will increasingly
play a role in the management of patients with hereditary predispostion for CRC. A good understanding of
the predisposing genetic mutations with regard to mutational and clinical heterogeneity is the basis for an op-
timized management. Prophylactic surgery is reserved for syndromes with a 100% penetrance. The principles
of oncologic resection should be respected as in sporadic CRC. The quality of life following surgical manage-
ment should be the focus of counselling and decision-making. Postoperative lifelong follow-up is an impor-
tant aspect of surgical management and must be discussed with patients at the time of their first surgery. The
potential role of chemoprevention in individuals with hereditary predisposition to CRC must be prospectively
studied and evaluated for less invasive options than prophylactic or prophylactically extended surgeries. Last
but not least: after identification of an index patient with a hereditary mutation, genetic counselling and the
option of predictive testing must be the focus of the surgeon.

DECLARATIONS
Authors’ contributions
Design, literature research and review, critically reviewed the manuscript, final approval: Ambe PC,
Möslein G
Drafted the manuscript: Ambe PC