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Dr. Sam Atallah is among the most well-known colorectal surgeons in the world, and is currently serving as the Director of Research and Clinical trials at The Digestive and Liver Center of Florida, Director of The Division of Colorectal Surgery at The EndoSurgical Center of Florida, and beginning in March, 2018, the Director of Colorectal Surgery at Oviedo Medical Center.

He moved to Orlando in 2007 after completing training at Houston's Texas Medical Center with Surgical Oncology training at MD Anderson Cancer Center where his training had earned him double-board certification in General Surgery and Colorectal Surgery. Two years to the day after completing fellowship training in colon & rectal surgery, Atallah performed the world's first TAMIS operation in Winter Park. This created a new approach to treating rectal cancers and polyps, that is now being practiced in more than 50 countries world-wide. Atallah is also a pioneer of robotic transanal surgery and was the first in the world to perform this technique. He is one of the leaders in advanced technology for rectal cancer surgery and has developed the technique of stereotactic navigation for transanal total mesorectal excision (taTME) -- an important step forward in the evolution of computer-assisted surgery. Complex treatment of rectal cancer and surgical management of this disease through the new techniques of TAMIS and taTME represent Atallah's principle interests in colorectal surgery; and he is currently in the works of producing a textbook on these topics on schedule to be published in 2019 by Springer Nature. He is also actively involved in the design and assessment of feasibility of next generation robotic systems that will be smaller, sleeker, and able to work in places and spaces never before imagined.

Other areas of Dr. Atallah's research interest include understanding the tumor biology of colon cancer at the molecular level. He is the principle investigator of a major study looking at biologic tumor markers that can lead to a better understanding of cancer tumors. This study is in collaboration with Sanford & Burnham Labs in La Jolla, California.

Atallah has become internationally recognized for his pioneering work in rectal cancer surgery and has trained hundreds of surgeons nationally and internationally. He has also performed live surgery and lectured globally -- traveling to six continents in 2017 alone. He has given lectures at the European Association of Endoscopic Surgeons' 14th World Congress in Paris, France; The Natural Orifice Surgery Consortium for Assessment and Research in Chicago; The Society of Robotic Surgeons held in both Orlando and Miami; The American College of Surgeons in Washington, DC., The Peking University Conference on Advanced Rectal Cancer Surgery, Beijing, China, and several other international society meetings in worldwide destinations -- including the 30th annual Japanese Society of Endoscopic Surgeons in Kyoto (2017); The Colorectal Surgical Society of Australia and New Zealand in Sydney and a taTME Workshop held in Brisbane, Australia; The 90th Annual Surgical Congress held in Pucon, Chile; The Rectal Cancer Summit held in Mexico City, Mexico; IRCAD Colorectal Masters Course held in Strausburg, France.

In this month's In Other Words forum, Dr. Atallah discusses the inherited nature of some colorectal cancer.

In Other Words...with Sam Atallah, MD

Inherited Colorectal Cancer

Most colon and rectal cancer is not inherited, but rather occurs sporadically. Although 80 percent of all colon cancer is sporadic, the remaining 20 percent is considered inheritable colon and rectal cancer, and there are two main categories of this. The first is called Familial Adenomatous Polyposis Syndrome or FAP, the second is termed Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC). Both FAP and HNPCC are inherited via an autosomal dominant pathway, so that offspring have a 50 percent chance of developing the disease if a parent is afflicted. In FAP, the gene responsible for the disease is the APC gene, and mutations in this gene result in the phenotypic expression of disease, usually during early adolescence. A gene test for the APC mutation can be performed in early childhood, however, the demonstration of hundreds of adenomatous polyps carpeting the lining of the colon and rectum is pathognomonic for FAP making gene testing unnecessary.

Once the diagnosis is made, surgery is recommended which consists of removal of the entire colon and rectum will ileal pouch-anal reconstruction, thereby avoiding a permanent stoma. In 2018, this is most often performed laparoscopically or robotically in a one or two stage operation. Timing of surgery is important as many young adults are still in high school or college when the surgery is performed for FAP, and so typically a surgeon and the patient will wait for a school break, such as summer or spring break to schedule the operation between semesters. Patients with phenotypic expression of FAP who do not receive surgical therapy will uniformly develop invasive colorectal carcinoma by age 40. This is true for classical FAP, however not for its genetic variants - AFAP and MUTYH/ MYH. These are similar to FAP but the phenotype and genetic mode of inheritance differs. In attenuated FAP (AFAP), the gene defect is inherited in an autosomal dominant fashion, however the phenotypic expressivity is diminished. Hence, in patients with AFAP, there are much fewer polyps throughout the colon and there is typically rectal sparing. Surgical intervention is often delayed, and in some instances a subtotal colectomy rather than a total proctocolectomy may be a better option, as such a procedure is less likely to result in urogenital and bowel dysfunction post-operatively. With MYH and MUTYH mutation, the expression is more analogous to AFAP. However, in contradistinction, the inheritance pattern is autosomal recessive, and this is often described as 'autosomal recessive form of FAP.'

HNPCC does not manifest until adulthood, but typically at a younger age than patients with sporadic colorectal cancer. Thus, patients with HNPCC develop this malignancy classically in their late 30s and early 40s. Because this is before the screening age of 50m the so-called Amsterdam criteria or 3-2-1 rule can be helpful in determining who may be at high risk for HNPCC. This rule is as follows: 3-persons with colorectal cancer; 2-consequtive generations; 1-relative with colorectal cancer <50. Persons who meet all three criteria have a significant probability of having HNPCC.

HNPCC cancers are more likely to be right-sided and more likely to be associated with other cancers, the most important of which is endometrial carcinoma. Women with HNPCC have an 80 percent lifetime risk of developing colorectal carcinoma; they also have an 80 percent lifetime risk of developing endometrial cancer. Thus, genetically proven HNPCC females should be counseled about hysterectomy once they have completed their family to minimize cancer risk later in life.

HNPCC occurs secondary to mutations in the DNA mismatch repair (MMR) genes, of which there are several. Thus, cell replication may contain errors that lead to dysplasia and subsequent carcinoma formation. HNPCC is not the only disease process to result from a defect in DNA repair mechanisms. The best example of this is probably a disease called xeroderma pigmentosum. Here, the mechanism of cells to recover from UV light damage is not functional, leading to multiple skin changes and dermal cancers. This is often so severe of a condition, that patients with xeroderma pigmentosum cannot be exposed to any sunlight at all.

The surgical approach to patients with HNPCC is typically individualized based on comorbid conditions, age, and other factors. In some instances, a subtotal colectomy is recommended, especially in good surgical risk patients, or in patients who simply are not willing to undergo aggressive surveillance post-operatively. However, in patients who may be too infirm to undergo a radical, subtotal colectomy, then a more limited resection is often performed instead. As stated previously, radical hysterectomy may also be recommended in females who exhibit MMR mutation.

Although HNPCC and FAP both result in colorectal cancer, they do so via radically different genetic pathways. Interestingly, both can result in similar combinations of malignancies via yet to be fully understood mechanisms. For example, patients with HNPCC and FAP both can develop brain tumors. The combination of a neurologic malignancy and inherited colorectal carcinoma (either HNPCC or FAP) is termed Turcot Syndrome. Oddly with this syndrome, patients with HNPCC are more likely to develop glioblastoma multiforme, while FAP patients would be more likely to develop a different type of brain tumor, classically medulloblastoma. This is an important example of genetic heterogeneity and demonstrates that we still do not understand all of the complexities of inherited disease.