Giorgio Maria Paolo Graziano1 Marco Cavallaro2 and Antonino Graziano3*
1University of Catania, Medical School, Italy 2Radiology unit ASP Ragusa, Italy 3University of Catania, Azienda Policlinico Dpt Sciences Surgery and advanced technologies, “G Ingrassia”, via S Sofia 86, Catania, Italy
Received: 16 November, 2015; Accepted: 09 January, 2016; Published: 19 January, 2016
Prof. Graziano Antonino, via s Sofia n 87 Catania, cap 95125 Sicilia Italy, University of Catania, Italy, Tel: 0953782880; E-mail:
Paolo Graziano GM, Cavallaro M, Graziano A (2016) The Familial Adenomatous Polyposis. A Difficult Problem, Between Prevention and Treatment. J Surg Surgical Res 2(1): 005-009.10.17352/2455-2968.000021
© 2015 Paolo Graziano GM et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hereditary familial adenomatous polyposis treatment
Introduction: The familial adenomatous polyposis of the colon (FAP) is a rare hereditary disease, transmitted as an autosomal dominant trait due to the mutation of the APC gene. The purpose of the study is to assess, even according to the data of our experience, the possibility of clinical application of the results of the new genetic research, linking the problem to prevention and/or treatment. Some operative remarks conclude the study.
Materials and methods: We observed (II clinical surgery Garibaldi Hospital in Catania, III Surgery, and Digestive Surgery Unit of the University of Catania) 16 patients on all. In Group I (FAP +) were observed 12 patients with FAP (5 male and 7 female). In group II (FAP-) 4 cases (male). All patients were part of No. 6 families. The diagnostic test and colonoscopy were diagnostics. 8 patients (and all their relatives), performed the genetic typing.
Results: The ileo-anal anastomosis with reservoir (IPAA), was, time to time, the operation chosen especially in cases of degeneration in the rectal tract. The ileo-rectal anastomosis (IRA) has been used mostly in the prevention phase of degeneration. The surgical treatment involved 12 patients (Group I). 7 of the cases treated, were subjected to a procedure proctocolectomy and reconstruction by J-pouch ileo-anal anastomosis or latero-terminal ileo-anal anastomosis, with temporary protective ileostomy. One patient underwent definitive ileostomy after proctocolectomy because of cancer involving the ano-pettinea line. The other 4 were subjected to IRA (3), with ileo-rectal anastomosis to 8-10 cm. A patient has developed a pelvic abscess, which required reoperation the definitive iliac anus. Mortality was absent. In the remaining 4 cases of Group II, the genetic test proposed reveal not mutations of the APC gene, so the presumed late degeneration of the polyp did opt for watchful waiting
Discussion: The therapeutic approach in FAP is particularly complex and challenging, because it includes the prophylaxis and treatment of the adenomas, for colorectal cancer and ECD (extra colonic diseases) dangerous according to their severity and location. In practice, the FAP has problems similar to the treatment of recto-ulcerative colitis (UC). The indication to anoproctocolectomia with definitive ileostomy can be offered only to those patients (1 case in our series) in which there is an invasive rectal cancer too close or involving the anal rhyme, with diffuse polyposis of the colon. In other cases (2 in our experience one in the rectum, and one in the recto-sigma junction) of cancerous evolution, and when the rectum is intensely involved from polyps (5 of our patients) is preferable to the lPAA and ileo pouch anal anastomosis in J, . In all cases where it is considered possible (4 cases came under our observation) the endoscopic procedure of the rectum and there is no cancer in situ, you can proceed to a total colectomy with ileo-rectum anastomosis about 6 cm or below to achieve good continence. It is advisable to carry out an T-L ileo-rectal anastomosisor with aJ pouch in cases where it is deemed necessary to remove of the proximal rectum with more intensely polyposis. A number of evacuations acceptable (up to 3-5 per day) are the functional results of these predictable surgical options. Dehiscence with sepsis of the small pelvis may complicate the postoperative evolution of IPAA, which can be controlled with a protective ileostomy. He IRA involves especially the risk of degeneration of the residual or recurrent rectal polyps, while the IPAA generally results in imperfect functional results, risk of dehiscence and septic complications
Conclusion: The FAP is a rare but potentially lethal disease (responsible for about 1% of all colic cancers, HPCC) for the patient, in which a genetic mutation is transmitted in 50% of the descendants. The introduction into clinical practice of test for molecular diagnosis is the innovation technology, which allows a more accurate assessment of the disease and the best indications of the time and type of treatment and surveillance program. , the prospects of Genetics for further more direct approaches, present choices ethically more complex of prevention and treatment.
The familial adenomatous polyposis of the colon (FAP) * is a rare hereditary disease, transmitted as an autosomic dominant trait due to the mutation of the APC gene **, characterized by the appearance of a high number of adenomatous polyps in the colon mucosa (> 100-1000 and over) In 1925 Lockhart-Mummery focused his attention on a particular characteristic of this disease and on his condition of almost mandatory precancerosis that in the short space of 10-15 years after the onset of polyps develop with certainty a cancer (BC Morson, T . Kozuka) [1-4]. Subsequent studies (C. Dukes, HJR Bussey) , have quantified the risk of degeneration in relation to age, size of the polyps, histological type, degree of dysplasia. In view of the malignant potential of the disease, surgical therapy has always been addressed to a principle of radical demolition, even at the stage of simple polyposis, and even with the risk of unsatisfactory functional results. However, since a considerable number of patients is subjected to interventions at an early age with a high need for productive and sexual activity and with a long lease of life remaining, the problems of continence and thus the quality of life must be held in high esteem and perhaps address towards solutions of compromise between radicalism and continence, at least in the phase of simple dysplasia. The purpose of the study is to assess, also based on the results of our experience, the impact that the new diagnostic possibilities offered by genetics can have on the screen, on the monitoring and treatment of the disease. Much over, between prevention and treatment to driving operative remarks of proceeding [6-8]. The role of heredity in colorectal carcinoma (RCC) is evident in the polyposis syndromes HPCC (FAP, with variants of Gardner and Turcot, rich in ECD, the AFAP and MAP) and especially in syndromes HNPCC (S. Lynch), ie the variants of polyposis or non-polyposis hereditary colorectal cancer. The FAP is characterized by the onset, early or late in ‘childhood or adolescence, of hundreds or thousands of polyps (still more than 100) on which sooner or later develops a malignancy [8-10] Inheritance is autosomal dominant and the prevalence is 1/8000 individuals. The HPCC carcinoma represents 1% of all colorectal carcinomas, while the HNPCC about 6-8%. Although colectomy and especially procto-colectomy can considerably reduce up to zero the risk of CCR, the disease requires frequent endoscopic surveillance, genetic typing and, in some variants, is associated with other diseases such as tumors and dermoid cysts (itself more therapeutic problems for the site and size that can reach), osteomas, pigmented hypertrophy of the retina, thyroid tumors, carcinomas of the duodenum and small intestine, hepatoblastomas and tumors of the CNS. The FAP is produced by mutations in the APC gene, in the locus 5q 21-22, 8538 bp long, consisting of 16 exons, coding for a protein of the type of beta catenin involved in the preservation of the contacts between epithelial cells and in the regulating their proliferation, through action on the cell cycle and apoptosis. Since 1994 there is a genetic test that has modified the guidelines allowing the disease to exclude from follow-up family members who do not carry congenital alteration, although it is seen that may come into play other polyposis mutations. In FAP are described over 300 mutations of the gene. Those of the first four exons are correlated with the phenotype AFAP. The hypertrophic chorio-retinitis is characteristic of the mutations of exons 10-15. Mutations between codons 1400 and 1600 are associated with extra-colonic localizations. Most interesting are alterations of codons 1250 and 1464, associated with increased risk for cancer of the rectal stump and alterations of codon 1309, related with the early onset of the disease (C. Dodaro: topical theme of family colonic polyposis, 2010). The AFAP is a condition in which patients are carriers of a few polyps, less than 100. The disease is caused by mutations at the 3’ or 5’ end of the APC gene or of certain areas of exon 9. The disease is defined as AFAP (attenuated FAP). In these cases, the CRC may arise later in life, are less common extra-intestinal lesions and the disease can appear sporadically. Have been described patients with a clinical picture similar to the above, even in the absence of a multi-generational history of polyposis and in the absence of alterations of the APC gene. It should be noted that mutations may occur in somatic cells and are therefore not to be heritable, but in the specific case there are important germline mutations. In these patients, typically 30 - 60 years old, with multiple polyps but no APC alterations can be detected a change in the gene MutYH (MYH) and the disease is called MAP. The gene in question , a BER (base excision repair), corrects the DNA damage caused by reactive oxygen species (ROS: super oxide ions, hydroxyl ions, etc.), chemical agents or ionizing radiation. From 23 to 30% of patients with more than 10 but less than 100 polyps are carriers of abiallelic mutation of MYH gene, which then is recessive, in the absence of inherited mutations of the APC gene. According to some, up to 2.8% of early CCR, could be ascribed to biallelic mutations (Y175C and G382D) of MYH gene, which means not only that these mutants may have the same clinical stigmata of FAP, but also reach out to colorectal cancer in the same if not greater extent. Genetic testing, to day available, should be reserved: a) to patients with clinical picture of FAP or AFAP when it’s not demonstrated PCA gene alteration; b) to those cases of CCR with a pattern of recessive inheritance or multiple adenomas; c) to the children of known carriers of MYH mutations, d) to partners of known carriers of MYH mutations (may themselves be carriers), with the risk, if monoallelic, to transmit the disease in 50% of the offspring. According to Jenkins (2006), the cumulative risk for cancer at age of 70 for MYH mutation carriers is 8% (4-19%) if monoallelic and 80% (35-100%) if biallelic. Therefore they should be treated the same way as the mutant APC, with colonoscopies and colectomy when indicated. However, being the later the age of onset of polyps and the risk of cancerous, endoscopic surveillance can begin at a later age, after 25 years. In patients with heredo-familiar colorectal cancer, but adverse for changes in MMR (HNPCC), shall still be looking for the alterations of genes APC and MYH, which in any case should be investigated in patients with more than one adenoma of the colon. Endoscopic and genetic screening is also recommended in relatives of first degree of biallelic carriers, particularly in the brothers who have a 25% risk of having mutations. The children biallelic mutants are still carriers of at least one mutation, if the partner is not a carrier. It is therefore reasonable to perform a base colonoscopy in these individuals and, if polyps are noticed, there will establish a surveillance program. The cornerstone of the treatment of colorectal polyps are celecoxib (seems that, for some authors, to reduce the number and size of polyps); endoscopic polypectomy, when possible, for AFAP and MAP is the first approach; the surgical option (colectomy and proctocolectomy), certainly in FAP characterized by a myriad of polyps, and in the already developed HPCC [7,8].
*Attenuated Familial Polyposis. **”Adenomatous Polyposis Coli” mutation
Materials and Methods
The case study refers to 16 patients observed, of which 12 surgically treated at the Surgery Clinic II from 1986 to1994, at the III Surgery unit from 1996 to 2004 and from 1996 to 2013 at the digestive system surgery unit of University of Catania, Azienda Policlinico. In Group I (FAP positive) have been cataloged 12 FAP patients * of which N 7 women en 5 males. In group II were observed in 4 cases of male (100%), suffering from multiple polyps of the colon, but negative for gene mutations FAP. All patients were part of No. 6 families in which most of the children had the FAP *. Adenomatous polyposis interested the entire colon and rectum in number> 100 cases FAP; multiple polyps in the small number were found in the other cases, FAP negative (Figures 1-3).
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