Search

Introduction Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) wingless-related integration site (WNT) subtype, the course of which has only recently been described. Methods We retrieved all patients with documented germline APC mutations and a diagnosis of MBL to examine their outcome, late effects of treatment, and further oncological events. Results Between 2007 and 2016, we treated six patients, all with a pathogenic APC variant mutation and all with MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine, and vincristine for a maximum of eight courses. Five of six diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Methylation profile score (in two cases) and copy number variation analysis (chromosome 6 deletion in two cases) performed on four of six retrieved samples confirmed WNT molecular subgroup. Four out of six patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other two cases. Four patients developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. Discussion Our data confirm a good prognosis for patients with MBL associated with FAP. Patients' secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

Background APC gene pathogenic variants are characterized by a lifetime risk of nearly 100% to develop a colorectal carcinoma. International guidelines suggest a prophylactic surgery in the second decade. Methods A descriptive analysis was performed evaluating a surgical series of adolescent patients with familial adenomatous polyposis (FAP) enrolled in the prospectively maintained hereditary polyposis registry. Results Thirty-eight adolescent patients (median age 16 years; range, 7-19) underwent laparoscopic prophylactic surgery. APC gene pathogenic variants were detected in all patients, and six patients were proband. No patients were converted to open surgery. Median postoperative stay was five days (4-16). Early postoperative complications were one dural puncture and one anastomotic leakage. Regarding late complications, we observed one patient having small bowel obstruction 56 months after surgery. Pathological reports showed one patient with pTis adenocarcinoma in two separate sites; 33 patients with low-grade dysplasia, four with high-grade dysplasia. One patient developed a desmoid tumor 37 months after surgery. After a median follow-up of 40.5 months, no patients died or had a second abdominal surgery because of cancer in rectal stump. Conclusions Rectal sparing surgery was the first choice in the major respect of patients' quality of life. Laparoscopic prophylactic surgery for FAP is well accepted from adolescents. It represents a safe option due to the low incidence of post-surgical desmoids and quick postoperative recovery.

Background Prophylactic surgery is still considered the standard treatment for patients with Familial Adenomatous Polyposis (FAP). Laparoscopic (Lap) surgery has been introduced as an alternative approach. The aim was to evaluate the feasibility and short- to long-term outcomes after prophylactic FAP surgery in adolescent. Procedures A retrospective review of a database of adolescent patients with FAP identified through the Hereditary Colorectal Tumor Registry in a single Institution between 2005 and 2011. Patients underwent Lap total colectomy (TC) with ileo-rectal anastomosis (IRA) or proctocolectomy (PC) with ileal-pouch anal anastomosis (IPAA). The main outcomes were: Hospital stay, postoperative complications, desmoid tumor rates, tumor recurrence, long-term complications. Results Sixteen consecutive patients with median age 16 (range 13–19) and median BMI 22 (17–29) underwent surgery. [correction made here after initial online publication]. Of them 14 patients had LAP TC with IRA and 2 had PC with IPAA. Operative time (median, range) was TC/IRA 270 (210–330) minutes; PC/IPAA 370 (360–380) minutes. Length of extraction site was cm (median, range) 6(5–8). Lymph Node harvest (median, range) 81 (32–139). Postoperative stay days (median, range) were 6 (4–24). Five patients (31.2%) showed dysplasia on the pathological report and 3 of them showed severe dysplasia. Median follow-up time (FU) was 39 months, range (10–82). The anastomotic leak rate for 30 days was 2 (12.5%). Pouch failure was 0. Post-surgical desmoid tumors rate was 1 (6.2%) and there was no tumor recurrence. Anastomotic stricture, SBO and mortality were zero. Conclusions Lap approach is feasible and shows acceptable postoperative outcomes. Lap surgery can be an appealing alternative for prophylactic surgery in adolescent FAP patients. Pediatr Blood Cancer 2012; 59: 1223–1228. © 2012 Wiley Periodicals, Inc.