Advanced colon cancer before the age of 20 years : A case for extension of the current colonoscopy surveillance guidelines in hereditary nonpolyposis colorectal cancer syndrome

1Division of Gastroenterology, Department of Medicine; 2Department of Radiology, University of British Columbia, Vancouver, British Columbia Correspondence: Dr Eric M Yoshida, Vancouver General Hospital, Division of Gastroenterology, 100-2647 Willow Street, Vancouver, British Columbia V5Z 3P1. Telephone 604-875-5371, fax 604-875-5447, e-mail eyoshida@interchange.ubc.ca Received for publication January 2, 2004. Accepted February 10, 2004 VK Wong, EM Yoshida, AG Ryan, SGF Ho, B Salh. Advanced colon cancer before the age of 20 years: A case for extension of the current colonoscopy surveillance guidelines in hereditary nonpolyposis colorectal cancer syndrome. Can J Gastroenterol 2004;18(5):319-320.

H ereditary nonpolyposis colorectal cancer (HNPCC) cur- rently accounts for 2% to 6% of all colorectal adenocarcinomas.The HNPCC syndrome has classically been divided into two subgroups based on clinical presentation: Lynch I, which has no history of associated cancers, and Lynch II, which can present along with other malignancies, including cancer of the stomach, uterus, urinary tract, small bowel and bile ducts.In families with HNPCC, the mean age of diagnosis is 48 years, with some patients presenting in their twenties.Seventy per cent of the lesions are proximal to the splenic flexure.
Previous recommendations for HNPCC-affected kindreds was to begin screening family members between 20 and 30 years of age (1,2).More recently, the recommendations have been revised such that colonoscopy should occur between 20 and 25 years of age.In the present article, we report a case of colon cancer in a 19-year-old man whose diagnosis of colon cancer fulfilled the criteria for HNPCC.

CASE PRESENTATION
A 19-year-old Japanese man presented to the emergency department with a complaint of transient self-limited left lower quadrant discomfort, a brief episode of fever and an isolated episode of passing a small amount of blood per rectum on one occasion.There was no previous history of passing blood per rectum and he was otherwise well, except for a 1.8 kg weight loss.His hematological parameters were unremarkable; specifically, his hemoglobin was 143 g/L (normal range 135 g/L to 175 g/L) with a normal mean cell volume.A flexible sigmoidoscopy performed 20 days after his emergency department presentation was unremarkable and he had not had a second episode of rectal bleeding in the intervening time period.His previous symptoms had resolved completely.The only remarkable feature about this patient was that his mother had undergone a right hemicolectomy 12 years previously at the age of 34 years for colon cancer in Japan.She had undergone annual surveillance barium enemas in Japan but had failed to pursue further follow-up after her immigration to Canada.The maternal grandfather had died at the age of 50 years, reportedly of metastatic colon cancer, and a maternal aunt reportedly had colonic polyps, but not cancer, at the age of 54 years.There was no family history of extraintestinal malignancy.Following the patient's flexible sigmoidoscopy, it was recommended he undergo colonoscopy at age 25 years or sooner if rectal bleeding recurred.
Three months later, the patient was investigated by his family physician for unexplained fever and a possible pelvic mass.A computerized tomography scan of the abdomen and pelvis, performed two days before his 20th birthday, revealed an 11.9 cm pelvic mass adjacent to the cecum.The patient underwent colonoscopy three days after his 20th birthday.A large polypoid mass was found in the ascending colon that, on histological examination of the biopsied tissue, was confirmed to be a moderately differentiated adenocarcinoma.
At laparotomy there was an obvious large tumour of the cecum extending halfway up the ascending colon and involving the terminal ileum and urinary bladder.There was mild evidence of ascites but there was no surface peritoneal tumour growth, nor were there any palpable liver metastases.He subsequently underwent a right hemicolectomy and partial cystectomy.Two of 17 sampled lymph nodes were positive for tumour.Since then, he has received four cycles (of eight planned) of FOLFOX chemotherapy (consisting of 150 mg oxaliplatin, 600 mg folinic acid, and 5-fluorouracil 600 mg bolus and 2400 mg via continuous infusion administered over 4 h).He has tolerated this well with only transient diarrhea following each dose.His clinical condition has improved with impressive weight gain from 46 kg to 55 kg and an associated improved sense of well being.

DISCUSSION
The diagnosis of HNPCC is based on guidelines known as the Amsterdam criteria (3), which includes the following: • At least three relatives with colorectal cancer, one of whom must be a first degree relative of the other two; • Involvement of two or more generations; • At least one case diagnosed before the age of 50 years; and • Familial adenomatous polyposis has been excluded.
It has clearly been established that screening is necessary because of the history of rapid adenoma to carcinoma progression in patients manifesting HNPCC.In one 15 year trial, colonoscopic screening at three-year intervals more than halves the risk of colorectal cancer, prevents deaths due to colorectal cancer, and decreases overall mortality by approximately 65% in HNPCC families (4).A task force organized by the National Human Genome Research Institute, has recommended colonoscopy every one to three years starting at age 25 years for individuals known to have HNPCC-associated mutations (1).Lynch et al ( 2) have suggested annual colonoscopies starting at the age of 20 years.With our current patient, clearly, there was advanced cancer present before the age of 20 years.This patient's family history was suggestive of HNPCC but the clinical diagnosis of the syndrome was not fulfilled until he himself was diagnosed with colon cancer.Unfortunately, in this situation there are no current recommendations for screening.This case illustrates the limitations of the current guidelines as it pertains to young people.In this era of quality assurance audits with respect to invasive procedures and medical insurance billing, we suggest that in similar cases, it would be appropriate for both physicians and patients to consider colonoscopic screening well before the lower age limit of current guidelines.In the future, the availability of commercial assays for HNPCC genetic marker screening, as well as sensitive and specific noninvasive colonoscopic imaging, such as three dimensional virtual colonoscopy (5), will make this suggestion easier to accept.
CONTRIBUTIONS: Dr Victor Wong wrote the preliminary discussion and compiled the reference list.Dr Yoshida wrote the preliminary introduction and case presentation section.Dr Salh rewrote the paper for its final presentation.Drs Ryan and Ho reviewed all of the computerized tomography scans and selected Figure 1.They also wrote the legend to Figure 1.There are no competing interests to declare.

ACKNOWLEDGEMENTS:
The patient reported has given written consent for the publication of this paper.