A 50-year-old woman had a partial colectomy performed for adenocarcinoma of the sigmoid colon, with apparent complete and uneventful recovery. At follow-up visits, her physician is particularly interested in changes that may occur in which of the following laboratory measures?
A. Human chorionic gonadotropin (hCG)
B. α-Fetoprotein (AFP)
C. Vanillylmandelic acid (VMA)
D. Carcinoembryonic antigen (CEA)
E. Estriol
The answer is D [Chapter 6, III C 4]. Although too nonspecific for initial diagnosis or screening, CEA is useful for follow-up of cancer of the colon. Increased serum hCG may be observed in normal pregnancy, hydatidiform mole, choriocarcinoma, and many testicular mixed germ cell tumors. Fetal neural tube defects are associated with increased levels of AFP in the mother. In addition, elevated levels of AFP (unrelated to pregnancy) may be associated with hepatocellular carcinoma, yolk sac (endodermal sinus) tumors, and some nonseminomatous germ cell tumors of the testes. VMA is a marker for neuroblastoma and pheochromocytoma. Granulosa cell tumors and thecomas of the ovary characteristically produce estrogen.
A 65-year-old man with a history of stage II adenocarcinoma of the colon inquires about colon cancer prevention for his son and two daughters, all of whom are healthy. Ten years ago, he was treated with a right hemicolectomy, with no postoperative chemotherapy or radiation, and was told by his oncologist that he was cured. He is not aware of any family history of colon cancer.
Which one of the following screening regimens is recommended for this patient’s children?
Colonoscopy beginning at age 40
Referral for genetic testing Fecal occult-blood testing and flexible sigmoidoscopy beginning at age 45 Colonoscopy beginning at age 50Colonoscopy beginning at age 45
First-degree relatives of patients who develop colorectal cancer before age 60 should start screening at either age 40 or 10 years before the age at which the index case was diagnosed, whichever comes first.
Family history in a first-degree relative is the greatest determinant of risk for colorectal cancer. For patients without a family history, current guidelines recommend screening with a full colonoscopy starting at age 50. For patients who have a first-degree relative with colorectal cancer, the risk is approximately double that of the general population. These individuals should undergo screening colonoscopy at either age 40 or 10 years before the age at which the index case was diagnosed, whichever comes first. In the scenario above, the index case was diagnosed at age 55, and thus the recommendation for his children would be to start screening at age 40.
Flexible sigmoidoscopy and fecal occult-blood testing are less effective screening modalities that should be offered in this scenario only if colonoscopy is refused.
Referral to a genetic counselor would be indicated if the first-degree relative had been diagnosed before age 50 or in the setting of a known heritable cancer syndrome.
Lieberman DA. Clinical practice. Screening for colorectal cancer. N Engl J Med 2009 Sep 18; 361:1179. > View Abstract
Weinberg DS and Schoen RE. In the clinic. Screening for colorectal cancer. Ann Intern Med 2014 May 6. > View Abstract
Qaseem A et al. Screening for colorectal cancer: a guidance statement from the American College of Physicians. Ann Intern Med 2012 Mar 6; 156:378. > View Abstract
- See more at: http://knowledgeplus.nejm.org/question-of-week/966/answer/A/#sthash.Ua5gPvmb.dpuf- See more at: http://knowledgeplus.nejm.org/question-of-week/966/#sthash.tk2L3xpZ.dpufWhich of the following history or physical examination findings should prompt investigation for hereditary nonpolyposis colon cancer screening in a 32-year-old man?
Father, paternal aunt, and paternal cousin with colon cancer with ages of diagnosis of 54, 68, and 37 years, respectively
Innumerable polyps visualized on routine colonoscopy
Mucocutaneous pigmentation
New diagnosis of ulcerative colitis
None of the above
The correct answer is A. You answered A.
The answer is A. A strong family history of colon cancer should prompt consideration for hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome, particularly if diffuse polyposis is not noted on colonoscopy. HNPCC is characterized by (1) three or more relatives with histologically proven colorectal cancer, one of whom is a first-degree relative and of the other two, at least one had the diagnosis before age 50; and (2) colorectal cancer in at least two generations. The disease is an autosomal dominant trait and is associated with other tumors, including in the endometrium and ovary. The proximal colon is most frequently involved, and cancer occurs with a median age of 50 years, 15 years earlier than in sporadic colon cancer. Patients with HNPCC are recommended to receive biennial colonoscopy and pelvic ultrasound beginning at age 25. Innumerable polyps suggest the presence of one of the autosomal dominant polyposis syndromes, many of which carry a high malignant potential. These include familial adenomatous polyposis, Gardner syndrome (associated with osteomas, fibromas, epidermoid cysts), or Turcot syndrome (associated with brain cancer). Peutz-Jeghers syndrome is associated with mucocutaneous pigmentation and hamartomas. Tumors may develop in the ovary, breast, pancreas, and endometrium; however, malignant colon cancers are not common. Ulcerative colitis is strongly associated with development of colon cancer, but it is unusual for colon cancer to be the presenting finding in ulcerative colitis. Patients are generally symptomatic from their inflammatory bowel disease long before cancer risk develops.
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A 48-year-old man with early stage colon cancer undergoes a partial resection of the colon. Molecular analysis reveals that the tumor tissue harbors a mutation in codon 12 of the ras oncogene. The mutant gene codes for a ras protein product that has
A. decreased GTPase activity.
B. decreased reverse transcriptase activity.
C. increased protein phosphatase activity.
D. increased responsiveness to growth factors.
E. increased tyrosine kinase activity.
The answer is A. GTPase activity, which is required for inactivation, is decreased in mutant ras (p21) proteins. This change is mediated by reduced responsiveness to GTPase-activating protein.
Which of the following lesions is considered premalignant on colonoscopy?
The correct answer is “C.”Adenomatous colon polyps are associated with transformation to cancer. Answers “A” and “D” are not correct as they do not indicate if the sessile or pedunculated polyps are adenomatous or hyperplastic. Hyperplastic polyps are considered benign.