Extraintestinal Cancers Research Articles

Increased risk for cancer in patients with the Peutz-Jeghers syndrome.

Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. Retrospective cohort study. Tertiary care center. 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. Cases of cancer documented by chart review and telephone follow-up. 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.

Diagnoses of extraintestinal manifestations and cancers in IBD in large population-based databases

Diagnoses of extraintestinal manifestations and cancers in IBD in large population-based databases

APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is caused by germline mutation of the adenomatous polyposis coli (APC) gene on chromosome 5q. This study assessed genotype-phenotype correlations for extraintestinal lesions in FAP. Mutations of the APC gene were compared with the occurrence of seven extraintestinal manifestations in 475 FAP patients from 51 families. The frequency of manifestations was adjusted for different ages of patients using person years of exposure. In pedigrees without identified APC gene mutation, analysis of linkage to chromosome 5q and/or assessment of neoplasms for replication errors characteristic of mutation in mismatch repair genes were performed. FAP patients from the 42 families (82%) with identified mutations of the APC gene had more frequent expression of extraintestinal manifestations than affected individuals without identified mutations (risk ratio 1.2-4.0; significant difference for cutaneous cysts). The presence of a cutaneous cyst or extraintestinal cancer significantly increased the likelihood of detection of a mutation in the APC gene (94% and 92% respectively; p < 0.05). In patients without identified APC gene mutation, linkage to the APC gene was found in one large family (lod = 5.1, theta 0.01), and replication error phenotype was absent in all 24 neoplasms from 16 members of these nine pedigrees. Expression of pigmented ocular fundus lesions was strongly associated with mutations in codons 541-1309, but no other extraintestinal manifestations were related to mutation position. Multiplicity of extraintestinal manifestations was high with mutation in codons 1465, 1546, and 2621. Patients with the colorectal phenotype of FAP but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or mismatch repair genes. The site of APC gene mutation is associated with pigmented ocular fundus lesions (codons 542-1309) and predisposition to multiplicity of extraintestinal manifestations (codons 1465, 1546, and 2621).

Prevalence of Crohn's disease and simultaneous occurrence of extraintestinal complications and cancer. An epidemiologic study in adults.

Very dissimilar prevalence figures for Crohn's disease (CD) have been reported from different regions of Scandinavia. There are few reports on the occurrence of liver, joint, skin, and eye disease and gastrointestinal cancer in CD. All patients > or = 16 years old with CD living in a well-defined catchment area on 1 March 1990 were identified from the previous 10 years' registers of inpatients and outpatients. The records were screened for evidence of extraintestinal complications and fistulas. The prevalence of CD was 94/10(5) (95% confidence interval, 84-104) inhabitants > or = 16 years old. Signs of liver disease were encountered in 1 of 10 patients, and other extraintestinal complications and intestinal cancer occurred in 1-3%. The true prevalence of primary sclerosing cholangitis could not be assessed. The prevalence of CD was midway between recent figures from Orebro and Copenhagen. Fistulas and pathologic liver laboratory test results were more prevalent when CD involved both the large and small bowel.

Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis.

Familial adenomatous polyposis has been associated with several extraintestinal cancers, but the relative and absolute risks of these malignancies have not been determined. Extraintestinal cancers reportedly associated with adenomatous polyposis (thyroid gland, adrenal gland, pancreas, and biliary tract) were identified in polyposis patients and their at risk relatives in The Johns Hopkins Registry. The incidence rates of identified tumours were then compared with the general population through person year analysis with adjustment for population. For comparison, the incidence rates of the two most common cancers not associated with polyposis (breast cancer in women and lung cancer) were also calculated. There was an increased relative risk of thyroid cancer (relative risk 7.6; 95% confidence limits (CL) 2.5-17.7) and pancreatic adenocarcinoma (relative risk 4.46; 95% CL 1.2-11.4) in polyposis patients and at risk relatives. The absolute risk was 26.8 and 21.4 cases/100,000 person years, respectively. No cases of adrenal or biliary cancer were found in this cohort. There was no increased relative risk of lung cancer (95% CL 0.04-1.4) or breast cancer (95% CL 0.04-1.4) over the general population. The relative risks of thyroid and pancreatic cancer are increased in familial adenomatous polyposis, but the absolute lifetime risk is low. Screening for pancreatic cancer may not be worthwhile with currently available methods, but careful physical examination of the thyroid gland is warranted along with consideration for ultrasonography.

Extraintestinal Cancers in Crohn’s Disease

We have observed 4 cases of extraintestinal cancer complicating Crohn's disease (CD). They included renal cancer, urinary bladder cancer, ovarian cancer and myeloma. A review of the literature showed a considerable number of reports of extraintestinal cancer complicating CD with a total of 75 further cases. The significance of those and our cases is discussed. The possibility of extraintestinal cancer must be kept in mind following patients with CD. Our report suggests there may be a nonnegligible risk of extraintestinal cancer, particularly genitourinary tumor, in CD. The causal relationship, if any, remains undetermined.

Malignancy in ulcerative colitis.

All patients with ulcerative colitis referred to Rigshospitalet, Copenhagen, from 1 April 1964 to 1 January 1983 (18 years and 9 months) were studied from time of referral until death, proctocolectomy, or end of the study (1983). There were 759 patients, 423 females (56%) and 336 males (44%). None was lost to follow-up study. Median time from onset of disease until death, proctocolectomy, or end of the study was 11 years (range, 0-54 years). Median age at onset was 28 years (range, 0-83) among the males and 28 years (range, 4-83) among the females. Pancolitis was present in 312 patients (41%), left-sided colitis in 212 (28%), and haemorrhagic proctitis in 235 (31%). Surgical treatment was performed in 299 patients (39%): proctocolectomy in 197 (26%), colectomy with occluded rectal stump in 72 (9%), and colectomy with ileorectal anastomosis in 30 (4%). Altogether, 49 patients developed cancer, 20 being intestinal and 29 extraintestinal cancer. Compared with the general population matched for age, sex, and calendar time, there was an excessive number with intestinal cancer in both sexes (p less than 0.05). In females the number with extraintestinal cancer was higher than in the general population (p less than 0.01), a finding that has not been reported elsewhere. We found a similar, significantly increased incidence of extraintestinal cancer in females with Crohn's disease in a previous report. We found no increased risk of colorectal cancer in patients with early onset of ulcerative colitis. For all age classes we found that the age of appearance of colorectal cancer followed the equation: age at colorectal cancer = 14 + age at onset of ulcerative colitis. We found no higher potential for development of colorectal cancer in patients with pancolitis. In our series the incidence of colorectal cancer in pancolitis and left-sided colitis was equal. The incidence in patients with haemorrhagic proctitis was zero.

Prospective evaluation of the diagnostic efficacy of CA 19-9 assay as a marker for gastrointestinal cancers.

Levels of a new carbohydrate antigen, CA 19-9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to conventional CEA assays in 615 sera from healthy controls, patients with benign gastrointestinal disorders, and patients with cancers of gastrointestinal or extragastrointestinal origin. Whereas CEA levels were higher in smokers, CA 19-9 values were independent of the smoking history. CA 19-9 was undetectable in lymphoma and myeloma patients, but some patients with extraintestinal epithelial cancers expressed this antigen in serum. For benign and malignant gastrointestinal diseases, CA 19-9 displayed higher sensitivity, specificity, and predictive values than CEA. CA 19-9 was elevated as frequently as CEA in patients with metastatic pancreatic cancer, but in patients with localized disease, CA 19-9 was elevated more often than was CEA. In colorectal cancer, patients with and without metastases were detected at similar rates by both assays. It is concluded that CA 19-9 is a marker of epithelial cancers, does not vary with the smoking status, and is superior to CEA in detecting gastrointestinal malignancies, especially those arising from the pancreatic gland.

Extraintestinal cancers in inflammatory bowel disease.

The case histories of 1961 patients with inflammatory bowel disease (IBD), 1227 with Crohn's disease (CD) and 734 with ulcerative colitis (UC), have been studied for the incidence of extraintestinal malignant neoplasms. There were 54 extraintestinal cancers in 51 patients: 28 patients with CD and 23 with UC; 25 men and 26 women. There were 9 breast, 7 skin, 15 reticuloendothelial, 11 genitourinary, 3 lung, 3 perianal, 2 pancreatic islet cell, and several miscellaneous cancers. The number of patient-years from the onset of disease to the last date of follow-up was calculated for men and women with each form of IBD. The observed number (O) of neoplasms was recorded. The expected number (E) of neoplasms was derived from the Department of Health, Education, and Welfare (DHEW) incidence figures for the same neoplasms that occurred in a standard age- and sex-matched population. The O/E ratio was then calculated for each type of cancer as well as for the entire series. There were no statistically significant increases in overall O/E ratios of extraintestinal cancers for either CD (0.76) or UC (1.32). On the other hand, several specific types of cancer did appear to occur with a frequency that was significantly greater than expected. These cancers were classified into two groups. The first group included reticuloendothelial neoplasms. There was an excess of leukemias in UC (P less than 0.005) and an excess of lymphomas in both UC and CD (P less than 0.005). The second group included three squamous cell cancers of the perianal region, an incidence 30 times greater than expected, and two squamous cell cancers of the vagina, also in excess of the expected number. Lymphoma, leukemia, and squamous cell cancers have been reported to occur in excess in immunosuppressed or irradiated patients. It may therefore be speculated that the apparently increased incidence of these neoplasms in the patients with ileitis and colitis might be related to immunologic deficiencies associated with IBD, to the long-term administration of steroids or other immunosuppressive medications that were given to most of the patients or, possibly, to increased exposure to ionizing radiation. The apparently increased incidence of perianal and vaginal cancers of the squamous variety might be a consequence of the combined effects of chronic inflammatory disease involving these areas and primary immune suppression.

Patterns of neoplasia in Crohn's disease and ulcerative colitis.

Cancer occurred in 28 of 579 patients (4.8%) with Crohn's disease (CD) and in 30 of 267 (11.2%) with ulcerative colitis (UC) admitted to the Mount Sinai Hospital between 1960--1976. The proportion of cancers that were extraintestinal was greater in CD than in UC (43 vs. 12%), as was the proportion of gastrointestinal cancers that arose in apparently normal bowels (33 vs. 4%). The incidence of gastrointestinal cancer increase with duration of disease in both CD and UC, but the absolute rates were three times higher in UC. For extraintestinal cancer, on the other hand, there was less correlation with increasing duration of disease, and no higher frequency in UC than in CD. Mortality from gastrointestinal cancer was 82% in CD and 50% in UC, but occurred only within two years of tumor diagnosis; survival beyond two years seemed to indicate a favorable prognosis.