Colorectal carcinoma in young females.Background: We sought to study the clinicopathologic characteristics of colorectal cancer colorectal cancer
Malignant tumour of the large intestine (colon) or rectum. Risk factors include age (after age 50), family history of colorectal cancer, chronic inflammatory bowel diseases, benign polyps, physical inactivity, and a diet high in fat. in young female patients. We also wanted to determine the association of colorectal cancer with anemia in these female patients and, finally, to determine the effect of gender on prognosis in young patients with colorectal cancer.
Methods: We performed a retrospective analysis of all young patients diagnosed with colorectal cancer between 1982 and 1999 in two teaching hospitals in New York List of hospitals in New York (U.S. state), sorted by hospital name. A to H
Results: A total of 3,546 cases of colorectal cancer were diagnosed. Sixty-one (1.63%) of these patients were young patients and 32 (0.85%) were female. Young refers to all patients in the study who were younger than 40 years of age. The clinical presentation and mean age at presentation were very similar in both male and female patients. At presentation, 87.5% of female patients had anemia compared with only 69% of male patients. Males had a statistically significant higher mean hemoglobin level compared with females (12.87 versus 10.29 g) at P = 0.0001. Seventy-nine percent of female patients compared with 86% of male patients presented with left-sided tumors. Fifty-five percent of males presented with late stage disease compared with 68% of females (P = 0.27). Female sex seemed to adversely affect the prognosis, although this did not reach statistical significance (P = 0.08). Stage of disease was associated with worse prognosis and this was independent of sex. Age and hemoglobin were not independent predictors of mortality.
Conclusion: Colorectal cancer does occur in females of childbearing age who might have a tendency to present with late stage disease as evidence from this study. Young female patients with anemia should be questioned about gastrointestinal symptoms, and colorectal cancer should definitely be in the differential diagnoses. This might conceivably allow for earlier diagnosis and potential for cure in this patient group.
Colorectal cancer remains a commonly diagnosed malignancy in the United States, and there are more than 50,000 deaths annually as a result of this malignancy. (1) It is generally considered a disease of older people, and the majority of cases are diagnosed in patients older than 55 years of age. (2) Therefore, it is not surprising that data regarding the clinical presentation and prognosis of colorectal cancer in young patients are scant. (3,4) The available data have been conflicting, but there are a few studies that suggest that the prognosis might be worse in this group of patients. (5,6)
Our objective was to study the clinicopathologic and prognostic characteristics of young female patients with colorectal cancer as compared with young male patients. We explored the association of colorectal cancer with anemia in these young female patients. We wanted to use this study to focus on how much family history and genetic factors might contribute to the development of cancer in this group of patients. In addition, we wanted to determine whether female sex might be more predictive of mortality when compared with male sex, after controlling for the stage of cancer in these young patients.
This is a descriptive retrospective cohort study of colorectal cancer in young females from two urban teaching hospitals in New York City. Our definition of young for this study was patients younger than 40 years. Anemia was defined as hemoglobin below 12 g for females and 13.5 g for males. We identified all young patients who were diagnosed with primary colorectal cancer at St. Vincent's Hospital Hospital:
[Listed in CACM 2(5):16 (May 1959)]. ), hereditary nonpolyposis colorectal cancer Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is characterized by an increased risk of colorectal cancer and other cancers of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. (HNPCC HNPCC Hereditary Nonpolyposis Colorectal Cancer
HNPCC Hereditary non-polyposis colon cancer ), and inflammatory bowel disease inflammatory bowel disease
n. Abbr. IBD
Any of several incurable and debilitating diseases of the gastrointestinal tract characterized by inflammation and obstruction of parts of the intestine. (IBD IBD
inflammatory bowel disease
Inflammatory bowel disease (IBD)
Disease in which the lining of the intestine becomes inflamed.
Mentioned in: Amebiasis
Tumor locations were classified according to ICD-9. The right side of the colon consisted of cecum cecum (sē`kəm): see intestine. , ascending colon ascending colon
The part of the colon between the ileocecal orifice and the right colic flexure. , hepatic flexure hepatic flexure
See right colic flexure. , and transverse colon transverse colon
The part of the colon that lies across the upper part of the abdominal cavity. . The left colon consisted of splenic flexure splenic flexure
See left colic flexure. , descending colon descending colon
The part of the colon extending from the left colic flexure to the pelvic brim. , sigmoid colon sigmoid colon
See sigmoid flexure.
The final portion of the large intestine that empties into the rectum.
Mentioned in: Diverticulosis and Diverticulitis , rectosigmoid junction, and the rectal ampulla rectal ampulla
A dilated portion of the rectum just above the anal canal. . Appendiceal and anal cancer Anal Cancer Definition
Anal cancer is an uncommon form of cancer affecting the anus. The anus is the inch-and-a-half-long end portion of the large intestine, which opens to allow solid wastes to exit the body. cases were excluded. Staging was done according to the American Joint Committee on Cancer The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards. External links
1. transfer of disease from one organ or part of the body to another not directly connected with it, due either to transfer of pathogenic microorganisms or to staging for colorectal cancer. All patients were assigned to stages according to the AJCC. Patients with Stages 0 to 2 disease were considered to have early disease, whereas patients with Stage 3 or 4 disease were considered to have late disease.
Histologic grading was recorded as well differentiated, moderately differentiated, or poorly differentiated poorly differentiated Oncology adjective Referring to a malignancy in which the malignant cells bear minimal resemblance to the cell from which they arose. Cf Well-differentiated. . Also, it was noted whether tumors were mucin mucin: see glycoprotein. producing or not. Pathologists familiar with the histologic characteristics of colorectal cancer assessed the tumors. Operative findings were reviewed in all of the patients. Since the early 1990s, adjuvant chemotherapy Adjuvant chemotherapy
Treatment of the tumor with drugs after surgery to kill as many of the remaining cancer cells as possible.
Mentioned in: Neuroblastoma has been recommended for those with cancer stage IIB IIB Institute for Independent Business
IIB Institute of International Business
IIB Institute of International Bankers
IIB International Investment Bank
IIB Indian Institute of Banking & Finance
IIB Included in Bankruptcy
IIB Ice, Ice, Baby or higher disease. In the majority of our patients, adjuvant chemotherapy was in the form of 5-fluorouracil (5-FU) and levamisole levamisole /le·vam·i·sole/ (le-vam´i-sol) an immunomodulator used with fluorouracil in the treatment of colon cancer, administered as the hydrochloride salt. . Most patients with rectal lesions also had adjuvant adjuvant /ad·ju·vant/ (aj?dbobr-vant) (a-joo´vant)
1. assisting or aiding.
2. a substance that aids another, such as an auxiliary remedy.
3. radiotherapy. Treatment was categorized as curative surgery, radiotherapy, and chemotherapy. Prognosis was defined as either alive or dead at the end of the follow-up period.
All categorical variables were expressed as proportions, and the continuous variables were expressed as means. The [chi square chi square (kī),
n a nonparametric statistic used with discrete data in the form of frequency count (nominal data) or percentages or proportions that can be reduced to frequencies. ] statistic was calculated as a measure of association between categorical variables while a two-sample t test was used to determine differences between two proportions of means. Significance level was set at P < 0.05 for all analysis. Significance level for comparisons was set at P < 0.05.
To determine the independent role of sex in predicting mortality, logistic regression models were constructed with mortality as the dependent variable. The independent variables were sex, age, hemoglobin, and stage of disease. Initially, bivariate bi·var·i·ate
Mathematics Having two variables: bivariate binomial distribution.
Adj. 1. analysis was performed with each variable and then loaded into a multivariate logistic regression model. To determine the predictive power of each variable in the multivariate model, each was removed one at a time with a backward selection process. Significance level was set at P < 0.05.
Sex was entered into this model as a dichotomous di·chot·o·mous
1. Divided or dividing into two parts or classifications.
2. Characterized by dichotomy.
di·chot variable, and age and hemoglobin were entered as continuous variables. Stage of disease was entered as a categorical variable. All analysis was conducted with Minitab software (release 13.1 for Windows 98; Minitab, Inc., State College, PA).
Young patients accounted for 61 (1.63%) of 3,546 of all colorectal cancers diagnosed. Thirty-two (0.85%) of all patients were young females while 29 were young males. Table 1 shows the demographic characteristics of the 61 patients followed in this study. The mean age at presentation was similar for both young males and females, and the age range for all patients was 22 to 39 years. More (87.5%) females presented with anemia in contrast to 69% of male patients. Young males had a statistically significant higher mean hemoglobin level compared with young females.
Clinical presentation and tumor characteristics are illustrated in Table 2. Aside from anemia, the clinical presentation was very similar in both males and females. The most common clinical complaints in both groups were abdominal pain, rectal bleeding, and change in bowel habit. Only four patients (all female) had a predisposing factor that could have led to development of colorectal cancer. One patient had a personal and family history of FAP and was diagnosed with cancer at age 23; another had Crohn's disease Crohn's disease: see colitis. from which she had suffered for 12 years; and the remaining two had an aunt and mother who developed colorectal cancer after the age of 50 which really placed these patients at only slightly increased risk of developing cancer as compared with the regular population. There were no documented cases of HNPCC by history. Most of the tumors were left-sided tumors in both males and females. Sixty-eight percent of the female patients and 55% of the male patients presented with late stage disease. Most of the tumors in both groups were either poorly differentiated or moderately differentiated, and seven females and four males had mucin-producing tumors. The treatment modality treatment modality Medtalk The method used to treat a Pt for a particular condition is illustrated in Table 3. At the end of the 2-year follow-up period, 9 females compared with 11 males were alive without disease while 6 females and 3 males were alive with disease. In this study, the only variable predictive of mortality in this group of patients was the stage of disease. Using bivariate and multivariate regression analysis In statistics, a mathematical method of modeling the relationships among three or more variables. It is used to predict the value of one variable given the values of the others. For example, a model might estimate sales based on age and gender. , patients with late stage disease were more likely to die compared with those with early stage disease (odds ratio [OR] = 27.1, 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [CI] = 3.32-222.73, P = 0.002). Table 4 illustrates that sex, age, and hemoglobin were not independent predictors of mortality. When all variables were loaded in the multivariate model, only stage of disease remained a statistically significant predictor of mortality (OR = 64.1, CI = 4.79-826.3, P = 0.01). In this multivariate model, there was, however, a trend toward a worse prognosis for young women compared with men (OR = 6.19, CI = 0.78-49.02, P = 0.08).
This study demonstrates that colorectal cancer is uncommon in young females. It constitutes almost 1% of all colorectal cancers in this series. This is similar to some of the other studies in medical literature. (7,8) When we compared our young female patients with the young male patients, we observed no significant differences in presenting symptoms, tumor site, and tumor differentiation. However, more of our young female patients presented with anemia. Iron deficiency iron deficiency A relative or absolute deficiency of iron which may be due to chelation in the GI tract, loss due to acute or chronic hemorrhage or dietary insufficiency Sources Meat, poultry, eggs, vegetables, cereals, especially if fortified with iron; per the is very common in young females and this is usually attributed to menstruation or the burden of pregnancy and childbirth. A study by Bini et al (9) of 186 premenopausal pre·me·no·paus·al
Of or relating to the years or the stage of life immediately before the onset of menopause.
premenopausal adjective patients with iron deficiency anemia Iron Deficiency Anemia Definition
Anemia can be caused by iron deficiency, folate deficiency, vitamin B12 deficiency, and other causes. The term iron deficiency anemia means anemia that is due to iron deficiency. showed that 6 (3%) of these patients were diagnosed with colorectal cancer after endoscopic en·do·scope
An instrument for examining visually the interior of a bodily canal or a hollow organ such as the colon, bladder, or stomach.
en workup work·up
n. Abbr. w/u
A thorough medical examination for diagnostic purposes. . Iron deficiency anemia has been shown to affect 9 to 11% of American female adolescents and women of childbearing age. (10) We think that further studies are needed to determine the best diagnostic and cost-effective approach for young female patients who present with anemia.
Only four of our patients (all female) had a reason that might have predisposed them to colorectal cancer. We did not document a history of HNPCC in any of our patients. This is in contrast to a study of young patients from Italy by Fante et al (11) in which 38.4% of all their young patients with colorectal cancer had either FAP or HNPCC. We are of the opinion that the reason why Fante et al had more patients with HNPCC and FAP is a result of the specialized nature of their cancer-screening registry, which allowed them to preferably accumulate patients with familial cancer syndromes. We think that our study is more representative of the population. The classic Amsterdam criteria (12) were the first developed to support the diagnosis of HNPCC. These criteria were found to be quite restrictive but, if present, the chance of HNPCC is quite high. The Amsterdam criteria consist of the following:
1. At least three relatives with histologically verified colorectal cancer, including a first-degree relative of the other two patients
2. At least two successive generations affected
3. In at least one of the above individuals, diagnosis of colorectal cancer before age 50
The stringency of the Amsterdam criteria has prompted some authors and experts to recommend the Bethesda criteria, which are somewhat more sensitive but less specific. (13) The Bethesda criteria include the following:
1. Individuals who meet the Amsterdam criteria
2. Individuals with two HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extra-colonic cancers (endometrial endometrial /en·do·me·tri·al/ (en?do-me´tre-il) pertaining to the endometrium.
n relating to the end-ometrium or cavity of the uterus. , ovarian, gastric, hepatobiliary, small bowel, or transitional cell cancer of the renal pelvis or ureter ureter (yrē`tər), thick-walled tube that conveys urine from the kidney to the urinary bladder. It is approximately 10 in. (25. )
3. Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or a colorectal adenoma adenoma: see neoplasm. . One of the cancers must have been diagnosed before age 45 and then adenoma at age less than 40 years
4. Individuals with colorectal cancer or endometrial cancer diagnosed before age 45
5. Individuals with right-sided colon cancer with an undifferentiated pattern (solid/cribriform) diagnosed before age 45
6. Individuals with signet ring cell signet ring cell A usually malignant cell containing copious clear cytoplasm that flattens a hyperchromatic nucleus to one side, having an appearance fancifully likened to a signet ring; CAs composed predominantly of SRCs often carry a worse prognosis; the type colorectal cancer (>50% signet ring cells) diagnosed before age 45
7. Individuals with colorectal cancer diagnosed before age 40
Testing for microsatellite instability in young patients with colorectal cancer might be a better way to screen for HNPCC. This makes sense because it is well documented that over 85% of HNPCC tumors demonstrate microsatellite instability. (14) A study by Gyrfe et al (15) of patients younger than 50 years of age demonstrated high-frequency microsatellite instability in 17% of their patients. Therefore, microsatellite instability could be performed on the tumors in these young patients as a screening test before more intensive DNA analysis is done to detect mutation in the HNPCC genes. Another approach that might be less expensive is to use immunochemistry Immunochemistry
A discipline concerned both with the structure of antibody (immunoglobulin) molecules and with their ability to bind an apparently limitless number of diverse chemical structures (antigens); with the structure, organization, and rearrangement to test for MSHLI and MSHL2 before specific genetic testing is performed. Another reason why we should probably be testing for microsatellite instability is recent studies that suggest that the presence or absence of microsatellite instability might have prognostic implications and might thereby affect the approach to patient management. (16,17)
This study again demonstrates that colorectal cancer can occur in pregnancy. Bernstein et al (18) demonstrated that no cases lower than cancer stage II were diagnosed in pregnant patients; this correlates with the poor survival rates documented in this group of patients. Many authors have attributed the delay in diagnosis in these patients to physicians attributing the signs and symptoms of colorectal cancer to those of pregnancy. (19,20) It is not clear whether hormonal effects might also be involved in the rapid spread of tumors in these patients. However, colorectal cancer does not seem to adversely affect gestation. Our two patients had normal live births. Woods et al (21) demonstrated that 25 (78%) of the 32 patients in their series had normal live births. Deaths were due to termination, intrauterine intrauterine /in·tra·uter·ine/ (-u´ter-in) within the uterus.
Within the uterus.
Situated or occuring in the uterus. deaths, prematurity, and stillbirths. Our two patients were unfortunately diagnosed during the peripartum period with Stage 4 disease.
It is important to note that recent studies from developed countries suggest that young patients with colorectal cancer might have similar or even better prognosis than older patients. (22,23) This trend might be a reflection of advances in technology and improvements in diagnostic and chemotherapeutic regimen. The improved prognosis in young patients might also be a reflection of lack of significant comorbidities and the ability of younger patients to better tolerate an aggressive surgical and chemoradiotherapy regimen. Before assuming any of the above, however, we would like to point out that incidence, stage of presentation, and mortality have been documented to be much higher in the young compared with older patients in developing countries. (24,25) These differences between developed and developing countries might be an indication that various environmental and genetic factors might vary in their effects on the development, biology, and behavior of colorectal cancer in different population groups. The female patients in our study had a tendency to present with more advanced disease, which translated to a poorer prognosis compared with young male patients. This did not reach statistical significance and we cannot say if this is because of the relatively small number of patients in this study. We think, however, that contributory factors to worse prognosis in young females might include the burden of anemia and pregnancy, which could conceivably result in a delay in diagnosis.
One of the major limitations of this study is the retrospective nature. However, we can conclude that colorectal cancer is not an exceptional rarity in young females. The most common clinical presentation is anemia, and a high index of suspicion index of suspicion Medtalk A phrase broadly used to indicate how seriously a particular disease is being entertained as a diagnosis; as an example, there is a high IOS that rapid and unexplained weight loss in an elderly Pt is due to pancreas CA, and a low IOS that is needed in these patients because of other confounding factors such as menstruation and pregnancy. Premenstrual premenstrual /pre·men·stru·al/ (pre-men´stroo-al) occurring before menstruation.
Of or occurring in the period just before menstruation. females, including pregnant patients who present with anemia coupled with symptoms like rectal bleeding, abdominal pain, and change in bowel habit, should be referred early to gastroenterologists for further workup to rule out potential colorectal cancer.
Table 1. Demographic characteristics (n = 61) Characteristics Males Females P value Age (yrs) 34.9 34.7 0.8 Race (%) Whites 28 31 * Blacks 48 37 * Others 24 32 * *[chi square] analysis of association between race and sex was not significant. Table 2. Clinical, staging, and pathologic characteristics of patients (a) Males Females P value Clinical symptoms Abdominal pain 10 12 NS Rectal bleeding 11 12 NS Change in bowel habit 8 5 NS Nausea/vomiting 2 3 NS Weight loss 4 2 NS Pregnant 0 2 NS Stage (%) Late 55 68 0.27 Anemia (%) 69% 87.5% Mean hemoglobin 12.87 10.29 0.0001 Pathologic characteristics Left-sided tumors (%) 86 79 NS Poorly differentiated 9 6 NS Moderately differentiated 11 14 NS Well differentiated 5 6 NS Undifferentiated 3 3 NS Unknown 1 3 NS Mucinous tumors 4 7 NS (a) NS, not significant. Table 3. Treatment modality Treatment Males Females Curative surgery (%) 23 (79%) 22 (69%) Radiation and surgery 9 (31%) 8 (25%) Chemotherapy and surgery 13 (45%) 15 (47%) Table 4. Multivariate odds ratio for mortality by stage, sex, age, and hemoglobin level Odds 95% CI Variable [beta] P ratio Lower Upper Stage (a) Late 4.16 0.001 64.10 4.97 826.3 Sex (b) Female 1.82 0.08 6.19 0.78 49.02 Age -0.15 0.08 0.85 0.71 1.02 Hemoglobin 0.29 0.25 1.35 0.80 2.25 (a) The referent value is early stage. (b) The referent value is male gender.
Accepted March 3, 2003.
Copyright [c] 2004 by The Southern Medical Association
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MLH Mint, Lightly Hinged
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RELATED ARTICLE: Key Points
* Colorectal cancer does occur in young women and even during pregnancy.
* Unfortunately, it is rarely diagnosed early in this group of patients.
* Anemia could be a presenting sign.
* Primary care physicians and gynecologists should be aware that patients with gastrointestinal symptoms coupled with anemia should probably be referred to a gastroenterologist for evaluation for colon cancer.
Olusola Olofinlade, MD, Olusegun Adeonigbagbe, MD, Nicholas Gualtieri, MD, Hal Freiman, MD, Olugbenga Ogedegbe, MD, and James Robilotti, MD
From the Section of Gastroenterology, Department of Medicine, St. Vincent's Hospital, New York, NY.
Reprint requests to Olusola Olofinlade, East Texas Gastroenterology Associates, 701 E. Marshall, Suite 200, Longview, TX 75601. Email: firstname.lastname@example.org