Health Articles

Colorectal cancer is second only to lung cancer as the most common malignancy among US and Western European men and women. In the USA, about 150,0(10 new cases of and 60.000 deaths from (his disease occur annually.
The incidence of colorectal cancer begins rising at age 40 and doubles every 5 yr thereafter, peaking in the eighth decade. Adenocarcinoma constitutes 95% of all colorectal cancers. Rectal cancer is more common in men; colon cancer apparently occurs equally in men and women. Synchronous colon cancers appear in about 3.5% of patients followed for > 25 yr, and metachronous lesions appear in 5% of such patients. Colonoscopic polypectomy in these palients will undoubtedly reduce these percentages.
Colorectal carcinoma is more common in upper socioeconomic classes. High-risk populations consume a diet higher in animal fat and refined sugar and lower in fiber than that consumed by low-risk populations. Other predisposing factors include age > 40, a history of colonic adenomatous polyps or cancer of the colon without follow-up colonoscopy surveillance, cancer of Ihe breast or female genital tract, first-degree relative with colon cancer, inflammatory bowel disease (eg, ulcerative colitis. Crohn’s disease, or radiation proctocolitis), and certain chronic parasitic infections (eg, schistosomiasis). Hereditary disorders (eg, familial polyposis) also arc associated with a high incidence of colorectal carcinoma, but they arc rare in the elderly.
The extent of tumor spread is graded by a modified Dukes classification. Dukes A lesions involve the mucosa; \i lesions extend through the wall but do nol involve lymph nodes; C lesions involve lymph nodes; and D lesions have distant metastases. Many modifications of this staging system exist.
Other colorectal malignancies include lymphoma, leiomyosarcoma, and carcinoid tumors.
Symptoms and Signs
Because colon cancer is asymplomalic in its early stages, screening is performed using routine sigmoidoscope examination every 3 lo 5 yr and annual fecal occull blood testing.
The location of a tumor in the colon influences the symptoms. Right-colon lesions are usually large, fungating. bleeding masses that cause iron deficiency anemia, fatigue, and weakness, and the large-caliber, thin-walled right colon contains fluid-like feces. These tumors usually do nol cause obstruction but may grow large enough to be palpable on abdominal examination. Left-colon lesions are usually “napkin-ring.” obstructive tumors that cause rectal bleeding, crampy abdominal pain, or altered bowel habits because of the narrower caliber of the left colon and the semisolid consistency of the feces. Patients with rectal lesions generally present with stool streaked or mixed with blood. They may also complain of tenesmus or a sensation of incomplete evacuation. Palpable lymphadenopathy, hepatomegaly, or both occur only in the late stages and suggest a very poor prognosis.
Diagnosis
Diagnosis is made by x-ray or endoscopy. A rigid sigmoidoscope may not be able to detect colon cancer because the instrument may not even reach its 25-cm iength. The fiberoptic sigmoidoscope can detect lesions in the rectum, the sigmoid colon, and the distal descending colon, the region where > 50% of cancers occur. The more proximal segments of the colon are examined by barium enema x-ray or colonoscopy. Air-contrast barium enema is usually superior lo the single-contrast technique in detecting colon cancer. Colonoscopy provides visualization and tissue for diagnosis and also allows inspection of the entire colon for synchronous polyps or cancers.
Fecal occult blood testing helps detect colonic tumors. Screening of elderly patients wilh annual fecal occult blood testing using six guaiac-impregnated slides over 3 days and sigmoidoscopy every 3 to 5 yr aids detection of early stage colon cancer, which is potentially curable. Wilh both screening tests, the positive predictive value is better in persons > 60 yr. Screening wilh fecal occult blood testing can reduce the mortality rate of colorectal cancer.
Carcinoembryonic antigen (CEA) levels may be elevated in patients with cancer of the colon, pancreas, breast, lung, prostate, stomach, or bladder as well as in those wilh benign conditions and !hus are nonspecific. An elevated CEA level is especially insensitive for early stage cancers. However, if the CEA level is elevated before surgery and decreases after it. a subsequent rise may indicate a recurrence.
Treatment
Treatment of colorectal cancer consists primarily of anatomic surgical resection (see Ch. 62). Except with lymphoma, radiation therapy ami chemotherapy do not cure. In Dukes C colon cancer and in Dukes B2 and C rectal cancer, adjuvant chemotherapy with 5-fluorouracil and levamisole combined with radiation therapy improves survival.
In patients with adenocarcinoma, the 5-yr survival r;ile is about 90% for piilienls with Dukes A lesions, 50% to 80% for those with B lesions, 30% to 40% for those with C lesions, and < 5% for those with I) lesions. Primary Gl tract lymphoma has an overall 5-yr survival rate of > 50%.

Incidence figures vary from 7% to 75% of the population > 50 yr. increasing with age and peaking in the seventh decade. Most benign tumors are polyps (a clinical term without pathologic significance that refers to any mass of tissue arising from a mucosal surface and protruding into the lumen). The relationship of colonic polyps to age, diet, geographic distribution, family history, and prior neoplasms is similar to that of adenocarcinoma of the colon, which is discussed below. Hamartomas, juvenile polyps, and congenital lesions usually do not occur in Ihe elderly.
Adenomatous polyps, the most common colorectal neoplasms, are found in 50% to 60% of persons > 60 yr at autopsy. Although they may involve the entire colon, they arc more concentrated in the distal region. Lesions may be sessile or pedunculated. Synchronous lesions (more than one at the same time) occur in about 50% of cases and are classified histologically as tubular, tubulovillous, or villous adenomas, depending on the proportion of villous elements. These polyps are true neoplasms with malignant potential, which varies wilh the size, proportion of villous elements, and degree of dysplasia. The overall risk for malignant change within an adenomatous polyp is about 1% to 2%.
Hyperplastic polyps are common benign tumors of the colon. They are small, dome-shaped, sessile lesions. Often a person has several of these lesions. These polyps have no inherent malignant potential.
Inflammatory polyps usually occur in persons with no associated disease; however, those with inflammatory bowel disorders, ischemic co-lilis, specific infections (eg. amebiasis and tuberculosis), toxic reactions to mineral oil and barium, and colitis cystica profunda are especially prone to such polyps.
Lipomas, the second most common benign tumors of the colon, usually occur at or near the ileocecal valve. Incidence peaks in the seventh to eighth decades. Colonic hemangiomas are predominantly found wilh advancing age. Frequently, many lesions appear. They may be classified as capillary, cavernous, or mixed and are a common cause of hemorrhage and a rare cause of intussusception. The incidence of leiomyomas seems to peak in the sixth decade and decline sharply thereafter.
Cronkhite-Canada syndrome is the only multiple polyposis syndrome affecting the elderly. The average age at diagnosis is 60, and ihe lesions resemble juvenile polyps. The syndrome occurs in bolh men and women, but il runs a relentless course in women with death occurring in 6 lo 18 mo, whereas men lend to have spontaneous remissions.
Symptoms and Signs
Most polyps are asymptomatic and arc found incidentally during evaluation for another disorder. The usual symptom is rectal bleeding, which most commonly is occult and rarely is massive; however, massive bleeding is more common with hemangiomas. Rarely, large villous adenomas cause a severe mucoid rectal discharge and diarrhea, which may result in hypokalemia and hyponatremia. Even more unusual are constipation caused by large, bulky tumors and rectal prolapse caused by distal lesions. In patients wilh Cronkhite-Canada syndrome, diarrhea is progressive, leading to inanition and cachexia, especially in women.
Patients wilh submucosal tumors (eg, lipomas, hemangiomas, and leiomyomas) may present with an abdominal mass or abdominal pain from intussusception.
Diagnosis and Treatment
Polyps are usually detected by fecal occult blood testing, sigmoidoscopy, barium enema, or colonoscopy. Although air-contrast barium enema is far superior (o (he single-contrast technique, it can miss up to 50% of polyps. With colonoscopy, polypectomy can he performed, and tissue can be obtained for diagnosis. Colonoscopy is usually performed when an adenomatous polyp is found on sigmoidoscopy because of the high frequency of additional polyps. Surgical excision may be necessary for submucosal tumors or polyps that cannot be removed en-doscopically.
When welt-differentia led carcinoma is detected in a polyp and no vascular, lymphatic, or stalk invasion exists and a clear resection margin does exist, the only treatment usually needed is endoscopic polypectomy. If these conditions are not met. surgery may be considered, depending on the location of the adenoma and other factors.
For patients with adenomatous polyps, repeated examinations every 3 to 5 yr after polypectomy are needed because additional lesions develop.

Benign colonic tumors have a high prevalence in the USA and Western Europe. Colorectal cancer is the second most common malignancy in the USA and Western Europe.

In the USA, about 24.000 new cases and 13,000 deaths from gastric cancer occur annually, and the incidence increases with age. The mean age at the time of diagnosis is 55 yr. Gastric cancer is more common in blacks and among poor socioeconomic groups; the male;female ratio is 2:1.
Adenocarcinoma accounts for 95% of all gastric malignancies. The worldwide incidence varies dramatically with low rates in the USA and high rates in Japan. Chile, and Costa Rica. Although an unexplained worldwide reduction has occurred over the past 50 yr (except in black men), the incidence around the gastroesophageal junction has increased. The cause of this increase is not clear, but the increase may result in part from an increase in Barren’s epithelium in the esophagus.
Lymphoma accounts for about 4% of gastric malignancies. The stomach is the most common site of primary extranodal lymphoma, accounting for up to 75% of all cases of primary Gl tract lymphomas. Most are histiocytic. Gastric lymphoma occurs mainly in men in the sixth decade.
Other malignancies, including leiomyosarcoma, carcinoid tumor, and Kaposi’s sarcoma, account for < \% of all gastric malignancies.
Gastric abnormalities with malignant potential include adenoma, mucosal atrophy with intestinal metaplasia (with or without associated pernicious anemia), and hypertrophic gastropathy. Helicobacter pylori infection may also be a risk factor for gastric adenocarcinoma and lymphoma. Gastroduodenal peptic ulcer disease has no etiologic association with gastric cancer, although a gastric ulcer that appears benign on endoscopy can have a microscopic malignant focus.
Pathology
Gastric cancer is generally classified as early or advanced, according to its gross appearance. Early gastric cancer is confined to the mucosa or submucosa and is divided into three types: (1) protruded, either polypoid or fungating; (2) superficial, either elevated, flat, or depressed: and (3) excavated. Advanced gastric cancer is defined as disease penetrating the muscularis propria with lymph node involvement: the prognosis is poor. It is divided into three types: (1) a mass lesion, either polypoid or fungating; (2) diffuse or infiltrating: and (31 ulcerated. Advanced gastric cancer may have more than one of these characteristics. If the tumor infiltration is diffuse and associated with a fibrous reaction, linitis plastica (leather-bottle stomach! may occur.
Gastric cancer develops predominantly in the distal portion of the stomach and is rarely multicentric. Cancer spreads by direct extension or metastasis via the lymphatics or the bloodstream.
Symptoms and Signs
In the early stages, symptoms may be insidious and dismissed as indite most common presenting symptom is vague epigastric dis
comfort followed by anorexia, early satiety, weight loss, hematemesis, melena, and severe abdominal pain as the tumor progresses. If the car-dia is involved, dysphagia may occur. If the prepyloric antrum is involved, symptoms of partial or complete gastric outlet obstruction (eg, epigastric fullness, nausea, and vomiting) may occur.
In the early stages, there are no specific signs of gastric cancer. In the later stages, weight loss, a palpable mass, and lymphadenopathy in the left supraclavicular region (Virchow's node) may be noted. Liver metastases can present as hepatomegaly. Dermatologic signs of gastric cancer include acanthosis nigricans and dermatomyositis.
Diagnosis
An upper Gl tract barium study is usually the initial test, but lesions are frequently missed. The double-contrast technique can improve detection, so that a mass, an infiltrating ulcer, or only thickened rugae can be seen.
Upper Gl endoscopy allows visualization of most lesions, provides a means of obtaining tissue for biopsy and cytologic examination, and yields the diagnosis in > 90% of cases. Endoscopic ultrasonography may provide information regarding the depth of invasion. When older patients can tolerate only one test, endoscopy is generally preferred to x-ray studies.
Other laboratory procedures provide little help. Elevated levels of carcinoembryonic antigen (CEA) and fetal sulfoglycoprotein and decreased levels of pepsinogen have been noted in about 15% of patients with gastric cancer, but because of poor sensitivity and specificity, these measures have no clinical role. An abdominal CT scan helps evaluate the extent of disease.
The differential diagnosis includes peptic ulcer and pancreaticobili-ary tract disease. Patients who have undergone partial gastrectomy or gastroenterostomy for peptic ulcer disease more often have gastric polyps, epithelial dysplasia, and carcinoma in the remaining gastric pouch beginning 10 to 15 yr after surgery. The only real chance of curing gastric cancer is early diagnosis and surgical excision.
The patient with gastric lymphoma presents with symptoms similar to those of gastric carcinoma. The radiographic appearance may also be similar, although large gastric folds and evidence of infiltration into the duodenum are more typical of lymphoma than of carcinoma. Endoscopy may confirm the diagnosis if multiple directed biopsies combined with brush cytology yield positive results. Because the lesions are submucosal, this approach may be unsuccessful, and laparotomy may be needed.
Treatment
Surgery is widely accepted as the initial therapy for early gastric cancer. Radiation therapy alone is ineffective for adenocarcinoma. Radiation therapy after resection is commonly used with good results in patients with gastric lymphoma. Chemotherapy for metastatic adenocarcinoma has a poor response rate. Chemotherapy for gas’tumors arc symptomatic. Adenocarcinoma produces symptoms more often than other small-intestine tumors. Adenocarcinoma is generally found in ihe proximal small intestine, predominantly in the duodenum. Predisposing factors include Klulen enteropathy, Crohn’s disease, and Ihe (il polyposis syndromes. Mich as Gardner’s syndrome. Tumors arc usually annular and constricting. Lymphoma occurs predominantly in the ileum and is usually of B-celt origin; lymphoma of T-cell origin is associated with adult celiac disease. Leiomyosarcoma is as common as lymphoma.
Symptoms, Signs, and Diagnosis
Although most small-intestine malignancies are asymptomatic, 60% to 75% of symptomatic small-intestine tumors arc malignant. Patients with advanced disease present with abdominal pain resulting from intestinal obstruction, recurrent intussusception, mesenteric thrombosis, perforation. (j| hemorrhage, or a palpable abdominal mass. The carcinoid syndrome, characterized by diarrhea and flushing, occurs usually when hepatic metastases develop. Lymphoma, especially Hodgkin’s disease, may present as malabsorption syndrome wilh weight loss, diarrhea, malaise, weakness, and edema.
Preoperative diagnosis is generally made by small-intestine \ i ay and CT scan. Endoscopy may provide visualization and tissue for diagnosis, and arteriography may show vascular malignancies. With advanced carcinoid tumors, urinary 5-hydroxyindoleacetic acid (5-H1AA) levels may be elevated.
Treatment
The usual treatment is surgical reseclion. Radiation therapy and chemotherapy are potentially effective only for lymphoma. The 5-yr survival rate for patients with adenocarcinoma is 30%; (”or those with lymphoma and leiomyosarcoma, it approaches 50%. The prognosis for patients wilh carcinoid tumors can be good wilh survival commonly exceeding 10 yr. Oclrcotide is often effective in treating severe flushing and diarrhea in palients wilh the carcinoid syndrome.

In clinical medicine, attempting !o separate the effects of aging from those of disease is a recurring challenge. The elderly who have no significant disease but whose biologic age appears greater than (heir chronologic age (as determined largely by functional assessment) are described as “frail.” Understanding the role of such frailty in liver aging isjust beginning. Mos! research on changes in the aging liver has been done in rodents and may not necessarily be extrapolated to humans.
There are no peculiar or characteristic diseases of the aged liver. Kur-thermore, the liver ages gracefully, without producing changes in the results of so-called liver function tests. In this context, the effects of aging on liver appearance, histologic characteristics, physiology, drug metabolism, and response to stress require more detailed comment.
Appearance
Autopsy studies and peritoneoscopy show that the liver becomes brown and more fibrotic with age. The increased capsular and parenchymal fibrosis should not be confused with cirrhosis. With age. hepatic weight declines: autopsy studies show a decrease of about 25% between ages 20 and 70 in men and women. In vivo ultrasound studies also show that liver volume is 17% to 28%’ lower in those over age 65 than in those under age 40.
Histologic Characteristics
Studies of age-related changes in hepatic fine structure have reported disparate results. Historically, it has been believed that human hepato-cytes enlarge with age; however, some studies report no change in size. Several studies on rodents report (hal hepatocytes enlarge with age, whereas others report that they enlarge with maturation but diminish with senescence.
Some studies report polyploidy and increases in nuclear size and binuclear liver cells with aging, although other studies report no significant changes. The structural changes found in hepatocyte mitochondria have been as disparate as an increased number of swollen, vacuolated mitochondria and a decreased number of mitochondria per liver volume. Unlike other componenls of hepatocytes, lysosomes and dense bodies increase consistency with age.
The brown pigment buildup with aging represents a lifetime accumulation of unexcretable metabolic residue and generally has no physiologic significance. An increased number of lipofuscin granules in hepatocytes accounts for much of this pigment. Lipofuscin is a brown pigment resulting from the accumulation of end-stage metabolic products of lipids and proteins; thus, it is a wear and tear pigment.
Hepatic changes caused by malnutrition and those caused by aging are similar in some ways. Both are associated with a brown, atrophic-appearing liver. However, in malnutrition the number of hepalocytes is normal, but they are smaller; in aging there are fewer hepatocyles. but they are usually larger.
Physiology
Decreased hepatic weight is accompanied by diminished hepatic blood flow (resulting from decreased splanchnic blood flow). In dye elimination tests using indocyanine green, the apparent hepatic blood flow declined by 35% in persons over age 65 compared with those under age 40. The diminished liver mass and blood flow may account for some changes in drug elimination in aging patients.
Protein synthesis and degradation appear to decrease with age. Several methods have been used to study hepatic protein synthesis, including cell-free systems, in vivo studies, hepatocyte suspensions, and liver perfusion systems. Although the results of the studies do not completely agree, most evidence points to decreased protein synthesis with age. However, the degree of decrease appears to vary widely among various proteins. No scx-rclated differences are apparent in studies involving male and female rodents.
Degradation of several proteins, including some enzymes, has been studied by following radiolabeled amino acids, using several techniques. The results suggest a decreased rate of degradation with age. The accumulation of abnormal proteins with aging may reflect a decreased ability of cells to degrade these proteins. In the only study on abnormal liver proteins as a function of age, a significant increase in their half-life was observed in mice. The extent to which these abnormal proteins are functional or represent inadequately broken down, deteriorated “junk” proteins is unclear.
As the liver ages, regeneration is delayed but not greatly impaired. In older rats mitotic activity is decreased more than in younger rats after partial hepatectomy. Although mitotic activity decreases, the hepato-cytes that do divide appear to undergo more cell cycles, and thus regeneration catches up.
Aging does not alter results of the so-called liver function tests, which measure hepatic damage, eg. hepatocellular injury (aminotransferases), selected protein synthesis (alkaline phosphatase), or transport of hepatocytes (bilirubin), rather than overall function. Thus, abnormal values for these tests in the elderly reflect disease, not the effects of aging.
Drug Distribution and Metabolism
Because the elderly take more prescription medications than any other age group, they are more likely to have adverse drug reactions. Therefore, much effort has been directed toward understanding the changes in drug metabolism that occur with aging. Many factors may influence drug disposition in the elderly, including changes in body composition (decreased lean body mass and increased fat), a general decrease in serum albumin concentration, decreased renal function, and environmental influences including dietary changes (see Ch. 21).
With the age-related increase in body fat. the distribution of lipid-soluble drugs increases. If plasma clearance remains unchanged, the half-life of the drug is prolonged, and the potential for toxic concentrations increases unless the dosing interval is modified appropriately.
With drugs that have a high rate of hepatic extraction, a significant change in bioavailability can occur with aging. Such drugs usually undergo significant metabolism before reaching the systemic circulation. Although absorption across the gut does not change significantly with aging, first-pass metabolism may decrease, most likely from reduced intrinsic clearance, and lead to increased bioavailability. Oral doses of nifedipine, propranolol, morphine, and labetalol, for example, achieve significantly higher plasma concentrations in the elderly.
The two major drug-binding proteins in serum are human serum albumin and ai-acid glycoprotein. With increasing age, serum albumin tends to decrease, whereas cu-acid glycoprotein tends to remain the same. Thus, in older patients there is less albumin-bound drug and more free drug. Because therapeutic effect is usually related to the amount of free drug, decreased serum albumin can result in increased levels of active drug. The clinical significance of this depends on the size of the increased free fraction, pharmacokinetics, and the drugs therapeutic index. Although large increases in the free fraction have been reported after acute administration of a few drugs (including naproxen, salicylate, and valproic acid) in the elderly, once steady state is achieved (chronic administration), increased total body clearance minimizes the clinical impact.