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Case Report - A 75-year-old Male with Weakness and Weight Loss
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Rose Domingo, MD
The patient is a 75 year old white male who went to the
emergency department complaining of longstanding fatigue and a recent
presyncopal episode. He also had lightheadedness upon standing up from a
sitting position and denied any loss of consciousness. The patient did not have
any chest pain, palpitations, shortness of breath or diaphoresis, nor did he
experience any focal weakness, convulsions, bowel or urinary incontinence surrounding
this episode. His past medical history
was significant for hypertension, diabetes, bradycardia, remote tobacco use and
poor medical follow-up.
In the emergency
department the patient was found to have orthostatic hypotension with a supine
blood pressure of 130/80 mmHg, heart rate of 60 bpm and standing blood pressure
of 80/60 mmHg without reflexive tachycardia.
He was noted to have heme-positive stool on rectal examination and
anemia on routine laboratory testing. Iron studies were consistent with iron
deficiency anemia. The patient was admitted to the hospital and placed on
telemetry monitoring which revealed bradycardia, with a heart rate of 50-60
bpm. The gastrointestinal service was consulted and planned to evaluate the
patient for the etiology of his GI blood loss however the patient decided to
leave against medical advice prior to completion of this workup.
One month after his initial presentation, the patient
returned to the emergency department with the complaint of continued weakness
and a change in the character of his stools.
He stated that his stools had become darker and were of a smaller
caliber recently. He also complained of constipation alternating with loose
stools. He denied melena, hematochezia,
abdominal pain, nausea or vomiting. The
patient denied any recurrence of lightheadedness or presyncopal symptoms, and
was otherwise without complaints. He
did, however, admit to roughly 50 pounds of unintentional weight loss over the
past year without an appreciable change in diet. Physical exam was notable for orthostatic
blood pressure changes: supine 170/90 mmHg and standing 130/80 mmHg with a
heart rate in the 60 bpm range in both positions. He remained anemic on
laboratory investigation, without a significant drop in hemoglobin or
hematocrit from his prior hospitalization.
The patient was again admitted to the hospital and agreed to a further
gastrointestinal workup.
Upper endoscopy revealed nonbleeding erythematous
gastropathy and erythematous duodenopathy but no visible bleeding lesions. Colonoscopy was attempted and aborted
secondary to bradycardia during the procedure. The procedure was terminated in
the sigmoid colon, which revealed multiple diverticuli. The following day the patient underwent a
barium enema to further evaluate for colonic pathology.
Based on the barium enema finding, what is the diagnosis?
Figure
1. Barium Enema (click to view larger version)
This barium enema shows a circumferential lesion with
luminal narrowing and ulceration in the distal descending colon suspicious for
a carcinoma roughly 3-4 centimeters in length, with associated inflammation in
the adjacent bowel wall and multiple sigmoid diverticuli.
DISCUSSION
Colorectal Cancer (CRC) is the second leading cause of
death due to malignancy in the United States. There are estimated to be greater
than 145,000 new cases of CRC diagnosed in the United States each year and more
than 55,000 deaths annually. Almost all
cases of colorectal cancer in the U.S. are adenocarcinomas. This type of CRC
forms bulky, exophytic masses (usually right sided lesions) or constricting
annular lesions (usually left sided colon lesions), and it is thought that most
cases arise from the malignant transformation of adenomatous polyps. Given the slow growth and rate of
transformation to CRC, screening is of the utmost importance in disease
prevention, recognition, and early treatment, and has a significant impact on
prognosis and mortality.
There are multiple risk factors associated with the
development of colorectal cancer. The
incidence of CRC increases with age greater than 45 and 90% of all cases of CRC
are diagnosed in patients over 50 years of age.
There is a positive family history of CRC in 20% of patients diagnosed
with this disease, and the risk increases proportionate to the number and age
of affected first degree family members with colon cancer. In addition, the lifetime risk of developing
colon cancer increases in first degree relatives of patients with a history of
nonmalignant adenomas, especially if the adenomas are diagnosed before the age
of 40. Interestingly, a family history
of colonic adenoma is of the same significance as a family history of CRC in a
patient’s lifetime risk of developing colon cancer. With either of these situations, the risk of
a 40-year-old patient approximates that of a 50-year-old without positive
family history, and colonoscopic surveillance is recommended beginning at the
age of 40 or 10 years earlier than the youngest diagnosed family case of
carcinoma. In patients with inflammatory
bowel disease, their lifetime risk increases roughly 7-10 years after the onset
of IBD, with the cumulative risk increasing 5-10% after 20 years and
approximately 20% after 30 years with the condition.
Diets high in fatty foods and red meats increase a
patient’s risk of developing CRC, whereas those rich in fruits, vegetables,
fiber, and those supplemented with vitamin B6, magnesium, calcium and folate
are linked with a lower risk. Increased
consumption of alcohol is associated with a higher risk of developing CRC,
which is thought to be related to interference in folate absorption and
decreased intake. The risk of developing
CRC is also increased in smokers, diabetics and patients with prior pelvic
irradiation. The risk of CRC decreases
with increased physical activity, and there is also a decreased risk observed
in female patients on hormone replacement therapy and patients on lipid
lowering therapy with HMG-CoA reductase inhibitors. Cohort and case-control
studies have shown that patients taking aspirin (at least 325mg twice weekly)
and nonsteroidal anti-inflammatories have an approximate 30-50% decreased
incidence of CRC and adenomas.
Additionally, daily low dose aspirin has shown to decrease the
recurrence of adenomas in 1-3 years in patients with a history of adenomas or
CRC.
Men are affected more frequently than women, with an
increased incidence in the black population.
Globally, the highest incidence of CRC is seen in North America,
Australia, and Northern and Western Europe, and less so in developing
countries. Interestingly, the diagnosis and early treatment in more developed
countries accounts for the lower mortality despite an increased numbers of cases.
The clinical presentation of a patient diagnosed with CRC
is dependent upon the anatomic site of the lesion. Right sided colon lesions are often
associated with chronic blood loss, and patients commonly present with fatigue,
weakness and laboratory data suggestive of iron deficiency anemia. Left sided colon lesions tend to involve the
bowel circumferentially and therefore present with obstructive symptoms,
colicky abdominal pain and changes in bowel habits, such as constipation
alternating with loose stools or a change in stool diameter. Rectal cancers often present with tenesmus,
urgency and recurrent episodes of hematochezia.
If locally advanced, rectal cancer may involve the sciatic or obturator
nerves, presenting as neuropathic pain syndromes. Rarely, colorectal cancer presents purely as
weight loss. The differential diagnoses for CRC include irritable bowel
syndrome, diverticular disease, ischemic colitis, inflammatory bowel disease,
infectious colitis, hemorrhoids and malignancies other than adenocarcinoma,
such as disseminated Kaposi’s sarcoma, primary Non-Hodgkin’s lymphoma,
carcinoid tumors or metastatic cancer (i.e. ovarian carcinoma.) Of note, Streptococcus
bovis bacteremia and Clostridium
septicum sepsis are due to underlying colonic malignancies in 10-25% of
patients.
Physical examination findings are usually relatively
benign until the CRC is advanced. A
focused physical exam should include evaluation for hepatomegaly, which may
indicate the presence of metastatic lesions, A digital rectal exam should be
performed in cases of distal rectal cancer to evaluate for extension to the
anal sphincter or fixation, suggestive of extension to the pelvic floor. Laboratory data is used to evaluate for the
extent of anemia, elevated liver function tests which would suggest metastatic
liver disease and carcinoembryonic antigen (CEA) levels pre and
post-operatively. Pre-op CEA levels of
>5ng/mL are associated with a poorer prognosis and failure of CEA levels to
normalize post-operatively should incite a more thorough investigation for
synchronous bowel lesions or local recurrence.
The diagnostic procedure of choice for colorectal cancer
is a colonoscopy, which allows for direct visualization and lesion biopsy. In cases where colonoscopy cannot be tolerated
or obstructive lesions do not allow the scope to pass, double contrast barium
enemas can be used to evaluate the bowel lumen, as well as CT colonography
(“virtual colonoscopy”). However, it is
important that the entire large bowel be evaluated for the presence of
synchronous lesions in patients with suspected CRC. In addition, chest radiographs can be useful
in evaluating for lung metastases, and abdominopelvic CT scans are sometimes
used for assistance in pre-operative staging in terms of the presence or
absence of metastasis (although they are not as useful in determining staging
and do not often alter the surgical management of patients). Intraoperative assessment of the liver by
direct palpation and ultrasound imaging is thought to be better for the
evaluation of liver metastases than CT. Pelvic MRI’s or endorectal ultrasounds
are commonly used to evaluate for depth of tumor infiltration through the
pelvic wall and for pararectal lymph node involvement in cases of rectal
carcinoma.
Colorectal cancer staging most often involves the TNM
method of classification and less often the Duke criteria. Surgical resection of primary colonic or
rectal carcinomas is the treatment of choice in patients with resectable
lesions who are able to undergo surgery, with regional lymph node dissection
performed for staging purposes. The use
of adjuvant therapy will be dependent upon the histologic staging of the
primary cancer, as will be the patient’s overall prognosis.
Stage I CRC (T1N0M0 or T2N0M0), which involves tumor
invasion to the submucosa or muscularis propria, is associated with a 90-100% 5
year survival rate and no adjuvant therapy is recommended
post-operatively.
Stage II CRC (T3N0M0 or T4N0M0) is associated with a
70-85% 5 year survival rate. There has
been no clear benefit demonstrated for the use of adjuvant therapy in patients
with T3 staging, (invasion of the subserosa or nonperitonealized
pericolic/perirectal tissues). However, patients with T4 staging, in which the
tumor perforates the visceral peritoneum or directly invades other organs or
structures, may be considered for study protocols for chemotherapy and/or
radiotherapy for control of local tumor recurrence.
Stage III CRC (node positive carcinoma) is associated with
a 30-50% 5 year survival rate with surgical resection alone. In these patients, post-operative
chemotherapy has been found to reduce mortality by 33% and is recommended for
all patients. 5-FU with leucovorin
therapy for 6 months is often used. 5-FU with levamisole is less effective,
requires a year of therapy and is rarely associated with cerebral
demyelination. Post-chemotherapy, Stage
III CRC patients with 1 to 3 positive lymph nodes have a 5 year survival rate
approaching 65%, and those with greater than 3 positive nodes have shown an
increased survival of up to 40%.
Of patients diagnosed with CRC, 15-20% will have distant
metastases at the time of their initial diagnosis and another 30% will
eventually develop metastatic disease.
The long-term survival of Stage IV CRC patients (metastasis-positive) is
approximately 5%, with a median survival anticipated at 8-15 months. Surgical resection of isolated liver or lung
metastases results in a greater than 5 year survival rate in 20-40% of
patients. If metastatic lesions are
unresectable, local ablative measures can be used. Chemotherapeutic regimens with leucovorin,
FU, and oxaliplatin (FOLFOX) or irinotecan (FOLFIRI, IFL) may lead to a 40%
improvement in tumor response rate and an overall mean survival of 10 to 20 months. IFL combined with bevacizumbab increases
median survival to 20 months versus 15 months when compared with IFL alone.
In general, patients who are symptomatic at the time of
diagnosis have an overall worse prognosis.
In one report, the 5 year survival rate for symptomatic patients was 49%
as compared with 71% in asymptomatic patients.
The duration of symptoms was not found to be an accurate predictor of
prognosis. Obstruction and perforation
are related to a poorer prognosis regardless of cancer stage. Possibly because
of earlier presentation, diagnosis and treatment, patients with GI hemorrhage
have a better prognosis. All patients
with a personal history of CRC or adenomatous polyps are at risk for the future
development of large bowel carcinoma. In
patients undergoing resection of a single colorectal cancer, metachronous
primary cancers develop in 1.5-3% of patients within the first 5 years
post-operatively. A personal history of
large (greater than 1 cm) adenomatous polyps and polyps with villous or
tubulovillous histology also increase the future risk of CRC, especially if
there are multiple polyps.
The Presenting Patient’s Course of Illness
After the barium enema finding of a mass the colorectal
surgical service was consulted and the patient underwent a hemicolectomy. Surgical pathology revealed an invasive,
moderately differentiated colonic adenocarcinoma with extension into the
pericolonic adipose tissue, along with diverticular disease. Metastatic adenocarcinoma was found in 1 of
15 pericolonic lymph nodes resected.
There was no vascular or lymphatic space invasion. Proximal, distal, and radial resection
margins were all free of malignancy.
Cancer staging based on histologic examination was T3N1M0. The patient’s CEA level pre-operatively was
1.1. Follow up CEA levels and evaluation
for adjuvant chemotherapy are currently pending.
REFERENCES
- Eddy DM. Screening for colorectal cancer. Ann Intern Med 1990; 113(5):373-84.
- Greene FL, Page DL, Fleming ID (Eds), et al. Cancer Staging Manual, 6th edition. AJCC (American Joint Committee on Cancer). Springer-Verlag, 2002:114.
- McQuaid KR. Alimentary Tract. In: Tierney, Jr. (Ed), et al. Current Medical Diagnosis & Treatment 2005. 44th edition. Lange Medical Books/McGraw-Hill, 2005:618-24.
- O'Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer 6th edition staging. J Natl Cancer Inst 2004; 96(19):1420-5.
- Speights VO, Johnson MW, Stoltenberg PH, Rappaport ES, Helbert B, Riggs B. Colorectal cancer: current trends in initial clinical manifestations. South Med J 1991; 84(5):575-8.
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