Case Report
The New Screening Guidelines for Colonic Neoplasms in Patients with Cystic Fibrosis; Are They Enough?
Ajaykumar C. Morani*, Ahmad A. Mubarak, David J Vining and Priya R Bhosale
Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas
*Corresponding author: Ajaykumar C. Morani, Department of Diagnostic Radiology, Unit 1473, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA
Published: 17 Nov, 2017
Cite this article as: Morani AC, Mubarak AA, Vining DJ,
Bhosale PR. The New Screening
Guidelines for Colonic Neoplasms in
Patients with Cystic Fibrosis; Are They
Enough?. Ann Clin Case Rep. 2017; 2:
1468.
Editorial
Cystic fibrosis (CF) is the most common lethal autosomal inherited disease of Caucasians[1,2].
The defect in CF transmembrane conductance regulator (CFTR) results in various degrees of
disrupted ion and fluid transport across epithelial cells, affecting respiratory, digestive, and
reproductive systems. Manifestations includes recurrent lung/sinus infections, pancreatic
insufficiency, constipation, and biliary dysfunction[1-3], with lung complications being the leading
cause of morbidity and mortality in these patients [4]. Previously CF was not considered a cancer
syndrome, as these patients used to haveshort life span in past and long-term complications were
not studied[5]. However survival has improved, to be specific, one cohort study reported increase
in the median age of survival from 31.9 years in 1990, to about 49.7 years in 2012 in cases of CF [6].
Contributing factors include early detection, better nutrition, and newer treatment options [4,6].
With increased survival now, a predisposition to digestive tract malignancies has been identified in
these patients[4].
Genetic studies have suggested that CFTR is in fact a tumor suppressor gene. In one study,
colonic and small intestinal tumors developed in the mice after intestinal CFTR gene was knocked
off in them [7]. It is hypothesizedthat the alterationin the luminal environment caused by CFTR
dysfunction leads to various changes that may ultimately lead to chronic inflammation with its
related risk of cancer, since CFTR normally plays important physiologic role in various digestive
tract organs[7,8]. In addition, various effects of the disease process (like deficiencies of protective
vitamins) could play a role in increasing the risk for cancer [2,8]. At the same time, interestingly and
for unknown reasons, the risk of melanoma is shown to be decreased in these cases, although the
risk of digestive cancers is increased [3]. Abdul Karim et al. reported the first case of digestive tract
cancer (biliary adenocarcinoma) in CF patient in 1982 [9]. Neglia et al. performed retrospective
cohort study on over 38,000 patients with CF from national databases in the US, Canada, and
Europeover a 7-year period [2], and despite no increased risk of other cancers, the risk of digestive
tract cancers was significantly increased, with an observed to expected risk ratio of 6.5. In this study,
most patients who developed digestive tract cancers were in their thirties and 23% of thosewere
colon cancers, making colon cancer the most prevalent. Mayer et al. studied the risk in posttransplant
CF patients and found a high risk of fatal colon cancer even in 3rd and 4th decades of life
[10]. A study by Sheldon et al. involving 412 CF patients showed an increase in pancreatic and small
intestinal cancers in these cases [5].
Therapy related immunosuppressive effect (post lung and/or liver transplant) may potentially
accelerate the cancer development process in CF. A 20-year US study followed 41,188 CF patients
and confirmed the risk of digestive tract cancers, particularly in post-transplant patients [3]. The
observed to expected risk ratio for digestive tract cancers was 3.5 (17.3 in post-transplant patients).
For the colon and small intestinal cancers analyzed separately, the observed risk was 6.2 and 11.5
(30.1 and 52.2 in post-transplant patients), respectively. Patients who had homozygous deletion
mutations for F508, had the highest risk for bowel cancers compared to those with other genetic
alterations in CF. This was especially high among those who held the diagnosis of distal intestinal
obstruction syndrome (impaction of inspissated stool in distal intestines) which preceded cancer
diagnosis by 9 years in many, but no similar increased risk was observed in association with other
CF complications. Their data also showed higher frequency of cancers in right colon.
In general, colon cancer is one of the more preventable cancersin the general population through
efficient screening andearly detection of premalignant adenomas and non-invasive cancers, often
detected by colonoscopy, CT colonography (CTC), or other screening strategies [11,12]. Screening
is advocated by the US Preventative Services Task Force to startat the age of 50 years [13], but earlier screening is recommended in the presence of genetic risk factors
[4,12,14]. After colonoscopy irrespective of the type of indication, the
risk for colon cancer has shown to be significantly reduced for up
to 10 years [4,15]. Until recently, there were no recommendations
for colon cancer screening in patients with CF [4]. Many studies on
screening colonoscopy had exclusion criteria for CF patients with
predicted FEV1<25, 40 or 50% [1,4,8]. However, these patients could
be at higher risk for developing cancer because of the severity of their
disease requiring organ transplantation [3].
The Minnesota Cystic Fibrosis centerhad recently recommended
screening colonoscopy for their in-center CF patients starting at
age 40, and they analyzed the data in 2 continuous studies [4,8].
Adenomas were found in half of their cases, with half of those being
advanced adenomas. Three out of their 88 patients developed colon
cancer. Surveillance of their study population revealed new adenomas
in 47%, with more advanced adenomas in those previously detected.
Findings suggested a high yield, even when screening was performed
at 1 to 2 year intervals in these patients. This study also suggested
that the adenoma progression to cancer is faster in CF. Furthermore,
in additional 27 patients aged 30-39 who underwent diagnostic
colonoscopy for various indications; 4 (15%) had adenomas, with one
of them advanced. In this study, CF related diabetes and homozygous
ΔF508 mutation were risk factors for polyp formation. Male gender,
lung transplantation, and homozygous mutation were associated
with advanced or multiple adenomas. This study supported early
screening colonoscopybeginning at age 40 in clinically stable patients,
and recommended annual surveillance colonoscopy if >3 polyps or
advanced polyp were detected.
The first consensus recommendations for colorectal cancer
screening in CF patients were developed in 2017 by a task-force
convened by the CF foundation [16]. They recommend screening
colonoscopy beginning at age 40 (30 in organ transplant recipients),
with 5-year screening intervals and 3-year surveillance intervals,
unless findings dictate shorter intervals. These guidelines are
considered to be beneficial tomost CF patients above age 40.
However, some studieshave reported colonic cancers in younger CF
patients, for example, in the 3rd decade of life [17,18] and even cases
of advanced cancer in 18- and 13-year olds reported by McKenna et
al.[19]and Ibele et al.[20], respectively. We recently encountered a 36-
year old CF patient who was found to have advanced sigmoid colonic
cancer (figure coronal CT showing pancreas and sigmoid ca). Neglia
et al. found many CF cases with cancer in their 3rd decade of life [2].
Newer colorectal cancer screening tests, including stool
DNA testing and CT colonography (CTC), offer promise as lessinvasive
screening exams for CF patients [11,21]. These can be
particularlymore useful for CF patientswith impaired respiratory
reserve and/or with sedation or anesthesia risks preventing them
from undergoing screening colonoscopy[11]. Plumb et al. studied
CTCas part of national screening program in patients in whom
colonoscopy was unfeasible or incomplete [11], and found it well
tolerated and extremely safe. They concluded that CTC can be
delivered across a national screening program. Devir et al. compared
CTC to conventional colonoscopy [22], and they indicated that CTC
is valuable alternative to colonoscopy with very high sensitivity and
specificity for various pathologic colon findings. Some studies have
reported 90-100% sensitivity of CTC in detecting colon cancer cases
[23-25].
In contrast to a limited number of colonoscopy studies in patients
with CF, there have been no studies evaluating use of CTC in CF
patients. Thus, in our opinion, studies are needed to evaluate the
utility of CTC in the younger CF population. Until then, a high index
of suspicion for colorectal adenoma and cancer should be maintained
in young symptomatic patients of CF. In summary, although new
guidelines have recommended early screening colonoscopy for
detection of colonic cancers or precancerous lesions in CF patients
above age 40 years, many CF patients are unable to undergo such
invasive procedures. This is particularly true for those that are
considered to be at high risk forcolonoscopy and related procedure
complications, and these cases are at the same time more prone to
developing colonic cancers. Furthermore, many colon malignancies
develop in CF patients who are younger than age 40. Therefore, more
studies are needed to explore the utility of alternative screening
methods like CTC and DNA stool testing with the potential of refining
future screening recommendations for young CF population.
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