Pitfalls in diagnosing colon cancer Theodore Rokkas  MD, PhD (UK), FACG, AGAF, FEBGH As. Professor Head, A’  Gastroenterology Clinic Henry Dunant Hospital Center Athens, Greece

TOP 5 CANCER KILLERS

CRC Epidemiology Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. In Western Europe, it is the seventh leading cause of death, the fourth leading cause of loss of life expectancy.

COLON CANCER

Treatable but……….. The stage of the tumor at the time of treatment is considered the most important predictor of survival. Thus, in Europe, survival is 93% after 3 years for Duke stage A tumors, but it is only 16% after 3 years for stage D tumours. 93% 16% 3 year survival rate

EARLY DIAGNOSIS

The early diagnosis of CRC in symptomatic patients remains a problem!! A complex process A diagnostic procedure is performed Detection of first symptoms PITFALLS

Clinical manifestations Pitfall composition Clinical manifestations (symptoms) Virtual colonoscopy PITFALLS Blood and stool markers Colonoscopy Diagnostic procedure Barium enema

Diagnostic modalities Symptoms Fecal Blood Tests DNA Test Cologuard Barium enema Virtual Colonoscopy Colonoscopy

Diagnostic accuracy of diagnostic tests (i) Sensitivity: The sensitivity of a clinical test refers to the ability of the test to correctly identify those patients with the disease. Specificity: The specificity of a clinical test refers to the ability of the test to correctly identify those patients without the disease. Positive predictive value: The proportion that is useful to clinicians since it answers the question: ‘How likely is it that this patient has the disease given that the test result is positive?’ Negative predictive value: The NPV of a test answers the question: ‘How likely is it that this patient does not have the disease given that the test result is negative?’ Likelihood ratio: A final term sometimes used with reference to the utility of tests is the likelihood ratio. This is defined as how much more likely is it that a patient who tests positive has the disease compared with one who tests negative.

Diagnostic accuracy of diagnostic tests (ii) Receiver operator characteristic curves (ROC):Receiver operator characteristic curves are a plot of false positives against true positives for all cut-off values.  The area under this curve (AUC): Represents the overall accuracy of a test, with a value approaching 1.0 indicating a high sensitivity and specificity.  Diagnostic accuracy meta-analyses

Clinical manifestations Pitfall composition Clinical manifestations (symptoms) PITFALLS

CRC Symptoms Rectal bleeding Change in bowel habits Diarrhea Iron deficiency anemia Abdominal mass

Symptoms……. Conclusion Summary of findings (sensitivity, specificity, predictive values) for symptoms for CRC detection. Symptoms……. Conclusion The value of symptoms for CRC detection is very poor. Symptoms alone are not adequate to establish a suspicion of CRC They must be synthesized with other variables.

Pitfall composition PITFALLS Virtual colonoscopy Barium enema Diagnostic procedure Abdominal CT Scan

Pitfalls in diagnosing colon cancer on abdominal CT E Pitfalls in diagnosing colon cancer on abdominal CT E. Klang et al, Clinical Radiology 72 (2017) 858e863 CONCLUSION: Colon cancer is undetected in 20% of abdominal CT examinations in patients subsequently proven to have colon cancer at colonoscopy. Clinicians should be aware of the limitations of abdominal CT. CT axial (a) and coronal (b) images of missed rectal cancer(arrows) in a 74-year-old woman. In this case no intravenous contrast medium was used. Notice the absence of fat stranding, vascular engorgement, and enlarged lymph nodes around the tumour.

Barium enema Synchronous annular carcinomas in the ascending colon and splenic flexure.

Pitfalls at CT Colography Perry J. Pickhardt, Abdom Imaging Pitfalls at CT Colography Perry J. Pickhardt, Abdom Imaging. 2013 February ; 38(1): 82–97. Cecal carpet lesion (laterally spreading tumor) at CTC Colon map from CTC screening exam (A) shows a bookmark in the cecum (red dot), marking the location of the lesion. At 3D CTC (B), 2D CTC (C), and OC (D), a large lobulated flat lesion is seen (arrowheads) traversing cecal folds opposite the ileocecal valve (arrows). The tumor bulk is relatively subtle relative to its linear size. This mass required surgical resection and proved to be a tubulovillous adenoma.

Pitfalls at CT Colography Abdom Imaging. 2013 February ; 38(1): 82–97. Causes of False Negative Interpretations at CTC Misses related to suboptimal technique Misses related to intrinsic lesion characteristics Misses related to anatomic location Misses related to imaging artifacts Causes of False Positive Interpretations at CTC Retained (untagged) fecal material Thickened or complex folds Non-neoplastic anorectal lesions Ileocecal valve variants Inverted appendiceal stump Imaging artifacts Non-neoplastic polyps Submucosal and extrinsic lesions Large adenoma within a diverticular sigmoid colon: 2D versus 3D detection 2D CTC images (A and B) show advanced diverticular disease involving the sigmoid colon. Focal soft tissue prominence (arrow) proved to be a large polypoid mass (arrowheads) at 3D (C), but the distinction from collapse of thickened folds is very difficult on 2D alone. The mass was confirmed at colonoscopy (D).

Volume 381, Issue 9873, Pages 1185-1193 (April 2013) Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial  Prof Steve Halligan, FRCR, Kate Wooldrage, MSc, Edward Dadswell, MSci, Ines Kralj-Hans, PhD, Christian von Wagner, PhD, Rob Edwards, PhD, Guiqing Yao, PhD, Prof Clive Kay, FRCR, David Burling, FRCR, Omar Faiz, FRCS, Julian Teare, FRCP, Prof Richard J Lilford, FFPHM, Prof Dion Morton, FRCS, Prof Jane Wardle, PhD, Prof Wendy Atkin, PhD  The Lancet  Volume 381, Issue 9873, Pages 1185-1193 (April 2013) DOI: 10.1016/S0140-6736(12)62124-2

Barium enema Vs CT Colography for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial Trial profile *Reasons why patients were not randomised can be found in the appendix. †19 had an alternative whole-colon examination; 52 did not have a whole-colon examination. ‡85 had an alternative whole-colon examination; 142 did not have a whole-colon examination. The Lancet 2013 381, 1185-1193DOI: (10.1016/S0140-6736(12)62124-2

Barium enema Vs CT Colography for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial Detection of colorectal cancer or large (≥10mm) polyps by sex and age group The Lancet 2013 381, 1185-1193DOI: (10.1016/S0140-6736(12)62124-2)

CT Colonography of Colorectal Polyps: A Metaanalysis AJR: 2008, 181, 1593-1603 RESULTS. Fourteen studies fulfilled all the study inclusion criteria and gave a total of 1,324 patients and 1,411 polyps. The pooled sensitivity for polyps 10 mm or larger was 0.88 (0.84–0.93), [95% CI] For polyps 6–9 mm it was 0.84 (0.80–0.89), and For polyps 5 mm or smaller it was 0.65 (0.57–0.73). Sensitivity for detection of polyps increased as the polyp size increased (p< 0.00005). The pooled overall specificity for detection of polyps larger than 10 mm was 0.95 (0.94–0.97). CONCLUSION. The specificity and sensitivity of CT colonography are high for polyps larger than 10 mm. Virtual Colonoscopy COLONOSCOPY

Colonoscopy: Spearhead in the diagnosis of CRC

Pitfall composition Colonoscopy PITFALLS

Rates of Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis BRIAN BRESSLER, LAWRENCE F. PASZAT, ZHONGLIANG CHEN, DEANNA M. ROTHWELL, CHRIS VINDEN, and LINDA RABENECK. GASTROENTEROLOGY 2007;132:96–102 Methods: They analyzed data from the Canadian Institute for Health Information, the Ontario Health Insurance Program, and Ontario Cancer Registry for all patients (>20 years of age) with a new diagnosis of right-sided, transverse, splenic flexure/descending, rectal or sigmoid CRC in Ontario from April 1, 1997 to March 31, 2002, who had a colonoscopy within the 3 years before their diagnosis. Patients with missed cancers were those whose most recent colonoscopy was 6 to 36 months before diagnosis. We examined characteristics that might be risk factors for new or missed CRC.

Rates of Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis BRIAN BRESSLER, LAWRENCE F. PASZAT, ZHONGLIANG CHEN, DEANNA M. ROTHWELL, CHRIS VINDEN, and LINDA RABENECK. GASTROENTEROLOGY 2007;132:96–102 Rates of missed cancers (%) 3288 (right sided) 777 (transverse) 710 (splenic flexure/ descending) 7712 (rectal or sigmoid) patients. 5.9% 5.5% 2.1% 2.3%

Independent risk factors for these cancers in men and women were: Rates of Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis BRIAN BRESSLER, LAWRENCE F. PASZAT, ZHONGLIANG CHEN, DEANNA M. ROTHWELL, CHRIS VINDEN, and LINDA RABENECK. GASTROENTEROLOGY 2007;132:96–102 Results: Independent risk factors for these cancers in men and women were: older age; diverticular disease; right-sided or transverse CRC; colonoscopy by an internist or family physician; and colonoscopy in an office.

Total colonoscopy with ileoscopy

COLON CANCER

COLON CANCER

PREVENTION AND IMPROVEMENT OF CRC PROGNOSIS Two strategies are widely used to improve CRC prognosis and to optimize the health resources consumed: Population-based CRC early diagnosis strategies in symptomatic patients. Population-based screening programs in asymptomatic patients. Both strategies have been demonstrated to reduce the incidence and mortality rates of CRC in two ways: Removing preneoplastic lesions with polypectomy. Diagnosing a higher proportion of CRCs at an early stage.

Stool tests for colorectal cancer Several stool tests may be used to determine whether the stool shows signs of blood or genetic markers, which may be a sign of cancer or pre-cancerous polyps. These lab tests include: Stool DNA test: This test requires a prescription and is sold under the brand name Cologuard®. It is approved by the U.S. Food and Drug Administration to detect mutated DNA in the stool. The stool sample is collected at home and mailed to a lab. The test does not require special preparation or medication restrictions. A stool DNA test may be an acceptable alternative to a colonoscopy for some low-risk patients, but is not recommended for patients who have had polyps, a family history of colorectal cancer or other risk factors. Fecal immunochemical test (FIT): This analysis uses antibodies to detect blood in the stool. This test may also be performed at home. Test kits include a brush or stick used to wipe the stool sample onto a test card. Some test kits offer results in minutes; others are mailed to a lab. The FIT test does not require special preparation or medication restrictions.  Fecal occult blood test (FOBT): This test uses the chemical guaiac to detect blood in the stool. Like the FIT test, a sample is wiped onto a test card. Results may be provided immediately or after the samples are sent to a lab. This test may also be performed at home and may require some dietary and medication restrictions.

ADOPTION OF A HEALTHY LIFE STYLE

Factors related to patient delay In sum, the main factors related to patient delay are caused by the lack of knowledge about symptoms, the importance and implications of CRC diagnosis at an early stage, and the diagnostic tools available. Therefore, an effort to educate the general population about CRC is warranted and may help to reduce delay.

COLON CANCER

EARLY DIAGNOSIS

Treatable but……….. The stage of the tumor at the time of treatment is considered the most important predictor of survival. Thus, in Europe, survival is 93% after 3 years for Duke stage A tumors, but it is only 16% after 3 years for stage D tumours. 93% 16% 3 year survival rate

Treatable The stage of the tumor at the time of treatment is considered the most important predictor of survival. 93% 16% 3 year survival rate 100%

COLON CANCER