Colonoscopy in prevention of colorectal carcinoma

Continuing from my previous post on colorectal carcinoma, I just came across a study by Hermann Brenner et al. showing the effectiveness of colonoscopy in preventing colorectal carcinoma. They had conducted a population based case-control study in Germany to quantify the effectiveness of colonoscopy. 1688 cases and 1932 controls aged over 50 years participated in the study. The selection criteria for the cases were - a first diagnosis of invasive colorectal carcinoma (>30 years), physically and mentally fit to participate and ability to communicate in German. The study used randomly selected population based controls without history of colorectal carcinoma and were age, sex and country matched. The use of population based control prevents selection bias in recruiting controls and Berkson's bias, so this can be counted as a strength of the study.

Colon and rectum. Modified screenshot from Google body browser.

The cases were interviewed by trained interviewers in hospital setting while the controls were examined at their home. It would have been better if the interviewers were blinded to remove interviewer bias. The data on endoscopies during the last 10 years were corroborated with medical records which were available in 84% of the cases; hence there isn't much chance of recall bias. The authors excluded from statistical analysis cases less than 50 years old as screening colonoscopy is not recommended in them, cases with history of inflammatory bowel disease as they undergo surveillance colonoscopy due increased risk of colorectal carcinoma, missing information regarding colonoscopy, had undergone any other endoscopic procedure or if the last colonoscopy was done less than 1 year or more than 10 years ago.

Flow diagram of the study.

The confounding factors accounted for were age, sex, and education level, family history of colorectal carcinoma, smoking, body mass index, non-steroidal anti-inflammatory drug use, hormone replacement therapy use and participation in health screening examinations. The risk of colorectal cancer was estimated by calculating Odds ratio (OR).

The findings of the study clearly show the benefit of colonoscopy in preventing colorectal carcinoma. It should be noted that colonoscopy by itself is not preventive, colonoscopy identifies the early adenomas which are removed. As development of colon cancer follows adenoma-carcinoma sequence, colonoscopy becomes protective by early detection and removal of adenomas. The study found that colonoscopy reduces the overall risk of colorectal carcinoma by 77%. This is substantial. The greatest risk reduction was seen in case of cancers located in the sigmoid colon (adjusted OR=0.14). The least risk reduction was for cancers located in the ascending colon. In general the risk reduction was more for left colon cancers than for right colon cancers.

Adjusted odds ratio according to the site of colorectal cancer (less OR means more protection by colonoscopy).

The beneficial effect of colonoscopy did not vary with sex or with family history of colorectal carcinoma. The risk reducing effect of colonoscopy increased with increasing age in case of right sided colon cancer but such an effect was not observed in case of left sided colon cancers.

The study has few limitations like unaccounted confounders, possible differential rate of participation in the study. Also the authors did not account for the dietary habits of the participants. Increased intake of dietary fiber has a protective effect in development of colorectal cancer while intake of red meat and animal fat has a deleterious effect. It can be argued that BMI is a measure of the diet but I don’t think it can replace dietary history. This is one major point that I think the authors should have addressed.

Brenner H, Chang-Claude J, Seiler CM, Rickert A, & Hoffmeister M (2011). Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Annals of internal medicine, 154 (1), 22-30 PMID: 21200035

Is it cancer? Another case study

As I wrote in my previous post, sometimes other diseases may masquerade as cancer. Tay CW et al. reports another such case published in the International Journal of Surgery Case Reports.

They reported a case of a 33 year old female patient who presented with difficulty in swallowing, technically termed as dysphagia. There were no other symptoms. She was a non-smoker and there were no significant previous medical conditions. Chest X-ray and routine blood examination was normal. Physical examination did not reveal much.

Now the differential diagnosis of dysphagia is pretty long, involving the mouth, pharynx and the esophagus. Whether the symptom of dysphagia is progressive or not have to be considered. Progressive dysphagia suggests a malignant lesion. The type of  food which is difficult to swallow is also significant. Dysphagia which was initially to solids and gradually progresses to liquids indicates a malignant lesion. Dysphagia to liquids from the onset indicates a motility disorder of the esophagus. Dysphagia particularly aggravated on eating acidic food indicates an ulcerative lesion of the esophagus. In this case, the dysphagia was progressive for two weeks.

During the course of further investigation an upper gastrointestinal endoscopy was done. Upper gastrointestinal endoscopy is done to directly visualize the esophagus to look for any abnormal mass, ulceration or stricture that may cause dysphagia. A large submucosal esophageal mass was found, 25 cm from the incisor teeth. In the esophagus, any position is denoted by its length from the incisor teeth. The end of the esophagus is at about 40 cm from the incisor teeth. The mass was soft and covered by normal esophageal mucosa. Subsequently, a CT scan was done which showed a mid-esophageal mass, 4X2 cm in size. It was suggested to be an esophageal carcinoma and the patient was advised to undergo surgery.

Smoking and alcohol consumption are high risk factors for the development of esophageal carcinoma. They were absent in the patient. Dysphagia was the only complaint of the woman without any associated symptoms of cough, weight loss, fever, and hemetemesis (vomiting of blood). Squamous cell carcinoma is the commonest type esophageal carcinoma; adenocarcinoma is the second commonest. Other types are rare.

Sub carinal space. Modified screenshot from Google body browser.

At this stage the patient was referred to the authors for a second opinion. They arranged for an endoscopic ultrasound (EUS) and surprise! EUS detected a heterogeneous mass, 46 mm X 23 mm in size in the subcarinal window (subcarinal space is the space in front of the esophagus below the bifurcation of the trachea which is called the carina). It was suggested to be a lymph node which has enlarged and compressed the esophagus, causing the symptom of dysphagia. Fine needle aspiration was done endoscopically and cytological examination of the aspirate revealed an epithelioid granuloma, typically seen in tuberculosis. Molecular analysis of the aspirate was positive for Mycobacterium tuberculosis.

This finding changed the picture radically. Instead of surgery, the patient underwent medical treatment for tuberculosis with antitubercular drugs. EUS was the pivotal diagnostic study.

What is intriguing is that the lungs of the patient were completely clear. I would have thought of the presence of a primary lung lesion. In fact I double checked the article to see if I had missed it. The chest X-ray and CT scan of the lungs were clear. No esophageal lesions were present either. It appears to be a case of primary  mediastinal lymph node tuberculosis. At least it is better than esophageal cancer considering the poor prognosis of esophageal cancer.

Happy new year!

Tay, C., Deans, D., Khor, J., Seet, J., & So, B. (2010). Suspected oesophageal cancer in a 33 year old lady International Journal of Surgery Case Reports DOI: 10.1016/j.ijscr.2010.10.002

Is it cancer or is it not? A case study

A diagnosis of cancer carries a lot of significance for the patient who receives the diagnosis. But is it always cancer? Can it be another disease masquerading as cancer? It is rare, but it can happen as a case report by Smulders YE et al. published in the Journal of Medical Case Reports demonstrates.

They report a case of a 50 year old Caucasian male referred to their clinic. He had complaints of dysphonia (difficulty in speaking), dysphagia (difficulty in swallowing), and odynophagia (pain while swallowing). He also had a complaint of pain going to his right ear. All these had been going on for two months. The patient also suffered from recurrent aspiration of liquids and had lost 3 kg of body weight.

The larynx. From Wikipedia.

The authors visualized his larynx (voice box) with a laryngoscope. There was an ulcer on the right false vocal cord (present above the true vocal cords, also called ventricular fold or vestibular fold) which extended to the epiglottis (a cartilage of the larynx). The right true vocal cord was edematous and mobility of the vocal cord was decreased. Contrast enhanced CT scan of the neck showed an enhanced mass present in the right false cord which had extended in to the anterior commissure (front end of the vocal cords) and upwards in to the piriform sinus.

(A) Initial antero-posterior chest X-ray. Miliary nodules predominantly bilaterally distributed in the upper parts of the lung parenchyma. (B) Axial contrast-enhanced computed tomography image of the neck: enhanced mass (arrows) in the false vocal cord which extends into the anterior commissure and obliteration of the paraglottic fat (arrowhead). (C) Axial high resolution computed tomography image of the chest: diffusely distributed interstitial nodular alterations with formation of central cavities (arrows).
Smulders et al. Journal of Medical Case Reports 2009 3:9288 doi:10.1186/1752-1947-3-9288

Direct laryngoscopy under general anesthesia showed a tumor covering the entire right false vocal cord with extension to the laryngeal surface of the epiglottis without involvement of the glottis (true vocal cord). A routine chest X-ray showed mainly bilaterally distributed miliary nodules in the upper part of the lung parenchyma. Full blood count and electrolytes were within normal limits. No lymph nodes were involved in the neck. The clinical diagnosis was T3N0 supraglottic laryngeal carcinoma. 

Let us stop here and take a look at the rationale behind the diagnosis. The man was 50 years old. Laryngeal carcinoma commonly occurs in this age group. He was a smoker for 40 years. Smoking is a known risk factor for laryngeal carcinoma. All the symptoms fit laryngeal carcinoma. Imaging and endoscopic visualization showed a tumor like mass in the larynx. T3 means the tumor is limited to the larynx with vocal cord fixation and/or invasion of the following – postcricoid area (area behind the cricoid cartilage), pre-epiglottic tissues, paraglottic space and/or minor cartilage invasion. N0 means no lymph nodes were involved by the carcinoma.

Is there any reason to doubt the diagnosis? The only thing is that the chest X-ray does not fit in the picture. The finding of the chest X-ray is more consistent with tuberculosis. But I can say this only because I have the advantage of hindsight; I already know what the diagnosis is. Moreover there are other conditions that may be consistent with the X-ray finding.

The authors then did a histopathological examination of the tumor mass. This is the diagnostic test and it sprang forth a surprise. They did not find any malignancy in the mass. Instead they found tuberculosis. This was a case of tuberculosis of the larynx in the guise of a laryngeal malignancy. They also found tubercle bacilli in the sputum of the patient meaning it was quite possible for the patient to infect others. A CT scan of the chest of the patient showed cavity formation in the lungs, indicating pulmonary tuberculosis. Two nurses, two of the patient’s relatives and two of his friends tested positive in skin with purified protein derivative (PPD). The patient was treated with antituberculous drugs and the contacts were treated prophylactically with tuberculostatics.

This case demonstrates that you can never be too sure in medicine. The features of laryngeal cancer and laryngeal tuberculosis are overlapping and there needs to be an index of suspicion to differentiate the two. Tuberculosis can cause all the symptoms of laryngeal carcinoma, from weight loss to tumor like mass. Here there was a clue in the chest X-ray finding but without a degree of suspicion, TB is not the first thing that would come to your mind. In this case, the laryngeal tuberculosis was probably secondary to the pulmonary tuberculosis with the larynx becoming infected from the coughed up tubercle bacilli. I would have been interested to know if the patient had been suffering from chronic cough, which I strongly suspect as his contacts came out to be positive in the PPD test. Erythrocyte sedimentation rate would also have given a clue as it would have been elevated in TB.

Merry Christmas!

Reference :

Smulders, Y., De Bondt, B., Lacko, M., Hodge, J., & Kross, K. (2009). Laryngeal tuberculosis presenting as a supraglottic carcinoma: a case report and review of the literature Journal of Medical Case Reports, 3 (1) DOI: 10.1186/1752-1947-3-9288