Gastrointestinal Cancers: How to recognize them H. Vahedi MD Gastroenterologist Associate Professor of Medicine DDRI The GI tract, including the: -hollow organs of the gut -and pancreas pancreas, liver -and biliary tree, is the site of more cancers z z The cancer epidemiology p gy is the wide variabilityy of tumor incidence from country to country by organ site z For example, an esophageal cancer belt extends from northeastern China through central Asia into northern Iran z In p parts of these regions, g , the incidence of SCC of the esophagus is more than 100-fold higher than that in adjacent low-incidence regions Esophageal cancer incidence in Central Asia and North Africa 25 20 15 10 5 male female 0 z These marked differences in cancer risk are not based on racial or genetic factors z The epidemiological observations strongly indicate the importance of environmental i l ffactors iin GI carcinogenesis i i z When people migrate: -from a high incidence region to a low incidence region -the organ specific rates of some cancers change to match that of the new region, g , usually y within two g generations z However, individual genetic differences may influence the effects of these factors Genetic syndromes z These include: z FAP predisposes sufferers ff to CRC C C as well as other GI cancers z Hereditary hemochromatosis causes too much iron to accumulate in the liver and increases risk of liver cancer z Hereditary non-polyposis colon cancer(HNPCC) z Family history of GI cancers Conditions that irritate or compromise the GI tract or organs z These conditions include: z z z z z z z z z z z z z z z z z Choledochal cysts Celiac disease Cirrhosis of the liver Crohn,s disease Chronic gastritis Chronic ulcerative colitis Fatty liver disease Gastric polyps Hepatitis p B or hepatitis p C infection Infection with aflatoxin B (through eating contaminated food) Infection with a Chinese liver fluke parasite Infection with the Helicobacter pylori bacterium Inflammatory bowel disease Intestinal metaplasia Pancreatitis Pernicious anemia Primary sclerosing cholangitis Symptoms of Gastrointestinal Cancer z In general, many of the GI cancers cause few symptoms until til th they h have advanced d d tto a llater t stage t and d spread d tto other organs z General symptoms of all GI cancers may include: -Abdominal pain -Appetite loss -Blood Blood in the stool -Unexplained fatigue or weakness -Unexplained weight loss -Nausea N -Vomiting CLINICAL MANIFESTATIONS OF ESOPHAGEAL CANCER Dysphagia z Both adeno Ca and SCC have similar clinical presentations except that adeno Ca rises much more commonly in the distal esophagus/GEJ z Obstruction Ob t ti off the th esophagus h b by th the ttumor causes progressive solid food dysphagia z This usually occurs once the esophageal lumen diameter is less than 13 mm Weight loss -dysphagia dysphagia -changes in diet -and tumor related anorexia z Early symptoms of esophageal cancer are subtle and nonspecific z Patients may also notice retrosternal discomfort or a burning sensation z Most early (superficial) esophageal cancers in the are detected serendipitously z Regurgitation of saliva or food uncontaminated by gastric secretions can also occur in patients with advanced disease z Aspiration pneumonia is infrequent z Hoarseness may occur if the recurrent laryngeal nerve is invaded z Chronic GI blood loss from esophageal cancer is common and may result in IDA z However, patients seldom notice melena, hematemesis or blood in regurgitated food z Acute upper GIB is rare and is a result of tumor erosion into the aorta or pulmonary or bronchial arteries z Tracheobronchial fistulas are a late complication of esophageal cancer z The fistulas are caused by direct invasion through the esophageal p g wall and into the main stem bronchus z Such patients often present with intractable coughing or frequent pneumonias z Life expectancy is less than 4 weeks following the development of this complication Palmar hyperkeratosis (Tylosis) z Keratoderma of the p palms and soles ((also known as tylosis) y ) presents as a yellow, symmetrical, smooth bilateral thickening of the epidermis z The inherited Th i h i d type off tylosis l i (Howell-Evans (H ll E syndrome) d )h has been most strongly associated with SCC of the esophagus z However, sporadic H di cases off tylosis t l i have h also l b been associated with: -Hodgkin lymphoma -leukemia leukemia -and breast cancer Investigations for patients with gastric cancer z BS z Endoscopy & biopsy z EUS z Chest and Abdominal CT Gastric Cancer ¾ Gastric cancer is one of the most common cancers worldwide with approximately pp y 989,600 , new cases and 738,000 deaths per year ¾ The incidence of cancer of the stomach continues to decrease in the United States S ¾ Sometimes occur in younger people ¾ Men have a higher incidence of gastric cancers than women ¾ The incidence of gastric cancer is much greater in Japan, which has instituted mass screening programs for earlier diagnosis Worldwide prevalence of cancer Stomach cancer incidence in Central Asia and North Africa 45 40 35 30 25 20 15 female 10 5 0 male ¾ Diet appears to be a significant factor ¾ A diet high in smoked foods and low in fruits and vegetables may increase the risk of gastric cancer ¾ Other factors related to the incidence of gastric cancer include: -chronic inflammation of the stomach -gastric ulcers -H. pylori infection -genetics genetics -smoking -and drink alcohol Pathology gy z Gastric cancer Adenocarcinoma z GIST (gastro-intestinal (gastro intestinal stromal tumour) z Carcinoid z Lymphoma z other z Adenocarcinoma z Diffuse Linitis plastica type z Poorer prognosis p g z z Intestinal Localised z Better prognosis z Distal stomach z Presentation z Early cancer z z z Asymptomatic Anaemia Dyspepsia 50% z M respond May d tto PPI z Advanced cancer z z z z z z z z Abdominal pain Weight loss Epigastric mass Ascites Acanthosis nigricans Supraclavicular mass Dysphagia Jaundice z Approximately 25% of patients have a history of GU z All gastric ulcers should be followed to complete healing z If GU that do not heal should undergo resection Signs of tumor extension or spread z The most common metastatic distribution is to the liver, peritoneal surfaces f ( (ascites) it ) z Since gastric cancer can spread via lymphatics, the physical examination may reveal: -a left supraclavicular adenopathy (a Virchow's node) -a periumbilical nodule (Sister Mary Joseph's node) -a a left axillary node (Irish node) z Peritoneal spread can present with: -an an enlarged ovary (Krukenberg's tumor) -or a mass in the cul-de-sac on rectal examination (Blumer's shelf) Paraneoplastic manifestations z Dermatologic findings may include: -the sudden appearance of diffuse seborrheic keratosis -or acanthosis nigricans z Neither finding g is specific p for gastric g cancer z Other paraneoplastic abnormalities that can occur in gastric cancer include: i l d -a microangiopathic hemolytic anemia -membranous nephropathy -and and hypercoagulable states (Trousseau (Trousseau's s syndrome) z Polyarteritis nodosa has been reported as the single y and surgically g y curable g gastric cancer manifestation of an early Tripe palm z Tripe p p palm refers to a characteristic velvety y thickening of the palms with a ridged or rugose appearance z The term is derived from its resemblance to the stomach mucosa z Tripe palm is predominantly associated with: -gastric gastric cancer -bronchogenic cancer -and rarely described in other malignancies Bazex's syndrome y z Bazex's syndrome (acrokeratosis paraneoplastica) is a rare paraneoplastic phenomenon z Strongly associated with SCC of the upper aerodigestive tract z It has also been reported with a number of other tumors Investigations for patients with gastric cancer z Endoscopy py & biopsy p y z CT chest & abdomen z EUS (endoscopic ultrasound) z Laparoscopy Referral for endoscopy z Routine endoscopy not necessary without alarm signs i !!! z Urgent g ((<2 weeks)) specialist p referral for endoscopic p investigation when dyspepsia with: z Chronic GI bleeding z Progressive w,loss z Progressive dysphagia z Persistent vomiting z Iron deficiency anaemia z Epigastric mass z Suspicious barium meal Referral for endoscopy z Indication for endoscopy when symptoms persist d despite it ttreatment t t (HP eradication) di ti ) if patients ti t h have: z z z z z z Prior gastric ulcer Prior gastric surgery Need for NSAID usage Raised gastric cancer risk Anxiety about cancer New onset dyspepsia age >55 requires endoscopy Treatment of gastric cancer z Endoscopic p treatment z z EMR (endoscopic mucosal resection) Ablation z Surgery z M lti d l ttreatment Multimodal t t z z z Neo-adjuvant Adjuvant Palliative treatment Colon Cancer IBD 1% Sporadic 80% Familial 15% Hereditary H dit 4% CRC Incidence z The annual incidence in North America and Europe is approximately 30–50/100,000 z This incidence is estimated to be approximately pp y 3–7/100,000 , in most MiddleEastern countries Colorectal cancer incidence in Central Asia and North Africa 20 18 16 14 12 10 8 6 4 M l Male 2 Female 0 GLOBOCAN 2002, IARC Comparison between colorectal and upper GI cancer incidence in C t lA i A bi countries t i and dN th Af i Central Asia, Arabic North Africa 25 20 15 10 Upper GI 5 0 Colorectal CRC epidemiology p gy z Developing countries have lower rates CRC particularly ti l l Af Africa i and dA Asia i z These geographic differences ff appear to be due to differences in: -dietary di t and d environmental i t l exposures -background of genetically susceptibility Risk Factors One of the most preventable cancers! Risk increases with age Nearly 90% of colon cancer patients are over the age of 50 Risk factors include: family or personal history of CRC or polyps chronic inflammatory bowel disease hereditary colorectal syndromes use of cigarettes and other tobacco products high-fat/low fiber diet physical inactivity z Some patients had more than one abnormality: -Abdominal Abd i l pain i 44% -Change in bowel habits 43 -Hematochezia or melena 40% -Weakness 20% -Anemia without other GI symptoms 11% -Weight loss 6% Metastatic disease z 20% of patients have distant metastatic disease at the time of presentation z CRC can spread by: -lymphatic l h ti and d hematogenous h t di dissemination i ti -by contiguous and transperitoneal routes z The mostt common metastatic Th t t ti sites it are the th regional i l lymph l h nodes, liver, lungs, and peritoneum z The presence of RUQ pain, pain abdominal distention, distention early satiety, supraclavicular adenopathy, or periumbilical nodules usually signals advanced often metastatic disease Polypectomy Technique Colon Cancer Testing The flat polyp p yp z Techniques to improve detection Narrow band imaging Narrow-band z Chromoendoscopy z Endocytoscopy z Soitenko et al. JAMA March 2008 Narrow Band Imaging g g Virtual Colonoscopy z Spiral CT to generate 3D images z Cleaning of bowel, distension with air z Non invasive, no complications z Not endorsed for CRC screening Virtual Colonoscopy py Limitations Virtual Colonoscopy z Variable results z No screening g studies z No longitudinal studies z Cost z Does not allow for therapy Current Recommendations Average Risk Test FOBT Sigmoidoscopy FOBT + Sigmoidoscopy Interval (years) Yearly Every 5 Yearly, every 5 C l Colonoscopy E Every 10* Barium enema Every y5 Approach to Colon Cancer Testing Asymptomatic Men and Women Age ≥ 50 yr Age < 50 yr No family Hx YES family Hx No Screening HNPCC or FAP Genetic Counseling NO family Hx Average Screening 2 or more first-degree first degree or 1 first-degree < 60 yrs Colonoscopy every 5 yrs, starting age 40 1 first first-degree degree ≥ 60 yrs Average risk Average-risk screening, starting age 40 Impact of symptoms on prognosis -Patients who are symptomatic at diagnosis typically have a worse p g prognosis -In one report, the 5 year survival rate for symptomatic and asymptomatic patients was 49 versus 71% -The duration of symptoms is not an accurate predictor of prognosis -Obstruction and/or perforation, carry a poor prognosis -Tumors presenting with hemorrhage have been thought to have a better prognosis Reduce Your Risk Choices for good health Follow testing guidelines Know your family history G t regular Get l exercise i Do not smoke or use other tobacco products Avoid excessive alcohol consumption Reduce Your Risk Choices for good health Eat 5 or more servings of fruits & vegetables a day Choose whole grain foods Limit your intake of red meat Maintain a healthy weight Squatting position for defecation z Dr. Burkitt had an alternate theory to explain what protects t t the th developing d l i world ld ffrom colon l cancer z He observed that the natives of Africa and Asia use the squatting position for defecation z This is the posture which all primates were designed to use and is the only posture in which the lower regions of use, the colon (sigmoid, cecum and rectum) can be fully evacuated z These lower regions are where 80% of colorectal cancers develop Pancreatic cancer z Cancer of the exocrine pancreas is the: -4 4th or 5th leading l di cause off cancer-related l t d z The majority of these tumors (85%) are adenocarcinomas d i arising i i ffrom th the d ductal t l epithelium z Surgical resection is the only potentially curative treatment z Because of the late presentation of the disease, only 15 to 20% of patients are candidates for pancreatectomy z The prognosis of pancreatic cancer is poor even in those with potentially resectable disease z The 5 year survival following pancreaticoduodenectomy is only about 25 to 30% for node-negative and 10% for node-positive tumors z Incidence rates were approximately 30% higher in men and 50% higher in blacks compared with whites and people of other races Risk factors z Summarized briefly, the major risk factors include: -smoking -hereditary predisposition to pancreatic cancer -chronic pancreatitis -diabetes diabetes CLINICAL FEATURES History z Most patients; weight loss, loss or jaundice z Pain is present in 80 to 85% of patients z The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back z Weight loss can be profound; it may be associated with anorexia, early satiety, diarrhea, or steatorrhea z Jaundice J di iis often ft accompanied i db by pruritus, it acholic h li stools, t l and dd dark k urine z Painful jaundice is present in approximately one-half of patients with l locally ll unresectable t bl disease di z Painless jaundice is present in approximately one-half of patients with a potentially resectable lesion Physical findings z An abdominal mass or ascites can be noted at presentation in patients with advanced pancreatic cancer z A non-tender but palpable gallbladder may be seen or felt at the right costal margin in those with jaundice z Virchow's node or a palpable rectal shelf are present in some patients with widespread disease z Rarely, subcutaneous areas of nodular fat necrosis (pancreatic panniculitis) may be evident z The most common sites of distant metastases include the liver, peritoneum, lungs, and less frequently, bone z Many patients with pancreatic cancer are in a hypercoagulable state Why are we not diagnosing early cancers despite improvements p in imaging? g g z Patients with early cancers are usually asymptomatic z Early cancers noted in asymptomatic patients are often overlooked byy radiologists g Why renewed emphasis on early diagnosis now? z Improved p resolution with CT/MRI z Advent of EUS-FNA to provide cytologic diagnosis in patients with early stage pancreatic cancers z Advances in molecular testing z Better understanding of pathogenesis and natural history of pancreatic cancer What speaks against screening? z Harm due to screening Complications z Overtreatment z z L yield/cost Low i ld/ z No proof that stage migration results in improved p outcome Is there a good case for screening pancreatic cancer? In ggeneral p population? p -Incidence is 1 in 100,000 In high risk patient groups? -New onset diabetes mellitus -Idiopathic d h acute pancreatitis in the h elderly ld l -New diagnosis of chronic pancreatitis -New New onset unipolar depression in the elderly Which tests are best potential candidates for pancreatic cancer screening 1. 2. 3 3. 4. 5 5. 6. Serum markers Cross sectional imaging with spiral CT or MRI EUS/FNA ERCP Abdominal US None of the above