How to recognize them. H. Vahedi MD Gastroenterologist Associate Professor of Medicine DDRI

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1 Gastrointestinal Cancers: How to recognize them H. Vahedi MD Gastroenterologist Associate Professor of Medicine DDRI

2 The GI tract, including the: -hollow organs of the gut -and pancreas, liver -and biliary tree, is the site of more cancers

3 The cancer epidemiology is the wide variability of tumor incidence from country to country by organ site For example, an esophageal cancer belt extends from northeastern China through central Asia into northern Iran In parts of these regions, the incidence of SCC p g, of the esophagus is more than 100-fold higher than that in adjacent low-incidence regions

4 Esophageal cancer incidence in Central Asia and North Africa male female 0

5 These marked differences in cancer risk are not based on racial or genetic factors The epidemiological observations strongly indicate the importance of environmental factors in GI carcinogenesis i 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, usually within two generations However, individual genetic differences may influence the effects of these factors

6 Genetic syndromes These include: FAP predisposes sufferers to CRC C as well as other GI cancers Hereditary hemochromatosis causes too much iron to accumulate in the liver and increases risk of liver cancer Hereditary non-polyposis colon cancer(hnpcc) Family history of GI cancers

7 Conditions that irritate or compromise the GI tract or organs These conditions include: Choledochal cysts Celiac disease Cirrhosis of the liver Crohn,s disease Chronic gastritis Chronic ulcerative colitis Fatty liver disease Gastric polyps Hepatitis B or hepatitis 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

8 Symptoms of Gastrointestinal Cancer In general, many of the GI cancers cause few symptoms until they have advanced d to a later stage and spread to other organs General symptoms of all GI cancers may include: -Abdominal pain -Appetite loss -Blood in the stool -Unexplained fatigue or weakness -Unexplained weight loss -Nausea -Vomiting

9 CLINICAL MANIFESTATIONS OF ESOPHAGEAL CANCER Dysphagia Both adeno Ca and SCC have similar clinical presentations except that adeno Ca rises much more commonly in the distal esophagus/gej Obstruction ti of fthe esophagus by the tumor causes progressive solid food dysphagia This usually occurs once the esophageal lumen diameter is less than 13 mm

10 Weight loss -dysphagia -changes in diet -and tumor related anorexia Early symptoms of esophageal cancer are subtle and nonspecific Patients may also notice retrosternal discomfort or a burning sensation Most early (superficial) esophageal cancers in the are detected serendipitously

11 Regurgitation of saliva or food uncontaminated by gastric secretions can also occur in patients with advanced disease Aspiration pneumonia is infrequent Hoarseness may occur if the recurrent laryngeal nerve is invaded Chronic GI blood loss from esophageal cancer is common and may result in IDA However, patients seldom notice melena, hematemesis or blood in regurgitated food

12 Acute upper GIB is rare and is a result of tumor erosion into the aorta or pulmonary or bronchial arteries Tracheobronchial fistulas are a late complication of esophageal cancer The fistulas are caused by direct invasion through the esophageal wall and into the main stem bronchus Such patients often present with intractable coughing or frequent pneumonias Life expectancy is less than 4 weeks following the development of this complication

13 Palmar hyperkeratosis (Tylosis) Keratoderma of the palms and soles (also known as tylosis) presents as a yellow, symmetrical, smooth bilateral thickening of the epidermis The inherited i type of tylosis (Howell-Evans syndrome) has been most strongly associated with SCC of the esophagus However, sporadic cases of tylosis have also been associated with: -Hodgkin lymphoma -leukemia -and breast cancer

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15 Investigations for patients with gastric cancer BS Endoscopy & biopsy EUS Chest and Abdominal CT

16 Gastric Cancer Gastric cancer is one of the most common cancers worldwide with approximately 989,600 new cases and 738,000 deaths per year The incidence of cancer of the stomach continues to decrease in the United States Sometimes occur in younger people Men have a higher incidence of gastric cancers than women The incidence of gastric cancer is much greater in Japan, which has instituted mass screening programs for earlier diagnosis

17 Worldwide prevalence of cancer

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19 Stomach cancer incidence in Central Asia and North Africa female male 5 0

20 Diet appears to be a significant factor A diet high in smoked foods and low in fruits and vegetables may increase the risk of gastric cancer Other factors related to the incidence of gastric cancer include: -chronic inflammation of the stomach -gastric ulcers -H. pylori infection -genetics -smoking -and drink alcohol

21 Pathology Gastric cancer Adenocarcinoma GIST (gastro-intestinal stromal tumour) Carcinoid Lymphoma other

22 Adenocarcinoma Diffuse Linitis plastica type Poorer prognosis Intestinal Localised Better prognosis Distal stomach

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24 Presentation Early cancer Asymptomatic Anaemia Dyspepsia 50% May respond to PPI Advanced cancer Abdominal pain Weight loss Epigastric mass Ascites Acanthosis nigricans Supraclavicular mass Dysphagia Jaundice

25 Approximately 25% of patients have a history of GU All gastric ulcers should be followed to complete healing If GU that do not heal should undergo resection

26 Signs of tumor extension or spread The most common metastatic distribution is to the liver, peritoneal surfaces (ascites) 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 left axillary node (Irish node) Peritoneal spread can present with: -an enlarged ovary (Krukenberg's tumor) -or a mass in the cul-de-sac on rectal examination (Blumer's shelf)

27 Paraneoplastic manifestations Dermatologic findings may include: -the sudden appearance of diffuse seborrheic keratosis -or acanthosis nigricans Neither finding is specific for gastric cancer Other paraneoplastic abnormalities that can occur in gastric cancer include: -a microangiopathic hemolytic anemia -membranous nephropathy -and hypercoagulable states (Trousseau's s syndrome) Polyarteritis nodosa has been reported as the single manifestation of an early and surgically curable gastric cancer

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30 Tripe palm Tripe palm refers to a characteristic velvety thickening of the palms with a ridged or rugose appearance The term is derived from its resemblance to the stomach mucosa Tripe palm is predominantly associated with: -gastric cancer -bronchogenic cancer -and rarely described in other malignancies

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32 Bazex's syndrome Bazex's syndrome (acrokeratosis paraneoplastica) is a rare paraneoplastic phenomenon Strongly associated with SCC of the upper aerodigestive tract It has also been reported with a number of other tumors

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34 Investigations for patients with gastric cancer Endoscopy & biopsy CT chest & abdomen EUS (endoscopic ultrasound) Laparoscopy

35 Referral for endoscopy Routine endoscopy not necessary without alarm signs!!! Urgent (<2 weeks) specialist referral for endoscopic investigation when dyspepsia with: Chronic GI bleeding Progressive w,loss Progressive dysphagia Persistent vomiting Iron deficiency anaemia Epigastric mass Suspicious barium meal

36 Referral for endoscopy Indication for endoscopy when symptoms persist despite treatment t t (HP eradication) if patients t have: Prior gastric ulcer Prior gastric surgery Need for NSAID usage Raised gastric cancer risk Anxiety about cancer New onset dyspepsia age >55 requires endoscopy

37 Treatment of gastric cancer Endoscopic treatment EMR (endoscopic mucosal resection) Ablation Surgery Multimodal l treatmentt t Neo-adjuvant Adjuvant Palliative treatment

38 Colon Cancer Sporadic 80% IBD 1% Familial 15% Hereditary 4%

39 CRC Incidence The annual incidence in North America and Europe is approximately 30 50/100,000 This incidence is estimated to be approximately 3 7/100,000 in most Middle- Eastern countries

40 Colorectal cancer incidence in Central Asia and North Africa Male 2 0 Female GLOBOCAN 2002, IARC

41 Comparison between colorectal and upper GI cancer incidence in Central Asia, Arabic countries and North Africa Upper GI Colorectal 0

42 CRC epidemiology Developing countries have lower rates CRC particularly l Africa and Asia These geographic differences appear to be due to differences in: -dietary and environmental exposures -background of genetically susceptibility

43 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

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45 Some patients had more than one abnormality: -Abdominal pain 44% -Change in bowel habits 43 -Hematochezia or melena 40% -Weakness 20% -Anemia without other GI symptoms 11% -Weight loss 6%

46 Metastatic disease 20% of patients have distant metastatic disease at the time of presentation CRC can spread by: -lymphatic and hematogenous dissemination i -by contiguous and transperitoneal routes The most common metastatic t ti sites are the regional lymph nodes, liver, lungs, and peritoneum The presence of RUQ pain abdominal distention early The presence of RUQ pain, abdominal distention, early satiety, supraclavicular adenopathy, or periumbilical nodules usually signals advanced often metastatic disease

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56 Polypectomy Technique

57 Colon Cancer Testing

58 The flat polyp Techniques to improve detection Narrow-band imaging Chromoendoscopy Endocytoscopy Soitenko et al. JAMA March 2008

59 Narrow Band Imaging g

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66 Virtual Colonoscopy Spiral CT to generate 3D images Cleaning of bowel, distension with air Non invasive, no complications Not endorsed for CRC screening

67 Virtual Colonoscopy

68 Limitations Virtual Colonoscopy Variable results No screening studies No longitudinal studies Cost Does not allow for therapy

69 Current Recommendations Average Risk FOBT Test Interval (years) Yearly Sigmoidoscopy Every 5 FOBT + Sigmoidoscopy Yearly, every 5 Colonoscopy Every 10* Barium enema Every 5

70 Approach to Colon Cancer Testing Asymptomatic Men and Women Age < 50 yr Age 50 yr No family Hx YES family Hx NO family Hx No Screening Average Screening HNPCC or FAP 2 or more first-degree or 1 first-degree < 60 yrs 1 first-degree 60 yrs Genetic Counseling Colonoscopy every 5 yrs, starting age 40 Average-risk risk screening, starting age 40

71 Impact of symptoms on prognosis -Patients who are symptomatic at diagnosis typically have a worse 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

72 Reduce Your Risk Choices for good health Follow testing guidelines Know your family history Get regular exercise Do not smoke or use other tobacco products Avoid excessive alcohol consumption

73 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

74 Squatting position for defecation Dr. Burkitt had an alternate theory to explain what protects t the developing world from colon cancer He observed that the natives of Africa and Asia use the squatting position for defecation This is the posture which all primates were designed to use, and is the only posture in which the lower regions of the colon (sigmoid, cecum and rectum) can be fully evacuated These lower regions are where 80% of colorectal cancers develop

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78 Pancreatic cancer Cancer of the exocrine pancreas is the: -4 th or 5 th leading cause of cancer-related The majority of these tumors (85%) are adenocarcinomas arising i from the ductal epithelium

79 Surgical resection is the only potentially curative treatment Because of the late presentation of the disease, only 15 to 20% of patients are candidates for pancreatectomy The prognosis of pancreatic cancer is poor even in those with potentially resectable disease The 5 year survival following pancreaticoduodenectomy is only about 25 to 30% for node-negative and 10% for node-positive tumors Incidence rates were approximately 30% higher in men and 50% higher in blacks compared with whites and people of other races

80 Risk factors Summarized briefly, the major risk factors include: -smoking -hereditary predisposition to pancreatic cancer -chronic pancreatitis -diabetes

81 CLINICAL FEATURES History Most patients; weight loss, or jaundice Pain is present in 80 to 85% of patients The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back Weight loss can be profound; it may be associated with anorexia, early satiety, diarrhea, or steatorrhea Jaundice is often accompanied by pruritus, acholic stools, and dark urine Painful jaundice is present in approximately one-half of patients with locally ll unresectable disease Painless jaundice is present in approximately one-half of patients with a potentially resectable lesion

82 Physical findings An abdominal mass or ascites can be noted at presentation in patients with advanced pancreatic cancer A non-tender but palpable gallbladder may be seen or felt at the right costal margin in those with jaundice Virchow's node or a palpable rectal shelf are present in some patients with widespread disease Rarely, subcutaneous areas of nodular fat necrosis (pancreatic panniculitis) may be evident The most common sites of distant metastases include the liver, peritoneum, lungs, and less frequently, bone Many patients with pancreatic cancer are in a hypercoagulable state

83 Why are we not diagnosing early cancers despite improvements in imaging? g Patients with early cancers are usually asymptomatic Early cancers noted in asymptomatic patients are often overlooked by radiologists

84 Why renewed emphasis on early diagnosis now? Improved resolution with CT/MRI Advent of EUS-FNA to provide cytologic diagnosis in patients with early stage pancreatic cancers Advances in molecular testing Better understanding of pathogenesis and natural Better understanding of pathogenesis and natural history of pancreatic cancer

85 What speaks against screening? Harm due to screening Complications Overtreatment Low yield/cost No proof that stage migration results in improved outcome

86 Is there a good case for screening pancreatic cancer? In general population? p -Incidence is 1 in 100,000 In high risk patient groups? -New onset diabetes mellitus -Idiopathic acute pancreatitis in the elderly l -New diagnosis of chronic pancreatitis -New onset unipolar depression in the elderly

87 Which tests are best potential candidates for pancreatic cancer screening 1. Serum markers 2. Cross sectional imaging with spiral CT or MRI 3. EUS/FNA 4. ERCP 5. Abdominal US 6. None of the above