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1. NEOPLASMA IN DIGESTIVE SYSTEM Group 1 PLENO 5

2. SCENARIO 5: WHY ARE THE CHAPTERS BLOOD AND SLIMY? Mrs. Wati, 78 years old, came to the Sawang Health Center with complaints of slimy and bloody bowel movements, weakness in her body, and losing weight. History of small bowel movements such as goat droppings since one year ago, these six months often have diarrhea. Based on the doctor's examination, it was found that the general condition was weak, and severely malnourished, while the vital sign showed blood pressure 100/60 mmHg, pulse 110x/minute, and temperature 37°C. On rectal toucher examination, a mass 8 cm from the anal verge was obtained, hard, lumpy, circular, and fixed, and blood and mucus were found on the handschoen. The doctor explained that Mrs. Wati might have a malignant tumor in the rectum and recommended that she be referred to the Digestive Surgery RSUCM for further examination and therapy. Mrs. Wati was then examined by a Digestive surgeon. Based on supporting examinations, Hb was 7 gr/dl, and CEA was 92 mg/dl. Ultrasound examination revealed metastatic nodules in the liver and the results of a biopsy via colonoscopy were found to be an adenocarcinoma. The doctor planned a CT scan of the abdomen with intravenous contrast for staging and carrying out further management. Mrs. Wati's husband asked if her wife's illness was the same as that of her younger sibling who had been diagnosed with GIST in the small intestine. How do you explain what happened to Mrs. Wati?

3. JUMP 1: TERMINOLOGY rectal toucher examination: clinical examination which is often performed as a diagnostic step for various diseases Adenocarcinoma:a type of cancer that starts in the glands that line the inside of organs, so it can affect different areas of the body GIST:type of cancer that begins in the digestive system CEA:The CEA (Carcinoembryonic Antigen) examination is a test used to check how well treatment is working on certain types of cancer, especially colon cancer.

4. JUMP 2 & 3 : PROBLEM FORMULATION & HYPOTHESIS

5. Why mrs. Wati that has been diagnosed a carcinoma suffering diarhea? In the large intestine, water is absorbed so that faeces or hii faeces become shaped and not watery. Those affected by diarrhoea, generally experience disturbances in the absorption of water in the large intestine. The presence of inflammation in that part inhibits the absorption of fluid," 2. what are the supporting examinations for neoplasms in the digestive system? Clinical laboratory examination PA lab test Colonoscopy radiologist

6. 3. what is the interpretation of the rectal toucher examination? -mass 8 cm from anal verge => mass in mid rectum - hard, lumpy, circular, fixed => malignant -blood, mucus => derived from mucosal epithelial cells 4. what causes bowel movements bu stone like goat droppings? = Small stools such as feces or goat feces can indicate constipation/constipation. Constipation itself can usually be caused by several causes, such as: Less food containing fiber and less drinking Blockage in the digestive tract / intestinal obstruction Tumor or cancer of the digestive tract Nerve disorders (Parkinson's disease, spinal cord injury, or stroke) Side effects of certain drugs

7. 5. Whats the treatment for gist small instestine? The main treatment for GIST in the small intestine is surgery. Another therapy is by administering Imatinib, which is a "tyrosine kinase inhibitor" which is often given as initial therapy in GIST. Imatinib administration can be done alone or in combination with surgery. Based on several studies, it was found that the administration of Imatinib followed by surgery showed a reduced risk of recurrence in GIST. Patients who are resistant or show severe side effects with Imatinib therapy can be given another "tyrosine kinase inhibitor" therapy, namely Sunitinib (Sutent) which functions as an anti-angiogenic. Sunitinib will inhibit the development and metastasis of tumors due to the absence of vessel formation new blood needed by tumor cells to develop. If Imatinib and Sunitinib therapy does not give a good response, another type of "tyrosine kinase inhibitor" therapy, namely Regorafenib (Stivarga, BAY 73-4506) can be given. Until now, research is still being carried out to find new drugs or therapies for GIST. Several types of drugs being studied to date are Olaratumab (IMC-3G3), Crenolanib (ARO-002 or CP-868,596), Linsitinib (OSI-906) and protein 90 (HSP90) inhibitors

8. 6. Is the adenocarcinoma a genetic disease? Yes adeno carcinoma is related to genetic factor Instability Chromosome: is the most common type found in 85% of the CRCs.This mutation causes the loss of heterozygosity in tumor suppressor genes and mutations in proto-oncogenes. Mutations affect the following genes: APC, TP53, and K-ras, allelic loss of 18q, and aneuploidy. For example,Familial adenomatous polyposis (FAP): It is characterized by hundreds or thousands of precancerous adenomatous polyps, which generate CRC and other cancers, Also may occur extracolonic manifestations (desmoid tumor, osteomas, epidermoid cysts, papillary thyroid carcinoma, pancreatic carcinoma, gastric cancer, duodenal cancer, hepatobiliary and CNS tumors), this is due to mutations in the gene (APC), which controls cell proliferation and the regulation of a new long non-coding RNA (lncRNA.

9. 7. Is there a relationship between GIST disease in her sister and Mrs. Wati's disease? Gastrointestinal Stromal Tumor (GIST) is a soft tissue sarcoma that grows in the digestive tract. The alimentary canal is a canal like a tube starting from the mouth, stomach, to the anus. As food passes through the digestive tract, nutrients are absorbed, and the remains are excreted.GIST usually occurs in the stomach or small intestine, but can develop anywhere along the digestive tract. It should be noted that not all GISTs are cancerous, GISTs can be benign and not grow to other areas or spread to other organs of the body.In GIST, genetic disorders are the main cause. A genetic change in one of several genes is involved in the formation of GIST. About 80 percent of cases are associated with mutations in the KIT gene, and about 10 percent of cases are associated with mutations in the PDGFRA gene.In addition there are several factors that are known to increase a person's risk of experiencing GIST, namely: Smoke Age 55 and over Male genderGenetics – While most GISTs are not inherited, in very rare cases, GISTs are found in several people in the same family. Having family members with the same history (GIST)Had surgery on the stomach

10. 8. What is the interpretation of the examination of the general condition and vital signs? ● general condition is weak → the patient looks weak ● severe malnutrition → patient looks very thin, low weight in comparison with age and tb ● blood pressure 100/60 mmHg → normal ● pulse 110x/minute → fast ● temperature 37°C → normal (afebric) 9. What causes Mrs. Wati's body to be limp and her weight to drop? stress worm infection diarrhea reduced food intake lots of physical activity certain drug side effects

11. Jump 4 : SCHEME

12. Jump 5 Learning Objective 1.Hepatobilier and pancreatic Neoplasma 2.Gastrointestinal Neoplasm 3.supporting investigation for abdominal neoplasm

13. JUMP 6 : SEARCHING INFORMATION JUMP 7 : SHARING INFORMATION

14. Hepatobilier and pancreatic Neoplasma

15. Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is a primary tumor of the liver. etiology virus hepatitis b,c non alcoholic fatty liver disease alcohol consumption epidemiology 5th most common neoplasma common in men developing country --> associate with hepatitis b,c western country --> associate with obese

16. physical sign of liver failure --> jaundice, pruritus, asites, palpable mass in abdomen intraperitoneal bleeding liver abcess evaluation biochemistry test --> alt, ast, albumin serum alpha fetoprotein test imaging usg ct

17. HEPATOBLASTOMA Pathology and causa: ▪ Common primary childhood hepatic malignancy; arises from primitive hepatic cells ▪ Usually occurs in right lobe of liver ▪ Morphologically diverse tumor: composed of many cell types including embryonal hepatocytes, tissues (e.g. bone, striated muscle) ▪ Extramedullary hematopoiesis may occur in sinusoids ▪ Usually present during fi rst two years of life sign and sypmtoms: ▪ Children ▫ Abdominal mass; discomfort ▪ Anorexia, weight loss, precocious puberty

18. PANCREATIC CANCER www.reallygreatsite.com pathology and causa Highly lethal malignancy of exocrine pancreas Usually unresectable at presentation RISK FACTORS ▪ Chronic pancreatitis ▪ Malignant transformation of pancreatic intraductal papillary mucinous neoplasm (IPMN) ▪ Genetic mutations (e.g. BRCA-1, BRCA-2, ATM, PALB2, CDKN2A, MLH1) ▪ Smoking; obesity; sedentary lifestyle COMPLICATIONS ▪ Hypercoagulability with possible venous/ arterial thromboembolism ▪ Paraneoplastic manifestations ▫ Bullous pemphigoid; nodular fat necrosis (pancreatic panniculitis) ▪ Metastasis

19. Recent onset of diabetes mellitus Clinical presentation ▫ Tumor location Pain ▫ Epigastric, abdominal, may radiate to the back, may worsen after eating/when lying down; asthenia: Physical weakness, loss of strength; anorexia, nausea; weight loss; jaundice, dark urine Hepatomegaly; right upper quadrant mass; Courvoisier’s sign (nontender, palpable gallbladder at right costal margin); cachexia; metastasis: left supraclavicular/periumbilical lymphadenopathy, ascites, abdominal mass

20. CHOLANGIOCARCINOMA Rare bile duct cancers; arise from epithelial cells of intrahepatic, extrahepatic bile ducts (not including gallbladder, ampulla of Vater) High fatality due to late diagnosis; highly proliferative Mostly adenocarcinomas; minority squamous cell carcinomas TYPES Determined by location (Bismuth–Corlette) Type I ▪ Located below confl uence of left, right hepatic ducts Type II ▪ Located at confl uence Type IIIa ▪ Occludes common hepatic duct Type IIIb ▪ Occludes right/left hepatic duct Type IV ▪ Multicentric

21. ▪ Primary ▫ Existing liver, gallbladder disease: primary sclerosing cholangitis (PSC); chronic liver disease (e.g. viral hepatitis, cirrhosis) ▪ Congenital abnormalities of biliary tree ▪ Genetic disorders ▫ Lynch syndrome; multiple biliary papillomatosis ▪ Obesity ▪ Liver fl uke infection (undercooked fi sh ) ▪ Intrahepatic cholangiocarcinomas ▫ Associated with mutations in gene encoding isocitrate dehydrogenase 1 Risk increases with age ▪ Slightly more common in individuals who are biologically male Risk Factor Often asymptomatic initially; malaise, weight loss, abdominal pain Extrahepatic disease (when bile drainage obstructed) ▫ Right upper quadrant pain, jaundice, pruritus, dark urine, clay-colored stools, weight loss Intrahepatic disease ▫ Dull right upper quadrant pain, malaise, weight loss Other fi ndings ▫ Hepatomegaly, palpated mass Sign and Symptoms

22. Uncommon malignancy; most frequently diagnosed cancer of biliary tract High fatality rate due to typically late diagnosis Most gallbladder cancers arise within fundus May obstruct bile fl ow at common bile duct/ duodenum GALLBLADDER CANCER Often asymptomatic in early stages; malignancy discovered incidentally after symptoms mimic benign gallbladder disease Non-specific symptoms ▫ Malaise, pain, anorexia, nausea, vomiting, weight loss Clinical manifestations (when bile drainage obstructed) ▫ Jaundice, dark urine Palpable gallbladder sign and symptoms

23. Gastrointestinal Neoplasm

24. ORAL CANCER Oral cavity malignancy; arises from mucosal surfaces ▫ Lips, buccal mucosa, anterior tongue, mouth fl oor, hard palate, gingiva, retromolar trigone ▫ Most often: squamous cell carcinoma May arise from normal mucosa/ premalignant lesions (e.g. erythroplakia, leukoplakia); undergo malignant transformation ▪ Tobacco (esp. with alcohol) ▪ Alcohol ▪ Human papillomavirus (HPV) infection: oropharynx ▪ Periodontal disease ▪ Chronic oral candidiasis ▪ Betel quid chewing ▪ Immunosuppression ▪ Hepatitis C infection Risk Factors

25. Sign and symptoms ▪ Asymptomatic initially ▪ Pain/burning sensation ▪ Lump/ulcer visualized, palpated ▪ Hard, fi xed lymph nodes

26. STOMACH (GASTRIC) CANCER Aggressive adenocarcinoma arising from gastric mucosa Risk Factors ▪ Primary cause (G-INT) ▫ H. pylori infection ▪ Family history of gastric cancer ▪ Autoimmune atrophic gastritis ▪ Lifestyle ▫ Smoking, alcohol consumption ▪ Diet ▫ Nitrates, nitrosamines, highly-salted foods; pickled/smoked foods ▪ Obesity ▪ Risk increases with age ▪ More common in individuals who are biologically male ▪ Protective factors ▫ Intake of fruit, vegetables, fiber, folate

27. Sign and symptoms ▪ Asymptomatic initially ▪ Early symptoms ▫ Vague constitutional symptoms (e.g. malaise, loss of appetite, dyspepsia) ▪ With disease progression ▫ Epigastric pain, nausea, vomiting, dysphagia, weight loss ▪ If GI bleeding ▫ Anemia, melena, coffee-ground hematemesis ▪ Pseudoachalasia syndrome (diffi culty moving food, liquids from esophagus to stomach) ▫ If tumor extends to Auerbach’s plexus/obstruction occurs near gastroesophageal junction

28. COLORECTAL CANCER ▪ Common malignancy of large bowel/rectum ▪ Third most common cancer worldwide ▪ Often arises from colonic epithelial tissue → adenomatous polyp formation → adenocarcinoma ▪ High metastatic potential after penetrating muscularis mucosa ▪ Hereditary ▫ Familial adenomatous polyposis; Lynch syndrome, MUTYH-associated polyposis ▪ Inflammatory bowel disease ▪ Lifestyle ▫ Smoking, physical inactivity ▪ Dietary ▫ High alcohol consumption; processed red meat; low consumption of fruits, vegetables ▪ Obesity ▪ Diabetes mellitus, insulin resistance ▪ Low socioeconomic status ▪ History of abdominal radiation ▪ Lack of screening colonoscopy Risk factor

29. sign and symptoms ▪ May be asymptomatic initially ▪ Vague constitutional symptoms ▫ Fatigue, anorexia, weight loss ▪ Change in bowel habits ▫ Narrowing of stool, constipation, diarrhea ▪ Rectal bleeding ▫ Frank/occult ▪ Rectal pain, tenesmus (feeling of incomplete defecation) ▪ Nausea, vomiting ▫ Bowel obstruction from advanced malignancy

30. ESOPHAGEAL CANCER Rare malignancy of esophageal epithelium Squamous cell carcinoma (most common)/ adenocarcinoma Commonly diagnosed when disease advanced Tendency for rapid metastasis Chronic exposure to irritants → metaplasia → dysplasia → malignant transformation RISK FACTORS ▪ Smoking ▪ Alcohol (esp. combined with smoking) ▪ Gastroesophageal refl ux disease (GERD); reflux esophagitis, Barrett esophagus ▪ Hiatal hernia ▪ More common in individuals who are biologically male ▪ Risk increases with age SIGN AND SYMPTOMS ▪ Asymptomatic initially; dysphagia; pyrosis; retrosternal pain; weight loss ▪ Late symptoms ▫ Coughing, chest discomfort when swallowing; hiccups if spread to diaphragm

31. GIST (gastrointestinal stromal tumor) is a tumor of the elements mesenchymal most frequently found in the gastrointestinal tract. GIST case in the small intestine about 30%. Diagnosis of GIST in the small intestine is based on history, physical examination, supporting examination and definite diagnosis with histopathological examination. Immunohistochemical examination requires for GIST in the small intestine is often found in adults over the age of 50 year. The clinical features of GIST in the small intestine are similar to those in stomach, namely the presence of masses and pain in the abdomen, nausea, vomiting, hematemesis and melena.

32. Juvenile polyposis syndrome (JPS) is a hereditary condition that is characterized by the presence of hamartomatous polyps in the digestive tract. Hamartomas are noncancerous (benign) masses of normal tissue that build up in the intestines or other places. These masses are called polyps if they develop inside a body structure, such as the stomach or intestines. The term “juvenile polyposis” refers to the type of polyp (juvenile polyp) that is found after examination of the polyp under a microscope, not the age at which people are diagnosed with JPS. JPS is suspected when a person’s symptoms and family history fit any of the following categories: More than 5 juvenile polyps of the colon and/or rectum Multiple juvenile polyps throughout the digestive tract Any number of juvenile polyps and a family history of juvenile polyps

33. supporting investigation for abdominal neoplasm

34. Tumor grading T1 means the tumour has started to grow into the wall of the stomach. It’s divided into T1a and T1b: T1a means the tumour is within the inner layers of the stomach (the mucosa) T1b means the tumour has grown through the mucosa and into a layer of supportive tissue called the submucosa T2 means the tumour has grown into the muscle layer of the stomach T3 means the tumour has grown into the outer lining of the stomach T4 means that the tumour has grown through the outer lining of the stomach. It’s divided into T4a and T4b: T4a means the tumour has broken through the outer lining of the stomach wall T4b means the tumour has grown through the stomach wall and into other organs or body structures nearby such as the liver, food pipe (oesophagus) or abdominal wall

35. There are 4 possible stages describing whether cancer cells are in the lymph nodes – N0, N1, N2 and N3: N0 means there are no lymph nodes containing cancer cells. N1 means there are cancer cells in 1 to 2 lymph nodes near to the stomach. N2 means there are cancer cells in 3 to 6 nearby lymph nodes. N3 is split into N3a and N3b: N3a means there are cancer cells in 7 to 15 nearby lymph nodes N3b means there are cancer cells in 16 or more nearby lymph nodes Metastasis (M) Metastasis describes whether the cancer has spread to a different part of the body. There are 2 stages of metastasis: • M0 means the cancer has not spread to other organs • M1 means the cancer has spread to other parts of the body

36. Chest X-ray showing irregular soft tissue opacity in proximal part of stomach

37. Tumor Marker

38. Tumor forms solid area without portal tracts (right). The tumor cells show ample eosinophilic cytoplasm and small round nuclei with frequent prominent nucleoli (left).in hepatocellular carcinoma Histopathological

39. Common histological patterns of gastrointestinal stromal tumour (GIST). a, Typical spindle cell pattern. b, Schwannoma-like gastric GIST. c, Epithelioid gastric GIST. d, Small bowel GIST with high mitotic rate.

40. looks inside the stomach with a thin, lighted tube called an endoscope. and it will be guiding through the throat and down into the stomach. the patient is sedated during this test Endoscopy Laparoscopy is a type of surgical procedure that allows a surgeon to access the inside of the abdomen (tummy) and pelvis without having to make large incisions in the skin.This is a small tube that has a light source and a camera, which relays images of the inside of the abdomen or pelvis to a television monitor.

41. The ERCP procedure is performed using an endoscope, where a thin tube equipped with a camera will be inserted through the patient's mouth. This tool will later pass through the patient's digestive tract from the esophagus to the end of the bile duct and pancreas.By using a contrast dye, ERCP combines an endoscope examination and an X-ray examination to take detailed pictures and examine the condition of the patient's bile ducts and pancreas.

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