1 Dr Amit Gupta Associate Professor Dept Of SurgeryCarcinoma Stomach Liver tumours Portal hypertension Chronic liver disease Dr Amit Gupta Associate Professor Dept Of Surgery

2 Carcinoma Stomach

3 Introduction Gastric cancer is endemic in JapanLate stage at diagnosis because of Low incidence Non specific symptoms Risk factors not definable Biologically more aggressive Increasing incidence of adenocarcinomas of proximal stomach and distal esophagus

4 Etiology Low acid production H pylori infection Low acid productionBody of stomach Esophagus & Cardia Low acid production Reflux

5 Obesity High BMI High glycaemic load diet GERD Smoking Alcohol Tobacco

6 Genetic abnormalities

7 Majority: AdenocarcinomaIntestinal type precancerous lesions men >women older people body/antrum Associated with H pylori infection Dominant in endemic regions Diffuse type low-incidence regions women and in younger patients familial occurrence (A Blood group) Anywhere in stomach No clear link to H. pylori infection CDH1 mutation (small %) Early metastases

8 Pathology Adenocarcinomas (95%) Squamous cell carcinoma AdenoacanthomaCarcinoid tumors Small cell carcinoma Mucinous carcinoma Hepatoid adenocarcinoma Oncocytic (parietal gland) carcinoma Sarcomatoid carcinoma Lymphoepithelioma -like carcinoma Adenocarcinoma with rhabdoid features Gastric carcinoma with osteoclast like giant cells Leiomyosarcoma

9 Although no normal lymphoid tissue is found in the gastric mucosa, the stomach is the most common site for lymphomas of the gastrointestinal tract

10 Borrmann classification(depending on macroscopic appearance)Type I: polypoid or fungating cancers Type II: ulcerating lesions surrounded by elevated borders Type III: ulcerated lesions infiltrating the gastric wall Type IV: diffusely infiltrating tumors Type V: unclassifiable cancers

11

12 Patterns of Spread Local extension Lymphatic metastasesleft supraclavicular fossa (Virchow’s node) left axilla (Irish’s node) S/c periumbilical tumour deposits (Sister Mary Joseph’s nodes) Peritoneal metastases Distant metastases

13 Clinical PresentationWeight Loss Anorexia Early satiety (Diffusely infiltrative type) Recurrent Vomiting (pyloric involvement ) Dysphagia Bleeding Anemia Fatigue Epigastric pain

14 Ascites, jaundice, or palpable mass indicates incurable diseaseTransverse colon is a potential site of malignant fistulization and obstruction from gastric primary tumor Diffuse peritoneal spread of disease frequently produces other sites of intestinal obstruction Large ovarian mass ( krukenberg’s tumor) Large peritoneal implant in the pelvis ( blumer’s shelf)

15 Staging (AJCC 7th Edition)

16 Japanese Staging SystemEmphasis on distinction between clinical, surgical, pathologic, and “final” staging (prefixes “c,” “s,” “p,” and “f,” respectively) Classifies 18 lymph node regions into four N categories (N0 to N3) perigastric lymph nodes (nodal stations 1 through 6) are considered group N1. Lymph nodes situated along the proximal left gastric artery (station 7), common hepatic artery (8), celiac axis (9), splenic artery (11), and proper hepatic artery (12) are defined as group N2. Para-aortic lymph nodes (16) are defined as group N3

17 Macroscopic description of the tumorExtent of peritoneal metastases (P0-1) Extent of hepatic metastases (H0-1) Peritoneal cytology findings

18 Resection ClassificationR0: no gross or microscopic residual disease R1: microscopic residual disease (+ margins) R2: gross residual disease

19 Diagnostic work up Tumour Markers: CA 19.9,CA 72.4, CEA, CA 50Endoscopy & Biopsy: Chromo endoscopy: identification of mucosal abnormalities through topical stains. Magnification Endoscopy: magnify standard endoscopic fields by 1.5- to 150-fold. Narrow band imaging: increased visualization of the microvasculature Confocal laser Endomicroscopy : 3D microscopy including subsurface structures

20 Overexpression or amplification of HER2 (EGFR2):occurs in approximately 20% of patients with gastric cancer Recommended in metastatic, recurrent gastric cancer Trastuzumab used in Her 2 neu + cancers

21 Endoscopic ultrasound (EUS) Computed Tomography Magnetic Resonance Imaging: to characterize liver lesions on CT scan Positron Emission Tomography: 50% of primary tumors are FDG-negative diffuse (signet cell) subtype most likely to be non-FDG avid

22 Staging Laparoscopy and Peritoneal Cytology:directly inspects the peritoneal and visceral surfaces done to spare nontherapeutic operations

23 Treatment Surgery (Gastrectomy with lymph node dissection) `Radical Gastrectomy (Proximal gastric cancer) Subtotal Gastrectomy (mid & distal gastric cancer) When the oncologic goal of an R0 resection can be achieved by a gastric-preserving approach, partial gastrectomy is preferred over total gastrectomy

24 A: Subtotal gastrectomy with a Billroth II anastomosisB: Total gastrectomy with a Roux-en-Y anastomosis

25 Lymphadenectomy 15 nodes for adequate pathologic stagingPartial Pancreatectomy and Splenectomy—Resect or Preserve? Splenectomy: Intraoperative evidence of direct tumor extension into the spleen Primary tumor is located in the proximal stomach along the greater curvature Partial Pancreatectomy: direct tumor extension into the pancreas

26 Stage specific Survival rates for gastric adenocarcinoma are higher in Japan than in Western countries because: Better-prognosis intestinal-type tumors are more common Poorer-prognosis proximal gastric cancers are less frequent Widespread use of extensive D2 or D3 lymphadenectomy

27 Chemotherapy Adjuvant Neoadjuvant: PeriperativeHigher rate of R0 resections Early treatment of micro metastatic disease Periperative

28 Adjuvant Intraperitoneal ChemotherapyHyperthermic intraoperative peritoneal chemotherapy (HIPEC) Normothermic intraoperative chemotherapy (NIIC) Early postoperative intraperitoneal chemotherapy (EPIC) Delayed postoperative intraperitoneal chemotherapy (DPIC)

29 Chemotherapy Drugs Cisplatin 5-Fluorouracil Taxanes EpirubicinIrinotecan Trastuzumab (targeted therapy in Her 2 neu + )

30 Radiotherapy Preoperative Intraoperative Postoperative

31 Liver Tumours

32 Benign tumours Focal Nodular hyperplasia HemangiomaLiver Cell Adenoma Focal Nodular hyperplasia Hemangioma Mesenchymal hamartomas

33 Liver Cell Adenoma benign proliferation of hepatocytesyoung women (aged years) associated with use of oral contraceptive pills (OCPs) usually singular Upper abdominal pain tumor markers are normal MRI scans of LCA have specific imaging characteristics two major risks are rupture & malignant transformation Hepatic artery embolization Resection of the mass

34 Focal nodular hyperplasiaSecond most common benign tumor young women small (<5 cm) nodular mass involves the right and left liver equally Related to developmental vascular malformation Nonspecific symptoms Contrast-enhanced CT and MRI scan Symptomatic pts: resection

35 Hemangioma Most common benign tumor of the liverWomen more common than men (3:1 ratio) Mean age of about 45 years Occur equally in the right and left liver Usually single Lesions > 5 cm are arbitrarily called giant hemangiomas Tumor markers are usually normal CT and MRI scan Resection: enucleation with inflow control

36 Hepatocellular carcinoma

37 Introduction Fifth most common malignancy worldwideMale-to-female ratio 2.4:1 Poor prognosis

38 Etiology Infections with hepatitis B and C viruses Ethanol abuseObesity Type 2 diabetes Non-alcoholic fatty liver disease Aflatoxin B1

39 Pathology Malignant epithelial neoplasms: 85% to 95% Benign: 6 %to 12%Malignant mesenchymal tumors: 1% to 3% Metastatic tumors

40 Tumors metastatic to the liver are:Peripheral Multiple Cause umbilication of surface of the liver Primary liver tumors are: Central Solitary Exophytic

41 HCC spreads most commonly toLymph nodes around the liver Peritoneal cavity Lung Characteristic feature of HCC is invasion of the portal vein

42 Staging

43 Clinical Features Symptoms Signs Abdominal pain Weight loss WeaknessFullness Anorexia Abdominal swelling Jaundice Vomiting Signs Hepatomegaly Hepatic bruit Ascites Splenomegaly Jaundice Wasting Fever Virchow-Troisier nodes Cutaneous metastases (red-blue nodules)

44 Paraneoplastic SyndromesHypoglycemia Erythrocytosis Hypercalcemia Hypercholesterolemia Dysfibrinogenemia Carcinoid syndrome Increased thyroxin-binding globulin Sexual changes (gynecomastia, testicular atrophy, and precocious puberty) Porphyria cutanea tarda

45 Diagnostic work up Liver function tests S. Alpha feto protein (70%)S.Des-γ-carboxy prothrombin protein (80%) Four-phase CT scan: unenhanced, arterial, venous, and delayed phases MR imaging Characteristic feature of HCC: rapid enhancement during the arterial phase of contrast administration and “washout” during the later portal venous and delayed phases

46 Portal venous phase of triphasic computed tomography scan

47 PET CT Scan: not recommendedCore biopsy: hallmark feature of HCC is stromal invasion

48 CHILD PUGH score for assessment of hepatic reserve

49 Quantitative assessment of hepatic reserveIndocyanine green clearance test Retention rate <10%: all resections are possible 10% to 20%: bisegmentectomy is well tolerated 20% to 29%: single segment can be excised ≥30% or more: risk of liver failure is high

50 Management Stage I and II HCC Surgical resectionLocal ablation (radiofrequency ablation) Local injection therapies (ethanol injection): maximum size of tumor reliably treated is 3 cm Transplantation Child-Pugh A: Resection Child-Pugh B and C patients with stage I HCC tumors : transplant, if appropriate

51 Adjuvant Therapy Trans arterial chemotherapy (TACE)Systemic chemotherapy Lipiodol Doxorubicin Mitomycin Cisplatin

52 Stage III and IV Tumors Systemic Therapy TACE Regional ChemotherapyExternal Radiotherapy (< 8 cm) Hepatic Arterial Radioisotopes yttrium-90 (90Y) 131 I antiferritin

53 Portal Hypertension

54 Anatomy

55 The normal portal pressure is 5-7 mmHg (8-12 cm of water).Portal hypertension is present when the portal vein pressure exceeds 12 mmHg

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58 Sequelae & Clinical picturePorto-systemic collaterals Splenomegaly Congestion of the whole GIT Bleeding varices Ascites

59 Intra-abdominal venous flow pathways leading to engorged veins (varices) from portal hypertension

60 Screening Tests for Portal Hypertension

61 Ultrasound with doppler blood flow assessment.MRI venogram Contrast-enhanced helical CT scan

63 Management Management of patients with actively bleeding oesophageal varices Resuscitation Correct coagulopathy Prevent encephalopathy Sclerotherapy Endoscopic Banding Drugs: Vasopressin,Somatostatin Balloon tamponade

64 Trans-juguJar Intra-hepatic Porto-Systemic Shunt(TIPSS )

65 Shunt operations Liver Transplant Portocaval shuntProximal spleno-renal shunt Mesocaval (Drapanas) shunt Selective shunt (Warren shunt) Liver Transplant

66 Chronic Liver Disease

67 glycogenolysis & gluconeogenesisCatabolism of hormones and other serum proteins Glucose homeostasis; glycogenolysis & gluconeogenesis Chronic Liver Disease Synthesis: Albumin Coagulation factors Storage: Glycogen Iron Cu, Iron, vitamins Bile excretion

68 Signs of CLD Chronic Liver Disease

69 Investigations Bedside Observations, BM, fluid balance, weightBlood tests LFTs (pre/post) (including albumin), INR FBC, U&Es, CRP Liver screen: autoantibodies, alpha-1 antitrypsin, caeruloplasmin, serum copper, ferritin, viral hepatitis serology Imaging US abdomen + portal vein doppler CXR, CT, MRI, MRCP Special tests Ascitic tap, OGD (oesophageal varices), liver biopsy

70 What is your management plan?Conservative Alcohol abstinence, optimise nutrition, low salt diet, fluid restriction Medical Vitamin B supplementation (IV/PO), chlordiazepoxide Diuretics Paracentesis (give albumin) NG feeding Antibiotics (? SBP) Steroids + albumin (N.B. avoid NaCl) Lactulose (in hepatic encephalopathy) Surgical TIPSS Liver transplantation

71 Complications of CLD Portal hypertension: oesophageal varices, ascitesSBP Hepatic encephalopathy (constipation, GI bleed, infection, renal failure) Hepatocellular carcinoma Coagulopathy Hepato-renal syndrome Liver failure 5 year survival rate in cirrhotic CLD 50% Child Pugh Score: bilirubin, INR, albumin, ascites, hepatic encephalopathy