gastric carcinoma

1. DR. Mohammad Masoom Parwez
PG Student, AIIMS Bhopal
Moderator: DR. M. P. Singh

2.  4th most common cancer type
 2nd leading cause of cancer death worldwide
 Elderly population
 Twice as common in blacks
 Younger patients– large, aggressive and poorly differentiated
 Highest incidence in low socioeconomic status with poor hygiene

6.  More common in patients with pernicious anemia, Blood group A, positive family
history
 Risk decreases on migration from high incidence to low incidence region–
Environmental factor-- more in intestinal form
Diet and Drugs:
 pickled, salted and smoked food
 gastric bacteria converts nitrate into nitrite – potent carcinogen
 Fresh fruits, vegetables, Vit C & E – protective
 Refrigeration of food – dramatic decrease in gastric ca
 Tobacco use: more risk; Alcohol: no effect; aspirin: protective

7. Helicobacter pylori:
 Chronic H. pylori: 3 fold risk
 h/o gastric ulcer more likely to develop CA (incidence ratio: 1.8)
 Duodenal ulcers less risk (incidence ratio: 0.6)
 Bone marrow derived stem cells – key role in pathogenesis of gastric adenoCA
with chronic H. pylori infection
Ebstein-barr virus:
 10% of adenoCA carry EBV virus
 Late step in gastric carcinogenesis – present in cancer cells but absent in
metaplastic cells

9. Genetic factors:
 Most common abnormality in
sporadic variety: p53 and COX-2
genes
 2/3rd of gasric CA –
deletion/suppression of p53 and
overexpression of COX-2
 Germline mutation in CDH1 gene
encoding E-cadherin a/w
hereditary diffuse gastric CA –
prophylactic total gastrectomy

11.  Most common : atrophic gastritis
 Chronic inflammation – both
genetic and epigenetic changes in
mucosal cells

12. POLYPS:
 Benign polyps – neoplastic: (Adenoma, fundic gland polyp)
non-neoplastic: (hyperplastic, inflammatory, hamartomatous)
 Gastric adenomas are premalignant
 Large hyperplastic polyps (>2cm) – may harbour dysplasia / CA in situ
 Patients with FAP have 50% prevalence of adenomatous polyps and 10 times more
chance of developing carcinoma
 Screening EGD – IOC
 Patients with HNPCC – at risk (10%) – intestinal type
 Menetrier’s disease: 5-10% risk

13. Atrophic gastritis:
 Chronic atrophic gastritis – m/c precursor in intestinal
subtype
 Prevalence higher in old age groups
 H. pylori – key role in pathogenesis of atrophic gastritis
Patterns of chronic atrophic gastritis:
 Autoimmune – involves acid secreting proximal
stomach
 Hypersecretory – involves distal stomach
 Environmental – multiple areas @ junction of oxyntic
and antral mucosa

14. Intestinal metaplasia:
 Risk of gasric CA directly proportional
to extent of intestinal metaplasia
 Complete type: glands lined with goblet
cells and intestinal absorptive cells
 Eradication of H. pylori – significant
regression of metaplasia and
improvement in gastritis

16. Benign gastric ulcer:
 All gastric ulcers to be considered malignant unless proven otherwise with
adequate biopsy and follow-up
Gastric remnant ulcer:
 Following subtotal gastrectomy – bile/alkali reflux gastritis near anastomosis
(precursor) following Billroth II
 Most tumors develop 10years post surgery
 Roux en Y anastomosis: seems protective but unproven

17. Other premalignant states:
 Mutations in E-cadherin gene CDH1--- hereditary diffuse gastric cancer (HDGC)
 HDGC – autosomal dominant with high degree of penetrance
 CDH1– tumor suppressor gene; 2nd somatic hit required for tumorigenesis
 Median age at diagnosis: 38 years
 Grave prognosis
 Prophylactic or early total gastrectomy
 Multifocal intramucosal CA– frequent intra-op finding
 Females with CDH1 mutation– increased risk of lobular CA

19. Dysplasia:
 Universal precursor to gastric adenoCA
 Severe dysplasia– considered for gastric resection if widespread/multifocal or
EMR if localized
 Mild dysplasia– followed up with endoscopic biopsy, surveillance and H. pylori
eradication

20.  Early Gastric cancer:
 Limited to mucosa (T1a) and submucosa (T1b)
 Common in Asians
 10% have lymph nodal metastases
 Subtypes (figure)
 70% are well differentiated
 Overall cure rate with adequate gastric resection and lymphadenectomy: 95%
 Selected patients can be treated with Endoscopic mucosal resection

23. Four morphological subtypes:
 Polypoid – not ulcerated
 Fungating – predominantly intraluminal with ulceration
 Ulcerative
 Scirrhous – infiltrate the entire thickness of stomach, poor prognosis
 Location of primary tumor is essential for planning resection
 Recently, proximal migration of tumor (40% distal, 30% middle, 30% proximal)

25. Prognostic indicators in gastric CA:
 Lymph node involvement
 Depth of tumor invasion
 Tumor grade
Several classification:
 WHO classification
 Lauren classification
 Ming classification

27. Lauren Classification:
 Intestinal type (53%) – a/w chronic atrophic gastritis/ metaplasia and dysplasia;
less aggressive than diffuse type
 Diffuse type (33%) – poor differentiation; younger patients and proximal tumors
 Unclassified (14%)
 Ming Classification:
 Expanding type (67%)
 Infiltrative (33%)

29.  Recently, HER 2 overexpression has been reported in 13-30% patients
 Targeting with Trastuzumab has improved the survival in patients with stage IV
gastric cancer
 Expression of other growth receptors lik HER 1 and HER 3
 HER 3 has poor prognosis

35.  Most common symptoms:
 Weight loss and decreased food intake – due to anorexia and early satiety
 Abdominal pain
 Nausea
 Vomiting
 Bloating
 Acute GI bleed (5%)
 Dysphagia (tumor involves cardia)
 Paraneoplastic syndromes – trousseau syndrome, acanthosis nigricans, peripheral
neuropathy (rare)

36.  Physical examination – typically normal’
 Examination of neck, chest, abdomen, rectum – must
 Clavicular, Supra clavicular (Virchow), axillary LN may be enlarged – FNAC
 Malignant pleural effusions, Ascites, or aspiration pneumonitis
 Abdominal mass may be a large T4 tumor, liver mets, or carcinomatosis
(Krukenberg)
 palpable umbilical nodule (Sister mary joseph) – pathognomonic (advanced
disease)
 Rectal exam: heme positive stool/ hard nodularity extraluminally and anteriorly
(rectal shelf of Blumer in POD)

38.  Age > 55yrs, new onset dyspepsia, weight loss, recurrent vomiting, dysphagia, GI
bleed or anemia, positive family history
 Prompt UGI endoscopy and biopsy for mucosal lesions
 High suspicion and biopsy negative – re-Endoscopy and more aggressive biopsy
 Double contrast Barium UGI examination -- very sensitive (75%)
 Endoscopy – Gold Standard
 Magnifying Endoscopy with narrow band imaging (NBI) – can observe
microvascular architecture of mucosa & micro-surface pattern of lesion

39.  Preoperative staging with abdomino-pelvic CT with IV and oral contrast
 MRI – comparable
 Best way for local staging: EUS (80% accuracy) – depth of invasion in gastric wall
and enlarged (>5mm) perigastric and celiac LN
 Most accurate in distinguishing early Gastric CA from more advanced
malignancies
 Limitations of EUS: operator dependent, underestimate LN (<5mm)
 Whole body FDG PET – evaluation of distant mets and in locoregional staging
 More accurate when combined with SPIRAL CT

41.  Staging Laparoscopy and Peritoneal Cytology – valuable adjunct
 Rapid identification of Macroscopic peritoneal metastases.
 Peritoneal Lavage identifies subsets with microscopic dissemination
 Gastrectomy can be deferred in such cases
 Standalone Laparoscopy may influence management in 36% of cases

44.  Surgical Resection – potentially curative treatment
 Goal: R0 resection with adequate lymphadenectomy
 Surgeon strives for grossly negative margin of atleast 5 cm
 Complete resection for diffuse tumor – frozen sections guided wider gross margins
to be resected
 Frozen section should rule out microscopic infiltration of serosa - indicate
incurable disseminated disease
 In such case, additional proximal and distal resection followed by complex
anastomosis/ stump closure provides no additional benefit

45.  More than 15 lymph nodes required for adequate staging
 Primary tumor should be resected en bloc with adjacent involved organs during
curative gastrectomy
 Stage IV gastric cancers are managed without major operation, surgery reserved
for palliation only (obstruction/GI bleed/perforation)

46.  Radical Subtotal Gastrectomy – Standard of care
 Unless for R0 resection, total gastrectomy offers no added survival benefit and
adversely affect nutrition and quality of life with high postop morbidity and
mortality
Subtotal Gastric resection:
 Ligation of left and right gastric arteries and gastroepiploic arteries at their origin
 En bloc removal of distal 2/3 of the stomach including pylorus and 2cm of
duodenum and all associated lymphatic tissue

48.  Reconstruction – Billroth II GJ or Roux en Y GJ
 Former a/w shorter operative time and precludes roux limb stasis
 Latter mitigates bile reflux and a/w better quality of life long term
 Japanese frequently perform Billroth I (gastroduodenostomy)
 In U.S. Roux en Y reconstruction preferred over Billroth II or I
 For R0 resection: Total Gastrectomy with Roux en Y esophagojejunostomy is
frequently the optimal surgery for proximal gastric CA

52.  Lymph node stations 1-12 are classified as regional
 Metastasis to any other lymph nodes – considered M1 metastasis
 D1 resection includes removal of primary tumor with perigastric nodes (1-7)
 D2 includes stations 8a, 9, 11p and 12a with superior peritoneum overlying the
mesocolon
 Long term follow up from Dutch Lymphadenectomy trial – disease specific
survival advantage with D2 dissection

54. D2 gastrectomy

55.  5 Year Survival rate for resected gastric adenoCA in US for stages I, II, and III are
75%, 50%, and 25% respectively
 Stage II or greater disease : adjuvant therapy is indicated
 Several studies in Japan and Korea indicate survival advantage with adjuvant
chemotherapy after D2 gastrectomy
 Intergroup trial, US, incorporates both chemotherapy and radiation as adjuvant
approach
 CT (5FU and leucovorin) and radiation (4500 cGy) – survival benefit in stage II
and III adenoCA.

56.  Neoadjuvant CT advantage: more consistent completion of multimodality therapy,
downstaging, earlier treatment of micrometastatic disease
 MAGIC trial (RCT) compared perioperative epirubicin, cisplatin and 5FU to
surgery alone and demonstrated a survival benefit in patients with at least stage
II disease (36.3% vs 23%)
 Recent Asian trials suggest potential benefit of adjuvant CT after D2 resection in
patients with advanced gastric CA
 Japan Clinical Oncology Group study showed 69% overall 5 year survival rate in
patients with clinically curable T2b, T3 and T4 gastric CA, treated with D2
gastrectomy alone
 CLASSIC Trial from Korea demonstrated overall survival advantage with
adjuvant Capecitabine + Oxaliplatin after D2 resection compared to Sx alone (83%
vs 78%) at 3 yr follow up

57.  Systemic CT – significant survival benefit over best supportive care in
metastatic/recurrent gastric CA.
 Agents like: 5FU, Cisplatin, Doxorubicin, Methotrexate, Taxanes and
Camptothecin
 Targeted molecular agents like Trastuzumab increases the effectiveness of
cytotoxic CT in patients with HER2 over-expressing CA
 Trastuzumab – Humanized molecular antibody against extracellular domain of
HER 2

58.  Early gastric CA – relatively infrequent dissemination to regional nodes
 Can be treated adequately by EMR
EMR is standard of care for:
 Well differentiated gastric CA confined to mucosa (T1a)
 Size <2cm
 Without signs of ulceration
 En-bloc resection is required for margin evaluation

60.  ESD allows en bloc resection of larger tumors (<3cm) at experienced centres
 If pathological specimen does not demonstrate ulceration, penetration of
muscularis mucosae or lymphatic invasion,
 Risk of LN metatstases is less than 1%

62.  In japan, screening programmes have significantly decreased risk of death from
gastric CA
 Screening is effective in high risk population – periodic endoscopy and biopsy
High risk include patients with:
 FAP
 HNPCC
 Gastric adenomas
 Menetrier’s disease
 Intestinal metaplasia / dysplasia’
 Previous gastrectomy or gastrojejunostomy

63.  Recurrence post gastrectomy ranges from 40-80%
 Most occur within first 3 years
 Locoregional failure rate 38-45%
 Peritoneal dissemination in 54% of patients
 M/C site of locoregional recurrence: anastomotic site in the gastric bed and in
regional nodes
 Hematogenous spread to liver, lung and bones

64.  Follow up should include complete history and physical examination
 Every 4 months for 1 year, every 6 months for 2 years and annually thereafter
 Lab tests CBCs, LFTs as clinically indicated
 Annual endoscopy for subtotal gastrectomy
 Chest Xrays and CT abdomen/pelvis – when clinically suspicious

66.  Early (within 20-30 mins of meal) – more common
 Late (2-3 hrs after meal)
 Early dumping syndrome:
 More of GI symptoms, less CVS effects
 GI symptoms like: nausea and vomiting, epigastric fullness, cramping abdominal
pain, often explosive diarrhea
 CVS symptoms: palpitations, tachycardia, diaphoresis, fainting, dizziness,
flushing, and blurred vision
 More common after partial gastrectomy with Billroth II reconstruction

67. Cause:
 Rapid passage of high osmolar food in the small intestine
 inducing shift of extracellular fluid into the lumen
 Rise in intraluminal pressure
 Induces the autonomic responses

68.  Late dumping syndrome:
 High carbohydrate diet delivered rapidly into proximal intestine
 Quick absorption – transient hyperglycemia
 Triggers large amount of insulin release (over-compensation)
 Profound hypoglycaemia – release of catecholamines – CVS symptoms

69.  Dietary measures: avoid high
carbohydrate food, frequent
small meals rich in proteins
and fats, separating liquids
from solids during a meal
 Non-responders, long term
octreotide agonists are
preferred– inhibit gastric
emptying and also affects
small bowel motility

70. Anemia:
 IDA (more common) or impairment in B12 metabolism
 IDA in 30% of patients post gastrectomy
 Cause: decreased intake, impaired absorption, chronic blood loss
 Addition of iron supplements to diet correct the problem
 Megaloblastic anemia is dependent upon amount of stomach removed
 Cause: poor absorption due to lack of intrinsic factor
 Long term / life long vit B12 therapy given

71.  Bone disease:
 Osteoporosis and osteomalacia -- Ca deficiency
 Fat malabsorption aggravates hypoCa – fatty acids bind Ca
 Incidence increases with extent of resection and a/w Billroth II
 Develops 4-5 years post Sx
 Treatment: Ca supplements (1-2g/day) with Vit D (500-5000U daily)
 Patients with Billroth II / Roux en Y should also receive fat soluble vitamins (A, D,
E, K)

72.  Due to partial obstruction of the afferent limb – pancreatic secretions accumulate
– distention – epigastric discomfort and cramping
 Eventually due to raised intraluminal pressure, contents are forcefully emptied
into the stomach – bilious vomiting – offers immediate relief
 Sometimes, bacterial overgrowth occurs in the loop due to stasis for a long time –
bacteria binds with Vit B12 and bile acids – def. of B12 – megaloblastic anemia
 Chronic aff loop obstruction – failure to visualise the loop on UGI endoscopy
 Also failure of the radionuclide imaging the hepatobiliary tree to enter the loop –
suggests obstruction
 Sx correction: Billroth II conversion to I, enteroenterostomy below the stoma or
Roux en Y creation

73.  Rare
 Making a diagnosis is difficult
 Presents with LUQ pain which is colicky in nature, bilious vomiting and
abdominal distention
 Diagnosis estb with UGI barium study – failure to enter the efferent limb
 M/M: operative intervention

74.  Reflux of bile is very common
 a/w severe epigastric abdominal pain accompanied by bilious vomiting and weight
loss
 HIDA scans demonstrate biliary secretions into stomach and esophagus
 UGI endoscopy – friable, beefy red mucosa
 Medical therapies have not shown any consistent benefit
 Procedure of choice : conversion of billroth II into Roux en Y GJ, roux limb > 40cm

75.  Schwartz Principles of Surgery, 11th edition
 Sabiston Textbook of Surgery, 20th edition
 Bailey and love’s Short Practice of Surgery, 27th edition
 Maingot’s Abdominal Operations,13th edition
 AJCC cancer staging manual 8th edition
 Internet