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Gastric Cancer

Gastric Cancer Overview

  • Worldwide Statistics:
    • Fourth most common cancer globally.
    • Second most common cause of cancer death.
  • Survival Rates:
    • Overall 5-year survival: 23%.
    • For disseminated disease: 5%.
  • Types:
    • 90-95% of gastric cancers are adenocarcinomas.

Genetic Factors (10% of Gastric Cancers)

  1. Hereditary Gastric Cancer Syndrome:
    • E-Cadherin mutation → 80% risk of gastric cancer.
    • Recommendation: Prophylactic total gastrectomy between 18-40 years.
  2. Peutz-Jeghers Syndrome
  3. Familial Adenomatous Polyposis (FAP)
  4. Li-Fraumeni Syndrome (p53 mutation)
  5. BRCA2 mutation
  6. Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Genetic Alterations in Sporadic Carcinomas

  1. Overexpression of Proto-Oncogenes:
    • c-met, k-sam, c-Erb2
  2. Inactivation of Tumor Suppressor Genes:
    • p53 and p16 in both diffuse and intestinal types.
    • FAP gene inactivation in intestinal type.
  3. E-Cadherin Mutation:
    • Present in 50% of diffuse type.
  4. Microsatellite Instability (MSI):
    • Seen in 20-30% of intestinal type.

MCQ: Genetic Alteration in Intestinal Type Gastric Cancer

Question:

Which of the following genetic alterations is not present in intestinal type gastric cancer?

  1. p53
  2. p16
  3. MSI
  4. E-Cadherin

Answer:

4) E-Cadherin

Explanation:

  • E-Cadherin mutation is primarily associated with diffuse type gastric cancer, not the intestinal type.
  • p53, p16, and MSI are common alterations in intestinal type gastric cancer.

Risk Factors and Protective Factors:

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H. pylori and Gastric Cancer Pathogenesis

  • Increased Risk:
    • H. pylori infection increases the risk of gastric cancer by 3.6-17 fold.
  • Primary Mechanism:
    • The main mechanism is chronic inflammation leading to intestinal metaplasia, which is a significant risk factor.
  • Genetic Factors:
    • Host overexpression of IL-1 in response to infection.
    • CagA gene positivity in H. pylori strains increases virulence.

  • Other Risk Factors:

    • Male gender
    • Low fat/protein diet
    • Diet high in complex carbohydrates

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MCQ 1: True Statement Regarding Gastric Cancer

Question:

Which of the following is true regarding gastric cancer?

  1. Nitrite is responsible for early changes in gastric mucosa in cancer pathogenesis
  2. H. pylori is responsible for progression of metaplasia to carcinoma
  3. High fat and protein in diet leads to gastric cancer carcinogenesis
  4. EBV is a causative factor

Answer:

4) EBV is a causative factor

Explanation:

  • Epstein-Barr Virus (EBV) is associated with certain subtypes of gastric cancer. H. pylori plays a role in the initiation of chronic inflammation but is not directly responsible for the progression from metaplasia to carcinoma.

MCQ 2: Most Important Risk Factor for Gastric Cancer ? ? ?

Question:

The most important risk factor for gastric cancer is:

  1. Hereditary
  2. H. pylori
  3. Environmental
  4. Ethnicity

Answer:

4) Ethnicity ? ? ?

Explanation:

  • While H. pylori is a major contributing factor, ethnicity plays a significant role in gastric cancer risk. Populations in regions with high prevalence of H. pylori infection and specific dietary habits, such as in East Asia, show higher gastric cancer rates.

MCQ 3: Most Common Gastric Polyp

Question:

The most common gastric polyp is:

a. Adenomatous polyp

b. Hyperplastic polyp

c. Fundic gland polyp

d. Inflammatory

e. Heterotopic

Answer:

c) Fundic gland polyp

Explanation:

  • Fundic gland polyps are the most common type of gastric polyps, followed by hyperplastic and adenomatous polyps. Fundic gland polyps generally have no malignant potential.

MCQ 4: Location of Hyperplastic Polyps

Question:

Hyperplastic polyps are most commonly found in the:

  1. Fundus
  2. Body
  3. Antrum
  4. Cardia

Answer:

3) Antrum

Explanation:

  • Hyperplastic polyps are most commonly located in the antrum of the stomach and carry a 2% risk of malignant transformation.

Adenomatous Polyps

  • Malignant Potential:
    • 10-20% risk of malignant transformation, which increases with polyp size.
  • Management:
    • Endoscopic removal is recommended for pedunculated lesions with no evidence of invasive cancer on histology.
    • Operative removal is indicated for:
      • Polyps larger than 2 cm.
      • Sessile polyps.
      • Polyps with proven invasive carcinoma.

Gastric Cancer Risk Factors and Types

  • Proximal Gastric Cancer:
    • GERD and increased BMI are risk factors.
    • GE junction tumors are not influenced by H. pylori.
  • Linitis Plastica:
    • Accounts for 10% of all gastric cancers.
  • Early Gastric Cancer (EGC):
    • Involves only the mucosa and submucosa.

LN involvement in Gastric Cancer

  • T1a (Tumor confined to mucosa):
    • 5% risk of nodal involvement.
  • T1b (Tumor invades submucosa):
    • 25% risk of nodal involvement.

Gastric Cancer Classification Systems

1. Lauren Classification (Pathological System)

  • Types:
    • Intestinal Type: Associated with environmental factors and H. pylori infection. Generally has a better prognosis.
    • Diffuse Type: Related to genetic factors such as E-cadherin mutation. Poorer prognosis due to early spread.

  • Prognostic and Treatment Value:

    • Used to guide prognosis and treatment options based on histological features.

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2. Borrmann Classification (Endoscopic Appearance)

  • Describes the endoscopic appearance of advanced gastric lesions:
    1. Type I: Polypoid
    2. Type II: Fungating
    3. Type III: Ulcerated with raised margins
    4. Type IV: Diffuse infiltrative (Linitis Plastica)

  • Prognosis:

    • More advanced lesions generally have a worse prognosis.

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3. Japanese Classification (EGC) (Early Gastric Cancer)

  • Focuses on early gastric cancer (EGC), which involves mucosa and submucosa with or without lymph node involvement.
  • Subtypes:
    • Type I: Protruding type
    • Type II: Superficial type (further divided into elevated, flat, and depressed)
    • Type III: Excavated type

  • Importance:

    • Useful for early detection, especially in screening programs, where endoscopic resection can be curative in selected cases.

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Gastric Cancer Symptomatology

  • Anemia:
    • 40% of patients with gastric cancer present with anemia, often due to chronic blood loss.
  • Hematemesis:
    • 15% of cases present with hematemesis (vomiting blood).

Staging of Gastric Cancer

  • N Stage (Nodal Involvement):
    • The N stage in gastric cancer staging is determined by the number of involved lymph nodes, not their anatomical station.

  • Lymph Node Harvesting:

    • A minimum of 15 lymph nodes should be harvested during surgery to accurately stage the disease and assess prognosis.

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MCQ 5: Spread of Linitis Plastica

Question:

Linitis plastica primarily spreads along:

  1. Mucosa
  2. Submucosa
  3. Muscularis propria
  4. Serosa

Answer:

2) Submucosa

Explanation:

  • Linitis plastica, a type of gastric cancer, primarily infiltrates and spreads through the submucosa, causing diffuse thickening of the stomach wall.

Investigations for Gastric Cancer

  • OGD and Biopsy:
    • The diagnostic procedure of choice for gastric cancer.
    • 6-8 biopsies are needed for accurate diagnosis.
    • One biopsy has a 70% sensitivity, while seven biopsies reach 98% sensitivity.
  • CECT:
    • Best tool for staging.

MCQ 6: Most Common Biopsy Forceps Used

Question:

The most commonly used biopsy forceps for gastric cancer are:

  1. Jumbo forceps
  2. Double bite
  3. Well biopsy
  4. Snare biopsy

Answer:

2) Double bite

Explanation:

  • Double bite biopsy forceps are frequently used to obtain multiple, deeper samples in one pass for more accurate diagnosis.

EUS in Gastric Cancer

  • EUS is highly effective in distinguishing high-risk from low-risk gastric cancers.
  • It is mandatory if endoscopic resection is planned.
  • EUS is not useful after neoadjuvant treatment.

MCQ 7: Malignant Lymph Node Characteristics on EUS

Question:

In EUS, a malignant lymph node is characterized by all of the following except:

  1. 1 cm

  2. Hypoechoic
  3. Rounded border
  4. Fat stranding

Answer:

4) Fat stranding

Explanation:

  • Malignant nodes on EUS are typically >1 cm, hypoechoic, and have rounded borders. Fat stranding is not a characteristic of malignant nodes; it is more commonly seen on CT in cases of inflammation.

MCQ 8: Characteristics of Malignant Nodes on EUS

Question:

A malignant node is characterized by all of the following except:

a. Discrete borders

b. Rounded contour

c. Hyperechoic

d. >1 cm

Answer:

c) Hyperechoic

Explanation:

  • Malignant nodes are typically hypoechoic, with discrete borders, a rounded contour, and are often >1 cm in size.

PET-CT in Gastric Cancer

  • PET-CT Utility:
    • Only 50% of gastric cancers show FDG uptake on PET-CT.
    • Useful in evaluating response to neoadjuvant chemoradiotherapy (CRT), especially on day 0 and day 14.
  • Additional Findings:
    • 10% of patients with M0 (no metastasis) on CT will show M1 disease on PET-CT, indicating metastasis not visible on CT.

MCQ 9: Best Investigation for Liver Metastasis in Gastric Cancer

Question:

What is the best investigation for detecting liver metastasis in gastric cancer?

  1. PET-CT
  2. CT
  3. Laparoscopic USG
  4. MRI

Answer:

3) Laparoscopic USG

Explanation:

  • Laparoscopic ultrasound (USG) is the most sensitive investigation for detecting liver metastasis in gastric cancer, especially in cases where other imaging techniques, like CT or PET-CT, might miss small lesions.

D-LAP and Her2-Neu in Gastric Cancer

Her2-Neu Testing:

  • Her2-Neu testing is indicated if the patient has M1 disease (metastatic gastric cancer).

Diagnostic Laparoscopy (D-LAP):

  • D-LAP spares 30% of patients from unnecessary laparotomies.
  • NCCN recommends routine D-LAP for staging (Category 2A recommendation).

Staging Laparoscopy:

  • Performed for T2 and above or N+ (node-positive) cases.
  • Indicated for all cases planned for neoadjuvant therapy.
  • Cytology of peritoneal washings is done:
    • If positive, it indicates M1 disease (metastatic).
    • Alters management in approximately 31% of cases (1 in 3 patients).

Endoscopic Mucosal Resection (EMR) Indications

  • Indications:
    1. Confined to mucosa (T1a)
    2. Tumor size < 2 cm
    3. No lymphovascular invasion (LVI)
    4. No ulceration
    5. Well-differentiated tumor
    6. N0 (No nodal disease)
  • Recurrence Rate:
    • EMR has a 6% recurrence rate.

MCQ 10: EMR Not Indicated In

Question:

EMR is not indicated in:

  1. Japanese III EGC
  2. Lamina propria involvement
  3. Muscularis mucosa involvement
  4. Size < 2 cm

Answer:

1) Japanese III EGC

Explanation:

  • Japanese III Early Gastric Cancer (EGC) refers to a more advanced type of cancer with submucosal invasion, which is not suitable for EMR. EMR is reserved for early-stage, mucosa-confined lesions.

Endoscopic Submucosal Dissection (ESD) Indications

  • Extended Criteria:
    1. SM1 involvement (submucosal invasion limited to the upper 1/3 of submucosa) and < 3 cm without ulceration.
    2. All intramucosal tumors without ulceration.
    3. Differentiated intramucosal cancer, < 3 cm, irrespective of ulceration status.

MCQ 11: Mandatory Investigation for EMR/ESD

Question:

What is the mandatory investigation for EMR/ESD?

  1. BX (Biopsy)
  2. EUS
  3. CT
  4. Chromoendoscopy

Answer:

2) EUS

Explanation:

  • Endoscopic Ultrasound (EUS) is essential for evaluating the depth of tumor invasion and assessing for submucosal invasion or lymph node involvement before performing EMR or ESD. This helps in determining whether the tumor is suitable for endoscopic resection.

Surgical Approach in Gastric Cancer

  • D2 Lymphadenectomy:
    • Recommended for Stage IB, II, III gastric cancers.
  • Resection Margins:
    • Proximal margin: At least 6 cm from the tumor.
    • Distal margin: The proximal duodenum.
  • D2 Lymphadenectomy with Pancreatectomy and Splenectomy:
    • Performed only if required for an R0 resection (complete tumor clearance with no residual disease).
  • Reconstruction Options:
    • Billroth II is recommended:
      • Prevents duodenal staple line and pancreatic surface recurrences which can lead to gastric outlet obstruction (GOO) if Billroth I is used.

    • If the gastric pouch is small, Roux-en-Y reconstruction is needed:

      • Roux-en-Y decreases the rate of alkaline reflux but increases the risk of marginal ulceration.

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Total Gastrectomy – D2 Lymphadenectomy

  • D0:
    • Lymphadenectomy less than D1.
  • D1:
    • Involves lymph nodes 1-7.
  • D1+:
    • Involves D1 nodes plus 8a, 9, and 11p nodes.
  • D2:
    • Involves D1+ nodes and includes nodes 10, 11d.

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Subtotal Gastrectomy – D2 Lymphadenectomy

  • D1:
    • Involves lymph nodes:
      • 1, 3, 4sb, 4d, 5, 6, 7
  • D1+:
    • Involves D1 nodes plus:
      • 8a, 9
  • D2:
    • Involves D1+ nodes plus:
      • 11p, 12a

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MCQ 12: ESD Contraindication

Question:

ESD is contraindicated in:

  1. T1b
  2. T1a, 4 cm without ulceration
  3. T1a with ulcer <3 cm, well-differentiated
  4. Node positive in EUS

Answer:

4) Node positive in EUS

Explanation:

  • ESD (Endoscopic Submucosal Dissection) is contraindicated if lymph node involvement is detected on EUS (Endoscopic Ultrasound), as this indicates more advanced disease requiring surgery. ESD is reserved for early-stage, node-negative lesions.

MCQ 13: D2 Distal Gastrectomy Excludes

Question:

D2 distal gastrectomy does not include dissection of which lymph node station?

  1. Left para-cardiac
  2. Proximal splenic
  3. Hepatoduodenal
  4. Celiac

Answer:

1) Left para-cardiac

Explanation:

  • Left para-cardiac (station 1) is typically included in proximal gastrectomy rather than distal gastrectomy. D2 distal gastrectomy includes dissection of the proximal splenic, hepatoduodenal, and celiac nodes, but not the left para-cardiac nodes.

Adjuvant Treatment in Gastric Cancer

  • Adjuvant Therapy:
    • Recommended for patients with pT2, pN1, and above (based on the CLASSIC trial).
    • Chemotherapy alone is recommended if D2 lymphadenectomy has been performed.
    • Chemoradiotherapy (CRT) is recommended if D1 lymphadenectomy has been performed (based on SWOG INTERGROUP 0116 and NCCN guidelines).
  • Neoadjuvant Therapy:
    • Recommended for patients with T2, N1, and above.

Monoclonal Antibodies

  • Trastuzumab (Herceptin):
    • A humanized monoclonal antibody targeting EGFR-1.
    • Used in a palliative regimen for stage IV gastric cancer with Her2 Neu overexpression (based on the ToGA trial).
  • Ramucirumab:
    • A monoclonal antibody targeting VEGFR.
    • Used as a second-line drug in stage IV gastric cancer.

Complications and Palliation

  • Palliation of Obstruction:
    • Gastrojejunostomy (GJ) is recommended if there are no distant metastases or only limited peritoneal deposits, with a life expectancy of more than 6 months.
    • Stenting can be considered for other cases.
  • Palliation of Bleeding:
    • Endoscopic methods should be the first line of treatment.
    • Hemostatic radiotherapy can be considered if endoscopic methods fail.
  • Palliation of Perforation:
    • Palliative resection or omental patching is recommended if the patient is unstable.

MCQ 14: All Are True Except

Question:

Which of the following is false?

  1. Hereditary risk is the most important causative factor
  2. Overall 5-year survival is 23%
  3. FAP, MSI mutations are found in intestinal type only
  4. Cag A expressing H. pylori is a risk factor

Answer:

1) Hereditary risk is the most important causative factor

Explanation:

  • Hereditary factors account for only a small percentage of gastric cancers (about 10%). Environmental factors, such as H. pylori infection, dietary habits, and smoking, are more significant.

MCQ 15: All Predispose to Malignancy Except

Question:

Which of the following does not predispose to malignancy?

  1. Ménétrier’s disease
  2. Pernicious anemia
  3. Low complex CHO consumption
  4. Epstein-Barr virus

Answer:

3) Low complex CHO consumption

Explanation:

  • A diet high in complex carbohydrates is generally considered protective against malignancy. The others, like Ménétrier’s disease, pernicious anemia, and EBV, increase malignancy risk.

MCQ 16: All Are True Except

Question:

Which of the following is false?

  1. Early gastric cancer involves muscularis mucosa
  2. Diffuse gastric cancer prefers hematogenous route
  3. Borrmann is an endoscopic classification
  4. Diffuse type cancer arises from lamina propria

Answer:

2) Diffuse gastric cancer prefers hematogenous route

Explanation:

  • Diffuse gastric cancer typically spreads locally and through the lymphatic system, not primarily through the hematogenous route.

MCQ 17: All Are False Regarding NCCN Guidelines Except

Question:

Which of the following is true regarding NCCN guidelines?

  1. Her 2 Neu testing should be done for all MO disease
  2. R1 resection can undergo redo surgery if LNR is favorable
  3. D-Lap is not necessary for distal gastric cancer
  4. Peritoneal wash cytology positivity means M1

Answer:

4) Peritoneal wash cytology positivity means M1

Explanation:

  • Positive cytology from peritoneal washing indicates M1 disease (metastatic), impacting the treatment plan.

MCQ 18: True Regarding Treatment of Gastric Cancer

Question:

Which of the following is true regarding the treatment of gastric cancer?

  1. Stage IB can be managed by ESD and not EMR
  2. D1 dissection for total gastrectomy includes left gastric nodes
  3. Extended gastric resection acceptable if R1 achieved
  4. Perioperative chemotherapy inferior to NACRT for locally advanced lesions

Answer:

2) D1 dissection for total gastrectomy includes left gastric nodes

Explanation:

  • D1 lymphadenectomy includes nodes along the left gastric artery and other perigastric nodes.

MCQ 19: MAGIC Trial for Gastric Cancer

Question:

The MAGIC trial for gastric cancer is about:

a. Adjuvant treatment

b. Neoadjuvant CRT

c. Perioperative chemotherapy

d. D2 lymphadenectomy

Answer:

c) Perioperative chemotherapy

Explanation:

  • The MAGIC trial established the role of perioperative chemotherapy in improving outcomes for patients with resectable gastric cancer.

MCQ 20: Station 8 Lymph Node in Gastric Cancer

Question:

Station 8 lymph node in gastric cancer is located at:

a. Left gastric

b. Common hepatic

c. Proper hepatic

d. Celiac artery

Answer:

b) Common hepatic

Explanation:

  • Station 8 refers to the common hepatic lymph nodes, which are part of the D2 lymphadenectomy in gastric cancer surgery.

MCQ 21: Lymph Node Station 12 in Gastric Cancer

Question:

In gastric cancer, lymph node station number 12 corresponds to:

a. Common hepatic

b. Hepatoduodenal

c. Retropancreatic

d. Superior mesenteric vessels

Answer:

b) Hepatoduodenal

Explanation:

  • Station 12 refers to the hepatoduodenal lymph nodes, which are part of the D2 lymphadenectomy.

MCQ 22: Radical Total Gastrectomy - False Statement

Question:

Which of the following is false regarding radical total gastrectomy?

a. Full stomach

b. N2 except station 10

c. Removal of spleen and pancreas

d. N1

Answer:

c) Removal of spleen and pancreas

Explanation:

  • In a radical total gastrectomy, the removal of the spleen and pancreas is generally not required unless an R0 resection (complete tumor clearance) necessitates it.

MCQ 23: D1 Gastrectomy for Distal Gastric Cancer

Question:

D1 gastrectomy for distal gastric cancer under Japanese classification does not involve:

a. CHA (common hepatic artery)

b. Rt paracardiac

c. HA (hepatic artery)

d. LGA (left gastric artery)

Answer:

a) CHA, c) HA

Explanation:

  • D1 gastrectomy focuses on perigastric nodes and does not involve the common hepatic artery (CHA) or hepatic artery (HA) lymph nodes.

MCQ 24: Duodenal Stump Closure - Procedure Not Used

Question:

One of the following is not a procedure for closure of a difficult duodenal stump:

a. Nissen

b. Finney

c. Bancroft

d. Kocher

Answer:

d) Kocher

Explanation:

  • Kocher maneuver is used to mobilize the duodenum, not for duodenal stump closure. Procedures like Nissen, Finney, and Bancroft are used for difficult stump closures.

MCQ 25: Treatment of Malignant Perforation Involving Distal Stomach

Question:

The treatment of choice for malignant perforation involving the distal stomach is:

  1. Distal gastrectomy
  2. Gastrostomy
  3. GJ with pyloric exclusion with FJ
  4. Omental patch closure

Answer:

1) Distal gastrectomy (if stable), 4) Omental patch (if unstable)

Explanation:

  • Distal gastrectomy is the preferred treatment if the patient is stable. In unstable patients, a simpler procedure like an omental patch closure is performed.

MCQ 26: False Statement Regarding Gastric Cancer

Question:

Which of the following is false regarding gastric cancer?

  1. Stage migration can occur in stage 2 of gastric cancer after resection histology
  2. Celiac lymphadenectomy has no role in tumors limited to the gastric wall
  3. Mucosal lesions - lymphadenectomy doesn't increase survival
  4. No survival advantage of para-aortic lymphadenectomy

Answer:

2) Celiac lymphadenectomy has no role in tumors limited to the gastric wall

Explanation:

  • Celiac lymphadenectomy can still play a role in certain cases, even with tumors limited to the gastric wall, especially for accurate staging and to ensure R0 resection.

Question:

All are done for duodenal stump leaks except:

a. Partial TPN

b. Percutaneous drainage

c. Open surgery and primary repair

d. Continue oral feeds

Answer:

c. Open surgery and primary repair

Explanation:

  • In cases of duodenal stump leaks, oral feeds are typically continued and managed with partial TPN if required, drainage, and never open abdomen and do primary repair.

MCQ 28: Maruyama Index is Used in Prognostication of?

Question:

The Maruyama index is used in the prognostication of:

A) Gastric cancer

B) Gallbladder cancer

C) Esophageal cancer

D) Colorectal cancer

Answer:

A) Gastric cancer

Explanation:

  • The Maruyama Index (MI) is used in gastric cancer to predict the likelihood of disease in lymph node stations left undissected during surgery. It is calculated based on patient factors like age, sex, tumor size, location, histology, and depth of invasion. An MI < 5 is associated with better survival outcomes and is an independent predictor of both overall survival and relapse risk.