<![CDATA[Mock17 Gastric Cancer]]>Stem
A 60-year-old lady who is chronic alcoholic was diagnosed with gastric cancer. She underwent gastrectomy and splenectomy due to iatrogenic injury. Patient has also osteoarthritis.

Pathology Report
Signet ring cell carcinoma.
Positive LNS.
R1
Spleen involved

Discuss this pathology report with the patient's family in four simple sentences. (Use layman language)

This is cancer of the stomach.
Not completely removed (i.e. incomplete resection)
The patient will require further resection and chemotherapy.
It may come back again (i.e. high possibility of recurrence)

What's the plan for the patient post-splenectomy?

Give vaccine for the patient after 2 weeks against polysaccharide encapsulated organisms (N. meningitides, H. influenzas, Strep. Pneumoniae)
Prophylactic antibiotics to protect the patient against post-splenectomy overwhelming infection (OPSI)
Influenza vaccine yearly

Mention 4 important risk factors for gastric cancer?

H. pylori infection.
Chronic atrophic gastritis
Intestinal metaplasia
Pernicious anaemia
Family history for gastric cancer
FAP
Adenomatous polyps more than 2 cm
Previous gastric surgery

How does gastric cancer develop?

Normal mucosa → Chronic gastritis → Intestinal metaplasia → Dysplasia → Intramucosal carcinoma → Invasive gastric carcinoma

What's the commonest histological type of gastric cancer?

Adenocarcinoma 95%

Do you know any classification for gastric cancer?

The WHO classification
The Lauren classification
Borrmann classification

Mention The WHO classification:

Tubular adenocarcinoma (most common).
Papillary adenocarcinoma.
Mucinous adenocarcinoma.
Mixed carcinoma (mix of types of adenocarcinomas).
Poorly cohesive carcinomas

10 days after resection the patient developed diffuse, painful swelling of the left arm. What do you think has happened?

DVT of Axillary vein

What are the predisposing factors in this patient?

Hypercoagulable state in malignancy
Venous stasis from Virchow LN

How can you define paraneoplastic syndromes?

Symptom complexes that occur in distal site of cancer origin, and that cannot be explained by:
Local or distant spread of the tumour
Or by the elaboration of hormones indigenous to the tissue of origin of the tumour.

Do you know any paraneoplastic syndromes associated with gastric carcinoma?

Acanthosis nigricans
Dermatomyositis.

How does gastric cancer spread first?

By lymphatics spread to LN (left gastric LN)

What are the other routes of spread?

Hematogenous
Transcoelomic
Direct invasion

6 months later the patient presented with abdominal distension, positive shifting dullness. What's your diagnosis now?

Metastasis (most likely Liver metastasis) → malignant ascites.

Mention 2 pathological tests to confirm?

Ascites tap (paracentesis) and cytology.
Liver biopsy from metastasis,
FNAC from the left supraclavicular lymph node
Tumour marker: CA 72-4 (for recurrence).

What would be your plan if this is a recurrence and advanced disease?

Palliative treatment including:
Feeding jejunostomy
Palliation of ascites by repeated tapping (paracentesis).
Pain relief using opioids
Palliative chemotherapy

How does ascites develop in this case?

Impaired liver function decrease synthesis of albumin (hypoalbuminemia) → low plasma oncotic pressure
High interstitial pressure (Portal Hydrostatic pressure).

How to treat malignant ascites?

Treating the underlying cancer with chemotherapy and/or surgery.
Paracentesis
Peritoneal venous shunt
Cell-free concentrated ascites reinfusion therapy

What are the procedure-specific complications of total gastrectomy?
Early

Anastomotic leak
Pancreatitis
Cholecystitis
Haemorrhage
Infection.

Late

Dumping syndrome
Vitamin B12 deficiency (lack of intrinsic factor)
Metabolic bone disease
Recurrence of malignancy

What's dumping syndrome?

Loss of the reservoir function of the stomach (e.g. following gastrectomy) results in the rapid transit of highly osmotically active substances into the duodenum following meals and may cause 'dumping syndrome'.

What are the types of dumping syndrome
Early dumping

30–60 minutes following a meal, rapid transit of the hyperosmolar gastric contents into the small bowel results in a fluid shift from the intravascular compartment to the gastric lumen and small bowel distension, colicky abdominal pain, diarrhoea and vasomotor symptoms, such as tachycardia and postural hypotension.

Late dumping

1–3 hours following meals. Rapid transit of carbohydrate into the small bowel results in sudden absorption of high levels of glucose and compensatory hyperinsulinemia, resulting in subsequent hypoglycaemia.

What is the name of familial type of gastric cancer?

Hereditary Diffuse Gastric Cancer (HDGC) syndrome

Gene mutation and mode of inheritance?

CDH1
Autosomal dominant

If you have a mutation in CDH1, genotypes of cancers may be associated?

Hereditary Diffuse Gastric Cancer (HDGC) syndrome.
Colon and rectum cancer
Lobular breast cancer d-Prostate cancer

The clinical criteria to select patients eligible for CDH1 mutations? / Which patients you will screen for CDH1 gene mutation?
Family criteria

Cases of gastric cancer in family regardless of age, with at least one diffuse gastric cancer (DGC).
Case of DGC at any age, and ≥1 case of lobular breast cancer at age <70 years in different family members.
Cases of lobular breast cancer in family members <50 years of age.

Individual criteria

DGC at age <50 years.
DGC at any age in individuals of Māori ethnicity.
DGC at any age in individuals with a personal or family history (first-degree relative) cleft lip or palate.
History of DGC and lobular breast cancer, both diagnosed at age <70 years.
Bilateral lobular breast cancer, diagnosed at age <70 years.
Gastric in situ signet ring cells or pagetoid spread of signet ring cells in individuals <50 years of age.

What is the Age of screening for CDH1 gene?

16-18 years old (legal age of consent).

What is the Age of prophylactic surgery?

Between 20 and 30 years of age.

Other than adenocarcinoma, what are other types of gastric cancer?

GIST
B-cell lymphomas (MALT type)
Neuroendocrine tumours like carcinoid
Hereditary diffuse gastric carcinoma
Others: rare Squamous cell carcinoma

What is CDH1 gene and function?

CDH1 (E-cadherin gene): is a tumour suppressor gene.
Encodes a protein called E-cadherin (epithelial cadherin): which is a transmembrane protein present in epithelial cells which has a role in maintaining cell adhesion & adherent junction & signalling for contact inhibition of cell proliferation.
Mutations & loss of function of CDH1 gene lead to Loss of normal intercellular junctions and results in cancer invasion & metastasis
E-cad also binds to ß-catenin preventing its translocation into nucleus and by this inactivates. WNT pathway.

Type of mutation in CDH1?

Autosomal dominant
Hereditary diffuse gastric carcinoma (HDGC) is an autosomal dominant. However, both copies of the CDH1 gene must be inactive (the unmutated copy of CDH1 gene undergoes mutation or inactivated during the lifetime) (germline mutation).

Causes of gall stones & cholecystitis following radical gastrectomy?

Loss of vagal innervation to gallbladder (damage to hepatic branch of anterior vagus nerve) leads to bile stasis & gallstone formation.
Another mechanism is loss of cholecystokinin release from duodenum after bypass of duodenum in a Roux-en-Y reconstruction.
GB contraction decreases & bile salt concentration increases

Causes of post gastrectomy acute pancreatitis?

Direct iatrogenic injury during gastrectomy
Microcirculation compromise.
Duodenal hyper pressure & postoperative spasm of major papilla.

Causes of post gastrectomy anaemia?

Due to B12 deficiency or Iron deficiency

Causes of iron deficiency?

Iron requires acidic gastric milieu for absorption, which is lost.
There is a lack of absorption of iron in post gastrectomy reconstructions bypassing the duodenum, such as the Roux-en-Y or Billroth II procedures, as iron gets absorbed in duodenum.

Causes of post-gastrectomy metabolic bone disease?

Osteoporosis & osteomalacia caused by reduced food intake & absorption & steatorrhea.
Steatorrhea interferes with absorption of calcium & vitamin D from gut.
Steatorrhea is caused by exocrine pancreatic insufficiency due to post-gastrectomy pancreatitis.

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