GASTRIC CARCINOMA

BACKGROUND
Second most common cancer-related death. Korea, Japan, China, Taiwan high rates. 22,000 diagnosed annually in US. 14th most common cancer. Difficult to cure, as advanced disease. Most die of recurrent disease even after resection for cure.

ANATOMY
Stomach begins at GE junction, ends at duodenum.

3 parts- uppermost is cardia, largest part in middle is body, the last part is pylorus.

Cardia contains mucin producing cells.

Fundus or body mucoid cells, chief cells, parietal cells. Pylorus has mucin producing cells.

ANATOMY
Five layers: Mucosa, submucosa, muscular layer, subserosal layer, serosal layer. Peritoneum of greater sac covers anterior surface A portion of lesser sac drapes posteriorly over stomach. The GE junction has limited serosal covering.

FREQUENCY
US: seventh leading cause of cancer deaths, with 22,000 diagnosed yearly, and 14,000 deaths. Internationally: second most common cancer. Tremendous geographic variation, with highest death rates in Chile, Japan, and former USSR.

RACE
Higher in Asian countries. Japanese detect patients at very early stage, patients appear to do quite well.

ETIOLOGY
Diet H. Pylori Previous stomach surgery Pernicious anemia Polyps( rarely a precursor) Atrophic gastritis Radiation, genetics

DIET
Certain diets are implicated. Rich in pickled vegetables, salted fish, excessive dietary salt, smoked meats. A diet that includes fruits and vegetables rich in vitamin C may have a protective effect. Excessive amounts of nitrates are converted to nitites and nitroseamine which are potential carcinogens.

HELICOBACTER
Implicated as precursor of gastric cancer. H. Pylori associated with atrophic gastritis, and patients with a history of prolonged gastritis have a 6-fold increase in risk. Particularly true of tumors of antrum, body, and fundus of stomach, but not in cardia.

PREVIOUS SURGERY
Peptic ulcer surgery- Partial gastrectomy, GastroJejunostomy, Pyloroplasty Implicated as risk factor, the rational being that previous gastric surgery alters normal pH of stomach as well as bile reflux gastritis Polyps may be premalignant.

GENETIC FACTORS
Poorly understood Some familial aggregation exists Mutation of H- ras oncogene and over expression of c-erb B2 genes APC Familial Polyposis P53 suppressor gene HNPCC

SITES OF DISTRIBUTION
The site of the lesion is classified on basis of relationship to long axis of stomach. CARDIA-21% FUNDUS-2% BODY-23% PYLORUS-47%

HISTORY
Early disease has no symptoms, some patients with incidental complaints get an early diagnosis. If symptoms, it reflects advanced disease; These may include indigestion, nausea, dysphagia, early satiety, anorexia, weight loss.

HISTORY
Late complications include: pleural effusions, peritoneal effusions, Gastric Outlet Obstruction, Gastro Esophageal obstruction, Small Bowel Obstruction, bleeding, jaundice, cachexia.

PHYSICAL EXAMINATION
All physical signs are late events. Too late for curative procedures. Palpable stomach with succussion splash, hepatomegaly, Virchow nodes, sister Mary Joseph nodes, Blumer shelf, weight loss, pallor from bleeding and anemia.

LABORATORY
Assists in determining optimal therapy. CBC identifies anemia, with may be caused by bleeding, liver dysfunction, or poor nutrition. 30% have anemia. Electrolyte panels and LFTs are also essential to better characterize patients clinical state.

IMAGING STUDIES
EGD: safe, simple, providing a permanent color photographic record. Obtains tissue for diagnosis. UGI: detects large tumors, but only occasionally detects extension into esophagus or duodenum, especially if small or submucosal.

IMAGING STUDIES
CXR: done to evaluate for metastases. CT scan or MRI of chest, abdomen, pelvis: evaluate local disease process, and areas of spread. Some tumors are deemed unresectable based on the testing. Accurately predicts stage 66-77%. Poor nodal status prediction.

ENDOSCOPIC ULTRASOUND
Endoscopic ultrasound: becoming extremely useful as a staging tool, when CT fails to show T3, T4, or metastatic disease. Used with neoadjuvant chemo to stratify pts Can achieve resolution of 0.1 mm. Cannot reliably distinguish between tumor and fibrosis. Overall staging accuracy of 75% Poor for T2 lesions (38%) Better for T1(80%), T3 (90%)

HISTOLOGY

Adenocarcinoma 95% Lymphomas 2% Carcinoids 1% Adenocathomas 1% Squamous cell 1%

HISTOLOGY
Adenocarcinoma is classified according to the most unfavorable microscopic element present: tubular, papillary, mucinous, signet-ring cells. Also identified by gross appearance: ulcerative, polypoid, scirrous, superficial spreading, multicentric, or Barrett ectopic. Variety of other schemes: Borrmann, Lauren.

LAUREN SYSTEM Type I- intestinal gastric cancer, arises intestinal metaplasia. -forms polypoid tumour or ulcer Type II- Diffuse gastric cancer- infiltarting in stomach wall without producing obvious mass lesion

MACROSCOPIC TYPES
Proliferative typecurvature. bulky, cauliflower like

Ulcerative type-the most type, Mc Pylorus antrum region towards lesser Colloid or mucoid type- rare variety, massive tumor of gelatinous
appearance. Cancer cells line the accumulation of colloid.

Linitis plastica- also a rare variety.tm cells infiltrate the

sub-mucosa and subserosa and muscle coat extensively without protuding into the lumen of the stomach.

Proliferation of fibrous tissue in the submucosa giving mother of pearl appearance. Localised involves usually pylorus region generalized.(whole stomach ios contracted and rigid)

STAGING
Primary tumor Tx- cannot be assessed T0- no evidence Tis- carcinoma in situ, no invasion of lamina T1- invades lamina propria or submucosa T2- invades muscularis or subserosa T3- penetrates serosa, no adjacent structure T4- invades adjacent structures

REGIONAL LYMPH NODES NX- cannot be assessed N0- no nodes N1- mets in 1-6 regional nodes N2- mets in 7-15 regional nodes N3- mets in more than 15 regional nodes

DISTANT METASTASES
MX- cannot be assessed M0- no distant metastases M1-distant metastases

EARLY GASTRIC CANCER

Gastic cancer confines to mucosa and submucosa irrespective of Lymph node status JAPANESE CLASSIFICATION OF EARLY GASTRIC CANCER Type I,II, a),b),c) III, Advanced Gastric Cancer- beyond submucosa coat and involves Muscularis propria

Bormanns classification Type I to IV

PROGNOSTIC FEATURES Depth of invasion through gastric wall, presence or absence of regional lymph node involvement The greater number of positive nodes, the greater the likelihood of local or systemic failure postoperatively

SPREAD PATTERNS
Directly, via lymphatics, or hematogenously Direct extension into omentum, pancreas, diaphragm, transverse colon, and duodenum. If lesion extends beyond wall to a free peritoneal surface, peritoneal involvement is frequent.

SPREAD PATTERNS
The visible gross lesion frequently underestimates true extent. Abundant lymphatic channels in submucosal and subserosal layers allow for easy spread. The submucosal plexus is prominent in esophagus, the subserosal plexus prominent in duodenum, which allows for proximal and distal spread. Liver mets common, from hematogenous spread.

LAPAROSCOPY
Inspect peritoneal surfaces, liver surface. Identification of advanced disease avoids non-therapeutic laparotomy in 25%. Patients with small volume metastases in peritoneum or liver have a life expectancy of 3-9 months, thus rarely benefit from palliative resection.

LYMPH NODE DISSECTION

AJCC: number rather than location of LN is prognostic. Extent of dissection controversial. Nodal involvement indicates poor prognosis, and more aggressive approaches to remove them are taking favor. Ongoing trials regarding this in Europe. Critics argue that the apparent benefit associated with extended LND reflects stage migration (each LN is reviewed more carefully).

RESIDUAL DISEASE R STATUS

Tumor status following resection. Assigned based on pathology of margins. R0- no residual gross or microscopic disease. R1- microscopic disease only. R2- gross residual disease. Long term survival only in R0 resection.

D NOMENCLATURE
Describes extent of resection and lymphadenectomy. D1- removes all nodes within 3cm of tumor. D2- D1 plus hepatic, splenic, celiac, and left gastric nodes. D3- D2 plus omentectomy, splenectomy, distal pancreatectomy, clearance of porta hepatis nodes. Current standards include a D1 dissection only.

TYPE OF SURGERY TOTAL GASTRECTOMY ( if required for negative margins), ESOPHAGOGASTRECTOMY for tumors of the cardia and GE junction, SUBTOTAL GASTRECTOMY for tumors of the distal stomach. Extensive lymphatics require 5cm margin.

OUTCOME
5-year survival for a curative resection is 30-50% for stage II disease, 10-25% for stage III disease. Adjuvant therapy because of high incidence of local and systemic failure.

COMPLICATIONS
Mortality 1-2% Anastamotic leak, bleeding, ileus, transit failure, cholecystitis, pancreatitis, pulmonary infections, and thromboembolism. Late complications include dumping syndrome, vitamin B12 deficiency, reflux esophagitis, osteoporosis.

ADJUVANT THERAPY
Rationale is to provide additional loco-regional control. Radiotherapy- studies show improved survival, lower rates of local recurrence when compared to surgery alone. In unresectable patients, higher 4 year survival with mutimodal tx, in comparison to chemo alone.

CHEMOTHERAPY Numerous randomized clinical trials comparing combination chemotherapy in the adjuvant setting to surgery alone did not demonstrate a consistent survival benefit. The most widely used regimen is 5-FU, doxorubicin, and mitomycin-c. The addition of leukovorin did not increase response rates.

ADVANCED UNRESECTABLE DISEASE

Surgery is for palliation, pain, allowing oral intake Radiation provides relief from bleeding, obstruction and pain in 50-75%. Median duration of palliation is 4-18 months

TUMOUR MARKERS
CEA CA 19-9 CA 50 CA 12-5 CA 72-4- MOST IMPORTANT