Gastric Carcinoma

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Gastric Carcinoma

• Vic Vernenkar, D.O.
• St. Barnabas Hospital
• Department of Surgery

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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.

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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.

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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.

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Anatomy

• The site of the lesion is classified on basis of
  relationship to long axis of stomach.
• 40 lower part
• 40 middle part
• 15 upper part
• 10 more than one part
• Recently the of lesions proximally has
  increased.

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Pathophysiology

• Understand vascular supply, allows for
  understanding of routes of spread.
• Derived from celiac artery.
• Left gastric supplies upper right stomach.
• Right gastric off common hepatic- lower portion.
• Right gastroepiploic -lower portion of greater
  curve.

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Pathophysiology

• Understanding lymphatic drainage can clarify
  nodal involvement.
• Complex drainage
• Primarily along celiac axis.
• Minor drainage along splenic hilum,
  suprapancreatic nodal groups, porta hepatis, and
  gastroduodenal areas

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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.

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Mortality and Morbidity

• 5-year survival for curative resections ranges
  from 30-50 for stage II disease and 10-25 in
  stage III.
• High likelihood of systemic and local relapse.
• Adjuvant therapy is offered .
• Operative mortality is less than 3 for curative
  resections.

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Race

• Higher in Asian countries.
• Japanese detect patients at very early stage,
  patients appear to do quite well.
• In Asian studies, patients with resected stage II
  and III disease have better outcomes than similar
  stages in the west.
• Some believe this reflects a biologic difference
  between diseases in Asia and west.
• Black race, low socioeconomic class.

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Sex, Age

• Mengtwomen
• Most are elderly at diagnosis. Median age 65
  years. The ones that present in younger patients
  may represent a more aggressive variant.
• Cigarettes

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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.

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History

• Late complications include pleural effusions,
  peritoneal effusions, GOO, GE obstruction, SBO,
  bleeding, jaundice, cachexia.

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Physical

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

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Etiology

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

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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.

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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.

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Previous Surgery

• Implicated as risk factor, the rational being
  that previous gastric surgery alters normal pH of
  stomach.
• Retrospective studies show that a small
  percentage of patients who have a gastric polyp
  removed have evidence of invasive carcinoma in
  the polyp.
• Polyps may therefore be premalignant.

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Genetic Factors

• Poorly understood
• Some familial aggregation exists

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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.

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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.

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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.

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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)

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Histology

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

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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.

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Borrmann Classification

• 5 categories
• Type I polypoid or fungating
• Type II ulcerating lesions with elevated borders
• Type III ulceration with invasion of wall
• Type IV diffuse infiltration
• Type V cannot be classified

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Lauren System

• Epidemic or endemic
• The intestinal, expansive epidemic type gastric
  cancer is associated with atrophic gastritis,
  retained glandular structure, little
  invasiveness, sharp margins. It would be a
  Borrmann I or II.

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Lauren System

• The epidemic or Borrmann I or II carries better
  prognosis, shows no family history.
• The diffuse, infiltrative, endemic, is poorly
  differentiated, with dangerously deceptive
  margins, invades large areas of stomach. Younger
  patients, genetic factors, blood groups, and
  family history.

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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

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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

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Distant Metastases

• MX- cannot be assessed
• M0- no distant metastases
• M1-distant metastases

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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

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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.

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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.

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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.

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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).

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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.

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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.

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Type of Surgery

• In general most surgeons perform total
  gastrectomy ( if required for negative margins),
  esophagogastrectomy for tumors of the cardia and
  GE junction, and a subtotal gastrectomy for
  tumors of the distal stomach.
• Similar 5 year rates for subtotal vs. total in
  tumors of distal stomach.
• Extensive lymphatics require 5cm margin.

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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.
• A recent Intergroup 0116 randomized study offers
  evidence of a survival benefit associated with
  postoperative chemoradiotherapy

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Complications

• Mortality 1-2
• Anastamotic leak, bleeding, ileus, transit
  failure, cholecystitis, pancreatitis, pulmonary
  infections, and thromboembolism.
• Late complications include dumping syndrome,
  vitamin B-12 deficiency, reflux esophagitis,
  osteoporosis.

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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.

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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.

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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