This document summarizes information about esophageal and gastric cancers. It discusses the different types of esophageal cancers including squamous cell carcinoma and adenocarcinoma. It describes risk factors, symptoms, diagnosis, and treatment options for esophageal cancers. It also summarizes gastric cancers, providing information on types, risk factors, clinical features, evaluation, staging, differential diagnosis, and treatment/management. Primary gastric lymphoma is also briefly mentioned.

1. W. P. Rivindu H. Wickramanayake
Group no. 04a
6th Year 2nd Semester – 2020 November
Tbilisi State Medical University, Georgia
Esophageal &
Gastric Cancers

2. Esophageal Cancers
● Cancer of the esophagus is an increasingly common and extremely lethal
malignancy.
● Almost all esophageal cancers are either squamous cell carcinomas or
adenocarcinomas; the two histologic subtypes have a similar clinical
presentation but different causative factors.
● Worldwide, squamous cell carcinoma is the more common.
● Familial increased risk has been observed in regions with high incidence,
although gene associations are not yet defined.
● More common in blacks than whites and in males than females; it appears most
often after age 50 and seems to be associated with a lower socioeconomic status.
● Such cancers generally arise in the cervical and thoracic portions of the
esophagus.
● Patients with head and neck cancer are at increased risk of squamous cell cancer
of the esophagus.

3. Etiologic Factors Associated with
Squamous Cell Cancer of the Esophagus

4. ● More than 75% of esophageal tumors are adenocarcinomas,
● In the distal esophagus in association with chronic gastric reflux, often in the
presence of Barrett’s esophagus (replacement of the normal squamous
epithelium of the distal esophagus by columnar mucosa), which occurs more
commonly in obese individuals.
● Adenocarcinomas arise within dysplastic columnar epithelium in the distal
esophagus.
● Even before frank neoplasia is detectable, aneuploidy and p53 mutations are
found in the dysplastic epithelium.
● These adenocarcinomas behave clinically like
gastric adenocarcinomas, although they are not
associated with Helicobacter pylori infections.
● Approximately 15% of esophageal
adenocarcinomas overexpress the HER2/neu gene.

5. ● About 5% occur in the upper third of the esophagus (cervical esophagus), 20% in the middle
third, and 75% in the lower third.
● Squamous cell carcinomas and adenocarcinomas cannot be distinguished radiographically or
endoscopically.
● Progressive dysphagia and weight loss of short duration are the initial symptoms.
● Dysphagia initially occurs with solid food, gradually progresses to semisolids and liquids.
● By the time these symptoms develop, the disease is already very advanced, because
difficulty in swallowing does not occur until >60% of the esophageal circumference is
infiltrated with cancer.
● Dysphagia may be associated with pain on swallowing (odynophagia), pain radiating to
the chest and/or back, regurgitation or vomiting, and aspiration pneumonia.
● The disease most commonly spreads to adjacent and supraclavicular lymph nodes, liver,
lungs, pleura, and bone.
● Tracheoesophageal fistulas may develop, primarily in patients with upper and mid-
esophageal tumors.
● With SCC, hypercalcemia may occur in the absence of osseous metastases, probably from
parathormone-related peptide secreted by tumor cells
Clinical Features

6. ● Esophagoscopy should be performed in all patients suspected of having an
esophageal abnormality, to both visualize and identify a tumor and also to
obtain histopathologic confirmation of the diagnosis.
● Endoscopic inspection of the larynx, trachea, and bronchi should also be
carried out. (i.e., smokers and drinkers has a high rate of cancers of the lung
and the head and neck region)
● A thorough examination of the fundus of the stomach (by retroflexing the
endoscope) is imperative as well.
● The extent of tumor spread to the mediastinum and para-aortic lymph nodes
should be assessed by computed tomography (CT) scans of the chest and
abdomen and by endoscopic ultrasound.
● Positron emission tomography scanning provides a useful assessment of the
presence of distant metastatic disease.
Diagnosis

7. ● The prognosis is poor. Approx. 10% of patients survive 5 years after the
diagnosis; thus, management focuses on symptom control.
● Surgical resection of all gross tumor (i.e., total resection) is feasible in only
45% of cases, with residual tumor cells frequently present at the resection
margins.
● Such esophagectomies have been associated with a postoperative mortality rate
of approximately 5% due to anastomotic fistulas, subphrenic abscesses, and
cardiopulmonary complications.
● Minimally invasive transthoracic esophagectomies.
● Endoscopic resections of superficial squamous cell cancers or adenocarcinomas
but with less succes.
● Endoscopic ablation of dysplastic lesions in an area of Barrett’s esophagus.
● Fundoplication surgery (i.e., the removal of the gastroesophageal junction) as a
means of cancer prevention in patients with Barrett’s esophagus.
Treatment

8. ● Cisplatin given in combination with single-agent chemotherapy.
● In overexpressing pts. of the HER2/neu gene, the addition of the monoclonal antibody
trastuzumab (Herceptin) enhance the likelihood of benefit, particularly in patients with
gastroesophageal lesions.
● The antiangiogenic agent bevacizumab (Avastin).
● Combination chemotherapy and radiation therapy as the initial therapeutic approach,
either alone or followed by an attempt at operative resection, seems to be beneficial.
● When administered along with radiation therapy, chemotherapy produces a better survival
outcome than radiation therapy alone.
● The use of preoperative chemotherapy and radiation therapy followed by esophageal resection
appears to prolong survival compared with surgery alone according to several randomized
trials and a meta-analysis.
● For the incurable, surgically unresectable patient with esophageal cancer, dysphagia,
malnutrition, and the management of tracheoesophageal fistulas are major issues.
● Approaches to palliation include repeated endoscopic dilatation, the surgical placement of
a gastrostomy or jejunostomy for hydration and feeding, endoscopic placement of an
expansive metal stent to bypass the tumor, and radiation therapy.

9. ● Two distinct types of gastric adenocarcinoma, intestinal (well-differentiated)
and diffuse (undifferentiated), which have a distinct morphologic appearance,
pathogenesis, and genetic profiles.
● The intestinal subtype encompasses tubular and glandular elements, with
multiple degrees of differentiation.
● The diffuse subtype displays poorly cohesive single cells without gland
formation. GC with signet ring cells is relatively prevalent, being classified
as a “diffuse type” according to the Lauren classification.
● The only potentially curative treatment approach for patients with gastric
cancer is surgical resection with adequate lymphadenectomy.
● Regrettably, patients with an unresectable, locally advanced, or metastatic
disease could solely be offered life-prolonging palliative therapy regimens.
Gastric Cancers

10. ● Factors linked with an increased risk of gastric cancer include;
- Nutritional factors such as high-salt (salt-preserved food),
- N-nitroso compounds consumption (dietary source),
- Smoking,
- A low vitamin A and C diet,
- Consuming large amounts of smoked
or cured foods,
- a deficit of refrigerated foods, and
- Contaminated drinking water.
● High body mass index (BMI), increased calorie consumption, gastroesophageal
reflux and smoking are associated with an increased risk of adenocarcinomas of
the distal esophagus, proximal stomach, and junction.
Etiology

11. ● Occupational exposure to rubber manufacturing, tin mining, metal processing,
and coal also increases the risk.
● Radiation exposure and prior gastric surgery.
● High consumption of fiber , fruits and vegetables have a probable protective
benefit against gastric cancer.
● Aspirin and other non-steroidal anti-inflammatory agent use - a lower risk.
● Host factors include type A blood with an approximate 20% more gastric cancer
cases than in blood groups O, B, or AB and particularly associated with the
diffuse type.
● Pernicious anemia, an autoimmune chronic atrophic gastritis has up to six-fold
increased risk of intestinal type gastric cancer.
● Benign gastric ulcer, hypertrophic gastropathy, and gastric polyps are risk
factors and are associated with an increased risk of stomach cancer.

12. ● Helicobacter pylori infection has an attributable risk of 46% to 63%,
while Epstein-Barr virus infection has an estimated of 5% to 10%
worldwide.
● Certain polymorphisms have been associated with gastric cancer, carriers
of IL-1B-511*T/*T or IL-1B-511*T/*C that are up-regulated by H.
pylori infection could cause a pro-inflammation and acid inhibition
leading to malignancy.
● Intestinal-type gastric carcinogenesis may have overexpressed oncogenes
(K-ras and c-met) or tumor suppressors (TP53, APC, TTF and
CDKN1B,p27); although, not consistently present.
● For cancer research, the World Health Organizations has classified H.
pylori as a definite gastric carcinogen and likewise concluded a positive
association between consumption of processed meat and stomach cancer.

13. ● Most gastric cancers are sporadic, but 5% to 10% of cases have a family
history of gastric cancer.
● Hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and
proximal polyposis of the stomach (GAPPS), and familial intestinal gastric
cancer (FIGC) are three major syndromes accounting up to 3% to 5% of
hereditary familial gastric cancer.
● Other hereditary cancer syndromes are:
• Hereditary non-polyposis colon cancer (HNPCC 13% lifetime risk, predominantly
intestinal type)
• Familial adenomatous syndrome (FAP, 10% risk)
• Peutz Jeghers syndrome (PJS, 29% risk)
• Juvenile polyposis syndrome (JPS, 21%)
• Li-Fraumeni syndrome
• Hereditary breast and ovarian cancer syndrome
• Phosphatase and tensin homolog (PTEN) or hamartoma tumor (Cowden's) syndrome.

14. ● Most patients have symptoms of an advanced stage at the time of
presentation.
● Weight loss, persistent abdominal pain, dysphagia, hematemesis,
anorexia, nausea, early satiety, and dyspepsia.
● Patients with a locally-advanced or metastatic disease usually present with;
- significant abdominal pain,
- potential ascites,
- weight loss,
- fatigue, and
- have visceral metastasis on scans and
- can have a gastric-outlet obstruction.
● A palpable abdominal mass indicates advanced disease.
Clinical Features

15. ● Signs of metastatic lymphatic spread distribution including Virchow’s node (left
supraclavicular adenopathy), Sister Mary Joseph node (peri-umbilical nodule),
and Irish node (left axillary node).
● Direct metastasis to peritoneum can present as Krukenberg’s tumor (ovary mass),
Blumer’s shelf (cul-de-sac mass), ascites (peritoneal carcinomatosis), and
hepatomegaly (often diffuse disease burden).
● Paraneoplastic manifestations may include dermatological (diffuse seborrheic
keratosis or acanthosis nigricans), hematological (microangiopathic hemolytic
anemia and hypercoagulable state [Trousseau’s syndrome]), renal (membranous
nephropathy), and autoimmune (polyarteritis nodosa) are rare clinical findings
and none is specific to gastric cancer.

16. ● Upper endoscopy is more invasive and costly, but it offers tissue diagnosis by direct biopsy
of esophageal, gastric or duodenal lesions.
● Any suspicious gastric ulcer should be biopsied multiple times for higher diagnostic
accuracy (one (70%) versus seven (98%) sensitivity).
● The American Joint Committee on Cancer/ Union for International Cancer Control (AJCC/UICC) Eight
Edition 2017 has outlined an new staging scheme based on tumor, node, metastasis (TNM) with 5-year
overall survival (5-y OS) according to pathological stage and intervention (surgery only IA-93.6%, IIA-
81.8%, and IIIA-54.2% or with neoadjuvant I-76.5%, II-46.3%, III-18.3% and IV-5.7%).
● Chest and abdominal imaging to rule out metastasis and to determine surgical resectability.
Chest computerized tomography (CT) is preferred over plain radiograph.
● Abdominopelvic computerized tomography is performed early to rule out gross
metastatic disease but does not accurately assess T, N, and small peritoneal metastases with
an overall accuracy of 42% to 82%.
● Endoscopic ultrasound has a better diagnostic accuracy of tumor depth (57% to 88%) and
lymph node status (30% to 90%), and hence, helps with accurate staging but is operator
dependent.
Evaluation

17. ● Suspicious solitary or oligometastatic sites should be confirmed by biopsies.
● Paracentesis should be performed if malignant ascites is suspected.
● If prior staging evaluation is negative for the metastatic disease, positron emission
tomography combined with computerized tomography imaging may be helpful to
determine the resectability of gastric cancers in select cases (T2N0).
● Serum markers (carcinoembryonic antigen, glycoprotein CA 125 antigen, carbohydrate
antigen 19-9, and cancer antigen 72-4).
● Staging laparoscopy with peritoneal cytology analysis is indicated prior surgery in the
absence of visible spread particularly for clinical stages with higher than T1b.
● Positive peritoneal cytology in the absence of identifiable peritoneal spread is an
independent predictor of high recurrence after curative resection, and hence, surgery is not
recommended.
● Human epidermal growth factor receptor 2 (HER2) gene positivity is more frequently
found in intestinal subtype (33%) than diffuse (8%) with lower rates in the United States
(19% and 6%, respectively).
● HER2 testing is recommended for all metastatic gastric cancer, first by using
immunohistochemistry score; negative for 0 or 1+ and positive for 3+, with reflex,
fluorescent, in situ hybridization for an equivocal 2+ score to confirm.

18. Staging System for Gastric Carcinoma

19. • Acute gastritis
• Atrophic gastritis
• Bacterial gastroenteritis
• Chronic gastritis
• Esophageal cancer
• Esophageal stricture
• Esophagitis
• Non-hodgkin lymphoma
• Peptic ulcer disease
• Viral gastroenteritis
Differential Diagnosis

20. ● Treatment modality for gastric cancer depends on an accurate preoperative
staging.
● Therapeutic approach can be endoscopic resection for;
- superficial, limited mucosa disease (< T1b, N0),
- upfront surgical resection with lymphadenectomy (< T3, any N),
- neoadjuvant (> T2) / adjuvant (> T1N1 or > T3N0) chemotherapy,
- radiation therapy, or combined with resectable lesions or
● Palliative systemic therapy for those locally advanced unresectable or
metastatic disease (T4, any N, or M1).
● Complete surgical removal of the tumor with resection of adjacent lymph nodes
offers the only chance for cure. However, this is possible in less than a third of
patients.
● A subtotal gastrectomy - for patients with distal carcinomas, whereas total or
near-total gastrectomies are required for more proximal tumors.
Treatment / Management

21. ● The inclusion of extended lymph node dissection in these procedures - added risk for complications.
● The prognosis following complete surgical resection depends on the degree of tumor penetration into the
stomach wall and is adversely influenced by regional lymph node involvement and vascular invasion.
● As a result, the probability of survival after 5 years for the 25–30% of patients able to undergo complete
resection is ∼20% for distal tumors and <10% for proximal tumors, with recurrences continuing for at least 8
years after surgery
● Reduction of tumor bulk is the best form of palliation and may enhance the probability of benefit from
subsequent therapy.
● Endoscopic screening programs has identified patients with superficial tumors & laparoscopic gastrectomy is
popular.
● 5-fluorouracil (5-FU) plus leucovorin was given in combination with radiation therapy, as a radiosensitizer
because Gastric adenocarcinoma is a relatively radioresistant tumor.
● The administration of combinations of cytotoxic drugs included cisplatin combined with epirubicin or
docetaxel and infusional 5-FU or capecitabine, or with irinotecan.
● Rather than bevacizumab (Avastin), antiangiogenic compound- ramucirumab (Cyranza)—in the treatment
of gastric cancer are encouraging.
● Combination chemotherapy administered before and after surgery (perioperative treatment) as well as
postoperative chemotherapy combined with radiation therapy reduces the recurrence rate and prolongs
survival.

22. Primary Gastric Lymphoma
● A far more treatable disease than adenocarcinoma of the stomach, a fact that
underscores the need for making the correct diagnosis.
● Antibiotic treatment to eradicate H. pylori infection has led to regression of
about 75% of gastric MALT lymphomas and should be considered before
surgery, radiation therapy, or chemotherapy.
● A lack of response to such antimicrobial treatment has been linked to a specific
chromosomal abnormality, i.e., t(11;18). Responding patients should undergo
periodic endoscopic surveillance .
● Subtotal gastrectomy, usually followed by combination chemotherapy, has led
to 5-year survival rates of 40–60% in patients with localized high-grade
lymphomas.
● Patients with preoperative radiographic evidence of nodal involvement, for
whom chemotherapy (CHOP [cyclophosphamide, doxorubicin, vincristine, and
prednisone]) plus rituximab is highly effective therapy.

23. .
● Leiomyosarcomas and GISTs make up 1–3% of gastric neoplasms.
● Involve the anterior and posterior walls of the gastric fundus and often ulcerate
and bleed.
● Even those lesions that appear benign on histologic examination may behave in a
malignant fashion.
● These tumors rarely invade adjacent viscera and characteristically do not
metastasize to lymph nodes, but they may spread to the liver and lungs.
● Leiomyosarcomas often are >5 cm in diameter and may be palpable on
abdominal examination.
● Bleeding, obstruction, and perforation are common.
● The treatment of choice is surgical resection.
● Combination chemotherapy should be reserved for patients with metastatic
disease. All such tumors should be analyzed for a mutation in the c-kit receptor.
Gastric (Nonlymphoid) Sarcoma

24. ● Arise from argentaffin cells of the crypts of Lieberkühn and are found from
the distal duodenum to the ascending colon, areas embryologically derived
from the midgut.
● More than 50% of intestinal carcinoids are found in the distal ileum, with
most congregating close to the ileocecal valve.
● Most intestinal carcinoids are asymptomatic and of low malignant potential,
but invasion and metastases may occur, leading to the carcinoid syndrome.
Carcinoid Tumors
● GISTs are unresponsive to conventional chemotherapy; yet ∼50% of patients experience
objective response and prolonged survival when treated with imatinib mesylate (Gleevec)
(400–800 mg PO daily), a selective inhibitor of the c-kit tyrosine kinase.
● Many patients with GIST whose tumors have become refractory to imatinib subsequently
benefit from sunitinib (Sutent) or regorafenib (Stivarga), other inhibitors of the c-kit
tyrosine kinase.

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