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gastric cancer

Etiology: 1) 60-70% of gastric carcinomas are causally related to infection with H pylori 2) dietary salt may play a role 3) 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are associated with H pylori 4) conversion of dietary nitrates to carcinogenic nitrites by gastric bacteria has been postulated 5) pseudoachalasia 6) risk stratified by gastric lesions on gastroscopy - *normal mucosa (0.4%) [10] - gastritis (1.2%) - atrophic gastritis (2.0%) - intestinal metaplasia (2.6%) - gastric dysplasia (5.3%) - gastric adenomas 7) genetic risk factors - familial adenomatous polyposis - MYH-associated polyposis - Lynch syndrome - Li-Fraumeni syndrome - juvenile polyposis syndrome - Peutz-Jeghers syndrome - gastric hyperplastic polyposis - hereditary diffuse gastric cancer [1] 8) other risk factors [1] - diet low in fruits & vegetable - smoking - history of gastric surgery - partial gastrectomy for benign or malignant disease [1] - low serum LDL cholesterol (RR-2.7) [15] Epidemiology: 1) increased incidence of gastric carcinoma in a) Native Americans b) Hispanics c) African Americans 2) gastric carcinoma is 2nd most common malignancy worldwide Pathology: 1) gastric adenocarcinoma 2) gastric mucosa-associated lymphoid tissue (MALT) lymphoma Genetics: 1) abnormal transcripts of FHIT found in ~50% 2) K-ras & p53 mutations may play a role 3) overexpression of TPBG, PLXNB1, TNFRSF6B, RTEL1, TDGF1, HER2 - 20% of gastric cancers & 30% of gastroesophageal junction cancers overexpress HER2 [1] 4) chromosomal deletion within 17q12 region involving CDK12 producing fusion transcripts with ERBB2 may be a cause of gastric cancer 5) chromosomal deletion involving UHRF2 is found in multiple kinds of malignancies 6) associated with defects in KLF6 7) other implicated genes: Zg14, ATAD2, AMIGO2, B3GNT6, CKAP2, LZIC, LETMD1, OLFM4, MYCT1, GUSB, CAPN9, SLC5A8, URG4, CASP10, CD97, CDH1, ADAMTS12, WISP1, TSPAN8, PSCA Clinical manifestations: 1) most patients have locally advanced or metastatic cancer at presentation [1] 2) epigastric pain, abdominal pain - anorexia, nausea, vomiting, dysphagia - GI bleeding, weight loss [1] - dark urine, dark stools 3) periumbilical nodule (Sister Mary Joseph's node) 4) left supraclavicular lymphadenopathy (Virchow's node) 5) enlarged ovary (Krukenberg's tumor) 6) mass in the cul-de-sac on rectal examination (Blumer's shelf) 7) ascites 8) acanthosis nigricans Laboratories: - HER2/neu in tissue - autoantibodies: KIAA1524 (research) Special laboratory: upper GI endoscopy with magnification [5] - biopsy or resection of gastric polyps [4] - resection is indicated for all adenomatous polyps, hyperplastic polyps >= 0.5 cm, & fundic gland polyps >= 1 cm - gastric sampling or resection is indicated in patients with familial adenomatous polyposis [4] - biopsy of surrounding mucosa in the setting of multiple adenomatous polyps or hyperplastic polyps [4] - surveillance endoscopy 1 year after resection of adenomatous polyps [4] - consider surveillance endoscopy in patients with intestinal metaplasia with risk factors (surveillance interval unclear) - surveillance endoscopy within 6 months of the diagnosis of pernicious anemia [4] - endoscopic resection & surveillance of intestinal metaplasia with high-grade dysplasia [4] - small (< 1 cm) tumors, types 1 & 2 carcinoids without aggressive features should be resected & undergo surveillance - types 3 & 4 carcinoids should be removed - >= 7 biopsy specimens from the margins of suspected malignant gastric ulcers [4] staging of gastric carcinoid tumors using endoscopic ultrasound (EUS) [4] - local staging of gastric adenocarcinoma using EUS with fine-needle aspiration (FNA) - evaluate submucosal gastric lesions by EUS with or without FNA - annual EUS surveillance of gastrointestinal stromal tumors < 2 cm [4] * 8% of newly diagnosed patients with gastric cancer had prior upper GI endoscopy within 3 years [9] - gastric ulcers found in 15% of these prior endoscopies & in 64% if prior endoscopy were within 1 year [9] Radiology: - CT of chest, abdomen & pelvis to identify regional & metastatic spread - PET scan is an option after CT scan Differential diagnosis: - MALT lymphoma - gastroesophageal junction cancer - achalasia with cancer at the gastroesophageal junction Management: 1) most patients present with advanced disease [1] 2) surgical resection a) most patients relapse after surgery [1,3] b) endoscopic mucosal resection may be useful for recurrence [4] c) malignant gastric obstruction should generally be treated with expanding metal stents [4] d) laparoscopic surgery non-inferior to open surgery for stage 1 gastric cancer [14] - shorter hospital stay, less blood loss, & fewer wound complications compared with open surgery [14] 3) adjunctive chemotherapy may be of benefit [3] a) standard of care after surgical resection for stage T2 or higher [1] b) cisplatin-based therapy - docetaxel, cisplatin + fluorouracil [6] c) 5-fluorouracil/leucovorin d) use in conjunction with radiation therapy may confer a survival advange [1,7] e) relapse remains common 4) HER2-overexpressing tumors - trastuzumab + cisplatin + 5 fluorouracil or capecitabine [1] 5) inoperable disease - capecitabine in combination with a cisplatin-based regimen 6) radiation therapy is at best palliative 7) gastric MALT lymphoma is treated with antibiotics for H pylori rather than surgery [1] 8) follow up: - lifelong surveillance for recurrence in patients with partial gastrectomy due to gastric cancer [1] - monitor serum vitamin B12 in patients who have had proximal or total gastrectomy 9) prevention - eradication of H pylori reduces risk 70% [15] - reduces risk by 73% in 1st-degree relatives of persons with gastric cancer [16] 10) screening low risk persons not recommended [1]

Related

gastroesophageal junction cancer/adenocarcinoma Helicobacter pylori staging of gastric carcinoma

General

gastrointestinal (GI) cancer gastric neoplasm

Database Correlations

OMIM correlations

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 569-71
  3. Journal Watch 21(19):152, 2001 Macdonald et al, N Engl J Med 345:725, 2001
  4. Yokoi C, Gotoda T, Hamanaka H, Oda I. Endoscopic submucosal dissection allows curative resection of locally recurrent early gastric cancer after prior endoscopic mucosal resection. Gastrointest Endosc. 2006 Aug;64(2):212-8. PMID: 16860071
  5. Fukui H, Shirakawa K, Nakamura T, Suzuki K, Masuyama H, Fujimori T, Hiraishi H, Terano A. Magnifying pharmacoendoscopy: response of microvessels to epinephrine stimulation in differentiated early gastric cancers. Gastrointest Endosc. 2006 Jul;64(1):40-4. PMID: 16813801
  6. Van Cutsem E et al, Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil and first-line therapy for advanced gastric cancer. A report of V325 Study Group. J Clin Oncol 2006, 24:4991 PMID: 17075117
  7. Macdonald JS, Smalley SR, Benedetti J et al Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. PMID: 11547741
  8. ASGE Standards of Practice Committee et al. The role of endoscopy in the management of premalignant and malignant conditions of the stomach. Gastrointest Endosc 2015 Apr 30 PMID: 25935705 http://www.giejournal.org/article/S0016-5107%2815%2902277-4/abstract
  9. Chadwick G et al. Gastric cancers missed during endoscopy in England. Clin Gastroenterol Hepatol 2015 Jan 30 PMID: 25645877
  10. Song H, Ekheden IG, Zheng Z, Ericsson J, Nyren O, Ye W. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population BMJ 2015;351:h3867 PMID: 26215280 Free PMC Article http://www.bmj.com/content/351/bmj.h3867
  11. Bang YJ, Van Cutsem E, Feyereislova A et al Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro- oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97 PMID: 20728210
  12. Guggenheim DE, Shah MA Gastric cancer epidemiology and risk factors. J Surg Oncol. 2013 Mar;107(3):230-6 PMID: 23129495
  13. Jomrich G, Schoppmann SF. Targeting HER 2 and angiogenesis in gastric cancer. Expert Rev Anticancer Ther. 2016;16(1):111-22. Review. PMID: 26567753
  14. Kim HH, Han SU, Kim MC et al. Effect of laparoscopic distal gastrectomy vs open distal gastrectomy on long-term survival among patients with stage I gastric cancer: The KLASS-01 randomized clinical trial. JAMA Oncol 2019 Feb 7; PMID: 30730546 https://jamanetwork.com/journals/jamaoncology/fullarticle/2723581 - Kim W, Kim HH, Han SU et al Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01). Annals of Surgery. 2016 263(1):28-35 PMID: 26352529
  15. Nam SY, Park BJ, Nam JH, Kook MC. Effect of Helicobacter pylori eradication and high-density lipoprotein on the risk of de novo gastric cancer development. Gastrointest Endosc 2019 Apr 26. PMID: 31034810 https://www.giejournal.org/article/S0016-5107(19)31659-1/pdf
  16. Choi IJ, Kim CG, Lee JY, et al. Family history of gastric cancer and Helicobacter pylori treatment. N Engl J Med 2020 Jan 30; 382:425. PMID: 31995688
  17. National Cancer Institute Stomach (Gastric) Cancer - Health Professional version https://www.cancer.gov/types/stomach/hp
  18. Guidelines on the management of oesophageal and gastric cancer Scottish Intercollegiate Guidelines Network (SIGN) http://www.sign.ac.uk/pdf/sign87.pdf