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*Biopsy-based testing at least 4 weeks after the completion of [[antibiotic]] therapy and after [[Proton pump inhibitor|PPI]] therapy has been withheld for 1–2 weeks.
*Biopsy-based testing at least 4 weeks after the completion of [[antibiotic]] therapy and after [[Proton pump inhibitor|PPI]] therapy has been withheld for 1–2 weeks.


== Screening ==
== Prevention Through Screening ==
In countries with a high incidence of gastric cancer such as east Asia countries, universal screening is recommended. [17-19]
* In countries with a high incidence of gastric cancer such as east Asia countries, universal [[Screening (medicine)|screening]] is recommended. ?
* Japan has a high [[incidence]] of gastric cancer; therefore annual [[Screening (medicine)|screening]] via double contrast [[Barium follow-through|barium radiography]] and photofluorography every year or [[upper endoscopy]] every two to three years.?
* [[Screening (medicine)|Screening]] interval is recommended to be every two years but may be extended to a three-year interval without significant difference in effect.  ??


In Japan, population-based screening for gastric cancer is recommended for individuals older than 50 years with conventional double-contrast barium radiograph with photofluorography every year or upper endoscopy every two to three years [20,33,34].
== Prevention of Hereditary Cancer  ==
 
Screening interval is recommended to be every two years but may be widened to a three-year rather than a two-year interval without significant effect [38-40].  
 
== Hereditary cancer prevention ==


=== '''Screening''' ===
=== '''Screening''' ===
In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups
* In areas of low gastric cancer [[incidence]], [[Screening (medicine)|screening]] for gastric cancer with [[upper endoscopy]] should be reserved for specific high-risk subgroups


Individuals at increased risk for gastric cancer include those with the following:
* Individuals at increased risk for gastric cancer include those with the following:
* Gastric [[adenomas]]
** Gastric [[adenomas]]
* [[Pernicious anemia]]
** [[Pernicious anemia]]
* Gastric intestinal [[metaplasia]]
** Gastric intestinal [[metaplasia]]
* [[Familial adenomatous polyposis]]
** [[Familial adenomatous polyposis]]
* [[Lynch syndrome]]
** [[Lynch syndrome]]
* [[Peutz-Jeghers syndrome]]
** [[Peutz-Jeghers syndrome]]
* [[Juvenile polyposis syndrome]]
** [[Juvenile polyposis syndrome]]


=== Prevention ===
=== Prevention ===
*  Asymptomatic patients with a family history of HDGC and ''CDH1'' mutations have a high probability of developing signet ring cell adenocarcinoma of the stomach. Prophylactic total gastrectomy is recommended for patients with family history of HDGC and ''CDH1'' mutations.<ref name="pmid10433926">{{cite journal| author=Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S et al.| title=Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. | journal=Am J Pathol | year= 1999 | volume= 155 | issue= 2 | pages= 337-42 | pmid=10433926 | doi=10.1016/S0002-9440(10)65129-2 | pmc=1866861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10433926  }}</ref>
*  [[Asymptomatic]] patients with a [[family history]] of HDGC and ''CDH1'' [[mutations]] have a high probability of developing [[Signet ring cell carcinoma|signet ring cell adenocarcinoma]] of the [[stomach]]. [[Prophylactic]] total [[gastrectomy]] is recommended for patients with [[family history]] of HDGC and ''CDH1'' [[mutations]].<ref name="pmid10433926">{{cite journal| author=Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S et al.| title=Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. | journal=Am J Pathol | year= 1999 | volume= 155 | issue= 2 | pages= 337-42 | pmid=10433926 | doi=10.1016/S0002-9440(10)65129-2 | pmc=1866861 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10433926  }}</ref>


* For patients with a ''CDH1'' mutation but who are not from an HDGC family, we recommend individualized evaluation at an experienced center before prophylactic total gastrectomy is offered.<ref name="pmid11729114">{{cite journal| author=Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage Consortium| title=Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. | journal=Gastroenterology | year= 2001 | volume= 121 | issue= 6 | pages= 1348-53 | pmid=11729114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11729114  }}</ref>  
* For patients with a ''CDH1'' [[mutation]] but who are not from an HDGC family, individualized evaluation at an experienced center before [[prophylactic]] total [[gastrectomy]] is recomended.<ref name="pmid11729114">{{cite journal| author=Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage Consortium| title=Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. | journal=Gastroenterology | year= 2001 | volume= 121 | issue= 6 | pages= 1348-53 | pmid=11729114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11729114  }}</ref>  


* Prophylactic gastrectomy is often advised between age 20 and 30.
* [[Prophylactic]] [[gastrectomy]] is often advised between age 20 and 30.
* Some suggest timing total gastrectomy in ''CDH1'' mutation carriers at an age that is five years younger than the youngest family member who developed gastric cancer.<ref name="pmid17522512">{{cite journal| author=Norton JA, Ham CM, Van Dam J, Jeffrey RB, Longacre TA, Huntsman DG et al.| title=CDH1 truncating mutations in the E-cadherin gene: an indication for total gastrectomy to treat hereditary diffuse gastric cancer. | journal=Ann Surg | year= 2007 | volume= 245 | issue= 6 | pages= 873-9 | pmid=17522512 | doi=10.1097/01.sla.0000254370.29893.e4 | pmc=1876967 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17522512  }}</ref>
* Some suggest timing total [[gastrectomy]] in ''CDH1'' [[mutation]] carriers at an age that is five years younger than the youngest family member who developed gastric cancer.<ref name="pmid17522512">{{cite journal| author=Norton JA, Ham CM, Van Dam J, Jeffrey RB, Longacre TA, Huntsman DG et al.| title=CDH1 truncating mutations in the E-cadherin gene: an indication for total gastrectomy to treat hereditary diffuse gastric cancer. | journal=Ann Surg | year= 2007 | volume= 245 | issue= 6 | pages= 873-9 | pmid=17522512 | doi=10.1097/01.sla.0000254370.29893.e4 | pmc=1876967 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17522512  }}</ref>
* Older patients are less likely to benefit from a prophylactic gastrectomy than younger patients because of a shorter life-expectancy and a higher perioperative risk.
* Older patients are less likely to benefit from a [[prophylactic]] [[gastrectomy]] than younger patients because of a shorter life-expectancy and a higher perioperative risk.


* patients who are older than 75 years should not undergo such a procedure, as their mortality from the procedure outweighs their mortality from gastric cancer.  
* Patients who are older than 75 years should not undergo such a procedure, as their mortality from the procedure outweighs their [[mortality]] from gastric cancer.  
* Decisions should be individualized based upon their comorbidities and the age of gastric cancer onset in their respective kindred.<ref name="pmid11443625">{{cite journal| author=Chun YS, Lindor NM, Smyrk TC, Petersen BT, Burgart LJ, Guilford PJ et al.| title=Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated? | journal=Cancer | year= 2001 | volume= 92 | issue= 1 | pages= 181-7 | pmid=11443625 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11443625  }}</ref>
* Decisions should be individualized based upon their comorbidities and the age of gastric cancer onset in their respective kindred.<ref name="pmid11443625">{{cite journal| author=Chun YS, Lindor NM, Smyrk TC, Petersen BT, Burgart LJ, Guilford PJ et al.| title=Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated? | journal=Cancer | year= 2001 | volume= 92 | issue= 1 | pages= 181-7 | pmid=11443625 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11443625  }}</ref>


== Gatric polyps ==
== Gastric Polyps ==
* [[Polypectomy]] should be performed for all known neoplastic polyps and for all polyps ≥1 cm in diameter, as biopsies alone cannot exclude foci of high-grade dysplasia or early gastric cancer.
* [[Polypectomy]] should be performed for all known [[neoplastic]] [[polyps]] and for all [[polyps]] ≥1 cm in diameter, as biopsies alone cannot exclude foci of high-grade [[dysplasia]] or early gastric cancer.
* In patients with multiple polyps, the largest polyp should be excised and representative biopsies obtained from the remaining polyps.
* In patients with multiple [[polyps]], the largest [[polyp]] should be excised and representative [[biopsies]] should be obtained from the remaining [[polyps]].


* [[Fundic gland polyposis|Fundic gland polyps]] are associated with a low risk of progression to cancer.  
* [[Fundic gland polyposis|Fundic gland polyps]] are associated with a low risk of progression to cancer.  
* Small proximal gastric polyps should be biopsied in patients with [[FAP]] to confirm their histology.
* Small proximal gastric [[polyps]] should be biopsied in patients with [[familial adenomatous polyposis]] ([[FAP]]) to confirm their [[histology]].
* Large or irregular appearing [[polyps]] should be biopsied or resected completely to assess for [[dysplasia]].  
* Large or irregular appearing [[polyps]] should be [[Biopsy|biopsied]] or resected completely to assess for [[dysplasia]].  
* Low-grade [[dysplasia]] is common in [[Fundic gland polyposis|fundic gland polyps]], but surgery should be reserved for high-grade [[dysplasia]] or [[cancer]].  
* Low-grade [[dysplasia]] is common in [[Fundic gland polyposis|fundic gland polyps]], but surgery should be reserved for high-grade [[dysplasia]] or [[cancer]].  
* [[Antrum|Antral]] polyps are usually [[adenomas]] and should be completely resected [[Endoscopy|endoscopically]] if possible. 
* [[Antrum|Antral]] [[polyps]] are usually [[adenomas]] and should be completely resected [[Endoscopy|endoscopically]] if possible. ?


=== Hyperplastic polyps ===
=== Hyperplastic polyps ===
* [[Hyperplastic polyp|Hyperplastic polyps]] occur in association with ''[[H. pylori]]-''related [[atrophic gastritis]].   
* [[Hyperplastic polyp|Hyperplastic polyps]] occur in association with ''[[H. pylori]]-''related [[atrophic gastritis]].   
* Surveillance with [[upper endoscopy]] should be performed based on the risk factors for gastric cancer one year after initial resection of [[Familial adenomatous polyposis|adenomatous gastric polyps]].  
* Surveillance with [[upper endoscopy]] should be performed based on the [[risk factors]] for gastric cancer one year after initial resection of [[Familial adenomatous polyposis|adenomatous gastric polyps]].  
* In individuals at high risk for gastric cancer, surveillance is continued long life.  
* In individuals at high risk for gastric cancer, surveillance is continued long life.  


== Juvenile polyposis syndrome ==
== Juvenile Polyposis Syndrome ==
* Screening the upper gastrointestinal tract with [[upper endoscopy]] starting at the age of 12 years.  
* [[Screening (medicine)|Screening]] the [[upper gastrointestinal tract]] with [[upper endoscopy]] starting at the age of 12 years.  
* If [[Polyp|polyps]] are detected, [[upper endoscopy]] should be repeated annually.  
* If [[Polyp|polyps]] are detected, [[upper endoscopy]] should be repeated annually.  
* In the absence of [[upper gastrointestinal tract]] [[polyps]], [[upper endoscopy]] can be performed every two to three years.  
* In the absence of [[upper gastrointestinal tract]] [[polyps]], [[upper endoscopy]] can be performed every two to three years.  


== Lynch syndrome ==
== Lynch Syndrome ==
* Individuals with a [[germline mutation]] in the [[DNA mismatch repair]] MMR or ''EPCAM'' genes have a definitive diagnosis of [[Lynch syndrome]] and should undergo [[Screening (medicine)|screening]] for Lynch syndrome associated cancers.
* Individuals with a [[germline mutation]] in the [[DNA mismatch repair]] MMR or ''EPCAM'' [[genes]] have a definitive diagnosis of [[Lynch syndrome]] and should undergo [[Screening (medicine)|screening]] for [[Lynch syndrome]] associated [[cancers]].
* Extent of [[Screening (medicine)|screening]] in these individuals can be individualized based on their personal and family cancer history and evidence of [[microsatellite instability]] on tumor testing.
* Extent of [[Screening (medicine)|screening]] in these individuals can be individualized based on their personal and family [[cancer]] history and evidence of [[microsatellite instability]] on [[tumor]] testing.
* Individuals at risk for [[Lynch syndrome]] include:
* Individuals at risk for [[Lynch syndrome]] include:
* Individuals in families meeting Amsterdam I or II criteria or revised Bethesda guidelines
** Individuals in families meeting Amsterdam I or II criteria or revised Bethesda guidelines


* [[Endometrial cancer]] prior to age 50 years
* [[Endometrial cancer]] prior to age 50 years
* First-degree relative of those with known MMR/''EPCAM'' [[gene mutation]]
* First-degree relative of those with known MMR/''EPCAM'' [[gene mutation]]
* Individuals with >5 percent chance of an MMR gene mutation
* Individuals with >5 percent chance of an MMR [[gene]] [[mutation]]


==References==
==References==

Revision as of 15:30, 22 December 2017


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2] Mohammed Abdelwahed M.D[3]

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Overview

Effective measures for the primary prevention of stomach cancer include smoking cessation, eradication of Helicobacter pylori infection, and having a balanced diet rich in fruits and vegetables. In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups. Individuals at increased risk for gastric cancer include; gastric adenomas, pernicious anemia, gastric intestinal metaplasia, familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome.

Primary prevention

Lifestyle modifications

  • Dietary modification is an important approach to control gastric cancer. There is a link between physical inactivity and obesity to many types of cancer.
  • Diet with low consumption of red meat, high in fruits and vegetables may have a protective effect against many cancers.
  • The World Health Assembly adopted the WHO Global Strategy on Diet, Physical Activity, and Health, in May 2004 to reduce deaths and diseases.

H.pylori eradication

Recommended first-line therapies for H pylori infection:

Regimen Drug dose Dosing frequency Duration(days) FDA approval
Clarithromycin triple PPI (standard or double dose)

Clarithromycin (500mg)

Amoxicillin (1gm) or Metronidazole (500mg TID)

BID 14 days YES
Bismuth Quadruple PPI (standard dose)

Bismuth subcitrate (120-300mg)or Subsalicylate (300mg)

Tetracyclin (500mg)

Metronidazole (250-500mg)

BID

QID

QID

TID to QID (500mg)

10-14 days NO
Concomitant PPI (standard dose)

Clarithromycin (500mg)

Amoxicillin (1gm)

Nitroimidazole (500mg)c

BID 10 -14 days NO
Sequential PPI (standard dose) + Amoxicillin (1gm)

PPI, Clarithromycin (500mg) + Nitroimidazole (500mg)

BID

BID

5-7 days

5-7 days

NO
Hybrid PPI (standard) + Amoxicillin (1gm)

PPI, Amoxicillin, Clarithromycin (500mg), Nitroimidazole (500mg)

BID

BID

7 days

7 days

NO
Levofloxacin triple PPI (standard dose)

Levofloxacin (500mg)

Amoxicillin (1gm)

BID

QID

BID

10-14 days NO
Levofloxacin sequential PPI (standard or double dose) + Amoxicillin (1 gm)

PPI, Amoxicillin, Levofloxacin (500mg QD), Nitroimidazole (500mg)

BID

BID

5-7 days NO
LOAD Levofloxacin (250mg)

PPI (double dose)

Nitazoxanide (500mg)c

Doxycycline (100mg)

QD

QD

BID

QD

7-10 days NO
: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval, PPI, Clarithromycin, Metronidazole are not an FDA approved treatment regimen.

‡: PPI, Bismuth, Tetracycline, and metronidazole prescribed separately are not an FDA approved treatment regimen.

  • BID, twice daily; FDA, Food and Drug Administration; PPI, proton pump inhibitor; TID, three times daily; QD, once daily; QID, four times daily.

c: Metronidazole or Tinidazole[1]

After the failure of first-line therapy, such patients should be considered for referral for salvage treatment.

Salvage therapies for Helicobacter pylori infection
Regimen Drugs(doses) Dosing frequency Duration(days) FDA approval
Bismuth quadruple BID

QID

QID

TID or QID

14 NO
Levofloxacin triple BID

QD

BID

14 NO
Concomitant BID

BID

BID

BID or TID

10-14 NO
Rifabutin triple BID

QD

BID

10 NO
High-dose dual TID or QID

TID or QID

14 NO
  • Whenever H. pylori infection is identified and treated, testing to prove eradication should be performed using:
  • A urea breath test
  • Fecal antigen test
  • Biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1–2 weeks.

Prevention Through Screening

  • In countries with a high incidence of gastric cancer such as east Asia countries, universal screening is recommended. ?
  • Japan has a high incidence of gastric cancer; therefore annual screening via double contrast barium radiography and photofluorography every year or upper endoscopy every two to three years.?
  • Screening interval is recommended to be every two years but may be extended to a three-year interval without significant difference in effect.  ??

Prevention of Hereditary Cancer

Screening

Prevention

  • For patients with a CDH1 mutation but who are not from an HDGC family, individualized evaluation at an experienced center before prophylactic total gastrectomy is recomended.[3]
  • Prophylactic gastrectomy is often advised between age 20 and 30.
  • Some suggest timing total gastrectomy in CDH1 mutation carriers at an age that is five years younger than the youngest family member who developed gastric cancer.[4]
  • Older patients are less likely to benefit from a prophylactic gastrectomy than younger patients because of a shorter life-expectancy and a higher perioperative risk.
  • Patients who are older than 75 years should not undergo such a procedure, as their mortality from the procedure outweighs their mortality from gastric cancer.
  • Decisions should be individualized based upon their comorbidities and the age of gastric cancer onset in their respective kindred.[5]

Gastric Polyps

Hyperplastic polyps

Juvenile Polyposis Syndrome

Lynch Syndrome

References

  1. "www.nature.com" (PDF).
  2. Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S; et al. (1999). "Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation". Am J Pathol. 155 (2): 337–42. doi:10.1016/S0002-9440(10)65129-2. PMC 1866861. PMID 10433926.
  3. Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage Consortium (2001). "Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families". Gastroenterology. 121 (6): 1348–53. PMID 11729114.
  4. Norton JA, Ham CM, Van Dam J, Jeffrey RB, Longacre TA, Huntsman DG; et al. (2007). "CDH1 truncating mutations in the E-cadherin gene: an indication for total gastrectomy to treat hereditary diffuse gastric cancer". Ann Surg. 245 (6): 873–9. doi:10.1097/01.sla.0000254370.29893.e4. PMC 1876967. PMID 17522512.
  5. Chun YS, Lindor NM, Smyrk TC, Petersen BT, Burgart LJ, Guilford PJ; et al. (2001). "Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?". Cancer. 92 (1): 181–7. PMID 11443625.

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