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{{CMG}}{{AE}}{{PSD}}
{{CMG}}; {{AE}} {{PSD}} {{MAD}}
{{Stomach cancer}}
{{Stomach cancer}}
==Overview==
==Overview==
Effective measures for the primary prevention of stomach cancer include smoking cessation, [[helicobacter pylori]] infection eradication, and having a balanced diet rich in fruits and vegetables.
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]] and [[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 [[gastric]] [[adenomas]], [[pernicious anemia]], gastric [[intestinal]] [[metaplasia]], [[familial adenomatous polyposis]], [[Lynch syndrome]], [[Peutz-Jeghers syndrome]], [[Juvenile polyposis syndrome]].  


==Primary prevention==
==Primary prevention==
=== Lifestyle modifications ===
Lifestyle modifications include following:<ref name="pmid25505712">{{cite journal |vauthors=Park JY, von Karsa L, Herrero R |title=Prevention strategies for gastric cancer: a global perspective |journal=Clin Endosc |volume=47 |issue=6 |pages=478–89 |date=November 2014 |pmid=25505712 |pmc=4260094 |doi=10.5946/ce.2014.47.6.478 |url=}}</ref>
* [[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 (nutrition)|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 ===
=== H.pylori eradication ===
*Recent meta-analyses have each found that the incidence of metachronous gastric cancer following the endoscopic resection of a gastric neoplasm was reduced by the eradication of H. pylori infection ( 31–33 ).
*The [[incidence]] of metachronous [[gastric cancer]] following the [[Endoscopy|endoscopic resection]] of a gastric neoplasm is known to be reduced by the eradication of [[Helicobacter pylori|H. pylori]] [[infection]]. <ref name="pmid25505712">{{cite journal |vauthors=Park JY, von Karsa L, Herrero R |title=Prevention strategies for gastric cancer: a global perspective |journal=Clin Endosc |volume=47 |issue=6 |pages=478–89 |date=November 2014 |pmid=25505712 |pmc=4260094 |doi=10.5946/ce.2014.47.6.478 |url=}}</ref><ref name="pmid27405145">{{cite journal |vauthors=García Martín R, Matía Cubillo Á |title=[INFLUENCE OF DIET IN PRIMARY PREVENTION OF GASTRIC CANCER, IN PATIENTS INFECTED WITH HELICOBACTER PYLORI] |language=Spanish; Castilian |journal=Rev Enferm |volume=39 |issue=5 |pages=33–8 |date=May 2016 |pmid=27405145 |doi= |url=}}</ref>
*Most recently, a meta-analysis comprising 24 studies (22 out of which were conducted in Asia) confirmed a lower rate of metachronous EGC following treatment of H. pylori infection; the incidence rate ratio was 0.54 (95% CI 0.46–0.65) ( 34 ).
 
'''Recommended first-line therapies for H pylori infection''':
{| class="wikitable"
!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<sup>'''†'''</sup>
|-
|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<sup>'''‡'''</sup>
|-
|Concomitant
|PPI (standard dose)
Clarithromycin (500mg)
 
Amoxicillin(1gm)
 
Nitroimidazole(500mg)<sup>c</sup>
|BID
|10 -14 days
|NO
|-
|Sequential
|PPI(standard dose)+Amoxicillin(1gm)
PPI,Clarithromycin(500mg)+Nitroimidazole(500mg)<sup>c</sup>
|BID
 
BID
|5-7 days
 
5-7 days
|NO
|-
|Hybrid
|PPI(standard)+Amoxicillin(1gm)
PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg)<sup>c</sup>
|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)<sup>c</sup>
|BID
BID
|5-7 days
|NO
|-
|LOAD
|Levofloxacin(250mg)
PPI(double dose)
 
Nitazoxanide(500mg)<sup>c</sup>
 
Doxycycline(100mg)
|QD
QD
 
BID
 
QD
|7-10 days
|NO
|-
|
| colspan="4" |'''†''': 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. However, Pylera, a combination product containing Bismuth subcitrate, Tetracycline, Metronidazole combination with PPI for 10 days is an FDA approved 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<ref name="urlwww.nature.com">{{cite web |url=https://www.nature.com/ajg/journal/v112/n2/pdf/ajg2016563a.pdf |title=www.nature.com |format= |work= |accessdate=}}</ref>
|}
 
After the failure of first-line therapy, such patients should be considered for referral for salvage treatment.
{| class="wikitable"
! colspan="5" |Salvage therapies for Helicobacter pylori infection
|-
|Regimen
|Drugs(doses)
|Dosing frequency
|Duration(days)
|FDA approval
|-
|Bismuth quadruple
|
* PPI(standard dose)
* Bismuth subciitrate 120-300mg or sub salicylate 300mg
* Tetracycline 500mg
* Metronidazole 500mg 
|BID
 
QID
 
QID
 
TID or QID
|14
|NO
|-
|Levofloxacin triple
|
* PPI(standard dose)
* Levofloxacin 500mg
* Amoxicillin 1gm
|BID
 
QD
 
BID
|14
|NO
|-
|Concomitant
|
* PPI(standard dose)
* Clarithromycin 500mg
* Amoxicillin 1gm
* Nitroimidazole 500mg
|BID


BID
== Prevention Through Screening ==
* 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 <ref name="pmid16232204">{{cite journal |vauthors=Ohata H, Oka M, Yanaoka K, Shimizu Y, Mukoubayashi C, Mugitani K, Iwane M, Nakamura H, Tamai H, Arii K, Nakata H, Yoshimura N, Takeshita T, Miki K, Mohara O, Ichinose M |title=Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography |journal=Cancer Sci. |volume=96 |issue=10 |pages=713–20 |date=October 2005 |pmid=16232204 |doi=10.1111/j.1349-7006.2005.00098.x |url=}}</ref>
* [[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<ref name="pmid16232204">{{cite journal |vauthors=Ohata H, Oka M, Yanaoka K, Shimizu Y, Mukoubayashi C, Mugitani K, Iwane M, Nakamura H, Tamai H, Arii K, Nakata H, Yoshimura N, Takeshita T, Miki K, Mohara O, Ichinose M |title=Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography |journal=Cancer Sci. |volume=96 |issue=10 |pages=713–20 |date=October 2005 |pmid=16232204 |doi=10.1111/j.1349-7006.2005.00098.x |url=}}</ref>


BID
== Prevention of Hereditary Cancer  ==
 
BID or TID
|10-14
|NO
|-
|Rifabutin triple
|
* PPI(standard dose)
* Rifabutin 300mg
* Amoxicillin 1gm
|BID
 
QD
 
BID
|10
|NO
|-
|High-dose dual
|
* PPI(standard to double dose)
* Amoxicillin 1gm TID or 750mg QID
|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.
 
== Screening ==
In countries with a high incidence of gastric cancer such as east asia countaries, universal screening is recommended. [17-19]
 
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].
 
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''' ===
In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups [41-52].
 
Individuals at increased risk for gastric cancer include those with the following:
* Gastric adenomas
* Pernicious anemia
* Gastric intestinal metaplasia
* Familial adenomatous polyposis
* Lynch syndrome
* Peutz-Jeghers 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 [11].
*  [[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><ref name="pmid10886930">{{cite journal |vauthors=Abreu Ed |title=[Primary prevention and detection of gastric cancer] |language=Portuguese |journal=Cad Saude Publica |volume=13 Suppl 1 |issue= |pages=105–108 |date=1997 |pmid=10886930 |doi= |url=}}</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.  [12].
 
* Prophylactic gastrectomy is often advised between age 20 and 30 [12]. 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 [20,21]. 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. 
 
== Gatric 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.
 
In patients with multiple polyps, the largest polyp should be excised and representative biopsies obtained from the remaining polyps.
* 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.
* Large or irregular appearing polyps should be biopsied or resected completely to assess for dysplasia.  
* Low-grade dysplasia is common in fundic gland polyps, but surgery should be reserved for high-grade dysplasia or cancer [1].  
* Antral polyps are usually adenomas and should be completely resected endoscopically if possible. 
Hyperplastic polyps occur in association with ''H. pylori-''related atrophic gastritis. They have some malignant potential. Hyperplastic polyps >0.5 cm should be resected completely. Surveillance with upper endoscopy should be performed based on the cancer risk due to concurrent chronic atrophic gastritis and other risk factors for gastric cancer.
 
We perform an upper endoscopy for surveillance one year after initial resection of adenomatous gastric polyps. In individuals at high risk for gastric cancer, surveillance is continued indefinitely.
 
For type 1 and 2 gastric neuroendocrine tumors smaller than 1 to 2 cm, endoscopic resection is the treatment of choice.


Type 3 tumors are treated by partial or total gastrectomy with local lymph node resection. 
* 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>


== Juvenile polyposis syndrome ==
* [[Prophylactic]] [[gastrectomy]] is often advised between age 20 and 30.
* Screening the upper gastrointestinal tract with upper endoscopy starting at the age of 12 years.  
* 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>
* If polyps are detected, upper endoscopy should be repeated annually.  
* 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.<ref name="pmid10886930">{{cite journal |vauthors=Abreu Ed |title=[Primary prevention and detection of gastric cancer] |language=Portuguese |journal=Cad Saude Publica |volume=13 Suppl 1 |issue= |pages=105–108 |date=1997 |pmid=10886930 |doi= |url=}}</ref>
* In the absence of upper gastrointestinal tract polyps, upper endoscopy can be performed every two to three years [9].


== Lynch syndrome ==
* [[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]].  
* Individuals with a pathogenic germline mutation in the DNA mismatch repair (MMR) or ''EPCAM'' genes have a definitive diagnosis of Lynch syndrome and should undergo screening for Lynch syndrome associated cancers. Screening recommendations for these individuals are discussed in detail below.
* 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>
* Screening for Lynch syndrome related cancers should also be considered in individuals at risk for Lynch syndrome who have either not undergone genetic evaluation or have indeterminate genetic test results.
* extent of 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 in families meeting Amsterdam I or II criteria or revised Bethesda guidelines:
* Endometrial cancer prior to age 50 years
* First-degree relative of those with known MMR/''EPCAM'' gene mutation
* Individuals with >5 percent chance of a MMR gene mutation by prediction models


==References==
==References==

Latest revision as of 20:12, 25 January 2019


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 and 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

Lifestyle modifications include following:[1]

  • 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

Prevention Through Screening

Prevention of Hereditary Cancer

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.[6]

References

  1. 1.0 1.1 Park JY, von Karsa L, Herrero R (November 2014). "Prevention strategies for gastric cancer: a global perspective". Clin Endosc. 47 (6): 478–89. doi:10.5946/ce.2014.47.6.478. PMC 4260094. PMID 25505712.
  2. García Martín R, Matía Cubillo Á (May 2016). "[INFLUENCE OF DIET IN PRIMARY PREVENTION OF GASTRIC CANCER, IN PATIENTS INFECTED WITH HELICOBACTER PYLORI]". Rev Enferm (in Spanish; Castilian). 39 (5): 33–8. PMID 27405145.
  3. 3.0 3.1 Ohata H, Oka M, Yanaoka K, Shimizu Y, Mukoubayashi C, Mugitani K, Iwane M, Nakamura H, Tamai H, Arii K, Nakata H, Yoshimura N, Takeshita T, Miki K, Mohara O, Ichinose M (October 2005). "Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography". Cancer Sci. 96 (10): 713–20. doi:10.1111/j.1349-7006.2005.00098.x. PMID 16232204.
  4. 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.
  5. 5.0 5.1 Abreu E (1997). "[Primary prevention and detection of gastric cancer]". Cad Saude Publica (in Portuguese). 13 Suppl 1: 105–108. PMID 10886930. Vancouver style error: initials (help)
  6. 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.
  7. 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.
  8. 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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