Difference between revisions of "Gastric lymphoma"

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__NOTOC__
 
__NOTOC__
 
{{SI}}
 
{{SI}}
{{CMG}}{{Mazia}}
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{{CMG}}; {{AE}}{{Mazia}}
  
 
==Overview==
 
==Overview==
 +
Primary gastric lymphoma is [[Cancer (disease)|cancer]] [[derived]] from [[lymphocytes]] (a type of [[White blood cells|white blood cell]]) that originates in the [[stomach]]. Most common cause of primary gastric lymphoma is [[Mucosa-associated lymphoid tissue (MALT) lymphoma|mucosa-associated lymphoid tissue (MALT)]] [[lymphoma]] and [[Diffuse large B-cell lymphoma|diffuse large B-cell lymphoma (DLBCL)]] of the [[stomach]]. Primary gastric lymphoma may be classified according to histology into MALT lymphoma and DLBCL. MALT lymphoma can be further divided into H. pylori positive MALT lymphoma and H. pylori negative MALT lymphoma. DLBCL can be divided into 3 subgroups germinal-center B-cell-like, activated B-cell-like, primary mediastinal DLBCL. The exact pathogenesis of primary gastric lymphoma is not fully understood. Common [[symptoms]] of primary gastric lymphoma include [[epigastric]] [[discomfort]], [[anorexia]], [[weight loss]], [[nausea]] associated with or without [[vomiting]], [[occult]] [[gastrointestinal bleeding]], [[early satiety]]. Less common [[symptoms]] include [[Fever|ever]] and [[night sweats]]. [[Patients]] with primary gastric lymphoma usually appear normal. Vital signs are within normal limits unless there is complication. [[Physical examination]] of [[patients]] with primary gastric lymphoma is usually remarkable for [[palpable]] [[mass]] and [[Lymphadenopathy|peripheral lymphadenopathy]]. Gastric lymphoma must be differentiated from conditions with similar presentation like [[acute gastritis]], [[Gastritis|chronic gastritis]], [[atrophic gastritis]], [[Crohn's disease]], [[gastroesophageal reflux disease]], [[peptic ulcer disease]], [[gastrinoma]] and [[gastric adenocarcinoma]]. Primary gastric lymphoma commonly affects [[elderly]] [[patients]] in the fifth or sixth decade of [[life]]. Primary gastric lymphoma is more [[Prevalence|prevalent]] in [[men]] than in [[women]]. [[Risk factors]] for gastric [[lymphoma]] include ''[[Helicobacter pylori]], l''ong-term [[immunosuppressant]] [[drug]] [[therapy]], [[HIV]] [[infection]]. The majority of [[patients]] with primary gastric lymphoma present with nonspecific [[symptoms]] in the 5th decade of life. Early [[clinical]] features include [[epigastric pain]], [[nausea]], and [[vomiting]]. If left untreated, patients with gastric lymphoma may progress to develop [[anorexia]], [[weight loss]], and [[early satiety]]. Common complications of gastric lymphoma include [[perforation]], [[hemorrhage]], and [[obstruction]]. [[Prognosis]] is generally good, and complete remission can be achieved after 6-8 rounds of [[chemotherapy]] or following [[surgery]]. [[Endoscopy|Upper gastrointestinal endoscopy]] with [[biopsy]] is the gold standard test for the [[diagnosis]] of [[gastric]] [[lymphoma]]. [[Laparotomy]] and [[laparoscopy]] should be performed when the [[patient]] presents with [[complications]] such as [[perforation]] or [[obstruction]]. An [[Endoscopic ultrasound|endoscopic ultrasound (EUS)]] will help assess the [[Depth of field|depth]] of [[lymphoma]] [[invasion]] and involvement of [[Lymph nodes|perigastric nodes]]. [[MALT lymphoma]] presents as [[superficial]] spreading or [[diffuse]] infiltrating [[lesion]] whereas [[diffuse]] [[Diffuse large B cell lymphoma|large B cell lymphoma]] has a [[Mass|typical mass]] forming [[lesion]] appearance on [[Endoscopy|endoscopic]] [[ultrasound]]. [[Imaging]] [[Investigational product|investigations]] including [[CT]] [[Scan|scans]] or [[endoscopic ultrasound]] are useful to stage [[disease]].  [[Hematological]] parameters are usually checked to assist with [[Staging (pathology)|staging]] and to exclude concomitant [[leukemia]]. An elevated [[lactate dehydrogenase|LDH]] level may be suggestive of [[lymphoma]]. There are no established measures for the [[Prevention (medical)|primary and secondary prevention]] of gastric lymphoma.
  
Primary '''gastric lymphoma''' is cancer derived from lymphocytes (a type of white blood cell) that originates in the stomach<ref>Dawson IMP, Cornes JS, Morrison BC. Primary malignant lymphoid tumours of the intestinal tract. Br J Surg. 1961;49:80-89.</ref>Gastric Lymphoma is a rare condition, that accounts for less than 15% of gastric malignancies and about 2% of all lymphomas. Stomach is the most common extra-nodal site for lymphomas<ref>Aisenberg AC. Coherent view of non-Hodgkin's lymphoma. J Clin Oncol. 1995;13:2656-2675.</ref>; it is also the most common source of lymphomas in the [[gastrointestinal tract]]<ref>Koch P ''et al.''  Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92.  J Clin Oncol 2001 Sep 15;19(18):3861-73.</ref>
+
==Classification==
 
+
Primary gastric lymphoma may be classified according to [[histology]] into the following subtypes:
==Primary Gastric Lymphoma==
+
*B-cell lymphomas are of two main types:
[[Image:Gastric MALT lymphoma 2.jpg|thumb|left|300px|Endoscopic image of gastric [[MALT lymphoma]] taken in body of [[stomach]] in patient who presented with [[upper gastrointestinal bleed|upper GI hemorrhage]].  Appearance is similar to [[gastric ulcer]] with adherent clot.]]
+
**[[MALT lymphoma]]
===Clinical presentation===
+
**DLBCL ([[Diffuse large B cell lymphoma|diffuse large B-cell lymphoma]])
Primary gastric lymphoma usually affects the elderly (with peak incidence in the sixth decade of life)<ref>Thirlby RC. Gastrointestinal lymphoma: a surgical perspective. Oncology (Huntingt). 1993;7:29-32.</ref> and presenting symptoms include [[epigastric]] pain, early satiety, fatigue and weight loss.
+
*[[MALT lymphoma]] can be further divided into:
 
+
**[[Helicobacter pylori|H. pylori]] positive [[MALT lymphoma]]
===Diagnosis===
+
**[[Helicobacter pylori|H. pylori]] negative [[MALT lymphoma]]  
These lymphomas are often difficult to differentiate from [[gastric carcinoma|gastric adenocarcinoma]]. The lesions are usually ulcers with a ragged, thickened [[mucosa]]l pattern on [[Radiography#Medicine|contrast radiograph]]s.
+
*[[Diffuse large B cell lymphoma|DLBCL]] can be divided into 3 subgroups based on the gene expression:
 
+
**Germinal-center B-cell-like
The diagnosis is typically made by [[biopsy]] at the time of [[gastroscopy|endoscopy]].  Several endoscopic findings have been reported, including solitary ulcers, thickened gastric folds, mass lesions and nodules. As there may be infiltration of the submucosa, larger [[biopsy]] [[forceps]], [[endoscopic ultrasound]] guided biopsy, [[endoscopic mucosal resection|endoscopic submucosal resection]], or [[laparotomy]] may be required to obtain tissue.
+
**Activated B-cell-like
 
+
**Primary mediastinal DLBCL
Imaging investigations including [[CT]] scans or [[endoscopic ultrasound]] are useful to stage disease.  Hematological parameters are usually checked to assist with staging and to exclude concomitant [[leukemia]].  An elevated [[lactate dehydrogenase|LDH]] level may be suggestive of lymphoma.
 
  
 +
==Pathophysiology==
 +
*The exact pathogenesis of primary gastric lymphoma is not fully understood.<ref name="pmid8683376">{{cite journal |vauthors=Hussell T, Isaacson PG, Crabtree JE, Spencer J |title=Helicobacter pylori-specific tumour-infiltrating T cells provide contact dependent help for the growth of malignant B cells in low-grade gastric lymphoma of mucosa-associated lymphoid tissue |journal=J. Pathol. |volume=178 |issue=2 |pages=122–7 |year=1996 |pmid=8683376 |doi=10.1002/(SICI)1096-9896(199602)178:2<122::AID-PATH486>3.0.CO;2-D |url=}}</ref><ref name="pmid20688564">{{cite journal |vauthors=Engels EA, Cho ER, Jee SH |title=Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study |journal=Lancet Oncol. |volume=11 |issue=9 |pages=827–34 |year=2010 |pmid=20688564 |pmc=2933963 |doi=10.1016/S1470-2045(10)70167-4 |url=}}</ref>
 +
*Primary gastric lymphoma is [[Cancer (disease)|cancer]] [[derived]] from [[lymphocytes]] (a type of [[White blood cells|white blood cell]]) that originates in the [[stomach]].<ref>Dawson IMP, Cornes JS, Morrison BC. Primary malignant lymphoid tumours of the intestinal tract. Br J Surg. 1961;49:80-89.</ref><ref>Aisenberg AC. Coherent view of non-Hodgkin's lymphoma. J Clin Oncol. 1995;13:2656-2675.</ref>
 +
*Most common cause of primary gastric lymphoma is [[Mucosa-associated lymphoid tissue (MALT) lymphoma|mucosa-associated lymphoid tissue (MALT)]] [[lymphoma]] and [[Diffuse large B-cell lymphoma|diffuse large B-cell lymphoma (DLBCL)]] of the [[stomach]]. These account for 90% of all [[Diagnosis|diagnosed]] cases. [[Lymphomas]] originating outside the [[lymph nodes]] are referred to as [[Lymphoma|extra nodal lymphoma]]. Primary gastric lymphoma is the most common type of [[Lymphoma|extra nodal lymphoma]].
 +
*Most of the [[MALT lymphoma|MALT lymphomas]] have an associated history of H.pylori infection. Chronic inflammation associated with H.pylori can cause T and B cell proliferation that increases the risk of malignant transformation.
 +
In case of [[Diffuse large B cell lymphoma|DLBCL]], antibiotic eradication therapy for H.pylori has shown to result in complete remission of lymphoma highlighting the role of H.pylori in the pathogenesis.
 +
*[[Hepatitis B virus|HBV]] plays a role in the pathogenesis of B-cell NHL, evidenced by an increased risk of developing [[Non-Hodgkin lymphoma|NHL]] in [[Hepatitis B surface antigen|HBsAg]] positive patients.
 
===Histopathology===
 
===Histopathology===
The majority of gastric lymphomas are [[non-Hodgkin's lymphoma]] of [[B-cell]] origin. These tumors may range from well-differentiated, superficial involvements ([[Mucosa-associated lymphoid tissue|MALT]]) to high-grade, large-cell lymphomas.
+
Most of the gastric lymphomas are predominantly [[Non-Hodgkin lymphoma|non-Hodgkin’s lymphoma]] of [[B-cell|B-cell origin]]. Primary gastric lymphoma can vary from being well-differentiated, low-grade [[lymphomas]] to high grade or large cell [[lymphomas]].<ref name="pmid19565363">{{cite journal |vauthors=Wang T, Gui W, Shen Q |title=Primary gastrointestinal non-Hodgkin's lymphoma: clinicopathological and prognostic analysis |journal=Med. Oncol. |volume=27 |issue=3 |pages=661–6 |year=2010 |pmid=19565363 |doi=10.1007/s12032-009-9265-1 |url=}}</ref>
  
Other lymphomas involving the stomach include [[mantle cell lymphoma]] and [[T-cell lymphomas]] which may be associated with [[enteropathy]]; the latter usually occur in the [[small bowel]] but have been reported in the stomach.
+
==Symptoms==
 +
=====Common Symptoms=====
 +
Common [[symptoms]] of primary gastric lymphoma include:<ref name="pmid5007387">{{cite journal |vauthors=Freeman C, Berg JW, Cutler SJ |title=Occurrence and prognosis of extranodal lymphomas |journal=Cancer |volume=29 |issue=1 |pages=252–60 |year=1972 |pmid=5007387 |doi= |url=}}</ref><ref name="pmid11559724">{{cite journal |vauthors=Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rübe C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M |title=Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92 |journal=J. Clin. Oncol. |volume=19 |issue=18 |pages=3861–73 |year=2001 |pmid=11559724 |doi=10.1200/JCO.2001.19.18.3861 |url=}}</ref>
 +
*[[Epigastric]] [[discomfort]]
 +
*[[Anorexia]]
 +
*[[Weight loss]]  
 +
*[[Nausea]] associated with or without [[vomiting]]
 +
*[[Occult]] [[gastrointestinal bleeding]]
 +
*[[Early satiety]]
 +
=====Less Common Symptoms=====
 +
Less common [[symptoms]] include:
 +
*[[Fever]]
 +
*[[Night sweats]]
  
===Risk Factors===
+
==Physical Examination==
Risk factors for gastric lymphoma include the following:
+
===Appearance of the Patient===
*''[[Helicobacter pylori]]'' <ref>[http://content.nejm.org/cgi/content/full/330/18/1267 NEJM article]</ref>
+
*[[Patients]] with primary gastric lymphoma usually appear normal.<ref name="pmid11559724">{{cite journal |vauthors=Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rübe C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M |title=Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92 |journal=J. Clin. Oncol. |volume=19 |issue=18 |pages=3861–73 |year=2001 |pmid=11559724 |doi=10.1200/JCO.2001.19.18.3861 |url=}}</ref>
*Long-term immunosuppressant drug therapy
+
===Vital signs===
*[[HIV]] infection
+
Vital signs are within normal limits unless there is complication.
 +
===Abdominal Examination===
 +
*[[Physical examination]] of [[patients]] with primary gastric lymphoma is usually remarkable for [[palpable]] [[mass]] and [[Lymphadenopathy|peripheral lymphadenopathy]].
  
 
==Differential Diagnosis==
 
==Differential Diagnosis==
Gastric lymphoma must be differentiated from:<ref name="pmid6710074">{{cite journal| author=Sugimachi K, Inokuchi K, Kuwano H, Ooiwa T| title=Acute gastritis clinically classified in accordance with data from both upper GI series and endoscopy. | journal=Scand J Gastroenterol | year= 1984 | volume= 19 | issue= 1 | pages= 31-7 | pmid=6710074 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6710074  }} </ref><ref name="pmid25901896">{{cite journal| author=Sipponen P, Maaroos HI| title=Chronic gastritis. | journal=Scand J Gastroenterol | year= 2015 | volume= 50 | issue= 6 | pages= 657-67 | pmid=25901896 | doi=10.3109/00365521.2015.1019918 | pmc=4673514 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25901896  }} </ref><ref name="pmid16819502">{{cite journal| author=Sartor RB| title=Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. | journal=Nat Clin Pract Gastroenterol Hepatol | year= 2006 | volume= 3 | issue= 7 | pages= 390-407 | pmid=16819502 | doi=10.1038/ncpgasthep0528 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16819502  }} </ref><ref name="pmid2789799">{{cite journal| author=Sipponen P| title=Atrophic gastritis as a premalignant condition. | journal=Ann Med | year= 1989 | volume= 21 | issue= 4 | pages= 287-90 | pmid=2789799 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2789799  }} </ref><ref name="pmid25133039">{{cite journal| author=Badillo R, Francis D| title=Diagnosis and treatment of gastroesophageal reflux disease. | journal=World J Gastrointest Pharmacol Ther | year= 2014 | volume= 5 | issue= 3 | pages= 105-12 | pmid=25133039 | doi=10.4292/wjgpt.v5.i3.105 | pmc=4133436 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25133039  }} </ref><ref name="pmid17956071">{{cite journal| author=Ramakrishnan K, Salinas RC| title=Peptic ulcer disease. | journal=Am Fam Physician | year= 2007 | volume= 76 | issue= 7 | pages= 1005-12 | pmid=17956071 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17956071  }} </ref><ref name="pmid17985090">{{cite journal| author=Banasch M, Schmitz F| title=Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. | journal=Wien Klin Wochenschr | year= 2007 | volume= 119 | issue= 19-20 | pages= 573-8 | pmid=17985090 | doi=10.1007/s00508-007-0884-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17985090  }} </ref><ref name="pmid15621988">{{cite journal| author=Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM| title=Gastric adenocarcinoma: review and considerations for future directions. | journal=Ann Surg | year= 2005 | volume= 241 | issue= 1 | pages= 27-39 | pmid=15621988 | doi= | pmc=1356843 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15621988  }} </ref><ref name="pmid21390139">{{cite journal| author=Ghimire P, Wu GY, Zhu L| title=Primary gastrointestinal lymphoma. | journal=World J Gastroenterol | year= 2011 | volume= 17 | issue= 6 | pages= 697-707 | pmid=21390139 | doi=10.3748/wjg.v17.i6.697 | pmc=3042647 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21390139  }} </ref>
+
Gastric lymphoma must be differentiated from conditions with similar presentation like [[acute gastritis]], [[Gastritis|chronic gastritis]], [[atrophic gastritis]], [[Crohn's disease]], [[gastroesophageal reflux disease]], [[peptic ulcer disease]], [[gastrinoma]] and [[gastric adenocarcinoma]] :<ref name="pmid6710074">{{cite journal| author=Sugimachi K, Inokuchi K, Kuwano H, Ooiwa T| title=Acute gastritis clinically classified in accordance with data from both upper GI series and endoscopy. | journal=Scand J Gastroenterol | year= 1984 | volume= 19 | issue= 1 | pages= 31-7 | pmid=6710074 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6710074  }} </ref><ref name="pmid25901896">{{cite journal| author=Sipponen P, Maaroos HI| title=Chronic gastritis. | journal=Scand J Gastroenterol | year= 2015 | volume= 50 | issue= 6 | pages= 657-67 | pmid=25901896 | doi=10.3109/00365521.2015.1019918 | pmc=4673514 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25901896  }} </ref><ref name="pmid16819502">{{cite journal| author=Sartor RB| title=Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. | journal=Nat Clin Pract Gastroenterol Hepatol | year= 2006 | volume= 3 | issue= 7 | pages= 390-407 | pmid=16819502 | doi=10.1038/ncpgasthep0528 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16819502  }} </ref><ref name="pmid2789799">{{cite journal| author=Sipponen P| title=Atrophic gastritis as a premalignant condition. | journal=Ann Med | year= 1989 | volume= 21 | issue= 4 | pages= 287-90 | pmid=2789799 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2789799  }} </ref><ref name="pmid25133039">{{cite journal| author=Badillo R, Francis D| title=Diagnosis and treatment of gastroesophageal reflux disease. | journal=World J Gastrointest Pharmacol Ther | year= 2014 | volume= 5 | issue= 3 | pages= 105-12 | pmid=25133039 | doi=10.4292/wjgpt.v5.i3.105 | pmc=4133436 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25133039  }} </ref><ref name="pmid17956071">{{cite journal| author=Ramakrishnan K, Salinas RC| title=Peptic ulcer disease. | journal=Am Fam Physician | year= 2007 | volume= 76 | issue= 7 | pages= 1005-12 | pmid=17956071 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17956071  }} </ref><ref name="pmid17985090">{{cite journal| author=Banasch M, Schmitz F| title=Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. | journal=Wien Klin Wochenschr | year= 2007 | volume= 119 | issue= 19-20 | pages= 573-8 | pmid=17985090 | doi=10.1007/s00508-007-0884-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17985090  }} </ref><ref name="pmid15621988">{{cite journal| author=Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM| title=Gastric adenocarcinoma: review and considerations for future directions. | journal=Ann Surg | year= 2005 | volume= 241 | issue= 1 | pages= 27-39 | pmid=15621988 | doi= | pmc=1356843 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15621988  }} </ref><ref name="pmid21390139">{{cite journal| author=Ghimire P, Wu GY, Zhu L| title=Primary gastrointestinal lymphoma. | journal=World J Gastroenterol | year= 2011 | volume= 17 | issue= 6 | pages= 697-707 | pmid=21390139 | doi=10.3748/wjg.v17.i6.697 | pmc=3042647 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21390139  }} </ref>
 
<div style="width: 85%;">
 
<div style="width: 85%;">
  
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!Aggravating Factors
 
!Aggravating Factors
 
!Alleviating Factors
 
!Alleviating Factors
 +
|-
 +
![[Gastric lymphoma|Primary gastric lymphoma]]
 +
|
 +
* ''[[H. pylori]]'' infection
 +
|
 +
* [[Abdominal pain]]
 +
* [[Chest pain]]
 +
|<nowiki>-</nowiki>
 +
|<nowiki>-</nowiki>
 +
|<nowiki>-</nowiki>
 +
|<nowiki>-</nowiki>
 +
|<nowiki>-</nowiki>
 +
| +/-
 +
|<nowiki>-</nowiki>
 +
|<nowiki>-</nowiki>
 +
|Useful in collecting the tissue for [[biopsy]]
 +
|'''Other symptoms'''
 +
* Painless swollen [[lymph nodes]] in neck and armpit
 +
* Night sweats
 +
* [[Fatigue]]
 +
* [[Fever]]
 +
* [[Cough]] or trouble breathing
 
|-
 
|-
 
![[Acute gastritis]]
 
![[Acute gastritis]]
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|Food
 
|Food
 
|[[Antacids]]
 
|[[Antacids]]
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|?
+
| +/-
 
|[[Melena|Black stools]]
 
|[[Melena|Black stools]]
 
|
 
|
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|Food
 
|Food
 
|[[Antacids]]
 
|[[Antacids]]
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|''[[H. pylori]] [[gastritis]]''
 
|''[[H. pylori]] [[gastritis]]''
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|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|
+
|<nowiki>+/-</nowiki>
|?
+
| +/-
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|''[[H. pylori]]''
 
|''[[H. pylori]]''
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|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|?
+
| +/-
|?
+
| +/-
 
|
 
|
 
* Chronic [[diarrhea]] often bloody with [[pus]] or [[mucus]]
 
* Chronic [[diarrhea]] often bloody with [[pus]] or [[mucus]]
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* [[Antacids]]
 
* [[Antacids]]
 
* Head elevation during sleep
 
* Head elevation during sleep
|?
+
| +/-
  
 
(Suspect delayed gastric emptying)
 
(Suspect delayed gastric emptying)
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
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* [[Radiation therapy]]
 
* [[Radiation therapy]]
 
* Medications
 
* Medications
* Zollinger-ellison syndrome
+
* [[Zollinger-Ellison syndrome]]
 
|
 
|
 
* [[Epigastric pain]] sometimes extending to back
 
* [[Epigastric pain]] sometimes extending to back
 
* [[Right upper quadrant pain]]
 
* [[Right upper quadrant pain]]
|
+
|'''[[Duodenal ulcer]]'''
'''[[Duodenal ulcer]]'''
 
 
*Pain aggravates with empty stomach
 
*Pain aggravates with empty stomach
 
'''[[Gastric ulcer]]'''
 
'''[[Gastric ulcer]]'''
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* [[Duodenal ulcer]]
 
* [[Duodenal ulcer]]
 
:*Pain alleviates with food
 
:*Pain alleviates with food
|?
+
| +/-
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
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|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|?
+
| +/-
  
 
(suspect [[gastric outlet obstruction]])
 
(suspect [[gastric outlet obstruction]])
|?
+
| +/-
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
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|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
|?
+
| +/-
 
|
 
|
 
* [[Melena|Black stools]], or blood in stools
 
* [[Melena|Black stools]], or blood in stools
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* Early [[satiety]]
 
* Early [[satiety]]
 
* Frequent [[burping]]
 
* Frequent [[burping]]
|-
 
![[Gastric lymphoma|Primary gastric lymphoma]]
 
|
 
* ''[[H. pylori]]'' infection
 
|
 
* [[Abdominal pain]]
 
* [[Chest pain]]
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|?
 
|<nowiki>-</nowiki>
 
|<nowiki>-</nowiki>
 
|Useful in collecting the tissue for [[biopsy]]
 
|'''Other symptoms'''
 
* Painless swollen [[lymph nodes]] in neck and armpit
 
* Night sweats
 
* [[Fatigue]]
 
* [[Fever]]
 
* [[Cough]] or trouble breathing
 
 
|}
 
|}
  
 
</div>
 
</div>
  
 +
==Demographics==
 +
* Primary gastric lymphoma commonly affects [[elderly]] [[patients]] in the fifth or sixth decade of [[life]].<ref>Thirlby RC. Gastrointestinal lymphoma: a surgical perspective. Oncology (Huntingt). 1993;7:29-32.</ref>
 +
 +
* Primary gastric lymphoma is more [[Prevalence|prevalent]] in [[men]] than in [[women]].
 +
 +
==Risk Factors==
 +
[[Risk factors]] for gastric [[lymphoma]] include the following:<ref>[http://content.nejm.org/cgi/content/full/330/18/1267 NEJM article]</ref>
 +
*[[Helicobacter pylori]]
 +
*Long-term [[immunosuppressant]] [[drug]] [[therapy]]
 +
*[[HIV]] [[infection]]
 +
 +
==Natural History, Complications and Prognosis==
 +
===Natural History===
 +
*The majority of [[patients]] with primary gastric lymphoma present with nonspecific [[symptoms]] in the 5th decade of life.
 +
*Early [[clinical]] features include [[epigastric pain]], [[nausea]], and [[vomiting]].
 +
*If left untreated, patients with gastric lymphoma may progress to develop [[anorexia]], [[weight loss]], and [[early satiety]].
 +
===Complications===
 +
*Common complications of gastric lymphoma include [[perforation]], [[hemorrhage]], and [[obstruction]].
 +
===Prognosis===
 +
*[[Prognosis]] is generally good, and complete remission can be achieved after 6-8 rounds of [[chemotherapy]] or following [[surgery]].
 +
 +
==Diagnosis==
 +
*[[Endoscopy|Upper gastrointestinal endoscopy]] with [[biopsy]] is the gold standard test for the [[diagnosis]] of [[gastric]] [[lymphoma]].<ref name="pmid1936785">{{cite journal |vauthors=Cogliatti SB, Schmid U, Schumacher U, Eckert F, Hansmann ML, Hedderich J, Takahashi H, Lennert K |title=Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients |journal=Gastroenterology |volume=101 |issue=5 |pages=1159–70 |year=1991 |pmid=1936785 |doi= |url=}}</ref><ref name="pmid7797116">{{cite journal |vauthors=Muller AF, Maloney A, Jenkins D, Dowling F, Smith P, Bessell EM, Toghill PJ |title=Primary gastric lymphoma in clinical practice 1973-1992 |journal=Gut |volume=36 |issue=5 |pages=679–83 |year=1995 |pmid=7797116 |pmc=1382669 |doi= |url=}}</ref><ref name="pmid19565363">{{cite journal |vauthors=Wang T, Gui W, Shen Q |title=Primary gastrointestinal non-Hodgkin's lymphoma: clinicopathological and prognostic analysis |journal=Med. Oncol. |volume=27 |issue=3 |pages=661–6 |year=2010 |pmid=19565363 |doi=10.1007/s12032-009-9265-1 |url=}}</ref>
 +
*[[Laparotomy]] and [[laparoscopy]] should be performed when the [[patient]] presents with [[complications]] such as [[perforation]] or [[obstruction]].
 +
*Findings on [[Endoscopy|upper gastrointestinal endoscopy]] suggestive of [[gastric]] [[lymphoma]]:
 +
**[[Mucosal]] [[erythema]]
 +
**A [[mass]] or [[Polypoidy|polypoid]] [[Lesions|lesion]] with or without [[ulceration]]
 +
**[[Benign]]-appearing [[gastric]] [[ulcer]]
 +
**[[Nodular]] [[Lesions|lesion]]
 +
**Thickened, cerebroid [[gastric]] folds
 +
<br clear="left" />[[Image:Gastric MALT lymphoma 2.jpg|thumb|left|300px|Endoscopic image of gastric [[MALT lymphoma]] taken in body of [[stomach]] in patient who presented with [[upper gastrointestinal bleed|upper GI hemorrhage]].  Appearance is similar to [[gastric ulcer]] with adherent clot.|thumb|By Samir at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=4647530]]<br clear="left" />
 +
*An [[Endoscopic ultrasound|endoscopic ultrasound (EUS)]] will help assess the [[Depth of field|depth]] of [[lymphoma]] [[invasion]] and involvement of [[Lymph nodes|perigastric nodes]].
 +
*[[MALT lymphoma]] presents as [[superficial]] spreading or [[diffuse]] infiltrating [[lesion]] whereas [[diffuse]] [[Diffuse large B cell lymphoma|large B cell lymphoma]] has a [[Mass|typical mass]] forming [[lesion]] appearance on [[Endoscopy|endoscopic]] [[ultrasound]].
 +
*[[Imaging]] [[Investigational product|investigations]] including [[CT]] [[Scan|scans]] or [[endoscopic ultrasound]] are useful to stage [[disease]].
 +
*[[Hematological]] parameters are usually checked to assist with [[Staging (pathology)|staging]] and to exclude concomitant [[leukemia]].  An elevated [[lactate dehydrogenase|LDH]] level may be suggestive of [[lymphoma]].
 +
===MRI===
 +
Findings of Gastric lymphoma on MRI includes:
 +
*Irregularly thickened mucosal folds
 +
*Irregular submucosal infiltration
 +
*Annular constricting lesion
 +
*Exophytic tumor growth
 +
*Retroperitoneal [[lymphadenopathy]].
  
 
==Treatment==
 
==Treatment==
Diffuse large B-cell lymphomas of the stomach are primarily treated with [[chemotherapy]] with [[CHOP]] with or without [[rituximab]] being a usual first choice.
+
*The predominant [[therapy]] for [[Diffuse large B-cell lymphoma|diffuse large B-cell lymphomas]] of the [[stomach]] is [[chemotherapy]].<ref name="pmid19707443">{{cite journal |vauthors=Hauptrock B, Hess G |title=Rituximab in the treatment of non-Hodgkin's lymphoma |journal=Biologics |volume=2 |issue=4 |pages=619–33 |year=2008 |pmid=19707443 |pmc=2727901 |doi= |url=}}</ref><ref name="pmid17659705">{{cite journal |vauthors=Morgner A, Schmelz R, Thiede C, Stolte M, Miehlke S |title=Therapy of gastric mucosa associated lymphoid tissue lymphoma |journal=World J. Gastroenterol. |volume=13 |issue=26 |pages=3554–66 |year=2007 |pmid=17659705 |pmc=4146794 |doi= |url=}}</ref>
 +
*Second line [[therapy]] for [[MALT lymphoma|MALT lymphomas]] is usually [[chemotherapy]] with a single agent, and complete response rates of greater than 70% have been observed.
 +
*[[Chemotherapy]] includes [[Treatments|treatment]] with [[CHOP]] with or without [[rituximab]].
 +
*The mainstay of [[therapy]] for [[MALT lymphoma|MALT lymphomas]] is [[antibiotic]] treatment to eradicate [[H.pylori peptic ulcer disease pathophysiology|H.pylori]]. Regression is seen in about 60% of cases with eradication therapy alone.
 +
*Single drug [[chemotherapy]] is recommended as a second line therapy for [[MALT lymphoma|MALT lymphomas]] and is associated with a complete resolution of symptoms in greater than 70% cases.
 +
*In case of complications like [[gastric outlet obstruction]], the recommended treatment is [[Gastrectomy|subtotal gastrectomy]] followed by post-operative.
  
Antibiotic treatment to eradicate [[H. pylori]] is indicated as first line therapy for [[MALT lymphoma]]s.  About 60% of MALT lymphomas completely regress with eradication therapy <ref>Bayerdorffer E ''et al.'', Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group, Lancet 1995 Jun 24;345(8965):1591-4.</ref>.  Second line therapy for MALT lymphomas is usually chemotherapy with a single agent, and complete response rates of greater than 70% have gain been reported <ref>Hammel P ''et al.''  Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.  J Clin Oncol 1995 Oct;13(10):2524-9.</ref>.
+
==Prevention==
 +
===Primary Prevention===
 +
Proper treatment of [[Helicobacter pylori]], can prevent [[MALT lymphoma]].
  
Subtotal [[gastrectomy]], with post-operative [[chemotherapy]] is undertaken in refractory cases, or in the setting of complications, including [[gastric outlet obstruction]].
+
===Secondary Prevention===
 +
There are no established measures for the secondary prevention of gastric lymphoma.
  
 
==References==
 
==References==
*Fauci, ''et al.'' ''Harrison's Principles of Internal Medicine'',16th Ed.
 
 
==Notes==
 
 
{{reflist|2}}
 
{{reflist|2}}
  

Latest revision as of 19:46, 7 February 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Overview

Primary gastric lymphoma is cancer derived from lymphocytes (a type of white blood cell) that originates in the stomach. Most common cause of primary gastric lymphoma is mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) of the stomach. Primary gastric lymphoma may be classified according to histology into MALT lymphoma and DLBCL. MALT lymphoma can be further divided into H. pylori positive MALT lymphoma and H. pylori negative MALT lymphoma. DLBCL can be divided into 3 subgroups germinal-center B-cell-like, activated B-cell-like, primary mediastinal DLBCL. The exact pathogenesis of primary gastric lymphoma is not fully understood. Common symptoms of primary gastric lymphoma include epigastric discomfort, anorexia, weight loss, nausea associated with or without vomiting, occult gastrointestinal bleeding, early satiety. Less common symptoms include ever and night sweats. Patients with primary gastric lymphoma usually appear normal. Vital signs are within normal limits unless there is complication. Physical examination of patients with primary gastric lymphoma is usually remarkable for palpable mass and peripheral lymphadenopathy. Gastric lymphoma must be differentiated from conditions with similar presentation like acute gastritis, chronic gastritis, atrophic gastritis, Crohn's disease, gastroesophageal reflux disease, peptic ulcer disease, gastrinoma and gastric adenocarcinoma. Primary gastric lymphoma commonly affects elderly patients in the fifth or sixth decade of life. Primary gastric lymphoma is more prevalent in men than in women. Risk factors for gastric lymphoma include Helicobacter pylori, long-term immunosuppressant drug therapy, HIV infection. The majority of patients with primary gastric lymphoma present with nonspecific symptoms in the 5th decade of life. Early clinical features include epigastric pain, nausea, and vomiting. If left untreated, patients with gastric lymphoma may progress to develop anorexia, weight loss, and early satiety. Common complications of gastric lymphoma include perforation, hemorrhage, and obstruction. Prognosis is generally good, and complete remission can be achieved after 6-8 rounds of chemotherapy or following surgery. Upper gastrointestinal endoscopy with biopsy is the gold standard test for the diagnosis of gastric lymphoma. Laparotomy and laparoscopy should be performed when the patient presents with complications such as perforation or obstruction. An endoscopic ultrasound (EUS) will help assess the depth of lymphoma invasion and involvement of perigastric nodes. MALT lymphoma presents as superficial spreading or diffuse infiltrating lesion whereas diffuse large B cell lymphoma has a typical mass forming lesion appearance on endoscopic ultrasound. Imaging investigations including CT scans or endoscopic ultrasound are useful to stage disease. Hematological parameters are usually checked to assist with staging and to exclude concomitant leukemia. An elevated LDH level may be suggestive of lymphoma. There are no established measures for the primary and secondary prevention of gastric lymphoma.

Classification

Primary gastric lymphoma may be classified according to histology into the following subtypes:

Pathophysiology

In case of DLBCL, antibiotic eradication therapy for H.pylori has shown to result in complete remission of lymphoma highlighting the role of H.pylori in the pathogenesis.

  • HBV plays a role in the pathogenesis of B-cell NHL, evidenced by an increased risk of developing NHL in HBsAg positive patients.

Histopathology

Most of the gastric lymphomas are predominantly non-Hodgkin’s lymphoma of B-cell origin. Primary gastric lymphoma can vary from being well-differentiated, low-grade lymphomas to high grade or large cell lymphomas.[5]

Symptoms

Common Symptoms

Common symptoms of primary gastric lymphoma include:[6][7]

Less Common Symptoms

Less common symptoms include:

Physical Examination

Appearance of the Patient

  • Patients with primary gastric lymphoma usually appear normal.[7]

Vital signs

Vital signs are within normal limits unless there is complication.

Abdominal Examination

Differential Diagnosis

Gastric lymphoma must be differentiated from conditions with similar presentation like acute gastritis, chronic gastritis, atrophic gastritis, Crohn's disease, gastroesophageal reflux disease, peptic ulcer disease, gastrinoma and gastric adenocarcinoma :[8][9][10][11][12][13][14][15][16]

Disease Cause Symptoms Diagnosis Other findings
Pain Nausea

&

Vomiting

Heartburn Belching or

Bloating

Weight loss Loss of

Appetite

Stools Endoscopy findings
Location Aggravating Factors Alleviating Factors
Primary gastric lymphoma - - - - - +/- - - Useful in collecting the tissue for biopsy Other symptoms
Acute gastritis Food Antacids +/- +/- +/- - +/- Black stools -
Chronic gastritis Food Antacids +/- +/- +/- +/- +/- - H. pylori gastritis

Lymphocytic gastritis

  • Enlarged folds
  • Aphthoid erosions
-
Atrophic gastritis Epigastric pain - - +/- - +/- +/- +/- - H. pylori

Autoimmune

Autoimmune gastritis diagnosis include:

Crohn's disease - - - - - +/- +/-
  • Mucosal nodularity with cobblestoning
  • Multiple aphthous ulcers
  • Linier or serpiginous ulcerations
  • Thickened antral folds
  • Antral narrowing
  • Hypoperistalsis
  • Duodenal strictures
GERD
  • Lower esophageal sphincter abnormalities
  • Spicy food
  • Tight fitting clothing
+/-

(Suspect delayed gastric emptying)

+/- - - - - Other symptoms:

Complications

Peptic ulcer disease Duodenal ulcer
  • Pain aggravates with empty stomach

Gastric ulcer

  • Pain aggravates with food
  • Pain alleviates with food
+/- +/- - - - Gastric ulcers
  • Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base
  • Most ulcers are at the junction of fundus and antrum
  • 0.5-2.5cm

Duodenal ulcers

Other diagnostic tests
Gastrinoma - - +/-

(suspect gastric outlet obstruction)

+/- - - - Useful in collecting the tissue for biopsy

Diagnostic tests

Gastric Adenocarcinoma - - +/- +/- +/- +/- +/- Esophagogastroduodenoscopy
  • Multiple biopsies are taken to establish the diagnosis
Other symptoms

Demographics

Risk Factors

Risk factors for gastric lymphoma include the following:[18]

Natural History, Complications and Prognosis

Natural History

Complications

Prognosis

Diagnosis


By Samir at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=4647530


MRI

Findings of Gastric lymphoma on MRI includes:

  • Irregularly thickened mucosal folds
  • Irregular submucosal infiltration
  • Annular constricting lesion
  • Exophytic tumor growth
  • Retroperitoneal lymphadenopathy.

Treatment

Prevention

Primary Prevention

Proper treatment of Helicobacter pylori, can prevent MALT lymphoma.

Secondary Prevention

There are no established measures for the secondary prevention of gastric lymphoma.

References

  1. Hussell T, Isaacson PG, Crabtree JE, Spencer J (1996). "Helicobacter pylori-specific tumour-infiltrating T cells provide contact dependent help for the growth of malignant B cells in low-grade gastric lymphoma of mucosa-associated lymphoid tissue". J. Pathol. 178 (2): 122–7. PMID 8683376. doi:10.1002/(SICI)1096-9896(199602)178:2<122::AID-PATH486>3.0.CO;2-D. 
  2. Engels EA, Cho ER, Jee SH (2010). "Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study". Lancet Oncol. 11 (9): 827–34. PMC 2933963Freely accessible. PMID 20688564. doi:10.1016/S1470-2045(10)70167-4. 
  3. Dawson IMP, Cornes JS, Morrison BC. Primary malignant lymphoid tumours of the intestinal tract. Br J Surg. 1961;49:80-89.
  4. Aisenberg AC. Coherent view of non-Hodgkin's lymphoma. J Clin Oncol. 1995;13:2656-2675.
  5. 5.0 5.1 Wang T, Gui W, Shen Q (2010). "Primary gastrointestinal non-Hodgkin's lymphoma: clinicopathological and prognostic analysis". Med. Oncol. 27 (3): 661–6. PMID 19565363. doi:10.1007/s12032-009-9265-1. 
  6. Freeman C, Berg JW, Cutler SJ (1972). "Occurrence and prognosis of extranodal lymphomas". Cancer. 29 (1): 252–60. PMID 5007387. 
  7. 7.0 7.1 Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rübe C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M (2001). "Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92". J. Clin. Oncol. 19 (18): 3861–73. PMID 11559724. doi:10.1200/JCO.2001.19.18.3861. 
  8. Sugimachi K, Inokuchi K, Kuwano H, Ooiwa T (1984). "Acute gastritis clinically classified in accordance with data from both upper GI series and endoscopy.". Scand J Gastroenterol. 19 (1): 31–7. PMID 6710074. 
  9. Sipponen P, Maaroos HI (2015). "Chronic gastritis.". Scand J Gastroenterol. 50 (6): 657–67. PMC 4673514Freely accessible. PMID 25901896. doi:10.3109/00365521.2015.1019918. 
  10. Sartor RB (2006). "Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis.". Nat Clin Pract Gastroenterol Hepatol. 3 (7): 390–407. PMID 16819502. doi:10.1038/ncpgasthep0528. 
  11. Sipponen P (1989). "Atrophic gastritis as a premalignant condition.". Ann Med. 21 (4): 287–90. PMID 2789799. 
  12. Badillo R, Francis D (2014). "Diagnosis and treatment of gastroesophageal reflux disease.". World J Gastrointest Pharmacol Ther. 5 (3): 105–12. PMC 4133436Freely accessible. PMID 25133039. doi:10.4292/wjgpt.v5.i3.105. 
  13. Ramakrishnan K, Salinas RC (2007). "Peptic ulcer disease.". Am Fam Physician. 76 (7): 1005–12. PMID 17956071. 
  14. Banasch M, Schmitz F (2007). "Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors.". Wien Klin Wochenschr. 119 (19-20): 573–8. PMID 17985090. doi:10.1007/s00508-007-0884-2. 
  15. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM (2005). "Gastric adenocarcinoma: review and considerations for future directions.". Ann Surg. 241 (1): 27–39. PMC 1356843Freely accessible. PMID 15621988. 
  16. Ghimire P, Wu GY, Zhu L (2011). "Primary gastrointestinal lymphoma.". World J Gastroenterol. 17 (6): 697–707. PMC 3042647Freely accessible. PMID 21390139. doi:10.3748/wjg.v17.i6.697. 
  17. Thirlby RC. Gastrointestinal lymphoma: a surgical perspective. Oncology (Huntingt). 1993;7:29-32.
  18. NEJM article
  19. Cogliatti SB, Schmid U, Schumacher U, Eckert F, Hansmann ML, Hedderich J, Takahashi H, Lennert K (1991). "Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients". Gastroenterology. 101 (5): 1159–70. PMID 1936785. 
  20. Muller AF, Maloney A, Jenkins D, Dowling F, Smith P, Bessell EM, Toghill PJ (1995). "Primary gastric lymphoma in clinical practice 1973-1992". Gut. 36 (5): 679–83. PMC 1382669Freely accessible. PMID 7797116. 
  21. Hauptrock B, Hess G (2008). "Rituximab in the treatment of non-Hodgkin's lymphoma". Biologics. 2 (4): 619–33. PMC 2727901Freely accessible. PMID 19707443. 
  22. Morgner A, Schmelz R, Thiede C, Stolte M, Miehlke S (2007). "Therapy of gastric mucosa associated lymphoid tissue lymphoma". World J. Gastroenterol. 13 (26): 3554–66. PMC 4146794Freely accessible. PMID 17659705. 




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