Gastroenterology and Digestive Endoscopy, ‡Haematology, “Nuovo Regina Margherita” Hospital, Rome, Italy; §Section of Gastroenterology, Department of Medical� ¶
ciences, University of Foggia, Foggia, Italy; Department of Experimental Medicine, “La Sapienza” University, Rome, Italy; Institut fur Pathologie, Klinikum Kulmbach,
ulmach, Germany; and #Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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ACKGROUND & AIMS: Different remission rates ofastric low-grade, B-cell, mucosa–associated lymphoid tissueMALT) lymphoma have been reported after Helicobacter pyloriradication. We assessed the long-term remission and relapseates of early stage MALT lymphoma in patients treated only by
pylori eradication and identified factors that might predictutcome. METHODS: This systematic review analyzed datarom 32 studies, including 1408 patients. RESULTS: The
ALT lymphoma remission rate was 77.5% (95% confidencenterval, 75.3�79.7), and was significantly higher in patientsith stage I than stage II1 lymphoma (78.4% vs 55.6%; P �
0003) and in Asian than in Western groups (84.1% vs 73.8%;� .0001). Neoplasia confined to the submucosa regressedore frequently than that with deeper invasion (82.2% vs 54.5%;� .0001); patients with lymphoma localized to the distal
tomach experienced regression more frequently than thoseith lymphoma of the proximal stomach (91.8% vs 75.7%; P �
0037). The remission rate was higher among patients withouthe API2–MALT1 translocation than in those with this translo-ation (78% vs 22.2%; P � .0001). In an analysis of data from94 patients, 7.2% experienced lymphoma relapse during 3253atient-years of follow-up evaluation, with a yearly recurrenceate of 2.2%. Infection and lymphoma were cured by additionalradication therapy in all patients with H pylori recurrence16.7%). Five (0.05%) of the patients initially cured of lymphomaeveloped high-grade lymphoma within 6 to 25 months ofherapy. CONCLUSIONS: H pylori eradication is effectiven treating approximately 75% of patients with early stageastric lymphoma. Long-term follow-up evaluation of theseatients is needed to detect early lymphoma relapse orrogression.
elicobacter pylori infection is the main pathogenic factorunderlying development of low-grade, B-cell, mucosa-
ssociated lymphoid tissue (MALT) lymphoma of the stom-ch.1,2 International guidelines strongly suggest bacterial erad-cation in all gastric MALT lymphoma patients3– 6; diseaseemission occurs in more than 70% of patients when thiseoplasia is treated at an early stage.7,8
Although the incidence of primary gastric lymphoma hasncreased in recent decades,9 it remains a rare disease. Conse-
uently, studies of the efficacy of curing H pylori infection in
hese patients are generally small and heterogeneous. Moreover,isease relapse has been reported after lymphoma remission,ith or without bacterial recurrence.1,8 Therefore, it is difficult
o determine the true effects of bacterial eradication on long-erm remission of MALT lymphoma. We performed a system-tic review of the literature to assess the lymphoma remissionate after H pylori eradication and disease relapse rates afterong-term follow-up periods.
MethodsLiterature SearchSeparate computer-assisted searches were performed
sing PubMed. Each search was performed on all English lan-uage articles through June 2008, using the exploded medicalubject heading terms lymphoma, Helicobacter pylori, therapy, erad-cation, remission, and follow up. Boolean operators (NOT, AND,
R) also were used in succession to narrow and widen theearch. Only studies concerning primary, low-grade, MALT lym-homa of the stomach associated with H pylori infection wereonsidered; diffuse large B-cell lymphoma with features of
ALT were excluded. Trials enrolling patients with either stageE1–IE2 or IIE1 lymphoma, according to Ann Arbor classifica-ion as modified by Musshof,10 were considered; series that alsoncluded cases staged IIE2 or higher were excluded unless it wasossible to correctly extrapolate data of a patient subgroup witharly stages. In detail, these stages correspond to lymphomaonfined to the gastric wall (stage I) or perigastric lymph nodesstage IIE1). Data of patients treated with only H pylori eradica-ion were considered. Full articles of all relevant studies wereetrieved, and manual searches of reference lists from identifiedelevant articles were performed to identify any additional stud-es that might have been missed. When more than one publi-ation from the same investigator or group was available, onlyhe most updated version, including the entire sample size, wasonsidered for this pooled-data analysis. Studies that includedediatric or transplant patients, those published only in ab-
Abbreviations used in this paper: CI, confidence interval; MALT,ucosa-associated lymphoid tissue.
106 ZULLO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 2
tract form, single case reports or studies of fewer than 5atients, reviews, and studies that were not published in En-lish were not included in the analyses.
Data ExtractionTwo investigators (A.Z. and C.H.) extracted the data
rom the studies that met the selection criteria. Data werextracted concerning the following: (1) number of patientsreated with only H pylori eradication therapy, (2) number ofatients in whom the infection was eradicated successfully
either directly provided or calculated), (3) number of patientsho finally achieved complete remission of lymphoma (partial
emission was not taken into account), and (4) number ofatients with lymphoma recurrence at follow-up evaluation. Hylori recurrence (re-infection or recrudescence) was defined ashe reappearance of bacteria after a verified eradication withifferent tests at least 1 month after antibiotic therapy.11,12
oth investigators of this study approved the data extractionethod and a final accord was achieved for the 2 trials with
iscordant data interpretation.
Statistical AnalysisThe percentage and 95% confidence intervals of com-
lete lymphoma remission after H pylori eradication were cal-
able 1. Data of Selected Studies Meeting the Inclusion Crit
Country (study) Study design Patients enrolleda Lymph
taly13 P 76taly14 P 7orea15 R 28ermany16 P 120apan17 P 38nited States18 P 28orea19 P 90rance20 P 34ermany21 P 90ortugal22 P 17pain23 P 24
taly24 R 13nited States25 P 65
taly-Swiss26 R 45aiwan27 P 31ustria28 R 22urope29 P 62apan30 P 74taly31 R 9he Netherlands32 R 23apan33 P 18orea34 P 99he Netherlands35 R 35apan36 P 21apan37 P 13apan38 P 10apan39 P 15ermany40 R 196ebanon41 R 19apan42 P 33taly43 R 60hina44 P 21
, prospective; R, retrospective.All H pylori–positive patients enrolled.
Remission rate observed in the H pylori eradicated patients.
ulated. Data from different patient subgroups were comparedy using the chi-squared test or the Fisher exact test. A P valuef less than .05 was considered statistically significant.
ResultsSearch ResultsAfter a thorough review of the titles, abstracts, and text
f the potentially relevant studies, the full text from 79 studiesf H pylori eradication in patients with gastric lymphoma wasetrieved and evaluated. Of these, 32 trials met inclusion criteriaor this pooled analysis13– 44; 47 studies were not included (Table). The exclusion criteria were as follows: (1) articles that re-orted preliminary data provided elsewhere (29 studies), (2)rticles that did not provide information about initial lym-homa stage (8 studies), and (3) studies that included patientsith lymphoma stages greater than IIE2 who had been treatedith therapies beyond bacteria eradication (chemotherapy, ra-iotherapy, or surgery), or that did not determine remissionate according to the lymphoma stage (10 studies).
Descriptive AnalysisOf the 32 studies analyzed in this pooled-data analysis,
3 were prospective and 9 were retrospective. The analysis
stage Follow-up period, mo (range) Lymphoma remission, %b
ncluded 16 studies from Europe (833 patients), 14 studiesrom Asia (510 patients), and 2 studies from the United States93 patients). In total, data from 1436 patients treated by only
pylori eradication were studied, including 1380 patients withtage I and 56 patients with stage II MALT lymphoma. The
edian study sample size was 30 patients, and ranged from 7 to96 patients.
Lymphoma RemissionH pylori eradication after one or more therapeutic at-
empts was achieved in 1408 patients (98%), including 1354ases of stage I and 54 cases of stage II lymphoma. Overall,omplete lymphoma remission was observed in 1091 (77.5%;5% confidence interval [CI], 75.3�79.7) patients. Remissionccurred in 1061 patients with stage I disease (78.4%; 95% CI,6.2�80.6) and 30 patients with stage II disease (55.6%; 95% CI,2.3�68.8); this difference was statistically significant (P �
0003). The remission rates among the selected studies rangedrom 45.5% to 100% in patients with stage 1 and from 0% to00% in patients with stage II disease. Lymphoma remissionas achieved in a median time of 5 months; complete remis-
ion was achieved in less than 24 months of follow-upvaluation in all but 3 patients (33, 37, and 45 months inhese patients).15,18,35 When data were analyzed based on geo-raphic area, lymphoma remission was achieved in 668 of 905estern patients (73.8%; 95% CI, 71�76.7), and in 423 of 503
sian patients (84.1%; 95% CI, 80.9�87.3); the difference wastatistically significant between subgroups (Table 2).
We extrapolated data from 13 studies on factors that mightredict lymphoma remission (Table 3).18 –22,27,30,34,37,41 Among87 of the patients analyzed, the regression rate was signifi-
able 2. Lymphoma Remission Rate After H pyloriEradication in Different Areas
Country
P valueAsian, n (%) Western, n (%)
tage I 401/478 (83.9) 660/876 (75.3) .0005tage II1 22/25 (88.0) 8/29 (27.5) .0001otal 423/503 (84.1) 668/905 (73.8) .0001
able 3. Lymphoma Remission According to Different Factors
OTE. Number of patients achieving lymphoma remission out of treated p
antly higher in those with lymphoma confined within theastric submucosa (82.2%; 95% CI, 78.2�86.3) than those withdeeper invasion (54.5%; 95% CI, 39.8�69.2), based on endo-
copic ultrasonography (P � .0001). Among a separate group of09 patients, a significantly higher remission rate was associ-ted with distal (antrum and/or angulus) localization of lym-homa (91.8%; 95% CI, 86.4�97.2) compared with proximal
gastric body and/or fundus) localization (75.7%; 95% CI,7.7�83.6) at endoscopy (P � .0037). Data on API2–MALT1ranslocation status were available from 123 patients enrolledn 4 studies.16,23,30,44 The lymphoma remission rate was signifi-antly higher in patients without (78%; 95% CI, 70.2�85.8) thanhose with this translocation (22.2%; 95% CI, 3�41.4) (P �0001).
Lymphoma RelapseData on the lymphoma relapse rate after a long-term
ollow-up period were available from all but 4 studies.35,38,39,42
he studies with long-term follow-up data included 994 pa-ients; the median follow-up period was 28 months (range,0�75 mo). Overall, 72 lymphoma relapses (7.2%; 95% CI,.6�8.8) were observed during 3253 patient-years of follow-upvaluation—the yearly recurrence rate was 2.2%. Of these, 12ases (16.7%) were associated with H pylori recurrence, 49 cases68.1%) occurred in uninfected patients, and data about infec-ion were unavailable for the remaining 11 cases. Nine of the 12atients with lymphoma relapse and infection recurrence weree-treated, resulting in H pylori eradication and lymphoma dis-ppearance. No information was available about the remainingpatients. Of note, 13 patients (26.5%) with neoplastic relapseithout bacterial recurrence achieved lymphoma remissionithout further treatment. In another 8 patients, H pylori in-
ection recurred without lymphoma relapse. Finally, 5 patients0.05%) initially cured of both H pylori infection and lymphomaeveloped high-grade lymphoma (at 6, 13, 16, 18, and 25onths of follow-up evaluation).
DiscussionPrimary gastric MALT lymphoma is a neoplasia that is
ssociated with H pylori infection. H pylori eradication leads toomplete remission of gastric low-grade lymphoma in 35% to
108 ZULLO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 2
00% of patients, according to different studies.1 A recent sys-ematic review described a high rate of remission (68.8% in 61ases) in patients with high-grade lymphoma after therapy vianly bacterial eradication.45 Current international guidelinesuggest bacterial eradication therapy for all patients with MALTymphoma.3– 6
This was a comprehensive pooled-data analysis of remissionates of early stage lymphoma in a large series of patientsreated by H pylori eradication. After a long-term follow-uperiod, lymphoma disappeared in more than 75% of patientsreated by bacterial eradication. Although the lymphoma remis-ion rate was significantly higher in patients with stage I dis-ase, neoplasia disappeared in more than 50% of the patientsith stage II1 disease treated only by H pylori eradication. Theseata indicate that bacterial eradication is effective in patientsith lymphoma confined to perigastric lymph nodes. We esti-ated that complete lymphoma remission occurred at a me-
ian of 5 months, but in a few patients it occurred after a muchonger follow-up period (3– 4 y).
Different predictive factors of lymphoma remission haveeen found, including depth of penetration in the gastric wall,46
PI2–MALT1 translocation status,47 the gastric site involved,34
icrosatellite instability,48 age of patients,20 MIB-1 status,49 andlood-soluble Fa antigen levels.50 Our pooled-data analysis of a
arge cumulative data set shows that it is possible to determineymphoma regression probability based on endoscopic ultra-onography results or lymphoma location in the stomach; theymphoma remission rate is significantly lower in patients witheoplastic cells beyond the submucosa layer, although the re-ression occurred in more than 50% of these patients. Patientsith a major neoplastic lesion in the proximal stomach have a
ignificantly lower probability of remission than those witheoplasms of the distal stomach. The presence of API2–MALT1ranslocation in lymphoma cells reduces a patient’s probabilityf remission to less than 25%.
Unexpectedly, we observed a significantly higher rate (�10%)
igure 1. Predictive factors for gastric lymphoma remission followingpylori eradication.
f lymphoma remission in Asian, compared with European/US
opulations, especially among stage II1 Asian patients, who hadremission rate as high as 88%. This observation might be
xplained by differences in staging procedures; additional stud-es are needed to determine whether gastric lymphoma in Asianatients is more responsive to H pylori eradication, possiblywing to genetic factors.33
Lymphoma relapse after H pylori eradication can occur withr without recurrence of bacterial infection;1 we observed aearly recurrence rate of 2.2%. Lymphoma relapse associatedith bacterial recurrence can be managed with further eradica-
ion therapy. Interestingly, spontaneous regression of lym-homa occurred in 25% of relapse patients without infectionecurrence; this observation strengthens the “watch and wait”trategy recently proposed for patients with minimal histologicesiduals of gastric MALT lymphoma after successful eradica-ion of H pylori.51 Scheduled, long-term, follow-up visits areecommended based on the findings that high-grade gastricymphoma occurs in some patients after both bacterial andymphoma regression.
In conclusion, H pylori eradication is effective for a largeumber of low-grade gastric lymphoma patients with stage Ind II1 disease, particularly when the neoplastic lesion is con-ned within the submucosa, the main lesion is localized in theistal stomach, and API2–MALT1 translocation is absent. Figure 1.
References
1. Stolte M, Bayerdörffer E, Morgner A, et al. Helicobacter pylori andgastric MALT lymphoma. Gut 2002;50(Suppl 3):19–24.
2. Andriani A, Zullo A, Di Raimondo F, et al. Clinical and endoscopicpresentation of primary gastric lymphoma: a multicentre study.Aliment Pharmacol Ther 2006;23:721–726.
3. Malfertheiner P, Megraud F, O’Morain C, et al. Current conceptsin the management of Helicobacter pylori infection—The Maas-tricht III Consensus Report. Gut 2007;56:772–781.
4. Chey WD, Wong BCY. American College of GastroenterologyGuideline on the management of Helicobacter pylori infection.Am J Gastroenterol 2007;102:1–18.
5. Fujioka T, Yoshiiwa A, Okimoto T, et al. Guidelines for the man-agement of Helicobacter pylori infection in Japan: current statusand future prospects. J Gastroenterol 2007;42(Suppl 17):3–6.
6. Caselli M, Zullo A, Maconi G, et al. Cervia II Working Group Report2006: guidelines on diagnosis and treatment of Helicobacterpylori infection in Italy. Dig Liver Dis 2007;39:782–789.
7. Nakamura S, Matsumoto T, Suekane H, et al. Predictive value ofendoscopic ultrasonography for remission of gastric low gradeand high grade MALT lymphomas after eradication of Helicobac-ter pylori. Gut 2001;48:454–460.
8. Bayerdörffer E, Morgner A. Gastric marginal zone B-cell lymphomaof the mucosa-associated lymphoid tissue type: management ofthe disease. Dig Liver Dis 2000;32:192–194.
9. Nakamura S, Matsumoto T, Iida M, et al. Primary gastrointestinallymphoma in Japan. A clinicopathologic analysis of 455 patientswith special reference to its time trends. Cancer 2003;97:2462–2473.
0. Musshof K. Klinische stadieneniteilung der nicht-Hodgkin lym-phoma. Strahlentherapie 1997;153:218–221.
1. Penston JG. Helicobacter pylori eradication: understandable cau-tion but no excuse for exertion. Aliment Pharmacol Ther 1994;8:369–379.
2. Zullo A, Rinaldi V, Hassan C, et al. Clinical and histologic predic-tors of Helicobacter pylori infection recurrence. J Clin Gastroen-terol 2000;31:38–41.
3. Savio A, Zamboni G, Capelli P, et al. Relapse of low-grade gastric
MALT lymphoma after Helicobacter pylori eradication: true re-
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
February 2010 H PYLORI AND GASTRIC LYMPHOMA 109
lapse or persistence? Long-term post-treatment follow-up of amulticenter trial in the north-east of Italy and evaluation of thediagnostic protocol’s adequacy. Recent Results Cancer Res2000;156:116–124.
4. Papa A, Cammarota G, Tursi A, et al. Helicobacter pylori eradica-tion and remission of low-grade gastric mucosa-associated lym-phoid tissue lymphoma. J Clin Gastroenterol 2000;31:169–171.
5. Lee SK, Lee YC, Chung JB, et al. Low grade gastric mucosaassociated lymphoid tissue lymphoma: treatment strategiesbased on 10 year follow-up. World J Gastroenterol 2004;10:223–226.
6. Wundisch T, Thiede C, Morgner A, et al. Long-term follow-up ofgastric MALT lymphoma after Helicobacter pylori eradication.J Clin Oncol 2005;23:8018–8024.
7. Akamatsu T, Mochizuki T, Okiyama Y, et al. Comparison of local-ized gastric mucosa-associated lymphoid tissue (MALT) lym-phoma with and without Helicobacter pylori infection. Helicobac-ter 2006;11:86–95.
8. Steinbach G, Ford R, Glober G, et al. Antibiotic treatment ofgastric lymphoma of mucosa-associated lymphoid tissue: an un-controlled trial. Ann Intern Med 1999;131:88–95.
9. Hong SS, Jung WY, Choi KD, et al. A prospective analysis oflow-grade gastric MALT lymphoma after Helicobacter pylori erad-ication. Helicobacter 2006;11:569–573.
0. Ruskoné-Fourmestraux A, Lavergne A, Aegerter PH, et al. Predic-tive factors for remission of gastric MALT lymphoma after anti-Helicobacter pylori treatment. Gut 2001;48:297–303.
1. Fischbach W, Goebeler-Kolve ME, Dragosics B, et al. Long termoutcome of patients with gastric marginal zone B cell lymphomaof mucosa associated lymphoid tissue (MALT) following exclusiveHelicobacter pylori eradication therapy: experience from a largeprospective series. Gut 2004;53:34–37.
2. Nobre-Lietao C, Lage P, Cravo M, et al. Treatment of gastric MALTlymphoma by Helicobacter pylori eradication: a study controlledby endoscopic ultrasonography. Am J Gastroenterol 1998;93:732–736.
3. Montalban C, Santon A, Redondo C, et al. Long-term persistenceof molecular disease after histological remission in low-gradegastric MALT lymphoma treated with H. pylori eradication. Lack ofassociation with translocation t(11;18): a 10-year updated fol-low-up of a prospective study. Ann Oncol 2005;16:1539–1544.
4. Savio A, Franzin G, Wotherspoon AC, et al. Diagnosis and post-treatment follow-up of Helicobacter pylori-positive gastric lym-phoma of mucosa-associated lymphoid tissue: histology, poly-merase chain reaction, or both? Blood 1996;87:1255–1260.
5. Wenston AP, Banerjee SK, Horvat RT, et al. Prospective long-termendoscopic and histologic follow-up of gastric lymphoproliferativedisease of early stage IE low-grade B-cell mucosa-associatedlymphoid tissue type following Helicobacter pylori eradicationtreatment. Int J Oncol 1999;15:899–907.
6. Pinotti G, Zucca E, Roggero E, et al. Clinical features, treatmentand outcome in a series of 93 patients with low-grade gastricMALT lymphoma. Leuk Lymphoma 1997;26:527–537.
7. Chen LT, Lin JT, Tai JJ, et al. Long-term results of anti-Helico-bacter pylori therapy in early-stage gastric high-grade transformedMALT lymphoma. J Natl Cancer Inst 2005;97:1345–1353.
8. Raderer M, Osterreicher C, Machold K, et al. Impaired responseof gastric MALT-lymphoma to Helicobacter pylori eradication inpatients with autoimmune disease. Ann Oncol 2001;12:937–939.
9. Bertoni F, Conconi A, Capella C, et al. Molecular follow-up ingastric mucosa-associated lymphoid tissue lymphomas: earlyanalysis of the LY03 cooperative trial. Blood 2002;99:2541–2544.
0. Terai S, Iijima K, Kato K, et al. Long-term outcomes of gastric
mucosa-associated lymphoid tissue lymphomas after Helico-
bacter pylori eradication therapy. Tohoku J Exp Med 2008;214:79–87.
1. Agresta F, Trentin G, Mainente P, et al. Gastric MALT lymphomas:the value of an endoscopic follow-up evaluation. Surg Endosc2000;14:1153–1155.
2. de Jong D, Vyth-Dreese F, Dellemijn T, et al. Histological andimmunological parameters to predict treatment outcome of Hel-icobacter pylori eradication in low-grade gastric MALT lymphoma.J Pathol 2001;193:318–324.
3. Kawahara Y, Mizuno M, Yoshino T, et al. HLA-DQA1*0103-DQB1*0601 haplotype and Helicobacter pylori-positive gastricmucosa-associated lymphoid tissue lymphoma. Clin Gastroen-terol Hepatol 2005;3:865–868.
4. Kim JS, Chung SJ, Choi YS, et al. Helicobacter pylori eradicationfor low-grade gastric mucosa-associated lymphoid tissue lym-phoma is more successful in inducing remission in distal com-pared to proximal disease. Br J Cancer 2007;96:1324–1328.
5. Vrieling C, de Jong D, Boot H, et al. Long-term results of stomach-conserving therapy in gastric MALT lymphoma. Radiother Oncol2008;87:405–411.
6. Yamashita H, Watanabe H, Ajioka Y, et al. When can completeremission of low-grade gastric lymphoma of mucosa-associatedlymphoid tissue be predicted after Helicobacter pylori eradica-tion? Histopathology 2000;37:131–140.
7. Ohashi S, Segawa K, Okamura S, et al. Gastrin and Helicobacterpylori in low-grade MALT lymphoma patients. Scand J Gastroen-terol 2002;37:279–286.
8. Ono S, Kato M, Ono Y, et al. Characteristics of magnified endo-scopic images of gastric extranodal marginal zone B-cell lymphomaof the mucosa-associated lymphoid tissue, including changes aftertreatment. Gastrointest Endosc 2008;68:624–631.
9. Hiyama T, Haruma K, Kitadai Y, et al. c-myc gene mutation ingastric mucosa-associated lymphoid tissue (MALT) and diffuselarge B-cell lymphoma. Oncol Rep 2001;8:289–292.
0. Wündisch T, Mösch C, Neubauer A, et al. Helicobacter pylorieradication in gastric mucosa-associated lymphoid tissue lym-phoma: results of a 196-patient series. Leuk Lymphoma 2006;47:2110–2114.
1. El-Zahabi LM, Jamali FR, El-Hajj II, et al. The value of EUS inpredicting the response of gastric mucosa-associated lymphoidtissue lymphoma to Helicobacter pylori eradication. GastrointestEndosc 2007;65:89–96.
2. Takenaka R, Yokota K, Mizuno M, et al. Serum antibodies toHelicobacter pylori and its heat-shock protein 60 correlate withthe response of gastric mucosa-associated lymphoid tissue lym-phoma to eradication of H. pylori. Helicobacter 2004;9:194–200.
3. Andriani A, Medico A, Tedeschi L, et al. Management and long-term follow up of early stage H. pylori-associated gastric MALT-lymphoma in clinical practice: an Italian, multicenter study. DigLiver Dis 2009;41:467–473.
4. Dong G, Liu C, Ye H, et al. BCL10 nuclear expression andt(11;18)(q21;q21) indicate nonresponsiveness to Helicobacterpylori eradication of Chinese primary gastric MALT lymphoma. IntJ Hematol 2008;88:516–523.
5. Cavanna L, Pagani R, Seghini P, et al. High grade B-cell gastriclymphoma with complete pathologic remission after eradicationof Helicobacter pylori infection: report of a case and review of theliterature. World J Surg Oncol 2008;6:35–38.
6. Caletti G, Zinzani PL, Fusaroli P, et al. The importance of endo-scopic ultrasonography in the management of low-grade gastricmucosa-associated lymphoid tissue lymphoma. Aliment Pharma-col Ther 2002;16:1715–1722.
7. Nakamura T, Seto M, Tajika M, et al. Clinical features andprognosis of gastric MALT lymphoma with special reference toresponsiveness to H. pylori and AP12-MALT1 status. Am J Gas-
troenterol 2008;103:62–70.
4
4
5
5
R
aM0
C
110 ZULLO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 2
8. Hiyama T, Haruma K, Kitadai Y, et al. Microsatellite instability atD18S61 is associated with no remission of gastric mucosa-associated lymphoid tissue lymphoma after Helicobacter pylorieradication. Oncol Rep 2001;8:293–297.
9. Kanda M, Suzumiya J, Ohshima K, et al. Changes in patterns ofimmunoglobulin heavy chain gene rearrangement and MIB-1staining before and after eradication of Helicobacter pylori ingastric mucosa-associated lymphoid tissue (MALT) lymphoma.Leuk Lymphoma 2002;42:639–647.
0. Doi T, Nishikawa Y, Endo H, et al. Serum soluble Fas antigen ingastric MALT (mucosa-associated lymphoid tissue) lymphomapatients. J Esp Clin Cancer Res 1999;18:343–345.
1. Fischbach W, Goebeler ME, Ruskone-Fourmestraux A, et al. Most
patients with minimal histological residuals of gastric MALT lym-
phoma after successful eradication of Helicobacter pylori can bemanaged safely by a watch and wait strategy: experience from alarge international series. Gut 2007;56:1685–1687.
eprint requestsAddress requests for reprints to: Angelo Zullo, MD, Gastroenterology
nd Digestive Endoscopy, “Nuovo Regina Margherita” Hospital, Via E.orosini, 30 00153 Rome, Italy. e-mail: [email protected]; fax: (39)6-58446533.
