Sequential H. pylori eradication and radiation therapy with reduced dose compared to standard dose for gastric MALT lymphoma stages IE & II1E: a prospective randomized trial.

BACKGROUND: In Helicobacter pylori (H. pylori) positive stage I gastric low-grade MALT lymphoma, eradication is the accepted first-line therapy. The role of eradication therapy in lymphoma > stage IE is still unclear. However, about 20% of patients show persistent lymphoma following successful eradication or primary H. pylori-negative lymphoma. A prospective study for salvage radiation therapy with standard 36 Gy in comparison to a reduced dose of 25.2 Gy is still missing. METHODS: A prospective, multicentre study investigated the efficacy of eradication in H. pylori-positive gastric low-grade MALT lymphoma stages IE and II1E (HELYX I). Refractory lymphoma or H. pylori-negative patients were treated in a prospective, randomised, multicentre, phase II study to receive either 25.2 Gy or 36 Gy radiotherapy (HELYX II). RESULTS: 102 patients (3 drop outs) were included in HELYX I: 75/99 (75.8%) showed complete remission after a median of 2.8 months. 18 (18.2%) had partial remission (PR) and 6 (6.0%) no change (NC). 29 patients (7 drop outs) were randomized in HELYX II (7 primarily H. pylori-negative, 15 patients from HELYX I with refractory disease after eradication). All patients achieved stable CR irrespective of radiation dose. Both presence of the t(11,18) translocation (OR 9.0, p = 0.01) and monoclonality of the tumour cells (OR 6.3, p = 0.006) were predictors for persistant lymphoma after eradication therapy. CONCLUSIONS: Most H. pylori-positive low grade gastric MALT lymphoma stage IE and II1E respond with stable CR after eradication therapy. In patients with refractory disease or H. pylori negative low grade gastric MALT lymphoma a dosage-reduced radiation therapy with 25.2 Gy is an effective standard dose in stage IE and II1E. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00154440.

A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas develop from a chronic Helicobacter infection. Phospholipase C gamma 2 (PLCG2) is important for B-cell survival and proliferation. We used BALB/c mice with a gain-of-function mutation in the Plcg2 gene (Ali5) to analyze its role in the development of gastric MALT lymphoma. Heterozygous BALB/c Plcg2Ali5/+ and wildtype (WT) mice were infected with Helicobacter felis (H. felis) and observed up to 16 months for development of gastric MALT lymphomas. In contrast to our initial hypothesis, Plcg2Ali5/+ mice developed MALT lymphomas less frequently than their WT littermates after long-term infection of 16 months. Infected Plcg2Ali5/+ mice showed downregulation of proinflammatory cytokines and decreased H. felis-specific IgG1 and IgG2a antibody responses. These results suggested a blunted immune response of Plcg2Ali5/+ mice towards H. felis infection. Intriguingly, Plcg2Ali5/+ mice harboured higher numbers of CD73 expressing regulatory T cells (Tregs), possibly responsible for impaired immune response towards Helicobacter infection. We suggest that Plcg2Ali5/+ mice may be protected from developing gastric MALT lymphomas as a result of elevated Treg numbers, reduced response to H. felis and decrease of proinflammatory cytokines.

Length of Barrett's oesophagus and cancer risk: implications from a large sample of patients with early oesophageal adenocarcinoma.

OBJECTIVE: Although it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate annual cancer transition rates for patients with long-segment (≥3 cm), short-segment (≥1 to <3 cm) and ultra-short-segment (<1 cm) Barrett's oesophagus. DESIGN: We used three data sources to estimate the annual cancer transition rates for each Barrett length category: (1) the distribution of long, short and ultra-short Barrett's oesophagus among a large German cohort with newly diagnosed T1 oesophageal adenocarcinoma; (2) population-based German incidence of oesophageal adenocarcinoma; and (3) published estimates of the population prevalence of Barrett's oesophagus for each Barrett length category. RESULTS: Among 1017 patients with newly diagnosed T1 oesophageal adenocarcinoma, 573 (56%) had long-segment, 240 (24%) short-segment and 204 (20%) ultra-short-segment Barrett's oesophagus. The base-case estimates for the prevalence of Barrett's oesophagus among the general population were 1.5%, 5% and 14%, respectively. The annual cancer transition rates for patients with long, short and ultra-short Barrett's oesophagus were 0.22%, 0.03% and 0.01%, respectively. To detect one cancer, 450 patients with long-segment Barrett's oesophagus would need to undergo annual surveillance endoscopy; in short segment and ultra-short segment, the corresponding numbers of patients would be 3440 and 12,364. Similar results were obtained when applying US incidence data. CONCLUSIONS: The large number of patients, who need to undergo endoscopic surveillance to detect one cancer, raises questions about the value of surveillance endoscopy in patients with short segment or ultra-short segment of Barrett's oesophagus.

The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns.

BACKGROUND: A prerequisite for endoscopic treatment (ET) of not only mucosal, but also submucosal early adenocarcinoma of the esophagus (EAC) would be a rate of lymph node (LN) metastasis below the mortality rate of esophagectomy (2-5%). The aim of the present study was to evaluate the rate of LN metastasis in patients with pT1b sm1 EAC. METHODS: 1996-2010, 1,718 patients with suspicion of EAC were referred to the Department of Internal Medicine II at HSK Wiesbaden. In 123/1718 patients, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of sm1 EAC (ER/surgery) was made. Rate of LN metastasis was analyzed separately for low-risk (LR; G1-2, L0, V0) and high-risk lesions (HR; G3, L1, V1; ≥ 1 risk factor). LN metastasis was only evaluated in patients who had a proven maximum invasion depth of sm1 (ER and/or surgery), and who in case of ET had a follow-up (FU) by EUS of at least 24 months. RESULTS: Of the 72/123 patients included into the study, 49 patients had LR (68%) and 23 HR lesions (32%). In endoscopically treated LR patients (37/49), mean EUS-FU was 60 ± 30 mo (range 25-146); in HR patients undergoing ET (6/23), it was 63 ± 17 mo (46-86; p = 0.4). Mean number of resected LN was 27 ± 16 (12-62) in operated LR patients and 27 ± 10 (12-47) in HR-patients. The rate of LN metastasis was 2% in the LR (1 patient) and 9% in the HR group (2 patients; p = 0.24). Mortality of esophagectomy was 3%. CONCLUSIONS: The rate of LN metastasis in pT1b sm1 early adenocarcinoma with histological LR pattern was lower than the mortality rate of esophagectomy. ER may therefore be used alternatively to surgery in this group of patients.

Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H. pylori eradication.

BACKGROUND: The aim of this investigation is to study the relationship between gastric morphology and serum biomarkers before and after Helicobacter pylori eradication. METHODS: First-degree relatives of gastric cancer patients underwent gastroscopy before and 2.5 years after H. pylori eradication. The morphological changes in two categories (normal to mild and moderate to severe) were compared with level of pepsinogens I and II before eradication (n = 369), after eradication (n = 115), and in those with persistent infection (n = 250). RESULTS: After eradication, pepsinogen I decreased to 70% and pepsinogen II to 45% of the previous values. Unlike pepsinogen II and pepsinogen I to II ratio that were affected by the severity of inflammation and atrophy in corpus in all groups, pepsinogen I generally did not change. After eradication, subjects with high mononuclear infiltration in corpus had lower pepsinogen I (54 versus 77.1 µ/mL), higher pepsinogen II (9.4 versus 6.9 µ/mL), and lower ratio (7.9 versus 11.6) than those without (P < 0.05). CONCLUSION: Pepsinogen II is a good marker of corpus morphological changes before and after H. pylori eradication.

Development of gastric cancer and its prevention.

Gastric cancer is a heterogeneous disorder; genetic factors, H. pylori infection and various environmental factors contribute to its development. Advanced atrophic corpus-predominant gastritis provides the histological base for its genesis. Low socio-economic status and poor hygienic conditions, smoking habits, heavy alcohol consumption, high salt and low intake of vegetables and fruits are important external factors for the occurrence of gastric cancer. For its prevention, the eradication of H. pylori infection at an early age is mandatory for subjects at high risk or those living in areas with high prevalence of gastric cancer. Given that an increased serum level of Pepsinogen II is a good biomarker for the presence of gastritis, it seems reasonable to screen all infected subjects at risk of gastric cancer with increased serum pepsinogen II at an early age (at around 30 years) to eradicate H. pylori. An endoscopy should be performed for subjects at an older age (40 years and older), when increased serum pepsinogen II level is associated with decreased serum pepsinogen I and pepsinogen I to II ratio.

Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus.

BACKGROUND & AIMS: Barrett's esophagus-associated high-grade dysplasia is commonly treated by endoscopy. However, most guidelines offer no recommendations for endoscopic treatment of mucosal adenocarcinoma of the esophagus (mAC). We investigated the efficacy and safety of endoscopic resection in a large series of patients with mAC. METHODS: We collected data from 1000 consecutive patients (mean age, 69.1 ± 10.7 years; 861 men) with mAC (481 with short-segment and 519 with long-segment Barrett's esophagus) who presented at a tertiary care center from October 1996 to September 2010. Patients with low-grade and high-grade dysplasia and submucosal or more advanced cancer were excluded. All patients underwent endoscopic resection of mACs. Patients found to have submucosal cancer at their first endoscopy examination were excluded from the analysis. RESULTS: After a mean follow-up period of 56.6 ± 33.4 months, 963 patients (96.3%) had achieved a complete response; surgery was necessary in 12 patients (3.7%) after endoscopic therapy failed. Metachronous lesions or recurrence of cancer developed during the follow-up period in 140 patients (14.5%) but endoscopic re-treatment was successful in 115, resulting in a long-term complete remission rate of 93.8%; 111 died of concomitant disease and 2 of Barrett's esophagus-associated cancer. The calculated 10-year survival rate of patients who underwent endoscopic resection of mACs was 75%. Major complications developed in 15 patients (1.5%) but could be managed conservatively. CONCLUSIONS: Endoscopic therapy is highly effective and safe for patients with mAC, with excellent long-term results. In an almost 5-year follow-up of 1000 patients treated with endoscopic resection, there was no mortality and less than 2% had major complications. Endoscopic therapy should become the standard of care for patients with mAC.

Prognostic risk factors of early esophageal adenocarcinomas.

OBJECTIVE: To define prognostic risk factors in patients with early adenocarcinomas of the esophagus (eACEs) who were treated by esophagectomy. BACKGROUND: Although endoscopic resection (ER) is more accepted for eACEs limited to the mucosa, the reported prevalence of lymph node metastases once the tumor infiltrates the submucosa seems to necessitate surgery in these cases. METHODS: We analyzed the results of 168 patients who had an esophageal resection because of an eACE. On the basis of specimen histologies and clinical follow-up (median, 64 months), we investigated the influence of lymph node metastases (N+), tumor infiltration depth, tumor differentiation (G1-3), and lymphatic or venous infiltration (L+ or V+) on overall and tumor-specific survival and recurrence rates. RESULTS: The 5-year survival rate was 79%. Lymph node infiltration was the only prognostic factor for the overall survival [hazard ratio (HR), 2.856; 1.314-6.207; P = 0.008], tumor-specific survival (HR, 8.336; 2.734-25.418; P < 0.001), and tumor recurrence (HR, 8.031; 3.041-21.206; P < 0.001) that was consistently present in all multivariate hazard Cox regression analyses. A total of 47% of the patients who had an N+ status developed tumor recurrences compared with 5.2% of those who had no lymph node involvement (P = <0.001). We found a significant correlation between N+ status and increasing depth of tumor infiltration (P = 0.004), lymphatic vessel infiltration (P = 0.002), tumor differentiation (G1 + G2 vs G3; P = 0.014) and vascular infiltration (P = 0.01). CONCLUSIONS: Lymph node status is the only independent risk factor for survival and recurrence rates. Tumor infiltration depth correlates with the rate of the lymph node metastases, but a clear watershed between deep mucosal and submucosal infiltration does not exist. As a consequence, careful staging procedures, including diagnostic ER, are mandatory to determine which patients can be treated by ER and which require an esophagectomy.

Verrucous Oesophageal Carcinoma: Single Case Report and Case Series Including 15 Patients - Issues for Consideration of Therapeutic Strategies.

BACKGROUND: Verrucous carcinomas (VC) of the oesophagus are a rarity. Due to their histological resemblance to squamous cell carcinoma, the diagnostic and treatment standards applicable to the latter have so far also been applied to VC as a disease entity. Quite limited data are available including two case series of 5 or 11 patients. The present study reports on a single case treated by local endoscopic therapy and a series of 15 patients, 9 of whom received local endoscopic therapy. METHODS: The data for patients diagnosed with VC of the oesophagus who had been treated from January 1999 to May 2011 were analysed retrospectively. RESULTS: 15 patients with the diagnosis of oesophageal VC were included. The male-female ratio was 3:1. 9 of 11 pT1-VC patients presented with the cardinal symptom dysphagia or odynophagia. For the majority of the patients, the growth pattern is one of extensive superficial expansion showing a median length of 9 cm (range: 2-22 cm). Surprisingly, none of the VC patients showed lymph node or distant metastasis. 9 of 15 VC patients received local endoscopic therapy; 4 were treated with curative intent and 5 were treated palliatively. 3 patients underwent oesophageal resection, and definitive chemoradiotherapy was administered in a further 3 patients. One severe complication, consisting of a postoperative anastomotic insufficiency with a fatal outcome, occurred in this group of patients. CONCLUSION: This is the largest published study describing patients diagnosed with VC of the oesophagus so far. The option of local endoscopic therapy and its results in 9 patients are reported for the first time. The superficial growth pattern of the tumour and the frequent absence of lymph node or distant metastasis suggest that endoscopic resection can be carried out as a diagnostic and/or therapeutic approach. Due to the rarity of this entity, the case numbers are unfortunately so limited that evidence-based recommendations are unlikely to become available even in the future.

Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion.

BACKGROUND & AIMS: Patients with early-stage mucosal (T1a) esophageal adenocarcinoma (EAC) are increasingly treated by endoscopic resection. EACs limited to the upper third of the submucosa (pT1b sm1) could also be treated by endoscopy. We assessed the efficacy, safety, and long-term effects of endoscopic therapy for these patients. METHODS: We analyzed data from 66 patients with sm1 low-risk lesions (macroscopically polypoid or flat, with a histologic pattern of sm1 invasion, good-to-moderate differentiation [G1/2], and no invasion into lymph vessels or veins) treated by endoscopic therapy at the HSK Hospital Wiesbaden from 1996 through 2010. The efficacy of endoscopic therapy was assessed on the basis of rates of complete endoluminal remission (CER), metachronous neoplasia, lymph node events, and long-term remission (LTR). Safety was assessed on the basis of rate of complications. RESULTS: Remissions were assessed in 61 of the 66 patients; 53 of the 61 achieved CER (87%). Of patients with small focal neoplasias ≤2 cm, 97% achieved CER (for those with tumors ≥2 cm, 77%; P = .026). Metachronous neoplasias were observed in 10 of 53 patients (19%; 9 of the 10 underwent repeat endoscopic resection). One patient developed a lymph node metastasis (1.9%). Fifty-one patients achieved LTR (84%); 90% of those with focal lesions ≤2 cm achieved LTR after a mean follow-up period of 47 ± 29.1 months (range, 8-120 months). No tumor-associated deaths were observed, and the estimated 5-year survival rate was 84%. The rate of major complications from endoscopic resection was 1.5%, and no patients died. CONCLUSIONS: Endoscopic therapy appears to be a good alternative to esophagectomy for patients with pT1b sm1 EAC, on the basis of macroscopic and histologic analyses. The risk of developing lymph node metastases after endoscopic resection for sm1 EAC is lower than the risk of surgery.

Progression of specialized intestinal metaplasia at the cardia to macroscopically evident Barrett's esophagus: an entity of concern in the ProGERD study.

OBJECTIVES AND AIMS: Histological Barrett's esophagus, defined as specialized intestinal metaplasia (SIM+) at the cardia without endoscopic suspicion of columnar epithelium, is found frequently in biopsies at the gastro-esophageal junction although its clinical relevance is unknown. The authors aim was to evaluate prospectively the progression of SIM+ to macroscopically evident Barrett's esophagus (BE/SIM+), and to identify risk factors for this progression. METHODS: Data were obtained from a sub-group of patients (no visible BE at presentation, but SIM+) included in the ProGERD study, a prospective evaluation of the clinical course of GERD under routine clinical care. They had esomeprazole 20-40 mg/day for 2-8 weeks. Symptom assessment was performed annually, and endoscopy with biopsy was planned at baseline, after healing treatment and after 2 and/or 5 years. RESULTS: 128 of 171 (74.8%) patients with unequivocal SIM at the z-line after healing were biopsied again after 2 and/or 5 years. At follow-up, 33 (25.8%) of these patients showed progression to BE/SIM+. Factors significantly associated with progression were smoking, a long history of GERD and severe esophagitis at baseline. Patients who had progressed to BE/SIM+ already at 2 years showed consistent findings at 5 years. CONCLUSION: More than 20% of GERD patients with SIM+ in this study were found to have BE/SIM+ within 2-5 years. This finding supports the hypothesis that SIM+ at the cardia could be the missing link explaining increased cancer risk in GERD patients without overt BE and merits further investigation in a prospective study.

Precancerous conditions after H. pylori eradication: a randomized double blind study in first degree relatives of gastric cancer patients.

BACKGROUND: Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives (FDR) of gastric cancer (GC) patients following H. pylori eradication. METHODS: Participants underwent endoscopy with antrum and corpus histological examinations. Subjects with pangastritis were randomly allocated to placebo or eradication therapy and followed over 4½ years.  RESULTS: Among 989 evaluated FDR, we excluded 468 patients as follows: 108 had macroscopic lesions, 243 had no evidence of any H. pylori infection, and 117 were excluded for other reasons. The remaining subjects (n = 521) were allocated to therapy (group A, n = 261) or placebo (group B, n = 260) groups. Interim analysis of 403 subjects (201 placebo, 202 therapy) showed regression of atrophy (60 out of 97 in the antrum and 37 out of 104 in the corpus) in H.pylori-eradicated versus regression of atrophy (57 out of 184 in the antrum and 23 out of 173 in the corpus) in non-H.pylori-eradicated cases over 2½ years (P < 0.0001). No regression of intestinal metaplasia (IM) occurred in the antrum and corpus of treated subjects over 4½ years. However, progression of IM occurred in the antrum in 17 out of 90 patients in the non-H. pylori-eradicated versus 4 out of 68 H. pylori-eradicated subjects after 4½ years (P < 0.05). CONCLUSION: Eradication of H. pylori is associated with regression of gastric atrophy but not IM, even in its early stages. Gastric atrophy and IM in the antrum have shown more rapid progression in cases not treated for H. pylori infection (over 4½ years follow-up) compared to H. pylori-eradicated cases.

Second cancers and residual disease in patients treated for gastric mucosa-associated lymphoid tissue lymphoma by Helicobacter pylori eradication and followed for 10 years.

BACKGROUND & AIMS: Cure of Helicobacter pylori infection induces remission in most patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) that is associated with these bacteria. We determined the long-term outcomes of these patients in a prospective multicenter trial and investigated whether they developed second cancers or had histologic residual disease. METHODS: We followed 120 patients with stage EI1 GML for a median of 122 months after H pylori eradication (range, 1-171 months). Remission was determined by histology analysis and development of second cancers was documented. RESULTS: Of the patients, 80% (96 of 120) achieved complete remission from GML, and 80% of those (77 of 96) remained disease free. Estimated mean survival time in the Kaplan-Meier analysis was 147 months (95% confidence interval: 138-156 months). Of the patients that achieved complete remission, 17% (16 of 96) had histologic residual disease after a median of 32 months (range, 3-68 months). Disease did not progress in any of these patients, and all but 1 achieved a second complete remission (median duration, 46 months). Standardized morbidity ratios revealed a significantly higher incidence of gastric cancer (8.567; 95% confidence interval, 3.566-20.582) or non-Hodgkin lymphoma (18.621; 95% confidence interval: 8.365-41.448) in the 96 patients that achieved a complete remission, compared with the general German population. CONCLUSIONS: Cure of H pylori infection leads to continuous complete remission in most patients with H pylori-associated GML. Patients are at risk for development of secondary cancers (ie, gastric cancer and non-Hodgkin lymphoma).

Cancer prevention in ulcerative colitis: long-term outcome following fluorescence-guided colonoscopy.

BACKGROUND: Patients with long-standing ulcerative colitis require repeated endoscopies for early detection of neoplasias, which, however, are frequently missed by standard colonoscopy. Fluorescence-guided colonoscopy is known to improve the detection rate but the long-term effects of fluorescence-guided colonoscopy are unknown. METHODS: Colitis patients with negative findings at index fluorescence-guided colonoscopy entered a prospective long-term study with conventional colonoscopies at 2-year intervals. Risk and time to progression were evaluated. The positive predictive value was assessed in patients with neoplasias at index fluorescence-guided colonoscopy who underwent immediate total colectomy. RESULTS: Thirty-one patients with negative fluorescence-guided colonoscopy were surveyed for a mean of 7.8 ± 0.9 years. Neoplasia was observed in only two of them (6%) after 7 and 8 years of follow-up, respectively. Neoplasia at index fluorescence-guided colonoscopy was observed in 10 patients. In all of them, multiple flat low-grade intraepithelial neoplasia was diagnosed. At immediate colectomy performed in eight of them, the diagnosis of flat low-grade intraepithelial neoplasia was confirmed, corresponding to a positive predictive value of 100%. However, synchronous more advanced neoplasia was detected in three of the eight patients (38%). All patients, those with and those without neoplasia, were alive at the end of the study. CONCLUSIONS: Fluorescence-guided colonoscopy misses, in contrast to standard colonoscopy, few, if any, patients with neoplasia. Most neoplasia-negative patients remain negative during prolonged follow-up. However, when low-grade dysplasia is diagnosed by fluorescence-guided colonoscopy, colectomy is recommended because more than a third of the patients harbor synchronous, more advanced neoplasia.

Randomized trial on 14 versus 7 days of esomeprazole, moxifloxacin, and amoxicillin for second-line or rescue treatment of Helicobacter pylori infection.

BACKGROUND: Triple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first-line treatment of Helicobacter pylori infection. AIM: To explore 1, the value of triple therapy with esomeprazole, moxifloxacin, and amoxicillin in second-line or rescue treatment of Caucasian patients and 2, the impact of treatment duration on eradication success. METHODS: H. pylori-infected patients with at least one previous treatment failure were randomized to oral esomeprazole 20 mg b.i.d., moxifloxacin 400 mg o.d., and amoxicillin 1000 mg b.i.d. for either 7 (EMA-7) or 14 days (EMA-14). Eradication was confirmed by 13C urea breath test. Antimicrobial susceptibility testing was performed in all patients at baseline and in patients who failed treatment. RESULTS: Eighty patients were randomized, and 60% had ≥ 2 previous treatment failures. Pretreatment resistance against clarithromycin and metronidazole was found in 70.5 and 61.5% of cases, respectively. The intention-to-treat eradication rate was significantly higher after EMA-14 compared with EMA-7 (95.0 vs 78.9%, p = .036). No independent risk factor for treatment failure could be identified. There were no serious adverse events. Five of the EMA-14 patients (12.5%) compared with none of the EMA-7 patients discontinued prematurely because of adverse events (p = .031). Post-treatment resistance against moxifloxacin was found in one of seven patients with isolated organisms (14.3%). CONCLUSION: Second-line/rescue H. pylori eradication therapy with esomeprazole, moxifloxacin, and amoxicillin is very effective and well tolerated. Fourteen days of treatment significantly increase the eradication rate but also the rate of adverse events.

Primary follicular lymphoma of the duodenum is a distinct mucosal/submucosal variant of follicular lymphoma: a retrospective study of 63 cases.

PURPOSE: Small series with limited follow-up have suggested primary follicular lymphoma of the duodenum (FL-D) to be an indolent disease. We report our experience on a large series of patients followed for a median time period of longer than 6 years. PATIENTS AND METHODS: The study comprised 63 patients with primary FL-D defined as stage I disease. Endoscopy and detailed pathologic work-up was performed at diagnosis and at restaging to monitor the behavior of the neoplastic process. RESULTS: Histologically, all 63 patients had FL, low grade (1 to 2). Duodenal endosonography demonstrated lesions confined to mucosa/submucosa in 19 of 20 patients. At an overall median follow-up of 77 months (range, 12 to 177 months), only two untreated patients had developed nodal disease, the remaining 61 patients never experienced extrasmall intestinal disease and large cell transformation did not occur at all. Among 24 patients followed by watch and wait strategy, seven showed spontaneous complete regression and 17 had stable disease; radiotherapy resulted in complete regression in all 19 patients; anti-CD20 antibody monotherapy achieved complete regression in four patients and stable disease in one patient. Various chemotherapy protocols in eight patients caused complete regression in all of them, but local relapses occurred in three. No patients required surgery or died of disease. CONCLUSION: These findings characterize primary FL-D as a remarkably indolent FL variant, which, even left untreated, does not develop tumorous growth, very rarely disseminates (two of 63 patients) and does not transform to high grade disease. A watch and wait approach appears to be the most sensible strategy.

Allelic variation of the matrix metalloproteinase-9 gene is associated with collagenous colitis.

BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown origin characterized by a thickened subepithelial collagen layer. Differential expression of matrix-metalloproteinases (MMPs) have been implicated in the pathogenesis of collagenous colitis. The aim was to assess genetic polymorphisms of MMP-1, -7, and -9 in a case-control setting for susceptibility to collagenous colitis. METHODS: Seventy-five patients with symptomatic collagenous colitis and 334 healthy blood donors were genotyped for single nucleotide polymorphisms (SNPs) in MMP-1-1607, MMP-7-153, MMP-7-181, and MMP-9 exon 6 using TaqMan technology. Susceptibility to collagenous colitis was tested by comparison of the carrier status of the rare allele. RESULTS: The carrier frequency of the allele GG of the coding SNP MMP-9 in exon 6 was 24% in patients with collagenous colitis and 14.3% in healthy blood donors (P = 0.039). The carriage of the allele GG significantly increased the risk for collagenous colitis with an odds ratio of 1.9 (95% confidence interval: 1.0-3.5). None of the other SNPs of MMP-1, MMP-7-153, and MMP-7-181 were associated with collagenous colitis. CONCLUSIONS: Allelic variation in the MMP-9 gene may be part of a complex genetic risk profile for collagenous colitis. Further studies are needed to confirm this observation and to explore the functional role of this gene polymorphism in collagenous colitis.

Correlation of serum pepsinogens and gastrin-17 with atrophic gastritis in gastroesophageal reflux patients: a matched-pairs study.

BACKGROUND AND AIM: An algorithm (GastroPanel) for the non-invasive diagnosis of atrophic gastritis has been previously proposed, based on serum pepsinogen-I, gastrin-17, and Helicobacter pylori (H. pylori) antibodies. The aim of the present study was to evaluate whether serum markers correlate with and predict gastric atrophy in gastroesophageal reflux disease (GERD) patients. METHODS: The baseline data of the prospective ProGERD study, a study on the long-term course of GERD (n=6215 patients), served to select patients with atrophic gastritis diagnosed in biopsies from gastric antrum and corpus, and control cases without atrophy. A total of 208 pairs were matched for age, sex, GERD status (erosive vs non-erosive), presence of Barrett's esophagus, and histological H. pylori status were retrieved. Serum pepsinogen-I, gastrin-17, and H. pylori antibodies were determined using specific enzyme immunoassays. RESULTS: A significant negative correlation was found between the degree of corpus atrophy and the level of serum pepsinogen-I. A previously-reported negative correlation between the degree of antral atrophy and serum gastrin-17 could not be confirmed. The low sensitivity (0.32) and specificity (0.70) of the GastroPanel algorithm were mainly due to over diagnosis and under diagnosis of advanced atrophy in the antrum. CONCLUSION: The diagnostic validity of the GastroPanel algorithm to diagnose gastric atrophy non-invasively is not sufficient for general use in GERD patients.

Twelve-month endoscopic and histological analysis following proton-pump inhibitor-based triple therapy in Helicobacter pylori-positive patients with gastric ulcers.

OBJECTIVE: To evaluate endoscopic and histological findings after Helicobacter pylori eradication therapy in gastric ulcer (GU) patients after 12 months' follow-up. MATERIAL AND METHODS: A total of 401 GU patients were randomized to receive either twice-daily (b.i.d.) esomeprazole 20 mg+amoxicillin 1000 mg+clarithromycin 500 mg (EAC) for 1 week followed by placebo for 3 weeks, EAC followed by once-daily (o.d.) esomeprazole 20 mg for 3 weeks or esomeprazole 20 mg b.i.d. plus placebo antibiotics for 1 week followed by esomeprazole 20 mg o.d. for 3 weeks. Endoscopy with biopsy was performed at baseline, after treatment and at 6 and 12 months' follow-up (healed patients). RESULTS: Endoscopic abnormalities, particularly in the stomach, were common at baseline and remained similar during follow-up, regardless of ulcer status and treatment. Helicobacter gastritis was present (antrum or corpus) in approximately 20% of patients following eradication therapy (versus approximately 80% with esomeprazole alone); these effects were sustained during follow-up. Similar trends were observed for other histological variables (granulocyte and lymphoplasmocytic cell infiltration, replacement of gastric surface cells by regenerative epithelium, and mucous depletion). No changes in atrophy or intestinal metaplasia were observed. Eighteen gastric cancer cases were detected: 11 at baseline endoscopy, and seven during treatment and follow-up. CONCLUSIONS: Endoscopic abnormalities are common in GU patients and persist after proton-pump inhibitor-based triple therapy for H. pylori eradication, which is associated with large, sustained improvements in histological variables. Follow-up endoscopy and histology may be necessary, even in patients with apparently non-malignant GU, to improve the detection rate of gastric malignancy in populations with a high prevalence of gastric cancer.