Isolated tumor cells in regional lymph nodes as relapse predictors in stage I and II colorectal cancer.

PURPOSE: Lymph node (LN) involvement is the most important prognostic factor in colorectal cancer (CRC), and pN-positive status identifies patients who require adjuvant chemotherapy. Approximately 15% to 20% of patients without nodal metastases (pN0) develop recurrent disease. In this study, we tested the prognostic significance of isolated tumor cells (ITCs) in LNs of patients with pN0 CRC (stages I and II). PATIENTS AND METHODS: ITCs in LNs regional to CRC were assessed in 312 consecutive patients with pN0 CRC who were followed up clinically and/or endoscopically for at least 6 months after surgery (mean, 67 months; median, 64 months; range, 8 to 102 months). LNs were dissected from gross surgical specimens according to a standardized protocol (with a mean of 17 LNs per patient; range, five to 107 LNs). In all, 5,313 pN0 LNs were collected and assessed by using cytokeratin immunostaining in two serial histology sections from each LN, which amounting to a total of 10,626 specimens. The correlation between ITC status and cancer recurrence was tested by using univariate and multivariate statistics. RESULTS: ITCs were documented in 185 of 312 patients (59%). CRC relapsed in 31 of 312 patients (10%), and 25 of 31 recurrences (81%) were documented among ITC-positive patients. CRC recurrence rates among ITC-positive and ITC-negative patients were 14% (25 of 185 patients) and 4.7% (six of 127 patients), respectively. In both univariate and multivariate analyses, ITC status was the only variable significantly associated with cancer relapse (Cox model; hazard ratio, 3.00; 95% CI, 1.23 to 7.32; P = .013). CONCLUSION: In patients with pN0 CRC, cancer relapse was significantly associated with ITCs in regional LNs. ITCs should be considered among the clinicobiologic variables that identify high-risk patients who can benefit from adjuvant chemotherapy.

Gastritis: the histology report.

Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.

OLGA gastritis staging in young adults and country-specific gastric cancer risk.

Geographical differences have been shown in the clinical outcomes of Helicobacter pylori-associated gastritis phenotypes and in gastric cancer risk. This study tested whether the Operative Link on Gastritis Assessment (OLGA) staging correlated with gastric cancer risk in populations from 3 continents. Mapped gastric biopsies were obtained from 316 dyspeptic adults aged less than 41 years from 8 geographic areas that differed in gastric cancer risk. Gastric atrophy was assessed according to internationally validated criteria. Gastritis stage was established according to the OLGA staging system. The most prevalent gastritis stages were 0 to II, which included all subjects entered from Chile, Germany, India, Italy, and Thailand. Gastritis Stages III and IV were limited to the Chinese and Korean populations. Indians had a high prevalence of H pylori infection without high-stage gastritis. In populations at different cancer risk, the gastritis OLGA stage mirrored the gastric cancer incidence. Gastritis staging identifies a subgroup of higher-risk patients.

Differential effects of Helicobacter pylori eradication on oxidative DNA damage at the gastroesophageal junction and at the gastric antrum.

BACKGROUND AND AIM: Helicobacter pylori-associated gastritis causes accumulation of reactive oxygen species in the mucosal compartment. This prospective study evaluates DNA oxidative damage in biopsy samples obtained from both the antrum and the gastroesophageal junction (GEJ) before and after H. pylori eradication. PATIENTS AND METHODS: Thirty-two consecutive H. pylori-positive patients underwent endoscopy with multiple biopsy sampling (i.e., antrum, incisura angularis, fundus, and cardia at the GEJ). After H. pylori eradication, 32 patients underwent a checkup endoscopy (mean interval, 5.7 months); in a subgroup of 13 subjects, a third endoscopy procedure was also performed (mean interval, 18 months). Additional biopsy samples (two from the antrum and two from the GEJ) were used to assess 8-hydroxydeoxyguanosine (8OHdG) levels using both high-pressure liquid chromatography with electrochemical detector and ELISA. RESULTS: In the antral compartment, no significant modifications of 8OHdG levels were assessed after H. pylori eradication. Conversely, following eradication, 8OHdG levels significantly increased (high-pressure liquid chromatography with electrochemical detector, P = 0.04; ELISA method, P = 0.05) in biopsy samples taken from the GEJ, and a further increase was documented in the subgroup of patients who underwent a third endoscopy (P = 0.01). The increasing trend was more relevant in patients in whom H. pylori-cagA-positive strains were eradicated and in those affected by hiatal hernia. CONCLUSIONS: The levels of DNA adducts in the antral mucosa are not modified by H. pylori eradication; conversely, H. pylori eradication significantly increases the oxidative adducts at the GEJ. The clinical and biological importance of this situation and whether and how it relates to a higher risk of precancerous lesions is open to debate.

Serological markers for gastric atrophy in asymptomatic patients infected with Helicobacter pylori.

OBJECTIVE: Atrophic gastritis is a precancerous condition that is commonly caused by chronic Helicobacter pylori (H. pylori) infection. This blinded, controlled study was designed to determine if serum gastrin and pepsinogens were reliable markers of atrophy in asymptomatic patients. METHODS: One hundred and forty-seven asymptomatic patients underwent endoscopy with multiple gastric biopsies obtained for histology, culture, and rapid urease test. Fasting serum gastrin (total and G-17) and serum pepsinogens (I-II) were determined by standard immunoassays. Gastric atrophy was histologically assessed in accordance with internationally accepted criteria; three main patterns of gastritis were distinguished: (a) nonatrophic gastritis, (b) atrophic antrum-restricted and antrum-predominant gastritis, and (c) corpus-restricted gastritis. Receiving operating characteristic (ROC) analysis was used to determine the best cut-off for each serum test in nonatrophic gastritis versus antrum-restricted/antrum-predominant atrophic gastritis. RESULTS: No significant differences in serum gastrin and pepsinogens I-II were detected in nonatrophic gastritis versus patients with antrum-restricted/antrum-predominant atrophic gastritis. The positive likelihood ratios for an abnormal serum test to detect antrum-restricted/antrum-predominant atrophy in the gastric body were total serum gastrin 2.13 (95% CI 0.99, 4.6), gastrin-17: 1.55 (95% CI 0.75, 36.17), pepsinogen I: 2.74 (1.4, 5.4), pepsinogen II: 1.74 (1.27, 2.39), and the ratio of pepsinogen I and II: 1.8 (1.2-2.8). Negative likelihood ratios ranged from 0.20 to 0.65. CONCLUSION: In an asymptomatic population, serum gastrin (total and G-17) and pepsinogens I-II (and their ratio) do not discriminate nonatrophic versus antrum-restricted/predominant atrophic gastritis.

Helicobacter pylori CagA status, mucosal oxidative damage and gastritis phenotype: a potential pathway to cancer?

BACKGROUND: Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori-cagA-positive strains are associated with the highest risk of gastric cancer. AIMS: To ascertain whether cagA-positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. PATIENTS AND METHODS: 118 patients were studied (65M/53F, age 61 +/- 14 years). Twelve were H. pylori-negative. Among the H. pylori-positive patients, 34 were cagA-positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8-hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. RESULTS: The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA-positive infection significantly correlated with a higher prevalence of atrophic-metaplastic lesions (p = 0.04). cagA-positive patients had higher 8-hydroxydeoxyguanosine levels than both cagA-negative and H. pylori-negative cases (p = 0.01). The 8-hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA-positive patients having 8OHdG levels above a cut-off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. CONCLUSIONS: cagA-positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer-prone biological context.