Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

OBJECTIVE: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS: There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS: We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Plasmablastic lymphoma affecting the lung and bone marrow with CD10 expression and t(8;14)(q24;q32) translocation.

Plasmablastic lymphoma is a rare variant of a diffuse, large B-cell lymphoma, which typically presents in the oral cavity in immunocompromised patients. In HIV positive patients, this tumor has a tendency to manifest in extramedullary sites. In this report, we document a rare instance in which this neoplasm besides affecting the bone marrow also involved the lung. In addition, the lymphoma in our case disclosed CD10 positivity on immunohistochemistry and t(8;14)(q24;q34) translocation on cytogenetic analysis, mimicking a Burkitt/atypical Burkitt lymphoma. The problems in diagnosis are discussed.

Early post-surgical recurrence of metastatic vertebral neuro-endocrine tumour treated effectively with chemo-radiotherapy.

Spinal metastasis of neuro-endocrine tumours (NETs) usually arise from a primary in the lung. We encountered such a patient with NET metastasis to T6 vertebra causing severe cord compression. Considering the neurological status, immediate decompression surgery along with T3-T8 posterior stabilization was done. Early recurrence of the tumour causing near total obliteration of the spinal canal leading to significant neurological compromise was noted within one month of surgery. A second surgery at this stage was avoided due to the risk involved and concurrent chemo-radiotherapy was initiated. The tumour was sensitive to chemo-radiotherapy and rapid resolution was noted on subsequent follow-up visits. With appropriate rehabilitation, patient regained full power to become ambulant with support. This case report highlights a rare, early and aggressive recurrence of metastatic vertebral NET following index surgery which was effectively managed with chemo-radiotherapy.

Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria.

BACKGROUND: This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. METHODS: The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. RESULTS: The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. CONCLUSION: The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.

Intraabdominal schwannomas: a single institution experience.

INTRODUCTION: Intraabdominal schwannomas are rare, benign tumors. This study presents a single institution experience with 12 such tumors. METHODS: Between 1991 to 2006, 12 patients with a pathologically proven intraabdominal schwannoma were identified from a series of 216 mesenchymal tumors and were reviewed retrospectively. RESULTS: There were nine females and three male patients with a median age of 58 years (range 35-88 years). Eleven patients were symptomatic, and the tumors were located in the stomach (n = 8), jejunum, colon, rectum, and lesser sac. Multiple preoperative investigations including endoscopies with biopsies and computed tomography (CT) scans were performed, but none yielded a correct definitive preoperative diagnosis. The median tumor size was 52 mm (range 18-95 mm). Pathological examination demonstrated the 11 gastrointestinal tract (GIT) schwannomas to be solid homogenous tumors, which were highly cellular and were composed of spindle cells with positive staining for S100 protein. The pathological appearance of the lesser sac schwannoma was distinct as it demonstrated cystic degeneration with hemorrhage and Antoni A and B areas on microscopy typical of soft tissue schwannomas. All 12 patients were disease-free at a median follow-up of 22 months (range 1-120 months). CONCLUSION: Intraabdominal schwannomas are rare tumors, which are most frequently located within the GIT. GIT schwannomas are difficult if not impossible to diagnose preoperatively as endoscopic and radiologic findings are nonspecific. The treatment of choice is complete surgical excision because of diagnostic uncertainty, and the long-term outcome is excellent as these lesions are uniformly benign.

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer.

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.

Diagnosis of adenoid cystic carcinoma of the lung by bronchial brushing: a case report.

BACKGROUND: A diagnosis of pulmonary adenoid cystic carcinoma on exfoliative cytology specimen is very uncommon. The diagnostic cytologic material typically is obtained following a tissue biopsy. No previous report of the diagnosis has been made on bronchial brushing cytologic material when the procedure preceded a tissue biopsy. CASE: A 44-year-old man who used to smoke cigarettes and was otherwise well complained of persistent cough for the past 6 months. A chest radiograph revealed a mass lesion in the left hilum. Computed tomography of the chest disclosed an irregular and spiculated soft tissue mass in the left apical anterior segment. Bronchial brushing via bronchoscope was performed, revealing carcinoma cells consistent with an adenoid cystic carcinoma on cytology. A bronchial biopsy and subsequent left upper lobectomy were performed, confirming the diagnosis of adenoid cystic carcinoma of the lung associated with tumor extension to the epithelial surface. CONCLUSION: A diagnosis of bronchial adenoid cystic carcinoma is possible on bronchial brushing. However, as a method in exfoliative cytology, the usefulness of bronchial brushing in diagnosing this tumor is limited by the neoplasm's proximity to the mucosal surface and whether the mucosa has been breached.

Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer: correlation with outcome of patients after radiotherapy.

PURPOSE: The expression of inducible nitric oxide synthase (iNOS) and bcl-2 proteins was evaluated and the prognostic significance determined in nasopharyngeal cancer (NPC) patients treated by radiotherapy. METHODS AND MATERIALS: Tissue sections from 55 patients with NPC were assessed for iNOS and bcl-2 protein expression by immunohistochemistry, immunoelectron microscopy, and in situ hybridization before treatment. The markers were correlated with apoptosis (detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay) and clinicopathologic parameters. RESULTS: All NPC sections exhibited positive iNOS and bcl-2 immunoreactivity, with a mean percentage of 6.24% +/- 0.58% and 17.09% +/- 2.48%, respectively. A significant positive correlation was observed between iNOS expression and the apoptotic index (p < 0.0001, Pearson's r = 0.8518), and bcl-2 expression correlated inversely with apoptosis (p = 0.0001; Pearson's r = -0.6170). A significant inverse correlation was found between iNOS and bcl-2 immunoreactivity (p < 0.0001, Pearson's r = -0.7144). Bcl-2 but not iNOS expression was associated with the stage of the tumor according to the criteria of the American Joint Committee on Cancer (1997) (p < 0.0001). Patients who had recurrence of the tumor and metastasis after radiotherapy had a lower expression of iNOS (p = 0.014 and p = 0.035, respectively), although overall survival was not significantly different statistically. Higher bcl-2 expression was also associated with local tumor recurrence (p = 0.005) but not with metastasis or overall survival. CONCLUSION: It appears that iNOS and bcl-2 expression may be potentially useful biomarkers for predicting the outcome of radiotherapy in NPC patients.

Glutathione S-transferase pi expression in nasopharyngeal cancer.

BACKGROUND: Glutathione S-transferase pi (GST-pi) is an enzyme that catalyzes the conjugation of electrophilic substrates and prevents oxidative damage. Although GST-pi expression has been analyzed in many cancers, the significance of GST-pi expression in nasopharyngeal cancer (NPC), a tumor with a high treatment failure rate, is still unclear. OBJECTIVE: To elucidate the significance of GST-pi expression in NPC. DESIGN: Evaluation of GST-pi expression in NPC tissue specimens and determination of its relationship with tissue iron (a pro-oxidant) and clinicopathological factors in NPC. MATERIALS AND METHODS: Immunohistochemical expression of GST-pi was carried out in 55 NPC and 4 normal nasopharyngeal tissue sections. Eleven nasopharyngeal biopsy specimens (4 normal and 7 NPC) were analyzed for tissue iron levels. The expression of GST-pi in NPC was correlated with corresponding tissue iron levels. The relationships between GST-pi expression with sex, race, tumor stage, cervical nodal status, and clinical staging were also analyzed. RESULTS: Glutathione S-transferase pi immunoreactivity was observed in all NPC sections, with the percentage of immunopositive cells ranging from 1.0% to 72.0%. Tissue iron levels were significantly higher in the NPC tissues compared with normal tissues (P =.001). A direct correlation was observed between GST-pi expression and total and nuclear iron levels in NPC (P =.01 and P =.047, respectively). A significant association was also observed between GST-pi expression and cervical nodal disease (P =.007). CONCLUSIONS: Nasopharyngeal tumor cells may respond to pro-oxidant conditions by modulating intracellular antioxidant defense. Glutathione S-transferase pi expression appears to be associated with lymphogenous metastasis in NPC.

Flat colorectal lesions: colonoscopic detection without dye spray or magnification and clinical significance.

OBJECTIVE: The detection of flat colorectal lesions with possible malignant potential has been described by Japanese endoscopists. This study looks at the detection of flat lesions using standard colonoscopic techniques and examines the clinical significance of these lesions. METHODS: The records of patients who underwent complete colonoscopy by a single colorectal surgeon in an outpatient setting over a 4-year period were reviewed. The site and number of flat lesions and their histology were noted. Patients with incomplete intubation of the colon were excluded. RESULTS: A total of 491 patients underwent 593 colonoscopic examinations. There were 236 flat lesions identified in 91 patients: 24% (56/236) were adenomas showing mild or moderate dysplasia, and 63% (148/236) were hyperplastic. CONCLUSIONS: Flat colorectal lesions are common and can be detected without the aid of dye spray and magnification. One-quarter of these lesions are adenomatous and we recommend routine hot biopsy or polypectomy of these lesions.