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.

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.

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.

Solitary fibrous tumor of the adrenal gland with unusual immunophenotype: a potential diagnostic problem and a brief review of endocrine organ solitary fibrous tumor.

Solitary fibrous tumor was initially thought to be a pleura-based tumor. However, over the last two decades, its involvement in a variety of extrapleural sites gained recognition. Nonetheless, a primary involvement of the endocrine organs is rare, and in this report, we detail an instance where the tumor affected the adrenal gland of a 71-year-old Arab man. On histology, besides the typical morphologic features seen in solitary fibrous tumor, the neoplasm also exhibited unusual features on immunohistochemistry such as positive staining for cytokeratin AE1/3 and calponin in conjunction with diffuse expression for S-100. The genetic tests for t(X:18) as seen in synovial sarcoma were negative, and the overall histological appearance favored a diagnosis of solitary fibrous tumor. To the best of our knowledge, this report represents the fifth case of a solitary fibrous tumor primarily occurring in the adrenal gland. The differential diagnoses of this neoplasm in our case and a brief summary of solitary fibrous tumor primarily involving the various endocrine organs are presented.

Outcome after curative resection of large (>or=10 cm) gastric gastrointestinal stromal tumors: how frequent is adjacent organ involvement and is concomitant distal pancreatectomy necessary?

INTRODUCTION: Complete tumor resection with clear margins including adjacent organs is the treatment of choice for gastrointestinal stromal tumors (GISTs). However, true tumor invasion of adjacent organs has been reported to be rare. Concomitant distal pancreatectomy (DP) for suspected tumor infiltration is not infrequently performed during resection of large gastric GISTs. This study aims to determine the true frequency of adjacent organ involvement by large gastric GISTs with particular attention to the pancreas and compares the outcome after curative resection with and without a concomitant DP in order to determine if DP is truly necessary. METHODS: A retrospective review of 37 patients who underwent curative resection of large (>or=10 cm) gastric GISTs was conducted. RESULTS: Wedge resections were performed in 22, partial gastectomies in nine, and total gastrectomies in six patients. The median operative time was 180 min (range, 60-330 min), and the patients had a median postoperative stay of 8 days (range, 4-29 days). Overall, there were eight (22%) morbidities including two (5%) mortalities. Nineteen (51%) had concomitant adjacent organ resection, and these included 15 (41%) DPs with splenectomies. Direct organ invasion was demonstrated in 5/19 patients (26%) and 7/30 organs (23%) resected. Only 1/15 (6.7%) DP specimens demonstrated tumor infiltration. Comparison between the patients with and without a concomitant DP demonstrated that performance of a DP was associated with a longer operation time [225 min (range, 105-305 min) vs 158 min (60-330 min), P=.002)], increased postoperative stay [9 days (range, 7-29 days) vs 7.5 days (4-19 days), P=.042], and increased postoperative morbidity [6 (40%) vs 2 (9%), P=.025]. The DP cohort also had a statistically significant poorer 5-year recurrence free survival (22% vs 60%, P=.017). CONCLUSION: Although adjacent organ involvement is not uncommon with large gastric GISTs, concomitant DP is usually unnecessary as direct pancreatic invasion is rare. Furthermore, concomitant DP with splenectomy is associated with an increase in postoperative morbidity.

A single-institution experience with eight CD117-positive primary extragastrointestinal stromal tumors: critical appraisal and a comparison with their gastrointestinal counterparts.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) arising from outside the gut wall also termed extragastrointestinal stromal tumors (EGISTs) are reported to be rare. Presently, their pathogenesis remains controversial, and recently, it has been proposed that EGISTs may be the result of extensive extramural growth of GISTs which lose contact with the gut wall. This study presents a single-institution experience with eight EGISTs and compares their clinicopathological features with mural GISTs in order to determine further insight to their possible origin. METHODS: Between 1997 and 2008, 156 patients with pathologically proven CD117-positive primary GISTs were retrospectively reviewed. Eight tumors were identified as EGISTs, 104 were gastric GISTs, and 44 were small-bowel GISTs. Mural GISTs were classified as extramural or intra/transmural according to their gross pattern of growth. RESULTS: There were five male and three female patients with a median age of 58 years (range, 42-81 years). All patients were symptomatic, and the tumors were located in the greater omentum (n = 2), lesser sac (n = 2), lesser omentum, retroperitoneum, small-bowel mesentery, and pancreas. The median tumor size was 140 mm (range, 55 to 220 mm). Seven of eight EGISTs were found to be in close association to the adjacent gut wall. Pathological examination demonstrated that two tumors demonstrated focal involvement of the muscularis propria of the adjacent gut wall. Four tumors demonstrated tumor abutting or adherent to the serosa but no muscle involvement and one tumor was separated from the serosa. Comparison between the clinicopathological features of EGISTs with extramural GISTs and intra/transmural GISTs demonstrated that EGISTs were significantly larger [140 range (55-220) mm vs 80 (5-260) mm vs 50 (15-190) mm, P = 0.049, P < 0.001 respectively]. CONCLUSION: The occurrence of true EGISTs is rare. Most cases demonstrate some form of communication or contact with the gut wall, and EGISTs are significantly larger than extramural or intra/transmural GIST. These observations suggest that most, if not all, cases of EGISTs are likely to represent mural GISTs with extensive extramural growth with eventual loss of contact with the muscle layer of the gut.

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.

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.

Outcome after surgical treatment of suspected gastrointestinal stromal tumors involving the duodenum: is limited resection appropriate?

INTRODUCTION: Present surgical opinion is divided regarding the optimal method for the treatment of duodenal gastrointestinal stromal tumor (GIST) with some supporting the selective use of limited resection (LR) versus others who prefer pancreaticoduodenectomy (PD). METHODS: A retrospective review of 22 patients who underwent surgery for suspected GIST involving the duodenum. RESULTS: There were 15 GISTs, 1 leiomyosarcoma and 6 other non-GIST benign submucosal tumors. Seven patients underwent LR and seven underwent PD for GIST. The median follow-up was 42 (range, 2-174) months. Patients who underwent LR versus PD had similar mean disease-specific survival [144 (95% CI, 92-196) vs. 130 (95% CI, 82-127) months, P = 0.808] and recurrence rates (14% vs. 29%, P = 0.515). All recurrences occurred at distant sites. Comparison between LR versus PD demonstrated that LR was associated with a significantly shorter operation time [125 (range, 50-305) vs. 350 (range, 210-465) min., P = 0.001] but similar morbidity rate (23% vs. 43%, P = 0.357). Comparison between GIST and other benign tumors demonstrated that size was the only statistically significant distinguishing factor [8.5 (range, 2.5-18.0) vs. 2.5 (range, 1.5-8.0) cm, P = 0.014]. CONCLUSION: Benign non-GIST tumors may be distinguished from duodenal GIST as they are smaller in size. LR is a viable treatment option for suspected GIST involving the duodenum.