Clinicopathologic analysis of gastric mucosa-associated lymphoid tissue lymphoma with or without c-Met expression.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is mainly associated with Helicobacter pylori infection, and H. pylori eradication therapy is often effective. However, 20-30% of the cases of MALT lymphoma are resistant to the eradication therapy, and translocation of the API2-MALT1 gene is often found in these cases. Most cases without translocation of API2-MALT1 are localized to the stomach, whereas some cases with this translocation are a more advanced stage of MALT lymphoma that spreads to other organs. The c-Met receptor is a prognostic factor involved in infiltration and metastasis in many malignant tumors, including gastric, pancreatic, lung, and kidney cancer. In the present study, the expression of c-Met in 43 cases of gastric MALT lymphomas was immunohistochemically examined and compared with clinicopathological factors. To elucidate the significance of c-Met in MALT lymphoma, the expression intensity of c-Met in 22 API2-MALT1 translocation-positive and 21 API2-MALT1 translocation-negative cases was scored, compared, and examined. The immunohistochemistry analysis revealed strong staining for c-Met in 21 API2-MALT1 translocation-positive cases and in 1 translocation-negative case (P = 0.00). This result indicates the relationship between strong expression of c-Met and the progression of MALT lymphoma with API2-MALT1 gene translocation.

Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients.

Pancreatic cancer has a poor prognosis; hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months; HR 1.89 (1.12-3.12); P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822 U/ml; P = 0.001), Dupan-2 (286 vs. 1133 U/ml; P = 0.000), and Span-1 (69.7 vs. 171.9 U/ml; P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-ß-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation.

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine.

Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10down ) GI-FL. The diagnosis of CD10down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10down GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P < 0.001). Compared to CD10+ GI-FL, CD10down GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10down GI-FL, and an identical clone was found between CD10down follicles and CD10+ BCL2+ neoplastic follicles. In the diagnosis of cases with CD10down BCL2+ follicles, careful examination with molecular studies should be carried out.

Association between CT-Diagnosed Pneumonia and Endoscopic Submucosal Dissection of Gastric Neoplasms.

BACKGROUND/AIMS: This prospective cohort study aimed to elucidate the incidence and characteristics of pneumonia associated with endoscopic submucosal dissection (ESD) of gastric neoplasms using CT. METHODS: We included consecutive 188 patients with gastric neoplasms treated with ESD. All patients underwent CT before ESD and the day after ESD. Pneumonia associated with ESD was defined as lung ground glass opacity or consolidation by CT the day after ESD. RESULTS: In 188 patients, 28 patients had diabetes mellitus. Pneumonia was observed by CT in 21 patients (11.2%) after ESD. Of those, 7 patients had diabetes mellitus. By univariate analysis, compared with patients with non-pneumonia complications, risk factors for pneumonia were significantly increased in patients with diabetes mellitus (p = 0.01) and in those who underwent a long procedure time (p = 0.02). By multivariate analysis, pneumonia was significantly increased in patients with diabetes mellitus (OR 4.06, 95% CI 1.35-12.19) and in those who underwent a long procedure time (OR 1.01, 95% CI 1.00-1.02). CONCLUSIONS: The incidence of CT-diagnosed pneumonia associated with ESD was relatively high. Furthermore, it was revealed that diabetes mellitus and a long procedure time were risk factors of CT-diagnosed pneumonia.

Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P.

The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in ABC-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041) and elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.

Risk factors for perforation and delayed bleeding associated with endoscopic submucosal dissection for early gastric neoplasms: analysis of 1123 lesions.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a useful procedure for the treatment of early gastric neoplasms; however, this advanced technique has also resulted in an increase in serious complications such as perforation and delayed bleeding. This study aimed to elucidate the risk factors for these complications. METHODS: A total of 1123 lesions diagnosed with early gastric neoplasms and treated by ESD at three institutions were investigated. Retrospectively, patients with or without these complications were compared on the basis of the patient characteristics and treatment results. RESULTS: Perforation occurred in 27 lesions (2.4%) and delayed bleeding in 56 lesions (5.0%). Multivariate analysis indicated that lesions located in the upper area of the stomach (odds ratio [OR]: 4.88, 95% confidence interval [CI]: 2.21-10.75) was associated with a significantly higher risk of perforation, and that age ≥ 80 years (OR: 2.15, 95% CI: 1.18-3.90) and a long procedure time (OR: 1.01, 95% CI: 1.001-1.007) were associated with a significantly higher risk of delayed bleeding after ESD. The en bloc resection rate (74% vs 94%) and curative resection rate (48% vs 85%) of lesions with perforation were significantly lower than those without perforation. The rate of residual disease or recurrence after ESD was significantly higher in lesions with delayed bleeding than that without delayed bleeding (5.4% vs 0.84%). CONCLUSIONS: This study demonstrated risk factors for perforation and delayed bleeding associated with ESD. Furthermore, it was clarified that perforation and delayed bleeding influenced post-procedure results and prognosis after ESD.

Small early gastric cancer with synchronous bone metastasis: A case report.

Bone metastasis during the early stages of gastric cancer is rare, and synchronous bone metastasis is even less common. The present report outlines a case of a small early gastric cancer, which was detected due to bone metastasis. A 63-year-old man was referred to Fukuyama Medical Center with back pain and anorexia of 2 weeks' evolution. MRI revealed multiple metastatic lesions in the thoracic and spinal bone. Fluorodeoxyglucose positron emission tomography revealed focal uptake in the lesser curvature of the stomach and in the spinal bone, pelvic and thigh bone, but uptake was not detected in the stomach. Esophagogastroduodenoscopy revealed a 10 mm slightly elevated lesion with a central depression in the middle-third of the stomach. Endoscopic ultrasonography confirmed that the tumor was confined to the mucosa. A biopsy specimen acquired from the gastric lesion indicated signet-ring cell carcinoma, and the specimen acquired from the lumbar spine revealed cell aggregation such as that found in signet-ring cell carcinoma. The patient received first-line chemotherapy with S-1 and cisplatin, and second-line chemotherapy with nab-paclitaxel. However, the patient died 120 days after consultation at Fukuyama Medical Center.

Risk factors for non-curative resection of early gastric neoplasms with endoscopic submucosal dissection: Analysis of 1,123 lesions.

Although the frequency of residual disease and recurrence following endoscopic submucosal dissection (ESD) has markedly decreased, a few cases of residual disease and recurrence following ESD are still observed. The aims of the present study were to clarify the causes of non-curative resection and to investigate the risk factors. A total of 1,123 early gastric neoplasm lesions treated by ESD were investigated. Non-curative resection was defined as histological positivity of the resected margins, vascular invasion or failure of en bloc resection. Cases of non-curative resection were classified as being caused by one of three reasons: Inadequate technique, pre-procedural misdiagnosis or problems in the histological diagnosis. Following classification, the cases of non-curative and curative resection were compared based on a range of patient characteristics: Procedure time, and size, type and location of the lesions. The frequency of non-curative resection was 16% (182 lesions). Non-curative resection occurred due to inadequate technique in 59 cases, pre-procedural misdiagnosis in 88 cases and problems in the histological diagnosis in 35 cases. Multivariate analysis revealed that a large lesion size, long procedure time and inexperienced endoscopist were associated with a significantly higher risk of non-curative resection due to an inadequate technique. Furthermore, it was found that lesions located in the upper area of the stomach and cancer with submucosal invasion were associated with a significantly higher risk of non-curative resection due to pre-procedural misdiagnosis. In conclusion, the present study has shown that the major reasons for non-curative resection are an inadequate technique and pre-procedural misdiagnosis. The risk factors for these problems have been clarified.