Detection of early stage gastric cancers in screening laser endoscopy using linked color imaging for patients with atrophic gastritis.

BACKGROUND AND AIMS: Laser endoscopy involves blue laser imaging in bright mode (BLI-bright). Linked color imaging (LCI) is superior to white light imaging (WLI) for detecting gastric cancers. This study aimed to detect gastric cancers on screening endoscopy using not only WLI but also BLI-bright and LCI in patients with atrophic gastritis. PATIENTS AND METHODS: A total of 500 patients with atrophic gastritis undergoing screening esophagogastroduodenoscopy were included. The gastric lumen was observed in the WLI mode, followed by the LCI and BLI-bright modes. When gastric neoplasms were suspected, the mode was changed to WLI, and we sprayed indigo carmine. Finally, biopsy specimens were taken for those lesions and pathological diagnosis was made. We compared the size, morphology, and color of gastric neoplasms found by the first WLI mode and those detected by only the LCI mode or BLI-bright mode. RESULTS: We detected 16 gastric neoplasms (3.2%), of which 13 were early gastric cancers (EGCs) and three were gastric adenomas. Ten EGCs and two gastric adenomas (75%) were detected by the first WLI mode; three EGCs and one gastric adenoma (25%) were missed by the first WLI mode and were detected by the LCI mode or BLI-bright mode. All were less than 1 cm in diameter and were reddish. Mean diameter of the lesions was significantly less for LCI-detected or BLI-bright-detected lesions than for WLI-detected lesions (7.8 vs 21.2 mm). CONCLUSIONS: Laser endoscopy is useful for detecting EGCs by LCI for patients with atrophic gastritis.

Chronic Enteropathy Associated with SLCO2A1 with Pachydermoperiostosis.

A 49-year-old man complained of chronic palpitation and shortness of breath, which had recently become exacerbated. A blood examination indicated severe refractory anemia and hypoproteinemia. Physical examinations revealed anemia, a systolic murmur, and spoon nails. Multiple nonspecific ileal ulcers were observed. A pathological examination indicated a small granuloma with CD68-positive histiocytes. He had a deeply wrinkled forehead, chiseled face, and clubbed fingers. Radiography revealed periostosis of the fingers and long bones in the limb. He was diagnosed with pachydermoperiostosis. SLCO2A1 demonstrated a c.1807C>T homo-mutation. He was also diagnosed with SLCO2A1-associated chronic enteropathy and thus was treated with 5-aminosalicylic acid, which temporarily improved the ileal ulcers, anemia, and hypoalbuminemia.

Randomized control trial of adenoma detection rate in Endocuff-assisted colonoscopy versus transparent hood-assisted colonoscopy.

BACKGROUND AND AIM: Transparent hood-assisted colonoscopy (TAC) has been reported to improve the cecal insertion rate and adenoma detection rate (ADR). An endoscopic cap (Endocuff) with two rows of soft wings was recently developed to improve ADR, by flattening the mucosal folds during withdrawal. This randomized prospective control study aimed to compare ADR between Endocuff-assisted colonoscopy (EAC) and TAC. METHODS: A total of 513 patients undergoing colon adenoma screening were included. EAC was performed in 256 patients and TAC in 260 patients. Cecal intubation rate, cecal intubation time, ADR, and mean adenoma number per patient (MAP) were investigated in both groups (clinical trial registration: UMIN000016278). RESULTS: We excluded six patients in the EAC group and two patients in the TAC group because of colonic stenosis due to colonic adenocarcinomas. Finally, 250 patients (151 men/99 women, median age 62.1 years) were assigned to EAC and 258 patients (165 men/93 women, median age 64.3 years) were assigned to TAC. There were no significant differences in cecal intubation rate, intubation time, withdrawal time, and cleanliness score between groups. The ADR was 50.8% in EAC and 52.7% in TAC, with no significant difference (P = 0.666). The MAP was 1.35 in EAC and 1.20 in TAC, with no significant difference (P = 0.126). However, The MAP of diminutive adenomas (< 5 mm) tended to be higher in EAC than in TAC (P = 0.077). There was no significant difference in MAP in each segment between groups. CONCLUSIONS: Endocuff-assisted colonoscopy might be equivalent to TAC in cecal intubation time, ADR, and MAP.

Endoscopic Features and Diagnostic Procedures of Eosinophilic Gastroenteritis.

No specific endoscopic features for eosinophilic gastroenteritis (EGE) have been reported previously. This study therefore evaluated the endoscopic findings of six patients with EGE. The diagnosis was confirmed based on gastrointestinal symptoms, pathological findings on biopsy, and the absence of other diseases. The site of the lesion was identified based on eosinophilic infiltration with ≥20 cells per high-power field during a pathological specimen analysis. Flattening of the small intestinal villi was observed in four patients; we speculate that this may be a specific feature in the diagnosis of EGE.

Irritable bowel syndrome evaluation using computed tomography colonography.

AIM: To evaluate the morphology of the colon in patients with irritable bowel syndrome (IBS) by using computed tomography colonography (CTC). METHODS: Twelve patients with diarrhea type IBS (IBS-D), 13 patients with constipation type IBS (IBS-C), 12 patients with functional constipation (FC) and 14 control patients underwent colonoscopy following CTC. The lengths of the rectosigmoid colon, transverse colon and the total colon were measured. The diameters of the rectum, sigmoid colon, descending colon, transverse colon, and ascending colon were measured. RESULTS: The mean length of the total colon was 156.5 cm in group C, 158.9 cm in group IBS-D, 172.0 cm in group IBS-C, and 188.8 cm in group FC. The total colon in group FC was significantly longer than that in group C (P < 0.05). The mean length of the rectosigmoid colon was 56.2 cm, 55.9 cm, 63.6cm, and 77.4 cm (NS). The mean length of the transverse colon was 49.9 cm, 43.1 cm, 57.0 cm, and 55.0 cm. The transverse colon in group IBS-D was significantly shorter than that in group IBS-C (P < 0.01) and that in group FC (P = 0.02). The mean diameter of the sigmoid colon was 4.0 cm, 3.3 cm, 4.2 cm, and 4.3 cm (NS). The mean diameter of the descending colon was 3.6 cm, 3.1 cm, 3.8 cm, and 4.3 cm. The descending colon diameter in group IBS-D was significantly less than that in group IBS-C (P = 0.03) and that in group FC (P < 0.001). The descending colon diameter in group FC was significantly greater than that in group C (P = 0.04). The mean diameter of the transverse colon was 4.4 cm, 3.3 cm, 4.2 cm, and 5.0 cm (NS). CONCLUSION: CT colonography might contribute the clarification of subtypes of IBS.

Eosinophil infiltration in the upper gastrointestinal tract of patients with bronchial asthma.

BACKGROUND: Eosinophilic esophagitis (EoE) is related to allergic diseases such as bronchial asthma (BA), atopic dermatitis, and allergic rhinitis. The aim of this study was to examine the eosinophil infiltration in the upper gastrointestinal (GI) tract in patients with BA using esophagogastroduodenoscopy. METHODS: Patients with BA who had upper GI tract symptoms were enrolled. Patients who received systemically administered steroids were excluded. Eosinophil infiltrations in the esophagus, stomach, and duodenum were examined with regard to the endoscopic findings and pathological findings of biopsy specimens (UMIN000010132). RESULTS: Ninety patients were enrolled from October in 2012 to September in 2014. Thirty-six were male, 54 were female, and the mean age was 57.5 years. Eighty-one (90%) used inhaled corticosteroids. Fourteen patients (15.6%) had reflux esophagitis, 8 of whom had grade A and 6 had grade B. No patient with EoE was observed. One female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic gastroenteritis, but endoscopy showed only mucosal edema in the antrum. Another female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic granulomatosis with polyangiitis, and endoscopy showed erosions in the antrum and the duodenum. Three patients had eosinophil infiltration in the stomach, but none of them had severe symptoms. CONCLUSIONS: Patients with asthma who had upper gastrointestinal symptoms rarely had eosinophilic gastrointestinal disorders. Biopsy specimens are of high importance in the diagnosis of eosinophilic gastrointestinal disorders even if there is no remarkable endoscopic finding.

Pyogenic granuloma of the ileum diagnosed by double-balloon enteroscopy.

A pyogenic granuloma (PG) is a capillary hemangioma that usually occurs on the skin or in the oral cavity; it is rarely observed in the gastrointestinal tract. We herein describe a case of a 86-year-old woman who presented with anemia. Esophagogastroduodenoscopy and colonoscopy did not reveal any significant bleeding focus, but capsule endoscopy revealed a bleeding focus in the small intestine. We performed double-balloon enteroscopy and identified a 7-mm-diameter, reddish, subpedunculated, hemispheric polyp with a smooth surface in the small intestine, approximately 100 cm from the ileocecal valve. The polyp was surgically removed, and the histological findings were consistent with a diagnosis of PG.

Inferior alveolar nerve canal and branches detected with dental cone beam computed tomography in lower third molar region.

PURPOSE: To evaluate the course of the inferior alveolar nerve and its branches, the detectable branches were investigated with dental cone beam computed tomography (CBCT). MATERIALS AND METHODS: Patients in whom the lower third molar (M3) and inferior alveolar nerve canal showed overlapping in the initial panoramic image were included. One hundred twelve impacted lower M3s were extracted after examination with dental CBCT. The detection ratio, the course of the branches, and their relation with the M3 were retrospectively investigated. RESULTS: One hundred fifty-five branches were observed in 106 cases (94.6%, 106/112) around the M3. Most branches coursed under the M3 (55.5%, 86/155), and 85 branches (54.8%, 85/155) were in contact with the M3. The inferior alveolar nerve canal and branch(es) were mostly in contact with the M3 (57.5%, 61/106). CONCLUSIONS: Dental CBCT can detect most tubular structures representing branches in the impacted lower M3 region.

Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners.

Osteoclasts are formed from the monocyte-macrophage lineage in response to receptor activator of nuclear factor kappaB ligand (RANKL) expressed by osteoblasts. Bone is the most common site of breast cancer metastasis, and osteoclasts play roles in the metastasis. The taxane-derived compounds paclitaxel and docetaxel are used for the treatment of malignant diseases, including breast cancer. Here we explored the effects of docetaxel on osteoclastic bone resorption in mouse culture systems. Osteoclasts were formed within 6 days in cocultures of osteoblasts and bone marrow cells treated with 1,25-dihydroxyvitamin D(3) plus prostaglandin E(2). Docetaxel at 10(-8) M inhibited osteoclast formation in the coculture when added for the entire culture period or for the first 3 days. Docetaxel, even at 10(-6) M added for the final 3 days, failed to inhibit osteoclast formation. Osteoprotegerin, a decoy receptor of RANKL, completely inhibited osteoclast formation when added for the final 3 days. Docetaxel at 10(-8) M inhibited the proliferation of osteoblasts and bone marrow cells. RANKL mRNA expression induced by 1,25-dihydroxyvitamin D(3) plus prostaglandin E(2) in osteoblasts was not affected by docetaxel even at 10(-6) M. Docetaxel at 10(-6) M, but not at 10(-8) M, inhibited pit-forming activity of osteoclasts cultured on dentine. Actin ring formation and L: -glutamate secretion by osteoclasts were also inhibited by docetaxel at 10(-6) M. Thus, docetaxel inhibits bone resorption in two different manners: inhibition of osteoclast formation at 10(-8) M and of osteoclast function at 10(-6) M. These results suggest that taxanes have beneficial effects in the treatment of bone metastatic cancers.

Effect of inorganic polyphosphate in periodontitis in the elderly.

AIM: Inorganic polyphosphate exists as chains of phosphate molecules and is distributed in osteoblasts, and regulates osteoblastic cell differentiation and bone matrix calcification. The purpose of this study was to clarify the effects of inorganic polyphosphate on periodontitis. MATERIAL AND METHODS: Subgingival local irrigation with inorganic polyphosphate was studied in a randomised double-blind study of 33 patients with periodontitis. Scaling and root planing were performed 1 week after the initial examination. RESULTS: No significant differences between the inorganic polyphosphate group and control were detected in each item except IL-1beta. Patients in whom both the bleeding on probing and gingival index at 1 week had improved were significantly older in the inorganic polyphosphate group than in the control group (p < 0.05). Bone regeneration was seen in one case of the inorganic polyphosphate group. CONCLUSIONS: Inorganic polyphosphate was useful in the treatment of periodontitis in the elderly, indicating a probable effect of anti-ageing, with similar bone regenerations occurring in both groups.

Multidrug resistance-associated protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines.

The aim of the present study was to clarify whether ATP binding cassette transporters are refractory factors in head and neck cancers. For in vitro and in vivo chemotherapeutic studies, we used the following head and neck cancer cell lines: a mouse oral squamous cell carcinoma (SCC) cell line, Sq-1979; a human SCC cell line, SCCHA; a mouse salivary gland adenocarcinoma (SGA) cell line, NR-PG; and a human SGA cell line, HSY. We used a vinca alkaloid anticancer drug, vincristine (VCR), as a chemotherapeutic anticancer drug. To determine the cause of multidrug resistance, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry of xenografted tumors in nude mice, drug efflux analysis, and drug efflux inhibitory assays were performed. VCR-treated cell lines, Sq-1979/VCR, SCCHA/VCR, NR-PG/VCR, and HSY/VCR, intensively expressed multidrug resistance (MDR) gene 1 mRNA and multidrug resistance associated protein (MRP) 1 mRNA. MRP7 mRNA and protein were expressed in NR-PG/VCR and HSY/VCR cells, but not in Sq-1979/VCR and SCCHA/VCR cells. In each cell clone of NR-PG/VCR and HSY/VCR, MRP7 mRNA was induced by VCR treatment, suggesting an acquired resistance to VCR in the context of MRP7 expression. In the in vivo chemotherapeutic nude mice model, VCR-treated xenografted SCCHA and HSY cells expressed MDR1 and MRP1. Moreover, MRP7 expression was immunohistochemically found in xenografted HSY cells of VCR-injected tumor-bearing mice, but not in SCCHA cells. Furthermore, doxorubicin accumulation was increased and drug cross-resistance to docetaxel decreased in HSY/VCR in the presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D-glucuronide). These results indicate that MDR1 expression, MRP1 expression, and MRP7 expression are refractory factors in head and neck cancer chemotherapy and suggest that induction of MRP7 expression is involved in drug resistance to natural products, especially to docetaxel in SGA.

Effects of oral squamous cell carcinoma-derived TGF-beta1 on CD26/DPPIV expression in T cells.

BACKGROUND: Enzymatic activity levels of serum CD26/dipeptidylpeptidase (DPP) IV in oral cancer patients are lower than those in healthy subjects. However, the mechanism for this decrease is not yet fully understood. MATERIALS AND METHODS: The influence of malignant cell-derived cytokines on cell surface CD26/DPPIV expression in human T cells was analyzed using an oral squamous cell carcinoma (SCC) cell line, KB, and peripheral blood T cells. RESULTS: Tumor growth factor (TGF)-beta1 in KB-conditioned medium (KBCM) down-regulated CD26/DPPIV expression in T cells, which was responsible for the decreased DPPIV activities in the cultured supernatant. Expression p27kip in T cells was maintained in addition to G1 arrest when cultured with KBCM but was abolished by inclusion of anti-TGF-beta1 antibody. CONCLUSION: SCC-derived TGF-beta1 down-regulates CD26/DPPIV expression in T cells, resulting in decreased serum CD26/DPPIV activity in oral cancer patients.

Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor.

The aim of this study was to clarify the effects of alpha-N-acetylgalactosaminidase (alpha-NaGalase) produced by human salivary gland adenocarcinoma (SGA) cells on the bioactivity of macrophage-activating factor (GcMAF). High exo-alpha-NaGalase activity was detected in the SGA cell line HSG. HSG alpha-NaGalase had both exo- and endo-enzyme activities, cleaving the Gal-GalNAc and GalNAc residues linked to Thr/Ser but not releasing the [NeuAc2-6]GalNac residue. Furthermore, GcMAF enzymatically prepared from the Gc protein enhanced the superoxide-generation capacity and phagocytic activity of monocytes/macrophages. However, GcMAF treated with purified alpha-NaGalase did not exhibit these effects. Thus, HSG possesses the capacity to produce larger quantities of alpha-NaGalase, which inactivates GcMAF produced from Gc protein, resulting in reduced phagocytic activity and superoxide-generation capacity of monocytes/macrophages. The present data strongly suggest that HSG alpha-NaGalase acts as an immunodeficiency factor in cancer patients.

Evidence of parasympathetic postganglionic neurons in the rat hypoglossal nerve trunk.

Previous studies have indicated that the geniohyoid (GH) muscle is innervated by efferent axons from both the hypoglossal nerve (CN XII) and ansa cervicalis. To clarify the physiological significance of this dual innervation of the GH muscle, we examined properties of efferent innervations in rat GH muscle using electrophysiological, horseradish peroxidase (HRP) tracing and immunohistochemical techniques. Recordings from the branch of the XII nerve that innervates the GH (GH.Br) revealed that bursts of impulses during fictitious swallowing were conducted via the XII nerve trunk, in which neuronal cell bodies were labeled in the ventrolateral subnucleus of the XII nucleus by HRP tracing. In contrast, in vivo experiments demonstrated that tonic discharges in GH.Br were conducted via the ansa cervicalis. However, HRP-labeled efferent neurons were observed in neither brainstem nor upper spinal cord, but sensory neurons were labeled in the most rostral cervical spinal ganglia via the ansa cervicalis. Tonic activity was abolished in vitro by mecamylamine, an antagonist of nicotinic acetylcholine receptors (nAChR), and by pirenzepine, an antagonist of muscarinic M1 receptors. Incubation of isolated XII nerve segments with antisera to vasoactive intestinal peptide, nAChR, and muscarinic M1 receptor yielded small numbers of labeled neurons with each antiserum. All labeled neurons displayed similar diameters and were located approximately 1.5 mm proximal to the bifurcation of the XII nerve into medial and lateral branches. Our findings indicate that GH muscle in the rat is innervated by both somatic and parasympathetic nervous systems.

Expression of ATP-binding cassette transporter in human salivary ducts.

P-glycoprotein expression has been observed in normal tissues as well as malignant tumours and thus does not appear to be induced by anticancer drugs. Knowledge of the distribution of ATP-binding cassette (ABC) transporters other than P-glycoprotein in normal salivary tissue is essential for understanding the physiological secretion or excretion of potentially toxic substances. Here the expression of ABC transporters was studied immunohistochemically in normal salivary gland tissue from nine patients. In striated duct cells, staining was strong for P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP 2/canalicular multispecific organic anion transporter (cMOAT), and lung resistance-related protein (LRP). The staining intensity of acinar and intercalated duct cells for MRP 1 expression was distinct from that for MRP2/cMOAT, but was similar to that for P-glycoprotein. LRP was observed as particles between the nuclear and luminal membranes in the cytoplasm of intercalated duct cells. The expression of ABC transporters suggests that numerous transporters other than those studied might be isolated from normal salivary tissues. These observations indicate that these ABC transporters may not arise from any previous contact with anticancer drugs but are expressed physiologically. The achieved drug resistance as well as the physiological secretory function of ABC transporters could contribute to the responsiveness to chemotherapy of malignant salivary tumours.