Adherence and Effectiveness of MoviPrepⓇ in Bowel Preparation for Colonoscopy: A Multicenter Study from the Hiroshima GI Endoscopy Research Group.

Objectives: Bowel preparation is burdensome because of long cleansing times and large dose volumes of conventional polyethylene glycol (PEG) lavage solution NiflecⓇ (Nif). MoviPrep (Mov)Ⓡ is a hyperosmolar preparation of PEG, electrolytes, and ascorbic acid; despite the smaller dose volume of 2 L, it can be challenging for many patients. We examined a more effective and acceptable bowel preparation method without compromising cleanliness and effectiveness, combining low-residue diet and laxative (Modified Brown Method) in Mov administered 1 day pre-colonoscopy. Methods: This multicenter, randomized, open-label, parallel-group comparative study, conducted at Hiroshima University Hospital and 7 affiliated hospitals in May 2015-March 2016, evaluated adherence to and effectiveness of Mov in bowel preparation. Participants (n=380) were allocated to receive 1 of 3 pre-colonoscopy regimens: Nif+Modified Brown Method (Group A), Mov+Modified Brown Method (Group B), or Mov+Laxative (Group C). Results: Total intake volume showed no significant difference among the groups. Bowel preparation time was significantly shorter in Group B (112.4±44.8 min, n=118) than in Groups A (131.3±59 min, n=105) and C (122.6±48.1 min, n=115). Sleep disturbance (37%) was significantly higher in Group B than Group A; distension (11%) was significantly lower in Group C than in Groups A and B (p<0.05, respectively). No severe adverse events occurred in any group. Conclusions: Mov+Modified Brown method provided significantly shorter bowel preparation time, with no significant difference in total intake volume among the regimens. Mov+Laxative yielded significantly less distension than the other groups, with bowel preparation equivalent to that of the Nif+Modified Brown method.

Multiple Looks of Auditory Empty Durations Both Improve and Impair Temporal Sensitivity.

Discrimination of two neighboring empty durations that are marked by three successive sounds is improved when the presentation of the first (standard, S) duration is repeated before that of the second (comparison, C), as SSSSC. This improvement in sensitivity, called the multiple-look effect, has been explained by a statistical model regarding variability. This model assumes that the perceived duration of the standard is averaged across observations (within a trial within an individual). The increasing of the number of observations thus reduces the standard error of the mean perceived duration. Alternatively, the multiple-look effect is attributed to the listener's prediction based on regular rhythm. Listeners perceive regular rhythm during the repetition of the standard, predict the timing of subsequent sounds, and detect a sound that is displaced from the predicted timing. These models were tested in the present experiment in which the main factor was a temporal separation between the standard and the comparison; i.e., these durations were adjacent to each other as SSSSC or separated by a temporal blank as SSSS_C. The results differed between stimulus structures. First, the multiple-look effect was replicated in the SSSSC condition (yielding a higher performance than SC), but disappeared in SSSS_C (having no difference with S_C). Second, no multiple-look effect occurred in CSSSS (no difference with CS), and moreover, an impairment effect was observed in C_SSSS (a lower performance than C_S). Finally, discrimination was improved in SSSS_CCCC compared with SSSSCCCC, the effect being kept even when sounds were aligned at irregular intervals. These findings are not consistent with those expected from the statistical model because the temporal separation should have produced no effects if the number of standards had been a sole parameter determining the multiple-look effect. The prediction-based model can explain the first finding; inserting a blank between the standard and the comparison violates the listener's prediction based on regular rhythm, thus reducing the multiple-look effect. However, it did not expect the other findings and required revisions. Notably, the second finding indicates that the formation of regular rhythm can impair temporal discrimination. In other words, an inversed multiple-look effect occurs.

[Dynamic Attending Binds Time and Rhythm Perception].

Relations between time and rhythm perception are discussed in this review of psychophysical research relevant to the multiple-look effect and dynamic-attending theory. Discrimination of two neighboring intervals that are marked by three successive sounds is improved when the presentation of the first (standard, S) interval is repeated before that of the second (comparison, C), as SSSSC. This improvement in sensitivity, called the multiple-look effect, occurs because listeners (1) perceive regular rhythm during the repetition of the standard interval, (2) predict the timing of subsequent sounds, and (3) detect sounds that are deviated from the predicted timing. The dynamic-attending theory attributes such predictions to the entrainment of attentional rhythms. An endogenous attentional rhythm is synchronized with the periodic succession of sounds marking the repeated standard. The standard and the comparison are discriminated on the basis of whether the ending marker of the comparison appears at the peak of the entrained attentional rhythm. This theory is compatible with the findings of recent neurophysiological studies that relate temporal prediction to neural oscillations.

Rapid progression of Epstein-Barr-virus-positive gastric diffuse large B-cell lymphoma during chemoradiotherapy: a case report.

A 61-year-old woman was referred to our hospital with epigastralgia and appetite loss. Barium examination and upper gastrointestinal endoscopy revealed uneven erythematous mucosa with multiple elevated lesions from the gastric fornix to the upper corpus. Abdominal computed tomography showed thickening of the wall of the fornix and swelling of perigastric lymph nodes, but whole-body gallium scintigraphy and bone marrow examination did not indicate further involvement. Biopsy specimens showed diffuse infiltration of large atypical lymphoid cells in which Epstein-Barr virus (EBV) was detected by in situ hybridization. Diffuse large B-cell lymphoma (DLBCL), stage II1, was diagnosed. Combination chemotherapy [cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP)], was given, and this was followed by radiotherapy. Partial remission was achieved by chemotherapy, but the disease progressed rapidly during radiotherapy. Because the reported prognosis of EBV-positive DLBCL is unfavorable, the therapeutic strategy for EBV-positive gastric DLBCL should be considered carefully.

Presence of poorly differentiated component correlated with submucosal invasion in the early diffuse-type gastric cancer.

BACKGROUND/AIMS: Diffuse-type gastric carcinoma is associated with a poor prognosis. However, the clinical behavior of diffuse-type gastric cancer is not fully understood. The aim of this study is to distinguish the behaviors of early diffuse-type gastric carcinomas by sub classifying tumors according to their histologic features. METHODOLOGY: A total of 114 cases of diffuse-type early gastric cancer were studied retrospectively. We analyzed and compared the resected cancer specimens according to the histologic components: as poorly differentiated adenocarcinoma component-present (poor+) versus poorly differentiated adenocarcinoma component-absent (poor-). Helicobacter pylori status was evaluated by Giemsa staining and IgG serology. We assessed the degree of cancer invasion and compared background status of gastritis in accordance with the updated Sydney System criteria and serologic markers. RESULTS: In comparison to the poor+ cancers, the poor- cancers had a significantly larger portion of cells confined to the mucosa (p=0.002). Only 8 of the 114 cases were regarded as H. pylori-negative. Although we could not detect any serologic markers specific for gastritis with poor+ cancer, but the serum levels of gastrin was slightly higher in patients with poor+ cancers than in those with poor- cancers. CONCLUSIONS: The biologic behavior of poor+ gastric carcinoma is worse than that of poor- carcinoma. There is a close relation between H. pylori infection and carcinogenesis of poorly differentiated adenocarcinoma.

Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.

PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has various roles in tumor development and progression. We previously reported that expression of MCP-1 is associated with macrophage infiltration and tumor vessel density in human gastric carcinomas. The present study was undertaken to obtain direct evidence that MCP-1 participates in recruitment of macrophages and induction of angiogenesis. EXPERIMENTAL DESIGN: We did transfection experiments to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression vector was transfected into the human gastric carcinoma TMK-1 cell line. We examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity with the orthotopic gastric xenograft model. We determined intratumor microvessel counts and tumor-infiltrating macrophage counts by immunohistochemical staining. RESULTS: There was no difference in in vitro proliferation between MCP-1-transfected TMK-1 cells and mock-transfected (control) cells; however, MCP-1 transfectants induced tumor growth in ectopic xenografts and increased tumorigenicity and induced lymph node metastases and ascites in orthotopic xenografts. In both ectopic and orthotopic xenograft models, strong infiltration of macrophages was observed within and around the tumors after implantation of MCP-1 transfectants whereas fewer macrophages were seen after inoculation of control cells. The microvessel density was significantly higher in tumors produced by MCP-1 transfectants than in control tumors. CONCLUSIONS: MCP-1 produced by gastric carcinoma cells may regulate angiogenesis via macrophage recruitment. MCP-1 may be a potential target for antiangiogenic therapy for gastric carcinoma.

Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in early gastric carcinoma: correlation with clinicopathological parameters.

In this study, we investigated whether expression of vascular endothelial growth factor (VEGF)-C and/or VEGF-D correlates with clinicopathological features of human gastric carcinoma. We immunohistochemically examined the expression of VEGF-C and VEGF-D in 140 archival surgical specimens of submucosally invasive gastric carcinoma. Of these specimens, 32 (22.9%) and 12 (8.6%) showed intense VEGF-C and VEGF-D immunoreactivity in cancer cells, respectively. VEGF-C immunoreactivity was associated with histological type, lymphatic invasion, lymph node metastasis, and microvessel density. No association was identified between VEGF-D immunoreactivity and clinicopathological variables. These results suggest that VEGF-C is a dominant regulator of lymphangiogenesis in early-stage human gastric carcinoma.

Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma.

UNLABELLED: Gastric carcinoma occurs in response to chronic inflammation of gastric mucosa infected with Helicobacter pylori. It is not known how cytokines affect the growth and progression of gastric carcinoma. MATERIALS AND METHODS: We measured tissue concentrations of the proinflammatory cytokines interleukin (IL)-1beta and IL-6 in gastric carcinoma and investigated the correlation between the levels of these cytokines and clinicopathological features. Biopsy specimens of tumors or adjacent normal mucosa were obtained from 42 Japanese patients with gastric carcinoma. Tissue levels of IL-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. RESULTS: IL-1beta levels were significantly higher in the neoplasm than in the corresponding normal mucosa. The IL-6 levels in the neoplasm correlated significantly with the depth of invasion and lymphatic invasion. High levels of IL-1beta and IL-6 were characteristic of non-scirrhous type gastric carcinoma. CONCLUSION: These results suggest that IL-1beta and IL-6 are involved in the growth and progression of human gastric carcinoma.

Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes.

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes.

Single nucleotide polymorphism in the hypoxia-inducible factor-1alpha gene in colorectal carcinoma.

Colorectal carcinoma is one of the most common malignancies in the world, and its incidence has increased in recent years. We have reported that expression of hypoxia-inducible factor (HIF)-1alpha correlates with expression of vascular endothelial growth factor (VEGF), tumor stage, lymphatic invasion, venous invasion, and liver metastasis. It has also been reported that a single nucleotide polymorphism (SNP) in exon 12 of HIF-1alpha gene is present in renal cell carcinoma and head and neck squamous cell carcinoma patients. We investigated the C1772T polymorphism in colorectal cancer patients and healthy control subjects to clarify the mechanism of HIF-1alpha activation in colorectal carcinoma. The exon 12 genotype was not associated with sex or age. The distribution of HIF-1alpha genotypes in controls was 89 C/C (89%), 11 C/T (11%), and 0 T/T (0%). The distribution of HIF-1alpha genotypes in colorectal cancer patients was 100 C/C (100%), 0 C/T (0%), and 0 T/T (0%). The difference in genotype distribution between patients and control subjects was significant (p<0.0005). These results suggest that the C1772T polymorphism in HIF-1alpha is not involved in progression or metastasis of colorectal carcinoma.

Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma.

Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic factors produced by tumour and stromal cells. The purpose of this study was to investigate the expression of VEGF-C and VEGF-D in the organ microenvironment. We implanted human KM12 colon carcinoma cell lines into the subcutis and caecal wall of nude mice. The expression of VEGF-C and VEGF-D mRNAs and proteins were examined by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Under culture conditions, VEGF-C mRNA was not detected in KM12 cells; however, VEGF-C expression was detected after implantation of KM12 cells into nude mice. VEGF-C and VEGF-D protein contents were higher in orthotopic (caecal wall) tumours than in ectopic (subcutis) tumours. Small vessels expressing VEGF receptor-3 were observed in the peripheral portions of caecal tumours. In metastatic liver tumours, VEGF-C and VEGF-D proteins were produced in lower amounts than those in caecal tumours. These data suggest that the expression of lymphangiogenic factors is influenced by the organ microenvironment. Therefore, experimental studies of colon cancer lymphangiogenesis should be performed with orthotopic implantation models.