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B-cell receptor (BCR) signaling is critically activated and targetable for mantle cell lymphoma (MCL); however, the underlying mechanism of the activated BCR signaling pathway is not clear. The pathogenic basis of miR-17-92 cluster remains unclear although the oncogenic microRNA (miRNA) miR-17-92 cluster is highly expressed in patients with MCL. This study revealed that miR-17-92 cluster overexpression is partly dependent on SOX11 expression and chromatin acetylation of MIR17HG enhancer regions. Moreover, miR-17-92 cluster regulates not only cell proliferation but BCR signaling activation in MCL cell lines. Pulldown-seq, where mRNA was captured using biotinylated miRNA transfection, was performed and analyzed with next-generation sequencing. Additionally, novel miRNA targets, including tumor suppressors such as BTG2, were identified to comprehensively define miR-17-92 cluster targets. Notably, gene expression profile data of patients with MCL revealed that BTG2 expression was negatively associated with those of BCR signature genes. Moreover, BTG2 silencing in MCL cell lines significantly induced BCR signaling overactivation. Our results suggest an oncogenic role of miR-17-92 cluster-activating BCR signaling throughout BTG2 deregulation in MCL.

This study reports a case of a 49-year-old woman having B-cell acute lymphoblastic leukemia with glycophorin A, a representative erythroid marker, expression. According to the WHO criteria for mixed phenotype acute leukemia (MPAL), erythroid lineage is not defined, and to the best of our knowledge, only one other case with erythroid/B-cell biphenotypic acute leukemia has been reported previously. To establish the disease entity and clarify the pathophysiology of erythroid/lymphoid MPAL, additional cases need to be analyzed.

We herein report the rare case of a 72-year-old female who presented with paraneoplastic pemphigus (PNP) and bronchiolitis obliterans (BO) associated with follicular lymphoma (FL), who was successfully treated with obinutuzumab (GA101; G) and bendamustine (B). The patient had severe erosive stomatitis and bilateral conjunctival hyperemia that persisted for more than 6 months. A huge mass was found in the abdominal cavity, and a biopsy revealed grade 1 FL (stage IV). Based on a lip biopsy result, the patient was diagnosed with PNP associated FL. The patient received bendamustine and obinutuzumab (BG) chemotherapy and FL and PNP responded very well, but BO was additionally associated during the course of BG. BO progressed without exacerbation as BG therapy progressed to a 2 year maintenance therapy with G, and combination of azithromycin, inhaled bronchodilator therapy, and corticosteroid. She was followed up at the outpatient department with no pulmonary function decline or FL and PNP recurrence. Our case suggests that BG could be a promising treatment option for PNP and BO.

Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip. In this screening, we focused on differentially methylated regions (DMRs) that were associated with LNM of ESCC, as prime candidates for DNA methylation markers. We extracted three genes, HOXB2, SLC15A3, and SEPT9, as candidates predicting LNM of ESCC, using pyrosequencing and several statistical analyses in the discovery cohort. We confirmed that HOXB2 and SEPT9 were highly methylated in LNM-positive tumors in 59 ESCC validation samples. These results suggested that HOXB2 and SEPT9 may be useful epigenetic biomarkers for the prediction of the presence of LNM in ESCC.

Introduction Complications such as severe infection may occur during the chemotherapy of malignant lymphoma. Phlegmonous gastritis (PG) is a rare acute bacterial infection associated with high mortality, requiring early diagnosis, and prompt management. In addition, Guillain-Barre syndrome (GBS) occasionally requires early treatment and intensive care management due to the occurrence of severe neuropathy and respiratory failure. Patient concerns A 70-year-old male was diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) after the detection of several polypoid tumors with ulcers. The patient underwent chemotherapy for DLBCL and exhibited adverse effects (i.e., fever, vomiting, epigastric pain, and neutropenia). Computed tomography indicated widespread thickening in the gastric wall. Furthermore, approximately 2 weeks later, the patient presented with gradual symmetric lower extremity weakness and respiratory failure due to paralysis of the respiratory muscle. Diagnoses DLBCL was diagnosed through a gastric tumor biopsy. On the basis of the computed tomography findings, a culture of gastric juice, nerve conduction studies, and clinical symptoms, this case of gastric lymphoma was complicated with PG and GBS. Interventions The patient was treated with antimicrobial therapy and administration of granulocyte colony-stimulating factor for PG, and with intravenous immunoglobulin and intensive care management for GBS. Outcomes Despite the aggressive progress of the condition, the patient improved without relapse of DLBCL. Conclusion PG was regarded as a precedent infection of GBS. In this article, we present the first reported case of gastric lymphoma complicated with PG and GBS.

Rabbit antithymocyte globulin (ATG) is an effective immunosuppressive therapy for patients with aplastic anemia (AA). However, Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is a rare but serious complication of the therapy. An 81-year-old man was diagnosed with severe AA on the occasion of melena. Because cyclosporine monotherapy did not improve his condition, rabbit ATG was additionally administered. Thirty-one days after the administration of rabbit ATG, the patient presented with fever and general malaise. His liver and renal function tests showed rapid decline, and the patient went into shock. Although atypical lymphocytes in the peripheral blood, hepatosplenomegaly, and lymphadenopathy were not detected, the peripheral blood EBV-DNA load and serum ferritin levels were high, and his bone marrow aspiration specimen revealed hemophagocytic findings, leading to a diagnosis of EBV-LPD. He was treated with rituximab and recovered immediately. A total of 480 days have passed since the patient was administered the rabbit ATG, and he remains in AA remission without EBV-LPD relapse. This case suggests that rituximab is an effective therapy for EBV-LPD manifesting as EBV-associated hemophagocytic lymphohistiocytosis and indicates that monitoring the EBV-DNA load contributes to the diagnosis.

Laparoscopic total gastrectomy(LTG)is one of the most increasing surgeries among gastric cancer surgery. Although LTG has many advantages on the patient, we should be more careful of its specific complications. Here we report a case of 72- year-old man with the complaint of severe acute upper abdominal pain due to strangulation ileus caused by incarcerated esophageal hiatal hernia(EHH)after LTG. Emergent operation has performed on the patient and total 180 cm length of necrotic small intestine was resected. EHH after gastrectomy was thought to be rare complication. However, some literature reported that EHH after gastrectomy, especially after LTG has more possibility than it has ever thought to be. Laparoscopic surgery has more advantages than open surgery in terms of less invasiveness, rapid postoperative recovery, and less intraabdominal adhesion. One of the causes for EHH after LTG is ironically thought to be its less intraabdominal adhesion. We concluded that crus repair is one of the effective methods for the prevention of EHH after LTG through experiencing this case.

The association between intraoperative hemorrhage and the type of recurrence was examined, with a focus on peritoneal metastasis. A total of 540 patients who underwent macroscopically curative gastrectomy for advanced gastric cancers were reviewed for various clinicopathological characteristics, such as the amount of intraoperative hemorrhage and the pattern of recurrence. Additionally, adhesion assays using gastric cancer cells and mesothelial cells were performed in the presence of blood plasma to assess its effects on cell adhesion. Large intraoperative hemorrhages were correlated with a higher risk of peritoneal metastasis, while small hemorrhages were not. However, there were no significant differences in the incidence of all recurrences or other types of recurrence between both groups. Multivariate analysis of all cases (T2–4) revealed that large intraoperative hemorrhages were not an independent risk factor for peritoneal recurrence (p = 0.144); however, the large hemorrhage group developed peritoneal recurrence more frequently than the small hemorrhage group in each T stage. In the adhesion assay, the ability of cancer cells and mesothelial cells to adhere to each other was enhanced by the addition of plasma to the culture medium. The addition of heparin significantly decreased the plasma-induced enhancement of cell adhesion of Kato III, but not MKN45 or MKN74. Advanced gastric cancer patients accompanied by a large amount of intraoperative hemorrhage are more likely to develop peritoneal recurrence, and this risk might be due, at least in part, to the increased ability of cancer cells and mesothelial cells to adhere to each other.

Serum soluble interleukin-2 receptor (sIL2R) levels are often measured to evaluate the state of lymphoma. The serum sIL2R level at diagnosis has been reported to be correlated with the prognosis of diffuse large B cell lymphoma (DLBCL) patients treated with the R-CHOP regimen. However, it is unclear whether interim sIL2R levels are associated with prognosis in DLBCL. Here, we analyzed the prognostic impact of interim serum sIL2R levels in DLBCL. We retrospectively examined data for DLBCL patients who started receiving chemotherapy at the Japanese Red Cross Society Kyoto Daini Hospital between January 2012 and December 2018. All of the patients received R-CHOP-like regimens (rituximab plus pirarubicin or adriamycin, cyclophosphamide, vincristine, and prednisolone). The interim sIL2R level (I-IL2R) was defined as the value measured after the third chemotherapy cycle. I-IL2R levels of >700 U/ml were regarded as positive. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). The unadjusted probabilities of PFS and OS were estimated using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. In total, 102 patients were enrolled. The patients' median age was 73.5 years (range, 35-88), 58 patients (56.9%) were male, and 52 (51.0%) had poor revised International Prognostic Index scores. The median follow-up time was 25.2 months (range, 3.7-88.6). Twenty-three patients (22.5%) were I-IL2R-positive (>700 U/ml). Univariate analysis revealed that I-IL2R-positivity was associated with a poor prognosis. The 3-y PFS rates of the I-IL2R-negative (700 U/ml) patients were 60.4% (95% confidence interval [95%CI], 46.2-71.9) and 37.5% (95%CI, 15.7-59.4; p The I-IL2R level of >700 U/ml patients had poor prognosis. The I-IL2R level can be used to predict the outcomes of DLBCL patients. IL2R levels should be measured during chemotherapy, and I-IL2R-positive patients could be targeted with high-dose or novel therapies. As this study was based on a retrospective analysis and involved a small cohort and a limited follow-up period, further studies are needed to confirm the prognostic impact of I-IL2R. Figure Disclosures No relevant conflicts of interest to declare.

Granulocyte colony-stimulating factor (G-CSF)-producing tumor is one of the rare types of cancer clinically characterized by an elevated fever and white blood cell (WBC) increment. Although G-CSF producing tumors have been reported in several types of cancer including those of the lungs, cervix and bladder, G-CSF producing hepatocellular carcinoma is extremely rare. Here, we report the case of a rapidly growing and poorly differentiated hepatocellular carcinoma producing G-CSF. The patient showed symptoms of continuous high fever, stomach pain and cough, and high serum WBC counts, C-reactive protein (CRP) and G-CSF levels were found in laboratory tests. After a radical hepatectomy, the patient completely recovered from the above symptoms and inflammatory state. The serum levels of G-CSF were reduced to normal levels after radical surgery. An immunohistochemical analysis revealed the overexpression of G-CSF in the cytoplasm of certain hepatocellular carcinoma (HCC) cell. The patient's serum WBC, CRP and G-CSF levels remained within normal levels in the six months after surgery without recurrence. This is the 9th case report of G-CSF producing hepatocellular carcinoma in English literature. We review the clinical characteristics of the G-CSF producing HCC and discuss a possible treatment strategy.

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family, which is characterized by a conserved RING finger, B-box, and coiled-coil domains, function as important regulators for carcinogenesis. In this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene through overexpression in gastric cancer. We analyzed seven gastric cancer cell lines and 112 primary tumors, which were curatively resected in our hospital between 2001 and 2003. Expression of the TRIM44 protein was detected in gastric cancer cell lines (2/7 cell lines; 29%) and primary tumor samples of gastric cancer (29/112 cases; 25%). Knockdown of TRIM44 expression using several specific siRNAs inhibited the proliferation, migration, and invasion of TRIM44-overexpressing cells. Overexpression of the TRIM44 protein was significantly correlated with an advanced type of macroscopic appearance, lymphatic invasion, and higher recurrence rate. TRIM44-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0038, log-rank test) in both intensity and proportion expression-dependent manner. TRIM44 positivity was independently associated with worse outcome in multivariate analysis (P = 0.0233, hazard ratio 3.37 [1.18-9.64]). These findings suggest that TRIM44 plays a crucial role in tumor cell proliferation through its overexpression, and highlight its usefulness as a predictor and potential therapeutic target in gastric cancer.

miR-21 and miR-375 are reported to be highly and poorly expressed in esophageal squamous cell carcinoma (ESCC) tissues, respectively. Recently, we demonstrated that circulating miR-21 and miR-375 were stably detectable in plasma and reflected tumor dynamics as a tumor marker for ESCC. We hypothesized that these plasma miRNA concentrations contributed to prognostic markers in patients with ESCC.Between 2008 and 2010, 50 preoperative plasma samples were collected from consecutive patients with ESCC, who underwent curative esophagectomy in our hospital. We examined the association between plasma miRNA concentrations and prognosis retrospectively.i) The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration tended to be poorer than low group (3-yr survival rate: 53.4 and 81.5%, p = 0.1038), while that of high plasma miR-375 group was better than low group (3-yr survival rate: 100 and 65.2%). ii) Patients with high miR-21 and low miR-375 concentrations in plasma had significantly poorer prognosis than other patients (3-yr survival rate: 48.4 and 83.1%, p = 0.039). Multivariate analysis revealed that the presence of high miR-21 and low miR-375 concentrations in plasma was an independent prognostic factor (p = 0.029, hazard ratio 3.8 (1.14-12.5)).Circulating miR-21 and miR-375 could be reliable prognostic markers for ESCC. These plasma markers might facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up for early detection of recurrences and additional treatments such as neo-adjuvant chemotherapy and postoperative chemotherapy in ESCC.

To evaluate the effects of switching from NPH insulin to insulin Detemir on blood glucose control (HbA1C),fasting plasma glucose (FPG) (before breakfast),intra-subject variability of FPG,and frequency of hypoglycemia in subjects with diabetes mellitus receiving medication under a basal-bolus regimen,we monitored these parameters in 26 diabetics for 6 months.We also investigated patients’level of satisfaction with the change using questionnaire.Although there was no significant improvement in glycemic control or FPG after switching,intra-subject variability of FPG (P

Cancer treatment in Japan is considered to be very progressive in the use of antineoplastic agents. Pharmacists are required to compound more antineoplastic preparations recently and thus are at risk for exposure to antineoplastic agents. In Japan, healthcare professionals have recognized the need for protection, but there have been few reports of environmental contamination or occupational exposure to antineoplastic agents. In the present study, urine samples over 24 hr from compounding pharmacists and wipe samples from the compounding room were collected to analyze levels of cyclophosphamide (CP). CP was detected in urine samples from all 4 pharmacists (mean = 165.3 ng/24 hr) and for all wipe samples of the compounding room. From the results of these tests, the standard operating procedure (SOP) of the pharmacy was revised as a protective measure. The tests were then repeated and CP was detected again in the urine of all 4 compounding pharmacists, though the mean CP level was reduced from 165.3 to 47.4 ng/24 hr after the revision of the SOP. Although there was no correlation between the amount of CP compounded and the CP levels in urine initially, the 2 values were significantly correlated after the revision of the SOP (R 2 = 0.87).

はじめに: 大腸穿孔は容易に敗血症性ショックを合併し, 死亡率も高い. 今回, その予後因子に関して検討を行ったので報告する. 方法: 過去12年間に当院で経験した大腸穿孔症例38例を対象に, 穿孔原因, 穿孔部位, 年齢, 手術までの時間, 術式, 術前血圧, base excess (以下, BE), 術前白血球数, APACHE II score, 術前合併症, エンドトキシン吸着療法 (以下, PMX-DHP) の有無を救命例と死亡例で比較検討した. また, PMX-DHP症例の中で, その施行前後で平均血圧, 時間尿量の変化と予後との関連についても比較検討した. 結果: 救命例は29例, 死亡例は9例であった (死亡率23.7%). 穿孔原因は, 癌による穿孔10例, 憩室9例, 特発性8例, 医原性7例, 外傷性2例, その他2例であり, 癌と特発性で死亡例が多かった (癌3例, 特発性4例). 術式はHartmann手術が19例と最多であった. BE≦-5は死亡率53.8%, APACHE II score 20以上は死亡率80%, 術前腎合併症症例は死亡率100%で有意に予後不良であった (それぞれP=0.023, P=0.007, P=0.001). PMX-DHP症例は16例あり, 死亡率は43.8%(7/16) であった. 時間尿量はPMX-DHPにより全体で61.0±61.0ml/hから127.6±98.1ml/hへと有意に増加 (P=0.038) しており, 救命例でその傾向が強かった (P=0.060). 考察:大腸穿孔症例においては, 術前のBE, APACHE II score, 術前腎合併症が予後規定因子と考えられた. PMX-DHPの有用性についてはさらなる検討が必要である.

今回われわれは，排便時の怒責が原因でS状結腸裂傷をきたし，腹腔内出血を合併した1例を経験したので報告する．症例は77歳の男性で，排便直後から急に出現した下腹部痛を主訴に受診した．下腹部中心に圧痛と反張痛を認めた．腹部造影CT検査では腹水の貯留を認め，S状結腸には多量の便塊を認めた．S状結腸周囲にairを認めたが，腸管内gas像とfree airとの鑑別は困難であった．大腸穿孔による腹膜炎の疑いで緊急手術したところ，腹腔内に約400ccの出血を認め，便塊により著明に拡張したS状結腸の漿膜が結腸紐に沿って4cmにわたり裂けていたが穿孔は認めなかった．明らかな腫瘍性病変による狭窄は認めなかった．病理組織所見では虚血性腸炎の所見で，漿膜から筋層にわたり断裂していた．これらより宿便によって慢性的に虚血性変化をきたしていたS状結腸が排便時の怒責によって漿膜・筋層が裂け，腹腔内出血をきたしたと推察された．

胆石が十二指腸球部に嵌頓するBouveret症候群は比較的稀な疾患である．今回われわれは瘻孔の自然閉鎖を認めたBouveret症候群の1例を経験したので報告する．症例は65歳，女性．20年前より胆石症を指摘されていたが時折胆石発作を認めるのみで放置していた．今回，腹痛嘔吐を主訴に外来を受診した．CTで胆嚢と総胆管内にガス像を認め，十二指腸に結石と思われる石灰化像を認めた．上部消化管内視鏡で十二指腸球部に結石を認め，十二指腸球部に嵌頓した胆石イレウス（Bouveret症候群）と診断した．入院後嘔吐の軽快を認め，上部消化管内視鏡では胆石は十二指腸球部から移動しており後壁に瘻孔を認めた．瘻孔から胆嚢が造影され胆嚢十二指腸瘻と診断した．入院後14日目に開腹術を行い，胆嚢頸部と十二指腸の癒着を切離すると肉眼的には瘻孔を認めなかった．胆嚢消化管瘻は自然閉鎖する可能性があり術式選択の余地があると考えられた．

To evaluate the effects of switching from NPH insulin(twice daily)to insulin glargine on blood glucose control(HbA1C),insulin dosage and frequency of hypoglycemia in Japanese patients with type 1 diabetes,we monitored these parameters in 37 type 1 diabetics for 12 months after switching.The patients were assigned to 3 groups according to HbA1C at switching :good(

Recent advances in anti-cancer drug treatments enable us to improve prognosis in Stage IV gastric cancer. In particular, in recent reports patients with only cytology positive (CY1) non-curative factors have comparatively better prognosis than others. This study was designed to evaluate our outcomes, to allow identification of CY1 gastric cancer patients and to investigate new treatment strategies.Between 2000 and 2008, 336 patients underwent peritoneal washing cytology for gastric cancer intra-operatively. Of these, 35 patients (10.4%) were diagnosed with CY1 gastric cancer.1 ) In all CY1 gastric cancers, 1-year, 3-year, and 5-year survival rates were 49%, 11%, and 5.7%, respectively. Clinical factors such as number of non-curative factors (p=0.008) and gastrectomy (p=0.001)were significantly related to poor prognosis. 2 ) The number of CY1 patients with only CY1 non-curative factors (Group C) and multiple non-curative factors (Group CM)were 14 and 21, respectively. The number of CY1 patients with gastrectomy and without gastrectomy were 30 (MST 366 days, Group C: 14 Group CM: 16) and 5 (MST: 88 days, Group CM: 5), respectively. 3 ) In CY1 patients with gastrectomy, patients treated with S-1 based chemotherapy had better prognosis in both Group C and Group CM. 4 ) 8 CY1 patients with neoadjuvant chemotherapy (NAC) followed by gastrectomy (MST 501 days, 1-year survival rate 62.5%) tended to have better prognosis than those without NAC (MST 132 days, 1-year survival rate 25.0% (p= 0.055).Gastrectomy, number of non-curative factor, S-1 based chemotherapy and NAC were keys to improving prognosis by subgroup analyses in CY1 gastric cancer.

A catalytic reaction pair, consisting of tetralin dehydrogenation/naphthalene hydrogenation, has newly been proposed as a storage medium of hydrogen for operating polymer-electrolyte fuel cells. The hydrogen storage capacity of tetralin (3.0 wt.%, 28.2 kg-H2/m3) is lower than that of decalin (7.3 wt.%, 64.8 kg-H2/m3), with the decalin dehydrogenation/naphthalene hydrogenation pair operated. Nevertheless, the rates of tetralin dehydrogenation and naphthalene hydrogenation to tetralin are much faster than the rates of the latter reaction pair. With respect to hydrogen storage for static or domestic use with space advantages, tetralin would be superior to decalin due to the ability of supplying hydrogen easily. Very high reaction rates and conversions of hydrogen evolution from tetralin were accomplished stationarily with “superheated liquid-film-type catalysis” by heating at 210–240 °C, in contrast to the poor results obtained with ordinary suspended catalysis. In particular, a carbon-supported nano-size platinum catalyst in the superheated liquid-film state exhibited efficient tetralin conversion as high as 95% within 25 min contact at 240 °C under distillation conditions. At the same temperature range, the dehydrogenation rates for decalin that had been obtained were ca. 3.9–6.3 times slower than those for tetralin, suggesting the excellent characteristics of tetralin as a hydrogen storage medium. In addition, carbon-supported nickel–ruthenium composite catalysts were found to give dehydrogenation activities at 240 °C comparable with those of the platinum catalyst at 210 °C.

MicroRNAs have been reported to be stably detectable in plasma/serum and to exhibit resistance to endogenous ribonuclease activity because of binding to proteins such as Argonaute-2 and high-density lipoprotein, or being packed by secretory particles such as exosomes. These secretory particles include specific microRNAs and can function as intercellular transmitters. These findings could open-up a new and promising field in the use of circulating microRNAs for cancer treatment. In particular, miR-18a, which is located in the potentially oncogenic miR-17-92 cluster, is a highly expressed microRNAs in several types of cancers. The concentration of miR-18a in plasma/serum of patients with cancer such as esophageal (AUC=0.944), pancreatic (AUC=0.936), hepatocellular (AUC=0.881), colorectal and other types of cancers is much higher than that of healthy volunteers. Such reports provide evidence that circulating miR-18 might be a next-generation biomarker and contribute to cancer screening in non-invasive liquid biopsy, to a clinically-satisfactory degree of sensitivity and specificity.

Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC). We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay. (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P

We examined the levels of long non-coding RNAs (lncRNAs) in the plasma of patients with gastric cancer to assess their clinical significance for diseases diagnosing and monitoring.We investigated the stability of plasma lncRNAs, and then confirmed the appropriateness of the lncRNA assay with a pre-amplification method. The levels of plasma lncRNAs, H19, HOX antisense intergenic RNA (HOTAIR), and metastasis associated lung adenocarcinoma transcript-1 (MALAT1), were then analyzed in patients with gastric cancer (GC) and healthy controls.Plasma lncRNAs exhibited minimal gradual instability only under several severe conditions. Analysis showed that samples with pre-amplification had a higher level of linearity in the reverse transcription polymerase chain reaction (RT-PCR) assay than those without pre-amplification. Plasma H19 levels were significantly higher in patients than in healthy controls. Plasma H19 levels were significantly reduced in postoperative samples.Circulating lncRNAs can be detectable in plasma, and the detection of circulating lncRNAs may provide new complementary tumor markers for gastric cancer.

MicroRNAs (miRNAs) such as miR-17-5p, miR-21, miR-106a and miR-106b are reported to be highly expressed in gastric carcinoma (GC) tissues. Recently, we reported that these miRNAs were consistently detectable in plasma and reflected tumor dynamics of GC. We hypothesized that these plasma miRNA concentrations could be used as prognostic markers in patients with GC.Between 2008 and 2009, preoperative plasma samples were collected from 69 consecutive patients with GC at our hospital. We retrospectively examined the association between plasma miRNA concentrations and prognosis.The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration was significantly poorer than those with a low concentration (p=0.0451), as was that of those with high plasma concentration of miR-106a (p=0.1132). There were no prognostic differences according to the plasma concentration of miR-17-5p and miR-106b. Those with high miR-21 concentration had also a slightly higher incidence of vascular invasion (p=0.0311). Multivariate analysis revealed that the presence of a high miR-21 concentration in plasma was an independent prognostic factor (p=0.0133, hazard ratio: 13.4 (95% CI: 1.72-104.4)).The level of circulating miR-21 could be a reliable prognostic marker in the plasma of patients with GC. These findings contribute to the stratification of patients in order to identify those who need meticulous follow-up for early detection of recurrence and additional or alternative treatments of GC.

This study aimed to investigate cytocidal effects of hypotonic shock on esophageal squamous cell carcinoma (ESCC) cell lines, and to apply pleural lavage with distilled water to surgery for ESCC. Three human ESCC cell lines, TE5, TE9 and KYSE170 were exposed to distilled water, and morphological changes in ESCC cells were closely observed under a differential interference contrast microscope connected to a high-speed digital video camera. Further, serial cell volume changes after hypotonic shock were measured using a high-resolution flow cytometer. To investigate the cytocidal effects of hypotonic shock on ESCC cells, re-incubation of ESCC cells was performed after hypotonic shock. Additionally, the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a Cl- channel blocker, during hypotonic shock were analyzed. Video recordings by high-speed digital camera demonstrated that hypotonic shock with distilled water induced cell swelling followed by cell rupture. Measurements of cell volume changes using a high-resolution flow cytometer indicated that severe hypotonicity with distilled water increased broken fragments of ESCC cells within 5 min. Re-incubation experiments demonstrated cytocidal effects of hypotonic shock on ESCC cells. Treatment of cells with NPPB increased cell volumes by the inhibition of regulatory volume decrease, which is observed during hypotonic shock, and enhanced cytocidal effects. These findings demonstrated the cytocidal effects of hypotonic shock on ESCC cells, and clearly support the efficacy of pleural lavage with distilled water during surgery for ESCC.

Thanks to recent advances of therapeutic devices, the less invasive surgical explorations such as endoscopic submucosal resection( ESD) and laparoscopic surgery have widely gained an acceptance and become more common. During laparoscopic partial gastrectomy for submucosal tumor such as gastrointestinal stromal tumor (GIST) of the stomach, it is important to avoid an excessive surgical resection of the gastric wall, which causes a deformity of the stomach and has a potential risk to decrease oral intake. We report here a successfully treated case without any deformity of the stomach and complications using laparoscopic and endoscopic cooperative surgery (LECS) for intraluminal type of GIST. LECS is a recently developed procedure and it enables us to resect a tumor with minimum surgical margin. This procedure could be applicable for clinically benign tumor, and it is effective especially for tumors located near esophagogastric junction or pyloric ring of the stomach.

A case of a double gallbladder, a congenital anomaly of biliary system is reported in a 71-year-old woman presenting with right hypochondrial pain. After a confirmed diagnosis of double gallbladder with gallstones was made by MRCP or ERCP, both gallbladders were removed laparoscopically. Double gallbladder is rare anatomic malformation of the biliary tract with only 88 cases, including ours, reported in the Japanese literature. Detailed preoperative investigations are required for an accurate preoperative diagnosis especially when considering laparoscopic removal to avoid inadvertent damage to biliary ductal system.

Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event that is associated with poor prognosis of ESCC patients. In the last few years, tumor-specific aberrations in DNA methylation of CpG islands around promoter regions of tumor-related genes have been investigated as possible biomarkers for early diagnosis, treatment and prognosis of human cancers. But, there are few DNA methylation markers that can predict the presence of LNM in patients with ESCC. To identify DNA methylation markers correlated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues by Illumina Infinium HumanMethylation450 BeadChip (covers more than 450,000 CpG sites). In this screening, we focused on some differentially methylated regions (DMRs), which were significantly associated with LNM of ESCC, as prime candidates for DNA methylation markers. In addition, these significant relationships were also confirmed by quantitative bisulfite pyrosequencing analysis in the same discovery cohort. Consequently, these results led us to consider that our selected DMRs might be useful epigenetic biomarkers for the prediction of the presence of LNM in primary ESCC cases. Therefore, we are continuing further analyses of these DMRs in an independent external validation cohort of ESCC patients. Citation Format: Ken-ichi Kozaki, Hiroaki Nagata, Kousuke Tanimoto, Naoto Fujiwara, Seiya Imoto, Daisuke Ichikawa, Satoru Miyano, Tatsuyuki Kawano, Eigo Otsuji, Johji Inazawa. Genome-wide screening of DNA methylation markers to predict the presence of lymph node metastasis in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1368. doi:10.1158/1538-7445.AM2014-1368