須田 康一

われわれは,各種病態において炎症性メディエーターとして注目されているHigh-mobility group box 1(HMGB1)に着目し,劇症肝不全に対する新治療の開発を試みている。劇症肝不全患者,薬剤誘導性ラット劇症肝不全モデルにおいて血漿中HMGB1,肝組織中HMGB1は健常群に比較してそれぞれ有意な上昇,低下を認めた。HMGB1に対する特異的中和抗体を薬剤誘導性ラット劇症肝不全モデルに投与したところ著明な病態改善効果を認めた。さらに,HMGB1の阻害剤であるBox Aタンパクの遺伝子導入,リコンビナントトロンボモジュリン投与,HMGB1吸着カラムを用いた体外循環などの有効性を大小の動物モデルで検証した。遺伝子導入,体外循環治療では一定の効果が認められつつあり,診療に役立つ劇症肝不全に対する新治療の開発が期待された。(著者抄録)

Background: Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor effective in acute lung injury (ALI) associated with systemic inflammatory response syndrome. Bowel ischemia reperfusion injury (IRI) induced by supravisceral aortic clamping is associated with an excessive systemic inflammatory response, resulting in remote organ damage, including ALI. In this study, we investigated whether sivelestat can attenuate neutrophil sequestration in the lung, alleviate ALI, and improve survival in a rat bowel IRI model. Methods: Adult male Sprague-Dawley rats underwent bowel IRI induced by supravisceral aortic clamping and were randomly assigned to receive sivelestat or saline (control) and monitored for survival. We randomly assigned other rats to undergo laparotomy alone (sham operation), IRI alone, or IRI and sivelestat treatment. We evaluated blood samples for organ function, cytokine levels, and neutrophil elastase activity after reperfusion. Organs were analyzed histologically. We also determined lung injury in another set of rats. Results: Bowel IRI induced a significant increase in serum variables indicative of organ function, cytokine concentrations, neutrophil elastase activity, and lung permeability and edema, which reflected the presence of both systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome. Treatment with sivelestat significantly improved survival rate, lung permeability and edema, and significantly decreased levels of creatinine, interleukin 6, interleukin 10, and neutrophil elastase activity. Histological studies showed that sivelestat-treated rats had less bowel IRI-induced damage to lung and liver tissue than controls. Conclusion: In a rat model, administration of sivelestat attenuated the effects of bowel IRI induced by supravisceral aortic clamping, and improved the survival rate. (C) 2013 Elsevier Inc. All rights reserved.

Laparoscopic gastrectomy has been widely accepted especially in patients with early-stage gastric cancer. However, the safety and oncologic validity of laparoscopic gastrectomy for advanced gastric cancer are still being debated. Since the late 90s', we have been engaged in developing a stable and robust methodology of laparoscopic radical gastrectomy for advanced gastric cancer, and have established laparoscopic distinctive technique for suprapancreatic lymph node dissection, namely the outermost layer-oriented medial approach. In this article, We present the development history of this method, and current status and future perspectives of laparoscopic gastrectomy for advanced gastric cancer based on our experience and a review of the literature. © 2013 by The Korean Gastric Cancer Association.

図１の内容に誤りがあったため、訂正いたします。

ロボット支援手術は従来の鏡視下手術の欠点を補完する新たな低侵襲手術として注目されている。本邦では、本年4月よりロボット支援前立腺全摘術が保険収載され、ロボット保有台数は50台を超えてアジア最多となった。近年、消化管領域ではfeasibilityのみならず短期成績の改善効果が報告されつつある。一方で、高いコスト、長い手術時間、エビデンスの不足などの問題点もあり、今後のさらなる検討と発展が期待される。(著者抄録)

ロボット支援手術は従来の鏡視下手術の欠点を補完する新たな低侵襲手術として注目されている. 本邦では, 本年4月よりロボット支援前立腺全摘術が保険収載され, ロボット保有台数は50台を超えてアジア最多となった. 近年, 消化管領域ではfeasibilityのみならず短期成績の改善効果が報告されつつある. 一方で, 高いコスト, 長い手術時間, エビデンスの不足などの問題点もあり, 今後のさらなる検討と発展が期待される.

Background: High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. Materials and Methods: In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. Results: The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37 degrees C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). Conclusion: These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine. (C) 2014 S. Karger AG, Basel

Background: High mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxic shock and sepsis. The purpose of the present study was to investigate the role of HMGB1 in response to ischemia-reperfusion injury. Methods: Ischemia-reperfusion injury was induced in male Wistar rats by clamping the superior mesenteric artery for 60 min. Using this model, the serum concentrations and localization of HMGB1 were investigated. The histologic findings from reperfused intestines and the survival rates were compared between the anti-HMGB1 antibody treatment groups (group A treated with 6.0 mg/kg antibody and group B with 0.6 mg/kg antibody) and the control antibody treatment group (control group). Results: Serum HMGB1 concentrations increased early after reperfusion and peaked at 3 h. Immunohistochemistry for HMGB1 revealed a high degree of positive staining in the epithelial cells of the damaged villi. Anti-HMGB1 antibody treatment significantly reduced this damage (P < 0.05) and improved the 48-h survival rate (90% in group A versus 50% in the controls; P < 0.05). Conclusions: These results suggest that HMGB1 plays a key role in small intestinal ischemia-reperfusion injury. (C) 2012 Elsevier Inc. All rights reserved.

胃癌に対する胃全摘、脾門リンパ節完全郭清目的の脾摘は、現時点では胃上部進行胃癌、特に大彎浸潤病変に対する標準術式である。しかし、病変の局在や進行度、耐術能、併存疾患のコントロール状態によっては脾温存術式も考慮する。脾摘後は、特に膵液瘻や血小板増加に伴う血栓形成などに注意し、脾摘後劇症型感染症(overwhelming postsplenectomy infection:OPSI)の予防のために肺炎球菌ワクチンを接種する。(著者抄録)

感染下において損傷組織から遊離される内因性物質alarmin(危険信号分子)の中でも、核内タンパクHMGB1が最近世界中の研究者から注目を浴びている。1999年にHMGB1の敗血症におけるlate mediatorとしての重要性が報告されて以来、急性肺損傷、心筋障害、膵炎、外傷、各種術後、DIC、虚血再灌流障害等の急性炎症のみならず、慢性関節リウマチ等の慢性炎症、悪性腫瘍の増殖や浸潤、転移等、さまざまな病態におけるkey mediatorの一つであることが明らかとなった。われわれも、この「運命決定因子」に着目し、敗血症、小腸・肝虚血再灌流傷害、劇症肝不全でのHMGB1動態を解明するとともに、各種のHMGB1制御法の開発を試みている。HMGB1中和抗体のほか、HMGB1の阻害剤タンパクA Boxの遺伝子導入、HMGB1吸着カラムによる体外循環等であり、市販薬の遺伝子組み換えヒトトロンボモジュリンにも注目している。(著者抄録)

da Vinci Surgical System(Intuitive Surgical社)によるロボット手術は、本邦でも急速に認知されつつある。当大学では、2009年1月にロボット手術を臨床導入して以来、上部消化管領域ではロボット胃切除120例、ロボット食道切除27例と積極的にロボット手術に取り組んできた。この自験例に基づき、上部消化管外科領域におけるロボット手術の現状と今後の展望について解説する。(著者抄録)

ダヴィンチ手術システム(da Vinci Surgical System:DVSS)によるロボット支援手術は、本邦でも急速に認知されつつある。2012年4月から前立腺全摘において内視鏡下手術後ロボット支援加算が保険収載された。藤田保健衛生大学では、2009年にDVSSの導入後2012年4月までに347件のロボット支援手術を行ってきた。そのうち、消化器領域の手術が204例と高い比率を占めている。特に、上部消化管外科ではロボット胃切除111例、ロボット食道切除26例と積極的にロボット支援手術に取り組んでいる。その結果、手術の定型化が進み、通常の内視鏡手術に対してロボット支援手術は出血量が少なく、術後入院期間が短いなどの低侵襲性が明らかになりつつある。また、食道切除においては、反回神経周囲リンパ節郭清における神経愛護的な効果も確認された。DVSSは高額医療であるが、消化器がんの治療においてDVSSの有用性をさらに検討する必要性が示唆された。消化器がん領域でも高精度・低侵襲なロボット支援手術の発展が期待される。(著者抄録)

Meticulous mediastinal lymphadenectomy frequently induces recurrent laryngeal nerve palsy (RLNP). Surgical robots with impressive dexterity and precise dissection skills have been developed to help surgeons perform operations. The objective of this study was to determine the impact on short-term outcomes of robot-assisted thoracoscopic radical esophagectomy performed on patients in the prone position for the treatment of esophageal squamous cell carcinoma, including its impact on RLNP. A single-institution nonrandomized prospective study was performed. The patients (n = 36) with resectable esophageal squamous cell carcinoma were divided into two groups: patients who agreed to robot-assisted thoracoscopic esophagectomy with total mediastinal lymphadenectomy performed in the prone position (n = 16, robot-assisted group) without insurance reimbursement, and those who agreed to undergo the same operation without robot assistance but with health insurance coverage (n = 20, control group). These patients were observed for 30 days following surgery to assess short-term surgical outcomes, including the incidence of vocal cord palsy, hoarseness, and aspiration. Robot assistance significantly reduced the incidence of vocal cord palsy (p = 0.018) and hoarseness (p = 0.015) and the time on the ventilator (p = 0.025). There was no in-hospital mortality in either group. There were no significant differences between the two groups with respect to patient background, except for the use of preoperative therapy (robot-assisted group < control, p = 0.003). There were no significant differences in estimated blood loss, operating time, number of dissected lymph nodes, completeness of resection, or the incidence of the other complications, except for anastomotic leakage (p = 0.038). Robot-assisted thoracoscopic esophagectomy with total mediastinal lymphadenectomy is feasible and safe. This method shows promise in preventing RLNP.

＜ポイント＞◆デバイスについての理解を深めることは重要である.そうでなければ不意の出血や合併症を起こすことになる.準備を十分にしておくことは開腹手術となんら変わりない.◆腹腔鏡下胃切除術の成否は術野展開に尽きる.術野展開でどのような切離ラインを出すか?それを理解しておくことが重要である.(著者抄録)

We evaluated the dual immuno-regulatory effects of Y-40138, inhibiting tumor necrosis factor (TNF)-alpha production and augmenting interleukin (IL)-10 productions, in animal models of organ dysfunction related to systemic inflammatory response syndrome. Male Sprague-Dawley rats received Y-40138 (1, 10 and 30 mg/kg) or saline subcutaneously, and were subjected to cecal ligation and puncture (CLP) surgery 15 min later. Male C57BI/6 mice received Y-40138 (30 mg/kg) or saline intravenously and were subjected to intratracheal instillation of hydrochloric acid (0.1 N, pH = 1.0) 30 min later. Survival after CLP surgery was monitored for 10 days and compared by Kaplan-Meier analysis and log rank statistics. Neutrophil count and cytokine concentrations in bronchoalveolar lavage (BAL) fluid at 12 h after intratracheal instillation were analyzed by one-way ANOVA. After CLP surgery, while 1 mg/kg of Y-40138 increased survival, 30 mg/kg of Y-40138 decreased survival (p < 0.01). After acid aspiration, Y-40138 significantly inhibited neutrophil recruitment by decreasing TNF-alpha / IL-10 ratio in BAL fluid (p < 0.05). Although the down regulation of pro-inflammatory cytokines and augmentation of anti-inflammatory cytokines seems a rational approach for SIRS-related multiple organ failure, further studies are needed for future clinical application of Y-40138, especially in situations compromised with microorganisms infection.

The efficacy of intravenous immunoglobulin G in the treatment of patients with severe sepsis or septic shock is still being debated. We investigated the impact of high-dose immunoglobulin administration on the survival rate and serum high-mobility group box chromosomal protein 1 (HMGB1) level in a rat model of sepsis created by cecal ligation and puncture (CLP). Rats received either CLP-induced sepsis or had additional immunoglobulin treatment in 1,500 or 300 mg/kg. After induction of sepsis and respective treatment conditions, pulmonary and renal tissues were examined histologically for pathological changes at postoperative hour (POH) 4, and serum cytokine and HMGB1 levels were measured at POH 4, 8, 20, and 44. Using other rats, we also observed the survival rate after CLP for 7 days. Treatment with immunoglobulin significantly improved survival rate at postoperative day 7 (73% in the high-dose group vs. 33% in the control group; p = 0.037). The serum lactate dehydrogenase, endotoxin, creatinine, and blood urea nitrogen levels were significantly lower in the high-dose group than in the other groups. The serum HMGB1 level had increased at 4 h postoperatively in the control group (10.2 +/- 3.3 ng/mL) and low-dose group (10.3 +/- 4.0 ng/mL), but it was significantly reduced in the high-dose group (4.2 +/- 0.8 ng/mL) compared with the control group (p = 0.03). Our results suggest that high-dose immunoglobulin therapy may improve the serum endotoxin and HMGB1 levels and overall survival rate in sepsis by inhibiting the inflammation.

Robotic surgery for the treatment of gastric cancer has been reported, but the technique is not yet established. The objective of this study was to assess the feasibility and safety of our novel integrated procedure for robotic suprapancreatic D2 nodal dissection during distal gastrectomy. At our hospital from January 2009 to December 2010, a total of 25 consecutive cases of gastric cancer were treated by robotic distal gastrectomy with intracorporeal Billroth I reconstruction. These patients were enrolled in a prospective study to assess the safety and feasibility of robotic distal gastrectomy with nodal dissection by our novel integrated approach, which consists of three elements: arm formation, the surgical approach, a cutting device. To evaluate the learning curves involved in this approach, clinicopathologic features and surgical outcomes were compared between the initial (n = 12) and late (n = 13) phases. All operations were completed without the need for open or conventional laparoscopic surgery. The mean operating time was 361 +/- A 58.1 min (range 258-419 min), and blood loss recorded was 51.8 +/- A 38.2 ml (range 4-123 ml). The median number of retrieved lymph nodes was 44.3 +/- A 18.4 (range 26-95). R0 resection was accomplished in all cases. There were no deaths or complications related to pancreatic damage. Operating time and surgeon console time for the late phase were significantly shorter than those for the initial phase. Our novel robotic approach for D2 nodal dissection in gastric cancer is feasible and safe.

In Japan, the usefulness of robot-assisted surgery using da Vinci surgical system (DVSS) has rapidly become widely acknowledged. At Fujita Health University, DVSS was introduced in 2009. Thus far, 347 patients were treated by DVSS at our institute, including 204 gastroenterological operations. In our department, robot-assisted gastrectomy (RAG, n=111) and robot-assisted esophagectomy (REG, n=26) have been technically standardized. Recently, we reported that both RAG and REG are minimally invasive. Moreover, we showed that the incidence of recurrent nerve palsy by lymphadenectomy was significantly reduced by REG, compared with conventional thoracoscopic esophagectomy. Although robot-assisted surgery is a highly expensive treatment, these results prompt the need for further evaluation of the effectiveness of robot-assisted surgery in the gastroenterological field. Development of a more accurate and less invasive robotic surgery system would contribute to a better quality of life patients with gastroenterological malignancies.

Background: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF). Patients and Methods: We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1. Results: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 +/- 0.3 in HVs, 4.0 +/- 2.0 in LC, 5.2 +/- 2.6 in CH, 8.6 +/- 4.8 in severe AH, 7.8 +/- 2.7 in FH with a history of PE, and 12.5 +/- 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 +/- 116 in FH vs. 874 +/- 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH. Conclusion: We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue. Copyright (C) 2012 S. Karger AG, Basel

Suda K, Eom J, Jaw J, Mui T, Bai N, Or C, Ngan D, Li Y, Wang X, Tsuruta M, Tam S, Man SP, Van Eeden S, Sin DD. Endotoxin-induced cardiovascular dysfunction in mice: effect of simvastatin. J Appl Physiol 111: 1118-1124, 2011. First published July 21, 2011; doi:10.1152/japplphysiol.00158.2011.-Lung infections are associated with acute lung injury (ALI), systemic inflammation, and vascular events. Clinical studies suggest that statins improve health outcomes of patients with pneumonia and ALI. The mechanisms by which this occurs are unknown. The aim of this study was to determine whether statins attenuate systemic inflammation and cardiovascular dysfunction related to ALI in mice. Simvastatin (SS; 20 mg/kg) or vehicle solution was instilled intraperitoneally into mice 24 h before and again just prior to intratracheal LPS instillation (1 mu g/g). These mice were then anesthetized with 2.0% isoflurane and underwent a short surgical procedure to instill LPS. Four hours later, IL-6 levels in bronchoalveolar lavage fluid and in arterial and venous serum were measured. Cardiac function was evaluated using 2-D echocardiography, and endothelial function was determined using wire myography on aortic sections. LPS induced a significant increase in serum IL-6 levels. SS reduced venous (P = 0.040) but not arterial concentrations of IL-6 (P = 0.112). SS improved the maximal vasodilatory response of the aorta to ACh (P = 0.004) but not to sodium nitroprusside (P = 1.000). SS also improved cardiac output (P = 0.023). Vasodilatory response to ACh was impaired when aorta from untreated mice was incubated with ex vivo IL-6 (P = 0.004), whereas in the aorta from mice pretreated with SS, the vasodilatory response did not change with IL-6 incubation (P = 0.387). SS significantly improved LPS-induced cardiovascular dysfunction possibly by reducing systemic expression of IL-6 and its downstream signaling pathways. These findings may explain how statins improve health outcomes in patients with ALI.

Primary cricopharyngeal dysfunction (PCD) is a rare idiopathic disorder of the upper esophageal sphincter (UES), characterized by oropharyngeal dysphagia, frequent aspiration, and narrowing at the level of the UES. Cricopharyngeal myotomy (CPM) has been used to treat oropharyngeal dysphagia of different causes including anatomic, neuromuscular, iatrogenic, inflammatory, neoplastic, and idiopathic; however, the indications for CPM and predictors of its outcome are not clearly defined. We report a case of PCD with hypertonic UES caused by a structural abnormality localized in the cricopharyngeus muscle, visualized as a cricopharyngeal bar, which we treated successfully by CPM, achieving long-term relief.

Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting beta 2 agonists (ICS/LABA) down-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were pretreated for 3 hours with intratracheal budesonide, formoterol, or both, before LPS was sprayed into their tracheas. IL-6-deficient mice were similarly exposed to LPS. Four hours later, bronchoalveolar lavage fluid (BALF) and serum were collected, and endothelial and cardiac functions were measured, using wire myography of the aortic tissue and echocardiography, respectively. LPS significantly impaired vasodilatory responses to acetylcholine (P, 0.001) and cardiac output (P - 0.002) in wild-type but not IL-6-deficient mice. Intratracheal instillations of exogenous IL-6 into IL-6-deficient mice restored these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac output, P = 0.025). Pretreatment with the combination of budesonide and formoterol, but not either alone, ameliorated the vasodilatory responses to acetylcholine (P 5 0.018) and cardiac output (P < 0.001). These drugs also attenuated the rise in the systemic expression of IL-6 (P < 0.05) related to LPS. IL-6 contributes to the cardiovascular dysfunction related to LPS, and pretreatment with budesonide/formoterol reduces the systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular events related to ALI.

障害局所で生成され、殺菌、自然免疫、修復反応などを生体に誘導する活性を持つ生体由来の因子をalarminと総称する。Alarminの代表格はhigh-mobility-group box chromosomal protein 1(HMGB1)である。HMGB1は近年敗血症の後期mediatorとして注目されており、HMGB1を標的とした敗血症の新たな治療法が開発されつつある。(著者抄録)

症例は54歳の男性で,平成18年4月,健診の上部消化管造影検査にて胃粘膜下腫瘍を指摘され,当院紹介受診となった.上部消化管内視鏡検査にて胃角部大彎前壁に径30 mmの粘膜下腫瘍を認めた.腹部CTにて同部に一致して,内部に変性または壊死性変化を伴う嚢胞性病変を認め,悪性病変の可能性を否定できず,8月に幽門側胃切除術を施行した.術中,腫瘤径45 mmと増大傾向を認め,胃漿膜面への浸潤を示唆する所見を認めた.病理組織学的検査所見にてLanghans型巨細胞を伴う類上皮肉芽腫を認めたこと,術後施行した胃液抗酸菌培養検査にて結核菌培養陽性であったことより,胃結核と診断した.退院後,外来にて6ヵ月間の抗結核化学療法を施行し,術後3年間無再発にて経過している.(著者抄録)

The biological mechanisms responsible for an association between elevated concentrations of ambient particulate matter (PM) and increased cardiovascular morbidity and mortality remain unclear. Our laboratory showed that exposure to PM induces systemic inflammation that contributes to vascular dysfunction. This study was designed to determine whether the lung is a major source of systemic inflammatory mediators, using IL-6 as a surrogate marker. We also sought to determine the impact on vascular dysfunction after exposure to PM of less than 10 mu m in diameter(PM(10)). C57BL/6 mice were intratracheally exposed to a single instillation of PM(10) (10 or 200 mu g) or saline. Four hours or 24 hours after exposure, venous and arterial blood samples were simultaneously collected from the right atrium and descending aorta. Concentrations of IL-6 were measured in bronchoalveolar lavage fluid (BALF) and serum samples. Vascular functional responses to acetylcholine (ACh) and phenylephrine were measured in the abdominal aorta. Concentrations of IL-6 in BALF samples were increased at 4 and 24 hours after exposure to PM(10). At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM(10) reversed this arteriovenous gradient, 4 hours after exposure. The relaxation responses of the abdominal aorta to ACh decreased 4 hours after exposure to 200 mu g PM(10). In IL-6 knockout mice, the instillation of recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM(10) did not cause vascular dysfunction. These results support our hypothesis that exposure to PM(10) increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.

A 54-year-old asymptomatic man diagnosed with submucosal tumor-like isolated gastric tuberculosis was found in an annual barium swallow checkup to have a gastric submucosal tumor. Gastrointestinal fi-berscopy and computed tomography (CT) showed a 3cm submucosal gastric tumor at the greater mid-gastric curvature. The tumor's swift growth to 45 mm in only 4 months and swollen regional lymph nodes necessitated distal gastrectomy with lymphadenectomy due to potential malignancy. Histological examination showed epithelioid granuloma with Langhans giant cells in the resected tumor and lymph nodes. To determine if the man had tuberculosis, we cultured gastric juice and sputum postoperatively, finding only the gastric juice to be positive for Mycobacterium tuberculosis. Given the possibility of remaining tubercular lesions, the man was administered antituberculosis medication for six months postoperatively. He remains alive and recurrence-free in the 3 years since surgery. © 2011 The Japanese Society of Gastroenterological Surgery.