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Background The presence of a foreign body in the common bile duct (CBD) is a rare phenomenon. Thus, the route and mechanism of its migration remain difficult to fully clarify, especially for cases that occur after gastrectomy with Roux-en-Y reconstruction. Herein, we present a case of a CBD stone that formed around a fish bone as a nidus subsequent to distal gastrectomy with Roux-en-Y reconstruction. Case presentation A 70-year-old man was admitted to our hospital due to repeated episodes of epigastralgia. He had undergone distal gastrectomy with Roux-en-Y reconstruction for gastric cancer approximately 10 years prior. Blood tests revealed obstructive jaundice, hepatobiliary dysfunction, and inflammation. Multi-plane reconstructed computed tomography (CT) revealed a CBD stone with a needle-shaped calcification density at the center, oriented along the length of the CBD. Surgery was performed using an upper median laparotomy approach. Lithotomy with choledochotomy was performed to remove one fragile bilirubin stone that had formed around a 3-cm, needle-shaped fish bone. A choledochoduodenal fistula was not detected intraoperatively. A review of the imaging of a prior examination revealed that the formation of the CBD stone around the fish bone was observable on a follow-up CT performed approximately 2 years prior. However, no clinical symptoms associated with the migration of the fish bone to the CBD were reported and the fish bone was not detected at that time. Conclusion In this case, transpapillary migration of the fish bone could only be speculated in the absence of an observable fistula, choledochostomy, or any clinical symptoms. Our case is clinically relevant as cholangitis developed after CBD stone formation around the fish bone that acted as a nidus.

Chagas' Disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for up to 41% of the heart failures in endemic areas in South America and is an emerging infection in regions of North America, Europe, and Asia. Treatment is suboptimal due to two factors. First, the lack of an adequate biomarker to predict disease severity and response to therapy; and second, up to 120-days treatment course coupled with a significant incidence of adverse effects from the drug currently used. Because the disease can manifest itself clinically a few years to decades after infection, controversy remains concerning the suitability of current drug treatment (benznidazole), and the efficacy of alternative drugs (e.g. posaconazole). We therefore followed the clinical course, and PCR detection of parasite burden, in a mouse model of infection for a full year following treatment with benznidazole or posaconazole. Efficacy of the two drugs depended on whether the treatment was performed during the acute model or the chronic model of infection. Posaconazole was clearly superior in treatment of acute disease whereas only benznidazole had efficacy in the chronic model. These results have important implications for the design and analysis of human clinical trials, and the use of specific drugs in specific clinical settings., Author summary Chagas disease is a parasitic infection that can be incapacitating, leading to heart failure with risk of sudden death. Currently, only one drug treatment is available, Benznidazole, but it demands a long period of treatment, has variable efficacy and leads to serious side effects that can lead to discontinuation of the treatment. An alternative therapy, the anti-fungal drug, Posaconazole, was repurposed for treatment of Chagas disease, but its use has been controversial with conflicting results in studies from different groups. In our approach, we followed the parasitic infection, disease symptoms and persistence of the pathogen in mice for a full year after treatment with Benznidazole or Posaconazole. Posaconazole treatment was more effective in the early infection (acute disease) whereas only Benznidazole had efficacy in the chronic model. This information can have important implications for the design and analysis of human clinical trials, and the use of specific drugs in specific clinical settings.

Background Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice. Methodology/Principal findings Both acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart. Conclusions/Significance The positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life., Author summary Chagas disease is a parasitic disease caused by the Trypanosoma cruzi. The infection may result in gastrointestinal manifestations and cardiomyopathy. Benznidazole, the current treatment, has limited efficacy and often leads to serious side effects. Aiming to develop new treatments, our group has identified new inhibitors that block the synthesis of parasitic lipids, resulting in parasite death. In this work, we evaluated the safety and efficacy of two of these compounds, 9 and 12, in mouse models of T. cruzi infection. Both compounds were well-tolerated by animals throughout the 28-day administration. In acutely infected mice, the compounds drastically reduced bloodstream parasites and increased survival. When treatment was initiated during the chronic phase, parasitemia dropped to background levels and remained undetectable for 4 weeks after drug withdrawal; parasites were re-activated by chemically-induced immunosuppression. Thus, the experimental compounds tested in these studies had an acceptable safety profile, achieved a marked reduction in parasite load and prevented heart injury due to inflammation, even in the absence of sterile cure. We conclude that the development of non-toxic medications capable of slowing the progression of cardiomyopathy is a valuable treatment option for Chagas disease patients because it could enhance the quality of life.

症例は65歳女性，下血，直腸脱を主訴に来院した．Hb6.8g⁄dlと高度の貧血を認め，排便時に手拳大の完全直腸脱を認めた．下部消化管内視鏡検査では肛門縁より５～15cmの直腸に全周性の粘膜浮腫，発赤，ポリープ状の隆起性病変が認められた．病理組織では異型性の無い腺管の増生，固有層間質に細血管の増生拡張・平滑筋組織の樹枝状増生が認められ臨床症状とあわせて完全直腸脱に伴った粘膜脱症候群（Mucosal Prolapse Syndrome: MPS）と診断した．MPSの治療の基本は排便時のいきみの制限，緩下剤による便秘の予防などの保存的治療である．本症例では高度な直腸脱を認めた為，経腹的直腸固定術を施行した．術後経過良好で直腸脱の再発なく，粘膜病変の改善も見られ，MPSに対しても良好な治療効果が得られた．また，MPSと直腸脱の関係を考える上でも重要な症例と考えられたため報告する．

近年，上部消化管穿孔症例（胃潰瘍穿孔，十二指腸潰瘍穿孔）に対する穿孔部閉鎖術として開腹術に比し低侵襲な腹腔鏡下手術が導入されてきている．しかし，腹腔鏡下手術は初心者には手技が困難であり手術時間が延長する．腹腔鏡補助下手術における低侵襲度と手術困難度は明らかでないので従来の開腹手術と比較検討した．腹腔鏡補助下手術（12例）では穿孔部直上に約５cmの小開腹下に，開腹手術（13例）では上腹部正中切開下に穿孔部を直接閉鎖し，有茎大網で被覆した．両群間で背景因子に差はなかった．腹腔鏡補助下群で入院期間，経口摂取までの期間は有意に短縮し，術後７日目のWBC，CRPは有意に低値であった．出血量，手術時間には有意差がなく，術後合併症，再発は両群共になかった．従って腹腔鏡補助下手術は開腹手術と比較して手術困難度は増大せず，低侵襲な術式であると考えられた．

症例は54歳,男性.主訴は下腹部痛. 2005年2月に,左尿管結石症で当院泌尿器科を受診し,その際に施行された腹部CTで,骨盤内腫瘍を指摘された.泌尿器科で,経直腸的に生検を施行された.生検後に下腹部痛を認めるようになった.腫瘍切除の目的で, 2005年4月に当科紹介となった.開腹時所見は,腹膜翻転部が発赤しており,炎症性変化で硬化していた.摘出標本は肥厚した壁に囲まれ,内部には角化物様の物質を認めた.また壁内側は表皮様組織で覆われていた.病理組織学的診断は,角化物と表皮を認め,表皮には毛髪や皮脂腺などの付属器,および軟骨成分などは認めず, epidermoid cystと診断された.術後経過は良好で,術後13日目に軽快退院した.仙骨前部に発生したepidermoid cystは,無症状のことが多く発見されにくいものの,感染や悪性化の可能性があるため,診断後は摘出術を施行するべきであると考えられた.

症例は56歳,男性,呼吸困難を主訴とし入院.右胸腔に巨大ブラがあり,健常肺虚脱,縦隔左方偏位がみられ, O221投与下でPaO271.1mmHg, PaCO258.6mmHg, VC1.751, FEV1.00.681, %VC 47.0%, FEV1.0%38.8%であった.右下葉bullaを穿刺し持続吸引後,症状の改善が得られ残存肺機能の評価ができ,安全に手術が可能であった.右腋窩中線第7肋間より胸腔鏡を挿入し第5肋間後側方小開胸下,ブラ壁境界健常肺に4-0 prolene SH水平マットレス縫合を置き,その直上で自動縫合器を掛け嚢胞を切除した.術後肺再膨張は良好でなり室内気でPaO276.4mmHg, PaCO245.9mmHg, VC3.021, FEV1.02.431, %VC 81.2, FEV1.0%85.3%に改善,術後13病日に退院した.巨大ブラのため呼吸困難に陥った症例に対する持続脱気は残存肺の機能評価,術後の再拡張後肺水腫の軽減に有用で,胸腔鏡補助下のブラ切除術は呼吸機能の保持に有用と考えられる.

症例は52歳, 男性, 左小胸筋下から第一肋間を貫通し胸腔内に発育した腫瘤の切除目的で入院となった.左襟状切開に第3肋間までの胸骨正中部分切開を加え前胸壁側と胸腔内から剥離を進めて腫瘍を完全切除した.病理組織診断はInfiltrating typeのintramuscular lipomaであり, 砂時計型経胸壁型成人脂肪腫と診断した.砂時計型経胸壁型成人脂肪腫は本邦で3例の報告が認められるのみである.本腫瘍は再発の可能性があるため脂肪腫といえども完全切除が必要である.また, 今回用いたアプローチは前胸部上部の胸壁内外に存在する腫瘍切除に有用と考えられた.

Background and Aims: Local autologous bone marrow cell implantation (BMCI) can induce therapeutic angiogenesis. We evaluated the safety and feasibility of this treatment for ischemic heart disease. Methods: The safety of BMCI was preclinically confirmed in dogs by giving a direct injection of either 2×107 bone marrow cells (n = 4) suspended in 0.1 mL phosphate-buffered saline (PBS), or 0.1 ml PBS only (n = 4, PBS group), into the myocardium of the left ventricle at six points. Electrocardiograph (ECG), echocardiography, and systemic biochemistry indexes were recorded 1, 7, 30, and 240 days after treatment, and histological change was examined 240 days after treatment. We also evaluated the clinical safety and feasibility of BMCI in six patients with ischemic heart disease, who were given BMCI treatment in combination with coronary artery bypass grafting (CABG), by recording Holter ECG, echocardiography, computed tomography, and systemic biochemistry indexes in the acute and chronic phases after treatment. Results: No significant changes in systemic biochemistry indexes were found after BMCI treatment in comparison with control groups, in either the experimental investigation or the clinical trial. No cardiac damage related to BMCI was detected by ECG or echocardiography, and histological examination showed minimal fibrotic change within the myocardium after BMCI or PBS injection in the dogs. Local calcification was not detected on histological slices 240 days after treatment in the dogs, or on computed tomography 1 year after treatment in the patients. Conclusions: BMCI treatment appears to be a safe and feasible method of inducing angiogenesis to treat ischemic heart disease. (J CARD SURG 2003;18 (Suppl 2):S69-S75)

Background. Local bone marrow cell implantation can induce angiogenesis. In the present study we investigated whether angiogenesis induced by bone marrow cell implantation improves deteriorated cardiac function in a rat heart model of hypoperfusion. Methods. A hypoperfusion heart model was created in Dark Agouti rats by ligating the left anterior descending artery placed against a copper wire (275 m), then pulling out the wire immediately. The left ventricular (LV) anterior wall was injected directly at six points, each with 1 10 7 bone marrow cells in 10 Lo f phosphate-buffered saline or with phosphate-buffered saline only, respectively. Echocardiography was performed to evaluate the cardiac function 7, 30, 60, and 90 days after treatment. Microvessel density and blood flow in the LV anterior wall were estimated 60 days after treatment. Results. Both the increase of LV end-systolic diameter and the decrease of percent of fractional shortening caused by myocardial ischemia were attenuated effectively by bone marrow cell implantation treatment. Bone marrow cell implantation treatment also increased the levels of angiopoietin-1 and vascular endothelial growth factor in the LV anterior wall. The microvessel density, blood flow, and thickness of the LV anterior wall significantly also increased after bone marrow cell implantation treatment compared with those after phosphatebuffered saline injection. Conclusions. The local implantation of autologous bone marrow cells induced angiogenesis and improved the perfusion of ischemic myocardium, thereby preventing LV remodeling and improving deteriorated cardiac function caused by myocardial hypoperfusion.

Background. Peripheral leukocytes and platelets (LAPs) contain many kinds of cells with the ability to secrete several growth factors and cytokines. We attempted to induce therapeutic angiogenesis by injecting self-LAPs into a rat ischemic hindlimb model. Materials and methods. Supernatants from cultured LAPs were used for the endothelial cell (EC) proliferation assay, and LAPs were used in a cornea model to evaluate angiogenic potency. LAPs were injected directly into the male Dark Agouti rat ischemic hindlimb model, after which a microangiogram was done and the capillary/muscle fiber ratio was examined histologically. ELISA revealed the levels of contributing growth factors and cytokines present in the ischemic muscles. Results. The EC proliferation assay showed that the supernatants of LAPs accelerated proliferation and that the LAPs induced angiogenesis in the cornea model. The microangiograms and histological evaluation revealed that angiogenesis was induced more effectively in the rats injected with LAPs (LAP group) than in the those injected with phosphate-buffered saline (PBS group). The levels of basic fibroblast growth factor (bFGF) in the ischemia, PBS, and LAP groups were significantly increased compared to those in the sham group. The level of interleukin-1β (IL-1β) in the LAP group was significantly more elevated than in the other groups. Conclusions. The injection of self-LAPs induced angiogenesis in a rat ischemic hindlimb model. Ischemia caused an elevation in the level of bFGF and also in IL-1β derived from LAPs, which contributed to angiogenesis. This is a novel, yet simple and safe method of inducing therapeutic angiogenesis.

開心術における虚血/再灌流障害に好中球が関与しているか否かを知る目的で,大動脈遮断前後で冠循環での顆粒球エラスターゼおよびミエロパーオキシダーゼ産生量を測定した.再灌流後,冠循環での顆粒球エラスターゼおよびミエロパーオキシダーゼ産生量は有意に上昇した.さらに再灌流後の冠循環での顆粒球エラスターゼ,ミエロパーオキシダーゼ産生量は大動脈遮断時間と正の相関を示した.これらの結果から,開心術における心虚血/再灌流障害に好中球が関与していることが示唆された.

体外循環中の肺障害に好中球が関与しているか否かを知る目的で, 体外循環前後で肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量および respiratory index を測定した. 体外循環後, 肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量および respiratory index 値は有意に上昇した. さらに体外循環後の肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量は術前肺動脈圧および respiratory index の変化率と正の相関を示した. これらの結果から, 体外循環中の肺機能障害に好中球が強く関与しており, 肺高血圧症例でそれがより顕著であることが示された.

The incidence of delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasms is reported to be approximately 5 %. We examined whether postprocedural combined treatment using the coagulation plus artery-selective clipping (2C) method is a useful measure for preventing delayed bleeding after ESD. A total of 234 gastric epithelial neoplasms were treated from June 2007 to May 2012. Post-ESD coagulation (PEC) and clipping for part of the vessels was performed for 154 lesions from June 2007 to June 2010. A total of 80 lesions were treated using the 2C method from July 2010 to May 2012. During ESD, the locations of the arteries were recorded on a schematic diagram of the lesion. Arteries were defined as regions of arterial bleeding that required coagulation or apparent arteries in which preventive coagulation was performed. When ESD was completed, soft coagulation was performed for arteries in the resection area using hemostatic forceps, followed by arterial clipping for additional strength. Coagulation also was performed continuously for visible vessels in the resection area. This was a retrospective study. The incidence rates of delayed bleeding after ESD, as evidenced by hematemesis or melena, or the presence of anemia (decline in Hb >2 g/dl) that required emergency endoscopy were recorded. Delayed bleeding occurred in 7 (4.5 %) of the 154 cases treated using PEC and in 1 (1.3 %) of the 80 cases treated using the 2C method. The mean time required for the 2C method was 15.0 ± 7.0 min (range, 5–44 min). The mean number of clippings per lesion was 3.8 ± 2.8 (range, 0–13). Almost all clips fell off within 2 months of the procedure. Coagulation plus artery-selective clipping (the 2C method) of post-ESD ulcers might effectively reduce the incidence of delayed bleeding after ESD for gastric neoplasms.

Aim. Delayed bleeding after endoscopic submucosal dissection (ESD) for gastric epithelial neoplasms is a major complication. We investigated factors related to post-ESD bleeding to identify preventive measures.Methods. The study included 161 gastric epithelial neoplasms in 142 patients from June 2007 to September 2010. Post-ESD bleeding was defined as an ulcer with active bleeding or apparent exposed vessels diagnosed by an emergency endoscopy or a planned follow-up endoscopy. We analyzed associations between bleeding and the following factors: age, sex, morphology, pathology, tumor depth, ulcer presence/absence, location, size of the resected lesion, duration of the procedure, the number of times bleeding occurred during ESD, and the use of anticoagulants and/or antiplatelet drugs. Subsequently, we examined characteristics of bleeding cases.Results. Post-ESD bleeding occurred in 21 lesions. Univariate analysis of these cases showed that ulcer presence/absence (P<0.001), middle or lower third lesions (P=0.036), circumference (P=0.014), and a post-ESD ulcer with an extended lesser curve (P=0.009) were significant predictors of bleeding. Multivariate analysis showed that ulcer presence/absence (OR 9.73, 95% CI 2.28–41.53) was the only significant predictor.Conclusion. Ulcer presence/absence was considered the most significant predictor of post-ESD bleeding.

A new therapy for severe ischemic heart disease has been developed; therapeutic angiogenesis induced by the local implantation of autologous bone marrow cells (BMC). After confirming that no detrimental changes were induced by this treatment in a canine heart model, a clinical trial was commenced in 1999. Thus far, 5 patients have been given this new treatment concomitant with coronary artery bypass grafting and all have been followed up for at least 1 year. Autologous BMC were implanted into the ungraftable area and postoperative cardiac scintigraphy showed specific improvement in coronary perfusion in 3 of the 5 patients. Postoperative chest radiography, electrocardiography, echocardiography and blood tests did not reveal any detrimental changes. In conclusion, this new therapy appears to be safe and could provide a treatment option for patients with otherwise untreatable ischemic heart disease.

Background . Therapeutic angiogenesis was induced by local autologous bone marrow cell implantation (BMCI) in ischemic hindlimb or ischemic heart models in rats. This study was designed to investigate the toxicity and therapeutic potency of local BMCI using a chronic coronary occlusion model in dogs. Methods . The canine chronic coronary occlusion model was created by ligating of the left anterior descending artery (LAD). The myocardium in the left ventricle was divided into distinct normal, marginal, and infarction areas 30 days after LAD ligation. Each area was injected at two locations, with either 2 × 10 7 bone marrow cells (n = 7, BMCI group) or 0.1 mL phosphate-buffered saline (PBS) only (n = 7, PBS group), respectively. Hemodynamics were evaluated by a single ultrasonic transducer and echocardiography before and 30 days after the treatment. Angiogenesis was evaluated by vessel count 30 days after the treatment. The toxicity of BMCI treatment was also evaluated in 8 normal dogs by following changes in electrocardiography (ECG), echocardiography, local histology, and systemic biochemistry indexes. Results . There was a significantly higher percentage of wall thickening in the marginal area in the BMCI group than in the PBS group 30 days after treatment (14.5 ± 2.28 versus 8.1 ± 3.00, p=0.002). Significantly more microvessels were observed in the marginal area in the BMCI group than in the PBS group 30 days after treatment (127.7 ± 20.1 versus 88.0 ± 10.2/field, p=0.0007). No systemic or local toxicity was found following BMCI treatment in the acute or chronic phases. Conclusions . BMCI treatment improved local wall thickening dynamics, presumably due to the angiogenesis induced by the treatment. This indicates that it might be a safe and effective therapy for ischemic heart disease.

When performing high-risk abdominal aortic aneurysm (AAA), aortic cross-clamp time was reduced to a mean of 9 minutes by performing retrograde anastomosis using a ringed Y-graft (RYG). Retrograde anastomosis with RYG was performed in nine patients, (eight men and one woman) with a mean age of 74 years (range: 65-82 years). Three patients had angina pectoris and chronic renal failure, two had angina pectoris, one had thoracoabdominal aortic aneurysm and chronic renal failure, one had renal failure, one had aortic regurgitation, and one had aortic stenosis. First, the right common, external, and internal iliac arteries were clamped, then, the right limb of the graft was anastomosed to the common iliac artery or external iliac artery. Next, the aorta and left common iliac artery were clamped, and a longitudinal incision was made in the aneurysm. The proximal end of the RYG was inserted into the aorta and blood flow was resumed. Finally, the left limb of the graft was anastomosed to the left common iliac artery or external iliac artery. The mean aortic cross-clamp time was 9 minutes (range: 8-18 minutes). There were no cardiac complications during surgery. The mean operating time was 3:34 hours (range: 3:05-4:35 hours), and the blood loss averaged 1156 ml (range: 200-2000 ml). None of the patients developed postoperative complications and all of them have remained well after discharge. Retrograde anastomosis using RYG is one type of surgery that could be used in cases of high-risk patients with AAA./hea