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Within the digestive organ surgery robot R&D project, our research team aims to develop a surgical robot training device with an interface identical to that of the actual device. The training device uses an organ model that changes shape in real time to train operators to grab, cut open, and cut off soft tissues and close wounds using the actual device. To increase the effectiveness of the training device, we added functions to save the movements of the robot in training and changes in the operation field. By recreating the situation during training, we were able to analyze in four dimensions (4D) various changes in the operation field that the operator cannot see during training. This new function not only enabled us to analyze the contents of the training in detail, but also to report any problems in development and design of the actual device.

Surgical operation is still one of the important options for treatment of many types of cancer. In the present-day treatment of cancer, patients' quality of life is focused on and surgeons need to provide minimally invasive surgery without decreasing the curability of disease. Endoscopic surgery contributed to the prevalence of minimally -invasive surgery. However it has also raised a problem regarding differences in surgical techniques among individual surgeons. Robot-assisted surgery provides some resolutions with 3D vision and increases the freedom of forceps manipulation. Furthermore, 3D visual magnification, scaling function, and the filtering function of surgical robots may make it possible for surgeons to perform microsurgery more delicate than open surgery. Here, we report the present status and the future of the representative surgical robot, and the da Vinci surgical system.

Background and Aims: Balloon-occluded retrograde transvenous obliteration (B-RTO) is an effective treatment for gastric varices (GVx), as well as hepatic encephalopathy. The aim of this study was to examine the changes of the hepatic vein pressure gradient (HVPG) after B-RTO and determine the relation between the changes of HVPG and liver function., Patients and Methods: B-RTO was performed in 30 patients with GVx and hepatic encephalopathy. HVPG was measured in 19 of 30 patients both before and after B-RTO., Results: The B-RTO was successful in all patients. The GVx and hepatic encephalopathy were improved, and no recurrence or bleeding was observed within the follow- up period. The serum albumin and prothrombin activity were significantly improved 6 months after B-RTO in all patients. HVPG was elevated 44% above the baseline after B-RTO. Liver function significantly improved 6 months after B-RTO in patients whose HVPG increased ≥ 20% from baseline., Conclusion: An elevated HVPG after B-RTO is one aspect of the effect of liver function, and an HVPG increase of ≥ 20% from baseline is a predictive factor for obtaining an improvement of liver function., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Purpose: Angiogenesis is an essential process in liver regeneration. Nitric oxide (NO) and vascular endothelial growth factor (VEGF) are the main regulators of normal and pathological angiogenesis. This study aimed to determine the roles of NO derived from endothelial nitric oxide synthase (eNOS) and VEGF in sinusoidal endothelial cell (SEC) proliferation during liver regeneration., Methods: Sprague-Dawley rats underwent a 70% partial hepatectomy (PHx), and were euthanized 0, 24, 48, 72, or 168 h later. Liver regeneration and SEC proliferation were evaluated. The protein expression of VEGF and eNOS was examined by a Western blot analysis. The rats were also treated with the NO synthase inhibitor N (G)-nitro-L-arginine-methyl ester (L-NAME) to examine its effects on liver regeneration and SEC proliferation., Results: The proliferating cell nuclear antigen (PCNA) labeling index of hepatocytes was significantly increased at 24 h after PHx. The eNOS protein expression and NO production were significantly increased from 72 to 168 h. The expression of VEGF protein was significantly increased at 72 h. L-NAME significantly inhibited the increases in the liver mass and decreased the PCNA labeling index of hepatocytes at 24 h. L-NAME also inhibited the induction of VEGF protein at 72 h., Conclusions: Endothelial NOS and VEGF coordinately regulate SEC proliferation during liver regeneration. Sinusoidal endothelial cell proliferation is necessary and is an important step in liver regeneration.

Protein-bound polysaccharide-K (PSK) is a biological response modifier that possesses antitumor effects against various tumors. Although an inflammatory response has been considered to play an important role in the development of colorectal cancer, the anti-inflammatory effect of PSK has yet to be elucidated. An inflammatory bowel disease (IBD)-induced colorectal tumor model with 1.2-dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS) was used to examine the effects of PSK on tumor suppression and survival. Although 90% of the mice that were not treated with PSK developed colitic tumors, oral administration of PSK suppressed tumor formation by less than 30%. Although deaths associated with DSS-induced melena were observed, PSK significantly reduced mortality. In conclusion, the present study showed that PSK not only suppressed colorectal tumor formation in the DMH+DSS-induced IBD model, but also improved the survival rate, indicating that anti-inflammatory activity is one of the mechanisms for the antitumor effects of PSK.

Aim:   Liver cirrhosis clinically shows thrombocytopenia and hypersplenism. Although splenectomy is performed to achieve higher platelet count and better hemostasis, the effect of splenectomy for liver cirrhosis remains unclear. The aim of the present study that was focused on serotonin was to investigate the relationship between splenectomy and liver regeneration in rats with secondary biliary cirrhosis., Methods:   Liver cirrhosis was induced in Sprague-Dawley rats by bile duct ligation (BDL). In addition, splenectomy and administration of ketanserin, which selectively antagonizes 5-HT2A and 2B serotonin receptors, were performed. Three weeks after the interventions, whole blood, plasma, serum, and liver specimens were obtained for the following studies: peripheral platelet counts, hemodynamics of serotonin, histopathological examination, immunostaining, and quantification of mRNA expression., Results:   Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters: hepatocyte ratio to the entire liver area, Ki67-positive hepatocyte count, and expression of phosphorylated extracellular signal-regulated kinases. This enhancement of liver regeneration was negated by ketanserin., Conclusion:   Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions., (© 2011 The Japan Society of Hepatology.)

The introduction of monoclonal antibodies into the treatment protocols for metastatic colorectal cancer(mCRC)has significantly improved outcomes. There are some patients with mCRC, initially judged unresectable, who become resectable after chemotherapy. For patients with isolated liver metastases, surgical resection is recommended when feasible. We experienced a case in which an initially unresectable mCRC liver metastases converted into a resectable one after cetuximab monotherapy as third-line treatment. The sample from hepatectomy was a pathologically complete response; no remnants were detected. The management of liver metastases contributes to improvements in the clinical setting. For conducting a multimodal treatment of mCRC, the participation of various specialists such as medical oncologists, colorectal/hepaticsurgeons and diagnostic/therapeutic radiologists is indispensable. Furthermore, it is necessary to construct an evidence-based consensus on potentially resectable CRC liver metastases in each hospital.

Purpose: To evaluate the trends in the treatment outcomes for patients with colorectal cancer in Japan., Methods: We performed a retrospective analysis of patients undergoing surgery for primary colorectal cancer during a 16-year period (Group A [1992-2000, n = 258]; Group B [2001-2008, n = 258]) at Fukuoka City Hospital. Because no significant differences were found in the survival rates in stage 0, I, II, and III patients between the two groups, we concentrated on examining stage IV patients., Results: The 3-year survival rate for stage IV patients in Group B (n = 26) was significantly higher than that in Group A (n = 31) (34.9% vs 3.9%, P < 0.05). The rate of curative resection for advanced liver metastases in Group B patients was also significantly higher than that of Group A patients (50.0% vs 13.3%, P < 0.05). As a result, the 2-year survival rate for the disease-free patients in Group B was significantly higher than that for the non-disease-free patients in Group B (46.0% vs 21.0%, P < 0.05). Group B had a greater proportion of patients receiving l-leucovorin/5-fluorouracil than Group A (8 patients vs none, P < 0.05)., Conclusions: Recent advances in surgical innovations and the utilization of new chemotherapeutic agents may have led to significant improvements in the treatment outcomes for advanced colorectal cancer in Japan.

The training in the surgical practice is of paramount importance to prepare the residents in performing surgical procedures on human subject and to provide exercise on new techniques for experienced surgeons. Usually, these trainings are carried out on live animals or in virtual environments and dry boxes; the complexity of the exercises is identical in both of the case, but the pressure in operating with a living subject could change the attitude and the movements of the trainee. Until now, it has not been possible to analyze this stress in details together in the surgical animal training and dry boxes. In this work we propose an innovative portable system that can measure two physiological parameters, the heartbeat and the surface electromyography, during a session of training in both of the environment. The preliminary results, for one subject, show a bigger average power in the shoulder muscles during the living operation together with a higher but stable heartbeat rate.

Background: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined., Methods: Sixty-four subjects with suspected hen's egg allergy, cow's milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis., Results: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA., Conclusions: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed., (Copyright © 2011 S. Karger AG, Basel.)

Single port access (SPA) surgery is a laparoscopic procedure using only one transumbilical-placed port. Natural orifice transluminal endoscopic surgery (NOTES) offers the possibility of surgery without visible scars. To address the access and stability problems in SPA and NOTES, we developed a device called rigid-flexible outer sheath. This sheath can be switched between flexible and rigid modes by a novel pneumatic shapelocking mechanism, and it has a double curvature structure that enables it to flex in four directions at the distal end and three directions on the rigid-flexible shaft. The insertion part of the prototype is 300 mm long with a 20 mm outer diameter, and the part is equipped with four working channels. In vivo experiments using a swine show that the outer sheath has high potential for solving access and stability problems. We expect that the outer sheath will be useful for SPA and NOTES.

Although the incidence of bleeding from gastric varices is relatively low (10%-36%), the bleeding is massive once it has occurred and it increases the patient's mortality. The management of esophageal variceal bleeding is highly differentiated with several effective treatments available. In contrast, bleeding from gastric varices continues to be a therapeutic challenge. In the last decade, there have been increasing reports regarding the management of gastric varices. In this article we review recent progress in the management of gastric varices and discuss further expected studies., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Recently, robotics systems are focused to assist in Single Port Endoscopic Surgery (SPS). However, the existing system required a manual operation of vision and viewpoint, hindering the surgical task. We proposed a surgical endoscopic robot for SPS with dynamic vision control, the endoscopic view being manipulated by a master controller. The prototype robot consists of a manipulator for vision control, and dual tool tissue manipulators (gripping: 5DOFs, cautery: 3DOFs) can be attached at the tip of sheath manipulator. In particular, this paper focuses on an in vivo experiment. We showed that vision control in the stomach and a cautery task by a cautery tool could be effectively achieved.

Purpose: To elucidate the relationship between the anatomic position of the inferior alveolar nerve (IAN) at the mandibular second molar and the occurrence of neurosensory disturbances of the IAN after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Also, the present study evaluated the difference in anatomic position of the IAN between patients with and without mandibular prognathism., Patients and Methods: Computed tomography images were taken of 28 patients with mandibular prognathism and 30 without prognathism. On these scans, the IANs from the mandibular second molar region to the mandibular foramen in the mandibular ramus were identified. The present study was designed as a cross-sectional study. The distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar regions was measured on the computed tomography images. Also, the linear distance between the superior aspect of the IAN canal and the alveolar crest in these regions was calculated. In addition, we investigated the presence or absence of contact between the IAN canal and the inner buccal cortical margin of the mandible from the mandibular second molar to the mandibular foramen in the mandibular ramus. Next, we examined whether neurosensory disturbances occurring after SSRO were related to the position of the IAN at the mandibular second molar., Results: A significant difference was found in the occurrence of neurosensory disturbances of the IAN after SSRO between men and women (χ(2) test, P < .05). For the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar region, a significant difference was found between groups with and without neurosensory disturbances (Student's t test, P < .01). The shorter the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin, the more frequent the occurrence of neurosensory disturbances of the IAN., Conclusions: The present results have demonstrated that gender and the anatomic position of the IAN canal at the mandibular second molar are significantly related to the occurrence of neurosensory disturbances of the IAN after SSRO. Therefore, surgeons should clearly inform patients of the increased possibility of neurosensory disturbances after SSRO when the patients are female and are found to have a shorter distance from the buccal aspect of the IAN canal to the outer buccal cortical margin., (Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Robotic end-effectors for single port endoscopic surgery (SPS) require a manual change of vision field that slows surgery and increases the degrees of freedom (DOFs) of the manipulator., Methods: A new surgical prototype robot has dynamic vision field control and a master controller to manipulate the endoscopic view. It uses positioning (4 DOF) and sheath (2 DOF) manipulators for vision field control, and dual tool tissue manipulators (gripping, 5 DOF; cautery, 3 DOF)., Results: The robot is feasible in vitro. 'Cut and vision field control' (using tool manipulators) was suitable for precise cutting tasks in risky areas; 'cut by vision field control' (using the vision field control manipulator) was effective for rapid macro cutting of tissues. A resection was performed using a combination of both methods., Conclusions: The novel robotic system is feasible, but further studies are needed to address its performance in vivo., (Copyright © 2010 John Wiley & Sons, Ltd.)

Purpose: Pediatric surgeons require highly advanced skills when performing endoscopic surgery, but their experience with such cases tend to be limited in comparison to general surgeons. The aim of this study was to evaluate the effectiveness of basic endoscopic surgery training for less-experienced young pediatric surgeons and then compare their skills with those of general surgeons., Methods: The surgeons (n = 477) subjected to this study underwent a 2-day endoscopic skill training program, consisting of lectures, box training, VR simulator training, tissue training, and live tissue training. The trainees were divided into two groups: P (pediatric surgeons, n = 33) and G (general surgeons, n = 444). The trainees were required to make a continuous suture along a circle measuring 2.5 cm in diameter and the findings were evaluated both before and after training. A statistical analysis was conducted using the unpaired t test., Results: The number of experienced cases totaled 20.8 ± 23.9 in P and 60.6 ± 80.5 in G (p < 0.001). The number of completed sutures before training was 1.4 ± 1.1 in P and 1.9 ± 1.5 in G (p < 0.05). The number of completed sutures after training was 4.1 ± 1.3 in P and 3.9 ± 1.9 in G (p > 0.05). The economy and speed of the forceps improved, however, the number of errors increased., Conclusion: Less-experienced pediatric surgeons improved their surgical skill and ability until reaching almost the same level as that observed in more experienced general surgeons during training, however, the number of errors after training increased in comparison to before training. As a result, this program needs to be modified to reduce the number of errors while enabling pediatric surgeons to master the safe and precise surgical techniques needed in this field.

Natural orifice translumenal endoscopic surgery (NOTES) is a sophisticated form of endoscopic surgery whose use has recently spread rapidly around the world. Although hundreds of reports of animal studies and clinical cases about NOTES have been published since 2004, NOTES is still in the experimental phase. The formation of an iatrogenic incision in the lumenal wall of intraperitoneal organs is a major disadvantage of NOTES. No reliable technique for complete closure has yet been established, and this problem must be resolved before NOTES can be adopted as a routine clinical practice. Several devices for the closure of lumenal incisions in the stomach or colorectum have been developed, and their safety and usefulness have been examined in animal studies and clinical cases. Kyushu University has been involved in furthering the adoption of NOTES as a routine clinical practice, and the Kyushu University Training Center for Minimally Invasive Surgery holds training sessions on endoscopic surgical techniques for surgeons from all over Japan. Studies to develop a navigation system and robotic technology for use with NOTES are also in progress at Kyushu University. The further development of endoscopy-related technologies and equipment, such as robotic technology, is therefore essential to allow the safe, widespread adoption of pure NOTES.

Purpose: The outcomes of surgery for portal hypertensive patients at a single community hospital in the last two decades were retrospectively examined., Methods: From June 1989 to March 2008, 13 of 848 (1.5%) portal hypertensive patients admitted and treated at the community hospital underwent surgery. The types of surgery performed were a distal splenorenal shunt for 2 patients, gastric devascularization and splenectomy for 8, laparoscopic gastric devascularization and splenectomy for 1, distal gastrectomy for 1, and splenectomy alone for 1. This study reviewed the postoperative records of the endoscopic findings and additional treatments, and the perioperative records., Results: No patient had bleeding from esophagogastric varices during the 75-month mean follow-up period after surgery. Five patients had one or two series of endoscopic treatment for recurrent likely-to-bleed esophageal varices. One patient needed interventional radiology for recurrent gastric varices. No patients died due to upper gastrointestinal bleeding. The survival rates were 87.5% after 5 years and 46.9% after 10 years., Conclusions: Surgery for portal hypertensive patients performed at a single community hospital is still safe and effective, and has been adequately incorporated into the late treatment strategy for portal hypertensive patients.

Background: Small intestinal variceal bleeding is an unusual cause of gastrointestinal hemorrhaging of portal hypertensive patients, but once it occurs it may lead to life-threatening bleeding because this problem is difficult to diagnose and treat. This study investigated the efficacy of balloon occluded retrograde transvenous obliteration (B-RTO) to treat small intestinal variceal bleeding., Methods: From 2003 to 2007, 6 patients with small variceal bleeding were treated by B-RTO. The characteristics of the patients, B-RTO procedures, prognosis, and occurrence of risky esophageal and gastric varices were evaluated according to their medical records., Results: Three-dimensional (3-D) angiography by MD-CT was useful for the diagnosis of small intestinal varices and the draining vessels. In all cases, variceal bleeding was controlled by B-RTO treatment, although rebleeding was recognized in one patient after 30 months (16.6%). All patients were alive throughout the follow-up except 1 patient who died of liver failure (6-44 months). Risky esophageal varices and gastric varices occurred in 2 patients (33.3%) after B-RTO. However, no variceal bleeding occurred., Conclusion: B-RTO was found to be an effective treatment modality which provided good initial hemostasis, thereby eradicating ectopic small intestinal varices., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: The aim of this study was to report on the early experiences using a real-time 3-dimensional (3D) virtual reality navigation system with open MRI for breast-conserving surgery., Study Design: We developed a real-time 3D virtual reality navigation system with open MRI, and evaluated the mismatch between the navigation system and real distance using a 3D phantom. Two patients with nonpalpable MRI-detected breast tumors underwent breast-conserving surgery under the guidance of the navigation system. An initial MRI for the breast tumor using skin-affixed markers was performed immediately before excision. A percutaneous intramammary dye marker was applied to delineate an excision line, and the computer software "3D Slicer" generated a real-time 3D virtual reality model of the tumor and the puncture needle in the breast. Excision of the tumor was performed in the usual manner along the excision line indicated with the dye. The resected specimens were carefully examined histopathologically., Results: The mean mismatch between the navigation system and real distance was 2.01 +/- 0.32 mm when evaluated with the 3D phantom. Under guidance by the navigation system, a percutaneous intramammary dye marker was applied without any difficulty. Fiducial registration errors were 3.00 mm for patient no. 1, and 4.07 mm for patient no. 2. Histopathological examinations of the resected specimens of the 2 patients showed noninvasive ductal carcinoma in situ. The surgical margins were free of carcinoma cells., Conclusions: Real-time 3D virtual reality navigation system with open MRI is feasible for safe and accurate excision of nonpalpable MRI-detected breast tumors. Long-term outcomes of this technique should be evaluated further., (Copyright (c) 2010 American College of Surgeons. All rights reserved.)

Background: This study aimed to evaluate whether laparoscopic splenectomy (Lap-Sp) contributes to the completion and curability of combined peginterferon and ribavirin (peg-IFN + RIB) therapy for cirrhotic patients with pancytopenia due to hypersplenism., Methods: From December 2004 to September 2007, 21 patients underwent Lap-Sp before treatment with peg-IFN + RIB. All the patients were Child-Pugh class A or B with a mean platelet count of 5.7 x 10(4)/mm(3) and a mean leukocyte count of 2,830/mm(3). The hepatitis C virus (HCV) genotype was 1b for 18 patients and 2b for 3 patients. Of the 21 patients, 17 had a viral load exceeding 100 KIU/ml, and 4 had a load of less than 100 KIU/ml., Results: All the patients underwent Lap-Sp without severe complications. The average hospital stay was 12.7 days (range, 6-23 days). Platelet counts increased from a mean of 5.7 +/- 2.2 x 10(4)/mm(3) preoperatively to 19.6 +/- 7.6 x 10(4)/mm(3) postoperatively and remained above 7.0 x 10(4)/mm(3) during the subsequent peg-IFN + RIB therapy. The full course of therapy was completed for nine patients, with five obtaining a sustained virologic response and one obtaining a biologic response. The five patients who obtained a sustained virologic response had either HCV type 2b or 1b with a low viral load (<100 KIU). At this writing, treatment is ongoing for the remaining 12 patients., Conclusions: Laparoscopic splenectomy allows patients with HCV cirrhosis and hypersplenism to receive full-dose peg-IFN + RIB therapy. Patients with HCV, genotype 2 or 1b and a low viral load, and hypersplenism may be good candidates for Lap-Sp.

Background and Aims: To evaluate and compare laparoscopic splenectomy and partial splenic embolization as supportive intervention for cirrhotic patients with hypersplenism to overcome peripheral cytopenia before the initiation of and during interferon therapy or anticancer therapy for hepatocellular carcinoma., Methods: Between December 2000 and April 2008, 43 Japanese cirrhotic patients with hypersplenism underwent either laparoscopic splenectomy or partial splenic embolization as a supportive intervention to facilitate the initiation and completion of either interferon therapy or anticancer therapy for hepatocellular carcinoma. We reviewed the peri- and post-intervention outcomes and details of the subsequent planned main therapies. For interferon therapy, the rate of completion, the rate of treatment cessation and virological responses were evaluated. Anti-cancer therapies for hepatocellular carcinoma included liver resection, ablation therapy, intra-arterial chemotherapy, and transarterial chemoembolization., Results: All patients tolerated the operations well with no significant complications. The platelet count was significantly higher in the laparoscopic splenectomy group than in the partial splenic embolization group at 1 and 2 weeks after the intervention. Interferon therapy was stopped in two patients in the partial splenic embolization group due to recurrent thrombocytopenia whereas all patients in the laparoscopic splenectomy group completed interferon therapy. The planned anticancer therapies were performed in all patients, and were completed in all patients without any problems or major complications., Conclusion: Laparoscopic splenectomy may be superior to partial splenic embolization as a supportive intervention for cirrhotic patients with hypersplenism. Future prospective, randomized controlled patient studies are required to confirm these findings.

Background/aims: Recently, partial splenic arterial embolization (PSE) has become a supportive intervention for cirrhotic patients with hypersplenism in the administration of interferon therapy. However, relapsed thrombocytopenia is often observed in patients following PSE. This study aimed to report the clinical efficiency of laparoscopic splenectomy as a salvage treatment for relapsed thrombocytopenia following PSE., Methods: From 2005 to 2009, 6 patients with prior PSE treatment underwent laparoscopic splenectomy. We reviewed the surgical method of laparoscopic splenectomy and the peri- and postoperative outcomes., Results: Laparoscopic splenectomy effectively provided sufficient increases in patient platelet counts. In all patients, laparoscopic splenectomy was performed safely with no significant complications despite PSE-associated dense adhesion to the diaphragm and/or retroperitoneal attachments., Conclusion: Laparoscopic splenectomy provides a sufficient increase in patient platelet counts in relapsed thrombocytopenia following PSE. Therefore, laparoscopic splenectomy appears to be a superior supportive therapy for the treatment of thrombocytopenia in cirrhotic patients., (Copyright © 2010 S. Karger AG, Basel.)

Background: The diagnosis of food allergy (FA) is usually based on oral food challenge tests (OFC). However, OFCs occasionally induce severe adverse reactions. CD203c expression on basophils is emerging as a potential diagnostic index. We evaluated whether CD203c expression on basophils would be a useful marker of OFC-associated symptoms in hen's egg and cow's milk allergies in children., Methods: Seventy-one patients who had been diagnosed with FA based on OFCs or a convincing history of FA symptoms in the Department of Pediatrics, Sagamihara National Hospital, were recruited. CD203c expression was assessed after stimulation with antigens (egg white, ovomucoid, milk or casein) using allergenicity kits. The CD203c stimulation index (SI = the allergen-induced CD203c expression level divided by the baseline expression level) and the threshold of CD203c expression (the minimum concentration of antigen to induce CD203c SI >or=2) were analyzed in association with tolerance acquisition., Results: For the CD203c SI, the areas under the receiver-operating characteristic curve were 0.72 for egg white, 0.82 for ovomucoid, 0.84 for milk and 0.67 for casein. The positive predictive value for the threshold of CD203c expression was 94.7% for egg white, 100% for ovomucoid, 85.7% for milk and 75.0% for casein., Conclusions: Assessment of food antigen-induced CD203c expression on basophils is useful to determine if children will outgrow FA as well as in decision making regarding whether or not to perform OFCs., ((c) 2010 S. Karger AG, Basel.)

Recently, a robotic system was developed to assist Single Port Endoscopic Surgery (SPS). However, the existing system required a manual change of vision field, hindering the surgical task and increasing the degrees of freedom (DOFs) of the manipulator. We proposed a surgical robot for SPS with dynamic vision field control, the endoscope view being manipulated by a master controller. The prototype robot consisted of a positioning and sheath manipulator (6 DOF) for vision field control, and dual tool tissue manipulators (gripping: 5DOF, cautery: 3DOF). Feasibility of the robot was demonstrated in vitro. The "cut and vision field control" (using tool manipulators) is suitable for precise cutting tasks in risky areas while a "cut by vision field control" (using a vision field control manipulator) is effective for rapid macro cutting of tissues. A resection task was accomplished using a combination of both methods.

Objective: The aim of this study was to determine the role of antithrombin III (AT-III) in portal vein thrombosis (PVT) after splenectomy in cirrhotic patients., Summary Background Data: There is no standard treatment for PVT after splenectomy in liver cirrhosis., Methods: A total of 50 consecutive cirrhotic patients who underwent laparoscopic splenectomy for hypersplenism were enrolled into this study. From January 2005 to December 2005, 25 cirrhotic patients received no prophylactic anticoagulation therapy after the operation (AT-III [-] group). From January 2006 to July 2006, 25 cirrhotic patients received prophylactic administration of AT-III concentrates (1500 U/d) on postoperative day (POD) 1, 2, and 3 (AT-III [+] group)., Results: In AT-III (-) group, 9 (36.0%) patients developed PVT up to POD 7, and risk factors for PVT were identified as: low platelet counts, low AT-III activity, and increased spleen weight. Although there were no significant differences in the clinical characteristics, including the above risk factors, between the 2 groups, only 1 (4.0%) patient developed PVT on POD 30 in AT-III (+) group, and the incidence of PVT was significantly lower than in AT-III (-) group (P = 0.01). In AT-III (-) group, AT-III activity was significantly decreased from POD 1 to POD 7, as compared with the preoperative level, whereas AT-III concentrates prevented the postoperative decrease in AT-III activity., Conclusions: These results demonstrate that low AT-III activity and further decreases in this activity are associated with PVT after splenectomy in cirrhotic patients, and that treatment with AT-III concentrates is likely to prevent the development of PVT in these patients.

A 30-year-old carpenter suffered accidental piercing of his jaw by a 3-inch nail from a nail gun. No neurological deficits were found on admission. Computed tomography showed that the tip of the nail had reached the foramen lacerum. Cerebral angiography revealed severe stenosis at the C(4) portion of the left internal carotid artery (ICA) and marked decrease in the flow of the distal ICA. He had developed right hemiparesis and sensory aphasia by the following morning. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance imaging showed a focal hyperintense signal in the left central region indicating cerebral infarction. Repeat angiography demonstrated that the antegrade blood flow from the occluded point on the admission day had partially resumed, and endovascular trapping of the ICA was successfully carried out. The nail was then removed safely without problematic bleeding. The patient suffered no additional deficit, and his sensory aphasia and right hemiparesis gradually improved. The fluctuating blood flow through the unstable stenosis of the ICA related to nail movement possibly caused the delayed cerebral infarction. To avoid the occurrence of such events, rapid treatment after necessary investigations is recommended in patients with craniofacial penetrating injuries that affect the ICA.

Background: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear., Objective: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA)., Methods: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs., Results: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively., Conclusion: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.

Aim: This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension., Methods: Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child-Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation., Results: The prevalence of PHG was significantly correlated with the severity of liver disease using the Child-Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child-Pugh score showed a significant improvement (6.8 +/- 1.4 to 6.2 +/- 1.2) at 3 months after laparoscopic splenectomy (P < 0.0001)., Conclusions: PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.

This study was intended to investigate the effect of wearing a wetsuit (WS) on physical performance capacity, which are maximal oxygen uptake (V O(2)max) and maximal mechanical power output (POmax), and to demonstrate whether wearing a WS affected the relationship between maximal 400m swim performance (V400) and V O(2)max, and between sprint swim performance (Vsprint) and V O(2)max. Twelve triathletes participated in this study. V O(2)max was determined during the continuous progressive swimming test. The mean velocity over maximal 400m swim was defined as V400. Active drag (AD), Vsprint and POmax were measured by a specific method called "perturbation method". Compared with wearing a swimsuit (SS), V400 was improved without enhancing V O(2)max and Vsprint was also improved without enhancing POmax and AD by wearing a WS. Significant correlations were found between V400 and V O(2)max and between Vsprint and POmax in the both suit conditions, but a higher correlation was found in the WS condition than in the SS condition. These results suggested that improved swim performance from wearing a WS was attributable only to improvement in technical factors, such as propulsion efficiency. In conclusion, during swimming with a WS, performance gain was not associated with physiological factors but with propulsion efficiency related to a gain in buoyancy and to drag reduction. However, when wearing a WS, V400 and Vsprint more reflected the values of V O(2)max and POmax, respectively.

This study was designed to determine whether lipocalin type-prostaglandin D synthase (l-pgds) deficiency contributes to atherogenesis using gene knockout (KO) mice. A high-fat diet was given to 8-week-old C57BL/6 (wild type; WT), l-pgds KO (LKO), apolipoprotein E (apo E) KO (AKO) and l-pgds/apo E double KO (DKO) mice. The l-pgds deficient mice showed significantly increased body weight, which was accompanied by increased size of subcutaneous and visceral fat tissues. Fat deposition in the aortic wall induced by the high-fat diet was significantly increased in LKO mice compared with WT mice, although there was no significant difference between AKO and DKO mice. In LKO mice, atherosclerotic plaque in the aortic root was also increased and, furthermore, macrophage cellularity and the expression of pro-inflammatory cytokines such as interleukin-1beta and monocyte chemoattractant protein-1 were significant increased. In conclusion, l-pgds deficiency induces obesity and facilitates atherosclerosis, probably through the regulation of inflammatory responses.

Background/purpose: The aims of this study were to standardize the techniques of laparoscopic splenectomy (LS) to improve safety in liver cirrhosis patients with portal hypertension., Methods: From 1993 to 2008, 265 cirrhotic patients underwent LS. Child-Pugh class was A in 112 patients, B in 124, and C in 29. Since January 2005, we have adopted the standardized LS including the following three points: hand-assisted laparoscopic surgery (HALS) should be performed in patients with splenomegaly (> or =1,000 mL), perisplenic collateral vessels, or Child-Pugh score 9 or more; complete division and sufficient elevation of the upper pole of the spleen should be performed before the splenic hilar division; and when surgeons feel the division of the upper pole of the spleen is too difficult, conversion to HALS should be performed., Results: There were no deaths related to LS in this study. After the standardization, conversion to open surgery significantly reduced from 11 (10.3%) of 106 to 3 (1.9%) of 159 patients (P < 0.05). The average operation time and blood loss significantly reduced from 259 to 234 min (P < 0.01) and from 506 to 171 g (P < 0.01), respectively., Conclusions: With the technical standardization, LS becomes a feasible and safe approach in the setting of liver cirrhosis and portal hypertension.

Purpose: We investigated the effects of thrombopoietin (TPO) on platelet counts and liver regeneration after partial hepatectomy in rats., Methods: We performed 70% partial hepatectomy on 60 rats given either TPO or a vehicle (controls). The rats were killed 6 h, 24 h, 72 h, or 168 h after the procedure, and we examined the platelet counts, weight of the regenerated liver, hepatocyte proliferation by bromodeoxyuridine (BrdU) labeling index, and expression of hepatocyte growth factor (HGF) mRNA by reverse transcription-polymerase chain reaction., Results: In the controls, the platelet counts were significantly lower than the basal levels, by about 20%, at 6, 24, and 72 h; then recovered to the basal level at 168 h. Conversely, in the TPO-treated rats, the platelet counts increased significantly by 17%, 35%, and 60%, at 24, 72, and 168 h, respectively. The regenerated liver regained 80% of the pre-hepatectomy weight by 72 h in the controls, whereas reconstitution of the liver was accomplished by 72 h in the TPO-treated rats. Thrombopoietin significantly enhanced the BrdU labeling index of hepatocytes and expression of HGF mRNA 24 h post hepatectomy in TPO-treated rats versus controls., Conclusion: Thrombopoietin increased platelet counts; thereby accelerating liver regeneration after partial hepatectomy with enhanced induction of HGF.

Portal hypertensive (PHT) gastric mucosa increases susceptibility to injury and delayed mucosal healing. It is possible that nitration of ERK by peroxynitrite might alter MAPK (ERK) signaling in PHT gastric mucosa, leading to delayed mucosal healing, since excessive nitric oxide production is implicated in PHT gastric mucosa and MAPK (ERK) signaling induces cell proliferation and leads to gastric mucosal healing in response to injury. Portal hypertension was produced by staged portal vein ligation, and sham-operation (SO) rats served as controls. Lipid peroxide (LPO) and nitrotyrosine increased significantly in PHT gastric mucosa compared with SO rats. ERK activation was impaired in PHT gastric mucosa in response to ethanol injury, whereas no significant difference in the phosphorylation of MEK, an upstream molecule of ERK, was seen between the two groups. The nitration of ERK by peroxynitrite, as detected by the coimmunoprecipitation of ERK and nitrotyrosine, was significantly enhanced in PHT gastric mucosa. Administration of rebamipide, a gastroprotective drug that acts as an oxygen-derived free radical scavenger, significantly decreased LPO and nitrotyrosine as well as the nitration of ERK by peroxynitrite in PHT gastric mucosa, therefore normalizing ERK activation and restoring the gastric mucosal healing response to ethanol injury. Enhanced nitration of ERK by peroxynitrite is involved in the impaired MAPK (ERK) signaling in PHT gastric mucosa. These findings demonstrate a new molecular mechanism in which PHT gastric mucosa is predisposed to injury and impaired healing.

Background and Aim: Balloon-occluded retrograde transvenous obliteration (B-RTO) is a new alternative treatment for gastric varices (GVx), but the long-term efficacy is not known. We investigated the long-term effects of B-RTO on rebleeding, prevention of first bleeding, mortality and occurrence of risky esophageal varices (EVx)., Methods: B-RTO was performed in 68 cirrhotic patients with GVx. Twenty patients had recent bleeding, transiently treated by endoscopic Histoacryl injection or balloon tamponade. Forty-eight patients had varices likely to bleed, but no bleeding. After B-RTO, the recurrent bleeding, occurrence of EVx and mortality over the long-term were evaluated., Results: B-RTO was successfully performed in 63 of 68 patients (92.6%). Varices eradication was confirmed by endoscopy in 61 of 63 patients (96.6%). During follow up, GVx bleeding occurred in two patients (3.2%). The 8-year cumulative rebleeding rates of patients with bleeding and risky GVx were 14% and 0%, respectively. Risky EVx occurred in 10 patients (17%) and the cumulative occurrence rate was 22% in 8 years. The cumulative occurrence rate of risky EVx was higher in GVx with EVx (GOV2-GVx) compared to GVx without EVx (IGV1, P < 0.05). No ectopic variceal bleeding occurred. No patients died from variceal bleeding. Hepatocellular carcinoma was the only significant prognostic factor (P < 0.05)., Conclusion: B-RTO is beneficial over the long-term, despite worsening EVx in some patients, because of excellent treatment efficacy and improved mortality. We believe that B-RTO can become a first-choice radical treatment following hemostasis for gastric variceal bleeding and prophylactic treatment for risky GVx.

Background and Aim: We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes., Methods: A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform., Results: Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child-Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child-Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child-Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance., Conclusions: Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.

Background: Hepatic resection for hepatocellular carcinoma (HCC) patients with liver cirrhosis and severe hypersplenic thrombocytopenia is risky and controversial., Methods: From 1989 to 2005, 341 patients underwent hepatic resection for HCC in our hospital. Of these, 15 patients were concomitant with severe thrombocytopenia (platelet count,

Background/aims: The factors influencing the development of small intestinal obstruction following gastrectomy for early gastric cancer are controversial., Methodology: Univariate and multivariate analyses were carried out using data from 136 patients with early gastric cancer who underwent gastrectomy. The mean follow-up interval was 5 years and 11 months., Results: Of these 136 patients, 15(11.0%) presented mechanical obstruction in the small intestine postoperatively. Re-operation for repair of the related ileus was required in 8 patients, 4 of whom had been treated with total gastrectomy, 7 with resection of the greater omentum, and 3 with concomitant resection of other organs. Development of an obstruction was not related to wide resectional procedures such as extended lymph node dissection or combined resection of other organs, but was significantly correlated with total gastrectomy and resection of the greater omentum (p < 0.05). In multivariate logistic regression analysis, total gastrectomy proved to be a significant risk factor related to the development of small intestinal obstruction., Conclusions: In patients with early gastric cancer, total gastrectomy should not be attempted to prevent postoperative ileus and to ensure a fairly sustained quality of life.

Gastrointestinal bleeding (GIB) is a serious gastroenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO).

Object: Prevalence of food allergy is the most frequent during infancy, and it is gradually decreasing with age. We can not distinguish patients developing tolerance from those with persistent food allergy, therefore we are unable to advice patients accelerating the development of tolerance. To clarify the factors developing tolerance or intolerance, we conducted the following study., Method: Patients who were diagnosed as food allergy to hen's egg, or cow's milk or wheat in infancy by the definitive history of positive food allergic reactions or food provocation tests were recruited to this study. Patients were divided into two groups; one (prolonged group, n=27) is those who needed to eliminate some of the main offending foods even at the age of 6 years old and the other (tolerized group, n=37) is those who had released all main offending foods by the age of 6 years old., Result: The factors which distinguished the prolonged group from the tolerized group were the positive clinical history of the atopic dermatitis and its prolonged clinical course, past history of anaphylactic shock, and maximum number of offending foods in the past clinical history. The specific IgE against main antigens such as egg white, cow's milk and wheat in the tolerized group was lower compared to that in the prolonged group, whereas no significant difference was found in non specific IgE value, peripheral eosinophil counts, and specific IgE against other antigens., Conclusion: We could find the clinical factors discriminating food allergy patients against three major food allergen among children developing tolerance by the age of 6 years old form those without tolerance.

Chronic portosystemic encephalopathy (CPSE) resulting from portosystemic shunts (PSS) is a devastating clinical problem. When CPSE is refractory to medical treatment, occlusion of the PSS should be considered. We report a case of CPSE due to a huge paraumbilical vein shunt that was successfully treated with laparoscopic disconnection. A 54-year-old woman diagnosed with liver cirrhosis was referred to our department for treatment of hepatic encephalopathy. She had repeatedly experienced episodes of disturbance of consciousness, and had hyperammoniemia refractory to medical treatment. Computed tomography showed a huge patent paraumbilical vein connected to the systemic circulation through the round ligament. Laparoscopic disconnection of the paraumbilical vein shunt was performed. The postoperative course was uncomplicated and there has been no recurrence of hepatic encephalopathy in the 2 years since, nor has there been a need for further medical treatment. We believe this is the first case report of CPSE treated laparoscopically, and it demonstrates that laparoscopic disconnection of PSS, especially paraumbilical vein shunts, can be a safe and effective procedure to treat CPSE.

To enhance the resectability of cancer of the pancreatic body, a new surgical technique should be developed. Of 25 patients with cancer of the pancreatic body who underwent distal pancreatectomy with curative intent, seven with cancer invasion around the celiac artery underwent stomach-preserving distal pancreatectomy with combined resection of the celiac artery. This procedure secured arterial blood supply to the whole stomach and liver via the inferior pancreaticoduodenal artery without arterial reconstruction. There was no postoperative mortality. One patient developed transient passage disturbance in the duodenum. Another one developed a minor pancreatic fistula. No patients had serious complications related to ischemia of the stomach or liver. The quality of life of the patients after surgery was well maintained, and planned adjuvant therapy was accomplished. Local recurrence was evident in only two patients. The median survival time of patients who underwent distal pancreatectomy with (n = 7) or without (n = 18) resection of the celiac artery was 19 and 25 months, respectively. The overall survival rate was not significantly different between the two groups (P = 0.5300). The present study suggests that this surgical procedure is a rational approach to locally advanced pancreatic body cancer invading around the celiac artery. In view of the feasibility of this procedure, it can also be adopted for less advanced cancer of the pancreatic body to enhance local control and survival.

We report a case of brain abscess caused by a penetrating head injury that occurred 9 years earlier. A 14-year-old girl presenting with fever, headache, and stiff neck was admitted to our hospital. She was diagnosed with aseptic meningitis and treated conservatively. Seven days after admission she became stuporous and showed left hemiparesis. Computed tomography (CT) revealed two ring-enhancing masses with perifocal edema in the right frontal lobe. We diagnosed brain abscess and performed right fronto-temporal decompressive craniectomy and stereotactic aspiration, followed by systemic antibiotic therapy. Post-surgery bone window CT revealed a well-defined, low-density foreign body passing from the left orbita to the right frontal lobe through the ethmoid sinus. We learned that the patient had been struck with a plastic chopstick in the left medial eyelid at the age of 5 years. No particular symptoms developed during the following 9 years. After the cerebral edema had diminished over the next 10 days, a second surgery was performed to remove the residual chopstick, repair the fistula at the base of the skull, and perform cranioplasty. The patient was discharged with only slight hyposmia after a 4-week course of antibiotics. This case showed that it is necessary to remove a residual foreign body and to close the dural fistula if there is a possibility of recurrent central nervous system infection. When a child presents with brain abscess, previous penetrating head injury should be considered.

Objective: We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen., Methods: We examined 99 definitive shrimp allergy cases with questionnaire., Results: Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE., Conclusion: We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.

Background: Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels., Methods: We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination., Results: Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012)., Conclusion: EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.