Histidine-Rich Glycoprotein Alleviates Liver Ischemia/Reperfusion Injury in Mice With Nonalcoholic Steatohepatitis.

Hepatic ischemia/reperfusion injury (IRI) is a major complication of liver surgery and transplantation, especially in patients with nonalcoholic steatohepatitis (NASH). The mechanism of NASH susceptibility to IRI has not been fully clarified. We investigated the role of liver-produced histidine-rich glycoprotein (HRG) in NASH IRI. A NASH mouse model was established using C57BL/6J mice fed a methionine-choline-deficient diet (MCDD) for 6 weeks. The MCDD and standard diet groups were exposed to 60 minutes of partial hepatic ischemia/reperfusion (I/R). We further evaluated the impact of HRG in this context using HRG knockdown (KD) mice. IRI increased HRG expression in the standard diet group, but not in the MCDD group after I/R. HRG expression was inversely correlated with neutrophil infiltration and the formation of neutrophil extracellular traps (NETs). HRG KD mice showed severe liver injury with neutrophil infiltration and the formation of NETs. Pretreatment with supplementary HRG protected against I/R with the inhibition of neutrophil infiltration and the formation of NETs. In vitro, hepatocytes showed that the expression of HRG was upregulated under hypoxia/reoxygenation conditions, but not in response to oleic acid-treated hepatocytes. The decrease in HRG expression in fatty hepatocytes was accompanied by decreased farnesoid X receptor and hypoxia inducible factor 2 alpha subunit expression. HRG is a hepatoprotective factor during hepatic IRI because it decreases neutrophil infiltration and the formation of NETs. The decrease in HRG is a cause of susceptibility to IRI in steatotic livers. Therefore, HRG is a new therapeutic target for minimizing liver damage in patients with NASH.

Feasibility of an AI-Based Measure of the Hand Motions of Expert and Novice Surgeons.

This study investigated whether parameters derived from hand motions of expert and novice surgeons accurately and objectively reflect laparoscopic surgical skill levels using an artificial intelligence system consisting of a three-layer chaos neural network. Sixty-seven surgeons (23 experts and 44 novices) performed a laparoscopic skill assessment task while their hand motions were recorded using a magnetic tracking sensor. Eight parameters evaluated as measures of skill in a previous study were used as inputs to the neural network. Optimization of the neural network was achieved after seven trials with a training dataset of 38 surgeons, with a correct judgment ratio of 0.99. The neural network that prospectively worked with the remaining 29 surgeons had a correct judgment rate of 79% for distinguishing between expert and novice surgeons. In conclusion, our artificial intelligence system distinguished between expert and novice surgeons among surgeons with unknown skill levels.

In vivo redox metabolic imaging of mitochondria assesses disease progression in non-alcoholic steatohepatitis.

Given the rising incidence of non-alcoholic fatty liver disease (NAFLD) in both adults and children, the development of a non-invasive diagnostic method for assessing disease progression to non-alcoholic steatohepatitis (NASH) has become an important research goal. Currently available non-invasive imaging technologies are only able to assess fat accumulation in the liver. Therefore, these methods are not suitable for a precise diagnosis of NASH. The standard diagnostic technique for NASH, liver biopsy, has several drawbacks, including the higher risk of complications that accompanies invasive procedures. Here, we demonstrated that in vivo mitochondrial redox metabolism was dramatically altered at an early stage, before histopathological changes, and NASH could be accurately diagnosed by in vivo dynamic nuclear polarization-magnetic resonance imaging, with carbamoyl-PROXYL as a molecular imaging probe. In addition, this technique was feasible for the diagnosis of NASH compared with histopathological findings from biopsies. Our data reveal a novel method for monitoring the dynamics of redox metabolic changes in NAFLD/NASH.

Integrated Endoscopic System Based on Optical Imaging and Hyperspectral Data Analysis for Colorectal Cancer Detection.

BACKGROUND/AIM: Two-dimensional hyperspectral data systems with enhanced area detection and diagnostic abilities are now available in gastrointestinal endoscopy for colorectal cancer. We evaluated a new hyperspectral system for diagnosis of colorectal cancer. PATIENTS AND METHODS: A resected-specimen spectrum observation module (stereoscopic macroscope, hyperspectral camera, and xenon lamp) was used to evaluate 21 resected colorectal cancer specimens (ex vivo experiment). A colonoscopy spectrum observation module (imaging fiberscope and hyperspectral camera) was used to perform 24 colonoscopic spectroscopy evaluations (in vivo experiment). RESULTS: An approximately 525-nm increase in spectral absorption occurred between normal mucosa and adenoma, with a tendency toward decreased absorption rates with aggravation of other tumor types. In vivo discrimination between tumorous and non-tumorous tissues showed 72.5% sensitivity and 82.1% specificity. CONCLUSION: This in vivo hyperspectral diagnostic system showed that reflectance spectra intensity may discriminate between normal and abnormal colonic mucosa.

Pancreatic fistula after laparoscopic splenectomy in patients with hypersplenism due to liver cirrhosis: effect of fibrin glue and polyglycolic acid felt on prophylaxis of postoperative complications.

BACKGROUND: This study aimed to determine the effect of fibrin glue and polyglycolic acid (PGA) felt on prevention of pancreatic fistula (PF) after laparoscopic splenectomy in patients with hypersplenism due to liver cirrhosis. METHODS: Fifty consecutive patients were enrolled in this prospective study. Twenty-three patients underwent laparoscopic splenectomy with a fibrin sheet (fibrin sheet group). The sealing ability of each treatment was evaluated by an ex vivo pressure test model. Based on the results from ex vivo experiments, 27 patients received prophylaxis using fibrin glue and PGA felt (PGA with fibrin group). The primary endpoint was the incidence of PF. RESULTS: Significantly more (5, 22%) patients developed PF in the fibrin sheet group than in the PGA with fibrin group (0%, P = .037). CONCLUSIONS: Our new application of fibrin glue and PGA felt is an effective prophylactic procedure for preventing development of PF after laparoscopic splenectomy.

Evaluation of the 10-year history of a 2-day standardized laparoscopic surgical skills training program at Kyushu University.

PURPOSE: Laparoscopic and open surgical skills differ distinctly from one another. Our institute provides laparoscopic surgical skills training for currently active surgeons throughout Japan. This study was performed to evaluate the effectiveness of our 2-day standardized laparoscopic surgical skills training program over its 10-year history. METHODS: We analyzed the data on trainee characteristics, outcomes of skills assessments at the beginning and end of the program, and self-assessment after 6 months using a questionnaire survey. RESULTS: From January 2004 to December 2013, 914 surgeons completed the 2-day training program. Peaks in postgraduate years of experience occurred at years 2, 8, and 17. Suturing and knot tying times were significantly shorter at the end than beginning of the program (p < 0.001). However, the numbers of misplaced and loose sutures, maximum misplacement distance, and number of injuries to the rubber sheet were significantly higher at the end of the program (p < 0.001). A questionnaire at 6 months post-training revealed significant improvements in the overall skills and forceps manipulation (p < 0.0001) and a significantly shorter mean operation time for laparoscopic cholecystectomy (p < 0.001). CONCLUSION: Our 2-day training program for active Japanese surgeons is thus considered to be effective; however, continued voluntary training is important and further outcomes assessments are needed.

Procedural surgical skill assessment in laparoscopic training environments.

PURPOSE: This study aimed to identify detailed differences in laparoscopic surgical processes between expert and novice surgeons in a training environment and demonstrate that surgical process modeling can be used for such detailed analysis. METHODS: Eleven expert surgeons each of whom had performed [Formula: see text] laparoscopic procedures were compared with 10 young surgeons each of whom had performed [Formula: see text] laparoscopic procedures, and five medical students. Each examinee performed a specific skill assessment task. During tasks, instrument motion was monitored using a video capture system. From the video, the corresponding workflow was recorded by labeling the surgeons' activities according to a predefined terminology. Activities represented manual work steps performed during the task, described by a combination of a verb (representing the action), a tool, and the involved structure. The results were described as the number of occurrences (times), average duration (seconds), total duration (seconds), minimal duration (seconds), maximal duration (seconds), and occupancy percentage (%). RESULTS: The terminology for describing the processes of this task included 10 actions, six tools, four structures, and three events for each hand. There were 63 combinations of different possible activities; significant differences in 12 activities were observed between the expert and novice groups (young surgeons and medical students). The expert group performed the task with fewer occurrences and shorter duration than did the novice group in the left hand. CONCLUSIONS: We identified differences in surgical process between experts and novices in laparoscopic surgical simulation. Our proposed method would be useful for education and training in laparoscopic surgery.

Novel Surgical Skill Evaluation with Reference to Two-handed Coordination.

INTRODUCTION: We evaluated the differences in instrument manipulation skills between expert laparoscopic surgeons and novices. METHODS: Six expert surgeons who had performed more than 500 laparoscopic surgeries and one skilled instructor at Kyushu University Training Center for Minimally Invasive Surgery, and 20 medical students who had experienced no laparoscopic surgery were enrolled. A new skill assessment task was designed using zippers on an unstable, mobile platform in a box trainer. The examinees were asked to close the zippers, while trying to avoid moving the platform. The path lengths of the tips of the instruments and of the platform were measured, and the performance time was also recorded. Surgical skill score was calculated from the correlation between the path lengths of the instruments and that of the platform, in addition to the performance time. RESULTS: The path lengths of the tips of both instruments and of the platform were significantly shorter in the experts than in the novices (all p < 0.05). The performance time was also significantly shorter for experts than novices (p < 0.05). The surgical skill score was significantly higher for experts than novices (p < 0.01). CONCLUSION: The differences in the instrument manipulation skills between expert laparoscopic surgeons and novices could therefore be evaluated using our surgical skill scoring system.

Clinical significance of the laparoscopic bariatric surgeries for morbid obesity: initial 30 cases at a single institution in Japan.

BACKGROUND: Bariatric surgical procedures are becoming a standard treatment for morbid obesity in many western countries and in some Asian countries. AIM: The aim of the current study was to evaluate the efficacy and safety of the initial 30 cases of bariatric surgical procedures performed for morbid obesity at a single institution in Japan. MATERIALS AND METHODS: From March 2012 until September 2014, 30 bariatric surgical procedures were performed for morbid obesity at a single medical center (Kyushu University Hospital) in Japan. RESULTS: All of the operations procedures were planned laparoscopic procedures, and none required conversion to laparotomy. There were no perioperative or postoperative mortalities. Postoperative complications occurred in 3 patients: 1 patient developed an intra-abdominal abscess, 1 patient experienced temporary food intolerance, and 1 patient developed small bowel obstruction. The excessive body weight reduction rates after surgery at 1 month, 3 months, 6 months, and 1 year post-surgery were 26.1%, 39.2%, 41.7%, and 51.2%, respectively. The mean body mass index (BMI) at the same time points were 38.3%, 36.4%, 35.5%, and 31.4%, respectively. Eighteen patients had type II diabetes mellitus (T2DM). The mean preoperative fasting blood glucose levels were 169 ± 37 mg/dL. Following surgery, the blood glucose levels at 3, 6 and 12 months were 113 ± 12, 115 ± 22, and 110 ± 19, mg/dL, respectively. The preoperative HbA1c percentage was 7.9 ± 0.5. Following surgery, the HbA1c percentages at 3, 6, and 12 months were 6.9 ± 0.5, 6.2 ± 0.9, and 5.9 ± 0.6, respectively. CONCLUSIONS: Bariatric surgical procedures are effective and safe for the treatment of morbid obesity. Our results indicate that the mechanism of improvement of diabetes and related diseases following bariatric surgical procedures is not simply as a result of calorie restriction and weight reduction.

Novel, high-definition 3-D endoscopy system with real-time compression communication system to aid diagnoses and treatment between hospitals in Thailand.

INTRODUCTION: Traditionally, laparoscopy has been based on 2-D imaging, which represents a considerable challenge. As a result, 3-D visualization technology has been proposed as a way to better facilitate laparoscopy. We compared the latest 3-D systems with high-end 2-D monitors to validate the usefulness of new systems for endoscopic diagnoses and treatment in Thailand. METHODS: We compared the abilities of our high-definition 3-D endoscopy system with real-time compression communication system with a conventional high-definition (2-D) endoscopy system by asking health-care staff to complete tasks. Participants answered questionnaires and whether procedures were easier using our system or the 2-D endoscopy system. RESULTS: Participants were significantly faster at suture insertion with our system (34.44 ± 15.91 s) than with the 2-D system (52.56 ± 37.51 s) (P < 0.01). Most surgeons thought that the 3-D system was good in terms of contrast, brightness, perception of the anteroposterior position of the needle, needle grasping, inserting the needle as planned, and needle adjustment during laparoscopic surgery. Several surgeons highlighted the usefulness of exposing and clipping the bile duct and gallbladder artery, as well as dissection from the liver bed during laparoscopic surgery. In an image-transfer experiment with RePure-L®, participants at Rajavithi Hospital could obtain reconstructed 3-D images that were non-inferior to conventional images from Chulalongkorn University Hospital (10 km away). CONCLUSION: These data suggest that our newly developed system could be of considerable benefit to the health-care system in Thailand. Transmission of moving endoscopic images from a center of excellence to a rural hospital could help in the diagnosis and treatment of various diseases.

Development of a robotic system with six-degrees-of-freedom robotic tool manipulators for single-port surgery.

BACKGROUND: Current robotic systems have limitations for single-port surgery (SPS) because the instruments are large, the arms collide and the field of vision requires manual readjustment. We have developed an SPS robotic system that manipulates the vision field. METHODS: The master-slave system included a six degrees of freedom (DOFs) tool manipulator, an easy set-up mechanism, a flexible shaft drive with sufficient DOFs and a vertical arrangement for improved vision. The robot manipulates an endoscope within the body. After assembly, the system was tested in vitro and in vivo. RESULTS: In vitro testing showed that the tool manipulators resected tissue precisely, with the range of motion required. In vivo testing indicated that an abdominal organ is accurately approached and diseased tissue removed by combined endoscopy and robotics. CONCLUSIONS: Our robotics allowed the operator to adjust the vision field intuitively. The tool manipulator approached and resected diseased tissue precisely.

Objective assessment of the suture ligature method for the laparoscopic intestinal anastomosis model using a new computerized system.

BACKGROUND: The purpose of this study was to develop a new objective assessment system for the suture ligature method employed in the laparoscopic intestinal anastomosis model. Suturing skills were evaluated objectively using this system. METHODS: This study compared 17 expert surgeons, each of whom had performed >500 laparoscopic procedures, with 36 novice surgeons, each of whom had performed <15 laparoscopic procedures. Each examinee performed a specific skill assessment task using an artificial model that mimics living tissue, which is linked with the Suture Simulator Instruction Evaluation Unit. The model used internal air pressure measurements and image processing to evaluate suturing skills. Five criteria were used to evaluate the skills of participants. RESULTS: The volumes of air pressure leak in the expert and novice groups were 21.13 ± 6.68 and 8.51 ± 8.60 kPa, respectively. The numbers of full-thickness sutures in the expert and novice groups were 2.94 ± 0.24 pairs and 2.47 ± 0.77 pairs, respectively. Suture tensions in the expert and novice groups were 60.99 ± 11.81 and 80.90 ± 16.63 %, respectively. The areas of wound-opening in the expert and novice groups were 1.76 ± 2.17 and 11.06 ± 15.37 mm(2), respectively. The performance times in the expert and novice groups were 349 ± 120 and 750 ± 269 s, respectively. Significant differences between the expert and novice groups for each criterion were observed. The acceptable range of values for each criterion except for the number of full-thickness sutures was statistically defined by the performance of the expert group. CONCLUSIONS: Our system is useful for the quantitative assessment of suturing skill in laparoscopic surgery. We believe that this system is a useful tool for training and assessment of laparoscopic surgeons.

A single port laparoscopic surgery robot with high force transmission and a large workspace.

INTRODUCTION: This study presents the design of a novel single port laparoscopic surgery robot that is actuated by plate-spring-driven mechanisms with high force transmission and a larger workspace. Many ongoing studies aim to develop robotic single port laparoscopic surgery platforms due to the potential advantages in terms of a short recovery period and fewer postoperative scars. Most of these investigations of single port access have focused on resolving the inconvenient maneuverability of manual single port laparoscopic surgery. However, drive mechanism structures are another requirement. MATERIALS AND METHODS: Most of the existing robotic platforms cannot transmit sufficient force, as many of them use wire-driven mechanisms, which are prone to mechanical deformation that also negatively affects the accuracy of the end effector. In addition, even the best-known laparoscopic surgical robot system has instruments with a limited workspace for single port laparoscopic surgery. Therefore, the purpose of this study was to propose a novel robotic single port laparoscopic surgery platform that uses plate springs to transmit higher forces during tissue handling. RESULTS AND CONCLUSION: Compared to wire- or link-driven mechanisms, the plate-spring mechanism provided surpassing force transmission, with >14 N force transmission achieved, which enables most laparoscopic surgery with single port access. In addition, the high degree of freedom structure of the proposed design permitted an expanded workspace, which might be the most competitive characteristic among the single port systems reported to date.

Intraoperative visualization of cerebral oxygenation using hyperspectral image data: a two-dimensional mapping method.

PURPOSE: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is an important technique for cerebrovascular reconstruction. Intraoperative hemodynamic imaging is needed to perform cerebrovascular reconstruction safely and effectively. Optical intrinsic signal (OIS) imaging is commonly used for assessing cerebral hemodynamics in experimental studies, because it can provide high-resolution mapping images. However, OIS is not used clinically due to algorithm, instrumentation and spectral resolution limitations. We tested the feasibility of a hyperspectral camera (HSC) for assessment of cortical hemodynamics with spectral imaging of the cerebral cortex in rats and in vivo humans. METHODS: A hyperspectral camera (HSC) was tested in a rat model of cerebral ischemia (middle cerebral artery occlusion) and during human revascularization surgery (STA-MCA anastomosis). Changes in cortical oxygen saturation were derived from spectral imaging data (400-800 nm) collected by exposing the cortex to Xenon light. Reflected light was sampled using the HSC. The system was then tested intraoperatively during superficial temporal artery to middle cerebral artery anastomosis procedures. Comparison with single-photon emission computed tomography (SPECT) imaging data was done. RESULTS: During middle cerebral artery occlusion in rats, the HSC technique showed a significant decrease in cortical oxygen saturation in the ischemic hemisphere. In clinical cases, the cortical oxygen saturation was increased after STA-MCA anastomosis, which agreed with the SPECT imaging data. CONCLUSION: Continuous collection of imaging spectroscopic data is feasible and may provide reliable quantification of the hemodynamic responses in the brain. The HSC system may be useful for monitoring intraoperative changes in cortical surface hemodynamics during revascularization procedures in humans.

Portal vein thrombosis in liver cirrhosis.

Portal vein thrombosis (PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to: (1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis; (2) describe the principal factors most frequently involved in PVT development; and (3) summarize the recent knowledge concerning diagnostic and therapeutic procedures.

Comparison of open, laparoscopic, and hand-assisted laparoscopic devascularization of the upper stomach and splenectomy for treatment of esophageal and gastric varices: a single-center experience.

INTRODUCTION: Laparoscopic devascularization of the upper stomach and splenectomy (Dev+Sp), is technically difficult in patients with portal hypertension because of enlarged collateral vessels and spleen. This report presents the efficacy and safety of hand-assisted laparoscopic (HALS) Dev+Sp. METHODS: Ten patients underwent HALS Dev+Sp as a treatment for esophagogastric varices between 2005 and 2012 (HALS group). A vessel-sealing system was used for devascularization of vessels. An autosuture device was applied to dissect the splenic hilum and the left gastric and enlarged short gastric vessels. The operative and postoperative data were compared between patients who previously underwent laparoscopic Dev+Sp (LAP group, n = 9) and conventional Dev+Sp (OP group, n = 10) between 2001 and 2008. RESULTS: The mean operative time was 328, 336, and 245 min (P < 0.05) and the mean blood loss was 1786, 981, and 250 mL (P < 0.05) in the OP, LAP, and HALS groups, respectively. Laparoscopic surgery was converted to HALS in one patient and to open surgery in three patients. There were no conversions in the HALS group. There was no significant difference in the cumulative recurrence rate and bleeding rate in the groups. CONCLUSION: HALS Dev+Sp is a feasible and effective surgery in patients with portal hypertension.

Analysis of hand motion differentiates expert and novice surgeons.

BACKGROUND: The number of operations performed by a surgeon may be an indicator of surgical skill. The hand motions made by a surgeon also reflect skill and level of expertise. We hypothesized that the hand motions of expert and novice surgeons differ significantly, regardless of whether they are familiar with specific tasks during an operation. METHODS: This study compared 11 expert surgeons, each of whom had performed >100 laparoscopic procedures, and 27 young surgeons, each of whom had performed <15 laparoscopic procedures. Each examinee performed a specific skill assessment task, in which instrument motion was monitored using magnetic tracking system. We analyzed the paths of the centers of gravity of the tips of the needle holders and the relative paths of the tips using two mathematical methods of detrended fluctuation analysis and unstable periodic orbit analysis. RESULTS: Detrended fluctuation analysis showed that the exponent in the function describing the initial scaling exponent (α1) differed significantly for experts and novices, being close to 1.0 and 1.5, respectively (P < 0.01). This indicated that the expert group had a greater long-range coherence with an intrinsic sequence and smooth continuity among a series of motions. Likewise, unstable periodic orbit analysis showed that the second period of unstable orbit was significantly longer for experts in comparison with novices (P < 0.01). This demonstrates mathematically that the hands of experts are more stable when performing laparoscopic procedures. CONCLUSIONS: Objective evaluation of hand motion during a simulated laparoscopic procedure showed a significant difference between experts and novices.

Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation.

PURPOSES: The purpose of our study was to evaluate the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients after living donor liver transplantation (LDLT). METHODS: Five patients with gastric varices (GVx) and/or liver dysfunction who were treated with B-RTO from January 2001 to December 2007 were enrolled in this study (GVx, n = 2; liver dysfunction, n = 1; both, n = 2). The eradication rate of the GVx, portal vein hemodynamics and improvement of liver function were evaluated. RESULTS: B-RTO was performed successfully, and the GVx disappeared or decreased markedly in all patients. Recurrence of GVx was not observed during the follow-up. Significantly increased portal vein inflow and improved liver function were observed in all patients. CONCLUSIONS: B-RTO may be an effective treatment for patients after LDLT to prevent bleeding from GVx or to modulate portal vein inflow that is reduced by prolonged large portosystemic shunts.

Merits of prophylactic sclerotherapy for esophageal varices concomitant unresectable hepatocellular carcinoma: prospective randomized study.

BACKGROUND: Several clinical studies of prophylactic therapy for esophageal varices have led to the conclusion that prophylactic therapy is of no value, and it is generally not accepted in the Western world. However, this is not the case in Japan. The present study evaluated the efficacy of prophylactic endoscopic injection sclerotherapy (EIS) in patients with unresectable hepatocellular carcinoma (HCC) and risky esophageal varices. PATIENTS AND METHODS: Twenty-seven patients with 'likely-to-bleed' esophageal varices concomitant with unresectable HCC were randomly allocated to two groups. Thirteen patients underwent prophylactic EIS (EIS group), whereas the remaining 14 patients were observed conservatively (control group). RESULTS: No bleeding from esophageal varices occurred in the EIS group during the entire period of this study, whereas in thecontrol group the cumulative bleeding rate was 44.8% in 6 months. Cumulative survival rates of patients in the EIS group and in the control group were 48.8% and 7.7% in 2 years, respectively. There was a statistically significant difference between the two groups in cumulative bleeding rate and survival rate (P < 0.01). CONCLUSION: This prospective study demonstrated that prophylactic EIS could prolong the survival of the patients with esophageal varices concomitant with unresectable HCC. Prophylactic EIS for patients with unresectable HCC may be, in part, justified according to the present study.