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Significance: In vivo molecular and metabolic imaging is an emerging field in biomedical research that aims to perform noninvasive detection of tissue metabolism in disease states and responses to ...

Background and aims Hepatic ischemia/reperfusion (I/R) injury is a major complication of liver surgery and transplantation, especially in non-alcoholic steatohepatitis (NASH). The mechanism of NASH susceptibility to I/R injury has not been fully clarified. We investigated the role of liver-produced histidine-rich glycoprotein (HRG) in NASH I/R injury. Approach and results A NASH mouse model was established using C57Bl/6j mice fed a methionine- and choline-deficient diet (MCD) for 6 weeks. The MCD and standard diet (SD) groups were exposed to 60 min of partial hepatic ischemia with reperfusion. We further evaluated the impact of HRG in this context using HRG knockdown (KD) mice. I/R injury increased HRG expression in the SD group but not in the MCD group after I/R. HRG expression was inversely correlated with neutrophil infiltration and neutrophil extracellular traps (NETs) formation. HRG KD mice showed severe liver injury with neutrophil infiltration and NETs formation. Pre-treatment with supplementary HRG protected against I/R with inhibition of neutrophil infiltration and NETs formation. In vitro, hepatocytes showed that the expression of HRG was upregulated under hypoxia/re-oxygenation 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 (FXR) and Hypoxia-inducible factor-2α (HIF-2α) expression. Conclusions HRG is a hepatoprotective factor during hepatic I/R injury by decreasing neutrophil infiltration and NETs formation. The decrease in HRG is a cause of susceptibility to I/R injury in steatotic livers. Therefore, HRG is a new therapeutic target for minimizing liver damage in NASH patients.

Background Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. Methods Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection. Results The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. Conclusion ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

Background The management of cardiac trauma requires rapid intervention in the emergency room, facilitated by a surgeon with prior experience to have good outcomes. Many surgeons have little experience in the requisite procedures. We report here 4 patients who suffered cardiac trauma, and all 4 patients survived with good neurologic outcomes. Case presentations Patient 1 suffered blunt cardiac trauma from a motor vehicle accident and presented in shock. Cardiac tamponade was diagnosed and a cardiac rupture repaired with staples through a median sternotomy after rapid transport to the operating room. Patient 2 suffered blunt cardiac trauma and presented in shock with cardiac tamponade. Operating room median sternotomy allowed extraction of pericardial clot with recovery of physiologic stability. Patient 3 presented with self-inflicted stab wounds to the chest and was unstable. She was brought to the operating room and thoracotomy allowed identification of a left ventricle wound which was repaired with a suture. Patient 4 presented in cardiac arrest with multiple self-inflicted stab wounds to the chest. Emergency room thoracotomy allowed repair of a right ventricle laceration with recovery of vital signs. Conclusions The management of all 4 patients was according to the principles taught in the ATOM course. Three of the 4 surgeons had no prior experience with management of cardiac trauma and credited the good outcomes to taking the ATOM course. These are uncommon injuries and formal training in their management is beneficial to patients.

According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.

Aim Idiopathic portal hypertension (IPH), extrahepatic portal obstruction (EHO), and Budd-Chiari syndrome (BCS) are characterized by aberrant portal hemodynamics of unknown etiology. The aim of this study was to explore trends in the descriptive epidemiology of these diseases through periodical nationwide surveys. Methods Nationwide epidemiologic surveys were undertaken in 1999, 2005, and 2015 using the same protocol. The survey targets were selected from all departments of gastrointestinal medicine, surgery, pediatrics, and pediatric surgery in Japan by stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of patients with IPH, EHO, and BCS during the preceding year. Results The estimated number of BCS patients increased from 280 (95% confidence interval, 200-360) in 1999 survey to 410 (300-530) in 2015 survey, whereas the number of IPH and EHO patients has remained largely unchanged during the 15 years (IPH was approximately 1000; EHO was approximately 770 in 2015 survey). The mean age at symptom onset was approximately 45 years for IPH, 30 years for EHO, and 40 years for BCS over the past 15 years. Those who described disease aggravation from the time of diagnosis accounted for approximately 10% of IPH, 15% of EHO, and 20% of BCS patients in each of the three surveys. Conclusions In Japan, the prevalence of BCS is increasing, while those of IPH and EHO appear to be stable. Clinical characteristics, including prognoses, have remained largely unchanged in the past 15 years.

RATIONALE: In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO. PATIENT CONCERNS: A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome. DIAGNOSES: He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent. INTERVENTIONS: Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min). OUTCOMES: Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient's respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased. LESSONS: TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.

This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO2) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology. Multispectral imaging also provides information about tissue oxygenation, perfusion, and potential function during surgery. Analytical algorithm has been examined, and indication of accurate map of relative hemoglobin concentration and SatO2 can be indicated with preferable resolution and frame rate. This technology is expected to provide promising biomedical information in practical use. Several studies suggested that blood flow and SatO2 are associated with gastrointestinal disorders, particularly malignant tumor conditions. The use and analysis of spectroscopic images are expected to potentially play a role in the detection and diagnosis of these diseases.

Background In laparoscopic gastrointestinal surgery, the location of the tumor is identified mainly with marking methods, such as ink tattooing and intraoperative gastrointestinal endoscopy and marking with a metal clip followed by confirmation with intraoperative x-ray fluoroscopy. Each method has disadvantages, such as complexity, instability of ink sticks, and radiation exposure. Thus, a simple and less-invasive marking method is needed. Methods We developed a wireless light-emitting marker with a miniature light-emitting diode that uses a magnetic field resonance mechanism. It emits 4 individual colors-red, blue, green, and white. We confirmed the usefulness of this marker system in ex vivo and in vivo animal experiments. Results In the ex vivo experiment in porcine intestines, use of the wireless marker was successful, as each color of emitted light was recognized from outside the intestine. In the live animal experiment, it was confirmed that the light emitted by the marker system was visible in the porcine intestinal tract during laparoscopic surgery. The light emitted by the wireless marker in the intestinal tract was confirmed with a laparoscope in a simulated animal surgery. Conclusion We have developed an innovative, radiation-free and reliable light-emitting marker system that uses a magnetic field resonance mechanism that emits four colors of light during laparoscopic surgery.

Background Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs). Methods This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU. Results Upon admission, the median age was 70 (range, 33–96) years, and RA duration was 10 (range, 0–61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission. Conclusion Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.

Background Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. Methods Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography–mass spectrometry. Results In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). Conclusion LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

Colonic endoscopic submucosal dissection (ESD) is time-consuming and bears a high risk of perforation. The aim of the present study was to compare the safety and efficacy between novel articulating devices and conventional ESD in live porcine colon models. Thirty ESDs in ten pigs were carried out at three different locations (15, 25, and 35 cm from the anus) by the conventional method (n = 15) and by the new method (n = 15). Procedure times, adverse events (perforation, bleeding), and damage to the muscular layer were recorded, and the ESD time per unit area of the specimens was calculated. The perforation rate using the conventional method was 6.7% (1/15), whereas that using the new method was 0.0%. The number of sites of muscular damage was significantly lower in the new than conventional method (6 vs. 37, respectively; P = 0.024). The mean procedure time was significantly shorter in the new than conventional method (4.6 ± 2.0 vs. 7.0 ± 4.1 min/cm2, respectively; P = 0.042). Use of the new ESD method allows for reduced adverse events and a shortened resection time.

Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices.

Background and study aims The association of tumor hypoxia and vascularization with malignant progression is recognized, and detection by measuring tissue hemoglobin (Hb) saturation and concentration has attracted attention. In this study, we designed a simple algorithm and multispectral image-processing endoscopy system to map relative Hb concentration and Hb saturation for detection of tumors in small animal viscera in vivo. Materials and methods We designed and validated an optical filter-equipped endoscope system for two-dimensional visualization of Hb concentration and saturation maps and used it in a real-time video examination. A simplified method based on spectral data capture and analysis of defuse reflection of mucosa, including image capture and data processing of the spectral features of Hb oxygenation, was developed. Results An Hb saturation calibration curve was obtained. Then, differences in oxygenation levels between normal mucosa and in vivo tumors in a small animal model were determined by using the new method and endoscope system. Conclusions A multispectral image-processing endoscopic system with a mapping frame rate comparable to that of white light imaging systems (7.5 frames/second) was developed.

Portal hypertension is affected by spleen blood flow. An enlarged spleen often increases portal blood flow and pressure. Therefore, splenectomy is an effective surgical management approach for portal hypertension. Laparoscopic surgery has developed in the last two decades. At present, splenectomy is performed laparoscopically. Laparoscopic devascularization of the upper stomach and splenectomy are effective for the treatment of esophageal and gastric varices.

Introduction: Fat embolism syndrome (FES) is a known complication of long bone fracture and can affect multiple organs. The organ most commonly affected with FES is the lung. Severe cases of FES from long bone fracture can cause acute respiratory distress syndrome (ARDS). Although the treatment of ARDS remains challenging, it is reported that a lung protection strategy and prone positioning are effective. In addition, early fixation is reported to be beneficial in respiratory failure due to FES, though it may exacerbate respiratory failure during the perioperative period. We report the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the successful perioperative management of a patient diagnosed with ARDS due to FES. Patient concerns: A 24-year-old man injured in a traffic accident was brought to our emergency department due to shock and consciousness disorder. Diagnosis: After examining the patient, we noted bilateral pneumothorax, liver and spleen injuries, and multiple long bone fractures. Four days after admission, he was diagnosed with FES due to a prolonged consciousness disorder, progressive hypoxia with diffuse lung damage, and cutaneous and mucosal petechiae. Intervention: As respiratory failure progressed, VV-ECMO was initiated on the 6th day. To improve the respiratory failure caused by ARDS, prone position therapy was necessary. Thus, we performed osteosynthesis on the 9th day under ECMO. Prone position therapy was started after surgery. Outcomes: Subsequently, his respiratory condition and chest radiographs improved steadily. VV-ECMO was discontinued on the 17th day and the ventilator was removed on the 28th day. His consciousness levels improved without residual central nervous system complications. Conclusion: Our study reveals the successful improvement of FES-induced ARDS by osteosynthesis and prone positioning under VV-ECMO. This strategy prioritizes supportive treatment over pharmacologic interventions.

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.

Case We report a 2-year-old boy with duodenal ulcer with active bleeding that occurred as a result of norovirus gastroenteritis. On admission, the patient presented with shock accompanied with vomiting and melena. Abdominal contrast enhanced computed tomography scan showed signs of duodenal bleeding. Outcome He was successfully treated with emergent transcatheter arterial embolization. After the treatment, endoscopic examination revealed duodenal ulcer and the stool norovirus antigen test was found to be positive. The patient recovered completely without any sequelae. Conclusion Life-threatening duodenal ulcer bleeding in children can be caused by viral gastroenteritis. When endoscopic therapy is unsuccessful or difficult, in cases of small children, angiographic intervention can be a safe alternative treatment option of gastrointestinal bleeding.

Aim Sarcopenia has been increasingly reported as a prognostic factor for outcome in settings such as cirrhosis, liver transplantation, and emergent surgery. We aimed to elucidate the significance of sarcopenia in severe blunt trauma patients. Methods We retrospectively analyzed 84 patients emergently admitted to the intensive care unit at Kyushu University Hospital (Fukuoka, Japan) from May 2012 to April 2015. We assessed the amount of skeletal muscle present according to computed tomography and its relevance to ventilation-free days, patients' length of stay in the intensive care unit, and 28-day mortality. Results Twenty-five (29.7%) patients were defined as sarcopenic. Sixteen (19.7%) patients required 15 days or more in the intensive care unit. The major reason was a prolonged ventilation requirement due to flail chest (n = 7) or pneumonia (n = 3). Sarcopenic patients' stays in intensive care were significantly longer than those of non-sarcopenic patients (18.7 versus 6.4 days, respectively; P < 0.001). Univariate and multivariate analyses showed sarcopenia to be a significant risk factor for prolonged intensive care unit stay. Conclusion Sarcopenia is a risk factor that predicts prolonged intensive care unit stay in high-energy blunt trauma patients.

Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension.We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS.Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014).Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS.

Anastomotic leakage is a major complication after anterior resection for rectal cancer. The double-stapling technique (DST) is the main method for creating a colorectal anastomosis. However, the rate of anastomotic leakage after DST remains high, and the technical risk factors have not been well established.Five methods of colorectal anastomosis were performed on the porcine rectum and colon: single-stapled double-purse-string (SSDP), DST, side-to-side with a linear stapler (SS-L), side-to-side with a circular stapler (SS-C), and SS-C with hand-sewn reinforcement (n = 6 for each method). In each group, burst pressures were tested, paying special attention to the locations of the first disruptions. The anastomosis line, including staples, was embedded in polyester resin, and polished sections were examined histologically.Burst pressures were significantly higher in the SS-L and SS-C than those in the SSDP and DST groups (P 0.001) and were higher in the SS-C with hand-sewn reinforcement than those in the SS-L and SS-C groups (P 0.001). Remarkably, in the SSDP, DST, and SS-C groups, the first disruptions occurred on the staple line created by the circular stapler.The experimentally strongest colorectal anastomosis created with instruments currently in use was a SS-C. This anastomosis does not overlap staple lines and does not require a purse-string suture. Hand-sewn reinforcement was effective in increasing the anastomotic strength.

Difficulties in endoscopic operations and therapeutic procedures seem to occur due to the complexity of operating the endoscope dial as well as difficulty in performing synchronized movements with both hands. We developed a prototype robotic-assisted flexible endoscope that can be controlled with a single hand in order to simplify the operation of the endoscope. The aim of this study was to confirm the operability of the robotic-assisted flexible endoscope (RAFE) by performing endoscopic submucosal dissection (ESD). Study 1: ESD was performed manually or with RAFE by an expert endoscopist in ex vivo porcine stomachs; six operations manually and six were performed with RAFE. The procedure time per unit circumferential length/area was calculated, and the results were statistically analyzed. Study 2: We evaluated how smoothly a non-endoscopist can move a RAFE compared to a manual endoscope by assessing the designated movement of the endoscope. Study 1: En bloc resection was achieved by ESD using the RAFE. The procedure time was gradually shortened with increasing experience, and the procedure time of ESD performed with the RAFE was not significantly different from that of ESD performed with a manual endoscope. Study 2: The time for the designated movement of the endoscope was significantly shorter with a RAFE than that with a manual endoscope as for a non-endoscopist. The RAFE that we developed enabled an expert endoscopist to perform the ESD procedure without any problems and allowed a non-endoscopist to control the endoscope more easily and quickly than a manual endoscope. The RAFE is expected to undergo further development.

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.

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.

Esophageal perforation due to blunt trauma is a rare clinical condition, and the diagnosis is often difficult because patients have few specific symptoms. Delayed diagnosis may result in a fatal clinical course due to mediastinitis and subsequent sepsis. In this article, we describe a 26-year-old man with esophageal perforation due to blunt chest trauma resulting from a motor vehicle accident. Because a severe disturbance of consciousness masked the patient's trauma-induced thoracic symptoms, we required 11 h to diagnose the esophageal perforation. Therefore, the patient developed septic shock due to mediastinitis. However, his subsequent clinical course was good because of prompt combined therapy involving surgical repair and medical treatment after the diagnosis.

Background and purpose Accurate diagnosis of acute aortic dissection (AAD) is sometimes difficult because of accompanying central nervous system (CNS) symptoms. The purpose of this study was to investigate the clinical characteristics of Type A AAD (TAAAD) with CNS symptoms. Methods We retrospectively reviewed the medical records of 8403 patients ambulanced to our emergency and critical care center between April 2009 and May 2014. Results We identified 59 TAAAD patients for the analysis (mean age, 67.3 ± 10.5 years; 37 (62.0%) male). Eleven patients (18.6%) presented CNS symptoms at the onset of TAAAD, and these patients complained less frequently of typical chest and back pain than those without CNS symptoms ( p p = 0.003, and p = 0.049, respectively) and involvement of the supra-aortic artery was more frequent in patients with CNS symptoms ( p Conclusion Because CNS symptom can mask chest and back pain caused by TAAAD, physicians should always consider the possibility of TAAAD in patients with CNS symptoms in emergency medicine settings.

Aim Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT-III). We designed this randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of AT-III for PVT in liver disease patients with those who received no treatment. Methods Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross-sectional lumen of the portal vein. Patients with 70% or less serum level of AT-III were included. The study drug was given up to three times in a 5-day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five-grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT-III group and 37 patients to the placebo group. Results The proportion of patients with complete response or partial response of PVT was significantly higher in the AT-III group (55.6%; 20/36 patients; 95% confidence interval, 38.1–72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2–36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups. Conclusion Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT-III.

Aims To recognize patients who require massive transfusion at the early stage of blunt trauma, we retrospectively investigated patients with high-energy blunt injuries transferred within 1 h post-trauma. Methods Between August 2007 and July 2011, 233 trauma patients were: (i) injured by a high-energy blunt mechanism with Injury Severity Score ≥9; (ii) not dead on arrival; (iii) older than 9 years; and (iv) at our center within 1 h after injury. The findings for 113 of those patients were analyzed, including those produced by ultrasonography, computed tomography, and arterial blood gas analyses. Results Of 113 patients, 33 underwent massive transfusion (≥6 units) within 8 h of arrival. A logistic regression analysis revealed that an arterial lactate level ≥28 mg/dL (P

Background The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients. Methods Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7–10 days after laparoscopic splenectomy were analysed. Results Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P < 0·050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P < 0·001). Portal vascular resistance was also reduced, by 21 per cent (P = 0·009). The peripheral blood concentration of ET-1 decreased from 2·95 to 2·11 pg/ml (P < 0·001), and that of NOx tended to decrease (from 29·2 to 25·0 pg/ml; P = 0·068). In hepatic venous blood, the level of ET-1 decreased from 2·37 to 1·83 pg/ml (P = 0·006), whereas NOx concentration tended to increase (from 24·5 to 30·9 pg/ml; P = 0·067). Conclusion In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed.

Background and Aim Thrombocytopenia (TCP) of chronic hepatitis C patients with cirrhosis has a negative impact on the management of interferon-based treatment. The aim of this study is to evaluate the efficacy and safety of telaprevir-based triple therapy for patients who have undergone splenectomy (Spx). Methods This prospective, multicenter study consisted of 80 patients, including 32 Spx and 48 non-Spx/TCP (platelet count: 60–99 × 109/L) patients with advanced fibrosis infected with hepatitis C virus genotype 1b. All received 12 weeks of telaprevir in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin. Results The sustained virological response (SVR) rate of the Spx group (75.0%) was significantly higher than that of the non-Spx/TCP group (52.1%) (P

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

Summary There is increasing interest in the role of T cell exhaustion and it is well known that the natural history of chronic hepatitis C virus infection (HCV) is modulated by CD8+ T cell immunobiology. There are many pathways that alter the presence of exhaustive T cells and, in particular, they are functionally impaired by inhibitory receptors, such as programmed death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). We obtained spleen, liver and peripheral blood (before and after splenectomy) lymphoid cells from 25 patients with HCV-related cirrhosis undergoing liver transplantation for end-stage disease or splenectomy for portal hypertension. In all samples we performed an extensive phenotypic study of exhaustion markers [PD-1, Tim-3, interferon (IFN)-γ) and their ligands (PD-L1, PD-L2, galectin-9] in CD8+ T cell subpopulations (both total and HCV-specific) and in antigen-presenting cells (APC; monocytes and dendritic cells). In the spleen, total and HCV-specific CD8+ T cells demonstrated enhanced markers of exhaustion, predominantly in the effector memory subpopulation. Similarly, splenic APC over-expressed inhibitory receptor ligands when compared to peripheral blood. Finally, when peripheral blood CD8+ T cells were compared before and after splenectomy, markers of exhaustion were reduced in splenic CD8+ T cells and APC. Our data in HCV-related cirrhosis suggest that CD8+ T cells in the spleen manifest a significantly higher exhaustion compared to peripheral blood and may thus contribute to the failure to control HCV. Counteracting this process may contribute to inducing an effective immune response to HCV.

We report a case of portal-systemic encephalopathy occurring secondary to a splenorenal shunt, 2 years after a pancreaticoduodenectomy for locally advanced duodenal carcinoma. A 55-year-old woman was brought to our hospital with a decreased level of consciousness. Laboratory testing revealed an elevated serum ammonia level (221 μg/dl) and normal liver function. Retrospective review of a series of contrast-enhanced computed tomography scans of the abdomen identified a splenorenal shunt, which had gradually enlarged over the past 2 years (Fig. 1). The decreased level of consciousness was thought to be due to portal-systemic encephalopathy secondary to the splenorenal shunt. We performed balloon-occluded retrograde transvenous obliteration to occlude the splenorenal shunt, following which her serum ammonia level returned to normal (28 μg/dl) and an alert level of consciousness was maintained.Fig. 1Review of abdominal computed tomography scans. a Preoperatively, b 6 months postoperatively, c 1 year postoperatively, d 2 years and 2 months postoperatively. The shunt vessel gradually enlarged after pancreaticoduodenectomy (circle)

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). 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. 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. 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.

Aim Whether hepatic function can recover in cirrhotic patients after splenectomy remains controversial. Methods All consecutive Japanese patients with hepatic cirrhosis due to hepatitis C who had undergone elective splenectomy in Kyushu University Hospital between January 2008 and December 2009 were included in this retrospective study. Prothrombin time, serum albumin and total bilirubin concentrations were reviewed before and after splenectomy and analyzed to clarify whether splenectomy improves hepatic function in patients with cirrhosis and to determine the factors predictive of improvement in hepatic function. Results Prothrombin time and total serum bilirubin concentration improved after splenectomy; however, serum albumin concentrations did not increase significantly. Twelve months after splenectomy, total serum bilirubin had decreased by over 0.3 mg/dL in 52.3% of patients and prothrombin time had improved by over 10% in 52.3% of patients. Multiple linear regression analysis identified hepatic vein waveform (HVWF) type I (P = 0.0174) and spleen weight (P = 0.0394) as independent predictors of improvement in prothrombin time and preoperative total serum bilirubin (P = 0.0002) as the only independent predictor of decrease in total bilirubin. Total bilirubin and prothrombin time were significantly improved after splenectomy in patients with HVWF type I, however, they were not improved in patients with HVWF type II. Conclusion Prothrombin time and total bilirubin improve in approximately half of cirrhotic patients within a year after splenectomy. HVWF type I and splenomegaly may be predictive factors for improvement in prothrombin time after splenectomy in patients with cirrhosis due to hepatitis C.

Image-guided surgery (IGS) for otological procedures requires minimal invasiveness and a high degree of accuracy. We have recently developed a noninvasive registration method, the Surface Template-Assisted Marker Positioning (STAMP) method, which uses a rigid template of the surface of the temporal bone. However, the STAMP method is not applicable when the bony surface is not exposed, such as in endoscopic surgery. Thus, we extended our research to apply the STAMP method onto the skin and tested its feasibility in this study. We designed a phantom made of a rigid box and soft material for the study. The target registration error (TRE) was measured at preset measuring points in the phantom. We modified the STAMP method to be applicable for use on the skin around the ears (S-STAMP). The same phantom was also registered using the conventional, manually scanned surface matching method. We compared the TRE after the different registration methods. The TRE after the S-STAMP registration method was significantly smaller than that of the conventional surface matching method at all error measurement points in the phantom. However, the TRE after the S-STAMP registration method was significantly larger than that of paired point registration using invasive fiducial markers. The S-STAMP method using a rigid template on the soft surface yields a significantly smaller TRE than that of conventional, manually scanned surface matching registration. This strategy provides an alternative option to improve the accuracy of IGS without loading patients with additional invasive procedures.

We recently experienced 10 patients with cirrhosis who underwent laparoscopic splenectomy. A portion of these patients underwent dissection with a flexible endoscope in the peritoneal cavity. This pilot study mainly focused on the technical aspects and immediate results. From November 2009 to September 2010, 10 patients with cirrhosis and hypersplenism were entered into this pilot study. They were indicated to undergo laparoscopic splenectomy to treat portal hypertension and to facilitate initiation and completion of either interferon therapy for liver cirrhosis or anticancer therapy for hepatocellular carcinoma. To dissect the upper end of the gastrosplenic ligament and the marginal region between the left diaphragm and upper pole of the spleen, a flexible single-channel endoscope was introduced into the peritoneal cavity simultaneously with the use of a rigid laparoscope. Dissection with the flexible endoscope in the peritoneal cavity was performed using an insulation-tipped electrosurgical knife through the channel of the flexible endoscope. The flexible endoscope offered a magnified operative view, a water-jet lens cleaner, and a powerful lavage and suction capability. The upper end of the gastrosplenic ligament and the marginal region between the left diaphragm and upper pole of the spleen were easily seen, and dissection of these critical regions was smoothly conducted with articulation of the tip of the flexible endoscope, even in patients with splenomegaly. No patient experienced major intraoperative complications or required conversion to open surgery. Dissection with a flexible endoscope in the peritoneal cavity may be an effective tactic for laparoscopic megasplenectomy, and significant implications for pure natural orifice translumenal endoscopic surgery have been raised. Although future randomized controlled prospective studies are needed to confirm these findings, surgeons might find this to be a typical example of an appropriate strategy for high-risk patients.

Aim: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Methods: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied. Results: There were significant differences in PVP (17.9 ± 0.91 vs 23.3 ± 3.91 cmH2O; P

Background and Aim: We intended to determine whether laparoscopic splenectomy (Lap-Sp) contributes to treatment with interferon therapy in hepatitis C virus (HCV)-cirrhotic patients with thrombocytopenia caused by hypersplenism. Methods: From December 2004 to August 2008, 100 cirrhotic patients (54 men and 46 women) underwent Lap-Sp for a clinical application of interferon therapy. All the patients were Child–Pugh class A or B with thrombocytopenia (average platelet count, 56 × 103/mm3). The HCV genotype was type 1 in 80 patients and type 2 in 20 patients. Results: Pure laparoscopic or hand-assisted laparoscopy was performed in 78 and 22 patients, respectively, without mortality. Conversion to open surgery was not required in any of the patients. The platelet counts improved (mean platelet count 172 × 103/mm3 1 month after surgery) and interferon (IFN) therapy was started in 97 patients. In this study period, 36 patients obtained a sustained virologic response. Eight patients discontinued IFN therapy because of depression, neutropenia or other reasons. Conclusions: Lap-Sp permits most patients with HCV cirrhosis and hypersplenism to receive sufficient IFN therapy. Therefore, Lap-Sp can become a strong supportive surgery for cirrhotic patients who require antiviral therapy.

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.

Aim: Although endoscopic injection of cyanoacrylate (CA) is the only effective method for treating isolated fundal gastric variceal bleeding, the rebleeding rate is relatively high. This study investigated the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) for management of isolated fundal gastric variceal bleeding. Methods: Patients (n = 110) with acute or recent bleeding from isolated fundal gastric varices (GV) were retrospectively studied. Acute bleeding was treated by CA injection or balloon tamponade. 44 patients underwent additional endoscopic injection of CA and ethanolamine oleate (EO) weekly until obturation of GVx from 1994 to 2002 (group A). 42 patients from 2003 to 2010 underwent B-RTO after initial hemostasis (group B). Both groups were assessed for the number of sessions required to achieve GV obturation, hospital stay, recurrent bleeding rate, morbidity and mortality. Results: Acute gastric variceal bleeding was successfully treated in all patients by CA injection or balloon tamponade. B-RTO was successfully performed except in two patients in group B. The average number of sessions required for obturation was 3.8 for groups A and 2.2 for B (P

The purpose of our study was to investigate predictive factors for platelet count at 1 month after splenectomy in patients with liver cirrhosis. A total of 60 patients with liver cirrhosis who were treated with splenectomy from January 2005 to December 2006 were enrolled in the study (hepatitis C, n = 50; hepatitis B, n = 6; alcoholism, n = 2; others, n = 2). Various preoperative clinical characteristics, including spleen weight, were analyzed by simple and multiple linear regressions to study the relationship between platelet count before and after splenectomy. Platelet count increased significantly after splenectomy. After simple linear regression, spleen weight, preoperative platelet count, lymphocyte count, and total bilirubin were significantly correlated with platelet count after splenectomy. Spleen weight, preoperative platelet count, and lymphocyte count also had a significant correlation after multiple linear regression analysis. Platelet count after splenectomy in cirrhotic patients can be predicted on the basis of preoperative clinical characteristics. When selecting patients for splenectomy, spleen weight, preoperative platelet count, and lymphocyte count should be taken into consideration.