Utility and advantage of the unroofing technique for gastrointestinal subepithelial tumors: A multicenter retrospective cohort study.

Background and aim: Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term "unroofing technique". We conducted a multicenter retrospective study to assess its efficacy and identify potential complications. Methods: This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis. Results: The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation. Conclusion: The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.

Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection.

Objective: Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) may effectively treat acute pulmonary embolisms (PEs). Here, we assessed the effectiveness of clot dissolution and safety of tissue plasminogen activator (t-PA) injection using EBUS-TBNI in a 1-week survival study of a porcine PE model. Methods: Six pigs with bilateral PEs were used: 3 for t-PA injection using EBUS-TBNI (TBNI group) and 3 for systemic administration of t-PA (systemic group). Once bilateral PEs were created, each 25 mg of t-PA injection using EBUS-TBNI for bilateral PEs (a total of 50 mg t-PA) and 100 mg of t-PA systemic administration was performed on day 1. Hemodynamic parameters, blood tests, and contrast-enhanced computed tomography scans were carried out at several time points. On day 7, pigs were humanely killed to evaluate the residual clot volume in the pulmonary arteries. Results: The average of percent change of residual clot volumes was significantly lower in the TBNI group than in the systemic group (%: systemic group 36.6 ± 22.6 vs TBNI group 9.6 ± 6.1, P < .01) on day 3. Considering the elapsed time, the average decrease of clot volume per hour at pre-t-PA to post t-PA was significantly greater in the TBNI group than in the systemic group (mm3/hour: systemic 68.1 ± 68.1 vs TBNI 256.8 ± 148.1, P < .05). No hemorrhage was observed intracranially, intrathoracically, or intraperitoneally on any contrast-enhanced computed tomography images. Conclusions: This study revealed that t-PA injection using EBUS-TBNI is an effective and safe way to dissolve clots.

Femoral prosthesis alignment of augmented reality-assisted versus accelerometer-based navigation in total knee arthroplasty: A noninferiority analysis.

INTRODUCTION: The purpose of this study was to examine the comparative precision of the augmented reality (AR)-assisted navigation system and the accelerometer-based navigation system in total knee arthroplasty (TKA). MATERIALS AND METHODS: We performed noninferiority analysis in a retrospective cohort. The coronal alignment of femoral prosthesis was compared between 109 TKAs performed using the AR-assisted navigation system and 118 TKAs performed using the accelerometer-based navigation system. All femoral prostheses were planned to be positioned perpendicular to the mechanical axis of the femur. The primary outcome was the success rate of coronal alignment of the femoral prosthesis defined as alignment error relative to neutral alignment <3°. We calculated the noninferiority margin as 7%-points using the 95%-95 % method and also confirmed the validity of the noninferiority margin using the fixed margin method. Noninferiority would be shown if the lower boundary of the 95 % confidence interval (CI) for the between-group difference in percentage of the success rate was not less than 0.93 (i.e., 1.00 - 0.07). RESULTS: Treatment success was achieved in 104 of 109 patients (95.4 %) in the AR-assisted navigation group and 110 of 118 (93.2 %) in the accelerometer-based navigation group. The risk ratio of success between the AR-assisted navigation group versus accelerometer-based navigation group was 1.02 (95 % CI, 0.96 to 1.09): the CIs did not include the noninferiority margin of 0.93. CONCLUSION: The AR-assisted navigation system was noninferior to the accelerometer-based navigation system in terms of coronal alignment of the femoral prosthesis in TKA.

Concurrent Nivolumab-Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma.

Immune checkpoint inhibitors, including nivolumab, can result in immune-related adverse events (irAEs) that may affect multiple organ systems. Among irAEs, both gastritis and cholangitis are uncommon. We present the case of a 65-year-old man who received nivolumab for lung adenocarcinoma presented with epigastric pain. He was diagnosed with immune-related gastritis and cholangitis based on imaging and pathological findings. We administered prednisolone (1 mg/kg/day), which improved the patient's gastritis and relieved his pain. However, he experienced recurrent epigastric pain during corticosteroid tapering, and magnetic resonance imaging showed biliary tract hemorrhage. After watchful waiting, the hemorrhage improved without additional immunosuppressants. Immune-related gastritis, immune-related cholangitis, and their coexistence should be considered in patients who develop epigastric pain during immune checkpoint inhibitor therapy. When patients with concurrent immune-related gastritis and cholangitis complain of recurrent epigastric pain, it is important to assess which of these two irAEs is worsening because the optimal immunosuppressants differ between the two.

AQDnet: Deep Neural Network for Protein-Ligand Docking Simulation.

We have developed an innovative system, AI QM Docking Net (AQDnet), which utilizes the three-dimensional structure of protein-ligand complexes to predict binding affinity. This system is novel in two respects: first, it significantly expands the training dataset by generating thousands of diverse ligand configurations for each protein-ligand complex and subsequently determining the binding energy of each configuration through quantum computation. Second, we have devised a method that incorporates the atom-centered symmetry function (ACSF), highly effective in describing molecular energies, for the prediction of protein-ligand interactions. These advancements have enabled us to effectively train a neural network to learn the protein-ligand quantum energy landscape (P-L QEL). Consequently, we have achieved a 92.6% top 1 success rate in the CASF-2016 docking power, placing first among all models assessed in the CASF-2016, thus demonstrating the exceptional docking performance of our model.

Does Augmented Reality-based Portable Navigation Improve the Accuracy of Cup Placement in THA Compared With Accelerometer-based Portable Navigation? A Randomized Controlled Trial.

BACKGROUND: Previous studies reported good outcomes of acetabular cup placement using portable navigation systems during THA. However, we are aware of no prospective studies comparing inexpensive portable navigation systems using augmented reality (AR) technology with accelerometer-based portable navigation systems in THA. QUESTIONS/PURPOSES: (1) Is the placement accuracy of the acetabular cup using the AR-based portable navigation system superior to that of an accelerometer-based portable navigation system? (2) Do the frequencies of surgical complications differ between the two groups? METHODS: We conducted a prospective, two-arm, parallel-group, randomized controlled trial involving patients scheduled for unilateral THA. Between August and December 2021, we treated 148 patients who had a diagnosis of osteoarthritis, idiopathic osteonecrosis, rheumatoid arthritis, or femoral neck fracture and were scheduled to undergo unilateral primary THA. Of these patients, 100% (148) were eligible, 90% (133) were approached for inclusion in the study, and 85% (126) were finally randomized into either the AR group (62 patients) or the accelerometer group (64 patients). An intention-to-treat analysis was performed, and there was no crossover between groups and no dropouts; all patients in both groups were included in the analysis. There were no differences in any key covariates, including age, sex, and BMI, between the two groups. All THAs were performed via the modified Watson-Jones approach with the patient in the lateral decubitus position. The primary outcome was the absolute difference between the cup placement angle displayed on the screen of the navigation system and that measured on postoperative radiographs. The secondary outcome was intraoperative or postoperative complications recorded during the study period for the two portable navigation systems. RESULTS: There were no differences between the AR and accelerometer groups in terms of the mean absolute difference in radiographic inclination angle (3° ± 2° versus 3° ± 2° [95% CI -1.2° to 0.3°]; p = 0.22). The mean absolute difference in radiographic anteversion angle displayed on the navigation screen during surgery compared with that measured on postoperative radiographs was smaller in the AR group than that in the accelerometer group (2° ± 2° versus 5° ± 4° [95% CI -4.2° to -2.0°]; p < 0.001). There were few complications in either group. In the AR group, there was one patient each with a surgical site infection, intraoperative fracture, distal deep vein thrombosis, and intraoperative pin loosening; in the accelerometer group, there was one patient each with an intraoperative fracture and intraoperative loosening of pins. CONCLUSION: Although the AR-based portable navigation system demonstrated slight improvements in radiographic anteversion of cup placement compared with the accelerometer-based portable navigation system in THA, whether those small differences will prove clinically important is unknown. Until or unless future studies demonstrate clinical advantages that patients can perceive that are associated with such small radiographic differences, because of the costs and the unquantified risks associated with novel devices, we recommend against the widespread use of these systems in clinical practice. LEVEL OF EVIDENCE: Level I, therapeutic study.

Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.

In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.

Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping.

OBJECTIVE: Lung sentinel lymph node mapping, where peritumorally injected material is tracked through the lymphatics, aims to find the first potential sites of nodal metastasis. We sought to evaluate the preclinical feasibility of bronchoscopic fluorescence-guided sentinel lymph node mapping. METHODS: Healthy Yorkshire pigs were used; sentinel lymph node mapping was performed with indocyanine green. The primary fluorescence imaging method was an ultrathin composite fiberscope placed in the bronchoscope working channel. Secondary methods used a fluorescence thoracoscope placed in the trachea (rigid bronchoscopy) and pretracheal fascial plane (mediastinoscopy) to validate ultrathin composite fiberscope settings for sentinel lymph node detection. A tracheostomy was created, and the pig was placed in a lateral decubitus position. Transbronchial intraparenchymal indocyanine green injection was performed primarily in the right lower lobe. Ultrathin composite fiberscope and rigid bronchoscopy were performed with (n = 6) or without (n = 2) mediastinoscopy, with the former group guiding dose and ultrathin composite fiberscope optimization. Fluorescent targets were interrogated by endobronchial ultrasound before ultrathin composite fiberscope-guided transbronchial needle aspiration. Specimen fluorescence was documented before creating cytological smears. Pigs were killed postprocedure for nodal dissection. RESULTS: A total of 100 µL of 10 mg/mL indocyanine green generated strong transbronchial fluorescence with low risk of indocyanine green contamination. Fluorescence was detectable by 10 minutes postinjection. There was concordance among ultrathin composite fiberscope, rigid bronchoscopy, and mediastinoscopy. Except for 1 pig with airway contamination, ultrathin composite fiberscope-guided endobronchial ultrasound transbronchial needle aspiration obtained fluorescent material in all pigs. Specimen fluorescence was associated with specimen adequacy. CONCLUSIONS: Bronchoscopic fluorescence-guided sentinel lymph node mapping was feasible, with specimen fluorescence providing real-time feedback on sentinel lymph node biopsy success. If translated to clinical practice, attention must be paid to minimizing indocyanine green leakage.

Augmented reality-aided unicompartmental knee arthroplasty.

PURPOSE: To illustrate a surgical technique for augmented reality (AR)-assisted unicompartmental knee arthroplasty (UKA) and report preliminary data. METHODS: We developed an AR-based navigation system that enables the surgeon to see the tibial mechanical axis superimposed on the patient's leg in addition to the tibial cutting angle. We measured the tibial resection angle in 11 UKAs using postoperative radiographs and calculated the absolute difference between preoperative target angle and postoperative measured angle. The target angle was determined for each patient: mean values were 0.7° ± 1.0° varus in coronal alignment and 5.3° ± 1.4° posterior slope in sagittal alignment. RESULTS: The angles measured on postoperative radiographs were 2.6° ± 1.2° varus in the coronal plane and 4.8° ± 2.5° posterior slope in the sagittal plane. The absolute differences between the target and measured angles were 1.9° ± 1.5° in coronal alignment and 2.6° ± 1.2° in sagittal alignment. No patients experienced complications, including surgical site infection and periprosthetic fracture. CONCLUSION: The AR-based portable navigation system may provide passable accuracy in terms of proximal tibial resection during UKA. LEVEL OF EVIDENCE: IV.

Clinical Significance of Serum Zinc Levels on the Development of Sarcopenia in Cirrhotic Patients.

Background/Aim: Sarcopenia increases the mortality in patients with cirrhosis. Approximately 60% of zinc is accumulated in skeletal muscle. We aimed to determine the role of subclinical zinc deficiency on sarcopenia development in patients with cirrhosis. Patients and Methods: We enrolled 151 patients with cirrhosis and divided them into the group with normal serum zinc levels (Group N: 80-130 µg/dl; n=38) and group with subclinical zinc deficiency (Group D: <80 µg/dl; n=113). The risk factors for sarcopenia were then investigated. Results: Group D had more sarcopenia cases than Group N (31.0% vs. 13.2%). In group D, HGS exhibited a weakly positive but significant correlation with serum zinc levels (R=0.287, p=0.00212), serum zinc levels negatively correlated with both ammonia and myostatin levels (R=-0.254, p=0.0078; R=-0.33, p<0.01), and low zinc levels were independently associated with sarcopenia development. Conclusion: Patients with cirrhosis showing subclinical zinc deficiency have a significantly higher risk of developing sarcopenia.

Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease.

The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25-0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26-0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Augmented Reality- vs Accelerometer-Based Portable Navigation System to Improve the Accuracy of Acetabular Cup Placement During Total Hip Arthroplasty in the Lateral Decubitus Position.

BACKGROUND: There have been no studies regarding the effectiveness of augmented reality (AR)-based portable navigation systems compared with accelerometer-based portable navigation systems in total hip arthroplasty (THA). METHODS: We retrospectively compared THAs performed using an AR-based portable navigation system (n = 45) and those performed using an accelerometer-based portable navigation system (n = 42). All THAs were performed with the patient in the lateral decubitus position. The primary outcome was the absolute difference between cup placement angles displayed on the navigation screen and those measured on postoperative X-ray. RESULTS: The mean absolute differences were significantly smaller in the AR-based portable navigation system group than the accelerometer-based portable navigation system group in radiographic inclination (2.5° ± 1.7° vs 4.6° ± 3.1°; 95% confidence interval 1.1°-3.2°, P < .0001). Similarly, the mean absolute differences were significantly better in the AR-based portable navigation system group in radiographic anteversion (2.1° ± 1.8° vs 6.4° ± 4.2°; 95% confidence interval 3.0°-5.7°, P < .0001). Neither hip dislocation, surgical site infection, nor other complications associated with use of the navigation system occurred in either group. CONCLUSION: The AR-based portable navigation system may provide more precise acetabular cup placement compared with the accelerometer-based portable navigation system in THA.

The Combination of Albumin-Bilirubin Score and Prothrombin Time Is a Useful Tool for Predicting Liver Dysfunction after Transcatheter Arterial Chemoembolization in Child-Pugh Class A Patients with Hepatocellular Carcinoma within Up-to-Seven Criteria.

Mortality and recurrence rates of hepatocellular carcinoma (HCC) are high. Recent studies show that for patients with HCC beyond up-to-seven criteria, treatment with molecular-targeted agents (MTAs) is recommended because the treatment efficiency of transcatheter arterial chemoembolization (TACE) is poor; further, TACE increases decline in liver function. However, the relationship between TACE and liver function decline in patients with HCC within up-to-seven criteria has not been clarified. Hence, we aimed to investigate this relationship. This retrospective observational study included 189 HCC tumors within up-to-seven criteria in 114 Child-Pugh class A patients. Twenty-four (12.7%) tumors were changed from Child-Pugh class A to B after TACE, and 116 (61.4%) tumors exhibited recurrence within 6 months after TACE. Prothrombin time (PT) and albumin-bilirubin (ALBI) score before TACE were significantly associated with liver dysfunction from Child-Pugh class A to B. The combination of PT and ALBI score before TACE had high predictive ability for liver dysfunction from Child-Pugh class A to B after TACE (specificity = 100%, sensitivity = 91.7%). The combined use of pre-TACE PT and ALBI score has a high predictive ability for liver dysfunction after TACE for Child-Pugh class A patients with HCC within up-to-seven criteria.

Microscopic Temperature Control Reveals Cooperative Regulation of Actin-Myosin Interaction by Drebrin E.

Drebrin E is a regulatory protein of intracellular force produced by actomyosin complexes, that is, myosin molecular motors interacting with actin filaments. The expression level of drebrin E in nerve cells decreases as the animal grows, suggesting its pivotal but unclarified role in neuronal development. Here, by applying the microscopic heat pulse method to actomyosin motility assay, the regulatory mechanism is examined from the room temperature up to 37 °C without a thermal denaturing of proteins. We show that the inhibition of actomyosin motility by drebrin E is eliminated immediately and reversibly during heating and depends on drebrin E concentration. The direct observation of quantum dot-labeled drebrin E implies its stable binding to actin filaments during the heat-induced sliding. Our results suggest that drebrin E allosterically modifies the actin filament structure to regulate cooperatively the actomyosin activity at the maintained in vivo body temperature.

Enhanced liver fibrosis score as a surrogate of liver-related complications and mortality in primary biliary cholangitis.

ABSTRACT: The presence of bridging fibrosis predicts survival of primary biliary cholangitis (PBC). This study aimed to compare serum parameters for the estimation of liver fibrosis and prediction of clinical outcomes in PBC.Out of 392 patients with PBC, 102 who underwent liver biopsy and in whom fibrosis indices, platelet count, hyaluronic acid, type IV collagen 7 second domain, procollagen type III amino-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, N-terminal type III collagen propeptide levels; fibrosis index based on 4 factors, aspartate aminotransferase-to-platelet ratio index, and enhanced liver fibrosis (ELF) score were determined, were included. The correlation of histological stages based on both Scheuer and Nakanuma classifications with fibrosis indices was investigated. The Nakanuma system comprises grading for liver fibrosis and bile duct loss. Diagnostic performances of 10 fibrosis indices were evaluated to identify patients with poor prognosis. Moreover, correlations of those with PBC clinical manifestation and survival were also investigated.Enhances liver fibrosis (ELF) score had the highest correlation coefficient for liver fibrosis evaluated according to either the Scheuer or Nakanuma classification among 10 serum fibrosis indices. It also had the highest diagnostic performance in estimating Scheuer stage III and Nakanuma fibrosis score 2, both of which represent portal-bridging fibrosis. Patients with an ELF score of ≥10.0 had shorter survival and presented more frequently clinical complications than those with an ELF score of <10.0.ELF score determines the severity of liver fibrosis and predicts the occurrence of complications and survival in patients with PBC.

The association between sarcopenia and endotoxin in patients with alcoholic cirrhosis.

ABSTRACT: We aimed to prospectively identify the risk factors of sarcopenia in patients with cirrhosis.Patients (n = 193) included in a discovery cohort (January 2011 and December 2014) were categorized into alcoholic (A1; n = 55) and non-alcoholic cirrhosis (NA; n = 138) groups, and those (n = 235) in a validation cohort (January 2015 to December 2019) were categorized into alcoholic (n = 92), non-alcoholic steatohepatitis-related (n = 27), and hepatitis C virus-related cirrhosis groups (n = 116). Skeletal muscle mass index (SMI) was determined using computed tomography (SMI-CT) and bioelectrical impedance analysis (SMI-BIA). Endotoxin activity (EA) was measured with an EA assay.SMI-CT correlated with grip strength in all the groups but significantly correlated with SMI-BIA of the men in group A1 (R = 0.64, P < .0001) and both sexes in group NA (male: R = 0.44, P = .0001; female: R = 0.35, P = .003). SMI-CT inversely correlated with the EA levels of the men in group A1 (R = -0.67, P < .0001) and myostatin levels in group NA (R = -0.53, P < .0001). Lower extremity SMI had a strong negative correlation with the EA levels of the men in group A1 (R = -0.58, P < .001), whereas upper extremity SMI showed an inverse trend with EA levels (R = -0.28, P = .08). SMI-CT also inversely correlated with the EA levels in groups A2 (R = -0.52, P = .003) and N (R = -0.67, P < .0001) and myostatin levels in group C (R = -0.65, P < .0001). Moreover, SMI-CT correlated with nutritional factors, including cholinesterase (R = 0.50, P = .005), zinc (R = 0.45, P = .01), branched amino acid-to-tyrosine ratio (R = 0.39, P = .02), and triglyceride (R = 0.33, P = .03) in group N.Sarcopenia risk factors differ among cirrhosis etiologies. Alcohol-induced, intestine-mediated peripheral endotoxemia could participate in sarcopenia development in patients with alcoholic cirrhosis.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma.

BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Clinical Significance of Gamma-Glutamyltranspeptidase Combined with Carbohydrate-Deficient Transferrin for the Assessment of Excessive Alcohol Consumption in Patients with Alcoholic Cirrhosis.

Background: This study aimed to compare the diagnostic performance of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (γ-GTP) to assess the single and combined benefits of these biological markers for the detection of chronic excessive alcohol consumption in patients with alcoholic cirrhosis. Methods: Biological markers were determined in blood samples from patients with alcoholic cirrhosis (drinking group, n = 35; nondrinking group, n = 81). The prediction accuracy of %CDT alone, γ-GTP alone, and their combination for the detection of excessive alcohol consumption was determined in patients with alcoholic cirrhosis. Results: Serum total bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-GTP, and alkaline phosphatase levels and %CDT were significantly higher and serum albumin levels were significantly lower in the drinking group than in the nondrinking group. The combination of %CDT and γ-GTP compared with %CDT or γ-GTP alone showed a higher prediction accuracy. The combination of %CDT and γ-GTP exhibited a higher specificity than γ-GTP alone. However, in terms of sensitivity, no significant difference was found between single or combined markers. Conclusions: The combination of %CDT and γ-GTP is considered a useful biomarker of chronic excessive alcohol consumption in patients with alcoholic cirrhosis.

Augmented Reality-Assisted Femoral Bone Resection in Total Knee Arthroplasty.

An augmented reality (AR)-based navigation system allows visualization of the center of the femoral head and femoral mechanical axis superimposed on the surgical field during total knee arthroplasty (TKA) and may help surgeons to improve the accuracy of distal femoral resection. METHODS: First, we resected 10 femoral Sawbones specimens using the AR-based navigation system and performed computed tomography (CT) to measure the resection angle of the distal part of the femur. We calculated the absolute values of the differences between angles measured using CT images and angles displayed on the smartphone screen of the navigation system. Second, we measured coronal alignment using standing long-leg radiographs for 72 patients undergoing TKA and compared the error in the resection angle between TKA using the AR-based navigation system and that using a conventional intramedullary guide. RESULTS: In the experimental study, the absolute values of the differences between angles measured on CT images and angles displayed using the AR-based navigation system were 0.8° ± 0.5° (range, 0.3° to 1.9°) in the coronal plane and 0.6° ± 0.5° (range, 0.0° to 1.4°) in the sagittal plane. In the clinical study, the mean absolute value of the error in coronal alignment was significantly smaller in the AR-based navigation group than the intramedullary-guide group (1.1° ± 1.0° [range, 0.0° to 3.2°] compared with 2.2° ± 1.6° [range, 0.0° to 5.5°], respectively; 95% confidence interval, 0.5° to 1.8°; p < 0.001). CONCLUSIONS: The AR-based navigation system may enable surgeons to perform distal femoral resection more accurately than with the conventional intramedullary guide during TKA. CLINICAL RELEVANCE: This study validates the use of AR technology to enhance the precision of bone resection in TKA.

Prognostic significance of preoperative haemoglobin A1c level in patients with lung adenocarcinoma.

OBJECTIVES: We investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery. METHODS: We reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence. CONCLUSIONS: Our results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery. CLINICAL REGISTRATION NUMBER: Hyogo Cancer Center, G-57.