A case report of simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy.

Introduction: Robot-assisted surgery is spreading across surgical specialities as a less invasive alternative to conventional laparoscopic and open surgery. Case presentation: In this report, robot-assisted total laparoscopic hysterectomy and robot-assisted nephroureterectomy were performed simultaneously for a 69-year-old Japanese female with giant cervical polyp and ureteral cancer. All specimens could be removed from the vagina. The operative time was 379 min, the estimated intraoperative blood loss was 29 mL, and the patient was discharged on the sixth postoperative day without complications. Conclusion: We reported our experience with simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy. To our knowledge, this is the first report of simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy surgery.

Machine learning-based Automatic Evaluation of Tissue Handling Skills in Laparoscopic Colorectal Surgery: A Retrospective Experimental Study.

OBJECTIVE: To develop a machine learning model that automatically quantifies the spread of blood in the surgical field using intraoperative videos of laparoscopic colorectal surgery and evaluate whether the index measured with the developed model can be used to assess tissue handling skill. BACKGROUND: Although skill evaluation is crucial in laparoscopic surgery, existing evaluation systems suffer from evaluator subjectivity and are labor-intensive. Therefore, automatic evaluation using machine learning is potentially useful. MATERIALS AND METHODS: In this retrospective experimental study, we used training data with annotated labels of blood or non-blood pixels on intraoperative images to develop a machine learning model to classify pixel RGB values into blood and non-blood. The blood pixel count per frame (the total number of blood pixels throughout a surgery divided by the number of frames) was compared among groups of surgeons with different tissue handling skills. RESULTS: The overall accuracy of the machine learning model for the blood classification task was 85.7%. The high tissue handling skill group had the lowest blood pixel count per frame, and the novice surgeon group had the highest count (mean [SD]: high tissue handling skill group 20972.23 [19287.05] vs. low tissue handling skill group 34473.42 [28144.29] vs. novice surgeon group 50630.04 [42427.76], P <0.01). The difference between any 2 groups was significant. CONCLUSIONS: We developed a machine learning model to measure blood pixels in laparoscopic colorectal surgery images using RGB information. The blood pixel count per frame measured with this model significantly correlated with surgeons' tissue handling skills.

Universal meta-competencies of operative performances: a literature review and qualitative synthesis.

BACKGROUND: Prioritizing patient health is essential, and given the risk of mortality, surgical techniques should be objectively evaluated. However, there is no comprehensive cross-disciplinary system that evaluates skills across all aspects among surgeons of varying levels. Therefore, this study aimed to uncover universal surgical competencies by decomposing and reconstructing specific descriptions in operative performance assessment tools, as the basis of building automated evaluation system using computer vision and machine learning-based analysis. METHODS: The study participants were primarily expert surgeons in the gastrointestinal surgery field and the methodology comprised data collection, thematic analysis, and validation. For the data collection, participants identified global operative performance assessment tools according to detailed inclusion and exclusion criteria. Thereafter, thematic analysis was used to conduct detailed analyses of the descriptions in the tools where specific rules were coded, integrated, and discussed to obtain high-level concepts, namely, "Skill meta-competencies." "Skill meta-competencies" was recategorized for data validation and reliability assurance. Nine assessment tools were selected based on participant criteria. RESULTS: In total, 189 types of skill performances were extracted from the nine tool descriptions and organized into the following five competencies: (1) Tissue handling, (2) Psychomotor skill, (3) Efficiency, (4) Dissection quality, and (5) Exposure quality. The evolutionary importance of these competences' different evaluation targets and purpose over time were assessed; the results showed relatively high reliability, indicating that the categorization was reproducible. The inclusion of basic (tissue handling, psychomotor skill, and efficiency) and advanced (dissection quality and exposure quality) skills in these competencies enhanced the tools' comprehensiveness. CONCLUSIONS: The competencies identified to help surgeons formalize and implement tacit knowledge of operative performance are highly reproducible. These results can be used to form the basis of an automated skill evaluation system and help surgeons improve the provision of care and training, consequently, improving patient prognosis.

Three-Dimensional Peripheral Bloodstream Model of the Uterus for Laparoscopic Radical Hysterectomy.

Trainees require extensive experience to perform radical hysterectomy. Before starting training during an actual operation, trainees should be familiar with the pelvic anatomy and should simulate surgical procedures. Many simulators are available for virtual reality training of laparoscopic operations, but they are very expensive. The materials required to construct our model included sponges and colored wires sold in home improvement stores that allowed for superior cost effectiveness. The model represented almost all peripheral vessels and nerves around the uterus, including the minor vessels. Attaching and detaching the vessels was easy, facilitating reconstruction of the dissected vessels. The wires were easy to bend, ensuring high operability. This model allows for the simulation of laparoscopic radical hysterectomy in a dry box. Our model was superior to a 2-dimensional picture for the memorization of branching and positional relationships of the blood vessels. Comparison of our model with actual operative videos showed that the dry box provided an identical surgical view of an actual laparoscopic radical hysterectomy. We developed a peripheral bloodstream model of the uterus for repeated simulation of laparoscopic radical hysterectomy with an actual surgical view using a dry box.

Difference in the size of the placenta and umbilical cord between women with natural pregnancy and those with IVF pregnancy.

PURPOSE: The purpose of this study was to compare the sizes of the placenta and umbilical cord in women with natural pregnancy versus those undergoing in vitro fertilization (IVF). METHODS: Overall, 1610 cases of uncomplicated single pregnancies with vaginal delivery at ≥ 37 weeks of gestation were included in this study. The patients were divided into two groups: natural pregnancy group (n = 1453) and IVF pregnancy not including intracytoplasmic sperm injection (ICSI) treatment (n = 157). The groups were compared in terms of gestational week, maternal age, parity, maternal weight gain, prepregnancy maternal BMI, infant weight at birth, infant head circumference, placental weight, cross section of the placenta, cross section of the umbilical cord, insertion site of the umbilical cord, and umbilical cord length. Stepwise selection and multivariate logistic regression were used for statistical analysis to correct the result as an independent factor. RESULTS: There was no difference in the size of the placenta and umbilical cord between women with natural pregnancy and with IVF, but the incidence of velamentous insertion of the cord was significantly increased in women with IVF pregnancy (adjusted odd ratio [AOR] 1.72, 95% confidence interval [CI] 1.08-2.72, p = 0.026). CONCLUSIONS: Although there is no difference in placental weight and cord size, velamentous insertion of the umbilical cord increases in IVF pregnancy and needs careful observation during the delivery process.

A three-step evaluation for safer curettage treatment of cesarean scar pregnancy.

Dilation and curettage is one of the treatment options for cesarean scar pregnancy, however, it sometimes requires a salvage therapy. Few reports discuss the methods of evaluating cesarean scar pregnancy before therapeutic procedures. We aimed to present a case study in which a three-step approach using a combination of preoperational sonohysterography, hysteroscopy, and laparoscopy was performed to evaluate cesarean scar pregnancy. A 33-year-old, G2P2, Japanese female with a history of two elective cesarean sections was diagnosed with viable cesarean scar pregnancy. We used the three-step approach right after undergoing bilateral uterine artery embolization and confirmed that there was a low possibility of fatal complications and we performed dilation and curettage. These steps could be done safely even if the cesarean scar pregnancy was viable. To perform safer curettage on cesarean scar pregnancy patients, these three steps seem to be useful.

Maternal Smoking History Enhances the Expression of Placental Growth Factor in Invasive Trophoblasts at Early Gestation Despite Cessation of Smoking.

Maternal smoking during early pregnancy is associated with a reduced risk for preeclampsia even after smoking cessation during pregnancy. Although the pathophysiology of preeclampsia has not been established, placental growth factor (PlGF) is believed to be a key factor. The aim of this study was to assess the effect of maternal smoking on the PlGF expression in invasive trophoblasts at early gestation. We collected villous tissues from women requesting surgical termination due to non-medical reasons at 7-8 weeks of gestation. The maternal smoking status was evaluated by measuring the serum cotinine level and patients were divided into two groups: active smokers and non-smokers. After separating invasive trophoblasts from villous tissues cultured initially under 2% O2 for 24 hours, the separated invasive trophoblasts were cultured under 2% or 8% O2 for 48 hours. The expression levels of the PlGF gene in villous tissue specimens and in invasive trophoblasts cultured after the conditions were quantified using qRT-PCR. The levels of PlGF protein in the medium were quantified using an ELISA. The gene expression level of PlGF in the villi in the active-smokers was significantly higher than that of the non-smokers. In comparison of the invasive trophoblasts under normoxia and oxygenated conditions, the ratio of PlGF gene expression and protein expression under oxygenation (2% O2+8% O2 / 2% O2+2% O2) in the active-smokers were both significantly higher than in the non-smokers. Maternal smoking history appears to stimulate PlGF expression in invasive trophoblasts under oxygenated conditions. This may be one of several causes leading to the protective effect of maternal smoking on preeclampsia.

IL-38: A new factor in rheumatoid arthritis.

The newly characterized cytokine IL-38 (IL-1F10) belongs to the IL-1 family of cytokines. Previous work has demonstrated that IL-38 inhibited Candida albicans-induced IL-17 production from peripheral blood mononuclear cells. However, it is still unclear whether IL-38 is an inflammatory or an anti-inflammatory cytokine. We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, or PR3 in vitro, overexpression of IL-38 cDNA produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene-deficient (-/-) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. As compared with control mice, IL-38 (-/-) mice showed greater disease severity, accompanied by higher IL-1ß and IL-6 gene expression in the joints. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of RA in humans.

Prediction of Fetal Growth Restriction by Analyzing the Messenger RNAs of Angiogenic Factor in the Plasma of Pregnant Women.

OBJECTIVE: To predict the occurrence of fetal growth restriction (FGR) by analyzing messenger RNA (mRNA) expression levels of vascular endothelial growth factor receptor 1 (fms-like tyrosine kinase 1 [Flt-1]) in maternal blood. STUDY DESIGN: Eleven women with FGR were matched with 88 controls. Plasma samples were obtained during each trimester. The Flt-1 mRNA expression levels were compared between groups. Predicted probabilities were calculated, and sensitivity-specificity (receiver-operating characteristic [ROC]) curves were assessed based on regression models for each trimester measurement and possible combinations of measurements. RESULTS: The mRNA levels of the FGR group during all trimesters were significantly higher than those of the control group. The ROC curve of combined first and second trimester data yielded a detection rate of 60% at a 10% false-positive rate, with an area under curve of 0.79. CONCLUSION: The Flt-1 mRNA expression in maternal blood can be used as a marker to predict the development of FGR, long before a clinical diagnosis is made.

Vitamin C Induces the Reduction of Oxidative Stress and Paradoxically Stimulates the Apoptotic Gene Expression in Extravillous Trophoblasts Derived From First-Trimester Tissue.

AIM: To investigate the effects of vitamin C on the expression of the genes related to apoptosis in extravillous trophoblasts (EVTs) in the first trimester. METHODS: Extravillous trophoblasts were cultured under 2% O2 followed by 2% O2 or 8% O2 with or without vitamin C. The level of reactive oxygen species (ROS) in the cultured medium was estimated using electron spin resonance spectroscopy. The expression levels of the genes TP53, BCL2, and BAX were quantified using real-time quantitative polymerase chain reaction. RESULTS: Reactive oxygen species were found to be decreased after adding vitamin C under increasing oxygen concentrations. In addition, the ratio of BAX/BCL2 also increased after adding vitamin C under conditions of 2% O2, while the gene expression level of BCL2 increased after adding vitamin C under increasing oxygen concentrations. In contrast, the gene expression level of TP53 and the ratio of BAX/BCL2 both decreased. CONCLUSION: We have revealed that vitamin C reduces ROS and may promote the apoptosis of EVTs under conditions of 2% O2 while paradoxically preventing apoptosis under increasing oxygen concentrations.

Effects of maternal smoking on the placental expression of genes related to angiogenesis and apoptosis during the first trimester.

OBJECTIVE: Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women. MATERIALS AND METHODS: We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6-8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR. RESULTS: The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group. CONCLUSIONS: Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.

The progression of comorbidity in IL-18 transgenic chronic obstructive pulmonary disease mice model.

Patients with severe COPD are known to have comorbidities such as emaciation, cor pulmonale and right heart failure, muscle weakness, hyperlipemia, diabetes mellitus, osteoporosis, muscle atrophy, arterial sclerosis, hypertension, and depression. Therefore, treatment for COPD needs to focus on these comorbidities as well as the lungs. We previously reported a new mouse model of COPD utilizing the human surfactant protein C promoter SP-C to drive the expression of mature mouse IL-18 cDNA; constitutive IL-18 overproduction in the lungs of transgenic (Tg) mice induces severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension with aging. In the present study, we evaluated the progression of comorbidity in our COPD model. In female Tg mice, significant weight loss was observed at 16 weeks and beyond, when compared with control wild-type (WT) mice. This weight loss was suppressed in IL-13-deficient (knockout; KO) Tg mice. Muscle weight and bone mineral density were significantly decreased in aged Tg mice relative to control WT and IL-13 KO Tg mice. The aged Tg mice also showed impaired glucose tolerance. IL-18 and IL-13 may play important roles in the pathogenesis of comorbidity in COPD patients.

Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers with fatal asthma.

BACKGROUND: The process of airway inflammation in the lungs of nonsmokers who die of asthma (fatal asthma) has not been reported in detail. OBJECTIVE: To examine nonsmokers who had died of asthma to exclude chronic obstructive pulmonary disease and investigate pulmonary inflammatory cells and the expression of interleukin-18 (IL-18) and its receptor in lung tissues compared with those in patients with well-controlled mild asthma and nonsmokers. METHODS: Lung tissues were obtained at autopsy examination from 12 nonsmokers with fatal asthma, excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers with well-controlled mild asthma and 10 nonsmokers who had undergone surgical resection for lung cancer. Pulmonary inflammatory cells were examined and the expression of the proinflammatory cytokine IL-18 and its receptor in the lungs was evaluated. RESULTS: The numbers of eosinophils and lymphocytes, but not basophils or macrophages, were significantly increased in the lungs of patients with fatal asthma compared with the other 2 groups. The lung neutrophil count did not differ significantly between the fatal and mild asthma groups but was significantly higher in the fatal asthma group than in nonsmokers. CD8(+) T cells, but not CD4(+) T cells, were significantly increased in the lungs of the fatal asthma group compared with the other 2 groups. IL-18 protein and IL-18 receptor were strongly expressed in the lungs in the fatal asthma group. CONCLUSION: Caspase-1 inhibitors, anti-IL-18 antibodies, anti-IL-18 receptor antibodies, IL-18 binding protein, or inhibitors of genes downstream of the IL-18 signal transduction pathway may be of clinical benefit for the treatment of patients with severe asthma.

IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma.

Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.

We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of -950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV(1). Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients.

Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.

INTRODUCTION: There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor α (IL-18Rα). In this study, we evaluated the levels and characteristics of soluble IL-18Rα (sIL-18Rα) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. METHODS: The sIL-18Rα complex was isolated from pooled human blood serum using an anti-IL-18Rα monoclonal antibody affinity column. The purified sIL-18Rα was then examined using Western blot analysis and used in experiments to evaluate the effects on an IL-18-responsive natural killer (NK) human cell line, NK0. An enzyme-linked immunosorbent assay was developed, and sera from 145 patients with RA, 6 patients with adult-onset Still's disease, 31 patients with osteoarthritis (OA), 39 patients with systemic lupus erythematosus (SLE) and 67 controls were tested, along with levels of immunoglobulin M, rheumatoid factor, anticyclic citrullinated peptide antibody, IL-18, IL-13 and interferon (IFN)-γ. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18Rα complex. RESULTS: The isolated sIL-18Rα complex can be associated with IL-18 and the soluble form of the IL-18Rß chain. The sIL-18Rα complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2 on the NK0 cell line and inhibited IFN-γ production by the cells. The serum levels of sIL-18Rα complex in RA (186.0 ± 33.5 ng/mL, n = 145) and adult-onset Still's disease (98.2 ± 8.9 ng/mL, n = 6) were significantly (P < 0.001) higher than those in the healthy controls (52.3 ± 8.5 ng/mL, n = 67), OA (38.6 ± 5.4 ng/mL, n = 31), SLE (44.6 ± 3.2 ng/mL, n = 39). The serum level of sIL-18Rα complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-γ in the RA patients were significantly (P < 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18Rα indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (P < 0.0001) decreased levels of sIL-18Rα in the sera of 29 RA patients 6 months after treatment. CONCLUSIONS: The sIL-18Rα complex could be a potentially useful biomarker for the diagnosis of RA.