Japanese Center Research Articles

Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction.

Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC. We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0-6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality-related cardiac phenotypes.

Safety and efficacy of endoscopic submucosal dissection with gel immersion technique for superficial esophageal neoplasms.

Gel immersion (GI) endoscopy provides a good visual field in endoscopic submucosal dissection (ESD); however, its clinical outcomes are poorly understood. This study aimed to compare the treatment outcomes between esophageal gel immersion endoscopic submucosal dissection (GI-ESD) and conventional ESD (C-ESD) to determine the safety and efficacy of GI-ESD. The data of 71 consecutive patients who underwent esophageal ESD between April 2021 and March 2023 at a Japanese tertiary center were retrospectively reviewed. GI was achieved using an additional irrigation tube. The treatment outcomes between the GI-ESD and C-ESD groups were compared using inverse probability of treatment weighting (IPTW) to control for confounding factors. A total of 75 superficial esophageal epithelial neoplasms (41 in the C-ESD and 34 in the GI-ESD groups) were treated using ESD. The mean procedure time in the GI-ESD group was significantly shorter than that in the C-ESD group (59.2±36.2 vs 85.3±45.7min, P=0.008). After IPTW adjustment, the mean procedural times were 62.6±36.6 and 82.9±41.7min in the GI-ESD and C-ESD groups, respectively (P=0.037), and the incidence rate of muscle layer damage was 4.2% in the GI-ESD group and 30.6% in the C-ESD group (P=0.001). In the multivariate analysis, specimen size ≥30mm (odds ratio [OR]: 9.44, 95% confidence interval [CI]: 2.46-36.30, P=0.001) was positively correlated with longer procedural time (≥90min), whereas GI-ESD (OR: 0.19, 95%CI: 0.05-0.68, P=0.011) showed a negative association. Esophageal GI-ESD may be useful in terms of safety and time efficiency. The GI technique could be an option for esophageal ESD.

Splenectomy Before Recipient Hepatectomy for Inflow Modulation Using a Very Small Modified Right Hemiliver Graft: A Case Report

Portal inflow modulation has become standard practice in many transplant centers performing living donor liver transplantation. This is believed to counteract the deleterious effects of excess portal flow into a small-for-size graft. A splenectomy negates the contribution of the splenic vein flow completely and thereby substantially reduces portal inflow. Although it has been adopted as a standard strategy by many Japanese centers for inflow modulation, especially while using left hemiliver grafts, there is justifiable apprehension about its usage due to potential increases in morbidity. Described here is a splenectomy performed while using a modified right hemiliver graft with a graft to recipient weight ratio of 0.49. The challenges in decision making and reasons regarding how such a small graft might have worked without manifestations of small-for-size/flow syndrome are discussed.

Safe and favorable prognosis of thoracic endovascular aortic repair for the low-risk patients with non-acute type B aortic dissection

ObjectivePreemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.DesignRetrospective multicenter analysis.MethodsWe analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.ResultsDuring follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p < 0.01), and the diameter of the false lumen was reduced (−8 ± 4.8 vs. −1.3 ± 8.0, p < 0.001).ConclusionsShort- and long-term outcomes of TEVAR for uncomplicated TBAD with a small aortic aneurysm were excellent, with few postoperative complications. After TEVAR, aortic remodeling was observed in the short term, suggesting that it may contribute to the prevention of aortic-related death due to rupture.

Clinical outcomes and impact of mitral valve surgery in atrial functional mitral regurgitation: the REVEAL-AFMR registry

Abstract Background The real-world impact and effective treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. The aim of this study was to investigate the prevalence, clinical characteristics, and the effectiveness of mitral valve surgery in AFMR. Methods The REal-world obserVational study for invEstigAting the prevaLence and therapeutic options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR) was a retrospective cohort study conducted across 26 Japanese centers. All transthoracic echocardiography performed in 2019 were reviewed and patients with moderate or severe AFMR defined by preserved left ventricular function, dilated left atrium, and absence of degenerative valvular changes. The primary composite outcomes were heart failure hospitalization and all-cause mortality. Besides traditional multivariable regression analysis, propensity score-based time-zero matching was performed to account for immortal time bias. Results In 177,235 patients who underwent echocardiography, 8,867 had moderate or severe MR. Within this group, 1,007 were diagnosed with AFMR (mean age 78±10, 56% female, 80% atrial fibrillation). Of these, 113 underwent MV surgery, with 81% receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR, larger left heart chambers, and a higher prevalence of heart failure than those who remained under medical therapy. During a median follow-up of 1050 days, 28% experienced the primary outcome, and 18% died. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had significantly lower rate of the primary outcome (hazard ratio 0.43 [0.29-0.64], p<0.001 after adjustment for 25 covariates). Propensity score-based time-zero matching also indicated a lower risk of the primary outcome in the surgical group (hazard ratio 0.39 [0.20–0.78], p=0.007). Multiple sensitivity analyses yielded consistent results. Subgroup analysis suggested a significantly greater benefit of surgery for patients with severe MR than those with non-severe MR (p for interaction=0.044). Conclusions Our registry revealed that patients with AFMR are typically old with predominantly with atrial fibrillation, facing poor outcomes. MV surgery was associated with fewer adverse events, a finding that should be validated in future clinical trials.

Effect of the COVID-19 Pandemic on the Mental Status of Pregnant Women: A Single-Center Study.

The coronavirus disease 2019 (COVID-19) pandemic has forced people to make major life changes, and there is concern that depressive tendencies have increased in pregnant women during the pandemic. This study used the Edinburgh Postnatal Depression Scale (EPDS), administered in the second trimester, to investigate the effect of COVID-19 on the mental health of Japanese women during pregnancy and to provide early intervention. The study included 1,320 pregnant women (663 pre-COVID-19 and 657 during COVID-19) with similar background characteristics and compared the results for the COVID-19 period (September 2020-August 2021) and control period (September 2018-August 2019). Women treated for psychiatric disorders were excluded. The EPDS cutoff score was 13. The median EPDS scores were 3 (1-6) points during the control period and 3 (1-5) points during the pandemic (p = 0.166) for the control and pandemic periods. Fourteen patients (2.1%) during the control period and 20 (3.0%) during the pandemic scored ≥13 points; however, the difference was not significant (odds ratio, 1.455; 95% confidence interval: 0.692-3.143). COVID-19 did not change mid-pregnancy EPDS scores at a single Japanese center.

Association between health-related hope and distress from restrictions in chronic kidney disease and dialysis

BackgroundIn chronic kidney disease (CKD), the durability of patient adherence to fluid and dietary restrictions may depend on the degree to which they have hope that they will enjoy life. Previous cross-sectional studies have shown that higher hope was associated with lower distress from fluid and dietary restrictions and better adherence in the short term. In this study, we aimed to examine the long-term relationship of hope with distress from fluid and dietary restrictions.MethodsThis prospective observational cohort study included 444 patients with CKD undergoing dialysis in one of five Japanese nephrology centers. Hope as a predictor was measured using an 18-item health-related hope scale. Outcomes were two-item measures of distress from fluid and dietary intake restrictions using the Japanese version of the Kidney Disease Quality of Life Short Form, Version 1.3 (higher scores indicate lower levels of distress). Multivariate linear mixed models were used to estimate the association of baseline health-related hope with distress from fluid and dietary restrictions at baseline and follow-up.ResultsThe mean age of the participants was 67 years, and 31.1% of them were females. In total, 124, 98, and 222 had non-dialysis CKD, peritoneal dialysis, and hemodialysis, respectively. Higher levels of baseline health-related hope were associated with lower levels of distress from fluid restriction after one year (per 10-point increase, 2.6 points (95% confidence interval, 1.0 to 4.1)); whereas the baseline score was not associated with the distress from fluid restriction at 2 years. Similarly, higher levels of baseline health-related hope were associated with lower levels of distress from dietary restriction after one year (per 10-point increase, 2.0 points (95% confidence interval, 0.3 to 3.6)); whereas the baseline score was not associated with the distress from dietary restriction at 2 years.ConclusionsHealth-related hope, regardless of depression, can potentially mitigate long-term distress from fluid and dietary restrictions in patients with a wide range of CKD severities.Trial registrationUMIN000054710.

Patients with anti-small ubiquitin-like modifier activating enzyme-positive dermatomyositis resembling antisynthetase syndrome with poor prognosis: a bicentric international retrospective study and literature review.

This study aimed to describe adult Brazilian and Japanese patients with anti-small ubiquitin-like modifier activating enzyme (SEA)-positive dermatomyositis (DM), as there are few studies in the literature. A literature review was also conducted. This bicentric international retrospective study, conducted between 2012 and 2023, included patients with anti-SAE-positive DM (2017 European League Against Rheumatism/American College of Rheumatology classification criteria). All demographic features and clinical, laboratory, therapeutic, and follow-up data were collected from Brazilian and Japanese centers using pre-standardized and parameterized information. We included 17 adult patients with a median age of 65 (56-76) and a predominance of females (82.4%). Constitutional symptoms at baseline were present in 58.8% of the patients. In addition to classical cutaneous DM lesions, one-third of the patients had myalgia and significant muscle weakness, whereas half presented with dysphagia, interstitial lung disease, and joint manifestations. The first-line treatment consisted of intravenous methylprednisolone and immunoglobulin pulse therapy in 41.2% and 28.6% of the patients, respectively. The median follow-up duration was 20 (13-74) months; at the last medical evaluation, half had active disease and were still using oral glucocorticoids (median dosage, 10.0 mg/day). Approximately one-fifth to one-third of the patients were diagnosed with different types of cancer, had severe infections, or died. Patients with anti-SAE-positive DM not only resemble the phenotype of antisynthetase syndrome but are also associated with a poor prognosis.

Carbon-Ion Radiation therapy for Adenocarcinoma of the Uterine Cervix: Clinical Outcomes of a Multicenter Prospective Registry-Based Study in Japan (2016-2020)

Cases of adenocarcinoma of the uterine cervix (AUC) have poorer prognoses than those of squamous cell carcinoma. Carbon-ion radiation therapy (CIRT) outcomes for AUC have been reported in retrospective or single-institutional prospective studies but not prospective multicenter studies. We present the results of CIRT for AUC in a prospective multicenter study using a nationwide hospital-based registry in Japan. Patients with locally advanced untreated AUC who received CIRT at 4 Japanese centers between June 2016 and April 2020 were included in this study. In the absence of organ dysfunction, up to 5 weekly 40 mg/m2 cisplatin courses were administered. The primary endpoints were 2-year overall survival and local control rates. The secondary endpoints were 2-year disease-free survival rate and late adverse events (AEs). Forty-two patients were enrolled with a median age of 54 years (range, 34-76 years). Patients were diagnosed with stage IIB (n = 26), IIIB (n = 12), or IVA (n = 4) disease. The median follow-up period was 24 months. The 2-year overall survival, local control, and disease-free survival rates were 97.5% (95% CI, 92.7%-100.0%), 80.9% (95% CI, 66.9%-94.8%), and 64.3% (48.1%-80.4%), respectively. Two patients developed grade 3 rectum/sigmoid AE. One patient required urinary diversion surgery during a salvage operation for local tumor recurrence (grade 3 genitourinary AE). No other grade 3 or worse toxicities were reported. CIRT is an effective treatment for locally advanced AUC. Further research is required to validate the safety and efficacy of CIRT for AUC.

Real-world antithrombotic strategies in patients with atrial fibrillation and recently developed acute coronary syndrome

BackgroundThe antithrombotic strategy for patients with atrial fibrillation (AF) and coronary artery disease following percutaneous coronary intervention is shifting towards less intensive. Nevertheless, for patients with AF and acute coronary syndrome (ACS), an optimal antithrombotic strategy is yet to be established. Methods and resultsWe conducted a multi-center cohort study involving 146 Japanese centers that had prospectively registered 460 patients with AF and ACS followed for 2 years. Primary endpoint was the composite of thrombotic and bleeding events, and secondary endpoints included heart failure hospitalization. At the time of study registration, 86% of participants had received direct oral anticoagulants (DOACs) and 75% had received aspirin-based triple antithrombotic therapy (TAT) between March 2017 and August 2019. Apixaban was the most frequently used DOAC (29%). While the proportion of anticoagulants did not change according to the time course, the intensity of antiplatelets significantly attenuated over time (dual antiplatelet at baseline: 75%, and at 2-years: 7%). The cumulative incidence of the primary outcome measure was similar in patients with warfarin and DOACs. However, the risk of heart failure hospitalization was significantly higher in those with warfarin compared to DOACs (Hazard ratio: 2.8, 95% confidence interval: 1.1-5.8, p=0.022). ConclusionsThe present findings suggest the appropriate optimization of antithrombotic medication balancing in patients with AF and ACS in Japan by reducing the intensity of antiplatelets during the study period.

Dexamethasone is non-inferior to antihistamine plus dexamethasone premedication in preventing ramucirumab plus nab-paclitaxel infusion-related reactions in gastric cancer: a multicenter retrospective study

PurposeRamucirumab (RAM) is recommended as premedication with H1-receptor antagonists (H1RA) to prevent infusion-related reactions (IRRs). However, RAM is a human antibody with a low incidence of IRRs. We evaluated the noninferiority of non-H1RA (dexamethasone [DEX] alone) premedication to H1RA (plus DEX) premedication in terms of IRRs in patients with gastric cancer receiving RAM plus nanoparticle albumin-bound paclitaxel (nab-PTX).MethodsThis was a noninferiority, multicenter, retrospective trial conducted in three Japanese centers to assess the incidence of IRRs in patients receiving RAM plus nab-PTX for gastric cancer between 2018 and 2023. Patients with gastric cancer receiving RAM plus nab-PTX were divided into groups with and without H1RA premedication. The incidence of IRRs was compared between the two groups.ResultsNinety patients were evaluated, with non-H1RA and H1RA premedications in 43 and 47 cases, respectively. After the first dose of RAM, IRRs were not observed in either group. IRRs during the overall doses were 0% for non-H1RA premedication and 2.1% for H1RA premedication (90% confidence interval (CI): –5.6%–1.3% for each comparison). The upper limit of the 90% CI (1.3%) did not exceed the noninferiority margin (Δ) of + 10% and therefore met the noninferiority criteria.ConclusionRAM plus nab-PTX for gastric cancer with DEX premedication may be possible without H1RA premedication.

“My Japanese is Blue, Because it Makes Me Blue”: Centering Emotion in Language Practices Through Language Mapping

Since the social turn in applied linguistics, there has been growing interest in the role of emotion in language practices. This role is especially relevant to self-access language learning in terms of how it influences learner autonomy and motivation. With its focus on autonomy and sociality, self-access learning offers unique affordances for facilitating learner and advisor awareness of emotion in language learning. To this end, this study used an arts-based method, language mapping, for learners to express their language practices in multimodal ways. Language mapping integrates body mapping and language portraits methods to catalyze individual and group reflection anchored by embodied, emotional experiences. The researchers collaborated with a Japanese university self-access language learning center to engage seven volunteer participants in a series of two workshops. Data were gathered through participants’ language maps, narratives shared in workshops, and questionnaire responses. Findings highlight the potential of language mapping in exploring learners’ affective connections to their named languages. While mother tongues were generally portrayed as comforting, vivid, default, and unconscious, relationships to learned languages were represented through more diverse visual and verbal metaphors. Key pedagogical considerations include the impact of exemplars and group processes.

“My Japanese is Blue, Because it Makes Me Blue”: Centering Emotion in Language Practices Through Language Mapping

Since the social turn in applied linguistics, there has been growing interest in the role of emotion in language practices. This role is especially relevant to self-access language learning in terms of how it influences learner autonomy and motivation. With its focus on autonomy and sociality, self-access learning offers unique affordances for facilitating learner and advisor awareness of emotion in language learning. To this end, this study used an arts-based method, language mapping, for learners to express their language practices in multimodal ways. Language mapping integrates body mapping and language portraits methods to catalyze individual and group reflection anchored by embodied, emotional experiences. The researchers collaborated with a Japanese university self-access language learning center to engage seven volunteer participants in a series of two workshops. Data were gathered through participants’ language maps, narratives shared in workshops, and questionnaire responses. Findings highlight the potential of language mapping in exploring learners’ affective connections to their named languages. While mother tongues were generally portrayed as comforting, vivid, default, and unconscious, relationships to learned languages were represented through more diverse visual and verbal metaphors. Key pedagogical considerations include the impact of exemplars and group processes.

Comparison of robotic versus laparoscopic total gastrectomy for gastric cancer: A single-center retrospective cohort study in a Japanese high-volume center

BackgroundRobotic-assisted surgery has become increasingly popular worldwide in recent years. This study aimed to compare the surgical outcomes of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) to figure out the advantages of RTG. MethodsThe eligible cases in this study were patients who underwent RTG or LTG for gastric adenocarcinoma at our hospital from January 2014 to December 2022. Propensity score matching (PSM) was employed to balance the underlying selection bias. Then, surgical outcomes of patients were analyzed to be compared. ResultsOverall, 255 patients (LTG: 178, RTG: 77) were included in this study. After PSM, 73 patients in each arm were assigned for analysis. Operation time was longer in the RTG than in the LTG (373 vs 336 min, p < 0.01). However, the RTG was associated with shorter postoperative hospital stays (8 vs 9 days, p = 0.04) and lower incidence of grade 3 or higher postoperative complications (1 % vs 11 %, p = 0.03). More lymph nodes were harvested in the RTG (59 vs 47, p < 0.01). ConclusionsAlthough RTG requires longer operation time, it has the potential to provide advantages to the patient such as quicker recovery, reduction in postoperative complication, or more yield number of lymph nodes. Regarding survival outcomes, further analysis with enough follow-up is needed.

A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy.

To evaluate the efficacy and safety of nanvuranlat [an L-type amino acid transporter 1 inhibitor] monotherapy as a later-line treatment in advanced, metastatic, and refractory biliary tract cancers. A multicenter, randomized, double-blind, placebo-controlled phase II study was conducted across fourteen leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of 5 consecutive days, followed by 9 days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and disease control rate. Subgroup analysis was performed in patients with high L-type amino acid transporter 1 expression and biliary tract cancer subtypes. A total of 211 patients were screened, of which 105 eligible patients were randomized. Among these, 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared with placebo (HR, 0.56; 95% confidence interval, 0.34-0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory biliary tract cancer with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.

Agile Innovation or Perfect Product? Cross-Cultural Management Challenges and Opportunities of Japanese In-House Software Centers in India

Agile Innovation or Perfect Product? Cross-Cultural Management Challenges and Opportunities of Japanese In-House Software Centers in India

Arkema establishes UV/LED/EB technologies innovation laboratory at its Japanese Technical Center

Arkema establishes UV/LED/EB technologies innovation laboratory at its Japanese Technical Center

Clinical and Angiographic Outcomes of Bilateral Internal Thoracic Artery Revascularization: In Situ vs Free Grafts

BackgroundBilateral internal thoracic artery (ITA) grafting is associated with improved long-term outcomes; however, the appropriate graft configuration remains controversial. We compared the long-term outcomes of different graft configurations. MethodsBetween 2009 and 2015, 1171 patients underwent isolated bilateral ITA grafting for left-sided complete revascularization at 4 Japanese cardiac surgery centers: underwent in situ left ITA to the left anterior descending artery plus in situ right ITA to the left circumflex artery (LR group, n = 278), in situ right ITA to the left anterior descending artery plus in situ left ITA to the left circumflex artery (RL group, n = 665), and in situ left ITA to the left anterior descending artery plus free right ITA to the left circumflex artery (free group, n = 228). Major adverse cardiovascular events (MACEs), including mortality, myocardial infarction and revascularization, and ITA patency, were compared. ResultsAmong the 3 groups, the free group showed significantly lower MACEs and overall mortality rates (P < .001). Nonfatal myocardial infarction and revascularization rates showed no marked differences among the groups. A weighted analysis revealed a decreased risk of MACEs and death in the free group. No marked difference was observed in the patency of the ITA anastomosed to the left anterior descending artery. Patency of the ITA grafted to the circumflex artery in the LR group was significantly lower relative to the other groups. Using a free right ITA grafted to the circumflex artery reduced the risk of graft failure. ConclusionsThe free right ITA configuration for left-sided revascularization might have better long-term outcomes and significantly better patency than other grafts.

Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets.

Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52-76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Standardization of robot-assisted radical nephroureterectomy via intraperitoneal approach: insights from a high-volume Japanese Center.

We present the trial-and-error process of standardizing robot-assisted radical nephroureterectomy (RANU) at a high-volume center in Japan. Our urology team performed 53 RANU cases using the Da Vinci Xi system, undergoing five major evolutionary stages. We performed RANU via transperitoneal approach in all cases and lymph-node dissection in selected cases. During the evolution, we adopted a lithotomy position and significantly modified port placement to facilitate lower ureter management. However, we ultimately arrived at a method that minimizes port and patient repositioning during lower ureter processing. By strategically placing ProGrasp™ forceps in the most caudal port, we effectively retracted the bladder and grasped the opened bladder wall during lower ureter manipulation. This approach also allowed us to perform pelvic, para-aortic, and renal portal lymph-node dissection without major changes in patient positioning or port placement. Nevertheless, we acknowledge that some variations in positioning and techniques may be necessary depending on specific case requirements.