Long-term outcomes of sentinel lymph node navigation surgery for early-stage cervical cancer.

BACKGROUND: Sentinel lymph node navigation surgery, which identifies the sentinel lymph node in early cervical cancers and omits systemic pelvic lymphadenectomy in cases where no lymph node metastasis is present, has recently gained attention. However, there are few reports on lymph node recurrence and the long-term outcomes of cervical cancer surgery performed using sentinel lymph node navigation surgery. In this study, we aimed to evaluate the long-term outcomes of sentinel node navigation surgery for early-stage cervical cancer. METHODS: One hundred thirty-eight patients with cervical cancer were enrolled. Sentinel lymph nodes were identified by injecting 99 m Technetium-labeled phytate and indocyanine green into the uterine cervix. Surgery and survival outcomes were also analyzed. RESULTS: The median age and body mass index of the patients were 40 years (20-78) and 21.7 kg/m2 (16.5-50.4), respectively. Open surgery, laparoscopic surgery, and robotic surgery were performed in 77 (56%), 53 (38%), and 8 (6%) patients, respectively. The overall and bilateral detection rates of the sentinel lymph node were 100% and 94%, respectively. Only one case (0.7%) exhibited lower extremity lymphedema, and pelvic lymphocele was observed in three cases (2.2%). Four cases (3%) experienced recurrence over a median follow-up of 57.5 months (range, 2-115 months), with five-year recurrence-free and overall survival rates of 97% and 97.3%, respectively. CONCLUSIONS: Our results demonstrate that sentinel node navigation surgery may be safe and effective for early-stage cervical cancer.

Potential prognostic predictors of treatment with immune checkpoint inhibitors for advanced endometrial cancer.

BACKGROUND: Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated. METHODS: Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors. RESULTS: The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10-17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26-24.49; P = 0.023) were independently correlated with overall survival. CONCLUSION: In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.

Serum calciprotein particle-to-phosphate ratio as a predictor of cardiovascular events in incident hemodialysis patients.

INTRODUCTION: Recent studies have identified increased blood calciprotein particle (CPP) levels as risk factors for vascular calcification and cardiovascular events in patients undergoing maintenance hemodialysis. Although positively correlated with serum phosphate levels, serum CPP levels vary considerably among patients with similar serum phosphate levels. We investigated the capacity of the ratio of serum CPP levels to serum phosphate levels (CPP/Pi ratio) to predict cardiovascular events in incident hemodialysis patients compared to the serum calcification propensity test (T50). METHODS AND RESULTS: The association between the CPP/Pi ratio and major adverse cardiac and cerebrovascular events (MACCE) was investigated in 174 incident hemodialysis patients. Multivariate analysis revealed that the CPP/Pi ratio was independently associated with MACCE [hazard ratio 1.60, 95% confidence interval (1.15-2.23), p = 0.006] but serum T50 levels were not. CONCLUSIONS: The CPP/Pi ratio is a useful, novel biomarker for predicting the risk of cardiovascular events in patients undergoing incident hemodialysis.

Potential Risks of Severe Infection Following the Exploratory Laparoscopy for Advanced Ovarian Cancer: A Case Report and a Literature Review.

Although exploratory laparoscopy in patients with advanced ovarian cancer is a diagnostic tool for determining treatment strategy, its safety has not been completely investigated. We report a case involving a severe abdominal abscess following an exploratory laparoscopy. A 65-year-old woman with advanced ovarian cancer developed a large abdominal abscess following exploratory laparoscopy and neoadjuvant chemotherapy. Emergent laparotomy was performed; while massive bowel adhesion surrounding the abscess did not allow for genital organ resection, an incision in the left port area was made to drain the abscess. The patient's chemotherapy was delayed because she experienced sub-ileus, postoperatively. Only a limited number of studies have been conducted on the safety of these techniques. This intense infection case emphasizes the need for further investigations into the safety of exploratory laparoscopy in patients with progressive diseases under heterogeneous conditions in real-world settings.

Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma.

BACKGROUND: Cabozantinib is highly effective against advanced renal cell carcinoma (RCC). However, approximately 60% of the patients require a dose reduction due to severe adverse events. Although associations between trough concentrations of cabozantinib and its efficacy and safety have been reported in other countries, reports on Japanese patients are unavailable. Therefore, we investigated the association of cabozantinib trough concentration with therapeutic efficacy and adverse events in Japanese patients with RCC and evaluated the usefulness of therapeutic drug monitoring. METHODS: In this prospective observational study, we measured the trough concentrations of cabozantinib in 10 Japanese patients with RCC enrolled between May 2022 and September 2023. The associations of trough concentration with treatment response, as determined by RECIST 1.1, and the occurrence of grade 2 or higher adverse events were assessed. RESULTS: Trough concentration was higher in patients with controlled cancer than in those with progressive cancer (1024 ± 352 versus 457 ± 216 ng/mL, P = 0.035). In addition, patients with grade 2 or higher adverse events showed a significantly higher trough concentration than those without (1560 ± 513 versus 807 ± 319 ng/mL, P = 0.032). In particular, grade 2 or higher dysgeusia, anorexia, fatigue, and dyspepsia significantly correlated with trough concentrations. CONCLUSIONS: This is the first clinical study to demonstrate a correlation between cabozantinib trough concentration, therapeutic efficacy, and adverse events in Japanese patients with RCC. The therapeutic drug monitoring of cabozantinib could be useful for improving therapeutic efficacy and avoiding serious adverse events.

[Penetrating Lung Injury Complicated by Hemodynamic Cerebral Infarction].

We encountered a case in which emergency surgery was performed for a penetrating lung injury complicated by a hemodynamic cerebral infarction. A 45-year-old man sustained a chest injury due to a scattered piece of metal and was admitted to a nearby hospital. He was confirmed to have hemorrhagic shock due to a right hemopneumothorax, and a chest tube was inserted he was transferred to our hospital. Chest radiography and computed tomography (CT) revealed a metal fragment in the right lung and confirmed the diagnosis of a penetrating lung injury due to a foreign body. The patient also presented with total blindness of an unknown etiology. Emergency surgery was performed to treat the injury and remove the foreign body. A large amount of blood and hematoma were removed from the right thoracic cavity, and a metal fragment was found in the lower lobe of the right lung. After removing the foreign body, pulmonary suturing was performed. On the following day, head magnetic resonance imaging revealed multiple cerebral infarctions in the bilateral occipital lobes, left frontal lobe, and left cerebellar hemisphere. However, no vascular occlusion or thrombus was found, and the patient was diagnosed with hemodynamic cerebral infarction due to hemorrhagic shock.

Three Cases of Serous Tubal Intraepithelial Lesions (STILs).

Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesions (STILs), and the p53 signature are considered to be related to precursor lesions of high-grade serous carcinomas (HGSCs). However, the clinical significance and prognostic implications of these lesion types are currently unknown. We diagnosed three patients with STILs according to the morphological evaluation criteria and combined this with p53 and Ki-67 immunostaining. One patient had an HGSC of the ovary that was incidentally discovered at the time of ovarian cyst resection, and the HGSC in the other two patients was characterized after they underwent risk-reducing salpingo-oophorectomy. Herein, we present a report of three patients with STILs diagnosed based on clinical data and pathological findings, along with a review of the literature.

Brief Report: Tepotinib as a Treatment Option in MET Exon 14 Skipping-Positive Lung Cancers-Investigating Discordance Between ArcherMET and the Oncomine Dx Target Test.

Introduction: NSCLC is a leading cause of cancer-related mortality worldwide. Specific genetic alterations, such as MET exon 14 (METex14) skipping, have been identified in NSCLC, allowing targeted therapy. Tepotinib, a highly selective MET inhibitor, has displayed promise in patients with advanced NSCLC. Nevertheless, challenges arise when identifying treatment strategies for patients with discordant results regarding METex14 skipping detection between diagnostic tests. Methods: We investigated patients with NSCLC and discordant results for METex14 skipping between the Oncomine Dx Target Test (ODxTT) and ArcherMET. Clinical response, adverse events, and the duration of tepotinib treatment were assessed, and statistical analysis was performed. Results: Among the 19 patients deemed METex14 skipping positive by ODxTT, only 10 had concordant results with ArcherMET. The number of METex14 skipping reads detected by ODxTT was significantly lower in discordant cases. Of the 19 patients, 14 received tepotinib, and comparable response and disease control rates were observed in both concordant and discordant cases. The duration of treatment did not significantly differ between the two groups. Conclusions: Our findings suggest that tepotinib has comparable therapeutic effects in patients with METex14 skipping-positive NSCLC irrespective of the concordance of results between ODxTT and ArcherMET. Tepotinib is a possible treatment option for patients with METex14 skipping, even in patients with discordant test results.

Robot-assisted radical cystectomy for bladder cancer after low anterior resection: A case report.

Radical cystectomy after low anterior resection is rare, and no cases of robotic surgery have been reported. Cystectomy in patients who have undergone a previous pelvic surgery, whether open or endoscopic, requires caution to avoid damaging other organs due to anatomical changes caused by adhesions in a limited space. Additionally, the curative nature of the treatment must be maintained. We describe a 69-year-old man with a history of open low anterior resection for rectal cancer who underwent robot-assisted radical cystectomy with extracorporeal ileal conduit construction. Although this procedure is challenging, it was performed safely with the collaboration of colorectal surgeons. The patient was discharged without perioperative complications and remained recurrence-free for 5 years.

Multiple-Community-Based Epidemiological Study of Stuttering among 3-Year-Old Children in Japan.

INTRODUCTION: Many epidemiological studies of the disorder of stuttering have been conducted during the 20th century, continuing during the current one. Unfortunately, only a few were carried out in Japan. This study aimed at assessing (1) the incidence and prevalence of stuttering in 3-year-old children in multiple Japanese communities and (2) factors associated with the onset of stuttering among these children. METHODS: A questionnaire aimed at screening for the presence of stuttering was employed for 2,055 children aged 3 years, who underwent a standard nationwide health checkup. Positive responses were confirmed in several ways: (1) direct interviews and assessment of the child's speech, (2) confirmatory questionnaire, or (3) telephone interviews by licensed Speech Language Hearing Therapists. RESULTS: Approximately 6.5% of the children were found to exhibit stuttering at the time of their health checkup. This figure rose to 8.9% after including individuals who previously, but not currently, were reported to have exhibited stuttering. Among the putative risk factors, higher stuttering odds (odds ratio, OR = 3.27) were detected in those with a family history of stuttering, those whose guardians had concerns about their child's development (OR = 1.75), and those with diagnosed diseases or disabilities (OR = 2.13). DISCUSSION/CONCLUSIONS: It was concluded that, in Japan, both the risk of stuttering incidence (8.9%) in children up to, and including, the age of 3 years, as well as its prevalence (6.5%) in this population, was similar to those reported by recent studies in other countries. Additionally, our findings also confirmed that an increased risk for stuttering at age 3 is associated with a family history of stuttering.

Efficacy of Transvaginal Surgery Using an ORIHIME Mesh With Wider Arms and Adjusted Length.

INTRODUCTION: Transvaginal mesh surgery (TVM) is an effective treatment measure for pelvic organ prolapse (POP). However, the ORIHIME mesh (Kono Seisakusho, Japan, Tokyo), which has the disadvantage of poor adherence to tissues, is currently the only product available for this procedure. Our research team has previously developed a modified ORIHIME mesh with wider arms with the aim of minimizing the risk of POP recurrence. Additionally, the length of the mesh behind the anterior vaginal wall has been adjusted to prevent urinary incontinence. The current study aims to examine the efficacy of this modified mesh in minimizing postoperative complications in patients undergoing uphold-type TVM. METHODS: The data of 84 patients who underwent TVM using ORIHIME at our hospital since July 2019 were retrospectively analyzed. The patients were divided into three groups as follows: (a) normal arms (NA; arm width < 6 cm; n = 29 cases); (b) wide arms without length adjustment (WA and LA (-); arm width > 6 cm; n = 27 cases); and (c) wide arms with length adjustment (WA and LA (+); n = 28 cases). Data were collected using various questionnaires, and the residual urine volume was measured before and after surgery. Additionally, the 60-minute pad test was performed where possible, and the recurrence and complication rates were recorded. RESULTS: The incidence of mesh exposure and urinary incontinence in daily life tended to be lower in the WA and LA (+) groups, although this difference was not statistically significant. The one-year postoperative POP recurrence rate, residual urine volume, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score were significantly lower in the WA and LA (+) groups compared to the other groups. CONCLUSION: Uphold-type TVM using the modified ORIHIME mesh with wider arms and adjusted length was associated with better postoperative treatment outcomes compared to TVM using the traditional ORIHIME mesh.

Invasive group A streptococcal infection can be fatal to pregnant women in restricted medical resources remote areas-Emergent alert after COVID-19 pandemic.

Invasive group A streptococcal (iGAS) infection is a leading cause of maternal death. The increase in the number of patients with iGAS in Japan is markedly greater than before the coronavirus pandemic. We encountered a case of iGAS infection, on a remote island with restricted medical resources, in a third-trimester pregnant woman, resulting in both maternal and fetal death. A 34-year-old woman was admitted via a local general hospital with a high fever. Intrauterine fetal death disseminated intravascular coagulation, and septic shock were confirmed. Broad-spectrum antibiotics were started, and the patient was returned to the local general hospital. Eight hours after arrival, the patient died of circulatory and respiratory dysfunction complications. iGAS infections in remote areas may directly lead to life-threatening conditions and should be treated as an emergency, comparable to the serious conditions of placental abruption or placenta previa.

Erratum: Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality.

[This corrects the article DOI: 10.1016/j.isci.2022.105766.].

Can Endometrial Cytology Identify Patients Who Would Benefit from Immunotherapy?

INTRODUCTION: Patients with polymerase epsilon (POLE) mutation (POLEmut) subtype, MMR-deficient (MMR-d) subtype as classified by The Cancer Genome Atlas (TCGA), and a high tumor mutation burden (TMB-high) potentially benefit from immunotherapy. However, characteristics of the cytological morphology within these populations remain unknown. METHODS: DNA extracted from formalin-fixed paraffin-embedded tissues was subjected to next-generation sequencing analysis. Genomic mutations related to gynecological cancers, TMB, and microsatellite instability were analyzed and were placed in four TCGA classification types. The following morphological cytological investigations were conducted on endometrial cancer using a liquid-based preparation method, prior to the commencement of initial treatment: (i) cytological backgrounds; (ii) differences between each count of neutrophils and lymphocytes as described below. RESULTS: Insignificant differences in the cytological background patterns of TCGA groups and TMB status were found. Although there was no significant difference in neutrophil count (p = 0.955) in the TCGA groups, POLEmut and MMR-d had significantly higher lymphocyte counts than no specific molecular profile (NSMP) (p = 0.019 and 0.037, respectively); furthermore, p53mut also tended to be significant (p = 0.064). Lymphocyte counts in TMB-high were also significantly greater than TMB-low (p = 0.002). POLEmut showed a positive correlation between TMB levels and lymphocyte counts. For predicting patients with POLEmut plus MMR-d, lymphocyte counts demonstrated a superior diagnostic accuracy of area under the curve (AUC) (0.70, 95% CI: 0.57-0.84), with a cutoff value of 26 high-power field. CONCLUSION: Lymphocyte count using liquid-based cytology for patients with endometrial cancer may predict POLEmut plus MMR-d of TCGA groups and TMB-high in those who can benefit from immunotherapy.

Favorable Postoperative Outcomes After Transvaginal Mesh Surgery Using a Wide-Arm ORIHIME® Mesh.

Introduction Transvaginal mesh surgery (TVM) is an effective treatment option for pelvic organ prolapse (POP). Although ORIHIME®, the only available mesh product, is thin, soft, and easy to handle, it has the disadvantages of sliding off or mildly adhering to the surrounding tissues. The current study compared the efficacy of using wide-arm ORIHIME (Kono Seisakusho, Japan, Tokyo), non-wide arm ORIHIME, Gynemesh PS (Johnson and Johnson, Japan, Tokyo), and Polyform (Boston Scientific Japan, Japan, Tokyo) meshes for TVM. Methods The study included 116 patients who underwent TVM (Prolift with Gynemesh PS (n = 14); Elevate with Polyform (n = 43); Uphold with non-wide-arm ORIHIME (n = 24); Uphold with wide-arm ORIHIME (n = 35)) at our hospital. Pre- and post-surgical changes in symptoms were measured using questionnaires and 60-minute pad weight testing and compared by mesh type and surgical methods used. Results The residual urine volume, 60-minute pad weight testing, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and international consultation on incontinence questionnaire-short form score (ICIQ-SF) significantly improved one year postoperatively in the TVM with the wide-arm ORIHIME group. Comparison of pre and one-year postoperative findings by mesh type and surgical methods used showed no significant differences in the 60-minute pad test, IPSS, Quality of Life (QOL), OABSS, and urinary incontinence in daily life scores, and improvement in residual urine volume, ICIQ-SF, and mesh exposure and POP recurrence rates in the TVM with the wide-arm ORIHIME group. Conclusion TVM with wide-arm ORIHIME had better postoperative outcomes compared to TVM with other mesh products.

Correction: Anti-inflammatory effects of cold atmospheric plasma irradiation on the THP-1 human acute monocytic leukemia cell line.

[This corrects the article DOI: 10.1371/journal.pone.0292267.].

Vasohibin-1 Expression Can Predict Pathological Complete Remission of Advanced Bladder Cancer with Neoadjuvant Chemotherapy.

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NAC) is a well-established standard practice in invasive bladder cancer (BCa), however patient selection remains challenging. High expression of vasohibin-1 (VASH1), an endogenous regulator of angiogenesis, has been reported in high-grade and advanced BCa; however, its prognostic value for chemotherapy outcomes remains unexplored. In this study, we sought to identify biomarkers of chemotherapy response focusing on the relationship between angiogenesis and tissue hypoxia. METHODS: Forty Japanese patients with BCa who underwent NAC and radical cystectomy were included in the present analysis. We compared the immunohistochemical expression of CD34, VASH1, and carbonic anhydrase 9 (CA9) between patients who achieved tumor clearance at operation (ypT0) and those with residual disease after cystectomy. RESULTS: There were 19 patients in the ypT0 group, while the remaining 21 patients had residual tumors at operation. Patients in the ypT0 group had high microvessel density (p = 0.031), high VASH1 density (p < 0.001), and stronger CA9 staining (p = 0.046) than their counterparts. Multivariate analysis identified microvessel and VASH1 density as independent predictive factors for pathological ypT0 disease (p = 0.043 and 0.002, respectively). The 5-year recurrence-free survival rate was higher in the high VASH1 density group than in the low VASH1 density group (66.3% vs. 33.3%, p = 0.036). CONCLUSION: VASH1 density is a potential therapeutic biomarker for chemotherapy response in BCa.

Intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer: association for pathological factors and oncologic outcomes.

OBJECTIVE: To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. METHODS: This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. RESULTS: Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). CONCLUSION: This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.