Prognostic Importance of Lymphovascular Invasion for Specific Subgroup of Patients with Prostate Cancer After Robot-Assisted Radical Prostatectomy (The MSUG94 Group).

OBJECTIVE: This study aimed to investigate whether lymphovascular invasion (LVI) was associated with oncological outcomes in patients with prostate cancer (PCa) undergoing robotic-assisted radical prostatectomy (RARP). METHODS: This retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP in nine institutions in Japan. The primary endpoints were the associations between biochemical recurrence (BCR) and LVI and between BCR and clinicopathological covariates, while the secondary endpoints were the association between LVI and the site of clinical recurrence and metastasis-free survival (MFS). RESULTS: In total, 2608 patients met the inclusion criteria. At the end of the follow-up period, 311 patients (11.9%) were diagnosed with BCR and none died of PCa. In patients with pathological stage T2 (pT2) + negative resection margins (RM-), and pT3+ positive RM (RM+), LVI significantly worsened BCR-free survival (BRFS). For patients with PCa who had pT3 and RM+, the 2-year BRFS rate in those with LVI was significantly worse than in those without LVI. Patients with LVI had significantly worse MFS than those without LVI with respect to pT3, RM+, and pathological Gleason grade (pGG). In multivariate analysis, LVI was significantly associated with BRFS in patients with pT3 PCa, and with worse MFS in PCa patients with pT3, RM+, and pGG ≥ 4. CONCLUSIONS: LVI was an independent prognostic factor for recurrence and metastasis after RARP, particularly in patients with pT3 and RM+ PCa. Locally advanced PCa with positive LVI and RM+ requires careful follow-up because of the high likelihood of recurrence.

Acute procedural efficacy and safety of a novel expandable diameter cryoballoon in atrial fibrillation ablation: Early results from a multicenter ablation registry.

INTRODUCTION: The major limitation of the current cryoballoon (CB) system is a fixed 28 mm balloon-size. We sought to analyze real-world early experience with novel-sized adjustable CB. METHODS: This multicenter observational study included 140 consecutive atrial fibrillation patients (71 years, 94 men, 86 paroxysmal) who underwent pulmonary vein (PV) isolation using expandable diameter CB capable of ablation at 28 or 31 mm. RESULTS: Out of 544 targeted PVs, 526 (96.7%) were successfully isolated by a size-adjustable CB with a 770 [690-870] second median application dose, while the remaining 18 required touch-up ablation. Among them, 326 (62.0%) PVs were isolated by a 31 mm balloon, and the rate was significantly higher for upper than lower PVs (73.0% vs. 45.7%, p < .0001) and highest for right superior (78.5%) and lowest for right inferior (39.9%) PVs. The biophysical parameters and time to isolation were comparable between the 28 and 31 mm balloons, however, the real-time PV potential monitoring capability was significantly higher for 31 mm than 28 mm balloons for the left superior PV. The esophageal temperature reached 15°C during left inferior PV ablation significantly more often with 31 mm than 28 mm balloons (43.1% vs. 18.2%, p = .008). Right phrenic nerve injury (PNI) occurred in 9 (6.4%) patients during applications (6 right superior, 2 right inferior PVs), and most occurred with a 31 mm balloon. CONCLUSIONS: Our real-world early data demonstrated high acute efficacy and safety of the novel-sized adjustable CB. The biophysical parameters were similar between the 28 and 31 mm balloons. No marked decrease in the incidence of PNI was observed even with 31 mm balloons.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

PURPOSE: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). METHODS: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. RESULTS: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. CONCLUSION: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Cytological Analysis of the Surgical Field During Transanal Total Mesorectal Excision for Rectal Cancer: A Prospective Study.

BACKGROUND: An unexpectedly large number of patients experienced local recurrence with transanal total mesorectal excision in Norway. This appears to be associated with cancer cell spillage during surgery. OBJECTIVE: To investigate the surgical field cytology during transanal total mesorectal excision. DESIGN: This was a prospective cohort study. SETTINGS: This study was conducted at a single center between June and December 2020. PATIENTS: Forty patients with rectal cancer underwent transanal total mesorectal excision. Following the irrigation of the surgical field, the water specimens were cytologically evaluated at six representative steps. The first sample was used as an initial control. The second, third, fourth, fifth, and sixth samples were collected after the 1st purse-string suture, rectotomy, the 2nd purse-string suture, specimen resection, and anastomosis, respectively. The clinicopathological features and intraoperative complications of the patients were reviewed. MAIN OUTCOME MEASURES: The primary outcome was to evaluate the presence of cancer cells in washing cytological samples. RESULTS: Of the 40 consecutive patients enrolled in this study, 18 patients underwent neoadjuvant chemoradiotherapy. Incomplete first pursestring suture and rectal perforation were observed in 4 (10.0%) and 3 (7.5%) cases, respectively. In the first sample, 31 (77.5%) patients had malignant cells. Malignant findings were detected in two patients (5.0%) from the second to fifth samples. None of the sixth sample exhibited any malignant findings. LIMITATIONS: This single center study had a small sample size. CONCLUSIONS: Cancer cells were initially detected by cytology, but only a few were observed throughout the procedure; however, cancer cells were not detected in the final surgical field. Further follow-up and novel studies are required to obtain clinically significant findings using cytology during transanal total mesorectal excision. See Video Abstract.

Incidence of phrenic nerve injury during pulmonary vein isolation using different cryoballoons: data from a large prospective ablation registry.

AIMS: Phrenic nerve injury (PNI) is the most common complication during cryoballoon ablation. Currently, two cryoballoon systems are available, yet the difference is unclear. We sought to compare the acute procedural efficacy and safety of the two cryoballoons. METHODS: This prospective observational study consisted of 2,555 consecutive atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) using either conventional (Arctic Front Advance) (AFA-CB) or novel cryoballoons (POLARx) (POLARx-CB) at 19 centers between January 2022 and October 2023. RESULTS: Among 2,555 patients (68.8 ± 10.9 years, 1,740 men, paroxysmal AF[PAF] 1,670 patients), PVIs were performed by the AFA-CB and POLARx-CB in 1,358 and 1,197 patients, respectively. Touch-up ablation was required in 299(11.7%) patients. The touch-up rate was significantly lower for POLARx-CB than AFA-CB (9.5% vs. 13.6%, p = 0.002), especially for right inferior PVs (RIPVs). The touch-up rate was significantly lower for PAF than non-PAF (8.8% vs. 17.2%, P < 0.001) and was similar between the two cryoballoons in non-PAF patients. Right PNI occurred in 64(2.5%) patients and 22(0.9%) were symptomatic. It occurred during the right superior PV (RSPV) ablation in 39(1.5%) patients. The incidence was significantly higher for POLARx-CB than AFA-CB (3.8% vs. 1.3%, P < 0.001) as was the incidence of symptomatic PNI (1.7% vs. 0.1%, P < 0.001). The difference was significant during RSPV (2.5% vs. 0.7%, P < 0.001) but not RIPV ablation. The PNI recovered more quickly for the AFA-CB than POLARx-CB. CONCLUSIONS: Our study demonstrated a significantly higher incidence of right PNI and lower touch-up rate for the POLARx-CB than AFA-CB in the real-world clinical practice.

Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

BACKGROUND: Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. METHODS: We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. RESULTS: The median follow-up was 56.9 months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). CONCLUSIONS: Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

Development of a laparoscopic sigmoidectomy simulator: Sigmaster.

The sigmoid colon simulator was designed to accurately reproduce the anatomical layer structure and the arrangement of characteristic organs in each layer, and to have conductivity so that energy devices can be used. Dry polyester fibers were used to reproduce the layered structures, which included characteristic blood vessels, nerve sheaths, and intestinal tracts. The adhesive strength of the layers was controlled to allow realistic peeling techniques. The features of the Sigmaster are illustrated through a comparison of simulated sigmoidectomy using Sigmaster and actual surgery. We developed a laparoscopic sigmoidectomy simulator called Sigmaster. Sigmaster is a training device that closely reproduces the membrane structures of the human body and allows surgeons to experience the entire laparoscopic sigmoidectomy process.

Valley Index as a Predictor of Prenatal Diagnosis of Total Anomalous Pulmonary Venous Connection.

INTRODUCTION: Total anomalous pulmonary venous connection (TAPVC) has a low prenatal diagnostic rate. Therefore, we investigated whether Doppler waveforms with a low pulsatility in the pulmonary veins can indicate fetal TAPVC. METHODS: This retrospective study included 16 fetuses with TAPVC, including 10 with complex congenital heart disease and 104 healthy fetuses that underwent fetal echocardiography. Pulmonary venous S and D wave flow velocities and the valley (representing the lowest velocity between the S and D waves) were measured. Valley indices I and II were then calculated as (velocity of valley/greater of the S and D wave velocities) and (velocity of valley/lesser of the S and D wave velocities), respectively. RESULTS: Supra/infracardiac TAPVC cases exhibited significantly greater valley indices than that of the healthy group. After adjusting for gestational age at fetal echocardiography, valley indices I (odds ratio [OR] 7.26, p < 0.01) and II (OR: 9.23, p < 0.01) were significant predictors of supra/infracardiac TAPVC. Furthermore, valley indices I and II exhibited a high area under the curve for detecting supra/infracardiac TAPVC, regardless of the presence of pulmonary venous obstruction. CONCLUSION: The valley index may be a useful tool for the detection of fetal TAPVC.

[Role of Bone Scan Index (BSI) in the Prognosis and Treatment Efficacy in Castration-Sensitive Prostate Cancer Patients with Bone Metastasis].

Bone is the most common metastatic site in prostate cancer (PCa). Although the extent of disease (EOD) grade is used for evaluating burden of bone metastasis, the accuracy of bone metastasis classification needs improvement. Bone scan index (BSI) was developed as a quantitative tool to enhance the interpretability and clinical relevance of the bone scan. This study aimed to explore the role of BSI using BONENAVI® software in determining the prognosis and treatment efficacy in castration-sensitive PCa (mCSPC) patients with bone metastasis. We retrospectively reviewed 61 mCSPC patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. All patients received PADT with luteinizing hormone-releasing hormone agonist or surgical castration accompanied by first-generation antiandrogen, bicalutamide. Bone scans were performed with 99[m]Tc-MDP. BSI (%) was divided into two groups (＜1.0 and ≧1.0), and BSI response rates(change at 0 months to after 6 months) were determined using thresholds of 45% decline. Castration-resistant prostate cancer (CRPC) -free survival (CRPC-FS) and Overall survival (OS) rates were analyzed using the Kaplan-Meier method. The median follow-up was 41. 9 months. Overall, 16 patients (26. 2%) died. Multivariate analysis on pretreatment factors revealed that hemoglobin (P＝0.03) and BSI (P＝0.04) were independent prognostic factors for OS. The 5-year OS rates in patients with low BSI and high BSI were 84.6% and 39.2%, respectively (P＝0.02). In 40 patients who had a bone scan before and after PADT, OS rates in patients with a good response (≧45%) were significantly higher than those with a poor response (＜45%) (P＝0.001). Nadir PSA titers within 6 months after the start of treatment (P＝0.005), Hb (P＝0.003), and BSI change (P＝0.014) were independent prognostic factors for OS. In mCSPC patients with bone metastases, BSI at diagnosis was an important predictor of CRPC progression and OS as a pre-treatment factor, and BSI change rate and PSA nadir as post-treatment factors.

Fibroblast-derived exosomal microRNA regulates NKX3-1 expression in androgen-sensitive, androgen receptor-dependent prostate cancer cells.

Androgen deprivation therapy (ADT) targeting androgen production and androgen receptor (AR) signaling is the primary antihormonal therapy in the treatment of advanced prostate cancer (PCa). However, no clinically established molecular biomarkers have been identified to predict the effectiveness of ADT before starting ADT. The tumor microenvironment of PCa contains fibroblasts that regulate PCa progression by producing multiple soluble factors. We have previously reported that AR-activating factor-secreted fibroblasts increase the responsiveness of androgen-sensitive, AR-dependent PCa cells to ADT. Thus, we hypothesized that fibroblast-derived soluble factors may affect cancer cell differentiation by regulating cancer-related gene expression in PCa cells and that the biochemical characteristics of fibroblasts may be used to predict the effectiveness of ADT. Here, we investigated the effects of normal fibroblasts (PrSC cells) and three PCa patient-derived fibroblast lines (pcPrF-M5, -M28, and -M31 cells) on the expression of cancer-related genes in androgen-sensitive, AR-dependent human PCa cells (LNCaP cells) and three sublines showing different androgen sensitivities and AR dependencies. The mRNA expression of the tumor suppressor gene NKX3-1 in LNCaP cells and E9 cells (which show low androgen sensitivity and AR dependency) was significantly increased by treatment with conditioned media from PrSC and pcPrF-M5 cells but not from pcPrF-M28 and pcPrF-M31 cells. Notably, no upregulation of NKX3-1 was observed in F10 cells (AR-V7-expressing, AR-independent cells with low androgen sensitivity) and AIDL cells (androgen-insensitive, AR-independent cells). Among 81 common fibroblast-derived exosomal microRNAs that showed 0.5-fold lower expression in pcPrF-M28 and pcPrF-M31 cells than in PrSC and pcPrF-M5 cells, miR-449c-3p and miR-3121-3p were found to target NKX3-1. In only LNCaP cells, the NKX3-1 mRNA expression was significantly increased by transfection of an miR-3121-3p mimic but not that of the miR-449c-3p mimic. Thus, fibroblast-derived exosomal miR-3121-3p may be involved in preventing the oncogenic dedifferentiation of PCa cells by targeting NKX3-1 in androgen-sensitive, AR-dependent PCa cells.

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells.

BACKGROUND: Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCa during androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration. METHODS: We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48). RESULTS: The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. CONCLUSIONS: pcPrF from PCa specimens increase the expression of aberrant AR-V7 in PCa cells. IL-8 may be a target for preventing the expression of aberrant AR-Vs in PCa.

Nomogram Predicting Locally Advanced Prostate Cancer in Patients with Clinically Organ-Confined Disease Who Underwent Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).

PURPOSE: We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort. PATIENTS AND METHODS: From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer. RESULTS: A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis. CONCLUSIONS: We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy.

Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain.

PURPOSE: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters. This discrepancy may be due to differences in regulation after transcription between presynaptic and postsynaptic proteins, which have not been studied in the dopaminergic system. Here, we focused on dopamine D1 and D2/D3 receptors and dopamine transporters and investigated their region-wise relationship between mRNA expression and protein distribution. METHODS: We examined the region-wise correlation between regional binding potentials of the target region relative to that of non-displaceable tissue (BPND) values of 11C-SCH-23390 and mRNA expression levels of dopamine D1 receptors (D1R); regional BPND values of 11C-FLB-457 and mRNA expression levels of dopamine D2/D3 receptors (D2/D3R); and regional total distribution volume (VT) values of 18F-FE-PE2I and mRNA expression levels of dopamine transporters (DAT) using Spearman's rank correlation. RESULTS: We found significant positive correlations between regional BPND values of 11C-SCH-23390 and the mRNA expression levels of D1R (r = 0.769, p = 0.0021). Similar to D1R, regional BPND values of 11C-FLB-457 positively correlated with the mRNA expression levels of D2R (r = 0.809, p = 0.0151) but not with those of D3R (r = 0.413, p = 0.3095). In contrast to D1R and D2R, no significant correlation between VT values of 18F-FE-PE2I and mRNA expression levels of DAT was observed (r = -0.5934, p = 0.140). CONCLUSION: We found a region-wise correlation between the mRNA expression levels of dopamine D1 and D2 receptors and their respective protein distributions. However, we found no region-wise correlation between the mRNA expression levels of dopamine transporters and their protein distributions, indicating different regulatory mechanisms for the localization of pre- and postsynaptic proteins. These results provide a broader understanding of the application of the transcriptome atlas to neuroimaging studies of the dopaminergic nervous system.

Characteristics of long working hours and subsequent psychological and physical responses: JNIOSH cohort study.

OBJECTIVES: This study aimed to examine the prospective association among objectively measured average working hours (AWHs), frequency of long working hours (FLWHs; defined as ≥205 working hours/month (≥45 hours/week)) for 6 months, and workers' self-reported psychological and physical health. METHODS: The study included 15 143 workers from 5 Japanese companies. We collected monthly attendance records over 6 months before distributing a questionnaire survey on psychological/physical stress responses and work-related demographics. We then evaluated the associations of those attendance records with psychological/physical measures using analysis of covariance adjusted for sex, age, employment, job type, working conditions, work site and experience of emergency state due to COVID-19. RESULTS: Irritability, anxiety and depression were significantly greater at ≥180 hours (≥45 hours/week), and fatigue and lack of vigour were greater at ≥205 hours than those of the normal working-hour group (140-180 hours/month [35-45 hours/week]). Psychological indices increased significantly with FLWH, with ≥3 times for irritability, depression and fatigue; ≥2 times for lack of vigour; and ≥1 time for anxiety when compared with no long working hours. No significant associations were observed between AWH or FLWH and physical stress responses. CONCLUSIONS: Longer AWH was associated with higher levels of psychological stress responses. The effects of FLWH in the past 6 months varied among the psychological stress responses and did not occur for physical complaints. Under circumstances requiring long hours, workers' mental health should be protected through minimising the frequency of long work hours.

A novel catheter ablation strategy for non-paroxysmal atrial fibrillation combining cryoballoon, radiofrequency, and Marshall-vein ethanol ablations.

BACKGROUNDS: Catheter ablation for non-paroxysmal atrial fibrillation (non-PAF) remains challenging and more effective strategy has been required to reduce postoperative arrhythmia recurrences. This study aims to investigate the efficacy and safety of a novel extensive ablation strategy for non-PAF, that is based on a combination of cryoballoon (CBA), radiofrequency (RFA), and Marshall-vein ethanol ablations (EA-VOM). METHODS: The study was a single-center, retrospective observational study. We enrolled 171 consecutive patients who underwent de-novo catheter ablation for non-PAF under conscious sedation with a novel extensive ablation strategy that included CBA for pulmonary vein isolation (PVI) and left atrial roof ablation (LARA), RFA for mitral isthmus (MI) ablation, superior vena cava isolation, and other linear ablations and EA-VOM. Recurrence of atrial arrhythmias over 1 year, procedure outcomes, and procedure-related complications were investigated. RESULTS: A total of 139 (81.3%) patients remained in sinus rhythm during 1-year follow-up. Of the 139 patients, 51 patients (29.8%) received antiarrhythmic drugs. The mean procedure time was 204 ± 45 min. PVI and LARA ablation by CBA and MI block by RFA and EA-VOM were completed in 171 (100%) and 166 (97.1%) patients, respectively. No serious procedure-related complications were observed except for one case of delayed pericardial effusion. CONCLUSION: Approximately 80% of the study patients were AF-free during 1-year follow-up period after a single procedure based on the novel extensive ablation strategy combining CBA, RFA, and EA-VOM. This strategy for non-PAF may be preferred in terms of maintenance of sinus rhythm, safety even in high-risk patients, and relatively short procedure time.

Prognostic differences among the positive surgical margin locations following robot-assisted radical prostatectomy in a large Japanese cohort (the MSUG94 group).

BACKGROUND: To investigate whether subgroups of prostate cancer patients, stratified by positive surgical margin locations, have different oncological outcomes following robot-assisted radical prostatectomy. METHODS: A retrospective multicenter cohort study in prostate cancer patients undergoing robot-assisted radical prostatectomy was conducted at 10 institutions in Japan. Pre- and post-operative outcomes were collected from enrolled patients. Biochemical recurrence and clinical and pathological variables were evaluated among subgroups with different positive surgical margin locations. RESULTS: A total of 3195 patients enrolled in this study. Data from 2667 patients (70.1% [N = 1869] with negative surgical margins and 29.9% [N = 798] with positive surgical margins based on robot-assisted radical prostatectomy specimens) were analyzed. The median follow-up period was 25.0 months. The numbers of patients with apex-only, middle-only, bladder-neck-only, seminal-vesicle-only and multifocal positive surgical margins were 401, 175, 159, 31 and 32, respectively. In the multivariate analysis, PSA level at surgery, pathological Gleason score based on robot-assisted radical prostatectomy specimens, pathological T stage, pathological N stage and surgical margin status were independent risk factors significantly associated with biochemical recurrence-free survival. Patients undergoing robot-assisted radical prostatectomy with multifocal positive surgical margins and seminal-vesicle-only positive surgical margins were associated with worse biochemical recurrence-free survival than those with apex-only, middle-only and bladder-neck-only positive surgical margins. Patients undergoing robot-assisted radical prostatectomy with apex-only positive surgical margins, the most frequent positive surgical margin location, were associated with more favorable biochemical recurrence-free survival that those with middle-only and bladder-neck-only positive surgical margins. The study limitations included the lack of central pathological specimen evaluation. CONCLUSIONS: Although positive surgical margin at any locations is a biochemical recurrence risk factor after robot-assisted radical prostatectomy, positive surgical margin location status should be considered to accurately stratify the biochemical recurrence risk after robot-assisted radical prostatectomy.

Comparison between preoperative chemoradiotherapy and lateral pelvic lymph node dissection in clinical T3 low rectal cancer without enlarged lateral lymph nodes.

AIM: The standard strategy for clinical T3 rectal cancer without enlarged lateral lymph nodes is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) in Western countries and TME with bilateral lateral pelvic lymph node dissection (LPLND) in Japan. This study compared surgical, pathological and oncological results of these two strategies. METHOD: Patients who underwent preoperative CRT followed by TME in France (CRT + TME group) and those who underwent TME with LPLND in Japan (TME + LPLND group) for clinical T3 rectal adenocarcinoma without enlarged lateral lymph nodes from 2010 to 2016 were retrospectively analysed. RESULTS: In total, 439 patients were included in this study. The estimated local recurrence rate (LRR), disease-free survival and overall survival at 5 years post-surgery was 4.9%, 71% and 82% in the CRT + TME group, and 8.6%, 75% and 90% in the TME + LPLND group, respectively. Lateral LRR versus non-lateral LRR was 0.5% versus 4.2% in the CRT + TME group and 1.8% versus 6.2% in the TME + LPLND group. Obturator nerve injury and isolated pelvic abscess were shown only in the TME + LPLND group. Urinary complications were more frequent in the TME + LPLND group than in the CRT + TME group. CONCLUSION: Disease-free survival was not significantly different after TME with LPLND and after CRT followed by TME. LRR was not significantly different after both strategies; however, there was a trend for higher LRR after TME with LPLND than after CRT followed by TME. Obturator nerve injury, isolated lateral pelvic abscess and urinary complications should be noted when TME with LPLND is applied.

Single-center comparative study of short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers.

BACKGROUND: Transanal total mesorectal excision is a promising surgical treatment for rectal cancer. However, evidence regarding the differences in outcomes between the transanal and laparoscopic total mesorectal excisions is scarce. We compared the short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers. METHODS: This retrospective study included patients who underwent low anterior or intersphincteric resection for middle (5-10 cm) or low (< 5 cm) rectal cancer at the National Cancer Center Hospital East, Japan, from May 2013 to March 2020. Primary rectal adenocarcinoma was confirmed histologically. Circumferential resection margins (CRMs) of resected specimens were measured; margins ≤ 1 mm were considered positive. The operative time, blood loss, hospitalization length, postoperative readmission rate, and short-term treatment results were compared. RESULTS: Four hundred twenty-nine patients were divided into two mesorectal excision groups: transanal (n = 295) and laparoscopic (n = 134). Operative times were significantly shorter in the transanal group than in the laparoscopic group (p < 0.001). The pathological T stage and N status were not significantly different. The transanal group had significantly lower positive CRM rates (p = 0.04), and significantly lower incidence of the Clavien-Dindo grade III (p = 0.02) and IV (p = 0.03) complications. Both groups had distal margin positivity rates of 0%. CONCLUSIONS: Compared to laparoscopic, transanal total mesorectal excision for low and middle rectal cancers has lower incident postoperative complication and CRM-positivity rates, demonstrating the safety and usefulness of local curability for middle and low rectal cancers.

Short-term prognosis of low-risk prostate cancer patients is favorable despite the presence of pathological prognostic factors: a retrospective study.

BACKGROUND: Prostate cancer patients with pathological prognostic factors have a poor prognosis, but it is unclear whether pathological prognostic factors are associated with prognosis limited to low-risk patients with good prognosis according to NCCN guidelines. The present study examined whether prognosis is influenced by pathological prognostic factors using radical prostatectomy (RP) specimens from low-risk patients. METHODS: We evaluated diagnostic accuracy by examining biochemical recurrence (BCR)-free survival with respect to clinical and pathological prognostic factors in 419 all-risk patients who underwent RP. Clinical prognostic factors included age, prostate-specific antigen (PSA) levels, PSA density, and risk stratification, while pathological prognostic factors included grade group, lymphovascular space invasion, extraprostatic extension, surgical margins, seminal vesicle invasion, intraductal carcinoma of the prostate (IDCP), and pT. In a subsequent analysis restricted to 104 low-risk patients, survival curves were estimated for pathological prognostic factors using the Kaplan-Meier method and compared using log-rank and generalized Wilcoxon tests. RESULTS: In the overall risk analysis, the presence of pathological prognostic factors significantly shortened BCR-free survival (p < 0.05). Univariable analysis revealed that PSA density, risk categories, and pathological prognostic factors were significantly associated with BCR-free survival, although age and PSA were not. In multivariable analysis, age, risk categories, grade group, IDCP, and pT significantly predicted BCR-free survival (p < 0.05). Conversely, no statistically significant differences were found for any pathological prognostic factors in low-risk patients. CONCLUSIONS: In low-risk patients, pathological prognostic factors did not affect BCR-free survival, which suggests that additional treatment may be unnecessary even if pathological prognostic factors are observed in low-risk patients with RP.

Association of hospital volume with perioperative and oncological outcomes of robot-assisted laparoscopic radical prostatectomy: a retrospective multicenter cohort study.

BACKGROUND: This retrospective multicenter cohort study investigated the association of hospital volume with perioperative and oncological outcomes in patients treated with robot-assisted radical prostatectomy (RARP). METHODS: We collected the clinical data of patients who underwent RARP at eight institutions in Japan between September 2012 and August 2021. The patients were divided into two groups based on the treatment site-high- and non-high-volume hospitals. We defined a high-volume hospital as one where RARP was performed for more than 100 cases per year. RESULTS: After excluding patients who received neoadjuvant therapy, a total of 2753 patients were included in this study. In the high-volume hospital group, console time and estimated blood loss were significantly (p < 0.001) lower than that of the non-high-volume hospital group. However, the continence rate at 3 months after RARP, positive surgical margins, and prostate-specific antigen (PSA)-relapse-free survival showed no significant differences between the two groups. Furthermore, the console time was significantly shorter after 100 cases in the non-high-volume hospital group but not in the high-volume hospital group. CONCLUSIONS: A higher hospital volume was significantly associated with shorter console time and less estimated blood loss. However, oncological outcomes and early continence recovery appear to be comparable regardless of the hospital volume in Japan.