Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise

Objective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Study Design: Randomized controlled trial. Setting: Animal study. Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise. Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo

Blood Transfusion Requirement and not Preoperative Anaemia is associated with Perioperative Complications following Intracorporeal Robotic Assisted Radical Cystectomy

OBJECTIVES: To assess the prevalence of preoperative anaemia and the impact of preoperative anaemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robotic assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS & METHODS: IRARC was performed on 166 patients between June 2011-March 2016. Prospective data was collected for patient demographics, clinical and pathological characteristics, perioperative variables, transfusion requirements and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan-Kettering Cancer Center Clavian-Dindo system. RESULTS: Preoperative anaemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p<0.001). Patients with preoperative anaemia were significantly more likely to have an Ileal conduit (p=0.033), higher cystectomy stage (≥pT3) (p=0.028) and a lower lymph node yield (p=0.031). Preoperative anaemia was not associated with increased perioperative morbidity but was associated with the need for blood transfusion (p=0.001). Blood transfusion was required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9% respectively. The 30-day all complication rate and 30-day major complication rate was 55.4% and 15.7% respectively while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3% respectively. Intraoperative blood transfusion was not associated with increased complications but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30 day complications (p=0.003), all 90-day complications (p=0.009) and 90-day major complications (p=0.004). CONCLUSION: The presence of preoperative anaemia in patients undergoing iRARC is not associated with increased surgical risk although preoperative anaemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion is independently associated with perioperative morbidity and is an important factor for the optimisation of postoperative outcomes

The Role of Robotics in the Invasive Management of Bladder Cancer

Robot-assisted radical cystectomy (RARC) has been adopted widely in many centres, owed largely to the success of robot-assisted laparoscopic prostatectomy (RALP). It aims to replicate the oncological outcomes of open radical cystectomy (ORC), while providing a shorter recovery period. Despite this, previous RCTs have failed to show a benefit for RARC over ORC. These trials have compared extracorporeal RARC (eRARC) with ORC, which requires a further incision to mobilise the bowel for urinary reconstruction with an open technique. For intracorporeal RARC (iRARC), this urinary reconstruction is performed robotically without further incisions. There are theoretical benefits to this approach such as reduced recovery time for the bowel and reduced ileus rates, but no level 1 evidence currently exists to support this. While there has been an improvement in patient outcomes since the adoption of RARC, various other factors, such as enhanced recovery programmes and surgical learning curve, have made it difficult to attribute this solely to the robotic approach as many centres performing ORC have also shown similar improvements. In this review, we will discuss implementation of RARC as well as perioperative measures that have helped improve outcomes, offer a comparison of outcomes between ORC and RARC and highlight upcoming RCTs that may offer new evidence for or against a paradigm shift in the future of bladder cancer surgery

Intracorporeal robotic assisted radical cystectomy together with an enhanced recovery programme improves postoperative outcomes by aggregating marginal gains

OBJECTIVE: To assess the cumulative effect of an enhanced recovery after surgery (ERAS) pathway and a minimally invasive RARC with intracorporeal urinary diversion (iRARC) in comparison to open radical cystectomy (ORC) on hospital length of stay (LOS) and perioperative outcomes. MATERIALS & METHODS: Between Feb 2009 and Oct 2017, 304 radical cystectomy cases were performed at a single institution (54 ORC, 250 RARC). Data were prospectively collected. We identified 45 consecutive ORC cases performed without ERAS before the commencement of the RARC programme (Cohort A), 50 consecutive iRARC cases performed without ERAS (Cohort B) and 40 iRARC cases with ERAS (Cohort C). Primary outcome measure was hospital LOS while secondary outcome measures included perioperative 90-day complications and readmission rates. Complications were accessed using the Clavian-Dindo classification. RESULTS: Patients in all cohorts were evenly match in age, sex, body mass index (BMI), neoadjuvant treatment, tumour stage, lymph node yield, previous pelvic radiotherapy and surgery, perioperative anaemia as well as physiological state. iRARC with ERAS patients had a significantly higher ASA (III-IV) and were more likely to receive neobladder reconstruction. Median hospital LOS were shorter in iRARC with ERAS (7 days, IQR: 6-10) compared to iRARC without ERAS (11, 8-15) and ORC (17 (14-21). In a propensity score-matched cohort of iRARC patients, patients with ERAS has a significantly lower 90-day readmission rates. Additionally, implementing ERAS in an iRARC cohort resulted in a significantly lower 90-day all (p<0.001) and GI related complications (p=0.001). the use of ERAS and younger patients were independently associated with a hospital LOS ≤10 days on multinomial logistic regression. CONCLUSION: A comprehensive ERAS programme can significantly reduce hospital LOS in patients undergoing iRARC without increasing 90-day readmission rates. An ERAS programme can augment the benefits of iRARC in improving perioperative outcomes. In studies comparing ORC and RARC, the presence or absence of an ERAS programme will be a confounding factor and only level I evidence can be interpreted reliably. This article is protected by copyright. All rights reserved

Attractiveness of a Four-component Pheromone Blend to Male Navel Orangeworm Moths

The attractiveness to male navel orangeworm moth, Amyelois transitella, of various combinations of a four-component pheromone blend was measured in wind-tunnel bioassays. Upwind flight along the pheromone plume and landing on the odor source required the simultaneous presence of two components, (11Z,13Z)-hexadecadienal and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene, and the addition of either (11Z,13Z)-hexadecadien-1-ol or (11Z,13E)-hexadecadien-1-ol. A mixture of all four components produced the highest levels of rapid source location and source contact. In wind-tunnel assays, males did not seem to distinguish among a wide range of ratios of any of the three components added to (11Z,13Z)-hexadecadienal. Dosages of 10 and 100 ng of the 4-component blend produced higher levels of source location than dosages of 1 and 1,000 ng

Aspirin-induced nuclear translocation of NFκB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency

Substantial evidence indicates nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC). However, the molecular basis for this anti-tumour activity has not been fully elucidated. We previously reported that aspirin induces signal-specific IκBα degradation followed by NFκB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. We have also reported the relative specificity of this aspirin-induced NFκB-dependent apoptotic effect for CRC cells, in comparison to other cancer cell types. It is now important to establish whether there is heterogeneity within CRC, with respect to the effects of aspirin on the NFκB pathway and apoptosis. p53 signalling and DNA mismatch repair (MMR) are known to be deranged in CRC and have been reported as potential molecular targets for the anti-tumour activity of NSAIDs. Furthermore, both p53 and MMR dysfunction have been shown to confer resistance to chemotherapeutic agents. Here, we set out to determine the p53 and hMLH1 dependency of the effects of aspirin on NFκB signalling and apoptosis in CRC. We specifically compared the effects of aspirin treatment on cell viability, apoptosis and NFκB signalling in an HCT-116 CRC cell line with the p53 gene homozygously disrupted (HCT-116p53−/−) and an HCT-116 cell line rendered MMR proficient by chromosomal transfer (HCT-116+ch3), to the parental HCT-116 CRC cell line. We found that aspirin treatment induced apoptosis following IκBα degradation, NFκB nuclear translocation and repression of NFκB-driven transcription, irrespective of p53 and DNA MMR status. These findings are relevant for design of both novel chemopreventative agents and chemoprevention trials in CRC

The Co-Regulation of Emotions Between Mothers and their Children with Autism

Thirty-four toddlers with autism and their mothers participated in an early intervention targeting joint engagement. Across the 24 intervention sessions, any significant distress episode in the child was coded for emotion regulation outcomes including child negativity, child emotion self-regulation, and mother emotion co-regulation. Results revealed that emotion regulation strategies by both mother and child were employed during distress episodes. An effect of intervention was found such that children decreased their expression of negativity across the intervention and mothers increased their emotional and motivational scaffolding. The results of this study indicate a positive effect of an intervention targeting joint engagement on emotion co-regulation outcomes

Expression of OATP Family Members in Hormone-Related Cancers: Potential Markers of Progression

The organic anion transporting polypeptide (OATP) family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04) which also trended lower with decreasing differentiation (P = 0.004) and lower magnitude in pancreatic cancer (P = 0.05). SLCO2B1 also had a higher frequency in thyroid cancer (67%) than normal (0%) and expression increased with stage (P = 0.04). SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03). SLCO1B3 expression was also higher in testicular cancer (P = 0.02). SLCO1B1 expression was lower in liver cancer (P = 0.04) which trended lower with liver cancer grade (P = 0.0004) and higher with colon cancer grade (P = 0.05). Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease