Recommendations for the management of advanced and metastatic renal cell carcinoma: joint consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

INTRODUCTION: Kidney cancer, primarily renal cell carcinoma (RCC), ranks among the top 10 most common malignancies in the male population of Hong Kong. In 2019, members of two medical societies in Hong Kong formed an expert panel to establish a set of consensus statements for the management of metastatic RCC. On 22 June 2021, the same panel met to review recent evidence and reassess their positions regarding the management of advanced and metastatic RCC, with the aim of providing recommendations for physicians in Hong Kong. PARTICIPANTS: The panel included 12 experts (6 clinical oncologists and 6 urologists) who had extensive experience managing patients with RCC in Hong Kong. EVIDENCE: The panel reviewed randomised controlled trials, observational studies, systematic reviews/meta-analyses, and international clinical guidelines to address key clinical questions that were identified before the meeting. CONSENSUS PROCESS: In total, 15 key clinical questions were identified before the meeting, covering the surgical and systemic treatment of advanced or metastatic clear cell, sarcomatoid, and non-clear cell RCCs. At the meeting, the panellists voted on these questions, then discussed relevant evidence and practical considerations. CONCLUSIONS: The treatment landscape for advanced and metastatic RCC continues to evolve. More immune checkpoint inhibitor (ICI)-based combination regimens will be indicated for the treatment of metastatic clear cell RCC. There is increasing evidence concerning the benefit of adjuvant ICI treatment for resected advanced RCC. This article summarises recent evidence and expert insights regarding a series of key clinical questions about the management of advanced and metastatic RCC.

Economic Evaluation of Budesonide Orodispersible Tablets for the Treatment of Eosinophilic Esophagitis: A Cost-Utility Analysis.

INTRODUCTION: Budesonide orodispersible tablets (BOT) have been approved in Europe and Canada for the treatment of eosinophilic esophagitis (EoE), a rare and chronic disease. The objective of this study was to assess the economic impact of BOT on both the induction and maintenance of clinico-pathological remission of EoE by performing a cost-utility analysis (CUA). METHODS: For both the induction and maintenance settings, BOT was compared to no treatment in a target population of adult patients with EoE non-responsive to proton pump inhibitor (PPI) treatment. Markov models were developed for the induction and maintenance settings over 52-week and life-time horizons, respectively. Analyses were performed from both a Canadian Ministry of Health (MoH) and societal perspective. The resulting incremental cost-utility ratios (ICURs) were compared to a willingness-to-pay (WTP) threshold of $50,000 Canadian dollars/quality-adjusted life-year (QALY). Sensitivity and scenario analyses were conducted to assess the robustness of the base-case results. RESULTS: In the base-case probabilistic analysis, BOT compared to no treatment resulted in an ICUR of $1073/QALY and $30,555/QALY from a MoH perspective in the induction and maintenance settings, respectively. BOT was a cost-effective option for both induction and maintenance in > 99% of Monte Carlo simulations. In the scenario analyses, the deterministic ICUR of BOT compared to no treatment varied from $682/QALY to $8510/QALY in the induction setting and $21,005/QALY to $55,157/QALY in the maintenance setting. CONCLUSION: BOT was cost-effective compared to no treatment for both the induction and maintenance of clinico-pathological remission of EoE in patients non-responsive to PPIs.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Survey on prevalence of lower urinary tract symptoms in an Asian population.

INTRODUCTION: Lower urinary tract symptoms (LUTS) have a strong effect on socio-economic and individual quality of life. The aim of the present study was to investigate the prevalence of LUTS in an Asian population. METHODS: A telephone survey of individuals aged ≥40 years and of Chinese ethnicity was conducted. The survey included basic demographics, medical and health history, drinking habits, International Prostate Symptom Score, overactive bladder symptom score, Patient Health Questionnaire (PHQ-9) score, and Short Form (SF)-12v2 score. RESULTS: From March to May 2017, 18 881 calls were made, of which 1543 fulfilled the inclusion criteria. In the end, 1000 successful respondents were recruited (302 men and 698 women). Age-adjusted prevalence of overactive bladder syndrome was 15.1%. The older the respondent, the more prevalent the storage symptoms and voiding symptoms (storage symptoms: r=0.434, P<0.001; voiding symptom: r=0.190, P<0.001). Presence of hypertension and diabetes were found to be significantly and positively correlated with storage and voiding symptoms. Storage and voiding symptoms were found to affect PHQ-9 scores (storage symptoms: r=0.257, P<0.001; voiding symptoms: r=0.275, P<0.001) and SF-12v2 scores (storage symptoms: r=0.467, P<0.001; voiding symptoms: r=0.335; P<0.001). Nocturia was the most prominent symptom among patients who sought medical help for their LUTS. CONCLUSIONS: Lower urinary tract symptoms are common in Asian populations. Both storage and voiding symptoms have a negative impact on mental health and general well-being of individuals.

Tumor inhibitory effects of intravesical Ganoderma lucidum instillation in the syngeneic orthotopic MB49/C57 bladder cancer mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (GL) has been traditionally used in oriental medicine as superior health tonic, and there are numerous scientific evidences of its antitumorigenic activities. AIM OF THE STUDY: To evaluate the intravesical chemopreventive effects of ethanol extract of GL (GLe) on bladder cancer. MATERIALS AND METHODS: Intravesical therapy is defined as the direct instillation of a liquid drug into bladder through a catheter. Bacille Calmette-Guerin(BCG) solution is applied intravesically as a conventional immunotherapy for preventing recurrence of bladder cancer. By adopting the MB49/C57 bladder cancer mice model, an overall 60 MB49-implanted mice were randomized into 3 groups and treated according to 3 treatment arms, including GLe, BCG and PBS. Additionally, wild-type mice without MB49 cell inoculation and treated with PBS were used as the negative control group. Testing agents were instilled intravesically for 2 h and repeated after one week for evaluating the effects on preventing the tumor formation and growth. The treated-mice were closely monitored for major adverse effects. RESULTS: GLe demonstrated more potent cytotoxic effects than BCG on MB49 cells, although both in dose-dependent manner. In the MB49-implanted mice, 80 µg/ml GLe was shown to delay the tumor formation by one week, whereas the averaged tumor volume measured at endpoint was 3.6-fold and 4.6-fold smaller than that of the BCG or PBS, respectively. However, no significant effects were observed on body weight and hematuria. CONCLUSION: Current findings in mice suggested intravesical GLe therapy as an effective and safe chemopreventive strategy for inhibiting bladder tumor formation.

"To screen or not to screen": Comparing the health and economic benefits of early peanut introduction strategies in five countries.

BACKGROUND: Early peanut introduction (EPI) in the first year of life is associated with reduced risk of developing peanut allergy in children with either severe eczema and/or egg allergy. However, EPI recommendations differ among countries with formal guidelines. METHODS: Using simulation and Markov modeling over a 20-year horizon to attempt to explore optimal EPI strategies applied to the US population, we compared high-risk infant-specific IgE peanut screening (US/Canadian) with the Australiasian Society for Clinical Immunology and Allergy (Australia/New Zealand) (ASCIA) and the United Kingdom Department of Health (UKDOH)-published EPI approaches. RESULTS: Screening peanut skin testing of all children with early-onset eczema and/or egg allergy before in-office peanut introduction was dominated by a no screening approach, in terms of number of cases of peanut allergy prevented, quality-adjusted life years (QALY), and healthcare costs, although screening resulted in a slightly lower rate of allergic reactions to peanut per patient in high-risk children. Considering costs of peanut allergy in high-risk children, the per-patient cost of early introduction without screening over the model horizon was $6556.69 (95%CI, $6512.76-$6600.62), compared with a cost of $7576.32 (95%CI, $7531.38-$7621.26) for skin test screening prior to introduction. From a US societal perspective, screening prior to introduction cost $654 115 322 and resulted in 3208 additional peanut allergy diagnoses. Both screening and nonscreening approaches dominated deliberately delayed peanut introduction. CONCLUSIONS: A no-screening approach for EPI has superior health and economic benefits in terms of number of peanut allergy cases prevented, QALY, and total healthcare costs compared to screening and in-office peanut introduction.

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review.

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26-1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.

LEAPing through the looking glass: secondary analysis of the effect of skin test size and age of introduction on peanut tolerance after early peanut introduction.

BACKGROUND: In the Learning Early About Peanut Allergy (LEAP) study, early peanut introduction in high-risk 4- to 11-month-olds was associated with a significantly decreased risk of developing peanut allergy. However, the influences of key baseline high-risk factors on peanut tolerance are poorly understood. METHODS: Secondary analysis was conducted on the publically available LEAP dataset, exploring relationships between peanut tolerance, baseline peanut/egg sensitization, eczema severity/duration, age of introduction, gender, and race. RESULTS: A multiple logistic regression model predicting odds of successful oral food challenge (OFC) at 60 months noted higher odds with early introduction (OR 9.2, P < 0.001, 95% CI 4.2-20.3), white race (OR 2.1, P = 0.04, 95% CI 1.1-3.9), and advancing age (OR 4.8, P = 0.04, 95% CI 1.1-20.8). Odds of peanut tolerance were lower with increasing peanut wheal size (OR 0.58, P < 0.001, 95% CI 0.46-0.74), increased baseline SCORAD score (OR 0.98, P = 0.04, 95% CI 0.97-1), and increased kUA /l of egg serum IgE (sIgE) (OR 0.99, P = 0.04, 95% CI 0.98-1). The probability of peanut tolerance in the early introduction group was 83% vs 43% in the avoidance group with SPT wheal of <4 mm. The probability of a successful OFC was significantly higher with peanut introduction between 6 and 11 months than at 4-6 months. Increasing eczema severity had limited impact on the probability of peanut tolerance in the early introduction arm. CONCLUSION: Increasing peanut wheal size predicted peanut tolerance only in the avoidance arm. Peanut introduction between 6 and 11 months of age was associated with the highest rates of peanut tolerance, questioning the 'urgency' of introduction before 6 months.

Bathroom greywater recycling using polyelectrolyte-complex bilayer membrane: Advanced study of membrane structure and treatment efficiency.

Polyelectrolyte-complex bilayer membrane (PCBM) was fabricated using biodegradable chitosan and alginate polymers for subsequent application in the treatment of bathroom greywater. In this study, the properties of PCBMs were studied and it was found that the formation of polyelectrolyte network reduced the molecular weight cut-off (MWCO) from 242kDa in chitosan membrane to 2.71kDa in PCBM. The decrease in MWCO of PCBM results in better greywater treatment efficiency, subsequently demonstrated in a greywater filtration study where treated greywater effluent met the household reclaimed water standard of <2 NTU turbidity and <30ppm total suspended solids (TSS). In addition, a further 20% improvement in chemical oxygen demand (COD) removal was achieved as compared to a single layer chitosan membrane. Results from this study show that the biodegradable PCBM is a potential membrane material in producing clean treated greywater for non-potable applications.

Peanut avoidance and peanut allergy diagnosis in siblings of peanut allergic children.

BACKGROUND: Studies suggest that siblings of children with peanut allergy (PNA) have a higher prevalence of PNA than the general population. OBJECTIVES: The Canadian Peanut Allergy Registry was used to assess the percentage of siblings of registered index PNA children who were 1) never exposed to peanut or 2) reportedly diagnosed with PNA by a physician without either a history of allergic reaction or a confirmatory testing. Sociodemographic and clinical factors that may be associated with either outcome were evaluated. METHODS: Parents completed a questionnaire on siblings' sociodemographic characteristics, exposure and reaction to peanut, confirmatory tests performed and whether PNA had been diagnosed. RESULTS: Of 932 Registry families, 748 families responded, representing 922 siblings. 13.6% of siblings had never been exposed to peanut, 70.4% (n = 88) of which were born after the index child. Almost 9% of siblings (80) were reported as PNA, but almost half of this group had no history of an allergic reaction to peanut, including five children who also had no testing to confirm PNA. Of these 5, 4 were born after PNA diagnosis in the index child. In a multivariate regression analysis for siblings at least 3 years old, those born after PNA diagnosis in the index child were more likely to have never been exposed to peanut. In a univariate analysis, siblings born after the diagnosis of PNA in the index child were more likely to be diagnosed with PNA without supportive history or confirmatory testing. CONCLUSIONS AND CLINICAL RELEVANCE: These data estimate that more than 10% of siblings of PNA patients will avoid peanut and that siblings born after the diagnosis of PNA in an index child are more likely to have never been exposed. Educational programs and guidelines that caution against unnecessary avoidance are required.

Incidence of postoperative deep vein thrombosis after robotic-assisted laparoscopic prostatectomy: a prospective study in Chinese patients.

OBJECTIVE: To investigate the incidence of deep vein thrombosis (DVT) in Chinese patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer and the need for prophylactic anticoagulation. METHODS: From August 2007 to September 2010, patients with prostate cancer undergoing RALP in our center were prospectively recruited for the study. Perioperative parameters, including patients' age, disease stage and pathology, and intraoperative findings were collected. All patients underwent Doppler ultrasonographic evaluation of their bilateral lower limbs on postoperation day 3 for any evidence of DVT. The incidence of and possible predisposing factors for DVT were determined. RESULTS: One hundred and nine consecutive patients were recruited during the study period. The incidence rate of post-RALP DVT was 16.9 % (18 cases), with only one patient (1 %) developing above-knee DVT. No patient developed DVT-associated complications during follow-up. Patients with DVT were older (69.2 ± 4.4 vs. 65 ± 5.8 years old; p = 0.05), had greater intraoperative blood loss (775 vs. 264.7 ml; p = 0.001) and required lengthier hospitalization (8.1 vs. 6.0 days; p = 0.013). However, no difference in smoking history, body mass index, history of diabetes, lymph node dissection or disease stage was observed between patients with and without DVT. CONCLUSIONS: The post-RALP incidence of DVT in Chinese populations is not low. However, the majority of DVT cases are below the knee level and asymptomatic.

Age, tumour stage, and preoperative serum albumin level are independent predictors of mortality after radical cystectomy for treatment of bladder cancer in Hong Kong Chinese.

OBJECTIVES: To evaluate the association between patient age, other clinical factors and mortality following radical cystectomy for treatment of bladder cancer. DESIGN: Historical cohort study. SETTING: A urology unit in Hong Kong. PATIENTS: The outcomes of 117 patients who had radical cystectomies performed in one urological unit from 2003 to 2011 were reviewed. Demographic and perioperative data, including tumour stage, Charlson Comorbidity Index, and preoperative serum albumin levels were retrieved from computerised medical records. Risk factors for 30-day mortality, and cancer-specific, other-cause, and overall death rates at 5 years were calculated. The data were subsequently stratified and analysed according to age. RESULTS: Of the 117 patients, 83 (71%) were aged 75 years or below. The mean follow-up duration was 31 (standard deviation, 29) months. Age, tumour stage, and preoperative serum albumin level, but not the Charlson Comorbidity Index, were found to be predictors of survival following radical cystectomy. The overall 30-day mortality rate was 3% in the full sample, 1% in patients aged 75 years or below, and 10% in patients aged over 75 years. There was no significant difference in 5-year cancer-caused mortalities between patients aged 75 years or below and those aged over 75 years (33% vs 33%, P=0.956). In patients older than 75 years, the 5-year other-cause and overall mortality rates were 47% and 80%, respectively; such rates were higher than those for younger patients (13% and 46%, respectively). CONCLUSION: Age, tumour stage, and preoperative serum albumin level were predictors of survival after radical cystectomy. Non-cancer-related death played a crucial role in the overall mortality rate in elderly patients having radical cystectomy for bladder cancer.

Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria.

BACKGROUND: Long-term overall survival after liver resection in patients with hepatocellular carcinoma (HCC) within the Milan criteria has been reported to improve in recent years. This study systematically reviewed the outcomes of surgical resection for HCC in patients with good liver function and meeting the Milan criteria for early HCC, published in the past 10 years. METHODS: A literature search was conducted in PubMed for papers on outcomes of surgical resection for HCC published between January 2000 and December 2010. Cochrane systematic review methodology was used for this review. The primary outcome was overall survival. Secondary outcomes included operative mortality and disease-free survival. Studies that focused on geriatric populations, paediatric populations, a subset of the Milan criteria (such solitary tumours) or included patients with incidental tumours were excluded, as were case reports, conference abstracts, and studies with a large proportion of Child-Pugh grade C liver cirrhosis or unknown Child-Pugh status. RESULTS: Of 152 studies reviewed, two randomized clinical trials and 27 retrospective case series were eligible for inclusion. The 5-year overall survival rate after resection of HCC ranged from 27 to 81 (median 67) per cent, and the median disease-free survival rate from 21 to 57 (median 37) per cent. There was a trend towards improved overall survival in recent years. The operative mortality rate ranged from 0 to 5 (median 0·7) per cent. CONCLUSION: Surgical resection offers good overall survival for patients with HCC within the Milan criteria and with good liver function, although recurrence rates remain high. Outcomes have tended to improve in more recent years.

The spatial location of the mandibular canal in Chinese: a CT study.

The inferior alveolar nerve (IAN) is vulnerable to injury from mandible fractures and surgical procedures so anatomical variations of IAN are important. Postoperative sensory alteration of the lip and chin region is high after mandibular orthognathic surgery. The incidence of IAN paresthesia following sagittal split ramus osteotomy (SSRO) ranges from 54% to 86% at 4-8 days, 41 to 75% at 1 month, 33 to 66% at 3 months, 17 to 58% at 6 months and 15 to 33% at 1 year postoperatively. This study determined the anatomical position of the mandibular canal in relation to cortical bone and molar teeth in Chinese using archived CT records. The mandibular canal was the farthest from the buccal cortex at the second molar region (mean 6.79mm; minimum distance 4.80mm). The anatomical location of the mandibular canal in local Chinese compares with studies on Asian cadavers. The mandible body was thickest in the region of the second molar (11.9mm). The vertical buccal cut for SSRO should be in the region of the mandibular second molar where the bone is thickest and the mandibular canal is furthest from the buccal cortex. The safe depth for the vertical buccal cut is 4.8mm (minimum horizontal distance).

Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G(2) cell-cycle arrest.

G-protein-coupled receptor-30 (GPR30) shows estrogen-binding affinity and mediates non-genomic signaling of estrogen to regulate cell growth. We here showed for the first time, in contrast to the reported promoting action of GPR30 on the growth of breast and ovarian cancer cells, that activation of GPR30 by the receptor-specific, non-estrogenic ligand G-1 inhibited the growth of androgen-dependent and androgen-independent prostate cancer (PCa) cells in vitro and PC-3 xenografts in vivo. However, G-1 elicited no growth or histological changes in the prostates of intact mice and did not inhibit growth in quiescent BPH-1, an immortalized benign prostatic epithelial cell line. Treatment of PC-3 cells with G-1 induced cell-cycle arrest at the G(2) phase and reduced the expression of G(2)-checkpoint regulators (cyclin-A2, cyclin-B1, cdc25c, and cdc2) and phosphorylation of their common transcriptional regulator NF-YA in PC-3 cells. With extensive use of siRNA-knockdown experiments and the MEK inhibitor PD98059 in this study, we dissected the mechanism underlying G-1-induced inhibition of PC-3 cell growth, which was mediated through GPR30, followed by sustained activation of Erk1/2 and a c-jun/c-fos-dependent upregulation of p21, resulting in the arrest of PC-3 growth at the G(2) phase. The discovery of this signaling pathway lays the foundation for future development of GPR30-based therapies for PCa.

Effect of temperature and salt concentration on rheological behavior of whey protein isolate-starch mixed dispersions.

Extensive studies have been carried out on the effect of temperature and salt concentration on the theological behavior of whey proteins and different starches individually, but not on mixed dispersions of whey protein isolates and starches. In the present studies, the rheological behavior of cross-linked waxy maize starch and whey protein isolate mixed dispersions during heating at 60-85 degrees C was investigated. Further, the effect of CaCl2 (25-100 mM ionic strengths) on the gelatinization of these dispersions was determined. It was found that at a 2:3 ratio and a 3:2 ratio of cross-linked waxy maize starch to whey protein isolate mixed gels form a compatible networkmM concentration the solution viscosity was higher.

Adenosine in inflammatory joint diseases.

Inflammatory joint diseases are a group of heterogeneous disorders with a variety of different etiologies and disease manifestations. However, there are features that are common to all of them: first, the recruitment of various inflammatory cell types that are attracted to involved tissues over the course of the disease process. Second, the treatments used in many of these diseases are commonly medications that suppress or alter immune function. The demonstration that adenosine has endogenous anti-inflammatory functions and that some of the most commonly used anti-rheumatic medications exert their therapeutic effects through stimulation of adenosine release suggest an important role for purinergic signaling in inflammatory rheumatic disorders.