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.

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.

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.

Treatment of acquired bilateral nevus of ota-like macules (Hori's nevus) with a combination of the 532 nm Q-Switched Nd:YAG laser followed by the 1,064 nm Q-switched Nd:YAG is more effective: prospective study.

BACKGROUND: Acquired bilateral nevus of Ota-like macules (Hori's nevus) is a common dyschromatosis among Asian women. Q-switched lasers have been used successfully as a treatment modality. OBJECTIVE: The purpose of this study was to compare the efficacy of using the Q-switched 532 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser followed by the 1,064 nm laser versus the Q-switched 1,064 nm Nd:YAG laser alone in the treatment of Hori's nevus. METHODS: This is a prospective left-right comparative study. Ten women with bilateral Hori's nevus were recruited and treated with a combination of the Q-switched 532 and 1,064 nm Nd:YAG lasers on the right cheek and the Q-switched 1,064 nm Nd:YAG laser alone on the left cheek. Only one laser treatment session was performed. The degree of pigmentation was objectively recorded with a mexameter. Subjective assessment was made by both patients and two blinded, nontreating dermatologists. RESULTS: At 6 months, there was a statistically significant difference (p = .009) of 35.10 points using objective mexameter measurements between the two sides, favoring the side treated with a combination of 532 and 1,064 nm laser treatment. Subjective grading by the patients and blinded dermatologists also confirmed that combination therapy was more successful after one treatment. Although combination treatment had a higher incidence of mild postinflammatory changes, this disappeared within 2 months. CONCLUSIONS: Concurrent use of the Q-switched 532 nm Nd:YAG laser in combination with the 1,064 nm laser is more effective in pigment clearance than the Q-switched 1,064 nm Nd:YAG laser alone for Hori's nevi.

A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is one of the commoner conditions seen in oral medicine clinics. Current treatments are palliative rather than curative. Numerous treatments have been tried but many have not been evaluated in randomized controlled trials (RCTs). OBJECTIVES: To review the effectiveness and safety of any therapy compared with placebo for the treatment of symptomatic OLP. METHODS: A systematic review of 11 RCTs, totalling 223 patients was done. The main outcome measures used were improvement of signs (erythema, reticulation, ulceration) and symptoms (pain, discomfort) usually after 8 weeks of therapy. RESULTS: Eleven interventions were grouped into four therapeutic classes (topical ciclosporins, topical or systemic retinoids, topical steroids and phototherapy) for comparison. No therapy was replicated exactly. Trials recording the same outcomes in each therapeutic class were pooled. The largest number of pooled trials was four. Small odds ratios with very wide confidence intervals indicating statistically significant but imprecisely known treatment benefits were seen in all but one trial. Only systemic agents were associated with treatment toxicities; all other side-effects were mild and mainly local. CONCLUSIONS: The results are tempered by the small study sizes, lack of replication, lack of standardized outcome measures and the very high likelihood of publication bias. Therefore this review provides only circumstantial evidence for the superiority of the assessed interventions over placebo for the palliation of symptomatic OLP. There is a need for larger placebo-controlled RCTs with carefully selected and standardized outcome measures.

Fludarabine in comparison to alkylator-based regimen as induction therapy for chronic lymphocytic leukemia: a systematic review and meta-analysis.

The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several studies but no studies have yet reported a pooled estimate of the treatment effect. We performed a systematic review of evidence from 5 randomized controlled trials involving approximately 1300 patients with CLL, comparing Fludarabine with several alkylator-based combination regimens in the primary treatment of CLL. Complete response rate was significantly higher for Fludarabine compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02), while overall response, though superior, did not reach statistical significance (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95% CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95% CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis supports the findings that Fludarabine as an induction agent for patients with CLL yields a better clinical response with acceptable toxicity when compared with alkylator-based combination therapy, but without a survival benefit by 5-6 years of follow up.

In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes.

Acticoat is a polyethylene mesh coated with nanocrystalline silver. It has been used widely as a dressing for chronic wounds, acute partial-thickness burn wounds and donor sites. In this study, the in vitro cytotoxicity of Acticoat on cultured keratinocytes is tested. Human keratinocytes are cultivated on a pliable hyaluronate-derived membrane (Laserskin) using dermal fibroblasts as the feeder layer. When the cultured Laserskin (CLS) is subconfluent it is covered by Acticoat, which is exposed to water (Group 1), phosphate-buffered saline (Group 2) or culture medium (Group 3). The control group is not exposed to the Acticoat. After 30 minutes incubation at 37 degrees C, the inhibitory effect of the nanocrystalline silver on keratinocyte growth is measured by an MTT assay. Compared with the control, the relative viability of the CLS dropped to 0%, 0% and 9.3%, respectively. Thus, Acticoat is cytotoxic to cultured keratinocytes and should not be applied as a topical dressing on cultured skin grafts.

Mathematical model for predicting biliary therapeutic endoscopic retrograde pancreatography (ERCP).

INTRODUCTION: Magnetic resonance cholangiopancreatography is as sensitive as endoscopic retrograde pancreatography in the evaluation of biliary tract diseases but does not offer therapeutic options. The aim of the present study was to develop a mathematical model to predict 'therapeutic endoscopic retrograde pancreatography' using clinical variables so that patients with low probability could be more appropriately investigated by magnetic resonance cholangiopancreatography in future. METHODS: Endoscopic retrograde pancreatography cases between January 1996 to December 1997 were retrospectively reviewed (before introduction of magnetic resonance cholangiopancreatography). Clinical, biochemical and radiological variables were analysed and a model was developed using multiple logistic regression. RESULTS: Case notes for 573 patients were successfully reviewed. A total of 330 patients underwent therapeutic endoscopic retrograde pancreatography (sphincterotomy or stent insertion). Clinical indications of obstructive jaundice and cholangitis, ultrasonographic findings of dilated common bile duct, and raised liver function tests (two or more elevated parameters) were each found to be predictive for 'therapeutic' endoscopic retrograde pancreatography. Using these variables, the mathematical model in the present study has specificity of 77% and sensitivity of 75% at the probability level of 50% or higher. This model has been tested in a separate group of endoscopic retrograde pancreatography cases carried out in 1998 and was found to have sensitivity 77.6%, specificity 80.3%, positive predictive value 68.5% and negative predictive value 86.6%. CONCLUSIONS: The model reported in the present study can help clinicians to identify cases for therapeutic endoscopic retrograde pancreatography and diagnostic magnetic resonance cholangiopancreatography.