Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

Knowledge, attitudes and intention on fertility preservation among breast cancer patients.

Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

Post-radiation primary hypothyroidism in patients with head and neck cancer: External validation of thyroid gland dose-volume constraints with long-term endocrine outcomes.

BACKGROUND: Post-radiation primary hypothyroidism is a common late complication in head and neck cancer (HNC) survivors. No radiation dose-volume constraint of the thyroid gland has been externally validated for predicting long-term thyroid function outcomes. MATERIALS AND METHODS: This external validation study evaluated the diagnostic properties of 22 radiation dose-volume constraints of the thyroid gland proposed in the literature. Radiation dosimetric data from 488 HNC patients who underwent neck irradiation from January 2013 to December 2015 at two tertiary oncology centers were reviewed. The diagnostic metrics of candidate constraints were computed by inverse probability of censoring weighting and compared using time-dependent receiver operating characteristic (ROC) curves with death designated as a competing event. Multivariable regression analyses were performed using the Fine-Gray sub-distribution hazard model. RESULTS: Over a median follow-up period of 6.8 years, 205 (42.0 %) patients developed post-radiation primary hypothyroidism. The thyroid volume spared from 60 Gy (VS60) had the largest area under ROC curve of 0.698 at 5 years after radiotherapy. Of all evaluated constraints, VS60 at a cutoff value of 10 cc had the highest F-score of 0.53. The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively (p < 0.001). The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 < 10 cc was 1.87 (95 % confidence interval, 1.22-2.87; p < 0.001). CONCLUSION: Thyroid VS60 is the best radiation dose-volume parameter to predict the long-term risk of primary hypothyroidism in patients with HNC who underwent neck irradiation. VS60 ≥ 10 cc is a robust constraint that limits the 5-year primary hypothyroidism risk to less than 15 % and should be routinely employed during radiotherapy optimization.

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

Background: In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations. Methods: A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose "Accept Completely" (Option A) or "Accept with Some Reservation" (Option B). Results: The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients. Conclusion: This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer.

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

[Impact of breast dimension in one-stage augmentation mastopexies on implant selection: review of 103 consecutive breast augmentations with nanotextured silicone implants]. / Einfluss der Brustdimension bei der einzeitigen Augmentationsmastopexie auf die Implantatauswahl ­ Erfahrungen aus 103 konsekutiven Brustaugmentationen mit nanotexturierten Silikonimplantaten.

INTRODUCTION: According to current studies, one-stage augmentation mastopexy (AM) is associated with only minor complications and a lower reoperation rate compared with a staged procedure. In AM, breast dimension can differ notably compared with those cases without simultaneous mastopexy. However, these differences have only been insufficiently investigated. This study aims to quantify the differences and then evaluate the effect of breast dimension on implant selection. In addition, it evaluates the influence of mastopexy on the outcome of augmentation mammoplasties with round nanotextured silicone gel implants. PATIENTS AND METHODS: Over a two-year period, all patients with primary augmentation mammoplasties using nanotextured implants were included in the study. Patients' demographic data, breast measurements, specifications of the implants placed, and complications in the breast augmentation group without mastopexy were compared with those of the group with AM. The satisfaction of patients and surgeons was documented using Likert scales. RESULTS: A total of 206 breast augmentations were performed in n = 103 patients. The mean follow-up was 24.0 ±â€…4.3 months. Compared with augmentations without an indication for simultaneous mastopexy, the AM group had wider breast bases and larger preoperative cup sizes; p < 0.001. As a result, implants selected for AM had greater diameters and lower volumes (p < 0.05) and were associated with smaller projections; p < 0.001. The total revision rates after augmentations without (n = 51) and with combined mastopexy (n = 52) were 5.9 % and 19.2 % (p < 0.05), respectively. AM increased tissue-related revisions from 2.0 % to 13.4 % (p < 0.05) without having an impact on implant-related revisions (3.9 % vs. 5.8 %, p = 0.663). The overall incidence of capsular contracture was 1.9 %. Satisfaction levels were approximately equal in both groups. CONCLUSION: In comparison to augmentations without mastopexy, wider breast bases and larger breast volumes before surgery lead to the selection of significantly different implant dimensions in AM. Nanotextured silicone implants are associated with low complication rates, while an increased risk for tissue-related revisions of the combined procedure remains. Further studies are necessary in order to evaluate possible advantages and disadvantages over established implants.

Aggravation of symptom severity in adult attention-deficit/hyperactivity disorder by latent Toxoplasma gondii infection: a case-control study.

Toxoplasma gondii (T. gondii) has a high worldwide prevalence and an underestimated impact on neuropsychiatric disorders. Previous studies related T. gondii to disorders associated with the dysfunctional dopaminergic system. However, an association between T. gondii infection and adult attention-deficit/hyperactivity disorder (ADHD) has not yet been studied. In a sex- and age-matched case-control study, we investigated the seropositivity, serointensity, and avidity of latent T. gondii infection in adult ADHD patients and examined the influence of those variables on the symptomatology of ADHD. Of 140 participants, 20.0% were seropositive for anti-T. gondii IgG and 0% for anti-T. gondii IgM. T. gondii seropositivity was associated with 2.8-fold increase in the odds of ADHD in a confounder-adjusted multivariable analysis. Age and consumption of raw/undercooked meat were confirmed as significant predictors of T. gondii seropositivity. Multiple linear regression analysis of self-rated ADHD-related symptom severity in all participants revealed a significant association with T. gondii seropositivity, elevated IgG titers (serointensity), and stronger anti-T. gondii IgG avidity. Overall symptom severity was increased in seropositive ADHD patients compared to seronegative subjects with ADHD. In particular, hyperactivity was significantly associated with serointensity. We conclude that there is a high rate of T. gondii seropositivity in adults with ADHD. Additionally, our results suggest a clinical impact of latent T. gondii infection on ADHD-related symptoms in a serointensity- and avidity-dependent manner.

Management of Capsular Contracture in Cases of Silicone Gel Breast Implant Rupture with Use of Pulse Lavage and Open Capsulotomy.

INTRODUCTION: Pulse lavage (PL) irrigation of prosthesis pockets has prior been described for breast implant salvages. However, PL for removal of leaked silicone from prosthesis pockets after implant ruptures has not been studied yet. Since open capsulotomies are regarded as equal treatment of capsular contracture (CC) than capsulectomies, this study analyzed the clinical outcome of PL for silicone removal and subsequent capsulotomy in cases of concurrent CC and breast implant rupture. METHODS: Between 2012 and 2017, 55 patients (75 breasts) with suspected silicone implant rupture and CC (Baker grade III/IV), after primary breast augmentation or implant-based breast reconstruction, were included in a retrospective, observational study. Mean patient follow-up was 12.2 ± 3.6 months. RESULTS: In all preoperatively suspected ruptured silicone breast implants, around a quarter were intact. In contrast to previously published data, implant exchanges in cases of implant ruptures did not lead to significantly higher CC recurrence rates (27.6% vs. 22.2% in cases of intact implants, p = 0.682), if the prosthesis pockets were treated with PL irrigation followed by open capsulotomy. PL reduced the amount of encapsulated silicone remnants histologically. The age of patients with CC after failed implant-based reconstruction was significant lower for salvage surgeries with flap reconstruction than for implant exchanges, p < 0.05. CONCLUSIONS: PL irrigation of prosthesis pockets prior to open capsulotomy is a safe and effective treatment of CC with concurrent silicone leakage. Remaining silicone remnants in breast capsules may affect the development of a recurrent CC. To avoid CC recurrences, patients should consider conversion to autologous tissue. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Predictors of Clinical Outcome after Reconstruction of Complex Soft Tissue Defects Involving the Achilles Tendon with the Composite Anterolateral Thigh Flap with Vascularized Fascia Lata.

BACKGROUND: The composite anterolateral thigh flap with vascularized fascia lata (ALT-FL flap) for covering complex soft tissue defects involving the Achilles tendon has shown promising results. The age and body mass index (BMI) are important predictors of clinical outcome after surgical treatment of Achilles tendon ruptures. In this study, we investigate whether these also influence the outcome of patients after Achilles tendon reconstruction using the ALT-FL flap. METHODS: Twenty patients (mean age: 55.9 ± 8.7 years) with complex tissue defects involving the Achilles tendon underwent reconstruction with the ALT-FL flap. Both the Achilles tendon Total Rupture Score (ATRS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score were assessed preoperatively and 12 months postoperatively. In addition, postoperative magnetic resonance imaging (MRI) studies and measurements of the ankle range of motion were performed and results compared with existing literature. RESULTS: All flaps survived and MRI studies confirmed complete anatomical integration of the fascia lata as "neotendon" at the recipient site. In our patient cohort, the age did not correlate with the outcome measurements, whereas the BMI showed significant negative correlation with the postoperative ATRS (p < 0.001) and AOFAS scores (p < 0.05). The ATRS and AOFAS scores of all patients improved significantly (p < 0.001). However, obese patients with a BMI of more than 30 kg/m2 achieved significant lower ATRS (p < 0.001) and AOFAS scores (p < 0.01), as well as patients with peripheral artery disease (PAD) (p < 0.05). The mean ankle range of motion after ALT-FL flap reconstruction remained statistical insignificant compared with previous avascular or vascularized tendon repairs of the Achilles tendon. CONCLUSION: The ALT-FL flap enables reconstruction of complex tissue defects involving the Achilles tendon with good functional results. However, the presence of an increased BMI or PAD, but not necessarily the age, proves to be a predictor of poor clinical outcome and therefore should be subject to scrutiny during patient selection.

The free medial sural artery perforator flap: Versatile option for soft tissue reconstruction in small-to-moderate size defects of the foot and ankle.

BACKGROUND: The medial sural artery perforator (MSAP) flap shows advantages for reconstruction in the foot and ankle, where bulk is a liability. We evaluated the versatility of this flap and provide further evidence on its use for covering small-to-moderate size defects by comparing the outcome depending on the region of reconstruction. METHODS: Twenty-two patients with variable defects of 4 × 4 to 18 × 7 cm underwent MSAP flap reconstruction. Final outcomes of all patients were evaluated 12-months postoperatively using the AOFAS ankle-hindfoot, midfoot and hallux scale for clinical-functional evaluation, and the SF-36 health survey for quality-of-life measurement. The scores were compared in three groups according to the anatomic region of MSAP flap reconstruction. RESULTS: The flap size ranged between 6 × 4 and 21 × 9 cm. One venous congestion was salvaged by venous thrombectomy and reanastomosis, and one marginal flap necrosis healed by secondary intention. All flaps survived, and all patients returned to ambulation. Patients with reconstruction of the ankle-hindfoot or hallux showed significantly lower AOFAS ankle-hindfoot (P = 0.021) or hallux scores (P = 0.034), whereas reconstruction of the midfoot led to equal AOFAS midfoot scores (P = 0.265) as compared with patients without reconstruction in the respective region. Comparison of SF-36 physical (P = 0.936) and mental (P = 0.855) scores of all three regions remained insignificant. CONCLUSION: The MSAP flap provides thin soft tissue coverage, enabling good functional recovery after defect reconstruction all around the foot and ankle, with evident advantages in the midfoot. However, the functional outcomes after reconstruction of the ankle-hindfoot or hallux region depend on the preexistent functional impairment.

EPR monitoring of wound oxygenation as a biomarker of response to gene therapy encoding hCAP-18/LL37 peptide.

PURPOSE: To investigate the value of electron paramagnetic resonance oximetry to follow oxygenation in wounds treated by a plasmid-encoding host defense peptide hCAP-18/LL37. METHODS: Flaps were created on diabetic mice (7- or 12-week-old db/db mice) presenting different levels of microangiopathy. The hCAP-18/LL37-encoding plasmids were administered in wounds by electroporation. Low-frequency electron paramagnetic resonance oximetry using lithium phthalocyanine as the oxygen sensor was used to monitor wound oxygenation in flaps during the healing process. Flaps were analyzed by immunohistochemistry to assess hypoxia and cell proliferation. Kinetics of closure was also assessed in excisional skin wounds. RESULTS: A reoxygenation of the flap was observed during the healing process in the 7-week-old db/db treated mice, but not in the untreated mice and the 12-week-old mice. Histological studies demonstrated less hypoxic regions and higher proportion of proliferating cells in hCAP-18/LL37-treated flaps in the 7-week-old db/db treated mice compared with untreated mice. Consistently, the kinetics of excisional wound closure was improved by hCAP-18/LL37 treatment in the 7-week-old db/db but not in the 12-week-old mice. CONCLUSIONS: Oxygenation measured by electron paramagnetic resonance oximetry is a promising biomarker of response to treatments designed to modulate wound oxygenation. Magn Reson Med 79:3267-3273, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.

Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing.

Host defense peptides, in particular LL-37, are emerging as potential therapeutics for promoting wound healing and inhibiting bacterial growth. However, effective delivery of the LL-37 peptide remains limiting. We hypothesized that skin-targeted electroporation of a plasmid encoding hCAP-18/LL-37 would promote the healing of wounds. The plasmid was efficiently delivered to full-thickness skin wounds by electroporation and it induced expression of LL-37 in the epithelium. It significantly accelerated reepithelialization of nondiabetic and diabetic wounds and caused a significant VEGFa and interleukin (IL)-6 induction. IL-6 was involved in LL-37-mediated keratinocyte migration in vitro and IL-6 neutralizing antibodies delivered to mice were able to suppress the wound healing activity of the hCAP-18/LL-37 plasmid. In a hindlimb ischemia model, electroporation of the hCAP-18/LL-37 plasmid increased blood perfusion, reduced muscular atrophy, and upregulated the angiogenic chemokines VEGFa and SDF-1a, and their receptors VEGF-R and CXCR-4. These findings demonstrate that a localized gene therapy with LL-37 is a promising approach for the treatment of wounds.