Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. Design, Setting, and Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models. Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001). Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

Efficacy and safety of acupuncture combined with analgesics on lung cancer pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Lung cancer (LC) is the malignant tumor with the highest incidence in the world, and treatment methods include surgery, radiotherapy, chemotherapy, and immunotherapy. Cancer pain is a common symptom in patients with LC, and the clinical treatment is to relieve it with analgesics. Acupuncture can relieve cancer pain. This study aims to systematically study the efficacy and safety of acupuncture combined with analgesics on cancer pain in patients with LC. METHODS: From the beginning to April 2021, search Medline, Embase, Cochrane Central Controlled Trials Register (Central), China National Knowledge Infrastructure (CNKI), Wanfang Database, China Biomedical Literature Database (CBM), and Chinese Science Journal Database (VIP database). Search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing or unpublished trials. The main outcome indicator is the total effective rate of analgesia, and the secondary outcome indicator is pain intensity score and adverse reactions. The RevMan 5.4 software will be used for statistical analysis. RESULTS: This study will provide the latest evidence for acupuncture combined with analgesics to relieve LC pain. CONCLUSION: The conclusion of this study is to evaluate the effectiveness and safety of acupuncture combined with analgesics in alleviating LC pain. INPLASY REGISTRATION NUMBER: INPLASY202150051.

Viral Venereal Diseases of the Skin.

Viral venereal diseases remain difficult to treat. Human papilloma virus (HPV) and herpes simplex virus (HSV) are two common viral venereal diseases. HPV infections are characterized by anogenital warts and less commonly by premalignant or malignant lesions. HSV infections classically present as grouped vesicles on an erythematous base with associated burning or pain; however, immunosuppressed patients may have atypical presentations with nodular or ulcerative lesions. This review discusses the epidemiology, diagnosis, and management of anogenital HPV and HSV infections with an emphasis on treatment modalities for the practicing dermatologist. Diagnosis of these diseases typically relies on clinical assessment, although multiple diagnostic techniques can be utilized and are recommended when diagnosis is uncertain or evaluating an individual with increased risk of malignancy. Management of HPV and HSV infections involves appropriate counseling, screening, and multiple treatment techniques. Particularly for HPV infections, a practitioner may need to use a combination of techniques to achieve the desired outcome.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products. METHODS: Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review. RESULTS: Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances. CONCLUSIONS: The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?

OBJECTIVE: To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use after resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. SUBJECTS AND METHODS: In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. RESULTS: Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. CONCLUSIONS: High-certainty evidence shows that SI-IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.

Liver transplantation and BCLC classification: Limitations impede optimum treatment.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) system has been endorsed by international guidelines as a staging algorithm of hepatocellular carcinoma. This analysis was performed to assess the outcome of liver transplantation in patients treated against the BCLC recommendations. METHODS: The data of 198 patients who underwent liver transplantation for hepatocellular carcinoma were extracted from a prospectively maintained database to classify the patients according to the BCLC system. RESULTS: BCLC staging was as follows: 0, n = 5; A, n = 77; B, n = 41; C, n = 53; and D, n = 22. Accordingly, liver transplantation was performed in the majority of patients against BCLC recommendations. Surgery (n = 16), radiofrequency ablation (n = 15) and transarterial chemoembolization (n = 151) preceded liver transplantation in 182 patients. Sixteen patients were transplanted without pretreatment. The1-, 5- and 10-year survival rates were 83.8%, 62.4% and 45.9%, and 1-, 5-, and 10-year recurrence rates were 7.7%, 22.7% and 26.7%. The BCLC classification did neither impact survival (P = 0.796) nor recurrence (P = 0.693). In the Cox analysis, RECIST tumor progression and initial alpha fetoprotein were independent predictors of outcome. CONCLUSIONS: Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome. Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.

Rationale for Use of Combination Therapy in Rosacea.

BACKGROUND: Rosacea is a chronic skin condition characterized by primary and secondary manifestations affecting the centrofacial skin. The primary diagnostic phenotypes for rosacea are fixed centrofacial erythema with periodic intensification, and phymatous changes. Major phenotypes, including papules and pustules, flushing, telangiectasia, and ocular manifestations, may occur concomitantly or independently with the diagnostic features. The phenotypes of rosacea patients may evolve between subtypes and may require multiple treatments concurrently to be effectively managed. We report the proceedings of a roundtable discussion among 3 dermatologists experienced in the treatment of rosacea and present examples of rosacea treatment strategies that target multiple rosacea symptoms presenting in individual patients. METHODS: Three hypothetical cases describing patients representative of those commonly seen by practicing dermatologists were developed. A roundtable discussion was held to discuss overall and specific strategies for treating rosacea based on the cases. RESULTS/DISCUSSION: With few exceptions, the dermatologists recommended combination therapy targeting each manifestation of rosacea for each case. These recommendations are in agreement with the current American Acne and Rosacea Society treatment guidelines for rosacea and are supported by several studies demonstrating beneficial results from combining rosacea treatments. CONCLUSIONS: Rosacea is an evolving condition; care should take into account all clinical signs and symptoms of rosacea that are present in an individual patient, understanding that symptoms may change over time, and utilize combination therapy when applicable to target all rosacea symptoms. J Drugs Dermatol. 2020;19(10): 929-934. doi:10.36849/JDD.2020.5367.

Prospective Evaluation of a Standardized Opioid Reduction Protocol after Anorectal Surgery.

BACKGROUND: Surgery for anorectal disease is thought to cause significant postoperative pain. Our previous work demonstrated that most opioids prescribed after anorectal surgery are not used. We aimed to evaluate a standardized protocol for pain control after anorectal surgery. METHODS: We prospectively evaluated a standardized opioid reduction protocol over a 13-mo period for all patients undergoing elective anorectal surgery at our institution. Protocol components include preoperative query, procedural local-anesthetic blocks, first-line nonopioid analgesic use ± opioid prescription of five pills, and standardized postoperative instructions. Patients completed questionnaires at postoperative follow-up. Patients with history of opioid abuse or use within 30 d of operation, loss to follow-up, or surgical complications were excluded. Primary outcome was quality of pain control on a five-point scale. Secondary outcomes included use of nonopioid analgesics, opioids used, and need for refill. RESULTS: A total of 55 patients were included. Mean age was 47 ± 17 y with 23 women (42%). Anorectal abscess/fistula procedures were the most common (69%) followed by pilonidal procedures (11%) and hemorrhoidectomy (7%). Most had general anesthesia (60%) with the remainder local anesthesia ± sedation. Fifty-four (98%) had procedural local-anesthetic blocks. Twenty-six patients (47%) were prescribed opioids with a median of five pills. Forty-seven patients (85%) reported the use of nonopioid analgesics. Forty-six patients (84%) reported excellent to very good pain control. About 220 opioid pills were prescribed, and 122 were reported to be used. One patient (2%) received an opioid refill. CONCLUSIONS: Satisfactory pain control after anorectal surgery can be achieved with multimodality therapy with little to no opioid use for most patients.

Mucormycosis treatment: Recommendations, latest advances, and perspectives.

Mucormycosis are life-threatening fungal infections especially affecting immunocompromised or diabetic patients. Despite treatment, mortality remains high (from 32 to 70% according to organ involvement). This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line. Many molecules are currently in development to fight against invasive fungal diseases but few have demonstrated efficacy against Mucorales. Despite in vitro efficacy, combinations of treatment have failed to demonstrate superiority versus monotherapy. Adjuvant therapies are particularly complex to evaluate without prospective randomized controlled studies, which are complex to perform due to low incidence rate and high mortality of mucormycosis. Perspectives are nonetheless encouraging. New approaches assessing relationships between host, fungi, and antifungal drugs, and new routes of administration such as aerosols could improve mucormycosis treatment.

Immunomodulatory effects of ablation therapy on tumors: Potentials for combination with immunotherapy.

As a promising area of tumor treatment, immunotherapies, such as immune checkpoint inhibitors, have been applied to various types of cancer. However, many patients do not respond to such therapies. Increasing application of tumor ablation therapy, a minimally invasive treatment, has been observed in the clinic. Although it can boost the anti-tumor immune response of patients in many ways, ablation alone is not sufficient to remove the tumor completely or stop tumor recurrence in the long term. Currently, there is emerging research focusing on ablation in combination with immunotherapy, aiming to confirm the therapeutic value of this treatment for cancer patients. Hence, in this article, we review the classification, guideline recommendations, and immunomodulatory effects of ablation therapy, as well as the pre-clinical and clinical research of this combination therapy.

Accounting for Range Uncertainties in the Optimization of Combined Proton-Photon Treatments Via Stochastic Optimization.

PURPOSE: Proton treatment slots are a limited resource. Combined proton-photon treatments, in which most fractions are delivered with photons and only a few with protons, may represent a practical solution to optimize the allocation of proton resources over the patient population. We demonstrate how a limited number of proton fractions can be optimally used in multimodality treatments and address the issue of the robustness of combined treatments against proton range uncertainties. METHODS AND MATERIALS: Combined proton-photon treatments are planned by simultaneously optimizing intensity modulated radiation therapy and proton therapy plans while accounting for the fractionation effect through the biologically effective dose model. The method was investigated for different tumor sites (a spinal metastasis, a sacral chordoma, and an atypical meningioma) in which organs at risk (OARs) were located within or near the tumor. Stochastic optimization was applied to mitigate range uncertainties. RESULTS: In optimal combinations, proton and photon fractions deliver similar doses to OARs overlaying the target volume to protect these dose-limiting normal tissues through fractionation. Meanwhile, parts of the tumor are hypofractionated with protons. Thus, the total dose delivered with photons is reduced compared with simple combinations in which each modality delivers the prescribed dose per fraction to the target volume. The benefit of optimal combinations persists when range errors are accounted for via stochastic optimization. CONCLUSIONS: Limited proton resources are optimally used in combined treatments if parts of the tumor are hypofractionated with protons and near-uniform fractionation is maintained in serial OARs. Proton range uncertainties can be efficiently accounted for through stochastic optimization and are not an obstacle for clinical application.

[Electroconvulsive therapy in combination with psychotropic and non-psychotropic pharmacological treatments: Review of the literature and practical recommendations]. / Électroconvulsivothérapie en association avec des traitements pharmacologiques psychotropes et non psychotropes : revue de la littérature et recommandations pratiques.

CONTEXT: Electro-convulsive therapy (ECT) is the most effective treatment for treatment resistant mood disorders and catatonia. ECT also appears to be an effective treatment in combination with clozapine in the context of treatment resistant schizophrenia spectrum disorders. Although increasingly codified (guidelines on indications, contraindications, methods of implementation), the practice of ECT still lacks consensual protocols. The concomitant use of psychotropic and/or non-psychotropic medication is a common situation when ECT treatment is considered. To our knowledge, there is to date no summary of studies or case reports in France, nor any proposal for guidelines concerning the management of medication of the patient to whom ECT sessions are offered. Indeed, several particularities must be considered. This article proposes to specify for each pharmacological class the possible interaction between ECT and medication. A first section of this article will be devoted to non-psychotropic treatments, and a second section to psychotropic treatments. A practical summary table is also provided. METHOD: A review of the literature was conducted including all articles published prior to January 2019 referenced in Pub Med database, combining research with Medical Subject Headings "Electroconvulsive Therapy" and each following pharmacological class: "Cardiovascular Agents" "Bronchodilator Agents" "Bronchoconstrictor Agents" "Theophylline" "Anticoagulants" "Hypoglycemic Agents" "Insulin" "Potassium" "Benzodiazepines" "Valproic Acid" "Carbamazepine" "Lamotrigine" "Lithium" "Antidepressive Agents" "Antipsychotic Agents". RESULTS: After reading the titles, abstracts and whole articles, then searching for additional articles in the references, 50 articles were selected. A summary table summarizing the main risks and proposing a course of action has been produced. DISCUSSION: It is essential to take into account the specificity and the different physiological mechanisms involved in the ECT treatment in order to adjust the associated pharmacological treatments. The prescription for each molecule should be reviewed when ECT treatment is initiated.

Treatment strategies and overall survival for incurable metastatic colorectal cancer - A EURECCA international comparison including 21,196 patients from the Netherlands and Norway.

BACKGROUND: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer. METHODS: National cohorts (2007-2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year. RESULTS: Of 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93-0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99-1.02; p = 0.741). CONCLUSIONS: Treatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients ≥75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options.

Indian clinical practice consensus guidelines for the management of squamous cell carcinoma of head and neck.

Head and neck cancers (HNCs) are malignant tumors of the upper aerodigestive tract and are the sixth most common cancer worldwide. In India, around 30-40% of all cancers are HNCs. Even though there are global guidelines or recommendations for the management of HNCs, these may not be appropriate for Indian scenarios. In an effort to discuss current practices, latest developments and to come to a consensus to recommend management strategies for different anatomical subsites of HNCs for Indian patients, a group of experts (medical, surgical and radiation oncologists and dentists) was formed. A review of literature from medical databases was conducted to provide the best possible evidence base, which was reviewed by experts during a consensus group meeting (January, 2019) to provide recommendations.