Search

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management. Funding Agencies|Empros Pharma AB

The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria.To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR).Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review.A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups.Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations.Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.

Surgical decisions for ductal carcinoma in situ (DCIS) are based on lesion sizes. This study aims to determine the accuracy of pre-operative imaging in estimating the size of DCIS.This was a retrospective review of clinicopathologic data of patients treated for DCIS with breast conserving surgery (BCS) between 2012 and 2018. Mammographic and sonographic lesion sizes were compared with final pathology sizes.For the 152 lesions visible on mammography, mean size on imaging was significantly smaller when compared to final pathology (2.3 vs. 3.6 cm, p 0.001). The mean difference of 1.3 cm was a significant underestimation with a correlation coefficient of 0.367 (p 0.001). For 48 sonographically visible lesions, the radiologic size was significantly smaller than pathologic size (1.7 vs. 4.1 cm, p 0.001), but the degree of underestimation was not significantly correlated (p = 0.379).DCIS size was significantly underestimated by imaging. This must be taken into consideration during surgical planning.

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

Background: In response to Choosing Wisely recommendations that sentinel lymph node biopsy (slnb) should not be routinely performed in elderly patients with node-negative (cN0), estrogen receptor–positive (er+) breast cancer, we sought to evaluate how nodal staging affects adjuvant treatment in this population. Methods: From a prospective database, we identified patients 70 or more years of age with cN0 breast cancer treated with surgery for er+ her2-negative invasive disease during 2012–2016. We determined rates of, and factors associated with, nodal positivity (pN+), and compared the use of adjuvant radiation (rt) and systemic therapy by nodal status. Results: Of 364 patients who met the inclusion criteria, 331 (91%) underwent slnb, with 75 (23%) being pN+. Axillary node dissection was performed in 11 patients (3%). On multivariate analysis, tumour size was the only factor associated with pN+ (p = 0.007). Nodal positivity rates were 0%, 13%, 23%, 33%, and 27% for lesions preoperatively sized at 0–0.5 cm, 0.5–1 cm, 1.1–2.0 cm, 2.1–5.0 cm, and more than 5.0 cm. Compared with patients assessed as node-negative, those who were pN+ were more likely to receive axillary rt (lumpectomy: 53% vs. 1%, p < 0.001; mastectomy: 43% vs. 2%, p < 0.001), and adjuvant systemic therapy (endocrine: 82% vs. 69%; chemotherapy plus endocrine: 7% vs. 2%, p = 0.002). Conclusions: Of elderly patients with cN0 er+ breast cancer, 23% were pN+ on slnb. Size was the primary predictor of nodal status, and yet significant rates of nodal positivity were observed even in tumours preoperatively sized at 1 cm or less. The use of rt and systemic adjuvant therapies differed by nodal status, although the long-term oncologic implications require further investigation. Multidisciplinary input on a case-by-case basis should be considered before omission of slnb.

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n=11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. PATIENT SUMMARY: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.

Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of “1” and were included in the ADH upstaging risk calculator. A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery—of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more “high-risk” lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.

Introduction and Objective Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. Materials and Methods We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). Results From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22–63.12%) and hilar (31.42%; 95% CI 17.4–49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7–43.2%), hilar (26.82%; 95% CI 14.7–43.2%), interaortocaval (26.82%; 95% CI 14.7–43.2%), and paracaval (17.07%; 95% CI 7.6–32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. Conclusions Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.

Quality Indicators (QIs), including the breast-conserving surgery (BCS) rate, were published by the European and American Breast Cancer Societies and this study assesses these in a Canadian population to look for opportunities to de-escalate surgery. A total of 2311 patients having surgery for unilateral, unifocal breast cancer between 2013 and 2017 were identified and BCS QIs calculated. Reasons for mastectomy had been prospectively collected with synoptic operative reporting. Our BCS rate for invasive cancer < 3 cm was 77.1%, invasive cancer < 2 cm was 84.1%, and DCIS < 2 cm was 84.9%. There was no statistically significant change in BCS rates over a five-year period, but there was a reduction in contralateral prophylactic mastectomies (CPM) from 28% in 2013 to 16% in 2017 (p < 0.001). Trend analysis looking at tumour size and medical need for mastectomy indicated that 80% of patients at our centre would be eligible for BCS with tumour cut off of 2.5 cm. Our institution met American but not European QI standards for BCS rates, potentially indicating a difference in patient demographics compared to Europe. Our results support the understanding that BCS rates are influenced by multiple factors and are challenging to compare across jurisdictions. CPM rates may offer a more actionable opportunity to de-escalate surgery for breast cancer.

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.

PurposeFibroepithelial lesions (FEL) range from benign fibroadenoma (FA) to malignant phyllodes tumor (PT), but can be difficult to diagnose on core needle biopsy (CNB). This study assesses risk factors for phyllodes tumor (PT) and recurrence and whether the policy to excise FELs over 3 cm in size is justified. MethodsPatients having surgery for FELs from 2009-2018 were identified. The association of clinical, radiology and pathological features with PT and recurrence were evaluated. Trend analysis was used to assess risk of PT based on imaging size. ResultsOf the 616 patients with FELs, 400 were identified as having FA on CNB and 216 were identified as having FEL with a comment of concern for phyllodes tumor (QPT). PT was identified in 107 cases, 28 had CNB of FA (7.0%) while 79 had QPT (36.6%). Follow-up was available for 86 with a mean of 56 months; 6 patients had recurrence of PT, all of whom had QPT on CNB. The finding of PT was associated with CNB of QPT, increasing age and size on multivariate logistic regression. All patients diagnosed with PT following CNB of FA had enlarging lesions with a mean size of 38.3 mm. ConclusionsOur data does not support routine excision of FELs at 3 cm. Patients with QPT on CNB should consider excision due to high risk of PT and recurrence and the decision to excise FAs to rule out PT should also consider whether the lesion is enlarging.

In recent years, routine excision of papillary neoplasms (PN) of the breast has been questioned and controversy exists over when excision is necessary. The aim of this study was to evaluate the upstage rate to malignancy of core needle biopsy (CNB) diagnosed PNs from multiple diagnostic centers in our area and to identify factors predictive of malignancy. Patients presenting to our surgical center between 2013 and 2017 for excision of CNB PN were evaluated. The primary endpoint was upstage to malignancy. The association of age, diagnostic center where CNB performed, type of CNB, palpability, discharge, clinical exam size, imaging size, family history of breast cancer, and presence of atypia, as risk factors for upstaging to cancer were also evaluated. Of the 317 PN cases, 83 upstaged to malignancy following surgical excision. 77% of patients with CNB of Atypical PN upstaged, 39% of PN with concurrent atypical ductal hyperplasia, and 0% of PN with concurrent atypical lobular hyperplasia/flat epithelial atypia. Of the 206 non-atypical PNs on CNB, 3.4% upstaged to malignancy, but further review demonstrated a 1% upstage rate when atypia excluded. Factors found to be associated with malignancy included: older patient age, larger size, and presence of atypia. We recommend excision of PN with atypia, concurrent cancerous lesion, or radiologic–pathologic non-concordance, and serial imaging follow up may be considered for image detected PN, less than 1 cm, with no atypia.

Surgery is the standard treatment for nonmetastatic renal cell carcinoma. Despite curative intent, patients with a high risk of relapse have a 5-year metastasis-free survival rate of only 30% and prevention of recurrence is an unmet need. In a Phase III trial (JAVELIN Renal 101), progression-free survival of axitinib + avelumab was superior to sunitinib with a favorable objective response rate and no added toxicity profiles as known for axitinib or avelumab single agent. NEOAVAX is designed as open label, single arm, Phase II trial with a Simon’s two-stage design evaluating neoadjuvant axitinib + avelumab followed by complete surgical resection in 40 patients with high-risk nonmetastatic clear-cell renal cell carcinoma. Primary end point is remission of the primary tumor (RECIST 1.1; Response Evaluation Criteria In Solid Tumors) following neoadjuvant therapy. Secondary end points include disease-free survival, overall survival, rate of metastasis and local recurrence, safety, and tolerability. Exploratory end points include investigation of effects on neoangiogenesis, immune infiltrates and myeloid-derived suppressor cell components to support a rationale for the combined use of axitinib and avelumab (NCT03341845).

Background Lymphedema is a prevalent long-term effect of breast cancer treatment associated with reduced quality of life. This study examined the efficacy of nighttime compression as a self-management strategy for women with chronic breast cancer-related lymphedema. Methods Th authors conducted a parallel 3-arm, multicenter, randomized trial. Women were recruited from 3 centers in Canada and randomized to group 1 (daytime compression garment alone [standard care]), group 2 (daytime compression garment plus nighttime compression bandaging), or group 3 (daytime compression garment plus the use of a nighttime compression system garment). The primary outcome was the change in excess arm volume from the baseline to 12 weeks. Participants from all groups used a nighttime compression system garment from weeks 13 to 24. Results One hundred twenty women were enrolled, 118 completed the randomized trial, and 114 completed the 24-week follow-up. The rates of adherence to nighttime compression were 95% ± 15% and 96% ± 11% in the compression bandaging and nighttime compression system groups, respectively. After the intervention, the addition of nighttime compression was found to be superior to standard care for both absolute milliliter reductions (P = .006) and percentage reductions (P = .002) in excess arm lymphedema volume. Significant within-group changes were seen for quality of life across all groups; however, no between-group differences were found (P > .05). Conclusions The trial demonstrated a significant improvement in arm lymphedema volume from the addition of nighttime compression whether through the application of compression bandaging or through the use of a nighttime compression system garment. Lay summary Lymphedema is swelling that occurs in the arm on the side of the surgery for breast cancer. Lymphedema occurs in approximately 21% of women. Lymphedema tends to worsen over time and can result in recurrent infections in the arm, functional impairment, and pain. Currently, treatment consists of intensive treatments to reduce the swelling followed by regular use of a compression sleeve during the day. This study examined and found a benefit from the addition of nighttime compression (whether through self-applied compression bandaging or through the use of a nighttime compression system garment) to the use of a daytime compression sleeve.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway. MATERIALS AND METHODS: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19. RESULTS: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice. CONCLUSION: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed.

The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naive metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. Patient summary New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

Immune checkpoint inhibitor (ICI) combination therapy has revolutionized therapy of metastatic renal cancer. The success of immunotherapy has renewed an interest to study these agents in adjuvant and neoadjuvant settings and prior to cytoreductive nephrectomy. This narrative review will give an overview of ongoing trials and early translational research outcomes.In nonmetastatic renal cell carcinoma (RCC), five phase 3 adjuvant and neoadjuvant trials with ICI monotherapy or combinations are ongoing with atezolizumab (IMmotion 010; NCT03024996), pembrolizumab (KEYNOTE-564; NCT03142334), nivolumab (PROSPER; NCT03055013), nivolumab with or without ipilimumab (CheckMate 914; NCT03138512) and durvalumab with or without tremelimumab (RAMPART; NCT03288532). Phase 1b/2 neoadjuvant trials demonstrate safety, efficacy and dynamic changes of immune infiltrates and provide rationales for neoadjuvant trial concepts as well as prediction of response to therapy. In primary metastatic RCC, two phase 3 trials investigate the role of deferred cytoreductive nephrectomy following pretreatment with ICI combination (NORDICSUN; NCT03977571 and PROBE; NCT04510597).The outcomes of the major phase 3 trials are awaited as early as 2023. Meanwhile, translational data from phase 1b/2 studies enhance our understanding of the tumour immune microenvironment and its dynamic changes.

The high number of mutations in the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes its immune escape. We report a longitudinal analysis of 111 vaccinated individuals for their antibody levels up to 6 months after the third dose of the BNT162b2 vaccine. After the third dose, the antibody levels decline but less than after the second dose. The booster dose remarkably increases the serum ability to block wild-type or Omicron variant spike protein's receptor-binding domain (RBD) interaction with the angiotensin-converting enzyme 2 (ACE2) receptor, and these protective antibodies persist 3 months later. Three months after the booster dose, memory CD4

To assess the impact of body mass index (BMI) on peri-operative outcomes of kidney and upper tract robot-assisted surgery. Medical audit of patients who underwent robot-assisted kidney and upper tract cancer surgery at a single institution between 2017 and 2019, categorized on BMI into obese patients with a BMI ≥ 30 kg/m

There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival.We collected data of consecutive patients who underwent nephrectomy and LND for TOf the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17-30 months) and the 5-year OS rate was 24% (95% CI 18-31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p 0.05) were significant predictors of ACM.Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival.

Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies.A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness.Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM.

Patients with spontaneous nipple discharge (SND) who have neither clinically palpable masses nor evidence of disease on imaging with mammogram and/or ultrasound are traditionally investigated with galactogram and duct excision. As breast imaging improves, it has raised the question whether galactography and microductectomy are necessary to diagnose breast cancer. The purpose of this study was to determine the incidence of malignancy in patients presenting with SND who underwent microductectomy and to evaluate the utility of duct excision and galactography in patients whose initial clinical and radiological evaluation were negative. A 10-year retrospective study was conducted in British Columbia’s largest tertiary breast referral center examining the clinical, radiological and pathological results for all patients who underwent a microductectomy procedure for SND between 2008 and 2017. A total of 231 microductectomies were performed and the overall incidence of malignancy was 13% (n = 32). Following initial work up, 155 patients (67%) had only discharge on exam and no radiologically suspicious findings of malignant disease. Of these patients, 14% (n = 21) were diagnosed with cancer by duct excision. Galactography yielded a sensitivity and specificity of 63% and 36%, respectively (PPV 15% and NPV 85%). Lastly, we found that 3% of patients (n = 8) initially diagnosed with benign disease later developed breast cancer. Patients with SND should continue to be evaluated with microductectomy to prevent missing a breast cancer. Moreover, we do not recommend performing galactography for diagnosing breast cancer due to poor sensitivity and specificity though it may assist in preoperative planning.

Patients with localised renal cell carcinoma (RCC) receiving curative surgery, either radical or partial nephrectomy, have been shown in contemporary studies to develop recurrence within 5 years in 20–30% of case. Therefore, post-operative follow-up (FU) imaging plays a crucial role in detecting recurrent or metastatic disease. A number of prognostic scores have been developed to predict risk of recurrence. This review summarises the current knowledge on established FU protocols and their limitations. A non-systematic literature search was conducted using Medline. Furthermore, major guidelines [European Association of Urology (EAU), American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN)] were reviewed and assessed. The EAU, AUA and NCCN post-operative follow-up guidelines differ in the frequency and type of imaging modalities recommended. The optimal duration of follow-up remains to be elucidated as does the impact of follow-up protocols on patient outcomes and quality of life. Established follow-up protocols do not take non-RCC-related factors, such as patient age and performance status into account. However, in the future individualised duration of FU based on competing risks of cancer recurrence and non-RCC death may be optimised, maximising resources and patient quality of life. There is a clear need to establish evidence-based follow-up protocols and to assess the impact of follow-up protocols on individual patients and society.

Introduction Breast Conserving Surgery (BCS) is considered standard of care for women with early stage breast cancer. Between 20 and 50% of women treated with BCS will require re-operation for positive or close margins and it has been suggested that routine cavity shave margins may reduce the frequency of positive margins. Methods Retrospective chart review of a prospectively maintained surgical database of patients undergoing BCS for early stage breast cancer, at a single institution, between January 2012 and December 2015. Cohort was followed until June 2016 to capture re-operations. Results Among 2096 patients with stage 0-III breast cancers, 872 (42%) underwent primary mastectomies and 1224 (58%) underwent primary BCS. Margins were positive in 128 (11%) and close in 442 (36%). Re-operation rate for patients after BCS was 19%. Conclusion A lower than predicted positive margin rate suggests that routine shave margins are not warranted at our institution.

BACKGROUND AND OBJECTIVES The purpose of this study was to assess the number of lymph nodes removed at SLNB, and what factors might bias a surgeon's decision to remove additional nodes. METHODS A prospectively maintained database was reviewed. All patients that had SLNB for primary treatment of breast cancer between January 2012 and March 2016 were identified. Clinicopathologic factors were used to compare the number of LNs and rates of node positivity. RESULTS One thousand six hundred and three patients were included. The average number of SLNs, non-SLNs, and total LNs was 2.53, 0.54, 3.08, respectively. Significantly more LNs were removed in age 40 (3.73, 3.04 P

To evaluate prospective surveillance and targeted physiotherapy (PSTP) compared to education (EDU) on the prevalence of arm morbidity and describe the associated program cost.Pilot randomized single-blinded controlled trial.Urban with assessments and treatment delivered in hospitals.Women scheduled for breast cancer surgery.Participants were randomly assigned (1:1) to PSTP ( n = 21) or EDU ( n = 20) and assessed presurgery and 12 months postsurgery. All participants received usual care, namely, preoperative education and provision of an education booklet with postsurgical exercises. The PSTP group was monitored for arm morbidity every three months and referred for physiotherapy if arm morbidity was identified. The EDU group received three education sessions on nutrition, stress and fatigue management.Arm morbidity was based on changes in the surgical arm(s) from presurgery in four domains: (1) shoulder range of motion, (2) strength, (3) volume, and (4) upper body function. Complex arm morbidity indicated ≥2 domains impaired. Second, the cost of the PSTP program was described.At 12 months, 18 (49%) participants (10 PSTP and 8 EDU) had arm morbidity, with EDU participants presenting more complex arm morbidity compared to PSTP participants. PSTP participants attended 4.4 of 5 assessments with 90% retention. The PSTP program cost was $150 covered by the Health Care Provider and the Patient Out-of-Pocket Travel cost was CAN$40.Our results suggest that PSTP is feasible among women with breast cancer for early identification of arm morbidity. A larger study is needed to determine the cost and effectiveness benefits.

Horseshoe kidney is a rare renal fusion anomaly, and because of limited mobilization of the kidney and its multiple arterial blood supplies, minimally invasive surgery for renal tumors can be challenging. We describe a case of a right-side oncocytoma in a horseshoe kidney managed robotically and review the literature of robotic-assisted laparoscopic surgical resection of kidney tumors in renal fusion anomalies. Robotic-assisted laparoscopic partial nephrectomy in a horseshoe kidney is feasible. Fusion-related limited mobility during the procedure, as well as an extremely variable blood supply, require meticulous planning. Multi-phase computed tomography and interactive 3D anatomical models are helpful tools to prepare for surgery.

Purpose of review Over the past few years the treatment options for renal cell cancer (RCC) have rapidly evolved. Even in the setting of metastatic disease, a consistent component of treatment in RCC patients has been cytoreductive nephrectomy based on the results of research carried out over a decade ago. Despite huge shifts in systemic treatment modalities, cytoreductive nephrectomy continued to be recommended despite a lack of evidence for its use in metastatic RCC in those patients receiving state-of-the-art therapies. Recent findings To address the lack of evidence, two recent trials [Cancer du Rein Metastatique Nephrectomie et Antiangioge[Combining Acute Accent]niques (CARMENA) and SURTIME] sought to assess the role and sequence of cytoreductive nephrectomy in metastatic RCC patients receiving vascular endothelial growth factor-targeted tyrosine kinase inhibitor treatment. The results of one of these trials, namely CARMENA, demonstrated no benefit of cytoreductive nephrectomy when used in combination with the vascular endothelial growth factor-targeted tyrosine kinase inhibitor Sunitinib. However, with further developments in medical treatment and questions regarding the specific methods of the trial - do these results change everything for the role of cytoreductive nephrectomy? Summary While the results from CARMENA and SURTIME are not conclusive, they suggest that those patients with advanced disease requiring systemic therapy should indeed receive this first prior to any cytoreductive nephrectomy.

Small-molecule modulation of protein-protein interactions (PPIs) is a very promising but also challenging area in drug discovery. The tumor suppressor protein p53 is one of the most frequently altered proteins in human cancers, making it an attractive target in oncology. 14-3-3 proteins have been shown to bind to and positively regulate p53 activity by protecting it from MDM2-dependent degradation or activating its DNA binding affinity. PPIs can be modulated by inhibiting or stabilizing specific interactions by small molecules. Whereas inhibition has been widely explored by the pharmaceutical industry and academia, the opposite strategy of stabilizing PPIs still remains relatively underexploited. This is rather interesting considering the number of natural compounds like rapamycin, forskolin and fusicoccin that exert their activity by stabilizing specific PPIs. In this review, we give an overview of 14-3-3 interactions with p53, explain isoform specific stabilization of the tumor suppressor protein, explore the approach of stabilizing the 14-3-3σ-p53 complex and summarize some promising small molecules inhibiting the p53-MDM2 protein-protein interaction.

Background Cancer du Rein Metastatique Nephrectomie et Antiangiogeniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting. Objective The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN). Design, setting, and participants Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN. Outcome measurements and statistical analysis Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group. Results and limitations Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0–51.0) compared with 22.8 mo (95% CI 17.9–30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52–0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort. Conclusions In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients. Patient summary In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.

Background Routine excision of flat epithelial atypia (FEA) of the breast found on core needle biopsy (CNB) is being questioned and a policy of selective excision of FEA was adopted in our area. The purpose of this study was to evaluate the upstage rate to malignancy across multiple diagnostic centers in our area following the policy of selective excision and to identify factors predictive of malignancy. Methods Patients having excision of CNB FEA at our regional Hospital between 2013 and 2017 were identified. The primary endpoint was upstage to malignancy after excision. We also assessed for clinical, radiological, and pathological features associated with malignancy. Results We identified 187 patients. Eighty-nine had pure FEA, 71 had concurrent ADH, and 18 had other pathological lesions. Following surgical excision, 9 patients were upstaged to malignancy (4. 8%) with 8 having concurrent ADH (2 invasive ductal carcinoma, 6 DCIS) and 1 with concurrent Complex Sclerosing Lesion (DCIS). None of the pure FEA cases upstaged. The presence of ADH or CSL in the CNB were the only factors found to be predictive of upstaging (p = 0.001, p = 0.0001 respectively). Conclusions The upstage rate to malignancy after excision of pure FEA at out center is 0%. Therefore, we recommend that pure FEA with radiology and pathology concordance does not require surgical excision and can instead be followed with serial imaging. However, patients with FEA in association with other high-risk lesions should be managed as per indicated for the other high-risk lesion and FEA with ADH should be excised.

Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. PATIENT SUMMARY: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naive). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.

To understand uncertainties and knowledge gaps regarding lymphatic drainage in renal tumors, we performed 2 prospective studies to demonstrate regional lymph node (LN) drainage with sentinel lymph node (SN) imaging and biopsy. Here, we report the technique and perioperative safety of retroperitoneal SN dissection with different surgical approaches.Seventy three patients from the 2 trials were included in the analysis. Patients had cT1-2N0M0 renal tumors (/=10 cm) and underwent nephrectomy (46/63%) or partial nephrectomy (27/37%) with SN dissection after intraoperative detection with a γ-probe, and locoregional LND. Twenty-nine of 73 patients had open surgery, 27 of 73 laparoscopic, and 17 of 73 robot-assisted laparoscopic (partial) nephrectomy. Surgery time, intraoperative adverse events (AE) according to CTCAE 5.0, and postoperative AE according to Clavien-Dindo (CD) were retrospectively assessed.There were no grade ≥3 intraoperative CTCAE 5.0 AEs. Postoperative AE rate was 16.4% of which 7 (9.6%) were CD grade 1-2 and 5 (6.8%) were 3a grade complications. There were no statistically significant differences between presence of AE, CD grade, and surgical modality (P = .27 and P = .13, respectively). Blood loss was a median of 550 ml (IQR 200-900 ml) and 225 (IQR 42-751 ml) for partial nephrectomy (PN) and radical nephrectomy, respectively. Length of the procedure was 170 minutes (IQR 149-184 minutes), 155 minutes (IQR 130-177 minutes) 180 minutes (IQR 162-202 minutes) in open, laparoscopic, and robot-assisted procedures, respectively.The addition of retroperitoneal SN dissection combined with locoregional LND during (partial) nephrectomy is surgically safe. Complication rate is low and does not differ between surgical approaches.

The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.To provide an updated RCC guideline based on standardised methodology including systematic reviews, which is robust, transparent, reproducible, and reliable.For the 2019 update, evidence synthesis was undertaken based on a comprehensive and structured literature assessment for new and relevant data. Where necessary, formal systematic reviews adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were undertaken. Relevant databases (Medline, Cochrane Libraries, trial registries, conference proceedings) were searched until June 2018, including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm, systematic reviews, and meta-analyses. Where relevant, risk of bias (RoB) assessment, and qualitative and quantitative syntheses of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Clinical practice recommendations were developed and issued based on the modified GRADE framework.All chapters of the RCC guidelines were updated based on a structured literature assessment, for prioritised topics based on the availability of robust data. For RCTs, RoB was low across studies. For most non-RCTs, clinical and methodological heterogeneity prevented pooling of data. The majority of included studies were retrospective with matched or unmatched cohorts, based on single- or multi-institutional data or national registries. The exception was for the treatment of metastatic RCC, for which there were several large RCTs, resulting in recommendations based on higher levels of evidence.The 2019 RCC guidelines have been updated by the multidisciplinary panel using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2019.The European Association of Urology Renal Cell Carcinoma Guideline Panel has thoroughly evaluated the available research data on kidney cancer to establish international standards for the care of kidney cancer patients.

Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options.To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice.A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of follow-up. Risk of bias assessment was performed using standard Cochrane methods.Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias.In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge.Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure.

Despite benefits in quality of life, patient satisfaction, overall healthcare costs, and number of surgeries, historically fewer than 30% of patients undergo immediate breast reconstruction following mastectomy for breast cancer. A paucity of qualified oncologic and plastic surgeons coupled with inefficient use of operating room (OR) resources presents challenges in offering immediate breast reconstruction in a timely manner. To address these challenges, an immediate reconstruction swing room (IRSW) program was developed. IRSW scheduling leverages two concurrently running ORs, with the surgical oncologist and plastic surgeon moving between rooms to complete 2–4 combined mastectomy cases with immediate reconstruction, in addition to 1–2 independent cases, each operative day. The final year of traditional booking was compared with IRSW scheduling to assess wait times and reconstruction rates. Comparing the 2 years, fewer surgical breast cases were performed with IRSW scheduling (1250 vs. 1178), however the overall number of oncology cases increased from 735 (59%) to 857 (73%). The number of immediate reconstructions performed increased from 75 to 139 (p

BACKGROUND A stabilized hyaluronic acid (HA)-based lidocaine-containing gel of nonanimal origin has been developed for lip enhancement. OBJECTIVE To evaluate the efficacy, safety, and injection procedure of the HA gel in subjects seeking lip enhancement. METHODS Thirty subjects were treated in the upper and lower lips. Retreatment was offered at 3 months. Efficacy was assessed over 9 months using the Global Aesthetic Improvement Scale (GAIS), the Medicis Lip Fullness Scale, and a subject questionnaire. Safety was assessed by a 14-day subject diary and recording of adverse events (AEs) during the whole study. RESULTS Over 9 months after treatment, 86% to 97% of subjects and independent evaluators assessed both lips as improved. At all study visits, 72% to 93% of the subjects were satisfied with their lips and ≥96% reported that their lips had a natural look. Most AEs were mild-to-moderate local injection site reactions. CONCLUSION Lip enhancement with this HA-based gel generated high subject satisfaction and natural-looking lips. The effect lasted for up to 9 months according to the GAIS ratings by subjects and independent evaluators. The product was well tolerated; most AEs were mild-to-moderate local injection site reactions.

The benefit of adding sentinel node biopsy (SNB) to extended pelvic lymph node dissection (ePLND) remains controversial. The aim of our study was to evaluate biochemical recurrence (BCR) after robot-assisted radical prostatectomy and ePLND in prostate cancer patients, stratified by the application of SNB. The results were compared with the predictions of the updated Memorial Sloan Kettering Cancer Center nomogram. Methods: Between January 2006 and November 2016, 920 patients underwent robot-assisted radical prostatectomy and ePLND with or without SNB (184 and 736 patients, respectively). BCR was defined as 2 consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox regression analyses were used to identify predictors of BCR. Results: Median follow-up was 28 mo (interquartile range, 13-56.7 mo). The 5-y BCR-free survival rate was 80.5% and 69.9% in the ePLND+SNB and ePLND groups, respectively. At multivariate analysis, prostate-specific antigen level, primary Gleason grade greater than 3, seminal vesicle invasion, and higher number of removed and positive nodes were independent predictors of BCR in the ePLND group. In the ePLND+SNB group, only the number of positive nodes was an independent predictor of BCR. The overall accuracy of the Memorial Sloan Kettering Cancer Center nomogram was higher in the ePLND+SNB than in the ePLND group. However, the nomogram was underestimating the probability of BCR-free status in the ePLND+SNB group, whereas the ePLND group was performing as predicted. Conclusion: Adding SNB to ePLND improves BCR-free survival, although the precise explanation of this observation remains speculative. Our results should be interpreted cautiously, given the nonrandomized nature and the selection bias of the study.

Background: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain. Material and methods: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0–24 years diagnosed in Denmark (1990–2010) and Sweden (1992–2009) in pediatric (n = 315, Denmark 2-test and Mantel–Haenszel trend test. The Kaplan–Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression. Results: Children (0–9 years) less often presented with advanced disease than adolescents (10–17 years) and young adults (18–24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p

PURPOSE: Lymphatic drainage from renal tumors is unpredictable and in vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern from renal tumors in vivo with SPECT/CT imaging after intra-tumoral radiotracer injection.MATERIALS AND METHODS: We conducted a phase II prospective single-arm study to investigate the distribution of SNs from renal tumors on SPECT/CT imaging. Patients with cT1-3 (RESULTS: Sixty-eight patients were included. Forty patients had preoperative SPECT/CT imaging of SNs and were used for primary endpoint analysis. Lymphatic drainage outside the LRT was observed in 14 (35%) patients. Eight patients (20%) had supradiaphragmatic SN.CONCLUSIONS: SNs from renal tumors were mainly located in their respective LRT, but simultaneous SNs located outside the suggested LND templates, including supradiaphragmatic SNs were observed in more than one third of the patients.

Although the broad use of ultrasound and computed tomography (CT) has led to an early diagnosis of the disease, renal cell carcinoma (RCC) remains one of the most lethal urological cancers. The present review is based on the latest data published on RCC management.A literature search was carried out searching recent publications from PubMed, MEDLINE, Embase up to December 2016 as well as European Association of Urology (EAU) and European Society of Medical Oncology (ESMO) guidelines.A narrative synthesis based on recent publications was undertaken. Current evidence regarding treatment strategies and guidelines is based on prospective randomized controlled trials and retrospective studies although the level of evidence for surgical management is generally lower than for systemic therapy.This narrative review depicts a summary of the evidence base for treatment of RCC. Management of RCC is a rapidly evolving and changing field. As a consequence guidelines need regular updating and patients may benefit from centralization of care and multidisciplinary approach.

Mastitis, an inflammation of the mammary gland and udder tissue, is the major endemic disease of dairy cattle. In addition to causing health problems to the animals, mastitis leads to the reduction of milk production and quality, representing a significant economic burden for farmers. To enable timely treatment of infected animals with pathogen-specific antibiotics, the development of automated analytical methods for rapid on-site identification and quantification of mastitis-causing pathogens in milk is particularly important. An immunosensing system for multiplex detection of the two most common mastitis-causing pathogens Staphylococcus aureus and Escherichia coli is proposed in the present study. This immunosensor combines Bead Injection Analysis (BIA), attachment of pathogens onto renewable micro-column, biorecognition of bound pathogens by specific antibodies, conjugated with different fluorescence markers and the measurement of fluorescence signals. The analysis takes 20min and exhibits detection limits of < 50 CFU mL-1 for E. coli and 100 CFU mL-1 for S. aureus in milk. The applicability of the immunosensor was demonstrated by analyzing milk samples from cows, who were suffering from acute clinical mastitis.

Axillary reverse lymphatic mapping (ARM) is a surgical technique that was first described in 2007 as a method for preserving the lymphatic drainage of the arm during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for breast cancer. We found that the ARM technique had several limitations that include a poor success rate for identification of arm lymph nodes (ARM nodes) and lymphatics. The occurrence of common lymphatic drainage pathways of the arm and the breast in a subset of patients also raises concerns regarding its oncological soundness. Furthermore, the effectiveness of the ARM procedure in reducing lymphedema risk in breast cancer patients that undergo a variety of treatments, has yet to be clearly defined.

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and clinical studies, combination therapies with VEGF- and checkpoint inhibitors have synergistic effect achieving improved response rates. However, toxicity in some combinations is high. In this article, we present a review of the ongoing trials with these drug combinations for RCC.

The aim of this study was to evaluate the axillary reverse lymphatic mapping (ARM) procedure for reducing the risk of arm lymphedema after breast cancer surgery.The ARM procedure was carried out with a subareolar injection of technetium-99 sulfur colloid the morning of surgery, and a patent blue dye injection into the upper inner arm after anesthesia.Fifty-two women made up our study population. Thirty-seven patients underwent sentinel lymph node biopsy (SLNB) and 15 patients underwent an axillary lymph node dissection (ALND) for known nodal metastasis. The sentinel lymph node was identified in 36 of the 37 cases who underwent SLNB alone and in 12 of 15 patients who underwent on ALND. In 13 patients, both blue and radioactive lymph nodes or lymphatics were clearly identified (25%) and 5 patients had a clear crossover with nodes being both blue and hot. Only a single patient with crossover lymphatics had metastases present in their sentinel node.The ARM technique did not prevent identification of the SLN and we identified much greater crossover than reported. We had a single patient, who underwent a sentinel node biopsy, with mild arm lymphedema (1.9%) after 2 years of follow up.