Soft Tissue Reconstruction After Revascularization.

Diabetic foot ulcer represents the primary cause of hospital admissions, amputations, and mortality in diabetic patients. The development of diabetic foot ulcers is influenced by peripheral neuropathy, infection, and ischemia, with diabetes contributing to peripheral artery disease. Free tissue transfer combined with revascularisation of the lower extremity provides the potential opportunity for limb salvage in individuals with lower extremity defects due to critical limb ischemia and diabetic foot.

A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy.

Introduction: Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy. Methods: A multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 µM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients' clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST). Results: The cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4-0.97) and a sensitivity of 96% (24/25, 95% CI 0.80-0.99). Conclusion: EVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Long-Term Survival and Functional Recovery of Cryopreserved Vascularized Groin Flap and Below-the-Knee Rat Limb Transplants.

Effective cryopreservation of large tissues, limbs, and organs has the potential to revolutionize medical post-trauma reconstruction options and organ preservation and transplantation procedures. To date, vitrification and directional freezing are the only viable methods for long-term organ or tissue preservation, but are of limited clinical relevance. This work aimed to develop a vitrification-based approach that will enable the long-term survival and functional recovery of large tissues and limbs following transplantation. The presented novel two-stage cooling process involves rapid specimen cooling to subzero temperatures, followed by gradual cooling to the vitrification solution (VS) and tissue glass transition temperature. Flap cooling and storage were only feasible at temperatures equal to or slightly lower than the VS Tg (i.e., -135°C). Vascularized rat groin flaps and below-the-knee (BTK) hind limb transplants cryopreserved using this approach exhibited long-term survival (>30 days) following transplantation to rats. BTK-limb recovery included hair regrowth, normal peripheral blood flow, and normal skin, fat, and muscle histology. Above all, BTK limbs were reinnervated, enabling rats to sense pain in the cryopreserved limb. These findings provide a strong foundation for the development of a long-term large-tissue, limb and organ preservation protocol for clinical use.

Prostate-specific antigen level association with COVID-19 infection and vaccination.

INTRODUCTION: The associations among SARS-CoV-2 infection, vaccination and total serum prostate serum antigen (PSA) levels in men undergoing screening for prostate cancer are unknown. METHODS: A retrospective analysis of data from a large health maintenance organization. Records of individuals aged 50 to 75 years with two serum PSA tests taken between March 2018 and November 2021 were included. Individuals with prostate cancer were excluded. Changes in PSA levels were compared between individuals who had at least 1 SARS-CoV-2 vaccination and/or infection between the two PSA tests and individuals who did not have an infection and were not vaccinated between the two PSA tests. Subgroup analyses were performed to assess the impact of the elapsed time between the event and the second PSA test on the results. RESULTS: The study and control groups included 6,733 (29%) and 16 286 (71%) individuals, respectively. Although the median time between PSA tests was shorter in the study vs. the control group (440 vs. 469 days, P<.001), PSA elevation between the tests was higher in the study group (0.04 vs. 0.02, P<.001). The relative risk for PSA elevation ≥1 ng/dL was 1.22 (95% CI 1.1, 1.35). Among individuals who were vaccinated, PSA increased by 0.03 ng/dL (IQR -0.12, 0.28) and 0.09 ng/dL (IQR -0.05, 0.34) after 1 and 3 doses, respectively (P<.001). Multivariate linear regression showed that SARS-CoV-2 events (ß 0.043; 95% CI 0.026-0.06) were associated with a greater risk for PSA elevation, after adjusting for age, baseline PSA and days between PSA tests. CONCLUSION: SARS-CoV-2 infection and vaccinations are associated with a slight increase in PSA, with the third anti-COVID vaccine dose having a more prominent impact, but its clinical significance is unknown yet. Any significant increase in PSA must be investigated and cannot be dismissed as secondary to SARS-CoV-2 infection or vaccination.

Single-Dose Post-Office Fulguration Mitomycin C Instillation Appears to Improve Recurrence-Free Survival in Patients With Low-Grade Noninvasive Bladder Cancer.

INTRODUCTION: Perioperative instillation of mitomycin-C (MMC) has shown effectiveness in reducing the recurrence of low-grade non-muscle invasive bladder cancer (NMIBC). Data is lacking about the impact of single-dose MMC following office fulguration of low-grade urothelial carcinoma. We compared the outcomes of small-volume low-grade recurrent NMIBC in patients treated with office-fulguration - with and without an immediate single-dose instillation of MMC. PATIENTS AND METHODS: A retrospective analysis of medical records of patients with recurrent small-volume (≤1 cm) low-grade papillary urothelial cancer who underwent fulguration in a single institution between January 2017 and April 2021 either with or without instillation of post-fulguration MMC (40mg/50 mL). The primary outcome was recurrence-free survival (RFS). RESULTS: Of 108 patients (27% women) who underwent fulguration, 41% received intravesical MMC. The treatment and control groups had similar sex ratio, mean age, mass size, tumor multifocality and or tumor grade. Median RFS was 20 months (95% CI 4-36) in the MMC group and 9 months (95% CI 5-13) in the control group (P = .038). Multivariate Cox regression analysis showed that MMC instillation was associated with longer RFS (OR = 0.552, 95% CI 0.320-0.955, P = .034) and multifocality was associated with shorter RFS (OR = 1.866, 1.078-3.229, P = .026). A higher rate of grade 1-2 adverse events was observed in the MMC group (18.2%) vs. the control (6.8%, P = .048). No complications grade 3 or higher were observed. CONCLUSION: A single dose of MMC instilled after office fulguration is associated with longer RFS compared to patients who did not receive MMC after the procedure, with no associated high-grade complications.

Use of Recanalized Vessels for Diabetic Foot Reconstruction: Pushing the Boundaries of Reconstruction in a Vasculopathic Lower Extremity.

BACKGROUND: Free flap after lower extremity revascularization may enable limb salvage in defects after critical limb ischemia. This study examined the outcomes of reconstruction of ischemic diabetic foot according to the severity of the vessel occlusion and assessed whether recanalized vessels may serve as a reliable recipient vessel. METHODS: A total of 62 patients who underwent diabetic foot reconstruction with free flaps after successful percutaneous transluminal angioplasty (PTA) from February of 2010 to February of 2016 were identified and divided into three groups: group 1, nonoccluded vessels as recipient ( n = 11); group 2, recanalized artery after PTA for partially occluded artery ( n = 30); and group 3, recanalized artery after PTA for completely occluded artery ( n = 21). RESULTS: Flap survival was statistically higher in group 2 (90%) compared with group 3 (67%) ( P < 0.05). Subsequent major amputation was significantly lower in groups 1 and 2 [0/7 and 1/30 (3.3%)] compared with group 3 [5/21 (23.8%)] ( P < 0.05). The patient survival and limb salvage rate was 90.9% at 1 and 3 years in group 1, 89.8% at 1 year and 86.3% at 3 and 5 years in group 2, and 76.2% at 1, 3, and 5 years in group 3. This difference was not statistically significant ( P = 0.485). CONCLUSIONS: The use of recanalized vessels after PTA can be safe for partially occluded arteries but requires caution for completely occluded arteries. Using completely occluded vessels after PTA can be attempted when other options are not available and achieves a 76% chance of limb salvage. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Neoadjuvant 177Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

BACKGROUND: High-risk localized prostate cancer (HRLPC) has a substantial risk of disease progression despite local treatment. Neoadjuvant systemic therapy before definitive local therapy may improve oncological outcomes by targeting the primary tumor and micrometastatic disease. OBJECTIVE: To evaluate whether a lutetium-177 prostate-specific membrane antigen radioligand (LuPSMA) can be safely administered to patients with HRLPC before robot-assisted radical prostatectomy (RARP) and to describe immediate oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-arm clinical trial. Patients with HRLPC and elevated radioligand uptake on PSMA positron emission tomography/computed tomography were enrolled. Two or three LuPSMA radioligand doses (7.4 GBq) were given at 2-wk intervals. RARP with lymph node dissection was performed 4 wk after the last LuPSMA dose. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rate of surgical complications, operative parameters, changes in functional and quality-of-life measures, and immediate oncological outcomes (histological findings and biochemical response) were measured. Data were analyzed descriptively. RESULTS AND LIMITATIONS: Fourteen patients participated (median age 67 yr). Prostate-specific antigen decreased by 17% (interquartile range [IQR] 9-50%) after two LuPSMA doses and 34% (IQR 11-60%) after three doses. Thirteen patients underwent RARP with no identifiable anatomical changes or intraoperative complications. Four patients (30%) had postoperative complications (pneumonia, pulmonary embolism, urinary leak with urinary tract infection). At 3 mo postoperatively, 12 patients (92%) required one pad or less. Final whole-mount pathology showed positive surgical margins (PSMs) in seven patients (53%) and downgrading to International Society of Urological Pathology grade group 3 in three patients (23%). Treatment-related effects included a clear vacuolated cytoplasm and pyknotic nuclei. CONCLUSIONS: LuPSMA followed by RARP appears to be surgically safe. While oncological outcomes are pending, continence recovery seems to be unaffected by LuPSMA treatment. PATIENT SUMMARY: We evaluated outcomes for patients with aggressive localized prostate cancer who received treatment with a radioactive agent before surgical removal of their prostate. This approach appears to be safe and feasible, but its therapeutic efficacy is still unknown.

Facial Nerve Repair following Acute Nerve Injury.

Background Acute facial nerve iatrogenic or traumatic injury warrants rapid management with the goal of reestablishing nerve continuity within 72 hours. However, reconstructive efforts should be performed up to 12 months from the time of injury since facial musculature may still be viable and thus facial tone and function may be salvaged. Methods Data of all patients who underwent facial nerve repair following iatrogenic or traumatic injury were retrospectively collected and assessed. Paralysis etiology, demographics, operative data, postoperative course, and outcome were examined. Results Twenty patients underwent facial nerve repair during the years 2004 to 2019. Data were available for 16 of them. Iatrogenic injury was the common category ( n = 13, 81%) with parotidectomy due to primary parotid gland malignancy being the common surgery ( n = 7, 44%). Nerve repair was most commonly performed during the first 72 hours of injury ( n = 12, 75%) and most of the patients underwent nerve graft repair ( n = 15, 94%). Outcome was available for 12 patients, all of which remained with some degree of facial paresis. Six patients suffered from complete facial paralysis (50%) and three underwent secondary facial reanimation (25%). There were no major operative or postoperative complications. Conclusion Iatrogenic and traumatic facial nerve injuries are common etiologies of acquired facial paralysis. In such cases, immediate repair should be performed. For patients presenting with facial paralysis following previous surgery or trauma, nerve repair should be considered up to at least 6 months of injury. Longstanding paralysis is best treated with standard facial reanimation procedures.

[BREAST CANCER-RELATED LYMPHEDEMA: INCIDENCE AND RISK FACTORS, PREVENTIVE MEASURES AND TREATMENTS].

INTRODUCTION: Lymphedema is a pathological condition in which intercellular protein-rich fluid accumulates and leads over time to inflammation, adipose tissue hypertrophy and fibrosis. Secondary lymphedema is caused by injury or blockage of the lymphatic system and the main cause in the Western world is the treatment of a variety of cancers, the main one being breast cancer. Chronic arm edema after breast cancer surgery is a common problem with an estimated incidence of 1 in 5 patients after breast cancer treatment. In this article we review the main risk factors, approaches to reducing the risk of developing lymphedema after treatment for breast cancer and existing treatment protocols for lymphedema including the surgical innovations in this field and our experience in these innovative surgical approaches. To date, 26 physiological surgeries have been performed at the Tel Aviv Medical Center using the microsurgical approach for treating lymphedema. These surgeries had no significant complications and the improvement was observed to be greater in the group of patients with secondary lymphedema. Lymphovenous anastomosis and vascularized lymph node transfer offer promising solutions for the treatment of breast cancer related lymphedema. The introduction of additional techniques and the refinement of these procedures will probably continue to improve the results in the future.

COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver.

Liver-resident macrophages Kupffer cells (KCs) and infiltrating Ly6Chi monocytes both contribute to liver tissue regeneration in various pathologies but also to disease progression upon disruption of orderly consecutive regeneration cascades. Little is known about molecular pathways that regulate their differentiation, maintenance, or inflammatory behavior during injury. Here, we show that copper metabolism MURR1 domain (COMMD)10-deficient KCs adopt liver-specific identity. Strikingly, COMMD10 deficiency in KCs and in other tissue-resident macrophages impedes their homeostatic survival, leading to their continuous replacement by Ly6Chi monocytes. While COMMD10 deficiency in KCs mildly worsens acetaminophen-induced liver injury (AILI), its deficiency in Ly6Chi monocytes results in exacerbated and sustained hepatic damage. Monocytes display unleashed inflammasome activation and a reduced type I interferon response and acquire "neutrophil-like" and lipid-associated macrophage differentiation fates. Collectively, COMMD10 appears indispensable for KC and other tissue-resident macrophage survival and is an important regulator of Ly6Chi monocyte fate decisions and reparative behavior in the diseased liver.

Trends in urological emergencies in the Era of COVID-19

ABSTRACT Purpose: To evaluate trends in emergency room (ER) urological conditions during COVID-19 pandemic lockdown. Materials and Methods: Retrospective analyses of renal colic, hematuria, and urinary retention in ER's admissions of a tertiary hospital during the lockdown period (March 19 to May 4, 2020) in Israel. Patient's demographics and clinical characteristics were compared to those in corresponding periods during 2017-2019, with estimated changes in ER arrival and waiting times, utilization of imaging tests, numbers of hospitalizations, and urgent procedure rates. Results: The number of ER visits for renal colic, hematuria, and urinary retention decreased by 37%, from an average of 451 (2017-2019) to 261 patients (2020). Clinical severity was similar between groups, with no major differences in patient's age, vital signs, or laboratory results. The proportion of ER visits during night hours increased significantly during lockdown (44.8% vs. 34.2%, p=0.002). There was a decrease in renal colic admission rate from 19.8% to 8.4% (p=0.001) without differences in urgent procedures rates, while the 30-day revisit rate decreased from 15.8% to 10.3% during lockdown (p=0.02). Conclusions: General lockdown was accompanied by a significant decrease in common urological presentations to the ER. This change occurred across the clinical severity spectrum of renal colic, hematuria, and urinary retention. In the short term, it appears that patients who sought treatment did not suffer from complications that could be attributed to late arrival or delay in treatment. The long-term implications of abstinence from seeking emergent care are not known and require further investigation.

Trends in urological emergencies in the Era of COVID-19.

PURPOSE: To evaluate trends in emergency room (ER) urological conditions during COVID-19 pandemic lockdown. MATERIALS AND METHODS: Retrospective analyses of renal colic, hematuria, and urinary retention in ER's admissions of a tertiary hospital during the lockdown period (March 19 to May 4, 2020) in Israel. Patient's demographics and clinical characteristics were compared to those in corresponding periods during 2017-2019, with estimated changes in ER arrival and waiting times, utilization of imaging tests, numbers of hospitalizations, and urgent procedure rates. RESULTS: The number of ER visits for renal colic, hematuria, and urinary retention decreased by 37%, from an average of 451 (2017-2019) to 261 patients (2020). Clinical severity was similar between groups, with no major differences in patient's age, vital signs, or laboratory results. The proportion of ER visits during night hours increased significantly during lockdown (44.8% vs. 34.2%, p=0.002). There was a decrease in renal colic admission rate from 19.8% to 8.4% (p=0.001) without differences in urgent procedures rates, while the 30-day revisit rate decreased from 15.8% to 10.3% during lockdown (p=0.02). CONCLUSIONS: General lockdown was accompanied by a significant decrease in common urological presentations to the ER. This change occurred across the clinical severity spectrum of renal colic, hematuria, and urinary retention. In the short term, it appears that patients who sought treatment did not suffer from complications that could be attributed to late arrival or delay in treatment. The long-term implications of abstinence from seeking emergent care are not known and require further investigation.

Cardiovascular Proteomics: A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer.

PURPOSE: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. MATERIALS AND METHODS: We performed a proteomics analysis of serum samples collected during a phase II randomized study among 80 men with advanced prostate cancer and preexisting CV disease who were randomized to receive a GnRH agonist (39) or GnRH antagonist (41) for 1 year. Serum samples were collected at baseline and at 3, 6 and 12 months following treatment, and analyzed levels of 188 proteins using the CV panel II and III of the Olink Multiplex platform (Olink Proteomics AB, Uppsala, Sweden). We fitted a linear mixed effects model to assess evidence of a treatment effect across CV related protein values. This included terms for treatment arm, protein levels and time-by-treatment interaction. Results were corrected for multiple testing using the Benjamini-Hochberg method. RESULTS: The CV proteomics analysis included 283 samples from 78 subjects. We identified 5 proteins with distinct patterns over time depending on study arm: human chitotriosidase, macrophage receptor with collagenous structure, cathepsin D, superoxide dismutase 2 and hydroxyacid oxidase 1. All 5 are associated with plaque stability and demonstrated an increased level among subjects in the GnRH antagonist arm compared to agonist. CONCLUSIONS: We compared longitudinal changes in CV proteins among men using androgen deprivation therapy. Our results support a direct protective effect of GnRH antagonist on plaque stability rather than a hazardous consequence of GnRH agonists on plaque rupture. This is a hypothesis generating study, and requires further confirmation.

Cardiac biomarkers in patients with prostate cancer and cardiovascular disease receiving gonadotrophin releasing hormone agonist vs antagonist.

BACKGROUND: Gonadotrophin releasing hormone (GnRH) agonists and antagonists reduce testosterone levels for the treatment of advanced and metastatic prostate cancer. Androgen deprivation therapy (ADT) is associated with increased risk of cardiovascular (CV) events and CV disease (CVD), especially in patients with preexisting CVD treated with GnRH agonists. Here, we investigated the potential relationship between serum levels of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP), D-dimer, C-reactive protein (CRP), and high-sensitivity troponin (hsTn) and the risk of new CV events in prostate cancer patients with a history of CVD receiving a GnRH agonist or antagonist. METHODS: Post-hoc analyses were performed of a phase II randomized study that prospectively assessed CV events in patients with prostate cancer and preexisting CVD, receiving GnRH agonist or antagonist. Cox proportional hazards models were used to determine whether the selected biomarkers had any predictive effect on CV events at baseline and across a 12-month treatment period. RESULTS: Baseline and disease characteristics of the 80 patients who took part in the study were well balanced between treatment arms. Ischemic heart disease (66%) and myocardial infarction (37%) were the most common prior CVD and the majority (92%) of patients received CV medication. We found that high levels of NTproBNP (p = 0.008), and hsTn (p = 0.004) at baseline were associated with the development of new CV events in the GnRH agonist group but not in the antagonist. In addition, a nonsignificant trend was observed between higher levels of NTproBNP over time and the development of new CV events in the GnRH agonist group. CONCLUSIONS: The use of cardiac biomarkers may be worthy of further study as tools in the prediction of CV risk in prostate cancer patients receiving ADT. Analysis was limited by the small sample size; larger studies are required to validate biomarker use to predict CV events among patients receiving ADT.

Propeller Flaps in the Posterior Trunk.

The reconstruction of complex posterior trunk defects remains challenging. But now with an increased knowledge of angiosomes and the practice of perforator flaps, the posterior trunk offers a new plethora of options for reconstruction. Propeller flaps based on such perforator(s) offer an elegant solution for managing defects while achieving primary donor-site closure without significant morbidity. We will discuss the relevant anatomy and design principles for propeller flaps based on a review of the literature and our experience. Steps beginning with preoperative planning, perforator selection, and intraoperative surgical technique will be discussed, together with pearls on both avoiding and managing complications.

[FACIAL NERVE PARALYSIS - THERAPEUTIC APPROACH, FACIAL REANIMATION AND ADJUNCTIVE TREATMENT].

INTRODUCTION: Paralysis of the facial mimetic muscles causes loss of voluntary and non-voluntary muscle function, as well as facial tone. This is a devastating condition with profound functional, aesthetic and psychological consequences. Etiologies include congenital paralysis and acquired paralysis following viral infection, trauma, head and neck tumors, iatrogenic damage and more. Clinical presentation includes ocular symptoms (dry eye, epiphora, corneal irritation), nasal symptoms (nasal obstruction) and oral symptoms (drooling and speech disturbances). Reconstruction of facial nerve function is based on renewing the neural input to the paralyzed face in parallel with transferring a functioning muscle. The gold standard in long term facial paralysis reanimation includes a two-stage procedure that involves cross-face nerve grafting and later on a free gracilis muscle transfer. This method allows reconstruction of a symmetric, spontaneous and voluntary smile. In cases when cross-face nerve grafting is impossible, a free-gracilis muscle transfer is performed with neural coaptation to another cranial nerve, most commonly the motor nerve to the masseter muscle (of the trigeminal nerve). Non-microsurgical methods for facial reanimation exist, however, nowadays they are rarely performed. In addition to the surgical reconstruction, other surgical and non-surgical procedures are performed for functional and aesthetic symmetrization purposes. These include fat injection to the face, botulinum toxin injection, oculoplastic procedures and more. In this article we describe our patient population with facial nerve paralysis, common facial reanimation procedures, considerations in choosing the appropriate reconstruction procedure and the general approach for treatment of facial paralysis in our multidisciplinary facial paralysis clinic.

Short-Term Outcomes of Active Surveillance for Low Risk Prostate Cancer among Men with Germline DNA Repair Gene Mutations.

PURPOSE: Men with germline mutations in DNA repair genes have a higher risk of prostate cancer. Active surveillance is the preferred treatment modality for low risk prostate cancer. However, many fear offering this alternative to men with germline mutations. We describe the short-term oncologic outcomes of active surveillance in a population of men with a high genetic predisposition for prostate cancer. MATERIALS AND METHODS: A prospective cohort of men with germline DNA repair gene mutations were diagnosed with Grade Group 1 prostate cancer. All men were offered active surveillance. Followup consisted of prostate specific antigen every 3 months, multiparametric magnetic resonance imaging and a magnetic resonance imaging-ultrasound fusion confirmatory biopsy within 1 year of diagnosis. The primary end points included treatment and progression-free survival. RESULTS: Eighteen carriers of DNA repair gene mutations were diagnosed with low risk prostate cancer (BRCA1 [8], BRCA2 [6], CHEK2 [2], Lynch syndrome [2]). Of these patients 15 (83%) initiated active surveillance and 3 (17%) declined. All but 1 were fully compliant with the active surveillance protocol (93%). Overall 20% (3) had upgrading at confirmatory biopsy and were treated. At a median followup of 28 months (IQR 8.5-42) 80% of patients (12) on active surveillance are free from upgrading or radical treatment. CONCLUSIONS: Active surveillance may be feasible among carriers diagnosed with low risk prostate cancer. If embarking on active surveillance, carriers should be very carefully monitored at a specialized clinic, optimizing patient compliance and minimizing risk. Until larger scale studies with long-term followup become available, this option should be cautiously discussed with the patient.