Management of high-grade papillary Ta or T1 bladder cancer after restaging transurethral resection: A retrospective study comparing Bacillus Calmette-Guerin therapy upfront versus a third resection.

PURPOSE: Performing restaging transurethral bladder resection (reTURB) for high-risk non-muscle invasive bladder cancer (NMIBC) reduces the risk of recurrence and tumour understaging. Management of residual high-grade papillary Ta or T1 after reTURB has changed this last 10years in international recommendations. This study aimed to compare the recurrence free survival according to the different management procedures performed. MATERIALS AND METHODS: Patients who underwent reTURB for initial high-risk NMIBC between 2011 and 2020 were included. Patients with residual high-grade papillary Ta or T1 tumour after reTURB were divided into two groups: BCG instillations upfront versus BCG following a third-look resection (3TURB). Patient and tumour characteristics, BCG instillations, recurrence-free survival were retrospectively analysed. RESULTS: A total of 162 high-risk patients were included. Sixty-one (37.7%) had residual high-grade papillary Ta or T1 at reTURB: 35 (21.6%) had BCG instillations upfront, 18 (11.2%) had a 3TURB and 8 (5%) had other management. The mean follow-up was 34.2weeks±20.2. Recurrence-free survival was significantly better in patients who underwent BCG instillations upfront (P<0.0043). Recurrence after BCG therapy following reTURB was significantly lower in patients with no residual NMIBC at 6 (92.5% vs. 72.4%, P<0.004) and 12months (85% vs. 67.3%, P<0.03). CONCLUSIONS: The efficacy of intravesical BCG is compromised in case of residual tumour following TURB. The role of a 3TURB following a positive reTURB is not yet determined. This study has confirmed that residual tumor following reTURB is a negative predictive factor but could not demonstrate the value of a 3TURB compared to upfront BCG.

Impaired bone morphogenetic protein signaling pathways disrupt decidualization in endometriosis.

It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in individuals with endometriosis. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from individuals with or without endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified differences in key pathways between the two groups, including defective bone morphogenetic protein (BMP)/SMAD4 signaling (ID2, ID3, FST), oxidate stress response (NFE2L2, ALOX15, SLC40A1), and retinoic acid signaling pathways (RARRES, RARB, ALDH1B1). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 and H3K27Ac in the decidualized stromal cells from individuals without endometriosis relative to those with endometriosis, with target genes enriched in pathways related to signaling by transforming growth factor ß (TGFß), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation in endometriosis patient-derived assembloids elevated the expression of decidualization markers. In summary, transcriptomic and genome-wide binding analyses of patient-derived endometrial cells and assembloids identified that a functional BMP/SMAD1/5/4 signaling program is crucial for engaging decidualization.

SMAD2/3 signaling in the uterine epithelium controls endometrial cell homeostasis and regeneration.

The regenerative potential of the endometrium is attributed to endometrial stem cells; however, the signaling pathways controlling its regenerative potential remain obscure. In this study, genetic mouse models and endometrial organoids are used to demonstrate that SMAD2/3 signaling controls endometrial regeneration and differentiation. Mice with conditional deletion of SMAD2/3 in the uterine epithelium using Lactoferrin-iCre develop endometrial hyperplasia at 12-weeks and metastatic uterine tumors by 9-months of age. Mechanistic studies in endometrial organoids determine that genetic or pharmacological inhibition of SMAD2/3 signaling disrupts organoid morphology, increases the glandular and secretory cell markers, FOXA2 and MUC1, and alters the genome-wide distribution of SMAD4. Transcriptomic profiling of the organoids reveals elevated pathways involved in stem cell regeneration and differentiation such as the bone morphogenetic protein (BMP) and retinoic acid signaling (RA) pathways. Therefore, TGFß family signaling via SMAD2/3 controls signaling networks which are integral for endometrial cell regeneration and differentiation.

Establishing 3D Endometrial Organoids from the Mouse Uterus.

Endometrial tissue lines the inner cavity of the uterus and is under the cyclical control of estrogen and progesterone. It is a tissue that is composed of luminal and glandular epithelium, a stromal compartment, a vascular network, and a complex immune cell population. Mouse models have been a powerful tool to study the endometrium, revealing critical mechanisms that control implantation, placentation, and cancer. The recent development of 3D endometrial organoid cultures presents a state-of-the-art model to dissect the signaling pathways that underlie endometrial biology. Establishing endometrial organoids from genetically engineered mouse models, analyzing their transcriptomes, and visualizing their morphology at a single-cell resolution are crucial tools for the study of endometrial diseases. This paper outlines methods to establish 3D cultures of endometrial epithelium from mice and describes techniques to quantify gene expression and analyze the histology of the organoids. The goal is to provide a resource that can be used to establish, culture, and study the gene expression and morphological characteristics of endometrial epithelial organoids.

Progesterone Receptor Signaling in the Uterus Is Essential for Pregnancy Success.

The uterus plays an essential role in the reproductive health of women and controls critical processes such as embryo implantation, placental development, parturition, and menstruation. Progesterone receptor (PR) regulates key aspects of the reproductive function of several mammalian species by directing the transcriptional program in response to progesterone (P4). P4/PR signaling controls endometrial receptivity and decidualization during early pregnancy and is critical for the establishment and outcome of a successful pregnancy. PR is also essential throughout gestation and during labor, and it exerts critical roles in the myometrium, mainly by the specialized function of its two isoforms, progesterone receptor A (PR-A) and progesterone receptor B (PR-B), which display distinct and separate roles as regulators of transcription. This review summarizes recent studies related to the roles of PR function in the decidua and myometrial tissues. We discuss how PR acquired key features in placental mammals that resulted in a highly specialized and dynamic role in the decidua. We also summarize recent literature that evaluates the myometrial PR-A/PR-B ratio at parturition and discuss the efficacy of current treatment options for preterm birth.

BMP/SMAD1/5 Signaling in the Endometrial Epithelium Is Essential for Receptivity and Early Pregnancy.

The biological processes that control endometrial receptivity and embryo implantation are critical for the successful outcome of pregnancy. The endometrium is the complex inner lining of the uterine wall that is under the cyclical control of estrogen and progesterone and is a site of intimate contact between mother and blastocyst. The bone morphogenetic signaling (BMP) pathway is a highly conserved signaling pathway that controls key cellular processes throughout pregnancy and exerts intracellular effects via the SMAD1/5 transcription factors. To delineate the endometrial compartment-specific roles of BMP signaling, we generated mice with epithelial-specific conditional deletion of SMAD1/5 using Lactoferrin-icre (Smad1flox/flox;Smad5flox/flox;Lactoferrin-cre, "Smad1/5 cKO"). Histological analysis of the reproductive tracts showed that Smad1/5 cKO mice were developmentally normal and displayed no defects in glandular morphology. In fertility analyses, single SMAD1 or SMAD5 deletion had no effect on fertility; however, double-conditional deletion of SMAD1 and SMAD5 resulted in severe subfertility. Timed mating analyses revealed endometrial receptivity defects in the Smad1/5 cKO mice beginning at 3.5 days post coitum (dpc) that perturbed embryo implantation at 4.5 dpc, as demonstrated by the detection of unattached blastocysts in the uterus, decreased COX2 expression, and FOXO1 cytoplasmic mislocalization. We also found that defects that arose during peri-implantation adversely affected embryonic and decidual development at 5.5 and 6.5 dpc. Thus, uterine epithelial BMP/SMAD1/5 signaling is essential during early pregnancy and SMAD1/5 epithelial-specific deletion has detrimental effects on stromal cell decidualization and pregnancy development.

[Assessment of trainee urologists' knowledge in urogenital anatomy]. / Évaluation des connaissances en anatomie uro-génitale des urologues en formation.

The purpose of this study was to assess trainee urologists' [interns and assistant heads of university hospitals (CHU)] knowledge of the anatomy of the urogenital system. An examination consisting of 10 timed (16minutes) multiple-choice questions (MCQ) based on urogenital anatomy assessments for students in third year of the general medical science diploma program (DFGSM3) was sent to members of the French Association of Trainee Urologists (AFUF) in May 2018 in order to compare the average scores of these two populations. In addition, a questionnaire consisting of epidemiological data, their opinion on the quality of education in anatomy and the willingness to have more courses on this subject was included in the examination. The same scale based on a score out of 20 was applied to both populations. Of the 501 AFUF members solicited, 144 answered all the questions (28.7%). The mean score for urologists was lower than that of DFGSM3 students (10.56±1.82 vs. 11.4±2.37 respectively) (P=0.0013). Moreover, the desire for further education in anatomy was widespread among urologists (87%). According to our study, urologists have less knowledge of urogenital anatomy than third year medical students. Many means are being implemented or are available to rectify this failing, especially since the majority of trainee urologists consider that there are insufficient anatomy lessons in the curriculum and would like to receive further education in anatomy. LEVEL IF EVIDENCE: 3.

Educational program in onco-urology for young urologists: What are their needs?

PURPOSE: The emergence of new communication media such as digital contents are progressively replacing more traditional medias in the field of educational programs. Our purpose was to assess urologist in training aspirations regarding urological education. METHODS: Members of a national urologist in training association were sent an anonymous online questionnaire regarding their medical formation in the field of urology. Responders interest for urological sub-specialty or education support (new tools and traditional support) were evaluated through a 5-point Likert scale. RESULTS: Overall, 109 young urologists (26%) responded to the survey. Most of the respondents worked during their training in an academic hospital (n=89, 82%). The three favorite tools for training chosen by the responders were: videos, workshop or masterclass, and podcasts (responders very interested were respectively n=64 (58.7%), n=50 (45.9%), and n=49 (45%)). E-mail newsletters were reported as the less useful educational tool by participants (n=38, 34.9%). Participants were very interested in improving their surgical skills and their radiological knowledge. Responders who were the most attracted by PCa were much more looking to improve their systemic treatment and radiological knowledges. CONCLUSIONS: Urologic-oncology was a priority regarding education for urologists in training. A majority of participants expressed a lack in their surgical education, revealing a reduced OR access and underlining utilization of new tools such as simulation. New digital contents such as social media or podcast achieved high interest for the participants, instead of more traditional media. There is a need that educational content evolve and uses new digital media. LEVEL OF EVIDENCE: 3.

Residents and patients benefit from surgical simulation on a live porcine model, could we consider it as ethical?

INTRODUCTION: The objective was to evaluate, by self-questionnaire, the feeling of participants in surgical training sessions on a live porcine model. METHODS: A computerized questionnaire (GoogleForm ©) was sent to the members of the French Association of Urologists-in-Training (AFUF) (fellows and residents). Only questionnaires from Urologists-in-training who had participated in surgical training sessions were included. The sessions consisted of performing surgeries such as laparoscopic nephrectomies or laparoscopic cystectomies. RESULTS: Overall, 198 met the inclusion criteria. A total of 36.4% (72/198) of the participants were fellows and 63.6% (126/198) were residents. According to the participants, the main interest of sessions was to be able to train for emergency situations. A total of 79.8% (158/198) of the participants wanted surgical simulation to become compulsory. To their opinion, the main advantage of surgical simulation on a live porcine model was: technical progress in 87.4% (173/198) of cases. A total of 13.1% (26/198) of the participants found it was unethical to perform the first technical procedures on live animal models. A total of 65.7% (130/198) of the participants considered that there is currently no system of substitution. CONCLUSION: For the participants, surgical training on a live porcine model allows technical progress while training for serious emergency situations. Surgeons and patients could benefit from this risk-free mock surgical scenario. LEVEL OF EVIDENCE: 3.

Management of long ureteral stenosis: Alternatives to indwelling ureteral stents.

OBJECTIF: Evaluate kidney autotransplantation (KAT) and ileal ureter substitution (IUS) practice and outcome as alternatives to indwelling ureteral stents for the management of long ureteral stenosis (US). MATERIAL: We included all patients treated for US with KAT or IUS in 5 French university urology centers between 2010 and 2018. We excluded US due to urothelial carcinoma. Primary endpoint was the preservation of ipsilateral kidney and renal function without any urinary diversion. RESULTS: 22 patients were treated with KAT (n=8, 36.4%) and IUS (n=14, 63.6%). Mean US length was 4.6cm and 6cm (P=0.52) in KAT and IUS groups respectively. US etiologies were lithiasis, iatrogenic, retroperitoneal fibrosis or extrinsic compression. US level was varied. The surgery was described as difficult because of peritoneal adhesions or major peri-ureteral fibrosis. Mean operating time and hospital stay were 336 and 346minutes (P=0.87) and 8 and 15 days respectively (P=0.001). Postoperative complications were mostly Clavien ≤2 (n=17, 77.3%). Revision surgery was required in the KAT group in 3 cases (37.5%), for textiles, renal vein thrombosis and anastomotic leak, none in the IUS group. The mean follow-up was 15.7 months. All but one (in the KAT group) ipsilateral kidneys were preserved, without renal function impairment (Δcreat +2.1 vs. +2.4µmol/l respectively, P=0.67), nor urinary diversion. CONCLUSION: KAT and IUS are safe alternatives whose indication depends on surgeons expertise. Our study pointed out the scarcity of this practice suggesting the need to refer patients to expert centers. LEVEL OF EVIDENCE: 3.

[Radical prostatectomy for prostate cancer, perioperative management by French urologists in 2018]. / Évaluation de la gestion per- et périopératoire d'une prostatectomie totale pour cancer de la prostate par les urologues français en 2018.

INTRODUCTION: Prostatectomy (PT) is a common procedure performed by many urologists. In 2018, 20,207 prostatectomies were performed in France, and few studies evaluated the perioperative habits of urologists. As part of writing guidelines for enhanced recovery after surgery (ERAS) we wished to evaluate practice of urologists in their hospital management of a prostatectomy. MATERIEL AND METHODS: A questionnaire was sent by Survey Monkey in June and July 2018 to all urologists who are members of the French Association of Urology. RESULTS: One hundred and sixty seven urologists (14%) answered the questionnaire, 62% have private practice. The average number of operators per center performing PT was 4, with a median number of 70 interventions (0 to 486) per center in 2018. Open surgery is still gold standard (39.13%), followed by the robot-assisted transperitoneal laparoscopic (34.78%) and standard laparoscopic (24.22%). Alimentation, like first stand-up, was re-established on the first post-operative day, and the average hospital stay was 4±2 nights. The removal of the bladder catheter was most often performed at home by nurse (49.06%), one week after surgery. Only 10.06% of urologists systematically perform a cystography before removal urinary catheter. CONCLUSION: The perioperative management of prostatectomy in France is relatively homogeneous, between urologists. The length of hospital stay remains important and could be reduced by proposing an ERAS protocol as has been obtained for cystectomy. LEVEL OF EVIDENCE: III.

[Benign prostatic hyperplasia surgery and patient's information: What do patients understand and remember?] / Chirurgie de l'hypertrophie bénigne de prostate et information des patients : qu'est ce que les patients comprennent et retiennent ?

INTRODUCTION: Preoperative information is a key to adherence to treatment for the patients, but may be misunderstood because of its density and complexity. The aim of this study was to assess comprehension and satisfaction of patients about preoperative information of benign prostatic hyperplasia (BPH) surgery. Factors influencing patient understanding were also studied. PATIENTS AND METHODS: It was a monocentric study on questionnaires including every patients planned for BPH surgery, whatever the surgical technique. A survey was sent at patient's home after the preoperative consultation. RESULTS: One hundred and six of 210 patients (50,5 %) returned the questionnaire. 38,68 % (n=41) found the quality of information excellent (9 or 10 out of 10), and 45,28 % (n=48) found the quality of information good (7 or 8 out of 10). The main recalled complications were retrograde ejaculation (39.6 %, n=42/106), and bleeding (29,2 %, n=31/106). 57.6 % of patients (n=61) remembered receiving the written information sheet of the French Association of Urology. 5.7 % (n=6) hesitated having the procedure. Only patient's age was significantly associated with difference of comprehension (p<0.005). CONCLUSION: Information given before a BPH surgery seems satisfactory although it was poorly understood, notably about complications. Providing complete oral information, insisting on complications, and giving the written information sheet are essential for a good doctor-patient relationship and a forensic serenity. LEVEL OF EVIDENCE: 3.

[Renal Trauma]. / Traumatismes du rein.

INTRODUCTION: Renal traumas are common, observed in 10% of patients with abdominal trauma. Most renal traumas are blunt, resulting from a direct hit or from an abrupt deceleration. MATERIAL AND METHODS: We realized a synthesis of renal trauma management for nurses. RESULTS: Clinical presentation often encompasses gross hematuria and lumbar pain. The best diagnostic tool is computed tomography (CT) urogram. Based on CT urogram images, renal traumas are classified according to the American Association for the Surgery of Trauma (AAST) classification in five grades of increasing severity. The management is conservative in the vast majority of cases and has been largely simplified over the past few years, being now mostly based on observation. Radiological interventional and endoscopic procedures are used only in very selected cases and surgical exploration has become extremely rare. CONCLUSION: The prognosis has also considerably improved and renal trauma rarely result in death or loss of the kidney nowadays.

Efficacy and security of continent catheterizable channels at short and middle term for adult neurogenic bladder dysfunction.

AIMS: The objective of this study was to assess the effectiveness and the complications rate following continent cutaneous channels (CCC) procedures, at short and medium term follow-up (FU). MATERIALS & METHODS: A continuous retrospective case series (2008-2018): all patients who have undergone a CCC for neurogenic bladder were included in our department. The primary outcome was the effectiveness of CCC defined by the status of catheterizability (by the patient or a care-giver), continence of the tube, and absence of reintervention at 3 and 12 months FU. The secondary outcome was the prevalence of postoperative complications at 3 and 12 months FU. RESULTS: Fifty-three patients were included during the study period in our department. Median follow up was 3,3 years (1.5-6.1). The overall effectiveness of CCC was 67.9% (n=36/53) at 3 months FU and 45,3% (n=24) at 12 months FU. The global rate of complications was 60.4% (n=32/53) at 3 months, and 73.6% (n=39/73) at 12 months FU. The statistical analysis showed no statistical differences on efficacy and complications in the different subgroups of CCC. CONCLUSIONS: In the current series, the effectiveness and the complications rates following CCC were comparable across the procedure types. LEVEL OF EVIDENCE: 4.

Readmissions, revisions, and mortality after treatment for proximal humeral fractures in three large states.

BACKGROUND: Proximal humeral fractures can be treated non-operatively or operatively with open reduction and internal fixation (ORIF) and arthroplasty. Our objective was to assess practice patterns for operative and non-operative treatment of proximal humeral fractures. We also report on complications, readmissions, in-hospital mortality, and need for surgery after initial treatment of proximal humeral fractures in California, Florida, and New York. METHODS: The State Inpatient Databases and State Emergency Department Databases from the Healthcare Cost and Utilization Project, sponsored by the Agency for Healthcare Research and Quality, were used for the states of California (2005-2011), Florida (2005-2014), and New York (2008-2014). Data on patients with proximal humeral fractures was extracted. Patients underwent non-operative or operative (ORIF or arthroplasty) treatment at baseline and were followed for at least 4 years from the index presentation. If the patient needed subsequent surgery, time to event was calculated in days, and Kaplan-Meier survival curves were plotted. RESULTS: At the index visit, 90.3% of patients with proximal humeral fractures had non-operative treatment, 6.7% had ORIF, and 3.0% had arthroplasty. 7.6% of patients initially treated non-operatively, 6.6% initially treated with ORIF, and 7.2% initially treated with arthroplasty needed surgery during follow-up. Device complications were the primary reason for readmission in 5.3% of ORIF patients and 6.7% of arthroplasty patients (p < 0.0001). All-cause in-hospital mortality was 9.8% for patients managed non-operatively, 8.8% for ORIF, and 10.0% for arthroplasty (p = 0.003). CONCLUSIONS: A majority of patients with proximal humeral fractures underwent non-operative treatment. There was a relatively high all-cause in-hospital mortality irrespective of treatment. Given the recent debate on operative versus non-operative treatment for proximal humeral fractures, our study provides valuable information on the need for revision surgery after initial treatment. The differences in rates of revision surgery between patients treated non-operatively, with ORIF, and with arthroplasty were small in magnitude. At nine years of follow-up, ORIF had the lowest probability of needing follow-up surgery, and arthroplasty had the highest.

[Enhanced recovery after robotic partial nephrectomy: Evaluation of patient's satisfaction]. / Réhabilitation précoce après tumorectomie rénale robot-assistée : quelle satisfaction des patients ?

INTRODUCTION: Several enhanced recovery protocols after surgery showed a benefit for postoperative recovery and reduction of hospital lengths of stay. Very few studies evaluated patient's satisfaction about these enhanced recovery protocols. The aim of this study was to evaluate patient's satisfaction about our enhanced recovery protocol for robotic-assisted partial nephrectomy (RAPN). METHODS: A validated survey EORTC In PATSAT32 with a specific questionnaire about protocol was sent to the first patients included in the enhanced recovery protocol for RAPN. The survey was sent after the postoperative consultation at postoperative day 30. Responses were anonymous. Satisfaction's scores for EORTC questionnaire were calculated for each dimension with Likert's method. Scores were transformed linearly into a scale ranging from 0 to 100, where 100 represent the highest level of care satisfaction (EORTC method). RESULTS: A total of 21 patients (50%) returned the completed questionnaire. The overall satisfaction score was 75.1% (37.3; 100) in the EORTC survey. In total, 71.4% of patients (n=15) were satisfied with the discharge at postoperative day 2 (POD2) and 5 patients (23.8%) found this premature. None of the patients had a negative impression on the clinical pathway. The average overall evaluation on the protocol by patients, on a satisfaction scale of 1 to 10 was 8.9/10. CONCLUSION: In this study, patients included in the enhanced recovery protocol after RAPN were very satisfied with their pre-, per- and postoperative care. Given patients satisfaction, reduction of LOS, patient's safety and the medicoeconomic advantage, these enhanced recovery protocol have become a priority to develop and evaluate. More large studies are needed to assess the patient's experience with these clinical pathways. LEVEL OF EVIDENCE: 4.

[Evaluation of spinal anesthesia in urological outpatient surgery, comparison between two local anesthetics (Chloroprocaine/Bupivacaine)]. / Évaluation de la rachianesthésie en chirurgie ambulatoire urologique, comparaison entre deux anesthésiques locaux (Chloroprocaïne/Bupivacaïne).

INTRODUCTION: Spinal anesthesia in outpatient urology is controversial (longer hospital stay, risk of urinary retention). The main goal was to evaluate outpatient spinal anesthesia and to compare 2 local anesthetics secondarily. MATERIAL: Monocentric retrospective study including all patients undergoing surgery in urological ambulatory surgery under spinal anesthesia between December 2011 and May 2015, split into two groups according to the local anesthetic used: bupivacaine (BP) and chloroprocaine (CP). Quantitative variables were compared by Student's t-test, qualitative variables by χ2 test. RESULTS: Seventy-one (95%) out of the 75 patients included have been discharged the same day. Discharge was impossible in these cases: patient alone at home (1), bladder clot (1), JJ intolerance (1), delayed micturition (1). The mean duration of the procedure was 27±19min, the SSPI's was 55±31min, the stay's was 360±91min. A total of 45 patients (60%) received BP and 30 (40%) received CP. The mean residence time in SSPI was significantly reduced in the CP group (47±24min vs. 61±34min, P=0.04). One patient experienced urination delay in the BP group with no significant difference. No significant difference for the other criteria studied despite the mean age, which is higher in the CP group (P=0.02). CONCLUSION: Spinal anesthesia is adapted to ambulatory urology, and does not increase the risk of urinary retention, especially with CP that would decrease the length of stay in SSPI compared to BP. LEVEL OF EVIDENCE: 4.

Genetic and familial predisposition to rotator cuff disease: a systematic review.

BACKGROUND: Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. METHODS: A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria. RESULTS: Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A 5-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears did. The other 3 studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGF3, ESRRB, and FGF10 and 2 single-nucleotide polymorphisms within SAP30BP and SASH1. CONCLUSION: Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions.