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PURPOSE: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. MATERIALS AND METHODS: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (

Background Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa. Materials and methods A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. Results Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority. Conclusions The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Objective To describe the X-Capsular Incision for Tumor Enucleation (X-CITE) technique to resect endophytic renal tumors while preserving the overlying renal parenchyma. Subjects and methods We reviewed 1-year outcomes of 12 consecutive patients with a history of bilateral or multifocal renal tumors who presented to our institution with completely endophytic renal masse(s) between August 2017 and August 2018. Endophytic tumors were resected by making an X-shaped incision in the renal capsule and developing parenchymal flaps overlying the tumor pseudocapsule. Following tumor enucleation, the overlying parenchymal flaps were reapproximated. Results Median follow up was 19.9 months (range 10.6-14.9). Most patients also had additional exophytic tumors with a median of 5 renal tumors removed per operation with a median largest renal tumor size of 3.2 cm. No intraoperative or postoperative complications occurred. There was no decline in renal function after surgery when comparing median pre- and 12-month postoperative eGFR (94.5 vs 91.5, P= 0.18).). Postoperative nuclear mercaptoacetyltriglycine (MAG-3) renal scans demonstrated equal differential kidney function after surgery. Limitations include short-term follow-up and referral bias at center specializing in multi-focal kidney surgery. Conclusion The X-Capsular Incision for Tumor Enucleation technique is feasible, safe and effective with minimal collateral damage in the treatment of completely endophytic renal masses. Further investigation should identify which patients may benefit from this procedure and explore intermediate and long-term outcomes.

PURPOSE: Active surveillance for patients with low and intermediate risk prostate cancers is becoming a more utilized option in recent years. However, the use of magnetic resonance imaging and imaging-targeted biopsy for monitoring grade progression has been poorly studied in this population. We aim to define the utility of magnetic resonance imaging-targeted biopsy and systematic biopsy in an active surveillance population. MATERIALS AND METHODS: Between July 2007 and January 2020, patients with diagnosed prostate cancer who elected active surveillance were monitored with prostate magnetic resonance imaging, imaging-targeted biopsy and standard systematic biopsy. Patients were eligible for surveillance if diagnosed with any volume Gleason grade 1 disease and select Gleason grade 2 disease. Grade progression (Gleason grade 1 to ≥2 disease and Gleason grade 2 to ≥3 disease) for each biopsy modality was measured at 2 years, 4 years and 6+ years. RESULTS: In total, 369 patients had both magnetic resonance imaging-targeted and systematic biopsy and were surveilled for at least 1 year. At 2 years, systematic biopsy, magnetic resonance imaging-targeted biopsy and combined biopsy (systematic+imaging-targeted) detected grade progression in 44 patients (15.9%), 73 patients (26.4%) and 90 patients (32.5%), respectively. Magnetic resonance imaging-targeted biopsy detected more cancer grade progression compared to systematic biopsy in both the low and intermediate risk populations (p

BACKGROUND: The ability of serial magnetic resonance imaging (MRI) to capture pathologic progression during active surveillance (AS) remains in question. OBJECTIVE: To determine whether changes in MRI are associated with pathologic progression for patients on AS. DESIGN, SETTING, AND PARTICIPANTS: From July 2007 through January 2020, we identified all patients evaluated for AS at our institution. Following confirmatory biopsy, a total of 391 patients who underwent surveillance MRI and biopsy at least once were identified (median follow-up of 35.6 mo, interquartile range 19.7–60.6). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All MRI intervals were scored using the “Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation” (PRECISE) criteria, with PRECISE scores ≥4 considered a positive change in MRI. A generalized estimating equation–based logistic regression analysis was conducted for all intervals with a PRECISE score of

ObjectiveTo evaluate the association of the MyProstateScore (MPS) urine test on the decision to undergo biopsy in men referred for prostate biopsy at a contemporary academic urology practice.MethodsMPS testing was offered as an alternative to immediate biopsy in men referred to the University of Michigan for prostate biopsy from October 2013 through October 2016. The primary endpoint was the decision to perform biopsy. The proportion of patients who underwent biopsy was calculated across MPS quintiles and compared to predicted risk scores from the Prostate Cancer Prevention Trial risk calculator (PCPTrc). Analyses were performed in the overall referral population and the intended-use population (PSA 3-10 ng/ml or PSA ResultsOf 248 patients, 134 (54%) proceeded to prostate biopsy. Clinical variables, PSA, and PCPTrc score did not significantly differ based on the decision to undergo biopsy, while MPS was significantly higher in biopsied patients (median 29 vs. 14, pConclusionIn a cohort of patients who underwent clinical MPS testing as an alternative to immediate prostate biopsy, 46% were able to avoid biopsy and increasing MPS was strongly associated with biopsy rates. These findings were robust to the use of mpMRI and consistent across pertinent subpopulations. Overall, these data suggest that the MPS assay may substantially reduce the number of men undergoing prostate needle biopsy.

OBJECTIVE: To evaluate the efficacy of combined MRI-targeted plus systematic 12-core biopsy (Cbx) to aid in the selection of patients for active surveillance (AS). METHODS: From July 2007 to January 2020, patients with Gleason Grade Group (GG) 1 or GG 2 prostate cancer were referred to our center for AS consideration. All patients underwent an MRI and confirmatory combined MRI-targeted plus systematic biopsy (Cbx), and AS outcomes based on Cbx results were compared. Cox regression was used to identify predictors of AS failure, defined as progression to ≥ GG3 disease on follow-up biopsies. RESULTS: Of 579 patients referred for AS, 79.3% (459/579) and 20.7% (120/579) had an initial diagnosis of GG1 and GG2 disease, respectively. Overall, 43.2% of patients (250/579) were upgraded on confirmatory Cbx, with 19.2% (111/579) upgraded to ≥ GG3. For the 226 patients followed on AS, 32.7% (74/226) had benign, 45.6% (103/226) had GG1, and 21.7% (49/226) had GG2 results on confirmatory Cbx. In total, 28.8% (65/226) of patients eventually progressed to ≥ GG3, with a median time to AS failure of 89 months. The median time from confirmatory Cbx to AS failure for the negative, GG1, and GG2 groups were 97, 97, and 32 months, respectively (p < .001). On multivariable regression, only age (hazard ratio 1.06 [1.02–1.11], p < .005) and GG on confirmatory Cbx (hazard ratio 2.75 [1.78–4.26], p < .005) remained as positive predictors of AS failure. CONCLUSION: The confirmatory combined MRI-targeted plus systematic biopsy provides useful information for the risk stratification of patients at the time of AS enrollment.

Background The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies per...

OBJECTIVES To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

Background While magnetic resonance imaging (MRI)-targeted biopsy (TBx) results in better prostate cancer (PCa) detection relative to systematic biopsy (SBx), the combination of both methods increases clinically significant PCa detection relative to either Bx method alone. However, combined Bx subjects patients to higher number of Bx cores and greater detection of clinically insignificant PCa. Objective To determine if prebiopsy prostate MRI can identify men who could forgo combined Bx without a substantial risk of missing clinically significant PCa (csPC). Design, setting, and participants Men with MRI-visible prostate lesions underwent combined TBx plus SBx. Outcome measurements and statistical analysis The primary outcomes were detection rates for grade group (GG) ≥2 and GG ≥3 PCa by TBx and SBx, stratified by Prostate Imaging-Reporting and Data System (PI-RADS) score. Results and limitations Among PI-RADS 5 cases, nearly all csPCs were detected by TBx, as adding SBx resulted in detection of only 2.5% more GG ≥2 cancers. Among PI-RADS 3–4 cases, however, SBx addition resulted in detection of substantially more csPCs than TBx alone (8% vs 7.5%). Conversely, TBx added little to detection of csPC among men with PI-RADS 2 lesions (2%) relative to SBx (7.8%). Conclusions While combined Bx increases the detection of csPC among men with MRI-visible prostate lesions, this benefit was largely restricted to PI-RADS 3–4 lesions. Using a strategy of TBx only for PI-RADS 5 and combined Bx only for PI-RADS 3–4 would avoid excess biopsies for men with PI-RADS 5 lesions while resulting in a low risk of missing csPC (1%). Patient summary Our study investigated an optimized strategy to diagnose aggressive prostate cancer in men with an abnormal prostate MRI (magnetic resonance imaging) scan while minimizing the risk of excess biopsies. We used a scoring system for MRI scan images called PI-RADS. The results show that MRI-targeted biopsies alone could be used for men with a PI-RADS score of 5, while men with a PI-RADS score of 3 or 4 would benefit from a combination of MRI-targeted biopsy and systematic biopsy. This trial is registered at ClinicalTrials.gov as NCT00102544.

Simple Summary Prostate cancer is one of the most common cancers in men. Traditionally, prostate cancer is diagnosed via transrectal ultrasound-guided prostate biopsy, using a systematic random template. Using multiparametric magnetic resonance imaging, lesions suspicious for prostate cancer can be identified, and subsequently targeted on biopsy, allowing for increased diagnostic accuracy. This article reviewed the current literature surrounding various types of targeted biopsy, such as transperineal biopsy, allowing for comparison not only between targeted biopsy and systematic biopsy, but also between different varieties of targeted biopsy. Abstract In this review, we evaluated literature regarding different modalities for multiparametric magnetic resonance imaging (mpMRI) and mpMRI-targeted biopsy (TB) for the detection of prostate cancer (PCa). We identified studies evaluating systematic biopsy (SB) and TB in the same patient, thereby allowing each patient to serve as their own control. Although the evidence supports the accuracy of TB, there is still a proportion of clinically significant PCa (csPCa) that is detected only in SB, indicating the importance of maintaining SB in the diagnostic pathway, albeit with additional cost and morbidity. There is a growing subset of data which supports the role of TB alone, which may allow for increased efficiency and decreased complications. We also compared the literature on transrectal (TR) vs. transperineal (TP) TB. Although further high-level evidence is necessary, current evidence supports similar csPCa detection rate for both approaches. We also evaluated various TB techniques such as cognitive fusion biopsy (COG-TB) and in-bore biopsy (IB-TB). COG-TB has comparable detection rates to software fusion, but is operator-dependent and may have reduced accuracy for smaller lesions. IB-TB may allow for greater precision as lesions are directly targeted; however, this is costly and time-consuming, and does not account for MRI-invisible lesions.

PURPOSE OF REVIEW: The goal of this study is to review recent findings and evaluate the utility of MRI transrectal ultrasound fusion biopsy (FBx) techniques and discuss future directions. RECENT FINDINGS: FBx detects significantly higher rates of clinically significant prostate cancer (csPCa) than ultrasound-guided systematic prostate biopsy (SBx), particularly in repeat biopsy settings. FBx has also been shown to detect significantly lower rates of clinically insignificant prostate cancer. In addition, a dedicated prostate MRI can assist in more accurately predicting the Gleason score and provide further information regarding the index cancer location, prostate volume, and clinical stage. The ability to accurately evaluate specific lesions is vital to both focal therapy and active surveillance, for treatment selection, planning, and adequate follow-up. SUMMARY: FBx has been demonstrated in multiple high-quality studies to have improved performance in diagnosis of csPCa compared to SBx. The combination of FBx with novel technologies including radiomics, prostate-specific membrane antigen positron emission tomography (PSMA PET), and high-resolution micro-ultrasound may have the potential to further enhance this performance.

Background: With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS). Methods: A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by >= 80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement. Results: Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community. Conclusions: FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS. United States Department of Health & Human Services National Institutes of Health (NIH) - USA ; European Urological Scholarship Programme (EUSP)

Contains fulltext : 232936.pdf (Publisher’s version ) (Closed access) The use of multiparametric MRI has been hastened under expanding, novel indications for its use in the diagnostic and management pathway of men with prostate cancer. This has helped drive a large body of the literature describing its evolving role over the last decade. Despite this, prostate cancer remains the only solid organ malignancy routinely diagnosed with random sampling. Herein, we summarize the components of multiparametric MRI and interpretation, and present a critical review of the current literature supporting is use in prostate cancer detection, risk stratification, and management.

Objective To summarize the recent literature discussing focal therapy for localized prostate cancer. Methods A thorough literature review was performed using PubMed to identify recent studies involving focal therapy for the treatment of localized prostate cancer. Results In an effort to decrease the morbidity associated with prostate cancer treatment, many urologists are turning to focal therapy as an alternative treatment option. With this approach, the cancer bearing portion of the prostate is targeted while leaving the benign tissue untouched. Multiparametric magnetic resonance imaging remains the gold standard for visualization during focal therapy, but new imaging modalities such as prostate specific membrane antigen/positron emission tomography and contrast enhanced ultrasound are being investigated. Furthermore, several biomarkers, such as prostate cancer antigen 3 and prostate health index, are used in conjunction with imaging to improve risk stratification prior to focal therapy. Lastly, there are several novel technologies such as nanoparticles and transurethral devices that are under investigation for use in focal therapy. Conclusion Focal therapy is proving to be a promising option for the treatment of localized prostate cancer. However, further study is needed to determine the true efficacy of these exciting new technologies.

Background Focal therapy (FT) and partial gland ablation (PGA) are quickly adopted by urologists and radiologists as an option for the management of localized prostate cancer. Objective To find consensus on a standardized nomenclature and to define a follow-up guideline after FT and PGA for localized prostate cancer in clinical practice. Design, setting, and participants A review of the literature identified controversial topics in the field of FT. Online questionnaires were distributed to experts during three rounds, with the goal to achieve consensus on debated topics. The consensus project was concluded with a face-to-face meeting in which final conclusions were formulated. Outcome measurements and statistical analysis Controlled feedback of responses of previous rounds were summarized and returned to the participants allowing them to re-evaluate their decisions. The level of agreement to achieve consensus on a topic was set at 80%. Results and limitations Sixty-five experts participated in this interdisciplinary consensus study (72% urologists; 28% radiologists). The experts propose the use of the herein standardized nomenclature for ablative procedures. After FT/PGA, the following tests should be performed to assess treatment outcomes: prostate-specific antigen (PSA), imaging, biopsies, and functional outcome assessment. Although not a reliable marker for treatment failure, PSA should be measured every 3 mo in the 1st year and every 6 mo thereafter. Magnetic resonance imaging is the preferred image modality and should be performed at 6 and 18 mo after treatment. A systematic 12-core transrectal ultrasound-guided biopsy combined with a targeted biopsy of the treated area should be performed 6–12 mo after treatment. Functional outcomes should be obtained 3–6 mo after treatment for the first time and until stability is attained. Conclusions The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of FT as a standard of care for select patients with localized prostate cancer. Patient summary In this report, we present expert opinion on the use of a standardized nomenclature, and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer.

Conventional staging for prostate cancer (PCa) is performed for men diagnosed with unfavorable-intermediate or higher risk disease. Computed tomography (CT) of the abdomen and pelvis and whole body bone scan remains the standard of care for the detection of visceral, nodal, and bone metastasis. The implementation of the 2012 United States Preventive Services Task Force recommendation against routine prostate specific antigen (PSA) screening resulted in a rise of metastatic PCa at the time of diagnosis, emphasizing the importance of effective imaging modalities for evaluating metastatic disease. CT plays a major role in clinical staging at the time of PCa diagnosis, but multi-parametric magnetic resonance imaging (MRI) is now integrated into many prostate biopsy protocols for the detection of primary PCa, and may be a surrogate for CT for nodal staging. Current guidelines incorporate both CT and MRI as appropriate cross-sectional imaging modalities for the identification of nodal metastasis in indicated patients. There is an ongoing debate about the utility of traditional cross-sectional imaging modalities as well as advanced imaging modalities in detection of both organ-confined PCa detection and nodal involvement.

INTRODUCTION AND OBJECTIVE:Early retrospective data has shown that vascular clamping and increased ischemia time during partial nephrectomy (PN) has led to higher rates of both acute and chronic ki...

Objective Robotic-assisted thoracoscopic transdiaphragmatic adrenalectomy (RATTA) represents a novel surgical approach for the management of adrenal pathology in patients with a history of extensive transperitoneal or retroperitoneal procedures. Methods Here we report the first described case of RATTA in a 56-year-old woman with metastatic renal cell carcinoma to the left adrenal gland and right lung. With the assistance of cardiothoracic surgery, this patient underwent robotic-assisted thoracoscopic pulmonary wedge resection and RATTA. In brief, after completion of the pulmonary wedge resection by thoracic surgery the diaphragm was incised starting at the left crus and extending laterally through the diaphragmatic muscle, exposing the retroperitoneal space and fat. The adrenal gland with mass was identified, dissected from surrounding structures, and extracted. The diaphragm was then closed using Ethibond suture with polytetrafluoroethylene felt pledgets. A 22-Fr chest tube was placed in the thoracic cavity. Results Operative and postoperative courses were uncomplicated. The patient was discharged on postoperative day 4. Pathology confirmed metastatic clear cell renal cell carcinoma in both the left adrenal and the right lung nodules with negative surgical margins. Conclusion The case described here highlights the surgical technique and ideal patient population in which RATTA serves as a feasible and safe alternative to conventional laparoscopic approaches in the treatment of adrenal pathologies.

INTRODUCTION AND OBJECTIVES:We conducted a phase II trial to evaluate combination therapy with BCG and Sunitinib for prevention of recurrence and progression of high-risk NMIBC with a primary endpoint of 3-month complete response (CR). We hypothesized that adding Sunitinib to BCG could increase the initial CR to therapy by synergistic inhibition of the VEGF pathway. We also measured urine levels of various biomarkers throughout treatment to identify trends that predict and/or explain a response to therapy.METHODS:Patients with high-grade clinical ≤T1N0M0 NMIBC who had not received BCG within 12 months of diagnosis were deemed eligible. Patients received a 6-week induction BCG course followed by 28 days of Sunitinib. CR was determined by biopsy and cytology. Urine samples were collected from patients before and after both BCG and Sunitinib. Urine biomarker levels were measured using a multiplexed bead assay for angiopoietin 2 (AP-2), fibroblast growth factor 2 (FGF-2), interleukin 8 (IL-8), and VEGF-A, -C,...

INTRODUCTION AND OBJECTIVES:MRI-TRUS fusion prostate biopsy(FB), also referred to as “targeted biopsy”, has been shown to improve detection of clinically significant prostate cancer and reduce the ...

Purpose of review Radical treatments for prostate cancer are associated with significant morbidity, including incontinence and erectile dysfunction. Advances in the field of prostate MRI and desire to reduce treatment morbidities have led to a rapid growth in focal treatments for prostate cancer. Here, we review novel focal prostate cancer treatments and their associated recent clinical data, with a particular focus on data reported within the last 24 months. Recent findings High-intensity focal ultrasound, focal laser ablation, irreversible electroporation, focal cryotherapy, and photodynamic therapy have been used as treatment modalities for localized prostate cancer treatment. Despite the great variety of treatment techniques, each of these modalities is characterized by a significant rate of prostate cancer persistence within treatment zones (6-50%) and the presence of residual cancer within the prostate on rebiopsy (24-49%). These treatments, however, are associated with very low rates of high-grade complications, rare incontinence, and only mild or transient reductions in erectile function. The most common adverse events are urinary tract infections, hematuria, and urinary retention. Summary Prostate cancer focal therapy is an attractive option for well-selected patients because of its low complication profile; however, long-term oncologic outcome is still lacking and early recurrence rates are high, limiting the ability of most urologic associations from endorsing its routine use.

INTRODUCTION AND OBJECTIVES:Multiparametric MRI (mpMRI) of the prostate has demonstrated great promise in aiding diagnosis of clinically significant prostate cancer. The Prostate Imaging Reporting ...

Repeat renal surgery is technically demanding with a high morbidity rate. We describe a novel surgical approach, a salvage robotic transmesenteric off-clamp partial nephrectomy for the management of a renal cell carcinoma in a patient with a history of VHL and multiple prior renal surgeries on the affected kidney. Upon pathological review, the specimen was diagnosed as clear cell RCC, Fuhrman Grade 3, with negative surgical margins. The patient suffered no post-operative complications and had a rapid convalescence. This approach is a feasible and safe alternative in select patients with a significant history of renal surgeries and favorable anatomy. Keywords: Partial nephrectomy, Renal cell carcinoma, Robotics, Surgical approach, von Hippel-Lindau

Objective Integrated 6-year cardiothoracic surgical residency programs have recently been implemented in the United States. We report the results of the first published nationwide survey assessing the motivations, satisfaction, and ambitions of integrated 6-year residents. Methods A 63-question web-based survey was distributed to 83 residents enrolled in 21 Accreditation Council for Graduate Medical Education–accredited integrated 6-year programs in November 2013. There was an outstanding 69% response rate. Results The median age of integrated 6-year residents was 29 years with women comprising 24%. A clear majority had faculty mentorship (95%) and significant clinical exposure in medical school. Focused (100%) and abbreviated (74%) training curricula were identified as the top advantages of integrated 6-year programs; the format itself was a significant factor (46%) in career choice. Most integrated 6-year residents (95%) were satisfied with their program; 80.7% were satisfied with their operative experience thus far. Career plans skewed toward adult cardiac surgery (67%), followed by pediatric cardiac (24%) and general thoracic (9%) surgery; 49% were not particularly concerned about future employment, with 65% foreseeing an increase in opportunities. Specialized training (eg, aortic, heart failure, minimally invasive, congenital) was anticipated by 77%. Most integrated 6-year residents envision an academic career (94.7%). Conclusions This survey takes an important snapshot of the nascent integrated 6-year format. Mentorship and intense clinical exposure are critical in attracting applicants. Purported advantages of the format are holding true among integrated 6-year residents, with the majority satisfied with their programs. These early data indicate that this format holds significant promise in attracting and retaining highly qualified trainees to academic cardiothoracic surgery.

While radical cystectomy (RC) with pelvic lymph node dissection (PLND) represents the accepted gold standard for the treatment of muscle-invasive bladder cancer, this treatment approach is associated with significant morbidity. As such, bladder preservation strategies are often utilized in patients who are either deemed medically unfit due to significant comorbidities or whom decline management with RC and PLND secondary to its associated morbidity. In a select group of patients, meeting strict criteria, bladder preservation approaches may be employed with curative intent. Trimodal therapy, consisting of complete transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation therapy has demonstrated durable oncologic control and long-term survival in a number of studies. The review presented here provides a description of trimodal therapy and the role of TURBT in bladder preservation for patients with muscle-invasive bladder cancer.

TNF, signaling through TNFR2, has been implicated in tissue repair, a process that in the heart may be mediated by activated resident cardiac stem cells (CSCs). The objective of our study is to determine whether ligation of TNFR2 can induce activation of resident CSCs in the setting of ischemic cardiac injury. We show that in human cardiac tissue affected by ischemia heart disease (IHD), TNFR2 is expressed on intrinsic CSCs, identified as c-kit+/CD45−/VEGFR2− interstitial round cells, which are activated as determined by entry to cell cycle and expression of Lin-28. Wild-type mouse heart organ cultures subjected to hypoxic conditions both increase cardiac TNF expression and show induced TNFR2 and Lin-28 expression in c-kit+ CSCs that have entered cell cycle. These CSC responses are enhanced by exogenous TNF. TNFR2−/− mouse heart organ cultures subjected to hypoxia increase cardiac TNF but fail to induce CSC activation. Similarly, c-kit+ CSCs isolated from mouse hearts exposed to hypoxia or TNF show induction of Lin-28, TNFR2, cell cycle entry, and cardiogenic marker, α-sarcomeric actin (α-SA), responses more pronounced by hypoxia in combination with TNF. Knockdown of Lin-28 by siRNA results in reduced levels of TNFR2 expression, cell cycle entry, and diminished expression of α-SA. We conclude that hypoxia-induced c-kit+ CSC activation is mediated by TNF/TNFR2/Lin-28 signaling. These observations suggest that TNFR2 signaling in resident c-kit+ CSCs induces cardiac repair, findings which provide further understanding of the unanticipated harmful effects of TNF blockade in human IHD.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice.

Perioperative injuries to an allograft exacerbate graft rejection, which in humans is primarily mediated by effector memory T cells. IL-6 transcripts in human coronary artery segments rapidly increase posttransplantation into immunodeficient mouse hosts compared with those of pretransplant specimens and fall dramatically by 30 d. Adoptive transfer of human PBMCs allogeneic to the artery 2 d postoperatively results in T cell infiltrates and intimal expansion 4 wk later. Ab neutralization of human IL-6 reduces the magnitude of intimal expansion and total T cell infiltration but increases the relative expression of CD161 while decreasing other Th17 markers. Coculture of MHC class II-expressing human endothelial cells (ECs) with allogeneic CD4+ memory T cells results in T cell activation and EC secretion of IL-6. Neutralizing IL-6 in primary allogeneic T cell–EC cocultures results in enhanced T cell proliferation of CD161+ CD4+ T cells, reduces total T cell proliferation upon restimulation in secondary cultures (an effect dependent on CD161+ T cells), increases expression of FOXP3 in CD161+ T cells, and generates T cells that suppress proliferation of freshly isolated T cells. These data suggest that IL-6 released from injured allograft vessels enhances allogeneic T cell infiltration and intimal expansion in a model of human allograft rejection by inhibiting an increase in CD161+ regulatory T cells.

Despite pro-fibrotic effects, transforming growth factor (TGF)-β prevents arteriosclerosis by suppressing effector leukocytes and promoting smooth muscle differentiation. However, previous observations of increased TGF-β expression in arteriosclerotic plaques are not consistent with that of an effective protective factor. We investigated the expression, regulation, and responses of TGF-β in human arterial tissues and cells.The expression of TGF-β by intrinsic vascular cells was lower in arteriosclerotic than non-diseased coronary arteries. Activation of resident and infiltrating leukocytes did not elicit TGF-β production from coronary artery segments in organ culture. Instead, the basal expression of TGF-β by coronary arteries decreased after vessel procurement and ex vivo culture. Activation of cultured smooth muscle cells and endothelial cells with phorbol ester and ionophore also decreased TGF-β expression. Isolated cell types representing those found in the artery wall were all capable of signaling in response to TGF-β, however production of the cytoprotective molecule, interleukin-11 was cell type-dependent and restricted to smooth muscle cells and fibroblasts. Interleukin-11 reduced smooth muscle cell apoptosis to T cell effectors.Inflammation and cellular activation diminish the basal expression of TGF-β by quiescent human vascular cells. Induction of interleukin-11 may contribute to the anti-arteriosclerotic actions of TGF-β.

Small bowel volvulus in the absence of a congenital anomaly is rare but has been described in post-operative patients after abdominal surgery and is usually related to inflammatory conditions. The authors describe an adolescent girl with small bowel volvulus secondary to an oral fiber bolus after laparoscopic appendectomy that required emergency laparotomy and reduction. She subsequently developed early post-operative complete bowel obstruction requiring re-laparotomy and resection.

Importance Locoregional anesthesia, conscious sedation, and exploration via a limited incision have become a well-accepted approach for the treatment of patients with primary hyperparathyroidism with image-localized, presumed single-gland disease. However, to our knowledge, this minimally invasive technique has never been investigated in patients with multigland disease. Objective To extrapolate the technique of locoregional anesthesia, conscious sedation, and exploration via a limited incision to perform minimally invasive bilateral exploration in patients who have multigland hyperplasia. Design, Setting, and Participants Retrospective analysis at a tertiary academic referral center of 100 consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism due to parathyroid hyperplasia between January 19, 2010, and July 30, 2013, who were included in a prospective database. Interventions All patients underwent subtotal parathyroidectomy using either conventional treatment (bilateral neck exploration under general anesthesia) or extended minimally invasive parathyroidectomy (ex-MIP; locoregional anesthesia, conscious sedation, and exploration via a limited incision). Patients in the ex-MIP group who required conversion to general anesthesia were analyzed in the ex-MIP group on an intent-to-treat basis. Main Outcomes and Measures Patient cure and complication rates, length of stay, and total hospital charges. Results Of the 100 consecutive patients with parathyroid hyperplasia, 29 received conventional treatment and 71 underwent ex-MIP. In the ex-MIP group, 11 of 71 patients (15.5%) required conversion to general anesthesia. There were no differences between the ex-MIP and conventional treatment groups in age (mean [SD], 62.2 [12.2] vs 57.7 [15.2] years; P = .12), sex (59 [83.1%] vs 23 [79.3%] female; P = .78), preoperative serum calcium level (mean [SD], 11.1 [0.9] vs 10.8 [0.8] mg/dL; to convert to millimoles per liter, multiply by 0.25; P = .15), preoperative serum parathyroid hormone level (mean [SD], 114.5 [56.8] vs 137.8 [83.4] pg/mL; to convert to nanograms per liter, multiply by 1; P = .10), complications (4 vs 0 complications; P = .32), or cure rates (98.6% vs 96.6%; P = .50). Importantly, the ex-MIP group had a significant reduction in length of stay compared with the conventional treatment group (mean [SD], 1.01 [0.02] vs 1.35 [0.24] days; P = .04). They also had lower total hospital charges, but the difference was not statistically significant (mean, $23 199 vs $27 312; P = .17). Conclusions and Relevance Parathyroidectomy with bilateral neck exploration under general anesthesia has been the standard of care for the treatment of parathyroid hyperplasia. We demonstrate that ex-MIP can provide equivalent cure and complication rates with a shorter hospital stay and a mean hospital charge reduction of more than $4000 per case.

Objective The recently implemented integrated 6-year (I-6) format represents a significant change in cardiothoracic surgical residency training. We report the results of the first nationwide survey assessing I-6 program directors' impressions of this new format. Methods A 28-question web-based survey was distributed to program directors of all 24 Accreditation Council for Graduate Medical Education-accredited I-6 training programs in November 2013. The response rate was a robust 67%. Results Compared with graduates of traditional residencies, most I-6 program directors with enrolled residents believed that their graduates will be better trained (67%), be better prepared for new technological advances (67%), and have superior comprehension of cardiothoracic disease processes (83%). Just as with traditional program graduates, most respondents believed their I-6 graduates would be able to independently perform routine adult cardiac and general thoracic operations (75%) and were equivocal on whether additional specialty training (eg, minimally invasive, heart failure, aortic) was necessary. Most respondents did not believe that less general surgical training disadvantaged I-6 residents in terms of their career (83%); 67% of respondents would have chosen the I-6 format for themselves if given the choice. The greater challenges in training less mature and experienced trainees and vulnerability to attrition were noted as disadvantages of the I-6 format. Most respondents believed that I-6 programs represent a natural evolution toward improved residency training rather than a response to declining interest among medical school graduates. Conclusions High satisfaction rates with the I-6 format were prevalent among I-6 program directors. However, concerns with respect to training relatively less experienced, mature trainees were evident.

Endometriosis is a common disease in women of childbearing age and is defined as the presence of endometrial glands and stroma in organs outside of the uterine cavity. Appendiceal endometriosis is very uncommon and accounts for a small fraction of all cases of extrapelvic endometriosis. Cases of that which occur during pregnancy are extremely rare with an incidence that ranges between 3 and 8 deliveries per 10 000. This makes the diagnosis extremely difficult and represents a challenge in the management of the patient. In this report we describe the case of a pregnant woman who underwent ileocecectomy for perforated appendicitis stemming from endometriosis and subsequent pre-term delivery of a 31-week-old fetus.

Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify β-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure β-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of β-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, β-cell function was preserved (P < 0.05) and the rates of β-cell were reduced significantly (P < 0.05). We conclude that there are higher rates of β-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased β-cell death. © 2013 by the American Diabetes Association.

Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation. The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease (CAD). Using a double-blind placebo wait-list control design, 90 subjects with CAD and vitamin D deficiency (< 20 ng/ml) were randomized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks. Endothelial function (reactive hyperemia peripheral arterial tonometry, RH-PAT), circulating adhesion molecules, and pro-inflammatory cytokines were measured at baseline and 12 weeks. The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group (between-group difference = 22 ng/ml, p < 0.001). The median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and −0.04 ± 0.63 with placebo (between-group difference = 0.17, p = 0.44). Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo (between-group difference = 6 ng/ml, p = 0.048). Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude (median difference between groups = 8.5 ng/ml, p = 0.79). There was no difference between groups in magnitude of reduction in interleukin (IL)-12 (−8.6 ng/ml, p = 0.72) and interferon-gamma (0.52 ng/ml, p = 0.88). No significant differences in blood pressure, e-selectin, high-sensitivity c-reactive protein, IL-6 or the chemokine CXCL-10 were found with treatment. In conclusion, repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health. These results question the role of vitamin D supplementation in modifying cardiovascular disease.

Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)-γ and IL-17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF-β, by regulatory lymphocytes is known to inhibit both the differentiation of naïve T cells into effector T cells and the development of arteriosclerosis in murine models. We investigated the role of TGF-β on the alloreactivity of human effector memory T cells (Tem). Quiescent vascular cells, but not Tem, expressed TGF-β. Blockade of TGF-β activity in cocultures of CD4(+) Tem with allogeneic endothelial cells significantly increased IFN-γ, but not IL-17, secretion. Additionally, serologic neutralization of TGF-β in immunodeficient mouse hosts of human coronary artery grafts into which allogeneic human T cells were adoptively transferred resulted in heavier medial infiltration by Tem, greater loss of medial smooth muscle cells and increased IFN-γ production within the grafts without significantly reducing either intimal injury or IL-17 production. Protective effects of TGF-β may be limited by fewer TGF-β-expressing vascular cells within the intimal compartment, by a reduction in the expression of TGF-β by vascular cells in rejecting grafts, or possibly to less effective suppression of Tem than naïve T cells.