Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

The Influence of Patient Exposure to Breast Reconstruction Approaches and Education on Patient Choices in Breast Cancer Treatment.

BACKGROUND: The landscape of surgical and medical management and patient choices for breast cancer treatment changes as breast reconstruction and oncoplastic approaches improve and diversify. Increased access to breast reconstruction, in addition to patient education, influences the breast cancer patient. Therefore, the examination of the possible impact of reconstructive surgery on all stages of the breast cancer management per se seemed timely. METHODS: Plastic surgery consults were arranged for 520 new patients diagnosed with breast cancer (2012-2016) including patients with noninvasive breast cancer but at high risk of further cancer development. To test the plastic surgery impact on patient choices regarding the management of the cancer, a subset of 90 patients was identified to test the plastic surgery impact on patient choices. These patients were referred to plastic surgery, following the first round of consultations by surgical and medical oncologists with only the preliminary oncological management plan defined. After a plastic surgery consultation, but prior to finalization of the overall oncological management plan, they were surveyed on the subject of modification of their personal choices and requests pertaining to their cancer management. RESULTS: In this subset of 90 patients 40 (44%) returned to their surgical or medical oncologist considering changes of the primary management plan after their plastic surgery consultation. Twenty-six (28%) ultimately altered their plan, and the following patient-driven changes were made: mastectomy as opposed to lumpectomy (18 patients [20%]), contralateral prophylactic mastectomy (11 patients [12%]), nipple/areola removal as opposed to nipple/areola sparing suggested by the oncologists (5 patients [6%]), oncoplastic breast reduction as part of lumpectomy (5 patients [6%]), and other modifications (3 patients [3%]). CONCLUSIONS: Decisions for altering the preliminary oncologic plan or choosing a specific alternative (eg, lumpectomy plus radiation vs mastectomy) resulted from patient education on (1) reconstructive options, (2) aesthetic pitfalls and results. and (3) their interfacing with the oncological outcomes. Ultimately, plastic surgeons influence the multispecialty breast cancer management and patient decision-making process. Therefore, oncological literacy for plastic surgeons is essential to provide state-of-the-art breast cancer care and avoidance of suboptimal patient decisions.

The Cost to Attending Surgeons of Resident Involvement in Academic Hand Surgery.

PURPOSE: For many types of surgical cases, there is an increase in length with the participation of a resident physician. The lost operative time productivity is not necessarily mitigated in any fashion other than to benefit the experience of the trainee. Moreover, increasing pressures to maximize productivity, coupled with diminishing reimbursements serve to disincentive resident involvement. The aim of this study was to examine the opportunity cost in the academic setting for intraoperative resident participation during specific hand surgery cases. METHODS: Retrospective analysis was performed on the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database from 2006 to 2015. Cases were identified by Current Procedural Terminology code to isolate distal radius fracture repairs, carpal tunnel releases, scaphoid fractures repairs, and metacarpal fracture repairs. Variables collected included operation time, presence or absence of resident physician, and postgraduate year level. Statistical analysis was performed using the statistical computing software R 3.4.2 (R Foundation for Statistical Computing, Vienna, Austria). Cost analysis was performed to quantify the effect of operative times in terms of relative value units (RVUs) lost. RESULTS: A total of 3727 cases were identified. Of those, 1264 cases were performed with a resident present. Residents participated in cases with higher total RVU (14.91 vs 13.16, P < 0.001). There was a statistically significant increase of 24.3 minutes (P < 0.001) in the mean operation time with a resident present as compared with those without. Moreover, RVU per hour in resident cases was significantly lower by 2.97 RVU per hour or 21% (P < 0.001). Using the late 2018 Medicare physician conversion factor of US $33.9996, the opportunity cost to attending physicians is US $159.20 per case. CONCLUSIONS: Resident participation in surgical cases is paramount to the education of future trainees, particularly in the era of trainee duty hour reform. Because residents are participating in higher total RVU cases, this selection bias may be playing a role in explaining our result. Nonetheless, resident involvement for certain procedures comes at an opportunity cost to faculty surgeons. How to balance the cost to train residents in the emerging value-based health systems will prove to be challenging but requires consideration.

Free functional muscle transfer for lower extremity reconstruction.

BACKGROUND: Free functional muscle transfer is a reconstructive strategy for the reconstruction of lost muscle units in the lower extremity after oncologic resection, trauma, compartment syndrome, or severe nerve injuries. Under appropriate circumstances, free functional muscle transfer may be the only suitable reconstructive option. This article reviews the underlying principles of free functional muscle transfer, its application to lower extremity reconstruction, appropriate patient selection, and surgical techniques. METHODS: The underlying principles of free functional muscle transfer, its application to lower extremity reconstruction, appropriate patient selection, and surgical techniques are presented. Commonly used donor muscles appropriate for each type of functional defect are discussed. A review of recent publications on free functional muscle transfer in the lower extremity was also performed. RESULTS: Good functional recovery with a Medical Research Council grade of up to 4/5 and full range of motion can be attained with free functional muscle transfer. Clinical outcomes and specific parameters for published case series in lower extremity free functional muscle transfer are presented and an illustrative case. CONCLUSION: Free functional muscle transfer is a suitable treatment for the appropriate patient to restore essential functions and potentially regain ambulation. However, additional published clinical outcomes are needed and represent a major area for further investigation.

The SIEA SHRIMP Flap: An Ultrathin Axial Pattern Free Flap Useable in Obese Patients.

The reconstruction of distal extremity wounds poses a unique surgical challenge. In free tissue transfer, a thin, pliable skin flap is the ideal. Obese patients have a paucity of thin skin donor sites. Herein we report the discovery of a free SHRIMP flap (Superthin Harvest of a Reliable Islanded Medial Pannus flap) based on the SIEA vessels, harvested from a thick abdominal pannus at the time of cosmetic abdominoplasty. A 61-year-old woman with a chronic wound of the right Achilles tendon was evaluated for reconstruction after failing conservative measures. At the time of consultation, the patient expressed interest in abdominoplasty. Therefore, a skin flap from the abdomen or rectus abdominis muscle flap in the context of an abdominoplasty was offered. Despite obesity affecting the pannus, the superficial inferior epigastric vessels were found to course superficially beneath the dermis at time of abdominoplasty. This allowed straightforward harvest of a superthin flap of skin and minimal subcutaneous fat, which contoured to the ankle with an aesthetically pleasing outcome. The patient was satisfied with the results of her abdominoplasty and coverage of her chronic wound. The SHRIMP flap provides a straightforward, axial pattern, superthin free skin flap based on the superficial inferior epigastric vessels, and represents a useful option in obese patients. The flap can be combined with abdominoplasty for an aesthetic donor site.