Vascular changes in vascularized composite allotransplantation.

PURPOSE OF REVIEW: Allograft vasculopathy in vascularized composite allografts (VCA) remains understudied. This review explores the vascular changes in VCA, focused on recent literature. RECENT FINDINGS: Allograft vasculopathy in VCA generally includes progressive concentric myointimal thickening and luminal narrowing of arterial vessels through endothelial deterioration and proliferation of smooth muscle cells. Microvascular changes are also noted, with thrombosis and lumen narrowing in microvessels of the skin even in the absence of large vessel vasculopathy. Histopathologic reports of skin containing VCA rejection document arteriosclerosis in deep vessels that are not always reflected in skin punch biopsies. The first revision of the Banff VCA scoring system 2022 was developed to include vascular changes in VCA. The scoring system for chronic changes and antibody mediated rejection continues to be under development. SUMMARY: The study of vascular changes in VCA continues to progress. Important data and advances in experimental and clinical VCA have been reported and continue to take place. Challenges ahead include capture of clinical data that will evolve beyond transient report forms and approaching on the problem of graft failure well grounded in sound scientific methodology.

Developing a Dedicated Leadership Curriculum for Radiation Oncology Residents.

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019. Prior to the curriculum, current and past residents in our institution's RO residency program were surveyed on their attitudes towards leadership in healthcare, emotional intelligence competencies, and leadership training interests. After the completion of the LDC, a post-curriculum survey was forwarded to current residents. The response rate was 84% (21 of 24) for the baseline survey and 90% (9 of 10) for the post-curriculum survey. Having a leadership training curriculum during residency was rated as extremely useful, with top training interests involving leading clinical teams, effective communication strategies, and conflict management. After the LDC, the residents reported high satisfaction with the curriculum and utilization of leadership training into their daily work. Our LDC demonstrates significant potential to engage trainees and improve their leadership skills at the graduate medical education level.

Colorectal Cancer Risk Factors and Screening Among the Uninsured of Tampa Bay: A Free Clinic Study.

INTRODUCTION: Uninsured patients with low socioeconomic status are at high risk for developing colorectal cancer (CRC), and data on risk factors and prevalence of CRC in this population are limited. The purpose of this study was to assess the risk factors for CRC in uninsured patients from free clinics in the Tampa Bay area of Florida. METHODS: We conducted a retrospective cohort study among patients 50 years or older who were provided service at 9 free clinics in the Tampa Bay area between 2016 and 2018. Demographics, chronic disease characteristics, and screening data were collected via a query of paper and electronic medical records. RESULTS: Of the 13,982 patients seen, 5,139 (36.8%) were aged 50 years or older. Most were female (56.8%), non-Hispanic White (41.1%), and unemployed (54.9%). Patients with CRC screening were more likely to be employed compared with patients without CRC screening (54.4% vs 44.4%, P = .01). Within the cohort, 725 (22.7%) patients were active smokers, 771 (29.2%) patients currently consumed alcohol, and 23 patients (0.4%) had a history of inflammatory bowel disease. Patients had a median body mass index of 29.4 (interquartile range, 25.4-34.2) kg/m2, and 1,455 (28.3%) had diabetes. Documented CRC screening was found among 341 (6.6%) patients. CONCLUSION: Uninsured patients had a high prevalence of CRC risk factors but a low reported screening rate for CRC. Free clinics are uniquely positioned to provide patients at high risk for CRC with strategies to decrease their risk and to be screened for CRC.

Clinical Factors and Outcomes of Octogenarians Receiving Curative Surgery for Esophageal Cancer.

BACKGROUND: The incidence of esophageal cancer is increasing in the United States. Although neoadjuvant therapy (NAT) for locally advanced cancers followed by surgical resection is the standard of care, there are no clearly defined guidelines for patients aged ≥79 y. METHODS: Query of an institutional review board-approved database of 1031 esophagectomies at our institution revealed 35 patients aged ≥79 y from 1999 to 2017 who underwent esophagectomy. Age, gender, tumor location, histology, clinical stage, Charlson Comorbidity Index (CCI), NAT administration, pathologic response rate to NAT, surgery type, negative margin resection status, postoperative complications, postoperative death, length of stay, 30- and 90-d mortality, and disease status parameters were analyzed in association with clinical outcome. RESULTS: The median age of the octogenarian cohort was 82.1 y with a male preponderance (91.4%). American Joint Committee on Cancer clinical staging was stage I for 20% of patients, stage II for 27% of patients, and stage III for 50% of patients, which was not statistically significant compared with the younger cohort (P = 0.576). Within the octogenarian group, 54% received NAT compared with 67% in the younger group (P = 0.098). There was no difference in postoperative complications (P = 0.424), postoperative death (P = 0.312), and recurrence rate (P = 0.434) between the groups. However, CCI was significantly different between the octogenarian and nonoctogenarian cohort (P = 0.008), and octogenarians had shorter overall survival (18 versus 62 mo, P<0.001). None of the other parameters assessed were associated with clinical outcomes. CONCLUSIONS: Curative surgery is viable and safe for octogenarians with esophageal cancer. Long-term survival was significantly shorter in the octogenarian group, suggesting the need for better clinical selection criteria for esophagectomy after chemoradiation and that identification of complete responders for nonoperative management is warranted.

The Use of Nitinol Staples as Reduction Aids in Fixation of Forearm Diaphyseal Fractures: Surgical Technique and Case Series.

Forearm diaphyseal fractures are common orthopedic injuries that typically require surgical intervention using various implants and approaches. Maintaining reduction while simultaneously achieving compression in radial and/or ulnar shaft fractures during compression plate application can be challenging, particularly with unstable segmental and/or transverse fracture patterns. Nitinol compression staples have become increasingly used as a reduction aid because of their ability to provide continuous compression between the staple legs at the fracture site, low profile, and ease of application. These staples have the potential to be an effective means of maintaining reduction and applying compression before definitive plate fixation for radial and ulnar shaft fractures. We present our surgical technique and an associated patient series detailing our institution's experience, highlighting favorable outcomes and potential considerations when using nitinol compression staples for forearm fracture management.

New Frontiers of Natural Language Processing in Surgery.

The vast and ever-growing volume of electronic health records (EHR) have generated a wealth of information-rich data. Traditional, non-machine learning data extraction techniques are error-prone and laborious, hindering the analytical potential of these massive data sources. Equipped with natural language processing (NLP) tools, surgeons are better able to automate, and customize their review to investigate and implement surgical solutions. We identify current perioperative applications of NLP algorithms as well as research limitations and future avenues to outline the impact and potential of this technology for progressing surgical innovation.

Ethical, Legal, and Financial Considerations of Artificial Intelligence in Surgery.

Machine learning systems have become integrated into some of the most vital decision-making aspects of humanity, including hiring decisions, loan applications, and automobile safety, to name just a few. As applications increase in both gravity and complexity, the data quality and algorithmic interpretability of the systems must rise to meet those challenges. This is especially vital for navigating the nuances of health care, particularly among the high stakes of surgical operations. In addition to inherent ethical challenges of enabling a "black box" system to influence decision-making in patient care, the creation of biased datasets leads to biased algorithms with the power to perpetuate discrimination and reinforce disparities. Transparency and responsibility are paramount to the implementation of artificial intelligence in surgical decision-making and autonomous robotic surgery. Machine learning has been permeating health care across diverse clinical and surgical contexts but continues to face sizable obstacles, including apprehension from patients and providers alike. To integrate the technology fully while upholding standard of care and patient-provider trust, one must acknowledge and address the ethical, financial, and legal implications of using artificial intelligence for patient care.

Isolated Scaphoid Dislocation From Low-Energy Wrist Trauma.

Isolated scaphoid dislocation is an extremely rare injury typically caused by high-energy trauma. We present the first observed case of isolated scaphoid dislocation resulting from a non-traumatic injury of the wrist in power-grip tension in a patient with a questionable history of Marfan Syndrome. A 20-year-old right-hand dominant man presented to the emergency department with right wrist pain and deformation after carrying a table. The patient reported a possible history of Marfan Syndrome, but it had never been definitively diagnosed. Imaging revealed radial dislocation of the scaphoid. Bedside closed reduction was performed followed by outpatient ligament reconstruction with return to normal activities at 6 months. Early diagnosis and management lead to an improved prognosis for isolated scaphoid dislocation. Regardless of patient history or mechanism of injury, treatment options include closed reduction, percutaneous fixation, and/or open reduction with internal fixation and ligamentous reconstruction.

Pretreatment CT and 18 F-FDG PET-based radiomic model predicting pathological complete response and loco-regional control following neoadjuvant chemoradiation in oesophageal cancer.

INTRODUCTION: To develop a radiomic-based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer. METHODS: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in-house data-chjmirocterization algorithm was used to extract 3D-radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, Fc  = α * FPET  + (1 - α) * FCT , 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco-regional control (LRC), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis, and compared using log-rank test. RESULTS: Median follow-up was 59 months. pCR was achieved in 34 (50%) patients. Five-year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0-1 indicative of complete response or minimal residual disease was significantly associated with improved 5-year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04-0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5-year LRC favouring low-score group (91.1% vs. 80%, 95% CI 0.09-1.77, P = 0.2). CONCLUSION: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes.

Cutaneous Carcinosarcoma: A Small Case Series and Review of the Literature of a Rare Skin Tumor.

Carcinosarcomas are composed of epithelial and mesenchymal elements and primarily present within visceral organs. Despite being potentially aggressive, they are a rare diagnosis in the skin, and few manifestations have been reported to date. In this report, we describe two separate cases of carcinosarcoma presenting as nonhealing scalp wounds. Patient A: a 57-year-old male with a nonhealing skin lesion of ten years successfully treated with wide-local excision and local ortichochea flap reconstruction. Patient B: a 75-year-old female that presented with a painless, slow-growing hemorrhagic mass of 7 years invading the skull and dura ultimately requiring craniectomy and free-tissue transfer with anterolateral thigh flap. Cutaneous carcinosarcomas have more favorable outcomes due to low metastatic rates likely due to earlier detection, but delayed presentation can be fatal. Histopathological analysis is critical for determining diagnosis and prognosis. Adequate reconstruction after wide base excision varies and follows the reconstructive ladder/elevator ranging from primary closure up through free-tissue transfer. With cutaneous manifestations of carcinosarcoma seldom reported in the literature, it is our hope that reporting unusual instances such as this will raise awareness and allow for earlier diagnoses, treatments, and reconstructions.

Pyoderma Gangrenosum after Fat Grafting in Alloplastic Breast Reconstruction: An Unusual Outcome.

Pyoderma gangrenosum (PG) is a rare and painful inflammatory skin disorder that has been recently associated with breast surgery. It is commonly mistaken for postoperative ischemia or wound infection and does not show response to antibiotics or debridement. We describe the first case of post-surgical PG (PSPG) after alloplastic breast reconstruction involving fat grafting. A 47-year-old woman underwent bilateral mastectomy and 2-stage alloplastic breast reconstruction, with fat grafting from the abdomen. Two days post-surgery, she developed bilateral erythema with tender grouped pustules that progressed rapidly into necrotic ulcerations. She did not respond to antibiotics and serial debridement. Subsequent biopsy confirmed a diagnosis of PG. She was started on steroid therapy and responded well. She was discharged on a steroid regimen, local wound care, and eventually a T-cell inhibitor. Over the next 12 months, her wounds healed without surgical intervention. PSPG has been observed in a variety of reconstructive breast surgeries, but never reported in the setting of fat grafting. As PG involves subcutaneous fat, fat grafting may accelerate and exacerbate the course of disease. Treatment for PSPG includes systemic steroid therapy or other immunomodulatory agents (or both). Surgical management remains controversial, as serial debridement and reconstruction have shown to exacerbate and stimulate disease progression. A long-term follow-up is recommended to monitor for wound healing. Delayed diagnosis of PG in breast reconstruction patients can lead to severe morbidity and disfigurement. This is first case of PSPG following fat grafting in the literature.

Clinical factors associated with the development of postoperative atrial fibrillation in esophageal cancer patients receiving multimodality therapy before surgery.

BACKGROUND: The incidence of esophageal cancer (EC) is increasing in the USA. Neoadjuvant therapy for locally advanced cancers followed by surgical resection is the standard of care. The most common post-esophagectomy cardiac complication is atrial fibrillation (AF). New-onset postoperative AF can require a prolonged hospital stay and may confer an overall poorer prognosis. In this study, we seek to identify clinical factors associated with postoperative AF. METHODS: Query of an IRB approved database of 1,039 esophagectomies at our institution revealed 677 patients with EC from 1999 to 2017 who underwent esophagectomy after neoadjuvant treatment. Age, treatment location (primary vs. other), gender, neoadjuvant radiation type [2D vs. 3D vs. intensity modulated radiation therapy (IMRT)], radiation dose, surgery type (transthoracic vs. transhiatal vs. three field), smoking history, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), operative time, blood transfusions, fluid management, and length of stay (LOS) were analyzed in relationship to the development of AF. Statistical analysis was performed with SPSS 24. RESULTS: The mean age of the entire cohort was 64.3 (range, 28-86 years), with a Caucasian and male preponderance (White: 94.5%; male: 83.6%). Of the 677 patients, 14.9% (n=101) developed postoperative AF. Increasing age (P<0.001), increased radiation dose (P=0.034), operative time (P=0.001), and blood transfusions (P=0.027) were associated with AF. LOS was longer in patients with AF than those without AF (10.5 vs. 10.0 days, P=0.001). On multivariate analysis, increasing age (95% CI: 1.023-1.080, P<0.001) and radiation dose (95% CI: 1.000-1.001, P=0.034) remained significant. None of the other parameters assessed were associated with the development of AF. CONCLUSIONS: Increasing age and radiation dose were associated with the development of postoperative AF in this cohort. This study suggests that older patients or patients receiving higher radiation dose should be monitored more closely in the postoperative setting and potentially referred earlier preoperatively for cardio-oncology assessment. Future study is required to determine if modification of current radiation techniques and cardiac dose constraints in this patient population may be warranted.

AMPK Activation and Metabolic Reprogramming by Tamoxifen through Estrogen Receptor-Independent Mechanisms Suggests New Uses for This Therapeutic Modality in Cancer Treatment.

Tamoxifen is the most widely used adjuvant chemotherapeutic for the treatment of estrogen receptor (ER)-positive breast cancer, yet a large body of clinical and preclinical data indicates that tamoxifen can modulate multiple cellular processes independently of ER status. Here, we describe the ER-independent effects of tamoxifen on tumor metabolism. Using combined pharmacologic and genetic knockout approaches, we demonstrate that tamoxifen inhibits oxygen consumption via inhibition of mitochondrial complex I, resulting in an increase in the AMP/ATP ratio and activation of the AMP-activated protein kinase (AMPK) signaling pathway in vitro and in vivo AMPK in turn promotes glycolysis and alters fatty acid metabolism. We also show that tamoxifen-induced cytotoxicity is modulated by isoform-specific effects of AMPK signaling, in which AMPKα1 promotes cell death through inhibition of the mTOR pathway and translation. By using agents that concurrently target distinct adaptive responses to tamoxifen-mediated metabolic reprogramming, we demonstrate increased cytotoxicity through synergistic therapeutic approaches. Our results demonstrate novel metabolic perturbations by tamoxifen in tumor cells, which can be exploited to expand the therapeutic potential of tamoxifen treatment beyond ER(+) breast cancer. Cancer Res; 76(11); 3295-306. ©2016 AACR.