Umbilical Fascial Defects are Common and Predict Trocar Site Hernias After Laparoscopic Appendectomy.

INTRODUCTION: Investigations have demonstrated that trocar site hernia (TSH) is an under-appreciated complication of laparoscopic surgery, occurring in as many as 31%. We determined the incidence of fascial defects prior to laparoscopic appendectomy and its impact relative to other risk factors upon the development of TSH. METHODS: TSH was defined as a fascial separation of ≥ 1 cm in the abdominal wall umbilical region on abdominal computerized tomography scan (CT) following laparoscopic appendectomy. Patients admitted to our medical center who had both a preoperative CT and postoperative CT for any reason (greater than 30 days after surgery) were reviewed for the presence of TSH from May 2010 to December 2018. CT scans were measured for fascial defects, while investigators were blinded to film timing (preoperative or postoperative) and patient identity. Demographic information was collected. RESULTS: 241 patients undergoing laparoscopic appendectomy had both preoperative and late postoperative CT. TSH was identified in 49 (20.3%) patients. Mean preoperative fascial gap was 3.3 ± 4.3 mm in those not developing a postoperative hernia versus 14.8 ± 7.3 mm in those with a postoperative hernia (P < .0001). Preoperative fascial defect on CT was predictive of TSH (P < .001, OR = 1.44), with an Area Under the Curve (AUC) of .921 (95%CI: .88-.92). Other major risk factors for TSH were: age greater than 59 years (P < .031, OR = 2.48); and obesity, BMI > 30 (P < .012, OR = 2.14). CONCLUSIONS: The incidence of trocar site hernia was one in five following laparoscopic appendectomy. The presence of a pre-existing fascial defect, advanced age, and obesity were strong predictors for the development of trocar site hernia.

Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial.

BACKGROUND: Availability of checkpoint inhibitors has created a paradigm shift in the management of patients with solid tumors. Despite this, most patients do not respond to immunotherapy, and there is considerable interest in developing combination therapies to improve response rates and outcomes. B7-H3 (CD276) is a member of the B7 family of cell surface molecules and provides an alternative immune checkpoint molecule to therapeutically target alone or in combination with programmed cell death-1 (PD-1)-targeted therapies. Enoblituzumab, an investigational anti-B7-H3 humanized monoclonal antibody, incorporates an immunoglobulin G1 fragment crystallizable (Fc) domain that enhances Fcγ receptor-mediated antibody-dependent cellular cytotoxicity. Coordinated engagement of innate and adaptive immunity by targeting distinct members of the B7 family (B7-H3 and PD-1) is hypothesized to provide greater antitumor activity than either agent alone. METHODS: In this phase I/II study, patients received intravenous enoblituzumab (3-15 mg/kg) weekly plus intravenous pembrolizumab (2 mg/kg) every 3 weeks during dose-escalation and cohort expansion. Expansion cohorts included non-small cell lung cancer (NSCLC; checkpoint inhibitor [CPI]-naïve and post-CPI, programmed death-ligand 1 [PD-L1] <1%), head and neck squamous cell carcinoma (HNSCC; CPI-naïve), urothelial cancer (post-CPI), and melanoma (post-CPI). Disease was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 after 6 weeks and every 9 weeks thereafter. Safety and pharmacokinetic data were provided for all enrolled patients; efficacy data focused on HNSCC and NSCLC cohorts. RESULTS: Overall, 133 patients were enrolled and received ≥1 dose of study treatment. The maximum tolerated dose of enoblituzumab with pembrolizumab at 2 mg/kg was not reached. Intravenous enoblituzumab (15 mg/kg) every 3 weeks plus pembrolizumab (2 mg/kg) every 3 weeks was recommended for phase II evaluation. Treatment-related adverse events occurred in 116 patients (87.2%) and were grade ≥3 in 28.6%. One treatment-related death occurred (pneumonitis). Objective responses occurred in 6 of 18 (33.3% [95% CI 13.3 to 59.0]) patients with CPI-naïve HNSCC and in 5 of 14 (35.7% [95% CI 12.8 to 64.9]) patients with CPI-naïve NSCLC. CONCLUSIONS: Checkpoint targeting with enoblituzumab and pembrolizumab demonstrated acceptable safety and antitumor activity in patients with CPI-naïve HNSCC and NSCLC. TRIAL REGISTRATION NUMBER: NCT02475213.

A Statewide Quality Improvement Collaborative's Adherence to the 2017 American Urological Association Guidelines Regarding Initial Evaluation of Patients With Clinical T1 Renal Masses.

OBJECTIVE: To evaluate MUSIC-KIDNEY's adherence to the American Urological Association (AUA) guidelines regarding the initial evaluation of patient's with clinical T1 (cT1) renal masses. METHODS: We reviewed MUSIC-KIDNEY registry data for patients with newly diagnosed cT1 renal masses to assess for adherence with the 2017 AUA guideline statements regarding recommendations to obtain (1) CMP, (2) CBC, (3) UA, (4) abdominal cross-sectional imaging, and (5) chest imaging. An evaluation consisting of all 5 guideline measures was considered "complete compliance." Variation with guideline adherence was assessed by contributing practice, management strategy, and renal mass size. RESULTS: We identified 1808 patients with cT1 renal masses in the MUSIC-KIDNEY registry, of which 30% met the definition of complete compliance. Most patients received care that was compliant with recommendations to obtain laboratory testing with 1448 (80%), 1545 (85%), and 1472 (81%) patients obtaining a CMP, CBC, and UA respectively. Only 862 (48%) patients underwent chest imaging. Significant variation exists in complete guideline compliance for contributing practices, ranging from 0% to 45% as well as for patients which underwent immediate intervention compared with initial observation (37% vs 23%) and patients with cT1b masses compared with cT1a masses (36% vs 28%). CONCLUSION: Complete guideline compliance in the initial evaluation of patients with cT1 renal masses is poor, which is mainly driven by omission of chest imaging. Significant variation in guideline adherence is seen across practices, as well as patients undergoing an intervention vs observation, and cT1a vs cT1b masses. There are ample quality improvement opportunities to increase adherence and decrease variability with guideline recommendations.

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner. In vitro, MGD019 mediates the combinatorial blockade of PD-1 and CTLA-4, confirming dual inhibition via a single molecule. MGD019 is well tolerated in non-human primates, with evidence of both PD-1 and CTLA-4 blockade, including increases in Ki67+CD8 and ICOS+CD4 T cells, respectively. In the ongoing MGD019 first-in-human study enrolling patients with advanced solid tumors (NCT03761017), an analysis undertaken following the dose escalation phase revealed acceptable safety, pharmacodynamic evidence of combinatorial blockade, and objective responses in multiple tumor types typically unresponsive to checkpoint inhibitor therapy.

Optimizing the management of castration-resistant prostate cancer patients: A practical guide for clinicians.

BACKGROUND: Advanced prostate cancer (PC) patients, especially those with metastatic prostate cancer (mPC), often require complex management pathways. Despite the publication of clinical practice guidelines by leading urological and oncological organizations that provide a substantial and comprehensive framework, there are numerous clinical scenarios that are not always addressed, especially as new treatments become available, new imaging modalities are developed, and advances in genetic testing continue. METHODS: A 14-member expert review panel comprised of urologists and medical oncologists were chosen to provide guidance on addressing specific topics and issues regarding metastatic castration-resistant prostate cancer (mCRPC) patients. Panel members were chosen based upon their experience and expertise in the management of PC patients. Four academic members (two urologists and two medical oncologists) of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association (LUGPA) practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, each assigned a specific mCRPC topic to review and discuss with the entire panel. RESULTS: This article describes the practical recommendations of an expert panel on the management of mCRPC patients. The target reading audience for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting. CONCLUSION: The panel has provided recommendations for managing mCRPC with regard to specific issues: (a) biomarker monitoring and the role of genetic and molecular testing; (b) rationale, current strategies, and optimal sequencing of the various approved therapies, including hormonal therapy, cytotoxic chemotherapy, radiopharmaceuticals and immunotherapy; (c) adverse event management and monitoring; and (d) imaging advanced PC patients. These recommendations seek to complement national guidelines, not replace them, and a discussion of where the panel agreed or disagreed with national guidelines is included.

Development of a Novel Scoring System Quantifies Opportunities to Reduce Surgery for Benign Renal Neoplasms: A Retrospective Quality Improvement Analysis within the MUSIC-KIDNEY Collaborative.

PURPOSE: Nonmalignant pathology has been reported in 15% to 20% of surgeries for cT1 renal masses. We seek to identify opportunities for improvement in avoiding surgery for nonmalignant pathology. MATERIALS AND METHODS: MUSIC-KIDNEY started collecting data in 2017. All patients with cT1 renal masses who had partial or radical nephrectomy for nonmalignant pathology were identified. Category for improvement (none-0, minor-1, moderate-2 or major-3) was independently assigned to each case by 5 experienced kidney surgeons. Specific strategies to decrease nonmalignant pathology were identified. RESULTS: Of 1,392 patients with cT1 renal masses 653 underwent surgery and 74 had nonmalignant pathology (11%). Of these, 23 (31%) cases were cT1b. Radical nephrectomy was performed in 17 (22.9%) patients for 5 cT1a and 12 cT1b lesions. Only 6 patients had a biopsy prior to surgery (5 oncocytoma, 1 unclassified renal cell carcinoma). Review identified 25 cases with minor (34%), 26 with moderate (35%) and 10 with major (14%) quality improvement opportunities. Overall 17% of cases had no quality improvement opportunities identified (12 partial nephrectomy, 1 radical nephrectomy). CONCLUSIONS: Review of patients with cT1 renal masses who underwent surgery for nonmalignant pathology revealed a significant number of cases in which this outcome may have been avoided. Approximately half of cases had moderate or major quality improvement opportunities, with radical nephrectomy for nonmalignant pathology being the most common reason. Our data indicate a lowest achievable and acceptable rate of nonmalignant pathology to be 1.9% and 5.4%, respectively. Avoiding interventions for nonmalignant pathology, particularly radical nephrectomy, is an important focus of quality improvement efforts. Strategies to decrease unnecessary interventions for nonmalignant pathology include greater use of repeat imaging, renal mass biopsy and surveillance.

Putting a halt to unnecessary transfers: Do patients with isolated subarachnoid hemorrhage and Glasgow Coma Scale of 13 to 15 need a trauma center?

OBJECTIVES: Trauma patients with isolated subarachnoid hemorrhage (iSAH) presenting to nontrauma centers are typically transferred to an institution with neurosurgical availability. However, recent studies suggest that iSAH is a benign clinical entity with an excellent prognosis. This investigation aims to evaluate the neurosurgical outcomes of traumatic iSAH with Glasgow Coma Scale (GCS) of 13 to 15 who were transferred to a higher level of care. METHODS: The American College of Surgeon Trauma Quality Improvement Program was retrospectively analyzed from 2010 to 2015 for transferred patients 16 years and older with blunt trauma, iSAH, and GCS of 13 or greater. Those with any other body region Abbreviated Injury Scale of 3 or greater, positive or unknown alcohol/drug status, and requiring mechanical ventilation were excluded. The primary outcome was need for neurosurgical intervention (i.e., intracranial monitor or craniotomy/craniectomy). RESULTS: A total of 11,380 patients with blunt trauma, iSAH, and GCS of 13 to 15 were transferred to an American College of Surgeon level I/II from 2010 to 2015. These patients were 65 years and older (median, 72 [interquartile range (IQR), 59-81]) and white (83%) and had one or more comorbidities (72%). Eighteen percent reported a bleeding diathesis/chronic anticoagulation on admission. Most patients had fallen (80%), had a GCS of 15 (84%), and were mildly injured (median Injury Severity Score, 9 [IQR, 5-14]). Only 1.7% required neurosurgical intervention with 55% of patients being admitted to the intensive care unit for a median of 2 days (IQR, 1-3 days). Furthermore, 2.2% of the patients died. The median hospital length of stay was only 3 days (IQR, 2-5 days), and the most common discharge location was home with self-care (62%). Patient factors favoring neurosurgical intervention included high Injury Severity Score, low GCS, and chronic anticoagulation. CONCLUSION: Trauma patients transferred for iSAH with GCS of 13 to 15 are at very low risk for requiring neurosurgical intervention. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

Clinical outcomes in men with prostate cancer who selected active surveillance using a clinical cell cycle risk score.

Aim: To evaluate active surveillance (AS) selection, safety and durability among men with low-risk prostate cancer assessed using the clinical cell cycle risk (CCR) score, a combined clinical and molecular score. Patients & methods: Initial treatment selection (AS vs treatment) and duration of AS were evaluated for men with low-risk prostate cancer according to the CCR score and National Comprehensive Cancer Network guidelines. Adverse events included biochemical recurrence and metastasis. Results: 82.4% (547/664) of men initially selected AS (median follow-up: 2.2 years), 0.4% (2/547) of whom experienced an adverse event. Two-thirds of patients remained on AS for more than 3 years; patient choice was the most common reason for leaving AS. Conclusion: The CCR score may aid in the identification of men who can safely defer prostate cancer treatment.

Severe anemia may not be a contraindication to debridement in a Jehovah's witness patient with necrotizng fasciitis of the lower extremity - A case report.

INTRODUCTION: Necrotizing fasciitis is a severe soft tissue infection characterized by rapidly progressing necrosis involving the fascia and subcutaneous tissue. Necrotizing fasciitis of the lower extremity in a Jehovah's Witness patient in the setting of severe anemia and systemic sepsis is uncommon. CASE PRESENTATION: A 62-year-old man of Jehovah's Witness faith with a history of alcohol use disorder and uncontrolled diabetes mellitus initially presented with a non-healing diabetic foot ulcer, subsequently developed sepsis and necrotizing fasciitis. He underwent an above the knee amputation and was transferred to our institution's Surgical Intensive Care Unit for further management. The patient presented in critical condition with a hemoglobin of 4.7 g/dL and progression of necrotizing fasciitis of the lower extremity stump. He underwent revision amputation and numerous excisional debridements along with IV antibiotics, epoetin alfa, and iron sucrose. He successfully recovered with minimal blood loss and was discharged with a hemoglobin of 8 g/dL. DISCUSSION: This case highlights some of the challenges involved in managing necrotizing fasciitis. The conversation with the Jehovah's Witness patient in a life-threatening condition must be held with the upmost respect. Surgical decision making and operative technique is critical in determining the boundary of excisional debridement to perform in the absence of the ability to transfuse blood. The medical management was focused on resuscitation for sepsis, severe anemia, hyperglycemia, and wound management. CONCLUSION: Severely anemic patients in critical condition can survive necrotizing fasciitis with a well-planned interdisciplinary approach without compromising patient autonomy.