11017 Background: Most GISTs are driven by mutations in KIT and PDGFRa and secondary mutations are felt to confer resistance to TKIs. In advanced/metastatic GIST, the benefit of second line TKIs and beyond is progressively less after imatinib failure. As such, novel non-TKI approaches are important to explore. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST refractory to at least imatinib were enrolled on a randomized, parallel group, unblinded Phase 2 trial of either nivo (240 mg Q2wks) or nivo (240 mg Q2wks) with ipi (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate(ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Imaging was assessed by investigator and 3 independent radiologists. Patients were randomized 1:1 and were restaged every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: At cutoff, 29 patients (27 evaluable) with a median of 3 (1-7) lines of prior therapies have started on trial. In the nivo only arm, 7/15 pts had a best response of SD for a CBR of 46.7% with the median PFS being 8.57 wks. In the nivo + ipi arm, 1/12 patients had a PR and 2/12 have SD for a CBR of 25.0% (95% exact C.I. 5.5%-57.2%) with a median PFS of 9.1 wks. 8 patients have been on therapy for more than 6 months and two patients with a KIT Exon 17 mutation had radiographic disease shrinkage. Most AEs were grades 1-2 with fatigue (37%) being the most common. 4 Grade 3/4 AEs occurred in the nivo and ipi arm (hyperglycemia, weakness, diarrhea x 2) and 4 grade 3/4AEs occurred in the nivo arm (DKA, hyperglycemia, rash, fatigue). Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, responses and disease control with both nivo and nivo + ipi were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.
Background Free tissue transfer (FTT) is critical for limb salvage of chronic lower extremity (LE) wounds. In patients with peripheral arterial disease (PAD), FTT LE reconstruction can be challenging due to limited vessel selection for anastomosis. The study aims to evaluate our surgical and functional outcomes after FTT to LE in patients with PAD. Methods A retrospective review identified patients who underwent LE free flap reconstruction between 2011 and 2021. All patients underwent preoperative arteriogram and subsequent FTT. Patients were classified into PAD or non-PAD cohorts, based on the presence of LE arterial stenoses or occlusions identified on arteriogram. Primary outcomes included complications, flap success, need for post-FTT vascular reintervention, limb salvage, and ambulatory status. Results A total of 253 patients underwent FTT to LE, with 84 patients (33.2%) in the PAD cohort. Patients with PAD had a higher prevalence of diabetes (83.3% vs 39.1%, P < 0.001) and end-stage renal disease (8.3% vs 2.4%, P = 0.028). Osteomyelitis was more common in the PAD group (73.8% vs 55.0%, P = 0.004). Free tissue transfer donor sites and flap composition were similar between cohorts. At a mean follow-up of 21.1 months, limb salvage rates were similar between non-PAD and PAD cohorts (90.5% vs 84.5%, P = 0.158), with no significant differences in ambulatory status or mortality. Higher complication rates occurred in the PAD cohort (38.1% vs 20.7%, P = 0.003), of which partial flap necrosis was more prevalent in the PAD group (6.0% vs 0.6%, P = 0.016). There was no difference in flap success rates between groups (P = 0.430). More postflap angiograms were performed in the PAD group (29.8% vs 7.1%, P < 0.001), with repeat percutaneous endovascular intervention performed in 68.0% of the PAD group versus 33.3% of the non-PAD group (P < 0.001). Conclusions This is the largest study to demonstrate excellent long-term limb salvage outcomes in patients with PAD who undergo FTT to LE. Percutaneous endovascular intervention and FTT are effective methods to achieve limb salvage in vasculopathic patients with chronic LE wounds.
Background: Free tissue transfer (FTT) reconstruction is associated with a high rate of limb salvage in patients with chronic lower extremity (LE) wounds. Studies have shown perioperative risk stratification tools (e.g., modified 5-factor frailty index (mFI-5) and Charlson Comorbidity Index (CCI)) to be useful in predicting adverse outcomes; however, no studies have compared them in patients undergoing LE reconstruction. The aim of this study is to compare the utility of mFI-5 and CCI in predicting postoperative morbidity in elderly patients receiving LE FTT reconstruction. Methods: A retrospective review of patients >60 years who underwent LE FTT reconstruction from 2011-2022 was performed. Comorbidity burden was measured by two validated risk-stratification tools: mFI-5 and CCI. Primary outcomes included prolonged postoperative length of stay (LOS), defined as >75th percentile of the cohort, postoperative complications, and eventual amputation. Results: One-hundred fifteen patients were identified. Median CCI and mFI-5 were 5 (IQR 4,6) and 2 (IQR 1,3), respectively. Average postoperative LOS was 16.4 days. Twenty-nine patients (25.2%) experienced a postoperative complication, and eight patients (7.0%) required LE amputation at a mean follow-up of 19.8 months. Overall flap success was 96.5% (n=111), and limb salvage rate was 93% (n=108). Increased CCI was found to be independently predictive of only eventual amputation (OR 1.59, p=0.039), while mFI-5 was not predictive of prolonged postoperative LOS, flap complications, or eventual amputation. Conclusion: This is the first study to compare the utility of mFI-5 and CCI in predicting adverse outcomes in elderly patients undergoing LE FTT reconstruction. Our results demonstrate CCI to be a superior predictor of secondary amputation in this patient population and mFI-5 to have limited utility. Further investigation in a prospective multicenter cohort is warranted.
Background: Plastic and reconstructive surgery (PRS) academic positions are more coveted each year. We aim to determine the requirement of fellowship training before PRS academic appointments. Methods: PRS faculty at U.S. academic institutions associated with the American Society of Plastic Surgeons were identified. Outcomes studied included integrated versus independent training, fellowships, gender, academic title, years on faculty, and publications before current hire. Results: Of the 1052 PRS faculty identified, 646 were included across 41 states and the District of Columbia. Seventy-four percent were identified as men (n = 477), and 26.2% (n = 169) identified as women. Academic faculty were significantly more likely to have completed fellowship before hire than not (p<0.0001). An integrated route of training was associated with higher odds of fellowship completion before appointment (OR = 2.19, 95% CI: 1.49-3.22). Odds of fellowship completion was significantly greater among faculty who graduated 5-10 years ago (OR = 2.55, 95% CI: 1.48-4.41) and within the last 5 years (OR = 1.93, 95% CI: 1.18-3.17). Professors were less likely to have completed fellowship training before appointment compared with assistant professors (OR = 0.51, 95% CI: 0.33-0.80). Regarding gender, number of prior publications, or completion of another degree, no significant difference was found between fellowship-and non-fellowship-trained faculty. Conclusions: Although more plastic surgeons enter the field through a shortened integrated residency, the increasing demand for further subspecialization may cause significant challenges for upcoming graduates pursuing an academic appointment. Undergoing additional training considerably impacts social and financial decision-making early in surgical careers for newly graduated residents.
Background: Simultaneous ventral hernia repair with panniculectomy (VHR-PAN) is associated with a high rate of wound complications. Closed incision negative pressure wound therapy (ciNPWT) has been shown to lower complications in high-risk wounds. There is a debate in the literature as to whether ciNPWT is effective at preventing complications in VHR-PAN. The aim of our study was to evaluate if ciNPWT improves outcomes of VHR-PAN. Methods: A retrospective review of patients who underwent VHR-PAN between 2009 and 2021 was conducted. Patients were divided into two groups: (1) those who received standard sterile dressings (SSD), or (2) ciNPWT. Primary outcomes were postoperative complications, including surgical site occurrences (SSO) and hernia recurrence. Results: A total of 114 patients were identified: 57 patients each in the SSD group and ciNPWT group. The groups were similar in demographics and comorbidities. There were more smokers in the SSD group (22.8% versus 5.3%, P = 0.013). Hernia defect size was significantly larger in patients who received ciNPWT (202.0 versus 143.4 cm 2 , P = 0.010). Overall SSO was similar between the two groups (23.2% versus 26.3%, P = 0.663). At a mean follow-up of 6.6 months, hernia recurrence rate was significantly higher in the SSD group compared with that in the ciNPWT group. (10.5% versus 0%, P = 0.027). Smoking, diabetes, component separation, mesh type, and location were not significantly associated with hernia recurrence. Conclusions: Application of incisional NPWT is beneficial in decreasing hernia recurrence in VHR-PAN, compared with standard dressings. Larger prospective studies are warranted to further elucidate the utility of ciNPWT in abdominal wall reconstruction.
Objective: Chronic lower extremity (LE) wounds are common in patients with peripheral vascular disease (PVD). Free tissue transfer (FTT) provides healthy soft tissue for wound coverage and additional blood supply to promote wound healing. Given previous studies demonstrate increased complications in LE fasciocutaneous flaps, it was hypothesized that low vascular resistance in muscle flaps may be more advantageous for wound healing in PVD patients. Therefore, this study compared outcomes in PVD patients undergoing LE reconstruction with fasciocutaneous versus muscle free flaps. Methods: Retrospectively reviewed PVD patients undergoing FTT between 2011 and 2021. Patients were stratified into fasciocutaneous and muscle free flap groups. Primary outcomes included complications, flap success, post-reconstruction vascular interventions, limb salvage, and ambulatory status. Results: One hundred thirteen patients with PVD were identified, of which 60.2% received fasciocutaneous (n = 68) and 39.8% received muscle flaps (n = 45). Fortytwo patients (37.2%) underwent pre-flap endovascular interventions. Flap success rate was 98.2% (n = 111). Overall complication rate was 41.2% following fasciocutaneous flaps compared to 24.4% in muscle flaps (p = 0.067). Fasciocutaneous flaps had higher odds of ulceration requiring repeat angiogram within 1 year of reconstruction compared to muscle flaps (OR 3.4, 95%
Background: Free tissue transfer (FTT) lower limb salvage requires costly multidisciplinary care. Traditionally, patients who undergo FTT reconstruction for lower extremity (LE) wounds were admitted to the intensive care unit (ICU) in the immediate postoperative period for close monitoring. During the COVID-19 pandemic, our practice shifted toward admitting FTT patients to the floor postoperatively instead of the ICU. The purpose of this study is to compare surgical outcomes in patients admitted to the floor versus ICU immediately following LE free flap reconstruction. Methods: We retrospectively reviewed patients undergoing LE FTT reconstruction from 2011 to 2021. Flap monitoring consisted of an implantable Cook-Swartz Doppler probe for muscle flaps and ViOptix tissue oximetry for fasciocutaneous flaps; clinical exam and hand-held dopplers were not the primary flap monitoring techniques. Patients were divided into two groups depending on whether they went to the ICU or floor postoperatively. To ensure proper comparability between cohorts, we corrected for age, BMI and Charlson Comorbidity Index (CCI) using 1:2 propensity score matching (floor: ICU). Primary outcomes included early postoperative complications, flap takeback and salvage, flap success, and postoperative length of stay (LOS).Results: A total of 252 patients were identified. Forty-five patients (17.9%) were admitted to the floor postoperatively and 207 patients (82.1%) to the ICU. Overall, microsurgical success rate was 97.2%, which was similar for floor and ICU patients.Flap takeback and salvage were similar between cohorts. Average postoperative LOS was significantly shorter in floor patients (15.7 vs. 19.1 days, p = 0.043). Conclusion:Our findings suggest that postoperative floor admission does not decrease flap success rates and should be considered in patients who undergo FTT to LE reconstruction and are otherwise stable. In the ongoing era of health care cost containment, microsurgery centers should consider appropriate floor training to allow medically stable free flap patients to avoid an ICU stay. | INTRODUCTIONMicrovascular free tissue transfer (FTT) is a reliable surgical option to reconstruct complex lower extremity (LE) wound defects, with flap success rates approaching 99% (Bigdeli et al., 2019;Khouri et al., 1998;Xiong et al., 2016). Postoperative management patterns differ between institutions, and no one protocol has been proven superior (Rohde et al., 2009). Nevertheless, many patients who
Supplementmonocyte populations (p<0.05). Epibolous wounds demonstrated reduced frequency of epithelialization as defined by pan-keratin signaling. In epibolous wounds without epithelialization, strong alpha-smooth-muscle actin signal was noted. When allowed to proceed to maturation, scars from epibole injuries remained significantly larger (p<0.05). This was true in both control and diabetic models. All wound-edge inversion injuries demonstrated gross and histologic evidence of dystrophic healing and collagen deposition compared to controls. Conclusion:Previously we demonstrated that wound-edge inversion to mimic epibole prolongs wound opening. Here we demonstrate that this translates to prolongs inflammation and a transition of murine healing to a more human-relevant granulation pattern. Furthermore, the delay of closure results in a consistent dystrophic scar without need for thermal, radiological, chemical or biological interference. Consequently, this simple surgical maneuver enhances our ability to study and intervene in the process of acute and chronic wound development and dystrophic scar formation in a histologically humanized model while retaining access to the genetic tractability of murine stock.
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