Folate-targeted intraoperative fluorescence, OTL38, in robotic-assisted laparoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and efficacy of OTL38, a folate-targeted, intraoperative fluorescence agent, in patients undergoing robotic-assisted laparoscopic partial nephrectomy. METHODS: Patients with proven or suspected localized renal cell carcinoma at a single academic institution were selected from 2016 to 2018. Patients received one dose of OTL38 at 0.025 mg/kg prior to robotic-assisted laparoscopic partial nephrectomy. The da Vinci Fluorescence Imaging Vision System was used to identify the tumor and inspect for residual disease after resection. Immunohistochemistry was performed to quantify folate receptor alpha in both the tumor and surrounding normal parenchyma. Patient follow-up was 1 month. Outcome data included descriptive statistics of the patient cohort and surgeon and pathologist surveys. RESULTS: Ten cases were performed. Mean patient age was 62.9 years (range = 50-70). Mean tumor size was 2.45 cm. Pathologic tumor stages ranged from T1a-T3a. Histologic tumor types included clear cell, chromophobe, type 1 papillary renal cell carcinoma and oncocytoma. The tumors did not fluoresce, while the surrounding normal parenchyma did show fluorescence. No adverse reactions were seen. Staining for folate receptor alpha was localized to the proximal renal tubules. Average staining in normal surrounding renal parenchyma was significantly greater than staining observed in tumor tissue (0.2086 vs 0.0467; p = 0.002). The mean difference in staining between tumor tissue and surrounding normal renal parenchyma was 0.1619 (95% CI = 0.0796-0.2442). CONCLUSIONS: Based on our initial experience, OTL38 shows potential as a safe, effective and easy to use tool to improve visualization and resection of renal tumors.

Sensor-based indicators of performance changes between sessions during robotic surgery training.

Training of surgeons is essential for safe and effective use of robotic surgery, yet current assessment tools for learning progression are limited. The objective of this study was to measure changes in trainees' cognitive and behavioral states as they progressed in a robotic surgeon training curriculum at a medical institution. Seven surgical trainees in urology who had no formal robotic training experience participated in the simulation curriculum. They performed 12 robotic skills exercises with varying levels of difficulty repetitively in separate sessions. EEG (electroencephalogram) activity and eye movements were measured throughout to calculate three metrics: engagement index (indicator of task engagement), pupil diameter (indicator of mental workload) and gaze entropy (indicator of randomness in gaze pattern). Performance scores (completion of task goals) and mental workload ratings (NASA-Task Load Index) were collected after each exercise. Changes in performance scores between training sessions were calculated. Analysis of variance, repeated measures correlation, and machine learning classification were used to diagnose how cognitive and behavioral states associate with performance increases or decreases between sessions. The changes in performance were correlated with changes in engagement index (rrm=-.25,p<.001) and gaze entropy (rrm=-.37,p<.001). Changes in cognitive and behavioral states were able to predict training outcomes with 72.5% accuracy. Findings suggest that cognitive and behavioral metrics correlate with changes in performance between sessions. These measures can complement current feedback tools used by medical educators and learners for skills assessment in robotic surgery training.

Outcomes of robot-assisted partial nephrectomy for completely endophytic renal tumors: A multicenter analysis.

INTRODUCTION: Multicenter retrospective analysis of robotic partial nephrectomy for completely endophytic renal tumors (i.e. 3 points for the 'E' domain of the R.E.N.A.L. nephrometry score) was performed. MATERIALS AND METHODS: Patients' demographics, tumor characteristics, perioperative, functional, pathological and oncological data were analyzed and compared with those of patients with exophytic and mesophytic masses (i.e. 1 and 2 points for the 'E' domain, respectively). Multivariable logistic regression analysis was used to assess variables for trifecta achievement (negative margin, no postoperative complications, and 90% estimated glomerular filtration rate [eGFR] recovery). RESULTS: Overall, 147 patients were included in the study group. Patients with a completely endophytic mass had bigger tumors (mean 4.2 vs. 4.1 vs. 3.2 cm; p < 0.001) on preoperative imaging and higher overall R.E.N.A.L. score. There was no difference in mean operative time. Estimated blood loss was higher in the endophytic group (mean 177.75 vs. 185.5 vs. 130 ml; p = 0.001). Warm ischemia time was shorter for the exophytic group (median 16 vs. 21 vs. 22 min; p < 0.001). Postoperative complications were more frequent in patients with endophytic tumor (24.8% vs. 19.5% vs. 14.8%; p < 0.001). Six (4.5%) patients had positive surgical margins, there was no difference between groups. Trifecta was achieved in 44 patients in endophytic group (45.4 vs. 68.8 and 50.9%, p < 0.001). Multivariable analysis for trifecta revealed that clinical tumor size (odds ratio: 0.667, 95% confidence interval: 0.56-0.79, p < 0.001) was only significant predictor for trifecta achievement. CONCLUSIONS: Our findings confirm that RAPN in case of completely endophytic renal masses can be performed with acceptable outcomes in centers with significant robotic expertise.

Outcomes of Robot-assisted Partial Nephrectomy for Clinical T3a Renal Masses: A Multicenter Analysis.

BACKGROUND: Use of partial nephrectomy (PN) in T3 renal cell carcinoma (RCC) is controversial. OBJECTIVE: To evaluate quality outcomes of robot-assisted PN (RAPN) for clinical T3a renal masses (cT3aRM). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter analysis of patients with cT3aN0M0 RCC who underwent RAPN. INTERVENTION: RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was a trifecta composite outcome of negative surgical margins, warm ischemia time (WIT) ≤25 min, and no perioperative complications. The optimal outcome was defined as achieving this trifecta and ≥90% preservation of the estimated glomerular filtration rate (eGFR) and no stage upgrading of chronic kidney disease. Multivariable analysis (MVA) identified risk factors associated with lack of the optimal outcome. Kaplan-Meier analysis was conducted for survival outcomes. RESULTS AND LIMITATIONS: Analysis was conducted for 157 patients (median follow-up 26 mo). The median tumor size was 7.0 cm (interquartile range [IQR] 5.0-7.8) and the median RENAL score was 9 (IQR 8-10). Median estimated blood loss (EBL) was 242 ml (IQR 121-354) and the median WIT was 19 min (IQR 15-25). A total of 150 patients (95.5%) had negative margins. Complications were noted in 25 patients (15.9%), with 4.5% having Clavien grade 3-5 complications. The median change in eGFR was 7 ml/min/1.72 m2, with ≥90% eGFR preservation in 55.4%. The trifecta outcome was achieved for 64.3% and the optimal outcome for 37.6% of the patients. MVA revealed that greater age (odds ratio [OR] 1.06; p = 0.002), increasing RENAL score (OR 1.30; p = 0.035), and EBL >300 ml (OR 5.96, p = 0.006) were predictive of failure to achieve optimal outcome. The 5-yr recurrence-free survival, cancer-specific survival, and overall survival, were 82.1%, 93.3%, and 91.3%, respectively. Limitations include the retrospective design. CONCLUSIONS: RAPN for select cT3a renal masses is feasible and safe, with acceptable quality outcomes. Further investigation is requisite to delineate the role of RAPN in cT3a RCC. PATIENT SUMMARY: Robot-assisted partial nephrectomy in patients with stage 3a kidney cancer provided acceptable survival, functional, and morbidity outcomes in the hands of experienced surgeons, and may be considered as an option when clinically indicated.

Robotic-assisted Partial Nephrectomy for "Very Small" (<2 cm) Renal Mass: Results of a Multicenter Contemporary Cohort.

BACKGROUND: Patient with "very small" (<2 cm) renal mass can be offered active surveillance, thermal ablation, or partial nephrectomy. The management strategy will consider patient preferences and prioritize potential harms associated with each of these options. To date, outcomes of robot-assisted partial nephrectomy (RAPN) in patients with "very small" renal masses have not been reported. OBJECTIVE: To assess the outcomes of RAPN among patients with "very small" renal masses. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional database including RAPN cases performed at eight high-volume US and European centers between 2009 and 2019. Patients were stratified into two groups according to clinical tumor size: <2 cm ("very small" renal mass, study group) and 2-4 cm (control group). INTERVENTION: RAPN for renal masses. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and intraoperative, pathological, and postoperative data were compared between the study and the control group. A "trifecta" was used as surrogate of "surgical quality." RESULTS AND LIMITATIONS: Overall, a total of 1019 patients were included in the analysis. Of these, 352 had a renal mass of <2 cm (34.5%) and 667 (65.5%) had a renal mass of 2-4 cm. At baseline, the study group presented a lower rate of chronic kidney disease ≥stage III (p < 0.001), a lower RENAL score (p = 0.001), and lower rates of hilar (p = 0.04) and endophytic (p = 0.02) masses. Warm ischemia time was shorter for the study group (median 14 vs 18 min, p < 0.001), which also showed a lower rate of overall postoperative complications (9.6% vs 14.7%, p < 0.001) and no major complications. In terms of oncological outcomes, three and ten patients developed a local recurrence in the study and the control group, respectively (p = 0.1). In the study group, higher estimated glomerular filtration rates were found at discharge (p = 0.001) and at the last follow-up (p = 0.007), which showed a "trifecta" achievement of 90.6%. The retrospective design may limit the generalizability of the findings. CONCLUSIONS: Whenever an active treatment is indicated or warranted, RAPN represents a minimally invasive management option for "very small" renal masses, as it carries minimal risk of complications and has minimal impact on renal function. While both active surveillance and kidney ablation remain valid management options in these cases, RAPN can be offered and discussed with patients as it provides excellent outcomes with low morbidity. PATIENT SUMMARY: In this report, we observed that robot-assisted partial nephrectomy represents a true minimally invasive active treatment for "very small" renal masses (<2 cm), as it carries minimal risk of complications and has minimal impact on renal function.

Robotic and open partial nephrectomy for intermediate and high complexity tumors: a matched-pairs comparison of surgical outcomes at a single institution.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when controlling for tumor and patient complexity.Methods: A retrospective review of 222 patients undergoing partial nephrectomy was performed. Patients with intermediate (nephrometry score NS 7-9) or high (NS 10-12) complexity tumors were matched 2:1 for RPN:OPN using NS, Charlson Comorbidity Index (CCI), and BMI. Patient demographics, peri-operative values, renal function, and complication rates were analyzed and compared.Results: Seventy-four OPN patients were matched to 148 RPN patients with no difference in patient demographics. Estimated blood loss in OPN patients was significantly higher (368.5 vs 210.5 mL, p < 0.001) as was transfusion rate (17% vs 1.6%, p < 0.001). Warm ischemia time was longer in OPN (25.5 vs 19.7 min, p = 0.001) while operative time was reduced (200.5 vs 226.5 min, p = 0.010). RPN patients had significantly shorter hospitalizations (5.3 vs 3.0 days, p < 0.001). GFR decrease after one month was not statistically significant (12.9 vs 6.6 ml/min, p = 0.130). Clavien III-V complications incidence was higher for OPN compared to RPN although not significantly (20.3% vs 10.8%, p = 0.055).Conclusion: When matching for tumor and patient complexity, RPN patients had fewer high grade post-operative complications, decreased blood loss, and shorter hospitalizations. RPN is a safe option for patients with intermediate and high complexity tumors.

Eye-Tracking Metrics Predict Perceived Workload in Robotic Surgical Skills Training.

OBJECTIVE: The aim of this study is to assess the relationship between eye-tracking measures and perceived workload in robotic surgical tasks. BACKGROUND: Robotic techniques provide improved dexterity, stereoscopic vision, and ergonomic control system over laparoscopic surgery, but the complexity of the interfaces and operations may pose new challenges to surgeons and compromise patient safety. Limited studies have objectively quantified workload and its impact on performance in robotic surgery. Although not yet implemented in robotic surgery, minimally intrusive and continuous eye-tracking metrics have been shown to be sensitive to changes in workload in other domains. METHODS: Eight surgical trainees participated in 15 robotic skills simulation sessions. In each session, participants performed up to 12 simulated exercises. Correlation and mixed-effects analyses were conducted to explore the relationships between eye-tracking metrics and perceived workload. Machine learning classifiers were used to determine the sensitivity of differentiating between low and high workload with eye-tracking features. RESULTS: Gaze entropy increased as perceived workload increased, with a correlation of .51. Pupil diameter and gaze entropy distinguished differences in workload between task difficulty levels, and both metrics increased as task level difficulty increased. The classification model using eye-tracking features achieved an accuracy of 84.7% in predicting workload levels. CONCLUSION: Eye-tracking measures can detect perceived workload during robotic tasks. They can potentially be used to identify task contributors to high workload and provide measures for robotic surgery training. APPLICATION: Workload assessment can be used for real-time monitoring of workload in robotic surgical training and provide assessments for performance and learning.

Treatment Trends and Long-Term Survival Associated with Cryotherapy and Partial Nephrectomy for Small Renal Masses in the National Cancer Database Using Propensity Score Matching.

Objective: Trends in the utilization of ablative therapy are unknown for the treatment of small renal masses. Our goal is to utilize the National Cancer Database (NCDB) to both assess the utilization of ablative therapies and long-term survival. Materials and Methods: The NCDB captures 70% of all cancer cases in the United States and was queried between 1998 and 2012 for renal cell carcinomas that were treated with ablative therapy, partial nephrectomy (PN), or radical nephrectomy. The analysis was limited to clinical stage T1a. Propensity score matching was used in 1:1 fashion. Kaplan-Meier survival analysis and a Cox proportional hazards model were used to compare overall survival (OS) for cryotherapy and PN. Results: A total of 119,240 cases of clinical stage T1a renal masses were treated between 1998 and 2012. Cryotherapy peaked at 927 (9.1%) cases in 2010 and had 913 (8.4%) in 2012. PN accounted for 18% of the cases in 1998, but surpassed the utilization of nephrectomy in 2008. By 2012, PN accounted for 6766 (62%) of renal mass cases. After matching, Kaplan-Meier OS was lower for cryotherapy compared with PN at 24 (94.5% vs 96.5%), 48 (86.8% vs 90.9%), and 96 months (66.0% vs 74.9%). Cryotherapy also had a lower OS (hazard ratio 1.46; p < 0.001) on adjusted analysis. Conclusion: Cryotherapy for small renal masses plateaued at 9% utilization in 2009. Cryotherapy had a lower OS than PN for tumors >2 cm on adjusted analysis, but this result should be used with caution until confirmed in randomized studies.

Robotic versus laparoscopic radical nephrectomy: a large multi-institutional analysis (ROSULA Collaborative Group).

OBJECTIVE: To compare the outcomes of robotic radical nephrectomy (RRN) to those of laparoscopic radical nephrectomy (LRN) for large renal masses. METHODS: This was a retrospective analysis of RRN and LRN cases performed for large (≥ cT2) renal masses from 2004 to 2017 and collected in the multi-institutional international database (ROSULA: RObotic SUrgery for LArge renal masses). Peri-operative, functional, and oncologic outcomes were compared between each approach. Descriptive analyses were performed and presented as medians with interquartile ranges. Inverse probability of treatment weighting-adjusted multivariable analyses were used to identify predictors of peri-operative complications. Kaplan-Meier analysis and Cox regression models were used to assess survival outcomes. RESULTS: A total of 941 patients (RRN = 404, LRN = 537) were identified. There was no difference in terms of gender, age, and clinical tumor size. Over the study period, RRN had an annual increase of 11.75% (95% CI [7.34, 17.01] p < 0.001) and LRN had an annual decline of 5.39% (95% CI [-6.94, -3.86] p < 0.001). Patients undergoing RRN had higher BMI (27.6 [IQR 24.8-31.1] vs. 26.5 [24.1-30.0] kg/m2, p < 0.01). Operative duration was longer for RRN (185.0 [150.0-237.2] vs. 126 [90.8-180.0] min, p < 0.001). Length of stay was shorter for RRN (3.0 [2.0-4.0] vs. 5.0 [4.0-7.0] days, p < 0.001). RRN cases presented more advanced disease (higher pathologic staging [pT3-4 52.5 vs. 24.2%, p < 0.001], histologic grade [high grade 49.3 vs. 30.4%, p < 0.001], and rate of nodal disease [pN1 5.4 vs. 1.9%, p < 0.01]). Surgical approach did not represent an independent risk factor for peri-operative complications (OR 1.81 95% CI [0.97-3.39], adjusted p = 0.2). The main study limitation is the retrospective design. CONCLUSIONS: This study represents the largest known multi-center comparison between RRN and LRN. The two procedures seem to offer similar peri-operative outcomes. Notably, RRN has been increasingly utilized, especially in the setting of more advanced and surgically challenging disease without increasing the risk of peri-operative complications.

Outcomes of Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA Collaborative Group).

BACKGROUND: While partial nephrectomy (PN) represents the standard surgical management for cT1 renal masses, its role for cT2 tumors is controversial. Robot-assisted PN (RAPN) is being increasingly implemented worldwide. OBJECTIVE: To analyze perioperative, functional, and oncological outcomes of RAPN for cT2 tumors. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a large multicenter, multinational dataset of patients with nonmetastatic cT2 masses treated with robotic surgery (ROSULA: RObotic SUrgery for LArge renal mass). INTERVENTION: Robotic-assisted PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients' demographics, lesion characteristics, perioperative variables, renal functional data, pathology, and oncological data were analyzed. Univariable and multivariable regression analyses assessed the relationships with the risk of intra-/postoperative complications, recurrence, and survival. RESULTS AND LIMITATIONS: A total of 298 patients were analyzed. Median tumor size was 7.6 (7-8.5) cm. Median RENAL score was 9 (8-10). Median ischemia time was 25 (20-32) min. Median estimated blood loss was 150 (100-300) ml. Sixteen patients had intraoperative complications (5.4%), whereas 66 (22%) had postoperative complications (5% were Clavien grade ≥3). Multivariable analysis revealed that a lower RENAL score (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21-0.65, p=0.02) and pathological pT2 stage (OR 0.51, 95% CI 0.12-0.86, p=0.001) were protective against postoperative complications. A total of 243 lesions (82%) were malignant. Twenty patients (8%) had positive surgical margins. Ten deaths and 25 recurrences/metastases occurred at a median follow-up of 12 (5-35) mo. At univariable analysis, higher pT stage was predictive of a likelihood of recurrences/metastases (p=0.048). While there was a significant deterioration of renal function at discharge, this remained stable over time at 1-yr follow-up. The main limitation of this study is its retrospective design. CONCLUSIONS: RAPN in the setting of select cT2 renal masses can safely be performed with acceptable outcomes. Further studies are warranted to corroborate our findings and to better define the role of robotic nephron sparing for this challenging indication. PATIENT SUMMARY: This report shows that robotic surgery can be used for safe removal of a large renal tumor in a minimally invasive fashion, maximizing preservation of renal function, and without compromising cancer control.

Role of Epigenetic Modification and Immunomodulation in a Murine Prostate Cancer Model.

INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC). MATERIALS AND METHODS: Gene microarrays were performed to compare expression of several CTA in murine prostate cancer (RM-1 cells) and normal prostate. RM-1 cells were treated with 5-AzaC and real-time PCR was performed to investigate the expression of several CTA. Western blotting was used to determine whether expression of CTA-specific mRNA induced by 5-AzaC resulted in increase in the corresponding protein. Effect of the epigenetic agents and immunomodulators was assessed on dendritic cells (DC) using flow cytometry, ELISA and T-cell proliferation assay. RESULTS: Gene arrays demonstrated decreased expression of 35 CTA in CaP tissue compared to normal prostate. 5-AzaC treatment of RM-1 prostate cancer cells upregulated the expression of all 13 CTA tested in a dose-dependent fashion. DC were treated with 5-AzaC and lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Combination of 5-AzaC and lenalidomide enhances the ability of DC to stimulate T-cell proliferation in mixed leukocyte reaction. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC or 5-AzaC and lenalidomide. CONCLUSIONS: Decreased expression of CTA by prostate cancer may be a means of escaping immune monitoring. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide increased tumor immunogenicity and enhanced DC function and may be used in the treatment of advanced prostate cancer. Prostate 77: 361-373, 2017. © 2016 Wiley Periodicals, Inc.

Intrarenal Adrenocortical Adenoma Treated by Robotic Partial Nephrectomy with Adrenalectomy.

BACKGROUND: We present an intrarenal adrenocortical adenoma discovered incidentally after robot-assisted partial nephrectomy and total adrenalectomy for a suspicious renal mass. Current literature describes the rare occurrence of an adrenocortical adenoma arising from a renal-adrenal fusion. This case represents an uncommon, benign pathology that should be considered in the differential diagnosis of an enhancing renal mass. CASE PRESENTATION: The patient is a 62-year-old female found to have an enhancing mass at the anterolateral aspect of the upper pole of the right kidney concerning for renal-cell carcinoma. CT imaging was performed to work up a cause for hyperparathyroidism. During robot-assisted partial nephrectomy, the lesion was found to be partially adherent to the lateral limb of the right adrenal gland. Microscopic evaluation with Melan-A staining showed the mass to be of adrenal origin with benign features and lack of capsulation, indicating an adrenal adenoma arising from intrarenal ectopic adrenal rests. CONCLUSION: An intrarenal adrenal adenoma arising from ectopic adrenal tissue is a unique pathology that represents a benign differential diagnosis in the evaluation of an enhancing renal mass. However, it cannot be differentiated from renal-cell carcinoma based on cross-sectional imaging alone and requires postoperative pathologic assessment to confirm the diagnosis.

Live Donor Renal Transplant With Simultaneous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease Is Feasible and Satisfactory at Long-term Follow-up.

BACKGROUND: Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant. METHODS: Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys. RESULTS: Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously. CONCLUSIONS: Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.

Secondary refinements of free perforator flaps for lower extremity reconstruction.

BACKGROUND: The aim of lower extremity reconstruction has focused on early wound coverage and functional recovery but rarely aesthetics. Free muscle flaps provide durable coverage; however, they require skin graft coverage and result in muscle atrophy limiting future revisions. Perforator-based flap reconstructions can be easily elevated to allow for both orthopedic and contouring procedures. The authors reviewed the role of secondary procedures in achieving improved functional and aesthetic results following perforator flap reconstruction of lower extremity defects. METHODS: A retrospective review identified 70 patients treated at R Adams Cowley Shock Trauma Center with 73 free perforator flaps for coverage of lower extremity wounds from 2002 to 2009. RESULTS: Seventy patients were identified who underwent reconstruction with a perforator flap: 65 with anterolateral thigh flaps and five with superficial circumflex iliac artery flaps. Nineteen of these patients underwent 32 refinement procedures of the reconstructed limb. Fifteen refinements were performed with suction-assisted lipectomy, 21 with complex tissue rearrangement, including sharp debulking, and one with tissue expanders. Twenty-seven of the 70 patients underwent 40 orthopedic-related secondary procedures in which the free flap was elevated. The most common reasons for the orthopedic interventions were tibial nonunion requiring bone grafting (n = 17) and osteomyelitis (n = 11). CONCLUSIONS: Limb salvage remains the primary goal of lower extremity reconstruction. Following convalescence and functional recovery, however, appearance becomes increasingly important with regard to quality of life. Initial flap selection with free perforator flaps, meticulous inset, and secondary refinements provide superior functional and aesthetic outcomes.

Increased expression of the collagen internalization receptor uPARAP/Endo180 in the stroma of head and neck cancer.

Local growth, invasion, and metastasis of malignancies of the head and neck involve extensive degradation and remodeling of the underlying, collagen-rich connective tissue. Urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 is an endocytic receptor recently shown to play a critical role in the uptake and intracellular degradation of collagen by mesenchymal cells. As a step toward determining the putative function of uPARAP/Endo180 in head and neck cancer progression, we used immunohistochemistry to determine the expression of this collagen internalization receptor in 112 human squamous cell carcinomas and 19 normal or tumor-adjacent head and neck tissue samples from the tongue, gingiva, cheek, tonsils, palate, floor of mouth, larynx, maxillary sinus, upper jaw, nasopharynx/nasal cavity, and lymph nodes. Specificity of detection was verified by staining of serial sections with two different monoclonal antibodies against two non-overlapping epitopes on uPARAP/Endo180 and by the use of isotype-matched non-immune antibodies. uPARAP/Endo180 expression was observed in stromal fibroblast-like, vimentin-positive cells. Furthermore, expression of the collagen internalization receptor was increased in tumor stroma compared with tumor-adjacent connective tissue or normal submucosal connective tissue and was most prominent in poorly differentiated tumors. These data suggest that uPARAP/Endo180 participates in the connective tissue destruction during head and neck squamous cell carcinoma progression by mediating cellular uptake and lysosomal degradation of collagen.