Effects of Neoadjuvant Chemotherapy on Autologous and Implant-Based Breast Reconstruction: A Systematic Review and Meta-Analysis of the Literature.

Neoadjuvant chemotherapy (NAC) is a standard modality of treatment for breast cancer. The exposure of patients to drugs that effect the cells and processes involved in healing prior to reconstructive surgical procedures is a source of concern for reconstructive surgeons. The reported effects of NAC on autologous and tissue expander to implant-based breast reconstruction vary from study to study and have not been comprehensively reviewed on a large scale. There is also significant variation from study to study regarding which outcomes are evaluated. The primary aim of this systematic review and meta-analysis is to evaluate the effect of neoadjuvant chemotherapy (NAC) on common and significant outcomes including total complication, reconstruction loss, and SSI (Surgical Site Infection) rates in breast reconstruction. The second aim of this study is to evaluate whether NAC has differing effects on implant-based reconstruction compared with autologous flap reconstruction. A systematic review of the literature published from 1991 to 2019 in the PubMed and Scopus library database was performed to identify studies reporting outcomes of breast reconstruction in patients receiving NAC. A meta-analysis was then performed. Primary outcomes reviewed included overall complication rates, SSI rates, and total loss of reconstruction (flap necrosis or premature tissue expander or implant removal). Outcomes were analyzed using a random effects model and chi-square statistical test. Our literature search yielded 22 manuscripts with a total of 3680 patients that fit our inclusion criteria, of which 12 reported on reconstruction loss, 14 reported on SSI rates, and 10 reported on overall complication rates. There was no significant difference in overall breast reconstruction loss rate (OR 1.30, P = .35), complication rate (OR 1.21, P = .06), and rate of SSI (OR 1.28, P = .85) between NAC vs. non-NAC groups. In patients undergoing autologous flap reconstruction there were no significant differences in complication (23.4% vs. 17.7%, P = 0.076), loss of reconstruction (3.1% vs. 4.4%, P = .393), or SSI (5.3% vs. 3.4%, P = .108) rates in patients who were treated with NAC compared to those who were not. Likewise, in patients undergoing TE/implant-based reconstruction there were no significant differences in complication (19.6 vs. 24.2 P = .069), loss of reconstruction (17.4% vs. 13.3%, P = .072), or SSI (7.9% vs. 5.1%, P = .073) rates in patients who were treated with NAC compared to those who were not. NAC was not associated with any significant differences in overall complication, reconstruction loss, or SSI rates in patients receiving implant-based or autologous flap breast reconstruction. Additionally, the lack of effect of NAC on overall complication, reconstruction loss or SSI rates did not differ with or depend on the type of reconstruction.

Panniculectomy Performed in Conjunction With Gynecologic Surgery in Obese and Morbidly Obese Patients: A National Surgical Quality Improvement Program Analysis and Systematic Review of the Literature.

INTRODUCTION: Panniculectomy is a common procedure in plastic surgery, often performed after massive weight loss and in morbidly obese patients. It is also performed in combination with various gynecologic procedures based on the rational that it will reduce complication rates and benefit the patient (Am J Obstet Gynecol, 2000. 182, 1502-1505; J Gynecol Technol, 1997;3:9-16; J Am Coll Surg, 1995). These and other studies fail to provide proof of these claims for a number of reasons, including study design, lack of a control group and the inclusion of nonmorbidly obese patients (J Am Coll Surg, 1995; Gynecol Oncol, 1998, 70, 80-86; Int J Gynecol Cancer, 2015;25(8):1503-1512). Recent medical practice has focused increasingly on minimizing patient morbidity and trends in reimbursement are moving toward penalizing practices, which increase complications. The aim of this study was to evaluate the premise that the addition of panniculectomy to gynecologic surgery in the obese and morbidly obese patient population results in a statistically significant improvement in measureable outcomes. METHODS/RESULTS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed to assess the association of complications with panniculectomy combined with gynecologic surgery in the morbidly obese patient population. The query identified 296 patients with a body mass index greater than 30 who had panniculectomy concomitant with gynecologic surgery. The results demonstrated a statistically significant relationship (P < 0.05) of these concomitant procedures with superficial infection, wound infection, pulmonary embolism, systemic sepsis, return to operating room, length of operation and length of stay. A systematic review of the literature was then performed which identified only 5 studies that included comparative cohorts of those with gynecologic surgery, with and without panniculectomy. There was no significant benefit across the studies in measured paramters. CONCLUSIONS: This NSQIP study and systematic review of the existing literature does not support the premise that there is a statistically significant benefit associated with performing panniculectomy in conjunction with gynecologic surgery in the morbidly obese patient population. The NSQIP data demonstrate significant elevation of negative outcomes in morbidly obese patients undergoing combined procedures. In the light of the risks to patients and current direction of medical practice the addition of elective panniculectomy to gynecologic surgery should be reevaluated in the a patient population with a body mass index greater than 30.

Near-Infrared Optical Contrast of Skull Base Tumors During Endoscopic Endonasal Surgery.

BACKGROUND: Near-infrared (NIR) tumor contrast is achieved through the "second-window ICG" technique, which relies on passive accumulation of high doses of indocyanine green (ICG) in neoplasms via the enhanced permeability and retention effect. OBJECTIVE: To report early results and potential challenges associated with the application of second-window ICG technique in endonasal endoscopic, ventral skull-base surgery, and to determine potential predictors of NIR signal-to-background ratio (SBR) using endoscopic techniques. METHODS: Pituitary adenoma (n = 8), craniopharyngioma (n = 3), and chordoma (n = 4) patients received systemic infusions of ICG (5 mg/kg) approximately 24 h before surgery. Dual-channel endoscopy with visible light and NIR overlay were photodocumented and analyzed post hoc. RESULTS: All tumors (adenoma, craniopharyngioma, chordoma) demonstrated NIR positivity and fluoresced with an average SBR of 3.9 ± 0.8, 4.1 ± 1.7, and 2.1 ± 0.6, respectively. Contrast-enhanced T1 signal intensity proved to be the single best predictor of observed SBR (P = .0003). For pituitary adenomas, the sensitivity, specificity, positive predictive value, and negative predictive value of NIR-guided identification of tumor was 100%, 20%, 71%, and 100%, respectively. CONCLUSION: In this preliminary study of a small set of patients, we demonstrate that second-window ICG can provide NIR optical tumor contrast in 3 types of ventral skull-base tumors. Chordomas demonstrated the weakest NIR signal, suggesting limited utility in those patients. Both nonfunctional and functional pituitary adenomas appear to accumulate ICG, but utility for margin detection for the adenomas is limited by low specificity. Craniopharyngiomas with third ventricular extension appear to be a particularly promising target given the clean brain parenchyma background and strong SBR.

Folate Receptor Overexpression in Human and Canine Meningiomas-Immunohistochemistry and Case Report of Intraoperative Molecular Imaging.

BACKGROUND: Meningiomas are well-encapsulated benign brain tumors and surgical resection is often curative. Nevertheless, this is not always possible due to the difficulty of identifying residual disease intraoperatively. We hypothesized that meningiomas overexpress folate receptor alpha (FRα), allowing intraoperative molecular imaging by targeting FRα with a near-infrared (NIR) dye. OBJECTIVE: To determine FRα expression in both human and canine meningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging. METHODS: Tissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FRα along with normal dura, skeletal muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma and tuberculum sella meningioma in a clinical trial in which the patient received an infusion of folate-linked, NIR fluorescent dye prior to surgery. RESULTS: In the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and 50% of grade III tumors overexpressed FRα. In the 7 canine meningioma samples, 100% stained positively for FRα. Both human and canine normal dura from autopsy samples demonstrated no evidence of FRα overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FRα immunohistochemistry staining. CONCLUSION: This study directly demonstrates FRα overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.

Intraoperative near-infrared imaging with receptor-specific versus passive delivery of fluorescent agents in pituitary adenomas.

OBJECTIVE: Intraoperative molecular imaging with tumor-targeted fluorescent dyes can enhance resection rates. In contrast to visible-light fluorophores (e.g., 5-aminolevulinic-acid), near-infrared (NIR) fluorophores have increased photon tissue penetration and less contamination from tissue autofluorescence. The second-window ICG (SWIG) technique relies on passive accumulation of indocyanine green (ICG) in neoplastic tissues. OTL38, conversely, targets folate receptor overexpression in nonfunctioning pituitary adenomas. In this study, we compare the properties of these 2 modalities for NIR imaging of pituitary adenomas to better understand the potential for NIR imaging in neurosurgery. METHODS: A total of 39 patients with pituitary adenomas were enrolled between June 2015 and January 2018 in 2, sequential, IRB-approved studies. Sixteen patients received systemic ICG infusions 24 hours prior to surgery, and another 23 patients received OTL38 infusions 2-3 hours prior to surgery. NIR fluorescence signal-to-background ratio (SBR) was recorded during and after resection. Immunohistochemistry was performed on the 23 adenomas resected from patients who received OTL38 to assess expression of folate receptor-alpha (FRα). RESULTS: All 16 adenomas operated on after ICG administration demonstrated strong NIR fluorescence (mean SBR 4.1 ± 0.69 [SD]). There was no statistically significant difference between the 9 functioning and 7 nonfunctioning adenomas (p = 0.9). After administration of OTL38, the mean SBR was 1.7 ± 0.47 for functioning adenomas, 2.6 ± 0.91 for all nonfunctioning adenomas, and 3.2 ± 0.53 for the subset of FRα-overexpressing adenomas. Tissue identification with white light alone for all adenomas demonstrated 88% sensitivity and 90% specificity. SWIG demonstrated 100% sensitivity but only 29% specificity for both functioning and nonfunctioning adenomas. OTL38 was 75% sensitive and 100% specific for all nonfunctioning adenomas, but when assessment was limited to the 9 FRα-overexpressing adenomas, the sensitivity and specificity of OTL38 were both 100%. CONCLUSIONS: Intraoperative imaging with NIR fluorophores demonstrates highly sensitive detection of pituitary adenomas. OTL38, a folate-receptor-targeted fluorophore, is highly specific for nonfunctioning adenomas but has no utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to both functioning and nonfunctioning pituitary adenomas, but it is less specific than targeted fluorophores. Thus, targeted and nontargeted NIR fluorophores play important, yet distinct, roles in intraoperative imaging. Selectively and intelligently using either agent has the potential to greatly improve resection rates and outcomes for patients with intracranial tumors.

Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs Associated with Breast Reconstruction.

INTRODUCTION: Impaired vascular perfusion in tissue expander (TE) breast reconstruction leads to mastectomy skin necrosis. We investigated factors and costs associated with skin necrosis in postmastectomy breast reconstruction. METHODS: Retrospective review of 169 women with immediate TE placement following mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient demographics, comorbidities, intraoperative, and postoperative outcomes were collected. Logistic regression analysis on individual variables was performed to determine the effects of tissue expander fill volume and mastectomy specimen weight on skin necrosis. Billing data was obtained to determine the financial burden associated with necrosis. RESULTS: This study included 253 breast reconstructions with immediate TE placement from 169 women. Skin necrosis occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8 times higher odds of skin necrosis [odd ratio (OR), 8.10, P < 0.001]. Patients with TE intraoperative fill volumes >300 cm(3) had 10 times higher odds of skin necrosis (OR, 10.66, P =0.010). Volumes >400 cm(3) had 15 times higher odds of skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43; P =0.003 and P <0.001, respectively). Mastectomy skin necrosis was associated with a 50% increased inpatient charge. CONCLUSION: Mastectomy flap necrosis is associated with HTN, larger TE volumes and mastectomy specimen weights, resulting in increased inpatient charges. Conservative TE volumes should be considered for patients with hypertension and larger mastectomy specimens.