Complications Following Alloplastic Chin Augmentation: A Systematic Review of Implant Materials and Surgical Techniques.

BACKGROUND: Alloplastic implantation has become a popular method of chin augmentation. Historically, silicone was the most commonly used implant, but porous materials have grown in favor due to improved fibrovascularization and stability. Nevertheless, it is unclear which implant type has the most favorable complication profile. This systematic review aims to compare the complications of published chin implants and surgical approaches to provide data-driven recommendations for optimizing chin augmentation outcomes. METHODS: The PubMed® database was queried on March 14, 2021. We selected studies reporting data on alloplastic chin augmentation excluding additional procedures such as osseous genioplasty, fat grafting, autologous grafting, and fillers. The following complications were extracted from each article: malposition, infection, extrusion, revision, removal, paresthesias, and asymmetry. RESULTS: Among the 39 articles analyzed, the year of publication ranged from 1982 to 2020; additionally, 31 were retrospective case series, 5 were retrospective cohort or comparative studies, 2 were case reports, and 1 was a prospective case series. More than 3104 patients were included. Among the 11 implants reported, the 3 implants with the highest number of publications were silicone, high-density porous polyethylene (HDPE), and expanded polytetrafluoroethylene (ePTFE). Silicone demonstrated the lowest rates of paresthesias (0.4%) compared to HDPE (20.1%, P < 0.01) and ePTFE (3.2%, P < 0.05). In contrast, there were no statistically significant differences in rates of implant malposition, infection, extrusion, revision, removal, or asymmetry when stratified by implant type. Various surgical approaches were also documented. Compared with subperiosteal implant placement, the dual-plane technique demonstrated higher rates of implant malposition (2.8% vs 0.5%, P < 0.04), revision (4.7% vs 1.0%, P < 0.001), and removal (4.7% vs 1.1%, P < 0.01), but a lower incidence of paresthesias (1.9% vs. 10.8%, P < 0.01). Compared with extraoral incisions, intraoral incisions resulted in higher rates of implant removal (1.5% vs 0.5%, P < 0.05) but lower rates of asymmetry (0.7% vs 7.5%, P < 0.01). CONCLUSION: Silicone, HDPE, and ePTFE had low overall complication rates, demonstrating an acceptable safety profile regardless of implant selection. Surgical approach was found to significantly influence complications. Additional comparative studies on surgical approach while controlling for implant type would be beneficial for optimizing alloplastic chin augmentation practices.

The Potential of Transexamic Acid Use for Wide Awake Local Anesthesia No Tourniquet.

Tranexamic acid (TXA) is a drug commonly used to decrease intraoperative bleeding. Its use in various types of surgery is well defined; however, its use in plastic surgery and even more so, hand surgery is not as well researched. Concurrently, the use of wide-awake local anesthesia no tourniquet (WALANT) procedures has increased in popularity. As the use of WALANT increases, it comes to question whether TXA could be used as an alternative to epinephrine during WALANT procedures. This case involves a 33-year-old woman status-post motor vehicle collision. On examination, the patient sustained transection of the flexor digitorum profundus on both her left middle and ring fingers along with absent sensation to her left middle finger. Due to the surgical preference for vascular monitoring, TXA was used alternatively to epinephrine to control intraoperative bleeding during the tendon repairs. It was observed that TXA allowed for controlled bleeding, preservation of the surgical visual field, successful tendon repair, and postoperative success. The successful use of TXA in this case prompts further investigation as to whether TXA could be used as an alternative to epinephrine in WALANT procedures.

Surgeon-Placed Continuous Wound Infusion Pain Catheters Markedly Decrease Narcotic Use and Improve Outcomes After Pancreatic Tumor Resection.

BACKGROUND: Pancreatectomy results in significant postoperative pain and typically requires opioid analgesia for adequate pain control. Local anesthetics may decrease postoperative pain and opioid requirements but can be limited by onset of action, duration of effect, and inability to titrate dosing after administration. This can be overcome by surgeon placement of tunneled peri-incisional catheters with continuous wound infusion (CWI). METHODS: This retrospective cohort study analyzed patients undergoing open pancreatic tumor resection. All the patients received patient-controlled analgesia (PCA), enabling an objective comparison of opioid requirements, and underwent the same recovery pathway. The patients received CWI (n = 45), PCA alone (n = 11), or epidural analgesia (EA) (n = 9). The primary outcome was total opioid use in terms of intravenous morphine milligram equivalents (MMEs) and patient-reported pain scores on a numeric rating scale (NRS) of 0 to 10. RESULTS: No differences in baseline patient or tumor characteristics were observed. In both the uni- and multivariate analyses, CWI was associated with lower opioid use than PCA (MME, 83 vs 207 mg; p = 0.004) or EA (MME, 83 vs 156 mg; p < 0.001) without having a negative impact on pain scores. Furthermore, CWI was associated with a greater percentage of time that patients experienced optimal pain control (NRS, ≤ 4: 63% vs 50%; p = 0.033) and a shorter time to PCA independence (4.0 vs 4.9 days; p = 0.004) than PCA alone. In addition, CWI was associated with earlier ambulation [EA vs CWI: odds ratio (OR), 0.05; p = 0.021], improved spirometry performance (CWI vs PCA: regression coefficient (coef), 267; p = 0.013), and earlier urinary catheter removal (EA vs CWI: coef, 1.30; p = 0.013). The findings showed no differences in time to return of bowel function, antiemetic use, or hospital length of stay. CONCLUSIONS: After open pancreatic tumor resection, CWI is safe and associated with decreased opioid requirements and improved functional outcomes without a negative impact on pain scores, supporting its potential for preferred use over PCA or EA alone.

MADD silencing enhances anti-tumor activity of TRAIL in anaplastic thyroid cancer.

ATC is an aggressive disease with limited therapeutic options due to drug resistance. TRAIL is an attractive anti-cancer therapy that can trigger apoptosis in a cancer cell-selective manner. However, TRAIL resistance is a major clinical obstacle for its use as a therapeutic drug. Previously, we demonstrated that MADD is a cancer cell pro-survival factor that can modulate TRAIL resistance. However, its role, if any, in overcoming TRAIL resistance in ATC is unknown. First, we characterized ATC cell lines as either TRAIL resistant, TRAIL sensitive or moderately TRAIL sensitive and evaluated MADD expression/cellular localization. We determined the effect of MADD siRNA on cellular growth and investigated its effect on TRAIL treatment. We assessed the effect of combination treatment (MADD siRNA and TRAIL) on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. The effect of combination treatment on tumor growth was assessed in vivo. We found increased levels of MADD in ATC cells relative to Nthy-ori 3-1. MADD protein localizes in the cytosol (endoplasmic reticulum and Golgi body) and membrane. MADD knockdown resulted in spontaneous cell death that was synergistically enhanced when combined with TRAIL treatment in otherwise resistant ATC cells. Combination treatment resulted in a significant reduction in MMP and enhanced generation of ROS indicating the putative mechanism of action. In an orthotopic mouse model of TRAIL-resistant ATC, treatment with MADD siRNA alone reduced tumor growth that, when combined with TRAIL, resulted in significant tumor regressions. We demonstrated the potential clinical utility of MADD knockdown in sensitizing cells to TRAIL-induced apoptosis in ATC.

Loss of MADD expression inhibits cellular growth and metastasis in anaplastic thyroid cancer.

Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, explored its effect on cellular proliferation and metastases and examined its therapeutic potential in an orthotopic ATC model in athymic nude mice. When compared to untreated control and scramble siRNA, MADD siRNA treatment inhibited the proliferative capacity of 8505C, C643 and HTH7 cells in vitro and 8505C-derived-orthotopic tumor growth in vivo. MADD ablation caused a significant reduction in cellular migration and invasion potential; clonogenic capacity; as well as, mitochondrial length and potential in vitro. This MADD siRNA-induced anti-migratory/invasive effect corresponded with inhibition of epithelial-mesenchymal transition (EMT) and Wnt signaling. Mechanistically, MADD siRNA inhibited TNFα induced activation of pERK, pGSK3ß and ß-catenin, suggesting that MADD knockdown might exert its anti-migratory/invasive effects, by blocking TNFα/ERK/GSK3ß axis. MADD siRNA can inhibit ß-catenin nuclear translocation and consequently, the expression of its target genes in ATC cells. In in vivo experiments, along with tumor regression, MADD siRNA treatment also decreased evidence of lung metastases. Immunohistochemically, MADD siRNA-treated tumor tissues exhibited a reduction in Ki67 and N-Cadherin expression, and an increase in E-Cadherin expression. In conclusion, we show the crucial role of MADD in ATC tumorigenesis and metastasis and its potential implications as a molecular target for ATC therapy.

Endovascular treatment of a penetrating injury of the suprarenal inferior vena cava.

In this case, a 22-year-old man sustained multiple gunshot wounds to the abdomen, which required in extremis surgical exploration with damage control laparotomy and hemostatic resuscitation in the surgical intensive care unit. Diagnostic angiography was negative and an inferior vena cava (IVC) injury was suspected. He was returned to the operating room, where the infrarenal IVC was accessed by direct puncture and venography demonstrated active extravasation of the suprarenal vena cava. The injury was successfully sealed with two overlapping endovascular aortic grafts, with care taken to preserve flow from the renal and hepatic veins. He made a full recovery and was discharged home on hospital day 20. Outpatient follow-up computed tomography at 2 months revealed a patent stent with preserved branches. Stent graft repair of penetrating IVC injury can be lifesaving and warrants further investigation.

Vaccination With Mitoxantrone-Treated Primary Colon Cancer Cells Enhances Tumor-Infiltrating Lymphocytes and Clinical Responses in Colorectal Liver Metastases.

BACKGROUND: Colorectal cancer remains a leading cause of cancer-related mortality worldwide. Metastases to the liver are often present at initial presentation and will form in most patients during their course of disease. We have previously demonstrated that enhanced trafficking and activation of tumor-infiltrating lymphocytes in colorectal liver metastases (CRLM) may improve antitumor immune responses. Thus, development of novel mechanisms to increase lymphocyte infiltration and activation are needed to improve patient outcomes. METHODS: CT26 murine colorectal cancer cells were treated with physiologic levels of the potent inducer of immunogenic cell death mitoxantrone (MTX). An in situ vaccine was created with treated cells in an established model of CRLM. Cells were evaluated by flow cytometry for cell cycle evaluation and calreticulin expression. Splenic and tumor-infiltrating lymphocytes were isolated for phenotypic studies. RESULTS: MTX-treatment of colon cancer cells resulted in a sub-G1 peak, inhibition of G1 cell cycle progression, and increased G2/M cell fractions while simultaneously increasing dynamic exposure of calreticulin on the cell surface (P < 0.05). Vaccination with MTX-treated cells resulted in significant decreases in CRLM formation associated with increased tumor-infiltrating leukocytes that displayed increased expression of the T cell surface activation marker CD69. CONCLUSIONS: Vaccination with MTX-treated primary colon cancer cells enhances tumor-infiltrating lymphocytes and clinical responses in CRLM.

A Technique to Define Extrahepatic Biliary Anatomy Using Robotic Near-Infrared Fluorescent Cholangiography.

BACKGROUND: Bile duct injury is a rare but serious complication of minimally invasive cholecystectomy. Traditionally, intraoperative cholangiogram has been used in difficult cases to help delineate anatomical structures, however, new imaging modalities are currently available to aid in the identification of extrahepatic biliary anatomy, including near-infrared fluorescent cholangiography (NIFC) using indocyanine green (ICG).1-5 The objective of the study was to evaluate if this technique may aid in safe dissection to obtain the critical view. METHODS: Thirty-five consecutive multiport robotic cholecystectomies using NIFC with ICG were performed using the da Vinci Firefly Fluorescence Imaging System. All patients received 2.5 mg ICG intravenously at the time of intubation, followed by patient positioning, draping, and establishment of pneumoperitoneum. No structures were divided until the critical view of safety was achieved. Real-time toggling between NIFC and bright-light illumination was utilized throughout the case to define the extrahepatic biliary anatomy. RESULTS: ICG was successfully administered to all patients without complication, and in all cases the extrahepatic biliary anatomy was able to be identified in real-time 3D. All procedures were completed without biliary injury, conversion to an open procedure, or need for traditional cholangiography to obtain the critical view. Specific examples of cases where x-ray cholangiography or conversion to open was avoided and NIFC aided in safe dissection leading to the critical view are demonstrated, including (1) evaluation for aberrant biliary anatomy, (2) confirmation of non-biliary structures, and (3) use in cases where the infundibulum is fused to the common bile duct. CONCLUSION: NIFC using ICG is demonstrated as a useful technique to rapidly identify and aid in the visualization of extrahepatic biliary anatomy. Techniques that selectively utilize this technology specifically in difficult cases where the anatomy is unclear are demonstrated in order to obtain the critical view of safety.

LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases.

The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte-mediated antitumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Furthermore, we demonstrated evidence of durable tumor-specific antitumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy. Cancer Res; 77(8); 1880-91. ©2017 AACR.

Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death.

Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell surface, a decrease in intracellular ATP, and the release of HMGB1. To confirm the ICD phenotype, we vaccinated immunocompetent animals with syngeneic colon cancer cells treated with RB. RB-treated tumors served as a vaccine against subsequent challenge with the same CT26 colon cancer tumor cells, and vaccination with in vitro RB-treated cells resulted in slower tumor growth following inoculation with colon cancer cells, but not with syngeneic non-CT26 cancer cells, suggesting a specific antitumor immune response. In conclusion, RB serves as an inducer of ICD that contributes to enhanced specific antitumor immunity in colorectal cancer.