ABSTRACT
ABSTRACT: There are 2 to 5 million laparotomies performed in the United States annually. Of these, 250,000 to 350,000 will undergo a ventral hernia repair. Repairs are often complicated by recurrence and infection. These risks are significantly increased in previously infected repairs, with reported recurrence rates varying from 17% to 28% after repair of infected ventral hernias, double the rates reported for first-time uninfected repairs. We describe here a novel treatment strategy involving the creation then use of bilateral prelaminated permanent mesh-reinforced tensor fascia latae flaps for abdominal wall reconstruction in patients who have recurrent ventral hernias and had undergone previous repairs complicated by infection. Previous repairs included anterior components separation, thereby making subsequent fascial release techniques and achievement of a reinforced repair extremely unlikely. Three patients were treated by a single surgeon using this 2-stage technique. There have been no incidences of recurrence and no infections after 2 to 10 years. In these patients, the only conventional option would have been a bridged repair with absorbable mesh. Combining the advantages of permanent mesh and well-vascularized autologous tissue optimizes the repair's tensile strength while mitigating the chance of recurrent infection associated with the use of permanent mesh. We propose that this strategy may be an appropriate treatment option for patients with recurrent ventral hernias that have not responded to other conventional modalities of treatment.
Subject(s)
Abdominal Wall , Hernia, Ventral , Abdominal Wall/surgery , Fascia Lata/transplantation , Hernia, Ventral/surgery , Herniorrhaphy , Humans , Recurrence , Surgical MeshABSTRACT
Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention.
Subject(s)
GTP-Binding Protein alpha Subunits, Gq-G11/genetics , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Mutation/genetics , Vascular Neoplasms/congenital , Vascular Neoplasms/genetics , Cells, Cultured , Child, Preschool , Enzyme Activation , GTP-Binding Protein alpha Subunits/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Infant , Infant, Newborn , Intercellular Signaling Peptides and Proteins/metabolism , Male , Melanocytes/metabolism , Melanocytes/pathology , Proto-Oncogene Proteins c-akt/metabolism , Vascular Neoplasms/enzymology , Vascular Neoplasms/pathologyABSTRACT
BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.
Subject(s)
Intestinal Neoplasms/secondary , Intestinal Neoplasms/surgery , Intussusception/etiology , Intussusception/surgery , Melanoma/pathology , Melanoma/surgery , Adult , Aged , Aged, 80 and over , Humans , Intestinal Neoplasms/diagnostic imaging , Intussusception/diagnostic imaging , Melanoma/diagnostic imaging , Middle Aged , Neoplasm Metastasis , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Melanoma in situ (MIS) is an early variant of melanoma in which the disease is limited to the epidermis. Standard therapy is currently surgical excision with at least 5-mm margins. In some instances, there are large or anatomically difficult lesions where complete excision will result in significant esthetic or functional impairment. Our experience has shown a 6-week course to be sufficient in certain patients compared with the suggested 12-week course. In this context, we propose a shortened duration of treatment of positive margins with topical imiquimod and propose an algorithm that results in the least amount of dysfunction for the patient. METHODS: Our inclusion criteria were patients undergoing excision of a lesion found to have postsurgical margins, which were positive for MIS. Patients applied 5% imiquimod 3 to 5 times per week for at least 6 weeks at the site of the positive margin(s). Duration and frequency of treatment were titrated based on response. A reexcision skin biopsy using 1-mm margins was performed after residual inflammation subsided. Our endpoints were recurrence and effectiveness with length of treatment. RESULTS: Sixteen patients met our criteria. All patients were found to have MIS in the margins after surgical excision. Twelve of those lesions were classified as MIS in the initial biopsy; the remaining 4 were either melanoma stage T1A or T1B. Mean follow-up time was 14.3 months, and 1 patient was lost to follow-up. We had 3 patients without response, and of these, 1 was found to have atypical squamous cell carcinoma and the other had a recurrence of MIS. Cure rate after use of topical imiquimod was 93.3% (14/15). DISCUSSION: The proposed algorithm for the treatment of residual disease in head and neck melanoma and MIS using topical imiquimod offers various advantages. This anatomical region is cosmetically sensitive, and the option of using 1 mm versus 5 mm reexcision margins after imiquimod treatment yields comparable cure rates with less tissue excised overall. Our algorithm demonstrates that 6 weeks of active inflammation provides comparable results with the traditional 12-week course. This decreased treatment time reduces patient discomfort and improves patient adherence.
Subject(s)
Algorithms , Antineoplastic Agents/administration & dosage , Head and Neck Neoplasms/drug therapy , Imiquimod/administration & dosage , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Female , Head and Neck Neoplasms/pathology , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm, Residual , Pilot Projects , Retrospective Studies , Skin Neoplasms/pathologyABSTRACT
INTRODUCTION: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). METHODS: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. RESULTS: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. CONCLUSIONS: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.
Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Melanoma/diagnostic imaging , Sentinel Lymph Node/diagnostic imaging , Single Photon Emission Computed Tomography Computed Tomography , Skin Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Humans , Lymphoscintigraphy , Melanoma/pathology , Retrospective Studies , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Malignant cutaneous granular cell tumors (mcGCTs) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. OBJECTIVE: To examine the incidence, secondary malignancies, treatment, overall survival, and disease-specific survival (DSS) of patients with mcGCT. METHODS: A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results database from 1973 to 2013 for patients with a diagnosis of mcGCT. Risk-adjusted associations between overall survival/DSS and patient characteristics and treatment modalities were assessed by Cox proportional hazard regression. Quantile regression was used to determine median survival times. RESULTS: The 5-year DSS rate was 62.8%. Patients demonstrated an increased risk for renal and pancreatic cancers. In risk-adjusted models, male sex (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.06-0.82; Pâ¯=â¯.02), advanced cancer stage (HR, 2.29; 95% CI, 1.40-3.72; Pâ¯<â¯.01), and surgical resection (HR, 0.06; 95% CI, 0.01-0.59; Pâ¯=â¯.02) predicted DSS. Median survival time in years increased for males (1.39), earlier stage (0.60), and surgical intervention (5.34). LIMITATIONS: Absent or incorrect reporting in retrospective Surveillance, Epidemiology, and End Results data is possible. The database is more likely to include academic centers. Some subanalyses may be underpowered because of the limited sample size for a rare cancer. CONCLUSIONS: Our study presents an in-depth assessment of factors that identify high-risk patients. Residency in a nonmetro area, black race, female sex, and no surgical resection were each associated with poorer DSS.
Subject(s)
Granular Cell Tumor/epidemiology , Granular Cell Tumor/pathology , Kidney Neoplasms/epidemiology , Pancreatic Neoplasms/epidemiology , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Adolescent , Adult , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Child , Female , Granular Cell Tumor/mortality , Granular Cell Tumor/surgery , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Residence Characteristics , Retrospective Studies , SEER Program , Sex Factors , Skin Neoplasms/mortality , Skin Neoplasms/surgery , Survival Rate , United States/epidemiology , White People/statistics & numerical data , Young AdultABSTRACT
OBJECTIVE: We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. BACKGROUND: The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. METHODS: From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300âmg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. RESULTS: Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. CONCLUSIONS: Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.
Subject(s)
Leptin/metabolism , Parathyroid Glands/metabolism , Parathyroid Hormone/metabolism , Adenoma/metabolism , Animals , Cells, Cultured , Humans , Hyperparathyroidism/metabolism , Hyperplasia/metabolism , Immunohistochemistry , Mice, Knockout , Microscopy, Confocal , Microscopy, Fluorescence , Microscopy, Immunoelectron , Parathyroid Glands/pathology , Parathyroid Neoplasms/metabolism , Prospective Studies , RNA, Messenger/metabolism , Receptors, Leptin/antagonists & inhibitors , Receptors, Leptin/metabolismABSTRACT
BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with intermediate-thickness melanoma, but the use of SLNB for patients with thick melanoma is debated. This report presents a single-institution study investigating factors predictive of sentinel lymph node (SLN) metastasis and outcome for thick-melanoma patients . METHODS: A retrospective review of a single-institution database from 1997 to 2012 identified 147 patients with thick primary cutaneous melanoma (≥4 mm) who had an SLNB. Clinicopathologic characteristics were correlated with nodal status and outcome. RESULTS: The median age of the patients was 67 years, and 61.9 % of the patients were men. The median tumor thickness was 5.5 mm, and 54 patients (36.7 %) had a positive SLN. Multivariable analysis showed that only tumor thickness significantly predicted SLN metastasis (odds ratio 1.14; 95 % confidence interval (CI) 1.02-1.28; P = 0.02). The overall median follow-up period was 34.6 months. Overall survival (OS) and melanoma-specific survival (MSS) were significantly worse for the positive versus negative-SLN patients. Multivariable analysis showed that age [hazard ratio (HR) 1.04; 95 % CI 1.01-1.07; P = 0.02] and SLN status (HR 2.24; 95 % CI 1.03-4.88; P = 0.04) significantly predicted OS, whereas only SLN status (HR 3.85; 95 % CI 2.13-6.97; P < 0.01) significantly predicted MSS. CONCLUSIONS: Tumor thickness predicts SLN status in thick melanomas. Furthermore, SLN status is prognostic for OS and MSS in thick-melanoma patients, with positive-SLN patients having significantly worse OS and MSS. These findings show that SLNB should be recommended for thick-melanoma patients, particularly because detection of SLN metastasis can identify patients for potential systemic therapy and treatment of nodal disease at a microscopic stage.
Subject(s)
Lymph Node Excision , Melanoma/secondary , Neoplasm Recurrence, Local/pathology , Sentinel Lymph Node/pathology , Skin Neoplasms/pathology , Tumor Burden , Age Factors , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Melanoma/surgery , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Sentinel Lymph Node/surgery , Sentinel Lymph Node Biopsy , Skin Neoplasms/surgery , Survival RateABSTRACT
BACKGROUND: Histopathologic diagnostic features such as tumor thickness, ulceration, mitoses, microsatellitosis and nodal metastases are principal pathologic staging components of cutaneous melanomas. We chose to focus on evaluating the presence of multinucleated giant cells in microscopic sections as a putative novel prognosticating diagnostic feature of melanoma. METHODS: We assembled a retrospective cohort comprised of 562 cases of melanoma. We annotated each case for a multitude of known clinicopathologic variables to allow robust statistical evaluation of our cohort. RESULTS: Only 37 cases (6.6%) exhibited the multinucleated giant cells phenotype. Virtually all multinucleated giant cells were localized in the reticular dermis. Of interest, melanomas with multinucleated giant cells were roughly twice more likely to occur on head and neck sites (p = 0.04). Melanomas with multinucleated giant cells phenotype had both comparable melanoma recurrence (p = 0.12) and similar melanoma-specific mortality when compared with melanomas without multinucleated giant cells phenotype (p = 0.26). CONCLUSION: Despite prior anecdotal reports possibly linking multinucleated giant cells phenotype to more aggressive clinical course, we find that melanomas with multinucleated giant cells phenotype is not associated with shorter survival.
Subject(s)
Giant Cells/pathology , Head and Neck Neoplasms/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
A 6-month-old girl presented with an irregular nodule on the right lateral neck. The lesion, which superficially resembled a lymphangioma or mastocytoma, had been present since birth but had recently been growing. The patient was referred for surgical resection. Microscopic findings were compatible with a recently described rare hamartoma termed "panfollicular nevus," which is a well-circumscribed lesion containing aberrantly differentiated, clustered hair follicles in high density.
Subject(s)
Hamartoma/pathology , Nevus/pathology , Skin Neoplasms/pathology , Female , Humans , InfantABSTRACT
Deep sternal wound infection (DSWI) is a life-threatening complication that develops in 5% of patients undergoing median sternotomy. One feared complication is major bleeding, associated with up to 50% mortality. We characterized a series of patients who experienced major bleeding following DSWI. We included eight patients with DSWI who experienced major bleeding at our institution from 1990 to 2012. The median age was 70.9 (range, 47-81) and the cohort consisted of seven male patients and one female patient. All eight patients required emergent surgical repair for the bleeding and all survived past 30 days postoperatively from the repair.
Subject(s)
Hemorrhage/etiology , Mediastinitis/complications , Aged , Aged, 80 and over , Female , Hemorrhage/surgery , Humans , Male , Middle Aged , Sternotomy , Surgical Wound Infection/complicationsABSTRACT
INTRODUCTION: The differentiation between Spitz nevi (SN) and Spitzoid malignant melanomas (SMM) represents a challenge to dermatopathologists. We recently demonstrated differential expression of vimentin and Actin in SN and SMM by mass spectrometry (MS). We sought to investigate whether this differential expression could be detected using conventional immunohistochemistry or automated quantitative analysis (AQUA) of histological sections. METHODS: Cases of SN and SMM, which were previously studied by MS and have readily available blocks and enough material in the block, were selected from the Yale Spitzoid Neoplasm Repository. The cases were stained for vimentin and muscle-specific actin using standard protocols. H-scores were calculated by multiplying the percentage of cells staining and the intensity of staining. Selected cases were also studied for quantitative immunofluorescent staining using the AQUA method. RESULTS: All 21 cases of SN showed strong and diffuse staining for vimentin; 19 of 21 (91%) cases had an H-score of 300 (average, 294). Similar staining results were observed in SMM; 13 of 14 (93%) cases had an H-score of 300 (average, 297). Muscle-specific actin was weakly and focally positive in 5 of 21 (24%) SN (H-score = 3.3) and 5 of 14 (39%) SMM (H-score = 3.5). The AQUA method showed no significant difference in the staining intensity of SN and SMM for both vimentin and actin. CONCLUSIONS: There was no difference in the expression of vimentin and actin in SN and SMM shown by conventional immunohistochemistry or the AQUA method. This study shows that MS has much grater sensitivity in detecting the differential expression of these proteins.
Subject(s)
Actins/analysis , Biomarkers, Tumor/analysis , Melanoma/chemistry , Nevus, Epithelioid and Spindle Cell/chemistry , Skin Neoplasms/chemistry , Vimentin/analysis , Adult , Aged , Aged, 80 and over , Automation, Laboratory , Biopsy , Child , Child, Preschool , Diagnosis, Differential , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Male , Melanoma/pathology , Middle Aged , Nevus, Epithelioid and Spindle Cell/pathology , Predictive Value of Tests , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally invasive soft tissue sarcoma with extensive subclinical involvement. The National Comprehensive Cancer Network guidelines recommend immediate reconstruction in most cases. Our study reviewed the methods of treatment of DFSP at our institution, examined the types of closure used after surgical excision, and analyzed the prevalence of positive margins on permanent pathology after immediate closure after conventional non-Mohs excision of DFSP. METHODS: The charts of 25 patients treated with surgical excision and 16 with Mohs surgery from 1990 to 2009 for lesions consistent with DFSP were reviewed for clinical variables including disease state, tumor site, closure type, permanent pathology margin status, disease recurrence/persistence, and excisional margin size. RESULTS: The trunk, followed by the head and neck, were the most common sites for DFSP. No patients had distant metastasis at diagnosis or experienced recurrence in either the surgical excision or the Mohs surgery group. Twelve (48%) patients were found to have positive margins after initial surgical resection. All lesions treated with Mohs surgery had clear histological margins at completion. Average margin size for surgical excision patients was 2.33 cm (range, 0.75-4.5 cm), and 1.36 cm (range, 0.74-2.55 cm) for Mohs excision. The average duration of follow-up was 107.9 months. CONCLUSIONS: The extent of DFSP is difficult to determine intraoperatively with traditional surgical excision, which leads to a higher rate of positive margins. Considering this difficulty and the complications of reconstruction with positive margins, we believe that reconstruction after tumor resection should be dependent on definitive pathologic clearance of the tumor.
Subject(s)
Algorithms , Decision Support Techniques , Dermatofibrosarcoma/surgery , Mohs Surgery , Skin Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Wound Closure Techniques , Young AdultABSTRACT
Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.
Subject(s)
Biomarkers/metabolism , Hemangioma, Capillary/metabolism , Neural Crest/metabolism , Pericytes/metabolism , Skin Neoplasms/metabolism , Adolescent , Child , Child, Preschool , Flow Cytometry , Fluorescent Antibody Technique , Hemangioma, Capillary/embryology , Humans , Immunohistochemistry , Infant , Real-Time Polymerase Chain Reaction , Skin Neoplasms/embryology , Stem Cells/metabolismABSTRACT
UNLABELLED: Cranial nerves (CN) are believed to be relatively resistant to radiotherapy (RT); however, there have been case reports of cranial nerve palsy (CNP) following RT. We present a case of a gentleman with cranial nerve palsy of CN V and VII after RT for nasopharyngeal carcinoma (NPC). CASE PRESENTATION: A 54-year-old male presented to our clinic with masticatory difficulty, facial hypoesthesia, and dysphagia. In 1998, he was treated with external beam RT for NPC. He underwent sural nerve grafting, anastomosing his functioning hypoglossal nerve to the buccal branch of the facial nerve in an end-to-side fashion, and direct implantation of a nerve graft from the spinal accessory to the masseter muscle. He unfortunately was unable to regain masticatory function postoperatively. CONCLUSION: Cranial nerve palsies are severely debilitating to patients and difficult to treat. Radiation-induced CNP is important to consider in the differential diagnosis in patients previously treated for NPC.
Subject(s)
Cranial Nerve Diseases/etiology , Facial Nerve Diseases/etiology , Nasopharyngeal Neoplasms/radiotherapy , Radiation Injuries/etiology , Trigeminal Nerve Diseases/etiology , Carcinoma , Deglutition Disorders/etiology , Humans , Hypesthesia/etiology , Male , Middle Aged , Nasopharyngeal CarcinomaABSTRACT
Oncology has been revolutionized by the ability to selectively inhibit the growth of cancerous cells while ostensibly avoiding the disruption of proteins and pathways necessary for normal cellular function. This paradigm has triggered an explosion of targeted therapies for cancer, creating a burgeoning billion-dollar industry of small molecules and monoclonal antibodies [1]. Largely due to these new treatments, spending on cancer pharmaceuticals has surpassed $100 billion worldwide [2]. In particular, the treatment of melanoma, a deadly and fast-spreading form of skin cancer, has been transformed by these new targeted therapies. In this mini-review, we summarize the progress made in the field of personalized treatment of melanoma, with an emphasis on targeted therapies. We then outline future directions for treatment, including novel cell-mediated therapies and new potential targets.
Subject(s)
Melanoma/therapy , Precision Medicine/methods , Humans , Immunotherapy/methods , Melanoma/drug therapy , Melanoma/genetics , Proto-Oncogene Proteins B-raf/drug effects , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
BACKGROUND: Spitz nevi and Spitzoid malignant melanomas are uncommon and may be difficult to distinguish histopathologically. Identification of clinical features associated with these lesions may aid in diagnosis. OBJECTIVE: We sought to identify clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas. METHODS: We conducted a retrospective cohort study of Spitz nevi and Spitzoid malignant melanomas from the Yale University Spitzoid Neoplasm Repository diagnosed from years 1991 through 2008. Descriptive statistics and multivariate logistic regression were used to compare select patient- and tumor-level factors associated with each lesion. RESULTS: Our cohort included 484 Spitz nevi and 54 Spitzoid malignant melanomas. Spitz nevi were more common (P = .03) in females (65%; n = 316) compared with Spitzoid malignant melanomas (50%; n = 27), occurred more frequently in younger patients (mean age at diagnosis 22 vs 55 years; P < .001), and more likely presented as smaller lesions (diameter 7.6 vs 10.5 mm; P < .001). Increasing age (odds ratio 1.16, 95% CI [1.09, 1.14]; P< .001) and male gender (odds ratio 2.77, 95% CI [1.17, 6.55]; P< .02) predicted Spitzoid malignant melanoma diagnosis. LIMITATIONS: Small sample size, unmeasured confounding, and restriction to a single institution may limit the accuracy and generalizability of our findings. CONCLUSIONS: Age and gender help predict diagnosis of Spitz nevi and Spitzoid malignant melanomas.
Subject(s)
Melanoma/pathology , Nevus, Epithelioid and Spindle Cell/pathology , Skin Neoplasms/pathology , Skin/pathology , Adolescent , Adult , Age Factors , Aged , Biopsy , Child , Child, Preschool , Cross-Sectional Studies , Diagnosis, Differential , Female , Humans , Infant , Male , Middle Aged , Predictive Value of Tests , Young AdultABSTRACT
We recently reported on the safety of minimally invasive parotid region sentinel node biopsy and level I-sparing radical neck dissection for head and neck melanoma. We therefore wished to assess the state of practice in the United States through a survey of specialists in head and neck surgery. We hypothesized that there would be significant variation in the management of these facets of head and neck melanoma. To test this hypothesis, a 10-question online survey on management of head and neck melanoma was distributed to the members of the American Head and Neck Society. Responses were matched to Internet Protocol addresses to ensure that each respondent completed the survey only once. Eighty-eight respondents completed the survey. For sentinel lymph nodes within the parotid gland, nearly half (47.7%) of surgeons surveyed perform a superficial parotidectomy, 13.6% perform a total parotidectomy, and only 38.6% perform parotid-sparing surgery; 71.6% of surgeons remove the submandibular nodes when carrying out a functional radical neck dissection. In conclusion, approaches to the management of head and neck melanoma vary widely, with only a minority of surgeons using morbidity-sparing surgical approaches. This study highlights the need for further randomized controlled trials in the surgical management of head and neck melanoma.
Subject(s)
Head and Neck Neoplasms/surgery , Melanoma/surgery , Neck Dissection/methods , Parotid Gland/surgery , Practice Patterns, Physicians'/statistics & numerical data , Skin Neoplasms/surgery , Head and Neck Neoplasms/pathology , Health Care Surveys , Humans , Lymphatic Metastasis , Melanoma/pathology , Neck Dissection/statistics & numerical data , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology , United StatesABSTRACT
Various surgical treatment modalities have been advocated for the treatment of Dupuytren's disease. However, recurrence following surgical treatment of Dupuytren's disease remains a common problem. Previous studies have demonstrated lower recurrence rates with use of a full-thickness skin graft. We therefore postulated that use of acellular dermal matrix may be associated with a similar outcome, based on the common inhibitory effect on underlying myofibroblasts. We performed a retrospective cohort study of 43 patients undergoing open fasciectomy for Dupuytren's disease from years 2005 to 2012 at our academic institution. Standard fasciectomies of the affected palmar and digital fascia were performed via Brunner incisions on all patients. Patients in the experimental group had a sheet of acellular dermal matrix (Alloderm; LifeCell, Bridgewater, NJ) sutured into the surgical bed with interrupted absorbable sutures before closure, whereas patients in the control group were not closed with acellular dermal matrix. Patients were then evaluated at follow-up for disease recurrence, defined as presence of Dupuytren's tissue in an area previously operated on with a contracture greater than that recorded following the surgical fasciectomy, or presence of contracture requiring surgery. Among our cohort of 43 patients, 23 (53.5%) were treated with acellular dermal matrix while 20 (46.5%) were not. The median age of our cohort was 66.5 years (range 54-91 years). The median follow-up was 1.8 years. During this follow-up period, recurrence of contracture was observed in 1 of 23 patients in the group receiving acellular dermal matrix, compared to 5 of 20 in the control group (P = 0.045). No differences in the incidence of minor wound complications were observed. Our novel technique of placement of acellular dermal matrix into the wound bed following fasciectomy for Dupuytren's disease may be an important surgical strategy to reduce recurrence rates in patients with Dupuytren's disease.
Subject(s)
Acellular Dermis , Dupuytren Contracture/surgery , Fasciotomy , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pilot Projects , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Intraoperative brachytherapy (IOBT) to the tumor bed coupled with surgery has been shown to increase survival and to improve locoregional disease control after head and neck tumor extirpation. Flap reconstruction attempts to restore patient anatomy, while also covering the radioactive implants. The purpose of this study was to better characterize the wound healing complications experienced by patients undergoing reconstruction in the setting of IOBT after tumor ablation, as well as to identify risk factors predicting complications and the need for reoperation. METHODS: A retrospective chart review of patients receiving IOBT for head and neck cancer at Yale-New Haven Hospital between 2005 and 2013 was conducted. Patient, tumor, treatment, and reconstructive details were recorded. The number and type of flap complications, as well as instances in which patients had to be taken back to the operating room, were documented. Bivariate and multivariate logistic regressions were performed to identify risk factors associated with the occurrence of 1 or more flap complications, as well as the need for reoperation. RESULTS: Ninety-three patients aged 31 to 93 years (mean, 64 ± 12 years) who underwent IOBT with flap reconstruction were included in the study. Of these, 94% had a prior history of radiation (external beam or previous IOBT). Overall, 48 (51.6%) patients experienced at least 1 flap complication, the most common of which was flap dehiscence (32% of patients). Thirty-two patients (34% of the cohort) had to be taken back to the operating room at least once for flap debridement or a revision procedure. On multivariate analysis, only the placement of mandibular hardware during flap reconstruction was significantly associated with the risk of developing any type of flap complication (odds ratio, 3.7; P = 0.009) or with subsequent return to the operating room (odds ratio, 3.9; P = 0.012). CONCLUSIONS: This study, the largest of its kind, demonstrated a very high complication rate for flaps used to cover brachytherapy implants in this patient cohort. However, many of the patient complications could be managed nonoperatively. Avoiding the use of mandibular hardware with IOBT suggests a method of reducing complications with reconstruction.