RESUMO
PURPOSE OF REVIEW: Cystic echinococcosis is a zoonotic infection frequently involving the liver. Treatment options, including surgery, are decided based on the staging of the disease. RECENT FINDINGS: Ultrasound is the cornerstone for diagnosis, staging, and follow-up of cystic echinococcosis. MRI can help to evaluate for cystobiliary complications and planning of the surgery. The two main surgical approaches for cystic echinococcosis include a radical approach, which entails a partial hepatectomy and total pericystectomy, and a conservative approach or endocystectomy. Recent data suggest a conservative approach is well tolerated with acceptable morbidity and no mortality. Recurrences in centers with experience are rare. Data on laparoscopic surgery is emerging, but long-term follow-up still needs to be improved. SUMMARY: Surgical treatment options should be carefully evaluated according to the cystic echinococcosis disease staging. A multidisciplinary approach, including diagnostic and interventional radiology, abdominal and liver surgery, and infectious diseases, results in better outcomes.
Assuntos
Equinococose Hepática , Equinococose , Humanos , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/cirurgia , Equinococose/diagnóstico por imagem , Equinococose/cirurgia , Hepatectomia/métodos , Estudos RetrospectivosRESUMO
OBJECTIVE: We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience. BACKGROUND: Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case. METHODS: We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021. RESULTS: We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22-4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22-3873), 444 days (range: 22-4824), and 1825 days (range: 868-3549). CONCLUSIONS: Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation.
Assuntos
Hepatectomia , Neoplasias Hepáticas , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Transplante AutólogoRESUMO
In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graft (HvG) T cell clonal ratios in their allografts. These GvH clones entered the circulation, where their peak levels were associated with declines in HvG clones early after transplant, suggesting that GvH reactions may contribute to chimerism and control HvG responses without causing GVHD. Consistently, donor-derived T cells, including GvH clones, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were simultaneously detected in the recipients' BM more than 100 days after transplant. Individual GvH clones appeared in ileal mucosa or PBMCs before detection in recipient BM, consistent with an intestinal mucosal origin, where donor GvH-reactive T cells expanded early upon entry of recipient APCs into the graft. These results, combined with cytotoxic single-cell transcriptional profiles of donor T cells in recipient BM, suggest that tissue-resident GvH-reactive donor T cells migrated into the recipient circulation and BM, where they destroyed recipient hematopoietic cells through cytolytic effector functions and promoted engraftment of graft-derived HSPCs that maintain chimerism. These mechanisms suggest an approach to achieving intestinal allograft tolerance.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Intestinos/transplante , Linfopoese/imunologia , Transplante de Órgãos , Linfócitos T/imunologia , Quimeras de Transplante/imunologia , Aloenxertos , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Intestinos/imunologia , Intestinos/patologia , Masculino , Linfócitos T/patologiaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has placed extraordinary strain on global healthcare systems. Use of extracorporeal membrane oxygenation (ECMO) for patients with severe respiratory or cardiac failure attributed to COVID-19 has been debated due to uncertain survival benefit and the resources required to safely deliver ECMO support. We retrospectively investigated adult patients supported with ECMO for COVID-19 at our institution during the first 80 days following New York City's declaration of a state of emergency. The primary objective was to evaluate survival outcomes in patients supported with ECMO for COVID-19 and describe the programmatic adaptations made in response to pandemic-related crisis conditions. Twenty-two patients with COVID-19 were placed on ECMO during the study period. Median age was 52 years and 18 (81.8%) were male. Twenty-one patients (95.4%) had severe ARDS and seven (31.8%) had cardiac failure. Fifteen patients (68.1%) were managed with venovenous ECMO while 7 (31.8%) required arterial support. Twelve patients (54.5%) were transported on ECMO from external institutions. Twelve patients were discharged alive from the hospital (54.5%). Extracorporeal membrane oxygenation was used successfully in patients with respiratory and cardiac failure due to COVID-19. The continued use of ECMO, including ECMO transport, during crisis conditions was possible even at the height of the COVID-19 pandemic.
Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Adolescente , Adulto , Idoso , COVID-19/mortalidade , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: Ex vivo surgery may provide a chance at R0 resection for conventionally unresectable tumors. However, long-term outcomes have not been well documented. In this study, we analyze our 11-year outcomes to define its role. STUDY DESIGN: We retrospectively analyzed 46 consecutive patients who underwent ex vivo surgery at our institution 2008-2019. RESULTS: The types of tumors were: carcinoma (n = 20), sarcoma (n = 20) and benign to low grade tumor (n = 6). The type of ex vivo surgery was chosen based on tumor location and vascular involvement. The most commonly performed procedure was ex vivo hepatectomy (n = 18), followed by ex vivo resection and intestinal autotransplantation (n = 12), ex vivo Whipple procedure and liver autotransplantation (n = 8) and multivisceral ex vivo procedure (n = 7). Twenty-three patients (50%) are currently alive with median follow-up of 4.0-years (11 months-11.8 years). The overall survival was 70%/59%/52%, at 1-/3-/5-years, respectively. Patient survival for benign to low grade tumors, sarcoma, and carcinoma was 100%/100%/100%, 65%/60%/50%, and 65%/45%/40%, at 1-/3-/5-years, respectively. Ninety-one percent patients had R0 resection, and 57% had no recurrence to date with median follow-up of 3.1-years. Two patients (4.3%) died within 30 days due to sepsis and gastroduodenal artety (GDA) stump blowout. Two additional patients died between 30 and 90 days due to sepsis. Perioperative mortality in the last 23 consecutive cases was limited to 1 patient who died of sepsis between 30 and 90 days. CONCLUSIONS: For a selected group of patients with conventionally unresectable tumors, ex vivo surgery can offer effective surgical removal with a reasonably low perioperative mortality at experienced centers.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Transplante Autólogo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Patients receiving extracorporeal membrane oxygenation (ECMO) often require prolonged mechanical ventilation. Providers may be reluctant to perform tracheostomies on patients during ECMO due to their tenuous clinical status and systemic anticoagulation. We report our experience with performing open and percutaneous tracheostomies on patients supported on ECMO from August 2009 to December 2017. Of the 127 patients who underwent tracheostomy during ECMO support, the median age was 42 years (interquartile range [IQR], 29-54), 99 (78%) patients had venovenous (VV) cannulation, 22 (17%) patients had venoarterial (VA) cannulation, and six (5%) patients had hybrid configurations. Percutaneous tracheostomy was performed in 110 (87%) patients. Median-activated partial thromboplastin time (aPTT) at the time of tracheostomy was 47.5 seconds (IQR, 41-57.6 seconds). The median time from ECMO initiation to tracheostomy was 7 days (IQR, 4-11 days). A total of 55 patients (43%) received packed red blood cell (pRBC) transfusions within 48 hours after tracheostomy with a median transfusion of 2 units (IQR, 1-3). There was no procedural mortality. Overall, 88 (69%) patients survived to decannulation and 74 (58%) survived to hospital discharge. Our experience with the largest published series of tracheostomies during ECMO demonstrates that excellent outcomes can be achieved without significant morbidity.
Assuntos
Oxigenação por Membrana Extracorpórea , Respiração Artificial/métodos , Traqueostomia , Adulto , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/mortalidade , Estudos Retrospectivos , Traqueostomia/efeitos adversos , Traqueostomia/mortalidadeRESUMO
BACKGROUND: Application of extracorporeal life support (ECLS) for advanced pulmonary hypertension (PH) is evolving and may be deployed as a bridge to transplantation (BTT) or in one of several non-BTT uses, such as bridge to recovery (BTR) to the chronic PH clinical state in the setting of an acute PH trigger, bridge through non-transplant surgery (BTNTS), or bridge post-transplantation (BPT). METHODS: We conducted a retrospective analysis of all adult patients with World Symposium on Pulmonary Hypertension Group 1, 3, 4, or 5 PH who received ECLS at Columbia University Medical Center/New York Presbyterian Hospital between January 1, 2010 and August 18, 2018. We describe patient characteristics, outcomes, and our approach to medical and surgical management of these patients. RESULTS: There were 98 patients with significant PH in the cohort (54 female; median age, 48 years [interquartile range, 32-58]). Of these, 44 (45%) patients with PH received ECLS as non-BTT with intent to recover back to their baseline functional state, optimize therapy, or support through a definitive surgery, including 19 BTR, 17 BTNTS, and 8 BPT, and 54 (55%) patients received ECLS as BTT. In the overall cohort, 67 (68.4%) patients received venoarterial ECLS and 31 (31.6%) received venovenous (VV) ECLS. Out of 83 patients, 52 (63%) were liberated from invasive mechanical ventilation, and 85.2% of BTT patients with PH ambulated while on ECLS. Management of PH medications was individualized, often requiring titration with use of inhaled pulmonary vasodilators increased after cannulation in non-BTT. Overall 30-day survival was 73.5%, survival to ECLS decannulation was 66.3%, and survival to hospital discharge was 54.1%. All 8 BPT patients (100%) survived to hospital discharge, 64.7% of BTNTS patients survived to hospital discharge, and 32 (59.3%) BTT patients survived to lung transplantation. Early-era use of VV-ECLS for BTT had worse survival to discharge than those initially configured with venoarterial ECLS, impacting the overall survival and leading to limited use of VV-ECLS in the current era for BPT, BTNTS, and select BTR cases. CONCLUSIONS: ECLS instituted by a specialized, multidisciplinary team has a role in the management of advanced PH as BTT or as non-BTT (including BTR, BTNTS, and BPT). Careful selection of ECLS cannulation configurations, patient-specific optimization of PH medical therapies, and avoidance of endotracheal intubation may be effective strategies in managing these complex patients.
Assuntos
Oxigenação por Membrana Extracorpórea , Hipertensão Pulmonar/cirurgia , Adulto , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is used to provide support for patients with cardiopulmonary failure. Best available medical management often fails in these patients and referring hospitals have no further recourse for escalating care apart from transfer to a tertiary facility. In severely unstable patients, the only option might be to use ECMO to facilitate safe transport. This study aimed to examine the characteristics and outcomes of patients transported while receiving ECMO. METHODS: Statistical analysis was performed on data gathered retrospectively from the electronic medical records of adult patients transported while receiving ECMO to Columbia University Medical Center between January 1, 2008, and December 31, 2017. RESULTS: Two hundred sixty five adult patients were safely transported while receiving ECMO with no transport-related complications that adversely affected outcomes. Transport distance ranged from 0.2 to 7084 miles with a median distance of 16.9 miles. One hundred eighty-three (69%) received on veno-venous, 72 (27%) veno-arterial, and 10 (3.8%) veno-venous arterial or veno-arterial venous configurations. Two hundred ten (79%) cannulations were performed at our institution at the referring hospital. Sixty-four percent of patients transported while receiving ECMO survived to hospital discharge. CONCLUSIONS: Interfacility transport during ECMO was shown to be safe and effective with minimal complications and favorable outcomes when performed at an experienced referral center using stringently applied protocols.
Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Transferência de Pacientes , Insuficiência Respiratória/terapia , Adulto , Registros Eletrônicos de Saúde , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Alta do Paciente , Segurança do Paciente , Encaminhamento e Consulta , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Transporte de Pacientes , Resultado do TratamentoRESUMO
BACKGROUND: Intestinal autotransplantation (IATx) and ex vivo resection is a novel surgical strategy to treat patients with unresectable abdominal neoplasms involving the mesenteric root. Nutritional challenges after IATx and ex vivo surgery have not been well described. METHODS: Eleven patients, aged 7-68 years (median, 49 years) underwent IATx and ex vivo resection at our center from 2009 to 2016. A retrospective chart review was performed to evaluate nutrition status, tolerance of an oral diet, and need for parenteral nutrition (PN) and enteral (EN) nutrition. These factors were assessed preoperatively and at 3 months postoperatively. RESULTS: Prior to surgery, 10 of 11 patients were tolerating oral diets without need for additional PN or EN. Postoperatively, PN was initiated in all patients from 1-15 days after surgery (median, 5 days) and continued from 12-122 days (median, 32.5 days), except for of 1 patient who underwent a total enterectomy and required subsequent allotransplantation with ongoing PN. EN was initiated in 9 patients from 4-117 days after surgery (median, 17 days) and has been ongoing in 5 patients. Oral diets were initiated in all patients from 5-115 days (median, 14 days) postoperatively; at 3 months, 11 of 12 patients were tolerating oral diets. CONCLUSION: IATx and ex vivo resection presents a unique challenge with respect to nutrition management. Patients undergoing these complex surgeries may have difficulty maintaining adequate nutrition with an oral diet alone in the immediate postoperative period and beyond and may require prolonged nutrition support.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Intestinos/transplante , Apoio Nutricional/métodos , Complicações Pós-Operatórias/prevenção & controle , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos , Adulto JovemRESUMO
Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62-year-old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow-up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.
Assuntos
Neoplasias da Mama Masculina/radioterapia , Neoplasias da Mama Masculina/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Terapia Combinada/métodos , Humanos , Cuidados Intraoperatórios/métodos , Masculino , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela , Resultado do TratamentoRESUMO
There are several low-grade pancreatic tumors whose biology permits the use of aggressive surgery to achieve a curative resection. Tumors that are deemed unresectable by conventional techniques due to mesenteric vessel involvement may benefit from ex vivo tumor resection and autotransplantation to allow complete resection while minimizing ischemic organ injury. Despite the excellent oncologic outcomes when used for these neoplasms, the procedure carries substantial morbidity and a high complication rate. But for patients who were otherwise offered total enterectomy and allotransplantation or told that their tumor was unresectable, ex vivo resection may offer them a hope for cure.
Assuntos
Intestinos/transplante , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Vísceras/transplante , Humanos , Transplante AutólogoRESUMO
BACKGROUND: Transporting patients receiving extracorporeal membrane oxygenation (ECMO) support is safe and reliable with a dedicated program and established management protocols. As our program has grown, our teams have had to adapt to manage surges in transport volume while maintaining patient safety. We assessed the outcomes at peak use of our ECMO transport services during surges. METHODS: We conducted a single-center retrospective review of all patients transported to our institution while supported with ECMO from September 2008 to September 2016. Survival to discharge was the primary outcome. Surge patients were defined as those transported during months with at least 8 transports or patients transported within 24 hours of another patient in nonsurge months. RESULTS: From 2008 to 2016, 222 patients were transported to our institution while supported with ECMO. Baseline characteristics and indices of disease severity were comparable between surge and nonsurge patients. Of the 84 patients transported during surges, 59 surge patients (70%) survived to hospital discharge vs 86 (63%) of nonsurge patients (p = 0.31). Multivariable logistic regression showed that age and APACHE II (Acute Physiology and Chronic Health Evaluation) severity index score were predictors of in-hospital death (p < 0.05), but transportation during a surge was not (odds ratio, 0.91; 95% confidence interval, 0.46 to 1.80; p = 0.79). CONCLUSIONS: Patient safety and clinical outcomes can be maintained during surges in ECMO transport volume if the ECMO program has developed plans for handling transient increases in volume and considers staff fatigue and burnout. Standardizing interhospital communication, patient selection, and management protocols are critical to maintaining quality of care.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Síndrome do Desconforto Respiratório/terapia , Transporte de Pacientes/organização & administração , Adulto , Segurança de Equipamentos , Oxigenação por Membrana Extracorpórea/normas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Transferência de Pacientes , Estudos RetrospectivosRESUMO
OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) transport has not been described in morbidly obese patients, a population that can pose significant challenges in obtaining vascular access, indexed flows and transport logistics. We sought to study the feasibility and safety of transporting obese and morbidly obese patients during extracorporeal support. METHODS: We conducted a retrospective review of all patients transported to our institution while receiving ECMO from September 2008 to September 2016. Survival to decannulation and survival to discharge were the primary outcomes. Obesity and morbid obesity were defined as a body mass index of greater than 30 kg/m2 and greater than 40 kg/m2, respectively. RESULTS: From 2008 to 2016, 222 patients were transported to our institution while receiving ECMO. Among these included patients, 131 were non-obese (interquartile range 22-27 kg/m2), 63 were obese (interquartile range 31-35 kg/m2) and 28 were morbidly obese (interquartile range 41-49 kg/m2), with 6 patients having a body mass index greater than 50 kg/m2 (range 52.3-79 kg/m2). Pre-ECMO arterial blood gases, disease severity indices, cannulation strategies and transport distances were similar between these 3 groups. There was no mortality of patients during transport, and survival to discharge was 66% (n = 87) in non-obese patients, 56% (n = 35) in obese patients and 82% (n = 23) in morbidly obese patients (P = 0.042). On multivariable logistic regression analysis, body mass index was not a predictor of in-hospital mortality (odds ratio 0.99, 95% confidence interval 0.95-1.03; P = 0.517). CONCLUSIONS: Transport of morbidly obese patients receiving ECMO may be performed safely and with excellent results in the setting of a dedicated ECMO transport programme with well-established management protocols.
Assuntos
Oxigenação por Membrana Extracorpórea , Obesidade Mórbida/complicações , Transporte de Pacientes , Adulto , Índice de Massa Corporal , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.
Assuntos
Diferenciação Celular , Células Progenitoras Endoteliais/citologia , Vasos Linfáticos/anormalidades , Adolescente , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Criança , Pré-Escolar , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/transplante , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Lactente , Vasos Linfáticos/citologia , Vasos Linfáticos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
Infantile hemangiomas (IHs) spontaneously involute, but some leave contour deformities necessitating surgical correction. There is a paucity of data reviewing predictive risk factors associated with a need for surgery to guide clinicians when counseling parents. Patients undergoing IH resection by a single surgeon from August 2004 to August 2011 were reviewed to determine patient (age, gender, birth history) and IH characteristics (size, location) associated with surgical intervention. Data were compared to published data from the Hemangioma Investigator Group (HIG). Statistical analysis was performed using Student's t-test, odds ratio, and logistic regression analysis. Out of 196 referred patients, 112 underwent surgery. There was a female preponderance (3.5:1). Two-thirds of patients (64.9%) first presented to the surgeon at ≤2 years of age, but most underwent surgery between 2 and 3 years (52.7%; average lag time, 11 months). 18 patients underwent surgery at ≤1 year of age. IH patients with preterm birth history had increased risk for needing surgical intervention (odds ratio 2.124, CI 1.31-3.44; p < 0.0012). A majority (84.7%) of resected IHs were located on the head or neck, significantly higher than the distribution from the HIG data (62.2%; p < 0.0001). Resected head and neck IHs were smaller than those below the neck (average, 8.85 cm(2) vs. 22.35 cm(2), p = 0.017). Preterm birth is associated with higher risk for requiring surgical intervention. IHs on the head and neck are more likely to be removed when compared to those below the neck, and at a smaller size threshold.
Assuntos
Hemangioma/classificação , Hemangioma/cirurgia , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/classificação , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND/PURPOSE: Despite high long-term survival rates in patients with Wilms tumor, there is a need to develop better prognostic biomarkers in order to maximize cure while avoiding treatment-associated morbidities. Tumor-associated macrophages have been recently associated with poorer prognosis and increased disease progression in a number of adult cancers. We investigated the relationship between macrophages and clinicopathological fators in this pediatric solid tumor. METHODS: Tissue microarray sections of 124 Wilms tumor cases obtained from the Cooperative Human Tissue Network were stained with CD68, a macrophage marker using standard immunohistochemical techniques and quantified using digital image processing techniques. Macrophage densities were correlated by tumor stage, and survival analyses were conducted with available clinical data. Immunohistochemistry was performed on 25 additional Wilms tumor cases obtained from the tumor bank at Columbia University Medical Center and correlated with presence of tumor microvascular invasion. RESULTS: Mean macrophage count densities in stage IV tumors were significantly greater than densities in stage I and III tumors (p=.021, .036). Although the overall and disease-free survival did not differ between high and low macrophage presence groups across all stages, increased macrophage presence was associated with decreased disease-free survival in patients with stage II tumors (p=0.035). Increased macrophage presence may have also correlated with decreased disease-free survival in stage IV patients, but the sample size was too small to allow detection of this difference with significance (p=0.575). Increased macrophage presence was associated with tumor microvascular invasion (p=0.0004). CONCLUSION: Our results suggest that macrophage recruitment may be associated with disease progression in Wilms tumor. Quantitation of macrophage presence may therefore be a useful adjunct in refining staging algorithms for patients with stage II Wilms tumor. Such data might be useful in the effort to reduce the risk of adverse effects associated with under- or overtreatment of this neoplasm.