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LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Discuss the key points in diagnosing lymphedema. 2. Understand the imaging modalities that facilitate diagnosis and surgical planning. 3. Appreciate the indications for both physiologic and ablative procedures. 4. Recognize the potential role of lymphaticovenular anastomosis and vascularized lymph node transfer in the treatment of patients with lymphedema. SUMMARY: Lymphedema is an incurable disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within the soft tissues. Although this condition may result from a primary structural defect of the lymphatic system, most cases in developed countries are secondary to iatrogenic causes. The diagnosis of lymphedema can be made readily by performing a clinical history and physical examination and may be confirmed by imaging studies such as lymphoscintigraphy, magnetic resonance lymphangiography, or indocyanine green lymphangiography. Nonsurgical treatment continues to be the mainstay of lymphedema management. However, advances in microsurgical techniques have revolutionized surgical options for treating lymphedema, and emerging evidence suggests that reconstructive methods may be performed to restore lymphatic flow. Procedures such as lymphaticovenular anastomosis and vascularized lymph node transfer can potentially offer a more permanent solution to chronic lymphedema, and initial studies have demonstrated promising results.
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Linfedema/cirurgia , Algoritmos , Humanos , Linfedema/diagnóstico , Linfedema/fisiopatologia , Procedimentos Cirúrgicos Operatórios/métodosRESUMO
BACKGROUND: Centrifugation (Cf) is a common method of fat processing but may be time consuming, especially when processing large volumes. OBJECTIVES: To determine the effects on fat grafting time, volume efficiency, reoperations, and complication rates of Cf vs an autologous fat processing system (Rv) that incorporates fat harvesting and processing in a single unit. METHODS: We performed a retrospective cohort study of consecutive patients who underwent autologous fat grafting during reconstructive breast surgery with Rv or Cf. Endpoints measured were volume of fat harvested (lipoaspirate) and volume injected after processing, time to complete processing, reoperations, and complications. A budget impact model was used to estimate cost of Rv vs Cf. RESULTS: Ninety-eight patients underwent fat grafting with Rv, and 96 patients received Cf. Mean volumes of lipoaspirate (506.0 vs 126.1 mL) and fat injected (177.3 vs 79.2 mL) were significantly higher (P < .0001) in the Rv vs Cf group, respectively. Mean time to complete fat grafting was significantly shorter in the Rv vs Cf group (34.6 vs 90.1 minutes, respectively; P < .0001). Proportions of patients with nodule and cyst formation and/or who received reoperations were significantly less in the Rv vs Cf group. Based on these outcomes and an assumed per minute operating room cost, an average per patient cost savings of $2,870.08 was estimated with Rv vs Cf. CONCLUSIONS: Compared to Cf, the Rv fat processing system allowed for a larger volume of fat to be processed for injection and decreased operative time in these patients, potentially translating to cost savings. LEVEL OF EVIDENCE 3.
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Tecido Adiposo/transplante , Centrifugação/economia , Técnicas Cosméticas/economia , Eficiência Organizacional , Custos de Cuidados de Saúde , Lipectomia/economia , Salas Cirúrgicas/economia , Salas Cirúrgicas/organização & administração , Procedimentos de Cirurgia Plástica/economia , Procedimentos de Cirurgia Plástica/métodos , Coleta de Tecidos e Órgãos/economia , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Orçamentos , Centrifugação/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Redução de Custos , Análise Custo-Benefício , Feminino , Humanos , Lipectomia/efeitos adversos , Pessoa de Meia-Idade , Modelos Econômicos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Coleta de Tecidos e Órgãos/efeitos adversos , Transplante Autólogo , Resultado do Tratamento , Fluxo de Trabalho , Adulto JovemRESUMO
Autologous fat grafting is widely used in breast surgery to refine and optimize aesthetic outcomes. Despite its widespread use, obtaining predictable, reliable, and consistent outcomes remains a significant challenge and is influenced by the technique used for procurement, processing, and placement of the fat. At present, there is no published consensus on the optimal technique. The purpose of this article is to review current techniques at each stage of fat grafting and provide tips on best practices based on the published literature as well as our extensive clinical experience.
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BACKGROUND: Botulinum toxin A has been successfully used in a variety of areas to temporarily obliterate muscle mobility for either functional or aesthetic gain. Tissue expander-based breast reconstruction has been plagued with pain and discomfort. OBJECTIVE: The purpose of this pilot study was to evaluate the role of a neurotoxin (Botulinum toxin A) in expander-based breast reconstruction. METHODS: Thirty patients underwent mastectomies with immediate expander or acellular dermal matrix reconstruction. The neurotoxin group (n = 15) received 40 units of neurotoxin (Botulinum toxin A, Allergan, Inc, Irvine, CA) into each pectoralis major muscle through 4 serial injections and the placebo group (n = 15) received 4 serial injections of 0.9% NaCl. All patients were followed over 1 year, and patient demographics, VAS (visual analog score), laterality, office visits, amount of expansion and number of times to full expansion, and amount of narcotics required were recorded. Statistical significance was considered as p < .05. RESULTS: There were no significant differences between the two groups in terms of age, laterality, expander size, or complications (p = .46-.66). There was a significant difference between the two groups in the VAS score, demonstrating decreased pain in the neurotoxin group (p < .05). In addition, there was a significant increase in the volume of expansion per visit in the neurotoxin group as compared to the placebo group (p < .05). There was no significant difference in narcotic use in the first 3 days after surgery; however, there was a significant decrease in use of narcotics from 7 to 45 days in the neurotoxin group (p < .05). There were no complications associated with the use of the neurotoxin. CONCLUSIONS: The infiltration of the pectoralis major muscle with neurotoxin in immediate, expander-based reconstruction may be beneficial in reducing pain and expediting expansions.
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Toxinas Botulínicas Tipo A/administração & dosagem , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Derme Acelular , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Fármacos Neuromusculares/administração & dosagem , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Projetos Piloto , Estudos Prospectivos , Expansão de Tecido/métodosRESUMO
Sushruta is considered the "Father of Plastic Surgery." He lived in India sometime between 1000 and 800 BC, and is responsible for the advancement of medicine in ancient India. His teaching of anatomy, pathophysiology, and therapeutic strategies were of unparalleled luminosity, especially considering his time in the historical record. He is notably famous for nasal reconstruction, which can be traced throughout the literature from his depiction within the Vedic period of Hindu medicine to the era of Tagliacozzi during Renaissance Italy to modern-day surgical practices. The primary focus of this historical review is centered on Sushruta's anatomical and surgical knowledge and his creation of the cheek flap for nasal reconstruction and its transition to the "Indian method." The influential nature of the Sushruta Samhita, the compendium documenting Sushruta's theories about medicine, is supported not only by anatomical knowledge and surgical procedural descriptions contained within its pages, but by the creative approaches that still hold true today.
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Cirurgia Plástica/história , História Antiga , Índia , Itália , Ayurveda/história , Rinoplastia/história , Retalhos Cirúrgicos/história , Livros de Texto como Assunto/históriaRESUMO
In 2008, the Centers for Medicare and Medicaid Service adapted a list from the National Quality Forum consisting of 10 hospital-acquired conditions, also known as never events. Deeming such events as preventable in a safe-hospital setting, reimbursement is no longer provided for treatments arising secondary to these events. A retrospective chart review identified 90 panniculectomy and abdominoplasty patients. The hospital-acquired conditions examined include surgical-site infections (SSI), vascular-catheter associated infections, deep venous thrombosis/pulmonary embolism, retained foreign body, catheter-related urinary tract infection, manifestations of poor glycemic control, falls and trauma, air embolism, pressure ulcers (stages III and IV), and blood incompatibility. Information regarding age, American Society of Anesthesiologists (ASA) classification, body mass index, smoking, and chemotherapy were collected. Patients were divided into 2 groups, namely, those who developed never events and those with no events. Of the 90 patients, 14 (15.5%) developed never events because of SSI. No events occurred in the remaining 9 categories. Statistically significant risk factors included American Society of Anesthesiologists classification, age, and diabetes mellitus. The most common never event was SSI. In light of the obvious prevalence of the risk factors in patients who develop these events, the question of whether never events are truly unavoidable arises. Despite this, awareness of the impact on patient care, health care and hospital reimbursement is vital to understanding the new paradigm of the "one size fits all."
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Abdominoplastia , Lipectomia , Medicaid/normas , Medicare/normas , Complicações Pós-Operatórias/etiologia , Mecanismo de Reembolso/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Estudos Retrospectivos , Fatores de Risco , Estados UnidosRESUMO
Massive localised lymphoedema (MLL) is a benign lymphoproliferative soft-tissue overgrowth in the morbidly obese patient. The diagnosis may be challenging, and is a form of secondary lymphoedema, often described as idiopathic scrotal elephantiasis. The lesion presents as a large mass in the morbidly obese, and patients seek treatment late in the disease course due to limitation of daily living or excoriation and wound breakdown. Resection, followed by reconstruction, is indicated in these cases. We present a unique case of a morbidly obese 52-year-old male with massive enlargement of the scrotum present for several years duration, despite massive weight loss (88.85 kg) from gastric bypass surgery and no other identifiable cause of lymphoedema. Scrotal lymphoedematous tissue was resected and scrotal reconstruction with a novel posterior fasciocutaneous flap from the scrotum was performed in addition to penile reconstruction with a skin graft and local fasciocutaneous flaps as well as a panniculectomy. Histologically, the tissue was characterised by marked oedema with dermal fibrosis and patchy mild perivascular chronic inflammation. Postoperative follow-up revealed wound integrity and patient satisfaction with the outcome. MLL is an important disease process with distinct clinical and histopathologic characteristics that often requires complex reconstruction. Although there are several opposing classification schema, we propose the incorporation of idiopathic scrotal elephantiasis into the diagnostic category of MLL.
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Linfedema/cirurgia , Obesidade Mórbida/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Escroto/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Abdominoplastia/métodos , Índice de Massa Corporal , Elefantíase/diagnóstico , Elefantíase/cirurgia , Seguimentos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Linfedema/diagnóstico , Linfedema/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Cuidados Pós-Operatórios/métodos , Doenças Raras , Medição de Risco , Escroto/fisiopatologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Plastic surgeons have been performing operations to improve the aesthetic aspect of the breast for centuries. Throughout ancient times, great controversy produced many theories of how breast cancer occurred and the best treatment. Because of beliefs that closure of mastectomy sites could conceal tumor recurrence, breast reconstruction did not gain wide acceptance until the mid-1900s. Today, plastic surgeons have a variety of techniques to reconstruct the breast. The first autologous muscle flap for breast reconstruction was the latissimus dorsi myocutaneous flap, described in 1896 by Iginio Tansini. The introduction of Carl Hartrampf's transverse rectus abdominis myocutaneous flap and Robert J. Allen's deep inferior epigastric perforator flap have also provided excellent reconstructive options. With regard to augmentation, Vincenz Czerny attempted to enhance a woman's breast in 1895 with implantation of a lumbar lipoma. Soon after, surgeons used paraffin injections and polyvinylic alcohol sponge implantation, which yielded disastrous results. In 1961, Thomas Cronin and Frank Gerow promoted the first silicone implant, paving the way for today's silicone and saline prototypes. Although reduction mammaplasty techniques had originated centuries earlier than mastopexy methods, the advancements of both have largely paralleled one another. In 1949, the Wise pattern was introduced to preoperatively plan safer and predictable outcomes in breast reductions. Efforts to minimize scars were achieved with Claude Lassus' introduction and Madeleine Lejour's subsequent modification of the vertical scar mammaplasty. In hopes of fostering an understanding of current post-mastectomy procedures and instilling passion for innovating future techniques, we provide a near-complete, surgically focused historical account of the primary contributors to breast reconstruction.
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Neoplasias da Mama/história , Mamoplastia/história , Mastectomia/história , Retalhos Cirúrgicos/história , Neoplasias da Mama/cirurgia , Feminino , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do TratamentoRESUMO
BACKGROUND: Although it is known that small intestinal carcinoids are derived from enterochromaffin (EC) cells, these cells remain poorly characterized and little is known of the growth regulatory mechanisms of these neuroendocrine cells. Down-regulation or loss of the transforming growth factor-beta1 (TGFbeta1) cytostatic program and activation of TGFbeta-mediated transcriptional networks is associated with uncontrolled growth and metastasis in other neural tumors, glioblastomas. Whether this phenomenon is common to small intestinal carcinoid tumors was investigated. METHODS: The effects of TGFbeta1 on cultured normal EC cells (isolated by FACS sorting) and the neoplastic EC cell line, KRJ-I, was assessed using the MTT assay. The TGFbetaRII transcript and protein were identified in tumor cells and the effects of TGFbeta1 on SMAD2 phosphorylation and nuclear translocation quantified. The time-dependent response of SMAD4, SMAD7, c-Myc, and P21(WAF1/CIP1) protein expression and c-Myc and p21(WAF1/CIP1) transcript was measured in response to TGFbeta1 and the transcript expression of candidate downstream targets, MTA1 and E-cadherin, were assessed. RESULTS: TGFbeta1 inhibited normal EC cell proliferation (IC(50) = 17 pM) but stimulated neoplastic EC cell proliferation (EC(50) = 22 pM). In tumor cells, significantly decreased transcript (P < .01) of TGFbetaRII was identified, but no receptor mutations were identified and protein expression was evident. TGFbeta1 (1 ng/mL) resulted in SMAD2 phosphorylation and <7% nuclear expression compared with 93% in normal EC cells. In neoplastic cells, TGFbeta1 (1 ng/mL) caused a decrease in SMAD4 (>16%, P < .05), whereas SMAD7 and c-Myc transcript and protein were respectively increased >21% (P < .05) and approximately 40% (P < .002). TGFbeta1 (1 ng/mL) also decreased p21(WAF1/CIP1) transcript by 60% (P < .001) and protein that was undetectable at 24 hours. Expression of the downstream targets of the c-Myc pathway, MTA1, was increased (20%) and E-cadherin decreased (30%). CONCLUSIONS: The neoplastic EC cell is characterized by loss of TGFbeta-1-mediated growth inhibition and, similar to glioblastomas, utilizes the TGFbeta system to induce gene responses associated with growth promotion (c-Myc and the ERK pathway), invasion (E-cadherin), and metastasis (MTA1).
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Tumor Carcinoide/patologia , Histona Desacetilases/genética , Neoplasias Intestinais/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta1/farmacologia , Western Blotting , Caderinas/metabolismo , Tumor Carcinoide/genética , Tumor Carcinoide/metabolismo , Proliferação de Células , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células Enterocromafins/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/metabolismo , Humanos , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Transativadores , Células Tumorais Cultivadas , Regulação para CimaRESUMO
OBJECTIVES: Small intestinal neuroendocrine tumors (SI-NETs) are the most common gastrointestinal neuroendocrine tumor, but their natural history and outcome remain poorly defined, which hinders both the prediction of disease progression and appropriate therapeutic options. We examined patterns, incidence, prognosis, and outcomes of these tumors over a 30-yr period. METHODS: Data were extracted from the NCI's SEER registry (1973-2002). Incidence rates, distribution, and 5-yr survival rates were analyzed and adjusted (U.S. decennial census data). RESULTS: Of the 18,641 NETs, 3,911 (21.0%) were SI-NETs, of which 1,953 (49.6%) were ileal. Since 1973, both SI-NET and its ileal variant have increased annually by 3.8% and 2.1%, respectively. Ileal tumors, as a percentage of SI tumors, have increased from 52% to 63.6%. The age-adjusted incidence of ileal, small intestinal, and digestive system NETs has increased 225%, 460%, and 720% over 30 yr. Ileal tumors have specifically increased in prevalence in white (274%) and black (500%) men and women (213% and 286%, respectively); an overall increase of fourfold in blacks and 2.4-fold in whites. Although 83.3% of SI-NETs were staged, 83.7% were histologically ungraded. Five-year survival rates for SI-NETs were 62.6 +/- 1% (all stages), 73.8% (localized), 72% (regional), and 43.2% (distant). These have not significantly altered since 1973 (P= 0.11). CONCLUSIONS: SI-NETs have increased, particularly in men and in the black population, which may be due to in vivo changes, increased clinical and pathological awareness, or increased detection of tumors. SI-NETs are malignant, diagnosed late, and survival rates have remained unchanged over 30 yr.
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Neoplasias Duodenais/epidemiologia , Neoplasias do Íleo/epidemiologia , Neoplasias do Jejuno/epidemiologia , Tumores Neuroendócrinos/epidemiologia , Progressão da Doença , Neoplasias Duodenais/diagnóstico , Feminino , Seguimentos , Humanos , Neoplasias do Íleo/diagnóstico , Incidência , Neoplasias do Jejuno/diagnóstico , Masculino , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Small intestinal carcinoids (SICs) are the most prevalent gastrointestinal carcinoid and characterized by local invasion metastasis and protean symptomatology. The proliferative and secretory regulation of the cell of origin, the enterochromaffin (EC) cell has not been characterized. The absence of either a pure preparation of normal EC cells or human EC carcinoid cell lines has hindered the development of therapeutic agents. We therefore further characterized the neoplastic SIC cell line, KRJ-I by assessing its secretory (serotonin (5-HT)) and proliferative responses and defining its log growth phase transcriptome. Electron microscopy demonstrated oval, lobulated nuclei and substance P, and 5-HT-positive cytoplasmic vesicles. RT-PCR detected transcripts for chromogranin A (CHGA), VMAT1 (SLC18A1), tryptophan hydroxylase (TPH1), substance P (TAC1), guanylin (GUCA2A), and SERT (SLC6A4). By immunohistochemistry, all cells were positive for CHGA, SERT, VMAT1, and TPH1. Transcriptome analysis (Affymetrix U133 Plus chips) identified somatostatin SSTR2/3, adrenergic alpha1C and beta1, dopamine D2, nicotinic-type cholinergic A5, A6, B1, muscarinic acetylcholine M4, and 5-HT-2A receptors. The presence of transcripts for SSTR1, SSTR2, and SSTR3 receptors was confirmed by RT-PCR and sequencing. Isoproterenol (ISO) resulted in a dose-dependent increase in intracellular cAMP (EC50=340 nM) and 5-HT (EC50=81 nM) which was completely inhibited by the cAMP antagonist 2',5'-dideoxyadenosine (10 microM). Preincubation with a SSTR agonist, lanreotide, inhibited Ip-stimulated 5-HT secretion (IC50=420 nM). Both lanreotide (10 nM) and rapamycin (50 nM) inhibited proliferation (20+/-12 and 35+/-5% respectively) in serum-free medium whereas gefitinib (1 nM-10 microM) inhibited proliferation at micromolar concentrations. KRJ-I is a neoplastic EC cell line that can be used as an in vitro model of SICs as it will allow elucidation and clarification of the secretory and proliferative mechanism(s) of neoplastic EC cells and the molecular signatures that characterize each of these responses.
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Células Enterocromafins/efeitos dos fármacos , Células Enterocromafins/metabolismo , Peptídeos Cíclicos/fisiologia , Sirolimo/farmacologia , Somatostatina/análogos & derivados , Linhagem Celular Tumoral , Humanos , Sistemas Neurossecretores/citologia , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Somatostatina/fisiologiaRESUMO
As early as the 2nd century, Galen proposed that 'vital spirits' in the blood regulated human bodily functions. However, the concept of hormonal activity required a further 18 centuries to develop and relied upon the identification of 'ductless glands', Schwann's cell and the recognition by Bayliss and Starling of chemical messengers. Bernard's introduction of 'internal secretion' and its role in homeostasis laid a physiological basis for the development of endocrinology. Kocher and Addison recognized the consequences of ablation of glands by disease or surgery and identified their necessary role in life. Detailed descriptions of the endocrine cells of the gut and pancreas and their putative function were provided by Heidenhain, Langerhans, Laguesse and Sharpey-Schafer. Despite the dominant 19th century concept of nervism (Pavlov), in 1902, Starling and Bayliss using Hardy's term 'hormonos' described secretin and in so doing, established the gut as an endocrine organ. Thus, nervism was supplanted by hormonal regulation of function and thereafter numerous bioactive gut peptides and amines were identified. At virtually the same time (1892), Ramón y Cajal of Madrid reported the existence of a group of specialized intestinal cells that he referred to as 'interstitial cells'. Cajal postulated that they might function as an interface between the neural system and the smooth muscles of the gut. Some 22 years later, Keith suggested that their function might be analogous to the electroconductive system of the heart and proposed their role as components of an intestinal pacemaker system. This prescient hypothesis was subsequently confirmed in 1982 by Thuneberg and a decade later Maede identified c-Kit as a critical molecular regulator in the development and function of the interstitial cells of Cajal and further confirmed the commonality of neural and endocrine cells. The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson's staining techniques, identified 'helle Zellen' within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system. Pearse subsequently grouped the various cells belonging to that system under the rubric of a unifying APUD series. Currently, the gut neuroendocrine system is viewed as a syncytium of neural and endocrine cells sharing a common cell lineage whose phenotypic regulation is as yet unclear. Their key role in the regulation of gastrointestinal function is, however, indubitable.
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Comunicação Celular/fisiologia , Gastroenterologia/história , Hormônios/história , Neuroendocrinologia/história , Sistemas Neurossecretores/fisiologia , Células APUD/fisiologia , Animais , Células Enteroendócrinas/fisiologia , Hormônios Gastrointestinais/história , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , HumanosRESUMO
Prior to the contributions of Friedrich Feyrter (1895-1973), the regulation of gastrointestinal function was an ill-understood field that was polarized by a combination of the inability of clinical scientists to perceive the relationship between the cellular elements of 'nervism' and the newly recognized chemical messenger system. Feyrter, an Austrian pathologist of luminescent intellect and possessed of rigorous analytic capacity, recognized the interface of the divergent elements (neural and endocrine) and established the concept of the diffuse neuroendocrine system. His pathological descriptions of the specialized neuroendocrine cells producing biologically active substances and regulating homeostasis by a network functioning via endocrine, paracrine, and neuracrine mechanisms laid the basis for contemporary understanding of gut function. In 1938, Feyrter identified Helle Zellen (clear cells) of the pancreas and gastrointestinal tract, which was later incorporated into the amine precursor uptake decarboxylation concept of endocrine cells by A.G.E. Pearse (1916-2003). Feyrter proposed a diffuse network as a functional regulatory system as opposed to the then current doctrine of 'organ' regulation in his 1938 manuscript Uber diffuse endokrine epitheliale Organe. In addition to this seminal contribution, the prodigious intellect of Feyrter produced an array of novel observations including benign and malignant tumors of the skin, gastrointestinal tract, and eyes, carcinoid tumors and the carcinoid syndrome, the genesis of the nevus, the transformation of lipids and disorders of cellular metabolism. Sadly, the contributions of Feyrter were obscured in the catastrophe of wartime Germany and his accomplishments little recognized. We describe the life and times of this gifted scientist, teacher, and pathologist, often referred to as the 'Father of Neuroendocrinology'.
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Gastroenterologia/história , Neuroendocrinologia/história , Sistemas Neurossecretores/fisiologia , História do Século XX , HumanosRESUMO
CONTEXT: Neuroendocrine regulation of small intestinal (SI) function is poorly understood because pure neuroendocrine cells are unavailable, whereas the biological basis of SI carcinoid tumors is unknown because neoplastic human enterochromaffin (EC) cells are unavailable. OBJECTIVE: The objective of this study was to define the secretory regulation and transcriptome of naive and neoplastic SI neuroendocrine cells. DESIGN: EC cells from human ilea were isolated and purified, and a malignant EC cell carcinoid cell line (KRJ-I) was characterized. METHODS: Human ilea from right hemicolectomies were pronase/collagenase digested and Nycodenz gradient centrifuged, and EC cells were fluorescence-activated cell sorting (FACS) sorted after acridine orange labeling. Enrichment was defined by immunostaining, gene expression, serotonin (5-HT) content, and real-time RT-PCR. Naive FACS-sorted EC and KRJ-I cells were cultured, and 5-HT secretion was measured after stimulation with forskolin, isoproterenol, acetylcholine, gamma-aminobutyric acid A (GABA(A)), pituitary adenylate cyclase-activating polypeptide (PACAP)-38, and gastrin. Normal and neoplastic EC cell transcriptomes were acquired by Affymetrix profiling (U133A). RESULTS: FACS produced 100 +/- 0.3% (chromogranin A staining) and 99 +/- 0.7% pure EC cells by immunostaining for tryptophan hydroxylase with greater than 67-fold enrichment and a 5-HT content of 180 +/- 18 ng/mg protein (mucosa, 3.5 +/- 0.9). Forskolin- and isoproterenol-stimulated 5-HT secretion was 10-100 times more potent for naive cells (EC(50), 1.8 x 10(-9) m; 5.1 x 10(-9) m) than neoplastic cells (EC(50), 2.1 x 10(-7) m; 8.1 x 10(-8) m), but the effect of PACAP-38 was similar (EC(50), 1 x 10(-7) m). Isoproterenol stimulated cAMP levels 1.6 +/- 0.1-fold vs. basal (EC(50), 2.7 x 10(-9) m). Acetylcholine inhibited naive EC cell 5-HT secretion more potently than neoplastic (IC(50), 3.2 x 10(-9) vs. 1.6 x 10(-7) m), whereas GABA(A) was more potent in neoplastic cells (IC(50), 3.9 x 10(-10) vs. 4.4 x 10(-9) m). Octreotide inhibited naive, but not neoplastic, basal 5-HT secretion. Gastrin had no effect on 5-HT secretion. Comparison of naive and neoplastic transcriptomes revealed shared neuroendocrine and EC cell-specific marker genes. Real-time PCR confirmed that expression of adrenergic (beta1), somatostatinergic (SST(R)2), and neural (VPAC(1) and GABA(A)) receptors occurred on both cell types, but PACAP type 1 (PAC(1)) and cholecystokinin type 2 (CCK(2)) were undetectable. The putative carcinoid malignancy genes (MTA1 and MAGE-D2) were unique to the neoplastic EC cell transcriptome. CONCLUSION: These data support novel methodology to purify live human EC cells for functional characterization and transcriptome assessment, which will allow identification of new targets to control the secretion and proliferation of SI carcinoids.
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Tumor Carcinoide/metabolismo , Células Enterocromafins/fisiologia , Neoplasias do Íleo/metabolismo , Serotonina/metabolismo , Tumor Carcinoide/patologia , Linhagem Celular Tumoral , Separação Celular , Humanos , Neoplasias do Íleo/patologia , Imuno-Histoquímica , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Transcrição GênicaRESUMO
Throughout past millennia, human beings have shared the common goal of improving health for longevity. However, different cultures around the world have developed their own approaches to achieve this goal. Various traditions have emerged, rendering distinct medical systems such as Ayurveda, Yoga, Chinese-Japanese medicine, shamanism, and Native American healing. Traditional medicine involves a holistic approach to the human body to integrate healing with culture, environment, and tradition. Modern allopathic medicine originated from Greco-Roman Medicine and Northern European traditions and is built on the science of anatomy, physiology, and biochemistry and the structure-function relationship between cells, tissues, and organs. This foundation focuses on diagnosis, treatment, and cure for acute illnesses via potent pharmaceutical drugs, surgery, radiation, and other treatment modalities. Within this past century, we have doubled the life-span of human beings. Genomic medicine, including stem cell research, cloning, and gene therapy, will increase our capability to treat even more diseases. In the new millennium, we face more chronic illnesses related to aging, environment, and lifestyle, such as cancer, diabetes. osteoporosis, and cardiovascular diseases. Thus, health care providers face the challenge of prospecting for health and disease prevention. Modern science and medical advancements provide the rationale for the integration of various traditional healing techniques, which have been termed Alternative and Complementary Medicine, to promote healing, health, and longevity. Advances in medicine must include the holistic approach of traditional medicine to face the current challenges in health care. Therefore, the New World of Medicine must fuse the antiquity of ancient healing with the innovations of modern medicine to increase life-expectancy and improve quality of life throughout the world.