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TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the ß-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is â¼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara -/-;tspearb -/- double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.
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Displasia Ectodérmica , Dente , Animais , Camundongos , Filogenia , Peixe-Zebra , Displasia Ectodérmica/epidemiologia , Dente/patologiaRESUMO
The YTH domain family member 3 gene (YTHDF3) encodes a reader of the abundant N6-methyladenosine (m6 A) modification of eukaryotic mRNA, which plays an essential role in regulating mRNA stability and is necessary to achieve normal development of the central nervous system in animal models. YTHDF3 has not previously been implicated in Mendelian disease despite a high probability of loss of function intolerance and statistical evidence of enrichment for gene-disruptive de novo variants in large-scale studies of individuals with intellectual disability and/or developmental delay. We report four individuals with deletion of 8q12.3, deletion size 1.38-2.60 Mb, encompassing YTHDF3, three of them were de novo, and in one case, the inheritance was unknown. Common features of the individuals (age range, 4-22 years) were developmental delay and/or intellectual disability. Two individuals underwent squint surgery. We suggest that haploinsufficiency of YTHDF3 causes a neurodevelopmental disorder with developmental delay and intellectual disability of variable degree.
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Alelos , Deleção Cromossômica , Cromossomos Humanos Par 8 , Predisposição Genética para Doença , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Proteínas de Ligação a RNA/genética , Adolescente , Criança , Feminino , Estudos de Associação Genética , Humanos , Perda de Heterozigosidade , Masculino , Fenótipo , Adulto JovemRESUMO
Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-ß pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.
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Adenosina Trifosfatases/química , Aquaporina 1/química , Hipertensão Pulmonar Primária Familiar/genética , Fatores de Diferenciação de Crescimento/química , Proteínas de Membrana Transportadoras/química , Mutação , Fatores de Transcrição SOXF/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Adulto , Aquaporina 1/genética , Aquaporina 1/metabolismo , Sequência de Bases , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Estudos de Casos e Controles , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/metabolismo , Hipertensão Pulmonar Primária Familiar/patologia , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Fator 2 de Diferenciação de Crescimento , Fatores de Diferenciação de Crescimento/genética , Fatores de Diferenciação de Crescimento/metabolismo , Células HEK293 , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , Prognóstico , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.
Assuntos
Pressão Arterial/genética , Hipertensão Pulmonar/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Artéria Pulmonar/fisiopatologia , Adulto , Idoso , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Análise Mutacional de DNA , Europa (Continente) , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hereditariedade , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations. In contrast to common unifocal venous malformation, which is most often caused by the somatic L914F TIE2 mutation, multifocal forms are predominantly caused by double (cis) mutations, that is, two somatic mutations on the same allele of the gene. Mutations are identical in all lesions from a given individual. T1105N-T1106P is recurrent in blue rubber bleb nevus, whereas Y897C-R915C is recurrent in sporadically occurring multifocal venous malformation: both cause ligand-independent activation of TIE2, and increase survival, invasion, and colony formation when expressed in human umbilical vein endothelial cells.
Assuntos
Neoplasias Gastrointestinais/genética , Predisposição Genética para Doença/epidemiologia , Mutação , Nevo Azul/genética , Receptor TIE-2/genética , Neoplasias Cutâneas/genética , Malformações Vasculares/genética , Bélgica , Estudos de Coortes , Feminino , Neoplasias Gastrointestinais/diagnóstico , Humanos , Incidência , Masculino , Nevo Azul/diagnóstico , Doenças Raras , Neoplasias Cutâneas/diagnóstico , Malformações Vasculares/diagnósticoRESUMO
OBJECTIVE: The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete). METHODS: Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016. RESULTS: Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen ('ultra-radical'), the combined rate of complete and optimal cytoreduction would be only 33.3%. CONCLUSIONS: Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.
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Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Idoso , Carcinoma Epitelial do Ovário , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologiaRESUMO
Proximal symphalangism (SYM1B) (OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands, typically of the ring and little finger, with the thumb typically being spared. SYM1 is frequently associated with coalition of tarsal bones and conductive hearing loss. Molecular studies have identified two possible genetic aetiologies for this syndrome, NOG and GDF5. We herein present a British caucasian family with SYM1B caused by a mutation of the GDF5 gene. A mother and her three children presented to the orthopaedic outpatient department predominantly for feet related problems. All patients had multiple tarsal coalitions and hand involvement in the form of either brachydactyly or symphalangism of the proximal and middle phalanx of the little fingers. Genetic testing in the eldest child and his mother identified a heterozygous missense mutation in GDF5 c.1313G>T (p.R438L), thereby establishing SYM1B as the cause of the orthopaedic problems in this family. There were no mutations identified in the NOG gene. This report highlights the importance of thorough history taking, including a three generation family history, and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity, and provides details of the spectrum of problems associated with SYM1B.
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Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC attaching/effacing (A/E) lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains.
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Blue rubber bleb naevus syndrome (BRBNS) is a rare vascular disorder characterized by rubbery blue-purple cutaneous nodules that are histologically thin-walled dilated vascular spaces. The exact inheritance of the disease in unknown but in cases of familial recurrence, there appears to be a pattern of autosomal dominant inheritance. The vascular lesions may manifest in any organ system but tend to predominate in the gastrointestinal tract (GI). There are only a handful of cases reported in the literature, but reported complications arising from the naevi include sponatenous GI bleeding requiring laparotomy and blood transfusion and the development of large naevi in the cervix thus preventing vaginal delivery. In this case we describe a patient with known BRBNS who developed symptomatic anaemia during her pregnancy which required antenatal admission and blood transfusion. She was managed expectantly in a multidisciplinary setting by obstetricians, gastroenterologists and an obstetric physician with the aim of a vaginal delivery. Nevertheless, she had an elective caesarean section at term for breech presentation. Surgery was complicated by the unexpected finding of venous malformations within the abdominal wall musculature and subcutaneous fat that resulted in a primary haemorrhage and required urgent blood transfusion. The patient made a good postoperative recovery and had a healthy male infant who at birth displayed no external features of BRBNS. This report demonstrates for the first time the appearance of naevi in the abdominal wall and the important considerations that need to be made regarding mode of delivery and future pregnancies.
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We report a case of recurrent chest wall abscesses overlying a right thoracotomy scar four years after a pneumonectomy for a right middle lobe bronchus squamous cell carcinoma. Exploration of the abscess cavities revealed no intra-thoracic or intra-abdominal communication. The patient developed sinuses in his thoracotomy scar and two years later, two gallstones were expelled from these sinuses. A cholecystocutaneous fistula was confirmed on a fistulogram.
Assuntos
Abscesso/diagnóstico , Fístula Biliar/diagnóstico , Cicatriz/patologia , Fístula Cutânea/diagnóstico , Pneumonectomia/efeitos adversos , Infecções Estreptocócicas/diagnóstico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Abscesso/terapia , Idoso de 80 Anos ou mais , Fístula Biliar/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cicatriz/etiologia , Fístula Cutânea/cirurgia , Diagnóstico Diferencial , Seguimentos , Cálculos Biliares/complicações , Cálculos Biliares/diagnóstico , Cálculos Biliares/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pneumonectomia/métodos , Recidiva , Medição de Risco , Infecções Estreptocócicas/terapia , Parede Torácica , Resultado do TratamentoRESUMO
BACKGROUND: Bimodal electric tissue ablation is a novel variation to standard radiofrequency ablation that produces significantly larger ablations by the addition of a direct electrical current. The negative electrode is attached to the radiofrequency current and the positive electrode is placed nearby. It has been identified that an electrolytic injury can occur at the positive electrode site. It is suggested that by increasing the surface area that is in contact with the positive electrode, the risk of tissue injury is reduced. This hypothesis was tested in a pig model. METHODS: Thirty-six ablations were carried out in the livers of six pigs (six ablations per pig). Two were standard radiofrequency ablation controls and two were carried out with positive electrode attached to a scalpel blade. Two were carried out with positive electrode attached to a grounding pad. After 48 h, liver was harvested and the ablation sizes were compared. Skin biopsies were taken from the scalpel site and one from the pad site and examined histopathologically. RESULTS: The scalpel blade ablations were significantly larger than controls and the grounding pad ablations (P < 0.001). The grounding pad ablation was significantly larger than controls. The scalpel blade skin site showed full-thickness tissue injury. The grounding pad site appeared microscopically normal. CONCLUSION: By increasing the surface area that connects to the positive electrode, significantly larger ablations can be carried out while minimizing the risk of associated tissue injury.
Assuntos
Ablação por Cateter/métodos , Fígado/cirurgia , Animais , Queimaduras/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Eletrodos/efeitos adversos , Fígado/anatomia & histologia , Modelos Animais , SuínosRESUMO
BACKGROUND: Radiofrequency ablation is a popular method of treating unresectable liver tumors but tumors greater than 3 cm in diameter have a much greater risk of local recurrence after treatment. Bimodal electric tissue ablation is a modified form of radiofrequency ablation that creates significantly larger ablations by the addition of extra direct current circuitry. This may help to reduce the risk of local recurrence in these larger tumors. Prior to use in a clinical setting, a long term study was performed to assess associated morbidity and the pathological changes in the ablations. METHODS: In eight pigs, six ablations were performed in each liver. Pigs were euthanized at 2 d, 2 wk, 2 mo, and 4 mo, and the ablations were assessed macroscopically and microscopically for pathological change. Regular blood tests were performed to assess changes in liver function. At death, any other abnormalities detected were reported. RESULTS: Histopathological examination of ablation zones revealed tissue death by coagulative necrosis and healing by fibrotic scarring. Transient rises in serum liver enzymes were seen in the postoperative period. Skin necrosis was noted at the site of the positive electrode of the direct electrical current but no other form of morbidity was seen associated with the procedure. CONCLUSIONS: Although the positive electrode placement requires further consideration, bimodal electric tissue ablation appears to be safe and behaves in a similar fashion to other thermal therapies such as standard radiofrequency ablation.
Assuntos
Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fígado/patologia , Fígado/cirurgia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Feminino , L-Lactato Desidrogenase/sangue , Fígado/metabolismo , Neoplasias Hepáticas/cirurgia , Necrose , Suínos , Fatores de Tempo , gama-Glutamiltransferase/sangueRESUMO
Radiofrequency ablation (RFA) is a method of treating non-resectable liver tumors by use of a high-frequency alternating electrical current. Concerns have been raised as the local recurrence rates following treatment have been reported to be as high as 47%. The size of the ablation is limited by charring of adjacent tissues. It is hypothesized that by hydrating the liver, we can reduce charring, thus producing larger ablations, and that this can be achieved by addition of a direct electrical current to the electrical circuit. Using a pig model, standard RFA control ablations were created in the left lobe of the liver. Ablations using the modified circuit were created in the right lobe. At the end of the procedure, the pig was killed by lethal injection and the liver harvested. From the explanted liver, the diameter of each ablation was measured and the modified ablations were compared with controls using restricted maximum likelihood variance analysis. From 4 pigs, 14 controls and 12 modified ablations were produced. The mean diameter of the controls was 27.78 mm (+/- SE 3.37 mm). The mean diameter of the modified ablation was 49.55 mm (+/- SE 3.46 mm), which was significantly larger than the controls (P < 0.001). This study has shown that by modification of the standard RFA circuit with the addition of a direct electrical current, significantly larger ablations can be produced. By using this technique, the number of ablations required to treat one tumor would be less and it is anticipated this could reduce the rate of local recurrence.
Assuntos
Ablação por Cateter/instrumentação , Ablação por Cateter/métodos , Eletrodos , Fígado/cirurgia , Animais , Ablação por Cateter/efeitos adversos , Feminino , Fígado/patologia , Neoplasias Hepáticas , Modelos Animais , Complicações Pós-Operatórias/prevenção & controle , Sus scrofaRESUMO
Lymphoepithelial cysts are rare pancreatic lesions. This case report describes the first excision of such a lesion by laparoscopic distal pancreatectomy which is a recognized procedure for treatment of cystic pancreatic neoplasms. Our patient underwent complete excision of the lesion and has enjoyed complete resolution of his symptoms. Laparoscopic distal pancreatectomy may be a suitable choice for first-line therapy for such lesions.
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Pancreatectomia/métodos , Cisto Pancreático/cirurgia , Humanos , Laparoscopia/métodos , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/patologia , Resultado do TratamentoRESUMO
Hepatic resection remains the "gold standard" for patients with resectable disease. Nevertheless, for a variety of reasons this is not feasible for the majority of patients. A wide range of locally ablative techniques has been developed for use in these patients with the aim of improving survival. Unfortunately, as with many recent techniques in surgery, much of the development of these methods, and particularly their introduction clinically, has not been based on sound scientific data. The relative merits and limitations of the more commonly used techniques are discussed, although this lack of prospective, randomized data precludes firm conclusions to be drawn from many of the studies reported. By far the most popular methods now employed, thermal techniques have certain limitations, particularly when treating tumors adjacent to major vascular or biliary structures. The authors believe that this situation represents the "niche" for which ablative techniques may ultimately find their logical application, where a single awkwardly placed metastasis deems a patient unresectable. If such a metastasis can be completely and safely ablated, a potentially curative resection may then become a realistic option. The relatively new, nonthermal technique of hepatic electrolysis has been extensively studied and shown to be safe and effective in close proximity to major intrahepatic veins due to a subtle electrochemical action rather than a rapid "burn". This technique is discussed in the context of other, more traditional thermal methods of ablation.
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Temperatura Alta/uso terapêutico , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Ablação por Cateter , Crioterapia , Eletrocoagulação , Eletrólise , Humanos , Hipertermia Induzida/métodos , Terapia a Laser , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , NecroseRESUMO
BACKGROUND: Intraoperative cholangiography during laparoscopic cholecystectomy reveals the anatomy of the biliary tree and any stones contained within it. The use of intraoperative cholangiography may be routine for all laparoscopic cholecystectomy. An alternative approach is a selective policy, performing intraoperative cholangiography only for those cases in which choledocholithiasis is suspected on clinical grounds, or those for which the anatomy appears unclear at operation. The literature pertaining to both approaches is reviewed, to delineate their respective merits. METHODS: Relevant articles in English were identified from the Medline database, and reviewed. RESULTS: The literature reviewed consisted of retrospective analyses. Overall the incidence of unsuspected retained stones was 4%, but only 15% of these would go on to cause clinical problems. The incidence of complete transection of the common bile duct was rare for both routine and selective intraoperative cholangiography policies, and did not differ between them. Rates of minor bile duct injury did not differ between groups, but was more likely to be recognized in the routine group than the selective (P = 0.01). CONCLUSIONS: Routine intraoperative cholangiography yields very little useful clinical information over and above that which is obtained with selective policies. Large numbers of unnecessary intraoperative cholangiography are performed under routine intraoperative cholangiography policy, and therefore a selective policy is advocated.
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Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia Laparoscópica , Cuidados Intraoperatórios , Ductos Biliares/anatomia & histologia , Cálculos Biliares/diagnóstico por imagem , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Per-ductal pancreatic electrolysis is a new minimally invasive ablation treatment. Possible applications include tumor debulking and treatment of chronic pancreatitis. Both solid organ ablation and pancreatitis are associated with the risk of an overwhelming systemic inflammatory response syndrome (SIRS) and multiorgan failure. TNF-alpha and IL1-beta are important cytokine mediators of this response. The aim of this study was to measure the circulating levels of IL1-beta and TNF-alpha following pancreatic electrolytic ablation as a marker of the risk of SIRS complicating per-ductal pancreatic electrolysis. METHODS: Serum TNF-alpha and IL1-beta were measured in six treatment and six control pigs before and after laparotomy and pancreatic electrolytic ablation via a per-ductal approach. RESULTS: There was no significant rise in serum TNF-alpha and IL1-beta in association with per-ductal pancreatic electrolysis. CONCLUSIONS: This study supports the evidence that per-ductal electrolysis is a safe procedure with potential for palliative treatment of pancreatic cancers.
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Eletrólise , Pâncreas , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Amilases/sangue , Animais , Proteína C-Reativa/metabolismo , Feminino , Interleucina-1/sangue , Fatores de Risco , Suínos , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Fulminant hepatic failure (FHF) is an important cause of death worldwide. Despite significant improvements in critical care therapy there has been little impact on survival with mortality rates approaching 80%. In many patients the cause of the liver failure is reversible and if short-term hepatic support is provided, the liver may regenerate. Survivors recover full liver function and a normal life expectancy. For many years the only curative treatment for this condition has been liver transplantation, subjecting many patients to replacement of a potentially self-regenerating organ, with the lifetime danger of immunosuppression and its attendant complications, such as malignancy. Because of the shortage of livers available for transplantation, many patients die before a transplant can be performed, or are too ill for operation by the time a liver becomes available. Many patients with hepatic failure do not qualify for liver transplantation because of concomitant infection, metastatic cancer, active alcoholism or concurrent medical problems. The survival of patients excluded from liver transplantation or those with potentially reversible acute hepatitis might be improved with temporary artificial liver support. With a view to this, bioartificial liver support devices have been developed which replace the synthetic, metabolic and detoxification functions of the liver. Some such devices have been evaluated in clinical trials. During the last decade, improvements in bioengineering techniques have been used to refine the membranes and hepatocyte attachment systems used in these devices, in the hope of improving function. The present article reviews the history of liver support systems, the attendant problems encountered, and summarizes the main systems that are currently under evaluation.
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Fígado Artificial , Células Cultivadas , Hepatócitos , História do Século XX , História do Século XXI , Humanos , Fígado Artificial/história , Resultado do TratamentoRESUMO
Morgagni herniae are rare congenital diaphragmatic hernia, which normally present late in adult life with minimal symptoms. They are always associated with a peritoneal hernial sac, and often contain transverse colon or stomach. We present an unusual case of a Morgagni hernia containing caecum in an 81-year-old woman, post ruptured aortic aneurysm repair.
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Hérnia Diafragmática/etiologia , Idoso , Idoso de 80 Anos ou mais , Ceco/anormalidades , Feminino , Hérnia Diafragmática/diagnóstico por imagem , Hérnia Diafragmática/cirurgia , Hérnias Diafragmáticas Congênitas , Humanos , Radiografia , RotaçãoRESUMO
BACKGROUND: Resection offers the only chance of cure for hepatic colorectal metastases. However, preoperative staging does not always reliably detect unresectable disease. The aim of this study was to investigate the role that laparoscopy with ultrasound may have in detecting unresectable disease, thus sparing patients from unnecessary laparotomy with the associated morbidity and cost. METHODS: A retrospective review of all patients considered for liver resection of colorectal metastases during a 3-year period was performed, analyzing factors likely to predict resectable disease, rates of resectability, and success of laparoscopic staging at detecting unresectable disease. RESULTS: Of 73 patients with resectable disease on computed tomography, 24 were deemed to need laparoscopy, and 49 proceeded directly to laparotomy. Those first undergoing laparoscopy had shorter disease-free intervals between diagnosis of colorectal cancer and detection of hepatic recurrence and greater numbers of hepatic metastases. Twelve of the 24 patients who underwent laparoscopy had unresectable disease, and 8 of these were detected at laparoscopy. Forty-six of the 49 patients proceeding to laparotomy directly had resectable disease. CONCLUSIONS: Laparoscopic staging of hepatic colorectal metastatic disease detects most unresectable disease, preventing unnecessary laparotomy. The likelihood of disease being unresectable is in part predicted by the disease-free interval and the number of hepatic metastases.