RESUMO
OBJECTIVE: The outcomes of fundoplication for gastroesophageal reflux disease are suboptimal in many children, and alternatives are clearly needed. Dextranomer hyaluronic acid (DxHA) copolymer, an agent with proven efficacy in vesicoureteral reflux, was studied with respect to its effects on the gastroesophageal junction (GEJ). METHODS: Twelve New Zealand white rabbits underwent measurement of lower esophageal sphincter pressure followed by laparotomy and injection into the muscular layer of the GEJ (controls, 1.0 mL saline; low-dose DxHA [0.5 mL]; high-dose DxHA [1.0 mL]). After a 12-week survival period, the animals underwent manometry, sacrifice, and necropsy. Organs were examined histologically by pathologists blinded to the injection delivered. RESULTS: All animals survived. Weight gain was equal in the 3 groups. There was no significant difference in mean lower esophageal sphincter pressure from baseline in any group (control 2.3 mmHg [95% confidence interval, CI -3.3 to 7.9]; low-dose group 3.2 mmHg [95% CI -0.8 to 7.2]; high-dose group -4.0 mmHg [95% CI -18.95 to 10.95]). Histologically, DxHA injection produced an intramural implant, with a foreign body giant cell reaction, and fibroblastic infiltration with collagen deposition. High-dose injection did not consistently result in a qualitative increase in the magnitude of the reaction. There was no mucosal injury or luminal stenosis. CONCLUSIONS: In this first study evaluating the effects of DxHA injection at the GEJ, a histologic bulking effect was observed without obvious functional complications. The agent may have a role in the treatment of gastroesophageal reflux disease.
Assuntos
Dextranos/administração & dosagem , Junção Esofagogástrica/efeitos dos fármacos , Ácido Hialurônico/administração & dosagem , Animais , Colágeno/análise , Relação Dose-Resposta a Droga , Esfíncter Esofágico Inferior/efeitos dos fármacos , Esfíncter Esofágico Inferior/fisiologia , Junção Esofagogástrica/anatomia & histologia , Fibroblastos/fisiologia , Reação a Corpo Estranho/induzido quimicamente , Refluxo Gastroesofágico/tratamento farmacológico , Células Gigantes de Corpo Estranho/fisiologia , Injeções Intramusculares/veterinária , Manometria/veterinária , Pressão , CoelhosRESUMO
Prenatal diagnosis of pericardial mass, with associated large pericardial effusion, resected postnatally and diagnosed to be ectopic hepatic tissue on pathology.
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Neoplasias , Derrame Pericárdico , Gravidez , Feminino , Humanos , Pericárdio , Diagnóstico Pré-Natal , Derrame Pericárdico/diagnóstico , Neoplasias/patologiaRESUMO
Mesenchymal hamartoma of the chest wall is a rare, benign chondro-osseous tumor of the bone. Although it most commonly presents at birth or soon after, prenatal detection is rare. We report a case of prenatally detected mesenchymal hamartoma, and provide the rationale, details, and outcomes of our management. The literature is reviewed, with particular attention to prenatal detection and postnatal management options.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Hamartoma/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Adulto , Neoplasias Ósseas/cirurgia , Pré-Escolar , Feminino , Seguimentos , Hamartoma/cirurgia , Humanos , Recém-Nascido , Mesoderma/diagnóstico por imagem , Mesoderma/cirurgia , Gravidez , Parede Torácica/cirurgia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Pré-Natal/métodosRESUMO
INTRODUCTION: The definition and treatment of gangrenous appendicitis are not agreed upon. We performed a prospective study in children to evaluate an objective definition of gangrenous appendicitis, as well as associated bacteriology, histopathology, and outcomes. METHODS: Five staff pediatric surgeons prospectively enrolled patients in the study at the time of appendectomy if the following five criteria were met: gray or black discoloration of the appendiceal wall; absence of fecalith outside the appendix; absence of visible hole in the appendix; absence of gross purulence or fibrinous exudate remote from the appendix; and absence of intraoperative appendiceal leak. Peritoneal fluid was cultured, and a standard histopathologic review was undertaken. Persistence of fever (>37.5°C) and ileus was documented daily. Patients were continued postoperatively on ampicillin, gentamicin, and metronidazole until they tolerated diet, manifested a 24-h afebrile period, and had a normal leukocyte count. Hospital stay, readmissions, and infectious complications were recorded. The study took place over a 12-mo period. RESULTS: Thirty-eight patients were enrolled, representing 17% of all patients with appendicitis treated during the year. Average age was 10.8 ± 3.5 y. Peritoneal cultures were positive in 53% of cases. Gangrene was documented histologically in 61% of specimens. Hospital stay was 3.2 ± 1.1 d. There were no postoperative infectious complications or readmissions related to the disease. Neither culture results nor histologic gangrene had a statistically significant effect on hospital stay. CONCLUSIONS: An objective definition of gangrenous appendicitis is reproducible and has good histopathologic association. Recovery from gangrenous appendicitis is not influenced by culture or pathology results, and postoperative complications are rare. Limiting postoperative antibiotics to 24 h in gangrenous appendicitis may significantly decrease the cost of treatment without increasing morbidity.
Assuntos
Apendicite/terapia , Adolescente , Apendicite/economia , Apendicite/patologia , Apêndice/patologia , Criança , Feminino , Gangrena/economia , Gangrena/terapia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.
Assuntos
Diabetes Insípido Nefrogênico/complicações , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Neoplasias Renais/complicações , Tumor de Wilms/complicações , Sequência de Bases , Aberrações Cromossômicas , Análise Mutacional de DNA , Diabetes Insípido Nefrogênico/genética , Diabetes Insípido Nefrogênico/patologia , Genes do Tumor de Wilms , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Imuno-Histoquímica , Lactente , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Mutação de Sentido Incorreto , Receptores de Vasopressinas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tumor de Wilms/genética , Tumor de Wilms/patologia , beta Catenina/genéticaRESUMO
Renal tubular dysgenesis (RTD) is a developmental abnormality of the nephron characterized by fetal anuria, oligohydramnios, and severe postnatal hypotension. Genetic forms have an autosomal recessive inheritance and are caused by mutations in genes encoding key components of the renin-angiotensin pathway. We report three patients from two unrelated families with RTD due to pathogenic variants of the angiotensin-converting enzyme (ACE) gene, in whom RTD was associated with microcolon. We also detail key variations of the renin-angiotensin system in one of these infants. The severe intestinal developmental abnormality culminating in microcolon and early terminal ileum perforation/necrotizing enterocolitis is a novel finding not previously associated with RTD, which points to a role of the renin-angiotensin system in gut development.
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Anormalidades Múltiplas/genética , Íleo/anormalidades , Túbulos Renais/anormalidades , Peptidil Dipeptidase A/genética , Fenótipo , Anormalidades Múltiplas/patologia , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
Onabotulinum toxin A (OBTXA) is an effective treatment for drooling. Our objective was to determine if there are histologic changes in the submandibular glands (SMGs) after repetitive OBTXA injections. The study included blinded histologic analysis and comparison of SMGs with ≥4 OBTXA injections versus controls who never received OBTXA. The number of acinar cells were counted, and the morphology of the cells was evaluated within each histologic sample of the SMGs. Thirty-one glands were analyzed (14 control, 17 cases). No physical differences were observed between the 2 acinar cell groups. There was no significant difference in the number acinar cells per surface area in the control group as compared with the OBTXA group (1.29 ± 0.13 vs 1.17 ± 0.11 cells/µm2, respectively). To conclude, no significant histologic findings were established in this first human study on SMGs post-OBTXA treatment.
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Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Sialorreia/tratamento farmacológico , Glândula Submandibular/efeitos dos fármacos , Criança , Feminino , Humanos , Injeções , Masculino , Sialorreia/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Haploinsufficiency of the GATA6 transcription factor gene was recently found to be the most common cause of pancreatic agenesis, a rare cause of neonatal diabetes mellitus. Although most cases are de novo, we describe three siblings with inherited GATA6 haploinsufficiency and the rare finding of parental mosaicism. CASE PRESENTATION: The proband was born at term with severe intrauterine growth restriction, the first child of non-consanguineous parents. Diabetes occurred on day of life 1 with pancreatic exocrine insufficiency noted at several months of age. Pancreatic agenesis with absent gallbladder was confirmed when he underwent congenital diaphragmatic hernia and intestinal malrotation repair. A patent ductus arteriosus and pulmonary stenosis were repaired in infancy. Neurocognitive development has been normal. A second pregnancy was terminated due to tetralogy of Fallot and pulmonary hypoplasia secondary to congenital diaphragmatic hernia. The fetus also demonstrated severe pancreatic hypoplasia, gallbladder agenesis and intestinal rotation abnormalities. Despite severe hypoplasia, the pancreas demonstrated normal islet histology. Another sibling was found to have multiple cardiac abnormalities, requiring procedural intervention. Given the proband's spectrum of congenital anomalies, Sanger sequencing of the GATA6 gene was performed, revealing a novel heterozygous c.635_660del frameshift mutation (p.Pro212fs). The mutation is predicted to be pathogenic, resulting in inclusion of a premature stop codon and likely degradation of the gene transcript by nonsense-mediated decay. The abortus and the sibling with the cardiac defect were both found to have the mutation, while the father and remaining sibling were negative. The mother, who is healthy with no evidence of diabetes or cardiac disease, is mosaic for the mutation at a level of 11% in her peripheral leukocytes by next-generation sequencing. CONCLUSION: We highlight a rare mechanism of pancreatic agenesis, this being only the second report of parental mosaicism for a GATA6 mutation and one of a handful of inherited cases. We also further define the phenotypic variability of GATA6 haploinsufficiency, even in individuals carrying the same mutation. Mutations in GATA6 should be strongly considered in cases of diabetes due to pancreatic hypoplasia or agenesis, and potentially affected family members should be tested regardless of phenotype.
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Anormalidades Múltiplas/genética , Diabetes Mellitus/genética , Mutação da Fase de Leitura , Fator de Transcrição GATA6/genética , Mosaicismo , Pâncreas/anormalidades , Retardo do Crescimento Fetal , Humanos , Recém-Nascido , MasculinoRESUMO
Lymphadenopathy continues to be a common problem to radiologists and treating physicians because of the difficulty in confidently categorizing a node as being benign or malignant using standard diagnostic techniques. The goal of our research was to assess whether magnetic resonance (MR) spectroscopy contains the necessary information to allow differentiation of benign from malignant lymph nodes in an in-vitro approach using a modern pattern recognition method. Tissue samples from a tissue bank were analyzed on a nuclear magnetic resonance (NMR) spectrometer. A total of 69 samples were studied. The samples included a wide variety of malignant and benign etiologies. Using 45 samples, we initially created a model which was able to predict if a certain spectrum originates from benign or malignant lymph nodes using a pattern-recognition technique which takes into account the entire magnetic spectrum rather than single peaks alone. The remaining 24 samples were blindly loaded in the model to assess its performance. We obtained an excellent accuracy in differentiating benign and malignant lymphadenopathy using the model. It correctly differentiated as malignant or benign, in a blinded fashion, all of the malignant samples (13 of 13) and 10 out of the 11 benign samples. We thus showed that magnetic spectroscopy is able to differentiate benign from malignant causes of lymphadenopathy. Additional experiments were performed to verify that the differentiating abilities of our model were not due to differential tissue decay in between benign and malignant tissues. If future experiments demonstrate that a similar approach could be executed with standard MR imaging, this technique could be useful as a problem-solving tool when assessing lymphadenopathy in general. Alternatively, our in-vitro technique could also be useful to pathologists faced with indeterminate pathologies of the lymph nodes after validating our results with a larger sample size.
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Linfonodos/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Diagnóstico por Computador , Diagnóstico Diferencial , Análise Discriminante , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Linfadenopatia/etiologia , Linfadenopatia/metabolismo , Linfadenopatia/patologia , Metástase Linfática/patologia , Metástase Linfática/fisiopatologia , Modelos Teóricos , Método Simples-Cego , SoftwareRESUMO
BACKGROUND: We previously demonstrated feasibility, safety, and a reproducible histologic bulking effect after injection of dextranomer hyaluronic acid copolymer (DxHA) into the gastroesophageal junction of rabbits. In the current study, we investigated the potential for DxHA to augment the lower esophageal sphincter (LES) in a porcine model of gastroesophageal reflux disease (GERD). METHODS: Twelve Yucatan miniature pigs underwent LES manometry and 24-hour ambulatory pH monitoring at baseline, after cardiomyectomy, and 6weeks after randomization to endoscopic injection of either DxHA or saline at the LES. After necropsy, the foregut, including injection sites, was histologically examined. RESULTS: Pigs in both groups had similar weight progression. Cardiomyectomy induced GERD in all animals, as measured by a rise in the median % of time pH <5 from 0.6 to 11.6 (p=0.02). Endoscopic injection of DxHA resulted in a higher median difference in LES length (1.8cm vs. 0.4cm, p=0.03). In comparison with saline injection, DxHA resulted in 120% increase in LES pressure, and 76% decrease in the mean duration of reflux episodes, but these results were not statistically significant. Injection of DxHA induced a foreign body reaction with fibroblasts and giant cells. CONCLUSIONS: Porcine cardiomyectomy is a reproducible animal GERD model. Injection of DxHA may augment the LES, offering a potential therapeutic effect in GERD.
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Dextranos/administração & dosagem , Esfíncter Esofágico Inferior/efeitos dos fármacos , Refluxo Gastroesofágico/terapia , Ácido Hialurônico/administração & dosagem , Animais , Modelos Animais de Doenças , Esfíncter Esofágico Inferior/patologia , Esfíncter Esofágico Inferior/fisiologia , Monitoramento do pH Esofágico , Esofagoscopia , Reação a Corpo Estranho/fisiopatologia , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/fisiopatologia , Manometria , Projetos Piloto , SuínosRESUMO
INTRODUCTION: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. METHODS: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. RESULTS: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. CONCLUSIONS: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.
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Adenocarcinoma/enzimologia , Neoplasias Pulmonares/enzimologia , Receptores Proteína Tirosina Quinases/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Canadá , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores Proteína Tirosina Quinases/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Females with 46,XY complete gonadal dysgenesis are at significant risk of developing germ cell tumors, mostly gonadoblastomas. We present here the case of 2 half-sisters, sharing the same father, diagnosed with 46,XY complete gonadal dysgenesis. The 1st sister developed a gonadoblastoma and an invasive dysgerminoma, whereas the 2nd sister developed a gonadoblastoma and an invasive choriocarcinoma within the same gonad. No SRY mutation, chromosome abnormalities, or mosaicism were detected in blood. Single nucleotide polymorphism (SNP) profiling of the choriocarcinoma revealed a complex hyperdiploid pattern with gains of 1 to 4 copies of material from several autosomes, as well as the loss of the Y chromosome and a homozygous SNP profile without copy number change for the X chromosome. Our results are in agreement with the recurrent chromosome gains and losses previously published in germ cell tumors, and the coexistence of both tumors within the same gonad suggests that choriocarcinomas may derive from gonadoblastomas.
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Coriocarcinoma não Gestacional/genética , Disgerminoma/genética , Disgenesia Gonadal 46 XY/genética , Gonadoblastoma/genética , Neoplasias Primárias Múltiplas , Polimorfismo de Nucleotídeo Único , Neoplasias Uterinas/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Criança , Coriocarcinoma não Gestacional/patologia , Coriocarcinoma não Gestacional/terapia , Deleção Cromossômica , Cromossomos Humanos Y , Disgerminoma/patologia , Disgerminoma/terapia , Evolução Fatal , Feminino , Disgenesia Gonadal 46 XY/patologia , Disgenesia Gonadal 46 XY/terapia , Gonadoblastoma/patologia , Gonadoblastoma/terapia , Humanos , Hibridização in Situ Fluorescente , Análise de Sequência com Séries de Oligonucleotídeos , Irmãos , Cariotipagem Espectral , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Adulto JovemRESUMO
Familial adenomatous polyposis (FAP) is a rare cause of colorectal cancer and rarely presents in early childhood. Various extracolonic manifestations, however, may be present before the development of overt polyposis. One of the rarest manifestations is the Gardner fibroma (GAF), which has particular histologic features. Here we report the case of a child who presented in the neonatal period with a paraspinal mass. Although the initial diagnosis was unclear, biopsy of a second lesion at 32 months of age, and a review of the first lesion, resulted in the diagnosis of GAF. After rectal bleeding at 47 months, colonoscopy revealed 75 to 100 colonic polyps. Adenomas were identified in multiple biopsies throughout the colon and from several polyps located in the duodenum. Polyps were visualized in the jejunum by wireless-capsule endoscopy. A total proctocolectomy was performed, and no malignant transformation was observed in the colon on pathologic inspection. A truncating mutation in APC (c.4479_4480delGG p.Glu1494LysfsX19) was identified in the child. Her parents and sister do not carry this mutation in lymphocyte DNA. To our knowledge, this is the first report of neonatal GAF as the presenting feature of a molecularly confirmed case of sporadic FAP and the earliest colonic and small bowel involvement reported of FAP. It illustrates the need to exclude FAP in a child who harbors fibromas suggestive of GAF, even in the absence of supportive evidence of FAP in the patient or relatives.