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1.
Mol Imaging Biol ; 25(3): 554-559, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36369484

RESUMO

AIM/PURPOSE: 18F-labeled PSMA ligands offer various advantages as PET tracers over 68Ga-labeled PSMA counterparts. Especially, an improved spatial resolution leads to improved detection rates of smaller prostate cancer (PCa) lesions. However, physiological PSMA uptake of ganglia of the sympathetic trunk can be quickly misinterpreted as possible PSMA-positive lymph node metastases. The aim of this retrospective study is to investigate [18F]PSMA-1007 uptake and its intra-individual reproducibility in ganglia of the sympathetic trunk. METHODS: We retrospectively included 28 consecutive patients (median age 69 ± 9 with a range of 49-90) with biochemical recurrence of PCa who underwent [18F]PSMA-1007 PET/CT scan and, accordingly, a follow-up examination between August 2018 and August 2021. Cervical, coeliac, and sacral ganglia were identified on the iterative PET reconstructions and correlated with CT component. Tracer uptake of ganglia was determined by measuring SUVmax and SUVmean values. Anatomical position of the ganglia in relation to adjacent vertebral bodies were noted. Statistical analyses were conducted using two-way repeated measures ANOVA and descriptive statistics. RESULTS: The highest [18F]PSMA-1007 uptake was found in coeliac ganglia followed by cervical and sacral ganglia. The SUVmax in coeliac ganglia was 3.13 ± 0.85 (follow-up scan 3.11 ± 0.93), in cervical ganglia 2.73 ± 0.69 (follow-up scan 2.67 ± 0.74), and in sacral ganglia 1.67 ± 0.50 (follow-up scan 1.64 ± 0.52). The SUVmean in coeliac ganglia was 2.28 ± 0.64 (follow-up scan 2.28 ± 0.66), in cervical ganglia 1.62 ± 0.43 (follow-up scan 1.61 ± 0.43) and in sacral ganglia 1.15 ± 0.33 (follow-up scan 1.12 ± 0.34). In a given ganglion station, there was no statistically significant difference of SUVmax or SUVmean values between baseline and follow-up scans. CONCLUSIONS: The first systematically described physiological [18F]PSMA-1007 uptake in ganglia of the sympathetic trunk showed a low variability of SUVmax or SUVmean and a good intra-individual reproducibility of [18F]PSMA-1007 uptake in follow-up scans. These findings might improve and guide the differentiation of ganglia from possible malignant lesions.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Reprodutibilidade dos Testes , Radioisótopos de Gálio , Neoplasias da Próstata/patologia , Gânglios/patologia , Ácido Edético
2.
BMC Pediatr ; 22(1): 723, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36536313

RESUMO

BACKGROUND: In the validation of new imaging technology for children with Hirschsprung's disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group. AIM: To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight. METHODS: This was an observational study of bowel specimens from children weighing 0-10 kg, operated on consecutively during 2018-2020. Ganglionic and aganglionic bowel walls were measured in digitalized microscopy images from 10 sites per trans-sectional specimen and compared regarding the thickness of their histoanatomical layers. RESULTS: Bowel walls were measured in 21 children. Full bowel wall thickness did not differ between aganglionic and ganglionic bowel (2.20 vs 2.04; p = 0.802) while weight at surgery correlated positively with both ganglionic and aganglionic bowel wall thickness (r = 0.688 and 0.849, respectively), and age at surgery with ganglionic bowel wall thickness (r = 0.517). In aganglionic segments, the muscularis externa layer was thicker compared to that in ganglionosis (0.45 vs 0.31 mm, p = 0.012) whereas the muscularis interna was thinner (0.45 vs 0.62 mm, p < 0.001). A diagnostic index was identified whereby a lower ratio of muscularis interna/externa thickness followed by a thinner muscularis interna differed between aganglionic and ganglionic bowel in all specimens. CONCLUSION: Thicknesses of the bowel wall's muscle layers differ between aganglionic and ganglionic bowel walls in children with HSCR. These findings support a diagnostic index that could be validated for transfer to instant diagnostic imaging techniques. LEVEL OF EVIDENCE: Diagnostic: 3.


Assuntos
Doença de Hirschsprung , Criança , Humanos , Lactente , Doença de Hirschsprung/genética , Intestinos/patologia , Gânglios/patologia
3.
World Neurosurg ; 166: e968-e979, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35953037

RESUMO

BACKGROUND: Advancements in imaging and an understanding of the pathomechanism for intraneural ganglion cyst formation have led to increased awareness and recognition of this lesion. However, the precise role of imaging has been advocated for but not formally evaluated. METHODS: We performed a systematic review of the world literature to study the frequency of imaging used to diagnose intraneural ganglion cysts at different sites and compared trends in identifying joint connections. RESULTS: We identified 941 cases of intraneural ganglion cysts, of which 673 had published imaging. Magnetic resonance imaging (MRI, n = 527) and ultrasonography (US, n = 123) were the most commonly reported. They occurred most frequently in the common peroneal nerve (n = 570), followed by the ulnar nerve at the elbow (n = 88), and the tibial nerve at the ankle (n = 58). A joint connection was identified in 375 cases (48%), with 62% of MRIs showing a joint connection, followed by 16% on US, and 6% on computed tomography (CT). MRI was statistically more likely to identify a joint connection than was US (P < 0.01). In the last decade, joint connections have been identified with increasing frequency using preoperative imaging, with up to 75% of cases reporting joint connections. CONCLUSIONS: Preoperative imaging plays an important role in establishing the diagnosis of intraneural ganglion cyst as well as treatment planning. Imaging has proved superior to the sole reliance of operative exposure to identify a joint connection, which is necessary to treat the underlying disease. Failure to identify cyst connections on imaging can result in an inability to truly address the underlying pathoanatomy at the time of definitive surgery, leading to a risk for clinical recurrence. Therefore, management should be guided by an intersection between new knowledge presented in the literature, clinical expertise, and surgeon experience.


Assuntos
Cistos Glanglionares , Gânglios/patologia , Cistos Glanglionares/diagnóstico por imagem , Cistos Glanglionares/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Nervo Fibular/diagnóstico por imagem , Nervo Fibular/patologia , Nervo Tibial/patologia
4.
J Pediatr Surg ; 57(7): 1269-1273, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35393117

RESUMO

BACKGROUND: Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy. METHODS: Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei. RESULTS: Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases. CONCLUSIONS: Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible. LEVEL OF EVIDENCE: LEVEL IV.


Assuntos
Doença de Hirschsprung , Obstrução Intestinal , Pré-Escolar , Gânglios/patologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/patologia , Humanos , Ileostomia , Recém-Nascido , Obstrução Intestinal/patologia , Plexo Mientérico/patologia , Estudos Retrospectivos
5.
Skeletal Radiol ; 51(7): 1439-1452, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35006278

RESUMO

OBJECTIVE: To present cases of juxtaneural ganglia arising from the hip with a discussion of the magnetic resonance imaging (MRI) findings, presenting symptoms, and possible treatment option. MATERIALS AND METHODS: Two radiologists performed a consensus review of MRI scans obtained between January 2013 and March 2021 to identify patients with juxtaneural ganglia around the hip. A total of 11 patients with 11 juxtaneural ganglia were identified. Medical records and MRI findings were retrospectively reviewed. RESULTS: Eight patients had lesions involving the sciatic nerve, and three patients had lesions involving the obturator nerve. Sciatic ganglia arose from a paralabral cyst in the posteroinferior quadrant and continued through a narrow channel running along the posterior acetabulum, showing increased diameter in the sciatic foramen and intrapelvic portion. Obturator ganglia showed a J- or reverse J-shape on the coronal imaging plane and extended from a paralabral cyst in the anteroinferior quadrant via the obturator canal. Nine patients (9/11, 81.8%) had symptoms resembling those of lumbosacral radiculopathy. Four patients underwent arthroscopic surgery, and one patient underwent ultrasound-guided aspiration, all of whom showed partial improvement. Spontaneous decrease in the extent of the ganglion was observed in three patients (3/11, 27.3%). CONCLUSION: This article describes rare cases of juxtaneural ganglia arising from the hip joint and involving the sciatic and obturator nerves. The lesions share similar MRI findings, and each type of cyst (sciatic or obturator ganglia) involves a specific labral quadrant.


Assuntos
Cistos Glanglionares , Articulação do Quadril , Gânglios/patologia , Cistos Glanglionares/diagnóstico por imagem , Cistos Glanglionares/cirurgia , Articulação do Quadril/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
6.
Pediatr Surg Int ; 37(2): 281-286, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33427922

RESUMO

PURPOSE: In anorectal malformations (ARMs), the epithelium of the distal rectal end is not well described. We histomorphologically evaluated epithelial and ganglionic distribution in the distal rectal end of ARMs resected during anorectoplasty to assess similarities and differences with normal anal canal structure. METHODS: In this single-center retrospective study, specimens from 60 ARM patients (27 males, 33 females) treated between 2008 and 2019 were evaluated. RESULTS: Epithelium type and alignment sequence as well as ganglionic distribution were similar in the distal rectal end and in a normal anal canal. Stratified columnar epithelium (anal transitional zone, ATZ) was seen in 49/60 (81.7%) cases and in all ARM types, including the no-fistula type. Anal crypts were identified in the stratified columnar epithelium (ATZ) of 46/49 (93.9%) patients. Regarding distal rectal end-resecting anorectoplasty, in 90% of patients, resection was performed distal to the Herrmann line. Ganglion cell distribution was exclusively proximal to the Herrmann line. CONCLUSION: Epithelial and ganglionic distribution was similar in the distal rectal end of ARMs and in a normal anal canal. The ATZ is the epithelial boundary between the rectum and skin in a normal anal canal. ATZ preservation could reproduce anal canal structure in ARM reconstruction.


Assuntos
Canal Anal/anormalidades , Malformações Anorretais/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Epitélio/patologia , Gânglios/patologia , Procedimentos de Cirurgia Plástica/métodos , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Malformações Anorretais/cirurgia , Feminino , Humanos , Recém-Nascido , Masculino , Reto/anormalidades , Estudos Retrospectivos
7.
Clin Nucl Med ; 46(1): 69-70, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33208621

RESUMO

A 74-year-old man with a history of prostate cancer with proven osseous metastatic disease underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT under antiandrogen therapy. The scan revealed a long segment of increased PSMA tracer uptake within the right sciatic nerve, which appeared edematous and swollen, and the respective ganglia. Clinically, the patient suffered from pain and paresis in the right leg. As infiltration of a long segment of a single nerve seems unlikely, primarily neuronal disease such as neuritis (induced by metastases or radiotherapy) was considered. The observed uptake of PSMA-targeting PET tracers may then represent a peripheral nerve disorder.


Assuntos
Ácido Edético/análogos & derivados , Gânglios/metabolismo , Nervos Periféricos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Transporte Biológico , Neoplasias Ósseas/secundário , Ácido Edético/metabolismo , Gânglios/diagnóstico por imagem , Gânglios/patologia , Humanos , Masculino , Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
8.
J Neuroimmunol ; 349: 577422, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068972

RESUMO

Plexitis in the proximal margin of intestinal resections are associated with post-operative recurrence of Crohn's disease. To understand their formation, in vitro analyzes were performed. T cells adhered preferentially to neuron and glial cells in mixed primary cultures of enteric nervous system and T cell activation increased their adhesion capacity. Higher number of T lymphocytes in close proximity to enteric glial cells was also observed in the myenteric ganglia of Crohn's patients as compared to control. These data show that close proximity between lymphocytes and enteric neural cells exists and may contribute to the formation of plexitis.


Assuntos
Adesão Celular/fisiologia , Doença de Crohn/metabolismo , Gânglios/metabolismo , Plexo Mientérico/metabolismo , Neurônios/metabolismo , Linfócitos T/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Doença de Crohn/patologia , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/patologia , Feminino , Gânglios/patologia , Humanos , Plexo Mientérico/patologia , Neurônios/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Linfócitos T/patologia
9.
PLoS One ; 15(4): e0231353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271824

RESUMO

Prohormone convertases (PCs) are subtilisin-like proteases responsible for the intracellular processing of prohormones and proneuropeptides in vertebrates and invertebrates. The full-length PC2 cDNA sequence was cloned from pleuropedal ganglion of Haliotis discus hannai, consisted of 2254-bp with an open reading frame of 1989-bp and encoded a protein of 662 amino acid residues. The architecture of Hdh PC2 displayed key features of PCs, including a signal peptide, a pro-segment domain with sites for autocatalytic activation, a catalytic domain, and a pro-protein domain (P-domain). It shares the highest homology of its amino acid sequence with the PC2 from H. asinina and to lesser extent with that of Homo sapiens and Rana catesbeiana PC2. Sequence alignment analysis indicated that Hdh PC2 was highly conserved in the catalytic domain, including a catalytic triad of serine proteinases of the subtilisin family at positions Asp-195, His-236, and Ser-412. The cloned sequence contained a canonical integrin binding sequence, and four cysteine residues involved in the formation of an intramolecular disulfide link. Phylogenetic analysis revealed that the Hdh PC2 is robustly clustered with the Has PC2. Quantitative PCR assay demonstrated that the Hdh PC2 was predominantly expressed in the pleuropedal ganglion rather than in other examined tissues. Although PC2 mRNA was expressed throughout the gametogenetic cycle of male and female abalone, the expression level was significantly higher in the ripening stage of female abalone. Also, a significantly higher expression was observed in the pleuropedal ganglion and gonadal tissues at a higher effective accumulative temperature (1000°C). In situ hybridization revealed that the PC2 mRNA expressing neurosecretory cells were distributed in the cortex region of the pleuropedal ganglion. According to the results, it can be concluded that pleuropedal ganglion is the highest site of PC2 activity, and this enzyme might be involved in the abalone reproduction process.


Assuntos
Gastrópodes/enzimologia , Pró-Proteína Convertase 2/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Feminino , Gânglios/metabolismo , Gânglios/patologia , Gônadas/metabolismo , Hibridização In Situ , Filogenia , Pró-Proteína Convertase 2/classificação , Pró-Proteína Convertase 2/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Temperatura
10.
J Pediatr Surg ; 55(10): 2166-2169, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32345500

RESUMO

PURPOSE: Occurrence of Hirschsprung's disease in anorectal malformation (ARM) patients is rare, but many surgeons still ask to pathologists to search for ganglia in the terminal rectum/fistula; the histological procedure is time and money consuming and the results confounding. A consecutive series of ARM patients, in which the presence of ganglia in terminal rectum was revised, is herein presented. MATERIALS AND METHODS: Rectal specimens of ARM patients who underwent corrective surgery in the last 6 years were retrieved. The histological protocol included H&E staining and calretinin immunohistochemistry. Each specimen is processed until all material is examined if no ganglia are retrieved after the first twelve sections. RESULTS: Forty cases were examined. Eight patients were younger than 1 month of age at operation. The mean length of the specimen was 1.5cm (range: 1-3 cm). Upon clinical request, ganglia were searched in 15/40 cases (37.5%) and resulted absent in 10/15 (66.5%). All patients have been followed and none developed signs or symptoms suggestive for Hirschsprung. CONCLUSIONS: The practice to search for ganglia in the terminal rectum/fistula in ARM patients should be abandoned, as incidence of associated colorectal diseases is rare. Moreover, the procedure is expensive both in terms of laboratory's reagents and working time of expert pathologists and technicians. LEVEL OF EVIDENCE: Level IV (Case Series with no Comparison Group).


Assuntos
Malformações Anorretais/patologia , Gânglios/patologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/patologia , Fístula Retal/patologia , Malformações Anorretais/complicações , Malformações Anorretais/cirurgia , Calbindina 2/metabolismo , Pré-Escolar , Feminino , Gânglios/metabolismo , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Fístula Retal/complicações , Fístula Retal/cirurgia , Reto/inervação
12.
Brain Res Bull ; 157: 90-99, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017970

RESUMO

Diabetic cardiac autonomic neuropathy (DCAN) is a serious complication of diabetes mellitus, which often leads to cardiac dysfunction and even threatens patients' life. Osthole, a natural coumarin derivative, has anti-inflammatory, anti-oxidant and antihypertensive effects. The P2X3 receptor is related to DCAN. The objective of this study will investigate whether osthole relieves DCAN associated with the P2X3 receptor in the stellate ganglia of diabetic rats. A type 2 diabetes mellitus rat model was induced by a combination of diet and streptozotocin. Our results showed that osthole improved the abnormal changes of blood pressure, heart rate, and heart rate variability in diabetic rats and significantly reduced the up-regulated expression levels of the P2X3 receptor, tumor necrosis factor-α and interleukin-1ß in stellate ganglia of diabetic rats. Meanwhile, osthole significantly decreased the elevated serum adrenaline concentration and phosphorylation level of extracellular regulated protein kinase 1/2. In addition, the molecular docking result indicated that osthole was a perfect fit for interacting with the P2X3 receptor. Overall, osthole alleviates the sympathetic relative excitation via inhibiting the expression of P2X3 receptors in the stellate ganglia, to achieve a balance between sympathetic and parasympathetic nerves, relieves the DCAN.


Assuntos
Cumarínicos/farmacologia , Neuropatias Diabéticas/tratamento farmacológico , Gânglios/efeitos dos fármacos , Receptores Purinérgicos P2X3/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Gânglios/patologia , Masculino , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Receptores Purinérgicos P2X3/metabolismo , Estreptozocina/farmacologia
13.
Histochem Cell Biol ; 153(3): 135-151, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894388

RESUMO

The present study investigated the influence of castration performed at neonatal age on neuronal elements in the anterior pelvic ganglion of the male pig with immunohistochemistry and quantitative real-time PCR (qPCR). The ganglia were examined 3 and 6 months after surgery. In 3-month-old castrated pigs (3MCP) 74% of adrenergic and 31% of cholinergic neurons stained for caspase-3 (CASP-3), and much greater numbers of perikarya than in the control animals expressed CGRP, galanin (GAL) and VIP (peptides known to have neuroprotective properties). In 6-months-old castrated pigs (6MCP), an excessive loss (90%) of neurons and intraganglionic nerve fibres was found. The survived adrenergic and cholinergic neurons also expressed CASP-3, CGRP, GAL or VIP. The qPCR results corresponded with immunofluorescence findings. In 3MCP, genes for CASP-3 and CGRP were up-regulated, while the expression of those for DßH, VAChT, GAL, VIP and SP displayed statistically insignificant variations. In 6MCP, distinctly up-regulated were genes for CGRP, GAL, VIP, SP, DßH and VAChT, while the expression of casp3 gene was down-regulated. The study revealed for the first time the excessive loss of pelvic neurons following castration, and a realistic assumption is proposed, that the neurons died due to apoptosis triggered by androgen deprivation.


Assuntos
Gânglios/metabolismo , Gânglios/cirurgia , Neurônios/metabolismo , Orquiectomia , Pelve/cirurgia , Animais , Gânglios/patologia , Masculino , Neurônios/patologia , Pelve/patologia , RNA/análise , RNA/genética , Suínos
14.
J Pediatr Surg ; 54(11): 2318-2324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31079866

RESUMO

BACKGROUND: Retained transition zone is a leading cause of obstructive symptoms after pull-through operation in Hirschsprung's disease. OBJECTIVE: We aimed to evaluate the extent of the histological transition zone in patients with Hirschsprung's disease. DESIGN: We performed an observational study. DAB+ immunohistochemistry for Protein Gene Product 9.5 was used to evaluate the neuronal networks in serial sections of pull-through specimens obtained from children with Hirschsprung's disease (n = 12). Reference ranges for ganglion size/density and nerve trunk diameter were statistically determined using healthy controls obtained from colostomy specimens from children with anorectal malformations (n = 8). The transition zone was defined as ganglionic bowel exhibiting ganglion hypoplasia, hypertrophic nerve trunks, or partial circumference aganglionosis. RESULTS: The mean submucosal nerve trunk diameter in controls was 19.56 µm +/- 3.87 µm. The median age at pull-through for Hirschsprung's disease was 5 months (3-14 months). The median length of the transition zone across the population was 8 cm (4-22 cm). Median transition zone extent was significantly longer in patients with long-segment aganglionosis (n = 6) compared to rectosigmoid aganglionosis (n = 6, 13 cm vs 6 cm, p = 0.041). Due to the age of the patients enrolled, long-term follow-up of bowel function is not yet available. CONCLUSION: Our data suggest that, in children with rectosigmoid Hirschsprung's disease, the transition zone can extend for up to 13 cm. In children with long-segment disease, a longer transition zone is possible. Extended resection at a minimum 5 cm beyond the most distal ganglionic intra-operative biopsy and intra-operative histological examination of the proximal resection margin are required to minimize transition zone pull-through. LEVEL OF EVIDENCE: 2.


Assuntos
Doença de Hirschsprung , Procedimentos Cirúrgicos do Sistema Digestório , Gânglios/patologia , Gânglios/fisiopatologia , Doença de Hirschsprung/patologia , Doença de Hirschsprung/fisiopatologia , Doença de Hirschsprung/cirurgia , Humanos , Lactente , Complicações Pós-Operatórias
15.
BMC Pediatr ; 19(1): 93, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953480

RESUMO

BACKGROUND: Total colonic and small bowel aganglionosis (TCSA) occurs in less than 1% of all Hirschsprung's disease patients. Currently, the mainstay of treatment is surgery. However, in patients with TCSA, functional outcomes are often poor. A characteristic transition zone in TCSA can be difficult to identify which may complicate surgery and may often require multiple operations. CASE PRESENTATION: We present the case of a male infant who was diagnosed with biopsy-proven total colonic aganglionosis with extensive small bowel involvement as a neonate. The patient was diverted at one month of age based on leveling biopsies at 10 cm from the Ligament of Treitz. At 7 months of age, during stoma revision for a prolapsed stoma, intra-operative peristalsis was observed in nearly the entire length of the previously aganglionic bowel, and subsequent biopsies demonstrated the appearance of mature ganglion cells in a previously aganglionic segment. CONCLUSIONS: TCSA remains a major challenge for pediatric surgeons. Our case introduces new controversy to our understanding of aganglionosis. Our observations warrant further research into the possibility of post-natal ganglion maturation and encourage surgeons to consider a more conservative surgical approach.


Assuntos
Gânglios/patologia , Doença de Hirschsprung/cirurgia , Intestino Delgado/inervação , Biópsia , Colo/anormalidades , Colo/patologia , Colo/cirurgia , Doença de Hirschsprung/patologia , Humanos , Recém-Nascido , Enteropatias/diagnóstico por imagem , Enteropatias/patologia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Masculino , Radiografia
16.
Pediatr Surg Int ; 35(1): 9-14, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30386899

RESUMO

PURPOSE: Smooth muscle cells are electrically coupled to ICC and PDGFRα+ cells, to regulate smooth muscle contraction. Recent studies have reported that the voltage-gated sodium channel type 1ß (Scn1b), and the chloride channel subunit, Fxyd1, are highly expressed by both ICC and PDGFRα+ cells in the mouse colon. We designed this study to investigate the expression of the Scn1b and Fxyd1 genes in the normal human colon and in HSCR. METHODS: HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify Scn1b and Fxyd1 gene expression, and immunolabelling of Scn1b and Fxyd1 proteins were visualized using confocal microscopy. RESULTS: qRT-PCR analysis revealed significant downregulation of Scn1b and Fxyd1 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a reduction in Scn1b and Fxyd1 protein expression in both aganglionic and ganglionic HSCR colon compared to controls. CONCLUSION: Scn1b and Fxyd1 expression was significantly downregulated in HSCR colon. These results add to mounting evidence suggesting that the pulled-through ganglionic segment of bowel in these patients is abnormal, despite the presence of ganglion cells.


Assuntos
Colo/patologia , Gânglios/metabolismo , Regulação da Expressão Gênica , Doença de Hirschsprung/genética , Proteínas de Membrana/genética , Fosfoproteínas/genética , RNA/genética , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/genética , Western Blotting , Colo/metabolismo , Regulação para Baixo , Imunofluorescência , Gânglios/patologia , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/cirurgia , Humanos , Lactente , Proteínas de Membrana/biossíntese , Microscopia Confocal , Fosfoproteínas/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/biossíntese
17.
Pediatr Surg Int ; 35(1): 15-20, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30386901

RESUMO

AIM OF THE STUDY: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is poorly understood. Inflammasomes are a large family of multiprotein complexes that act to mediate host immune responses to microbial infection and have a regulatory or conditioning influence on the composition of the microbiota. Inflammasomes and the apoptosis-associated speck-like protein (ASC) lead to caspase-1 activation. The activated caspase-1 promotes secretion of pro-inflammatory cytokines (IL-1ß and IL-18) from their precursors (pro-IL-1ß and pro-IL-18). Inflammasomes have been implicated in a host of inflammatory disorders. Among the inflammasomes, NLRP3, NLRP12 and NLRC4 are the most widely investigated. Knock-out mice models of inflammasomes NLRP3, NLRP12, NLRC4, caspase-1 and ASC are reported to have higher susceptibility to experimental colitis. The purpose of this study was to investigate the expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 in the bowel specimens from patients with HSCR and controls. METHODS: Pulled-through colonic specimens were collected from HSCR patients (n = 6) and healthy controls from the proximal colostomy of children with anorectal malformations (n = 6). The gene expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 was assessed using qPCR. The protein distribution was assessed using immunofluorescence and confocal microscopy. MAIN RESULTS: qRT-PCR analysis revealed that NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls. Confocal microscopy revealed a markedly decreased expression of NLRP3, NLRP12, NLRC4 and ASC protein in the colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls. CONCLUSIONS: To our knowledge, this is the first study analyzing NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions in patients with HSCR. Decreased expression of NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß in the aganglionic and ganglionic bowel may increase susceptibility of HSCR patients to develop HAEC.


Assuntos
Regulação da Expressão Gênica , Doença de Hirschsprung/genética , Inflamassomos/genética , RNA/genética , Criança , Gânglios/metabolismo , Gânglios/patologia , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Humanos , Inflamassomos/biossíntese , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Microscopia Confocal , Reação em Cadeia da Polimerase
18.
Anal Cell Pathol (Amst) ; 2019: 3085181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32082967

RESUMO

Chronic inflammation induced by Helicobacter pylori (H. pylori) infection plays a major role in development of gastric cancer. However, recent findings suggested that progression of inflammation and neoplastic transformation in H. pylori infection are more complex than previously believed and could involve different factors that modulate gastric microenvironment and influence host-pathogen interaction. Among these factors, gastric myenteric plexus and its potential adaptive changes in H. pylori infection received little attention. This study is aimed at identifying the impact of H. pylori-associated gastritis on number and morphology of nerve cells in the stomach. The distribution of density, inflammation, and programmed cell death in neurons was immunohistochemically assessed in full-thickness archival tissue samples obtained from 40 patients with H. pylori infection who underwent surgery for gastric cancer and were compared with findings on samples collected from 40 age- and sex-matched subjects without bacteria. Overall, significant differences were noted between H. pylori-positive and H. pylori-negative patients. The analysis of tissue specimens obtained from those with infection revealed higher density and larger surface of the myenteric nervous plexus, as well as a significant increase in the number of gastric neuronal cell bodies and glial cells compared to controls. A predominant CD3-immunoreactive T cell infiltrate confined to the myenteric plexus was observed in infected subjects. The presence of mature B lymphocytes, plasma cells, and eosinophils was also noted, but to a lesser extent, within the ganglia. Myenteric ganglionitis was associated with degeneration and neuronal loss. Our results represent the first histopathological evidence supporting the hypothesis that H. pylori-induced gastric inflammation may induce morphological changes in myenteric gastric ganglia. These findings could help gain understanding of some still unclear aspects of pathogenesis of H. pylori infection, with the possibility of having broader implications for gastric cancer progression.


Assuntos
Carcinoma/patologia , Gânglios/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Plexo Mientérico/citologia , Neurônios/citologia , Neoplasias Gástricas/patologia , Idoso , Apoptose , Linfócitos B/citologia , Complexo CD3/metabolismo , Carcinoma/microbiologia , Estudos de Coortes , Eosinófilos/citologia , Feminino , Gânglios/citologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Plexo Mientérico/microbiologia , Plexo Mientérico/patologia , Neurônios/patologia , Estudos Retrospectivos , Neoplasias Gástricas/microbiologia , Linfócitos T/citologia , Linfócitos T/metabolismo
19.
Pediatr Surg Int ; 34(2): 121-128, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29383490

RESUMO

AIMS AND OBJECTIVES: Hirschsprung's disease-associated enterocolitis (HAEC) is the most serious complication of Hirschsprung's disease (HSCR). HAEC occurs in 17-50% of patients with HSCR and may occur before or after a properly performed pull-through operation. The pathogenesis of HAEC is poorly understood. It is well recognized that a complex mucosal barrier protects, as the first line of defense, the surface of healthy intestinal tract from adhesion and invasion by luminal micro-organisms. Within the intestinal epithelium, goblet cells secrete gel-forming mucins, the major component of mucus, which block the direct attachment of commensal bacteria to the epithelial layer. Mucin 2 (MUC2) is the predominant mucin expressed in humans. Trefoil factor 3 (TFF3) synergizes with mucin and enhances the protective barrier properties of the mucus layer. SAM pointed domain-containing ETS transcription factor (SPDEF) drives terminal differentiation and maturation of secretory progenitors into goblet cells. Krueppel-like factor 4 (KLF4) is a goblet cell-specific differentiation factor in the colon and controls goblet cell differentiation and activates mucin synthesis. We hypothesized that the goblet cell function in the ganglionic pulled-through bowel in HSCR is abnormal and, therefore, we investigated the changes in goblet cell differentiation and functional expression of mucin in the bowel specimens from patients with HSCR. MATERIAL AND METHODS: We investigated MUC2, TFF3, SPDEF and KLF4 expression, and the goblet cell population in the ganglionic and aganglionic bowel of HSCR patients (n = 10) and controls (n = 10) by qPCR, Western blotting, confocal immunofluorescence, and alcian blue staining. RESULTS: The qPCR and Western blotting analysis revealed that TFF3, SPDEF and KLF4 expressions were significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR as compared to controls (p < 0.05). Alcian blue staining revealed that the goblet cell population was significantly decreased in aganglionic and ganglionic colon as compared to controls (p < 0.05). Confocal microscopy revealed a markedly decreased expression of TFF3, SPDEF and KLF4 in colonic epithelium of patients with HSCR as compared to controls. CONCLUSION: This is, to our knowledge, the first report of decreased expression of TFF3, SPDEF, KLF4, and goblet cell population in the colon of patients with HSCR. Altered goblet cell function may result in intestinal barrier dysfunction contributing to the development of HAEC.


Assuntos
Regulação da Expressão Gênica , Células Caliciformes/metabolismo , Doença de Hirschsprung/genética , Fatores de Transcrição Kruppel-Like/genética , Mucina-2/genética , Proteínas Proto-Oncogênicas c-ets/genética , Fator Trefoil-3/genética , Western Blotting , Diferenciação Celular , Criança , Colo/metabolismo , Colo/patologia , Gânglios/metabolismo , Gânglios/patologia , Células Caliciformes/patologia , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/biossíntese , Microscopia Confocal , Mucina-2/biossíntese , Proteínas Proto-Oncogênicas c-ets/biossíntese , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator Trefoil-3/biossíntese , Dedos de Zinco
20.
Mod Pathol ; 30(7): 978-985, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28304401

RESUMO

Intestinal neuronal dysplasia type B is a controversial entity expressed by complex changes in the enteric nervous system. Diagnosis depends on rectal biopsy histopathology and diagnostic criteria, both qualitative and quantitative, have changed over time, hindering the diagnostic practice. We analyzed the morphological criteria for the histological diagnosis of intestinal neuronal dysplasia type B in a series of patients with intestinal neuronal dysplasia type B according to the 1990 Frankfurt Consensus criteria and verified the applicability of the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. Qualitative criteria adopted for the histological diagnosis of intestinal neuronal dysplasia type B included hyperplasia of the submucous plexus with hyperganglionosis and hypertrophy of the nerve trunks. Quantitative criteria considered more than 20% giant ganglia in the submucosa, with more than eight neurons each on 25 ganglia, and children aged over 1 year. Distal colon surgical specimens from 29 patients, aged 0-16 years, diagnosed with intestinal neuronal dysplasia type B were retrospectively analyzed using sections processed for conventional histology (H&E) and calretinin immunohistochemistry. Hyperplasia of the submucosal nerve plexi with hyperganglionosis and hypertrophy of the nerve trunks was observed in all cases. Ganglia with small, immature neurons were detected in the majority of cases. Quantitative analysis confirmed hyperganglionosis (mean number=10.7 neurons per ganglion) and hypertrophy of the nerve trunks (median=44.6 µm thickness). Neurons showed immunostaining for calretinin, but neuron counts in calretinin-stained sections were lower compared with H&E (P<0.01). No significant differences were verified between children aged under and over 1 year regarding hyperganglionosis (P=0.79), neuron counts (P=0.36), and immature ganglia (P=0.66). Only one patient met the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. In conclusion, the numerical criteria showed limited applicability when transposed to conventional histopathology. Children aged over 1 year presented very similar histological features of neuronal immaturity to younger children, questioning the need for an age criterion when diagnosing intestinal neuronal dysplasia type B.


Assuntos
Colo/patologia , Sistema Nervoso Entérico/patologia , Enteropatias/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Neurônios/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Gânglios/patologia , Humanos , Lactente , Recém-Nascido , Enteropatias/patologia , Mucosa Intestinal/patologia , Masculino , Doenças do Sistema Nervoso/patologia , Estudos Retrospectivos
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