ABSTRACT
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dSaCas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×1014 vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial effusion developed, followed by acute respiratory distress syndrome (ARDS) and cardiac arrest 6 days after transgene treatment; the patient died 2 days later. A postmortem examination showed severe diffuse alveolar damage. Expression of transgene in the liver was minimal, and there was no evidence of AAV serotype 9 antibodies or effector T-cell reactivity in the organs. These findings indicate that an innate immune reaction caused ARDS in a patient with advanced DMD treated with high-dose rAAV gene therapy. (Funded by Cure Rare Disease.).
Subject(s)
Dystrophin , Genetic Therapy , Muscular Dystrophy, Duchenne , Respiratory Distress Syndrome , Transgenes , Adult , Humans , Antibodies , Dystrophin/genetics , Genetic Therapy/adverse effects , Genetic Therapy/methods , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Transgenes/genetics , Transgenes/immunology , Fatal Outcome , Immunity, Innate/genetics , Immunity, Innate/immunologyABSTRACT
BACKGROUND: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1, CALM2, or CALM3, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function. METHODS: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of CALM1 pathogenic variants. RESULTS: Human CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes. Similarly, an ASO targeting murine Calm1 depleted Calm1 transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in CalmN98S/+ mice without a deleterious effect on cardiac electrical or contractile function. CONCLUSIONS: These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.
ABSTRACT
A 2-year professional master of health science program at the University of Toronto provides a unique integrated educational program to train allied health science personnel to practice as physician extenders and health care professionals in two high-demand clinical laboratory disciplines, Pathologists' Assistant (PA) and Clinical Embryologist (CE). This report describes an integrated graduate program developed and delivered in a research-intensive laboratory medicine department. The core courses in fundamental biomedical science and in general medical laboratory function and operations formed the foundation on which the requisite clinical skills required to practice as a PA or CE were subsequently delivered as comprehensive CE and PA specialty courses and practicums. Students acquired research skills through courses that teach research methods, critical analysis of research articles, and biostatistics for clinical research scientists. A capstone research project provided students the opportunity to design a research project relevant to the CE or PA fields, perform and analyze the findings, and present the project as an oral abstract and a written scientific article. Students learn to face the clinical challenges by focusing on critical analysis of evidence-based professional practice. The PA field received a 5-year accreditation. CE and PA students presented their clinical research at national and international meetings, with some receiving awards, and published scientific articles. All graduates found meaningful employment in their respective fields, and initial employer response has been favorable.
ABSTRACT
Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.
ABSTRACT
The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.
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BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.
ABSTRACT
Objective: We aimed to share the post-workshop survey results of a pediatric pathology course held in Jakarta, Indonesia. Methods: Questionnaires were distributed to participants; responses from practicing pathologists and pathologists-in-training were analyzed. Results: The respondents (107 pathologists of 143 attendees) were predominantly female (83.2%) and 31-60 years of age (77.5%). Over half (71.7%) signed out pediatric and perinatal specimens but only a third (34.3%) were comfortable handling such cases. Most (70.0%) felt that their exposure to pediatric and perinatal cases during their training was inadequate. All respondents thought that the workshop was helpful, and would highly recommend it to their colleagues. Post-workshop, the respondents claimed expansion of differential diagnoses (49.5%) and better understanding of what to include in pathology reports (41.1%). Conclusions: Our experience affirms the need for subspecialty courses to address training gaps in developing countries. Post-workshop surveys are helpful in determining actionable deficiencies and effectiveness of outreach teachings.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Surgical Oncology , Carcinoma, Hepatocellular/pathology , Child , Humans , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Retrospective StudiesABSTRACT
Pediatric acute liver failure (PALF) is a life-threatening disorder characterized by acute hepatocellular injury occurring in children without recognized underlying liver disease. The clinicopathologic evaluation of PALF requires a different approach from that in adults. The diagnostic considerations differ depending on the age, personal and family history, geographical region, and clinical presentation. Distinct entities such as gestational alloimmune liver disease, herpes simplex virus infection, and metabolic disorders should be considered in neonates with acute liver failure, while acetaminophen toxicity and autoimmune hepatitis are more frequently seen in older children and adolescents. An identified cause for PALF despite a negative complete evaluation (indeterminate) is lacking in 30 to 50% of cases. Although not routinely performed in the setting of PALF, liver biopsy may be helpful in assessing the etiology, potential mechanisms of injury, determining the appropriateness of liver transplantation, and prognostication of the patients. In this article, we review the clinicopathologic characteristics of PALF with an emphasis on general approach of pathologic evaluation and histopathologic characteristic of selected entities.
Subject(s)
Liver Failure, Acute , Adolescent , Child , Humans , Infant, Newborn , Liver Failure, Acute/pathology , Liver Failure, Acute/therapy , Liver TransplantationABSTRACT
ABSTRACT: Meningothelial hamartoma of the scalp is a rare entity characterized by a mix of meningothelial tissue and various connective tissue elements. To the best of the authors' knowledge, there has only been one reported case of meningothelial hamartoma of the scalp in the setting of Gorlin syndrome in the literature. In this report, we describe the case of a 3-year-old boy with Gorlin syndrome who presented with a congenital scalp lesion. Histologic examination revealed scattered islands of meningothelial cells in a background of dense fibrous and vascular tissue, in keeping with meningothelial hamartoma of the scalp. The differential diagnoses of congenital scalp lesions and the association between Gorlin syndrome and meningothelial hamartoma of the scalp are discussed.
Subject(s)
Basal Cell Nevus Syndrome/complications , Hamartoma/diagnosis , Skin Diseases/diagnosis , Child, Preschool , Diagnosis, Differential , Hamartoma/complications , Hamartoma/surgery , Humans , Male , Scalp , Skin Diseases/complications , Skin Diseases/surgeryABSTRACT
Background: Bladder exstrophy is a congenital malformation occurring more commonly in males. The occurrence of polyps in these bladders represents a well-known phenomenon to the treating urologist. However, they might not be as familiar to pathologists since they are generally not biopsied. Case report: We present a male infant who was diagnosed with bladder exstrophy and epispadias at birth. He subsequently underwent surgical repair of the malformation with bladder polypectomies at 7 months of age. Pathologic examination showed multiple polyps with extensive squamous metaplasia of surface urothelium. Von Brunn nests, cystitis cystica, and cystitis glandularis with focal intestinal metaplasia were noted at variable depths within polyps. These epithelial nests were surrounded by concentric fibrosis. Conclusion: Bladder exstrophy polyp is a distinct pathologic entity with a combination of various nonspecific findings. Pathologists should be cognizant of the histologic spectrum of this uncommon entity.
Subject(s)
Bladder Exstrophy , Polyps , Bladder Exstrophy/pathology , Bladder Exstrophy/surgery , Humans , Infant , Male , Pathology, Surgical , Polyps/pathology , Polyps/surgeryABSTRACT
Background Choledochal cysts (CCs), congenital cystic dilatation of the biliary tract, are more commonly identified in females and have been associated with a myriad of other developmental abnormalities. Case Report: We present a male infant who was diagnosed with type I CC prenatally. He subsequently underwent cyst and gallbladder resection with hepaticoduodenostomy reconstruction at the age of 6 months. Pathologic examination confirmed type I CC with co-existing septate gallbladder and ectopic pancreas (Heinrich type 1). Conclusions: Although the clinical significance is unclear, this second case of CC with septate gallbladder and ectopic pancreas highlights the embryologic association of these abnormalities.
Subject(s)
Choledochal Cyst , Choledochal Cyst/diagnosis , Choledochal Cyst/surgery , Female , Gallbladder/pathology , Humans , Infant , Male , Pancreas/pathologyABSTRACT
INTRODUCTION: We aimed to evaluate the reliability and validity of the Ulcerative Colitis (UC) Endoscopic Index of Severity (UCEIS) and Mayo Endoscopy Score (MES) and to validate the Robarts Histopathology Index (RHI) and Nancy Index (NI) in pediatric UC. We examined rectosigmoid and pancolonic versions of each instrument. METHODS: Single-center cross-sectional study of 60 prospectively enrolled participants. Through central endoscopy review, 4 pediatric gastroenterologists assigned rectosigmoid and pancolonic (mean of 5 colonic segments) UCEIS and MES scores. Two blinded pathologists assigned rectosigmoid and pancolonic RHI and NI scores. We assessed reliability with intraclass correlation coefficients and weighted kappa statistics and explored construct validity with correlations, boxplots, and receiver operator characteristic curves. RESULTS: The UCEIS and MES displayed almost perfect intra-rater and inter-rater reliability (intraclass correlation coefficient and weighted kappa ≥0.85), moderate-to-strong correlation with histologic/clinical activity and fecal calprotectin (FC), and very strong correlation with global endoscopic severity (r > 0.9). Rectosigmoid UCEIS and MES scores of 0 were highly specific (≥95%) for endoscopic and histologic remission throughout the colon. Pancolonic endoscopy scores correlated more strongly with histologic activity, clinical activity, and systemic inflammatory markers and better discriminated between degrees of active disease. RHI and NI showed moderate-to-strong correlation (r = 0.5-0.83) with endoscopic/clinical activity and FC. DISCUSSION: Our findings support the reliability and construct validity of the UCEIS and MES and the construct validity of the RHI and NI in pediatric UC. Normal rectosigmoid findings predicted pancolonic healing, but, given active disease, pancolonic endoscopic assessment more accurately captured global disease burden.
Subject(s)
Colitis, Ulcerative/pathology , Colonoscopy , Severity of Illness Index , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Observer Variation , Prospective Studies , Reproducibility of ResultsABSTRACT
Heterotopic liver tissue in the umbilical cord is rare, and the outcome is quite unpredictable based on the few reported cases. We present a case of heterotopic liver nodule in the umbilical cord of a midtrimester fetus who died in utero. Although such association has only been reported once, heterotopic nodular tissue in the umbilical cord must be regarded as a potential cause of fetal demise by a mechanism analogous to the more common umbilical cord abnormalities resulting in umbilical vessel compromise.
Subject(s)
Choristoma/pathology , Fetal Death/etiology , Liver/pathology , Umbilical Cord/abnormalities , Umbilical Cord/pathology , Female , Humans , Pregnancy , Single Umbilical Artery/pathologyABSTRACT
OBJECTIVE: This review aims to highlight the clinicopathological characteristics and differential diagnosis of central hepatic regenerative nodules (CHRNs) in patients with Alagille syndrome. METHODS: A review of the literature for cases of CHRNs and their differential diagnoses in patients with Alagille syndrome was performed and the main findings were collated. RESULTS: Large, regenerative hepatic nodules are seen in approximately 30% of patients with Alagille syndrome. They are thought to be a functional adaptation to vascular changes rather than a neoplastic process. The nodules are typically centrally located, and normal hepatic vasculature coursing through the lesions are noted radiologically. Microscopically, they are characterized by well-circumscribed hepatic lesions with preserved architecture, lesser degrees of fibrosis and relative preservation of interlobular bile ducts compared to the background cirrhotic liver. CONCLUSION: Regenerative nodules are common in Alagille's syndrome, and should be distinguished from hepatocellular carcinomas and adenomas for appropriate management and prognostication.
Subject(s)
Alagille Syndrome , Carcinoma, Hepatocellular , Liver Neoplasms , Alagille Syndrome/diagnosis , Diagnosis, Differential , Humans , Liver , Liver Neoplasms/diagnosisABSTRACT
The molecular classification of hepatocellular adenomas highlights a distinctive genotype-phenotype correlation. Malignant transformation is an exceptionally rare complication of hepatocyte nuclear factor 1α (HNF1A)-inactivated hepatocellular adenomas. This subtype is characterized by loss of liver fatty acid binding protein immunoexpression. In this study, we characterized the histopathologic spectrum of 13 liver fatty acid binding protein-deficient hepatocellular adenoma cases showing malignant transformation from multiple centers. Clinicopathologic characteristics of these patients were evaluated. Stains for reticulin, liver fatty acid binding protein, beta-catenin and glutamine synthetase were applied to these lesions. Moreover, the findings were compared to patients with ß-catenin mutated hepatocellular adenoma. Liver fatty acid binding protein-deficient hepatocellular adenomas with borderline features/carcinoma were seen predominantly in females (77%) with an average age of 46 ± 18 years and multiple lesions (77%; five patients with adenomatosis). Meanwhile, ß-catenin mutated hepatocellular adenoma patients with malignant transformation were predominantly male (67%, p = 0.018) with single lesion (86%, p = 0.0009). The largest liver fatty acid binding protein-deficient hepatocellular adenoma nodule in each patient ranged from 4 to 15.5 cm. Loss of liver fatty acid binding protein by immunohistochemistry was noted in all adenoma and borderline/carcinoma components. Features of malignant transformation were pseudoglandular architecture (85%), cytologic atypia (85%), architectural atypia (100%) and lack of steatosis (100%). Other findings included myxoid change (39%), peliosis (46%) and sinusoidal dilatation (46%). Molecular studies confirmed somatic inactivation of HNF1A in 3 cases and absence of TERT promotor and exon 3 CTNNB1 mutations in five cases. To summarize, liver fatty acid binding protein-deficient hepatocellular adenoma with malignant transformation is most frequently seen in female patients with multiple lesions. Most of these lesions demonstrate pseudoglandular architecture, cytologic and architectural atypia, with lack of steatosis. The natural history of these lesions is relatively benign with the exception of disease recurrence in 1 patient.
Subject(s)
Adenoma, Liver Cell/chemistry , Biomarkers, Tumor/deficiency , Cell Transformation, Neoplastic/chemistry , Fatty Acid-Binding Proteins/deficiency , Liver Neoplasms/chemistry , Adenoma, Liver Cell/genetics , Adenoma, Liver Cell/pathology , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Chromogranins/genetics , Europe , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Gene Silencing , Hepatocyte Nuclear Factor 1-alpha/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Mutation , Prognosis , Retrospective Studies , Sex Factors , Telomerase/genetics , United States , Young Adult , beta Catenin/geneticsABSTRACT
OBJECTIVE: To assess the value of qualitative and quantitative MRI radiomics features for noninvasive prediction of immuno-oncologic characteristics and outcomes of hepatocellular carcinoma (HCC). METHODS: This retrospective, IRB-approved study included 48 patients with HCC (M/F 35/13, mean age 60y) who underwent hepatic resection or transplant within 4 months of abdominal MRI. Qualitative imaging traits, quantitative nontexture related and texture features were assessed in index lesions on contrast-enhanced T1-weighted and diffusion-weighted images. The association of imaging features with immunoprofiling and genomics features was assessed using binary logistic regression and correlation analyses. Binary logistic regression analysis was also employed to analyse the association of radiomics, histopathologic and genomics features with radiological early recurrence of HCC at 12 months. RESULTS: Qualitative (r = - 0.41-0.40, p < 0.042) and quantitative (r = - 0.52-0.45, p < 0.049) radiomics features correlated with immunohistochemical cell type markers for T-cells (CD3), macrophages (CD68) and endothelial cells (CD31). Radiomics features also correlated with expression of immunotherapy targets PD-L1 at protein level (r = 0.41-0.47, p < 0.029) as well as PD1 and CTLA4 at mRNA expression level (r = - 0.48-0.47, p < 0.037). Finally, radiomics features, including tumour size, showed significant diagnostic performance for assessment of early HCC recurrence (AUC 0.76-0.80, p < 0.043), while immunoprofiling and genomic features did not (p = 0.098-0929). CONCLUSIONS: MRI radiomics features may serve as noninvasive predictors of HCC immuno-oncological characteristics and tumour recurrence and may aid in treatment stratification of HCC patients. These results need prospective validation. KEY POINTS: ⢠MRI radiomics features showed significant associations with immunophenotyping and genomics characteristics of hepatocellular carcinoma. ⢠Radiomics features, including tumour size, showed significant associations with early hepatocellular carcinoma recurrence after resection.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Immunity, Cellular , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Adult , Aged , Carcinoma, Hepatocellular/immunology , Endothelial Cells/immunology , Endothelial Cells/pathology , Female , Humans , Liver Neoplasms/immunology , Male , Middle Aged , Neoplasm Recurrence, Local , Predictive Value of Tests , Prospective Studies , Retrospective StudiesABSTRACT
OBJECTIVES: Barrett esophagus (BE) and intestinal metaplasia of gastroesophageal junction (IMGEJ) are rare in the pediatric population. This multi-institutional retrospective study evaluated the clinicopathologic characteristics and natural history of BE and IMGEJ in children. METHODS: Data from 20 BE patients (70% boys, mean age: 14.9 years) and 17 IMGEJ patients (71% boys, mean age: 14 years) were retrospectively obtained from chart review. Endoscopic and pathologic findings from index and follow-up endoscopies were analyzed. RESULTS: Most patients (70% BE and 59% IMGEJ) had underlying conditions which put them at risk for gastroesophageal reflux disease. Increased body mass index (BMI) was observed in patients without underlying conditions (BE: 30.1â±â9.8; IMGEJ: 23.9â±â6.3) compared with those with underlying conditions (BE: 19.6â±â7.8; IMGEJ: 16.4â±â2.1) (BE, Pâ=â0.02; IMGEJ, Pâ=â0.01). Incomplete intestinal metaplasia (IM) was the predominant histology seen in BE (80%) and IMGEJ patients (75%). Dysplasia and malignancy were not identified in the initial and follow-up biopsies. Concurrent gastric biopsies showed various findings (79% BE and 40% IMGEJ were normal), with 1 IMGEJ patient showing coexisting gastric IM (7%). Follow-up in 12 BE patients (mean follow-up time 51.6 months) showed 100% persistent endoscopic disease and 58% persistent IM histologically. Three of 6 IMGEJ patients (mean follow-up time 24 months) demonstrated endoscopic and histologic features consistent with BE on subsequent procedures. Moreover, a subset of BE (57%) and IMGEJ patients (67%) who underwent endoscopy before initial diagnosis showed nongoblet columnar mucosa above the anatomic gastroesophageal junction. CONCLUSIONS: Increased BMI may be a risk factor for BE and IMGEJ in pediatric patients without underlying conditions. Nongoblet columnar metaplasia and IMGEJ might represent incomplete forms of BE. Our data suggest that these patients should be closely monitored.
Subject(s)
Barrett Esophagus , Gastroesophageal Reflux , Adolescent , Biopsy , Child , Esophagogastric Junction , Female , Gastroesophageal Reflux/etiology , Humans , Male , Metaplasia , Retrospective StudiesABSTRACT
BACKGROUND: Our previous case series suggested that a 1-week, low-calorie and low-fat diet was associated with decreased intraoperative blood loss in patients undergoing liver surgery. OBJECTIVE: The current study evaluates the effect of this diet in a randomized controlled trial. METHODS: We randomly assigned 60 patients with a body mass index ≥25âkg/m(2) to no special diet or an 800-kcal, 20 g fat, and 70 g protein diet for 1 week before liver resection. Surgeons were blinded to diet assignment. Hepatic glycogen stores were evaluated using periodic acid Schiff (PAS) stains. RESULTS: Ninety four percent of the patients complied with the diet. The diet group consumed fewer daily total calories (807 vs 1968 kcal, P < 0.001) and fat (21 vs 86 g, P < 0.001) than the no diet group. Intraoperative blood loss was less in the diet group: mean blood loss 452 vs 863 mL (P = 0.021). There was a trend towards decreased transfusion in the diet group (138 vs 322 mL, P = 0.06). The surgeon judged the liver to be easier to manipulate in the diet group: 1.86 versus 2.90, P = 0.004. Complication rate (20% vs 17%), length of stay (median 5 vs 4 days) and mortality did not differ between groups. There was no difference in hepatic steatosis between groups. There was less glycogen in hepatocytes in the diet group (PAS stain score 1.61 vs 2.46, P < 0.0001). CONCLUSIONS: A short-course, low-fat, and low-calorie diet significantly decreases bleeding and makes the liver easier to manipulate in hepatic surgery.
Subject(s)
Diet/methods , Hepatectomy/adverse effects , Postoperative Hemorrhage/prevention & control , Preoperative Care/methods , Body Mass Index , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Postoperative Hemorrhage/epidemiology , Prognosis , Retrospective Studies , Time Factors , United States/epidemiologyABSTRACT
Adipocytic neoplasms in the pediatric population demonstrate a different histologic spectrum and frequency than in adults. The vast majority of these tumors are benign, with lipoma being the most common entity. The identification of signature cytogenetic and molecular alterations for certain lesions, such as PLAG1 gene rearrangement in lipoblastoma and FUS-DDIT3 fusion in myxoid liposarcoma, has been helpful in approaching these neoplasms and aiding in confirming the diagnosis. Furthermore, it is important for pathologists to recognize that adipocytic neoplasms may be associated with different syndromes with potential impact in managing such patients. This review provides a summary of the clinical pictures, histologic characteristics, molecular alterations, differential diagnoses, and syndromic associations of the commonly encountered fatty tumors in children.