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1.
Pancreas ; 50(5): 719-726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34016898

RESUMO

OBJECTIVES: The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS). METHODS: Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface. RESULTS: Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43-0.68; P < 0.0001), 0.45 (95% CI, 0.32-0.59; P = 0.0002), 0.50 (95% CI, 0.40-0.61; P < 0.0001), and 0.24 (95% CI, 0.03-0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19-0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68-5.91). CONCLUSIONS: Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.


Assuntos
Neoplasias Gastrointestinais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Tumores Neuroendócrinos/imunologia , Neoplasias Pancreáticas/imunologia , Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Adolescente , Adulto , Idoso , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Complexo CD3/análise , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Receptor de Morte Celular Programada 1/análise , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
2.
Cancer Immunol Res ; 7(5): 805-812, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30902819

RESUMO

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8+ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1+ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1+ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8+ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.


Assuntos
Antígenos CD/imunologia , Antígenos B7/imunologia , Antígeno B7-H1/imunologia , Carcinoma Hepatocelular/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Neoplasias Hepáticas/imunologia , Receptor de Morte Celular Programada 1/imunologia , Adulto , Feminino , Humanos , Tolerância Imunológica , Masculino , Adulto Jovem , Proteína do Gene 3 de Ativação de Linfócitos
3.
Mod Pathol ; 31(10): 1532-1538, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29849115

RESUMO

Neurofibromatosis type 1 (NF1) is a hereditary cancer predisposition syndrome characterized by frequent cutaneous and nervous system abnormalities. Patients with NF1 also have an increased prevalence of multiple gastrointestinal and peripancreatic neoplasms-neuroendocrine tumors of the ampulla that express somatostatin are particularly characteristic of NF1. In this study, we characterize the genetic alterations of a clinically well-characterized cohort of six NF1-associated duodenal neuroendocrine tumors using whole-exome sequencing. We identified inactivating somatic mutations in the NF1 gene in three of six tumors; the only other gene altered in more than one tumor was IFNB1. Copy number analysis revealed deletion/loss of heterozygosity of chromosome 22 in three of six patients. Analysis of germline variants revealed germline deleterious NF1 variants in four of six patients, as well as deleterious variants in other tumor suppressor genes in two of four patients with deleterious NF1 variants. Taken together, these data confirm the importance of somatic inactivation of the wild-type NF1 allele in the formation of NF1-associated duodenal neuroendocrine tumors and suggest that loss of chromosome 22 is important in at least a subset of cases. However, we did not identify any genes altered in the majority of NF1-associated duodenal neuroendocrine tumors that uniquely characterize the genomic landscape of this tumor. Still, the genetic alterations in these tumors are distinct from sporadic neuroendocrine tumors occurring at these sites, highlighting that unique genetic alterations drive syndromic tumors.


Assuntos
Neoplasias Duodenais/genética , Tumores Neuroendócrinos/genética , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Adulto , Neoplasias Duodenais/etiologia , Feminino , Genes da Neurofibromatose 1 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Tumores Neuroendócrinos/etiologia , Sequenciamento do Exoma
4.
Histopathology ; 73(2): 220-229, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29667709

RESUMO

AIMS: Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus. METHODS AND RESULTS: We identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months-73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2-55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non-oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar-type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms. CONCLUSIONS: We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.


Assuntos
Canal Anal/patologia , Coristoma/patologia , Doenças do Colo/patologia , Doenças Retais/patologia , Estômago , Adolescente , Adulto , Idoso , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
5.
Pancreatology ; 17(3): 490-496, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28416122

RESUMO

BACKGROUND/OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date. METHODS: We compared 142 MCNs and 746 IPMNs resected at a single institution. MCNs were reviewed for confirmation of ovarian-type stroma and reclassified according to current WHO guidelines. RESULTS: MCNs presented almost exclusively in middle-aged women (median 47.5 years, 96.5% female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas (92.1%). IPMNs were distributed equally by sex in an older population (median 69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1% vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs (9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs. Patients with an MCN-associated invasive carcinoma had a much better prognosis than did patients with an IPMN-associated invasive carcinoma with 10-year disease-specific survival of 79.6% versus 27.2%, respectively. CONCLUSION: MCNs have a stereotypical clinical profile that is readily distinguishable from IPMNs based on demographic features, imaging, and pathology. Most MCNs are noninvasive and curable with surgical resection. Prognosis remains excellent even for invasive disease with 10-year survival approaching 80% following resection.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Pancreáticas/cirurgia , Papiloma Intraductal/cirurgia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico por imagem , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Papiloma Intraductal/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Resultado do Tratamento
6.
Virchows Arch ; 470(4): 391-400, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28188442

RESUMO

McCune-Albright Syndrome (MAS) is a rare sporadic syndrome caused by post-zygotic mutations in the GNAS oncogene, leading to constitutional mosaicism for these alterations. Somatic activating GNAS mutations also commonly occur in several gastrointestinal and pancreatic neoplasms, but the spectrum of abnormalities in these organs in patients with MAS has yet to be systematically described. We report comprehensive characterization of the upper gastrointestinal tract in seven patients with MAS and identify several different types of polyps, including gastric heterotopia/metaplasia (7/7), gastric hyperplastic polyps (5/7), fundic gland polyps (2/7), and a hamartomatous polyp (1/7). In addition, one patient had an unusual adenomatous lesion at the gastroesophageal junction with high-grade dysplasia. In the pancreas, all patients had endoscopic ultrasound findings suggestive of intraductal papillary mucinous neoplasm (IPMN), but only two patients met the criteria for surgical intervention. Both of these patients had IPMNs at resection, one with low-grade dysplasia and one with high-grade dysplasia. GNAS mutations were identified in the majority of lesions analyzed, including both IPMNs and the adenomatous lesion from the gastroesophageal junction. These studies suggest that there is a broad spectrum of abnormalities in the gastrointestinal tract and pancreas in patients with MAS and that patients with MAS should be evaluated for gastrointestinal pathology, some of which may warrant clinical intervention due to advanced dysplasia.


Assuntos
Displasia Fibrosa Poliostótica/patologia , Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Adulto , Cromograninas/genética , Feminino , Displasia Fibrosa Poliostótica/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Gastroenteropatias/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
7.
Gastroenterology Res ; 9(4-5): 65-69, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27785328

RESUMO

BACKGROUND: Gastroparesis is a condition classically characterized by delayed gastric emptying and is associated with considerable morbidity. While the etiology of gastroparesis remains elusive, autonomic dysfunction may play an important role, especially as many patients with gastroparesis also have diabetes. The aim of this study was to determine whether measures of autonomic function differ between adults with diabetic gastroparesis (DG) and adults with idiopathic gastroparesis (IG). METHODS: Tests of systemic autonomic function were performed among 20 adults with GD (six men and 14 women, mean age: 42 years) and 21 adults with IG (seven men and 14 women, mean age: 37 years). Measures included vagal cholinergics by R-R interval percentage variation (RRI-PV) and sympathetic adrenergics by vasoconstriction to cold (VC) and postural adjustment ratio (PAR). The two groups were compared using Wilcoxon rank sum tests and linear regression analysis (STATA 10.0). RESULTS: In univariate analysis, the following autonomic measures differed significantly between DG and IG: VC (P = 0.004), PAR (P = 0.045), VC + PAR (P = 0.002) and RRI-PV (P < 0.001). In multivariate analysis (P = 0.002, R2 = 0.55), only RRI-PV (adjusted odds ratio (aOR): 1.02, 95% confidence interval (CI): 1.01 - 1.03) differed significantly between DG and IG patients. CONCLUSIONS: Vagal cholinergics are affected to a greater degree in DG compared to IG, suggesting that impaired vagal tone is not a universal mechanism for gastroparesis.

9.
Am J Surg Pathol ; 39(12): 1611-20, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26291507

RESUMO

Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG are frequently overlooked, especially in the early stages of the disease. The purpose of our study, therefore, was to catalogue the progression of histologic changes that precede the development of AMAG in affected individuals. Over a 2-year period (2012 to 2014), the diagnosis of AMAG was rendered on material from 113 patients seen at Johns Hopkins Hospital (∼1.8% of "in house" gastric biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in the cohort, and the majority of these specimens had also shown AMAG. Eighteen of the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor-like effect. Upon review of these 18 biopsies, the most common histologic findings were heavy full-thickness or deep lamina propria chronic inflammation (12), inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric, or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and parietal cell pseudohypertrophy (4). At least 2 of these features were present in the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients were also found to have another autoimmune or inflammatory disorder before the diagnosis of AMAG. Although subtle, histologic features of developing AMAG are identifiable in routine gastric body biopsies. When metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction are seen, a note suggesting laboratory testing and/or close clinical follow-up in this subset of patients may be warranted.


Assuntos
Doenças Autoimunes/patologia , Gastrite Atrófica/patologia , Estômago/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/metabolismo , Baltimore , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Erros de Diagnóstico , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Gastrite Atrófica/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Metaplasia , Pessoa de Meia-Idade , Células Parietais Gástricas/química , Células Parietais Gástricas/patologia , Valor Preditivo dos Testes , Prognóstico , Estômago/química , Fatores de Tempo
10.
Am J Surg Pathol ; 39(12): 1668-72, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26291509

RESUMO

Tactile corpuscle-like bodies (TCLB) are microscopic Schwannian structures that simulate the superficial mechanoreceptors of the peripheral nervous system (Wagner-Meissner corpuscles). They have been described nearly exclusively in peripheral nerve sheath tumors, namely diffuse neurofibromas, and schwannomas but also in cellular nevi. There are rare reports of these structures in the gastrointestinal tract (predominantly the lower tract), with the presumption that they are incidental reactive neural proliferations. We compiled 9 cases showing this rare phenomenon in gastrointestinal-type mucosa in nonsyndromic patients to further characterize its features. There were 6 men and 3 women (age range, 39 to 79 y, mean 56 y) with lesions involving esophagus/gastro-esophageal junction (n=7), sigmoid colon (n=1), and gastric heterotopia of the cricopharynx (n=1). Endoscopic examination was abnormal in 6 of the 7 cases (including changes consistent with Barrett esophagus and polypoid/nodular mucosa) and normal in 1 of 7 cases for which this information was available. The histologic features were similar in all cases, with unencapsulated clusters of lamellated and concentrically arranged spindle cells in the lamina propria. The foci of TCLB ranged in size from <0.1 to 1.5 mm in the greatest dimension. Abnormal histopathologic findings were identified in the background mucosa in 6 of 9 cases (including Barrett esophagus, active and inactive chronic gastritis, enterochromaffin-like cell hyperplasia, and gastric intestinal metaplasia). None of the patients showed signs of neurofibromatosis type 1, multiple endocrine neoplasia type 2B, Cowden syndrome, or other inherited syndrome. No morbidity related to TCLB was reported for the patients with available follow-up.


Assuntos
Trato Gastrointestinal/patologia , Mecanorreceptores/patologia , Células de Schwann/patologia , Adulto , Idoso , Biomarcadores/análise , Biópsia , Linhagem da Célula , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Trato Gastrointestinal/química , Humanos , Imuno-Histoquímica , Achados Incidentais , Masculino , Mecanorreceptores/química , Pessoa de Meia-Idade , Mucosa/química , Mucosa/patologia , Valor Preditivo dos Testes , Regeneração , Células de Schwann/química , Estados Unidos
11.
N Engl J Med ; 372(26): 2509-20, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-26028255

RESUMO

BACKGROUND: Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. METHODS: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair-deficient colorectal cancers, patients with mismatch repair-proficient colorectal cancers, and patients with mismatch repair-deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. RESULTS: The immune-related objective response rate and immune-related progression-free survival rate were 40% (4 of 10 patients) and 78% (7 of 9 patients), respectively, for mismatch repair-deficient colorectal cancers and 0% (0 of 18 patients) and 11% (2 of 18 patients) for mismatch repair-proficient colorectal cancers. The median progression-free survival and overall survival were not reached in the cohort with mismatch repair-deficient colorectal cancer but were 2.2 and 5.0 months, respectively, in the cohort with mismatch repair-proficient colorectal cancer (hazard ratio for disease progression or death, 0.10 [P<0.001], and hazard ratio for death, 0.22 [P=0.05]). Patients with mismatch repair-deficient noncolorectal cancer had responses similar to those of patients with mismatch repair-deficient colorectal cancer (immune-related objective response rate, 71% [5 of 7 patients]; immune-related progression-free survival rate, 67% [4 of 6 patients]). Whole-exome sequencing revealed a mean of 1782 somatic mutations per tumor in mismatch repair-deficient tumors, as compared with 73 in mismatch repair-proficient tumors (P=0.007), and high somatic mutation loads were associated with prolonged progression-free survival (P=0.02). CONCLUSIONS: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Reparo de Erro de Pareamento de DNA , Metástase Neoplásica/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética
13.
Arch Pathol Lab Med ; 138(12): 1685-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25427047

RESUMO

Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple. Visceral malignancies most often arise in the colorectum and endometrium. Because a subset of patients with phenotypic MTS will have germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1, MTS is considered a phenotypic subtype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), in which inherited defects in DNA mismatch repair genes result in microsatellite instability. Pathologists have an important role in the early detection and initial diagnosis of MTS: identification of at-risk individuals allows appropriate screening and surveillance for visceral malignancies, thereby reducing morbidity and mortality. Herein, we describe the clinicopathologic features of MTS.


Assuntos
Síndrome de Muir-Torre , Humanos , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/terapia
14.
Urology ; 83(2): 455-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24231219

RESUMO

Urachal anomalies are relatively uncommon and result because of incomplete obliteration of the urachus prenatally. In children, urachal cysts and sinuses constitute the common presentations, and these can sometimes become secondarily infected. Malignant involvement of the urachus in the pediatric population is rare, and primary urachal adenocarcinoma is reported exclusively in adults. Herein, we present the case of an adolescent girl with a low-grade mucinous neoplasm arising in a urachal cyst and discuss its significance.


Assuntos
Adenocarcinoma Mucinoso/complicações , Adenocarcinoma/complicações , Cisto do Úraco/complicações , Neoplasias da Bexiga Urinária/complicações , Adolescente , Feminino , Humanos
15.
Clin Gastroenterol Hepatol ; 12(2): 246-52.e1, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23920033

RESUMO

BACKGROUND & AIMS: Gastric ischemia is infrequently reported in the medical literature and under-recognized clinically and histopathologically. Various medical terms are used to describe gastric ischemia. We define and review the pathogenesis, diagnosis, and management of gastric ischemia. METHODS: We describe 6 cases of gastric ischemia. We discuss features of the gastric vascular supply and review literature on this disorder. RESULTS: Gastric ischemia results from diffuse or localized vascular insufficiency caused by etiologies such as systemic hypotension, vasculitis, or disseminated thromboembolism. The disorder is managed by fluid resuscitation, nasogastric tube placement (for intermittent air and fluid aspiration, to prevent or reduce gastric distention), aggressive acid reduction (via intravenous administration of proton pump inhibitors), and selective use of broad-spectrum antibiotics for patients with sepsis or gastric pneumatosis. CONCLUSIONS: Gastric ischemia has a poor prognosis. Early diagnosis is required for appropriate patient management.


Assuntos
Isquemia/patologia , Estômago/irrigação sanguínea , Adulto , Idoso de 80 Anos ou mais , Artéria Celíaca/anatomia & histologia , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/patologia , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Isquemia/terapia , Pessoa de Meia-Idade , Prognóstico , Estômago/patologia , Volvo Gástrico/complicações
16.
Case Rep Med ; 2013: 797264, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24198839

RESUMO

First described in 1998, Russell body gastritis is a rare chronic inflammatory condition characterized by abundant intramucosal polyclonal plasma cells, which contain intracytoplasmic eosinophilic globules of immunoglobulins (Russell bodies) that displace the nucleus, with an accompanying chronic inflammatory infiltrate. Russell bodies represent a cellular response to overstimulation of plasma cells, leading to the accumulation of abundant, nondegradable, condensed immunoglobulin in dilated rough endoplasmic reticulum cisternae. Russell body gastritis usually occurs in the gastric antrum, but two cases of Russell body duodenitis have been recently described. Herein, we report an unusual case of Barrett esophagus with prominent lymphoplasmacytic infiltration and Russell bodies, which expands the current spectrum of Russell body gastritis/duodenitis. Given the various anatomic locations in which Russell body gastritis may arise, we suggest that "Russell body gastroenteritis" may be a more appropriate designation for this uncommon reactive condition.

18.
Am J Cancer Res ; 3(2): 230-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593544

RESUMO

Gene expression profiling reveals elevated Notch1 mRNA expression in triple negative breast cancers (TNBC), both basaloid and claudin-low subtypes. Notch ligands, Jagged1 and Jagged2, have been correlated with poor prognosis in TNBC. AKT, an oncogenic protein kinase family that is activated downstream of Notch in breast cancer cell lines, is frequently activated in breast cancer. Recent publications suggest that inhibition of cell growth, migration, invasion, and induction of apoptosis caused by Notch1 or Jagged1 inhibition may be attributed in part to inactivation of the AKT signaling pathway. There is significant evidence that Notch1 activates NF-κB in several models, and that AKT can mediate NF-κB activation. In this study, we evaluated Notch1 protein expression by immunohistochemistry (IHC) and correlated this with expression of pAKT and nuclear NF-κB p65 (RelA) in TNBC. A tissue microarray (TMA) containing 32 formalin-fixed, paraffin-embedded (FFPE) TNBC tumor specimens was constructed from the archival tissue database of the Department of Pathology at UMMC and IHC for Notch1 protein, pAKT 1/2/3 (Ser473), and NF-κB, p65 subunit was performed on the TMA with appropriate positive and negative controls. Of the 32 TNBC in our cohort, 100% expressed Notch1 protein by IHC: 24 (75%) showed cytoplasmic expression, 25 (78%) showed membranous expression, and 17 (53%) showed both cytoplasmic and membranous expression. Overall, 29 (91%) expressed pAKT by IHC: 28 (97%) showed cytoplasmic expression, 14 (48%) showed nuclear expression and 13 (45%) showed both cytoplasmic and nuclear expression. Nuclear staining for NF-κB p65 was detected in all 32 TNBC specimens with variable intensities. On bivariate analysis, cytoplasmic Notch1 was significantly correlated with cytoplasmic pAKT (r = 0.373, P = 0.035) and nuclear NF-κB (r = 0.483, P = 0.005); both cytoplasmic and nuclear pAKT significantly correlated with nuclear NF-κB (r = 0.391, P = 0.027; r = 0.525, P = 0.002, respectively). These results suggest that 1) the cross-talk between Notch1, AKT and NF-κB identified in preclinical models may operate in a significant fraction of human TNBC, and 2) combination therapy with agents targeting these pathways warrants further investigation.

20.
J Investig Med High Impact Case Rep ; 1(2): 2324709613484302, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26425572

RESUMO

BACKGROUND: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. RESULTS: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. CONCLUSIONS: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

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