RESUMO
BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.
Assuntos
Injúria Renal Aguda/virologia , COVID-19/complicações , SARS-CoV-2/isolamento & purificação , Carga Viral , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/análise , COVID-19/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Urina/virologiaRESUMO
Pleomorphic fibroma is a rare benign cutaneous neoplasm characterized by spindle-shaped cells and multinucleated giant cells scattered throughout collagenous stroma. These morphologic features can lead to diagnostic confusion, including atypical lipomatous tumor as one consideration. In contrast to atypical lipomatous tumor, previous studies have found pleomorphic fibroma to be negative for MDM2 immunohistochemical staining and MDM2 gene amplification. Here, we present a case of pleomorphic fibroma of skin with nuclear MDM2 immunoreactivity in the absence of MDM2 gene amplification, underscoring the superiority of fluorescence in situ hybridization as a diagnostic test in this differential diagnosis. The RB1 locus is also explored for differential diagnosis with pleomorphic/spindle cell lipoma and related entities.
Assuntos
Biomarcadores Tumorais/análise , Histiocitoma Fibroso Benigno/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Neoplasias Cutâneas/diagnóstico , Feminino , Histiocitoma Fibroso Benigno/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/análise , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
A 5-year-old boy presented with unilateral, focal superonasal conjunctival injection in the absence of vision changes or trauma. He was treated with a topical steroid for possible phlyctenule or episcleritis, but the lesion progressed to an elevated nodule, raising concern for nodular scleritis with no evidence of posterior involvement. Systemic work-up for underlying inflammatory conditions was unremarkable. There was some improvement in the level of injection with topical steroid, topical fluoroquinolone, and oral nonsteroidal anti-inflammatory drugs, but the nodular lesion persisted. Excisional biopsy revealed an inflamed dermoid cyst in the sub-Tenon's space.
Assuntos
Cisto Dermoide , Esclerite , Anti-Inflamatórios não Esteroides/uso terapêutico , Pré-Escolar , Cisto Dermoide/diagnóstico , Humanos , Masculino , Esclera , Esclerite/diagnóstico , Esclerite/tratamento farmacológicoRESUMO
Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse causes. The presence of the apolipoprotein L1 (APOL1) high-risk genotype is a major risk factor for collapsing glomerulopathy in African Americans. Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations. However, kidney involvement is being frequently noted and is associated with higher mortality. Currently, kidney pathology data for COVID-19 are scant and mostly come from postmortem findings. We report 2 African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 infection. Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells. Both patients had the APOL1 high-risk genotype. We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 infection, especially in people of African descent with APOL1 risk alleles.
RESUMO
A 58-year-old woman with a surgical history of jejunoileal bypass in 1980 for weight reduction sought medical attention with multiple complaints. The patient had not been taking any nutritional supplements since her bypass surgery, 26 years previously. She was found to have osteomalacia, chronic diarrhea, secondary hyperparathyroidism, and hyperoxaluria with a frequent history of nephrolithiasis. Because of her severe osteodystrophy and metabolic complications, reversal of her jejunoileal bypass was recommended. Reversal of the jejunoileal bypass with a sleeve gastrectomy was performed. Laparotomy revealed brown discoloration of the entire alimentary limb with atrophy of the bypassed intestinal limb. Histologic examination of the resected small bowel demonstrated brown pigment deposits within smooth muscle cells of the bowel wall. The pigment stained positive with Fontana-Masson most likely representing lipofuscin. We report a case of brown bowel syndrome complicating jejunoileal bypass, the first case reported in the literature to the best of our knowledge.
Assuntos
Enteropatias/etiologia , Derivação Jejunoileal/efeitos adversos , Síndromes de Malabsorção/etiologia , Transtornos da Pigmentação/etiologia , Feminino , Gastrectomia/métodos , Humanos , Enteropatias/patologia , Enteropatias/cirurgia , Lipofuscina/análise , Síndromes de Malabsorção/patologia , Síndromes de Malabsorção/cirurgia , Pessoa de Meia-Idade , Músculo Liso/química , Músculo Liso/patologia , Osteoporose/etiologia , Transtornos da Pigmentação/patologia , Transtornos da Pigmentação/cirurgia , Síndrome , Deficiência de Vitamina D/etiologiaRESUMO
Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.
Assuntos
Eosinófilos/patologia , Neoplasias de Cabeça e Pescoço/patologia , Hemangioma Capilar/patologia , Corpos de Inclusão/patologia , Lisossomos/patologia , Síndrome POEMS/patologia , Idoso , Antígenos CD34/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/diagnóstico , Hemangioma Capilar/irrigação sanguínea , Hemangioma Capilar/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fator de von Willebrand/metabolismoRESUMO
A unique pattern of cytokeratin (CK) 7/20 immunostaining (diffuse staining with CK7 and surface and superficial crypt staining with CK20) has been reported to be useful in differentiating Barrett esophagus (BE) from intestinal metaplasia of the stomach. However, there are conflicting results regarding the prevalence of a BE CK7/20 staining pattern in BE between different studies. Therefore, this study was performed to determine the degree of variability in interpretation of a BE CK7/20 pattern and to determine the reasons for variability when present. Esophageal and gastric mucosal biopsies from 67 patients with BE and antral intestinal metaplasia at 2 institutions were immunostained for CK7/20. All cases were evaluated for the presence of a BE CK7/20 pattern by 2 gastrointestinal pathologists from each institution, and the degree of agreement between institutions was determined. To determine the effect of tissue fixation and staining methods on the pattern of CK7/20 staining, unstained slides were exchanged between institutions, stained separately by each institution, and reexamined by all pathologists. There was excellent agreement on the presence of a BE CK7/20 staining pattern between pathologists at the same institution but only moderate agreement between pathologists at different institutions (71% overall, kappa = 0.58). Among BE cases, a BE CK7/20 staining pattern was identified in 50 (96%) of 52 cases by Cleveland Clinic Foundation pathologists but only 35 (67%) of 52 cases by Brigham and Women's Hospital pathologists. The major source of disagreement related to the interpretation of weak or variable CK7 staining of deep intestinalized mucosa in BE biopsies that were fixed in Hollande, but not those that were fixed in formalin. After the creation of a new set of criteria for a positive BE CK7/20 staining pattern, which took into account the effects of Hollande's fixative, the degree of agreement between pathologists at each of the 2 institutions was excellent (100%, kappa value = 1.0). Therefore, the CK7/20 staining pattern is influenced by the type of fixative used. Only a moderate level of interobserver agreement among pathologists regarding a BE CK7/20 pattern can be achieved if one is not aware of these effects. Nevertheless, specific criteria for interpretation of CK7/20 staining can be successfully applied between institutions and need to be developed before use of this technique in clinical practice.
Assuntos
Esôfago de Barrett/metabolismo , Imuno-Histoquímica/normas , Proteínas de Filamentos Intermediários/metabolismo , Queratinas/metabolismo , Metaplasia/metabolismo , Fixação de Tecidos , Esôfago de Barrett/patologia , Diagnóstico Diferencial , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Queratina-20 , Queratina-7 , Metaplasia/patologia , Reprodutibilidade dos TestesRESUMO
We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.
Assuntos
Adenocarcinoma/diagnóstico , Antagonistas de Androgênios/uso terapêutico , Próstata/patologia , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/patologia , Atrofia/diagnóstico , Diagnóstico Diferencial , Humanos , Queratinas , Masculino , Hiperplasia Prostática/diagnóstico , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To assess mature burn scars treated with a fractional carbon dioxide laser for changes in histological architecture, type I to III collagen ratios, density of elastic tissue, and subjective measures of clinical improvements. DESIGN: Uncontrolled, prospective study of patients with mature burn scars, from a clinical and histological perspective. Biopsy specimens were obtained before and 2 months after 3 treatment sessions. The tissue was prepared with Verhoff von Giesen (VVG) stain to discern elastic tissue and Herovici stain to differentiate types I and III collagen. SETTING: Subjects were recruited from the Grossman Burn Centers. PARTICIPANTS: Of 18 patients with mature burn scars, 10 completed the entire treatment protocol. INTERVENTION: Participants received 3 treatments with a fractional carbon dioxide laser. MAIN OUTCOME MEASURES: Vancouver Scar Scale and Patient and Observer Scar Assessment Scale survey scores. In histological analysis, imaging software was used to measure changes in collagen subtype and elastic tissue. A rating scale was developed to assess normal vs scar architecture. RESULTS: The first hypothesis that significant histological improvement would occur and the second hypothesis of a statistically significant increase in type III collagen expression or a decrease in type I collagen expression were confirmed. There were no significant changes in elastic tissue. Statistically significant improvements were seen in all survey data. CONCLUSIONS: Treatment with a fractional carbon dioxide laser improved the appearance of mature burn scars and resulted in a significant improvement in collagen architecture following treatment. Furthermore, in treated skin specimens, a collagen subtype (types I and III collagen) profile resembling that of nonwounded skin was found.
Assuntos
Queimaduras/complicações , Cicatriz/terapia , Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Lasers de Gás/uso terapêutico , Adulto , Cicatriz/etiologia , Cicatriz/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Coloração e Rotulagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome (OS) is a vaguely defined entity demonstrating features of AIH and PBC. We investigated the usefulness of IgG and IgM immunostaining for the distinction of AIH and PBC and their staining pattern in cases of possible OS. The approximate quantity of IgG+ and IgM+ periportal inflammatory cells in immunohistochemical analysis were compared in cases of AIH, PBC, and OS. AIH cases showed predominant IgG immunostaining of periportal inflammatory cells. A significant number of PBC cases also demonstrated IgG predominance rather than IgM. Six OS cases had IgG predominance, 4 had IgM predominance, and 1 was equivocal. The usefulness of IgG and IgM immunostaining is limited in PBC cases with IgM predominance for excluding AIH. IgG predominance is not specific for AIH. OS does not demonstrate either IgG or IgM predominance (P > .2) and does not help classify OS into either category.
Assuntos
Hepatite Autoimune/diagnóstico , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Cirrose Hepática Biliar/diagnóstico , Fígado/imunologia , Linfócitos/imunologia , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Fibrose/imunologia , Fibrose/metabolismo , Hepatite Autoimune/imunologia , Hepatite Autoimune/metabolismo , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Síndrome , Análise Serial de TecidosRESUMO
BACKGROUND: Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC. METHODS: Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained. RESULTS: Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively. CONCLUSIONS: For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC.
Assuntos
Biomarcadores Tumorais , Carcinoma/diagnóstico , Queratinas , Proteínas de Membrana , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias Cutâneas/diagnóstico , Carcinoma/química , Carcinoma/secundário , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Neoplasias de Anexos e de Apêndices Cutâneos/química , Estudos Retrospectivos , Neoplasias Cutâneas/química , Neoplasias Cutâneas/secundárioRESUMO
BACKGROUND: Solitary sclerotic fibroma (SF) presents as a well circumscribed dermal nodule, composed of sparse spindle cells with alternating wavy collagen fibers arranged in a storiform pattern. The histogenesis and nature of this histologically distinct lesion are uncertain. Whether this peculiar tumor represents a true hamartoma or a degenerating end of various fibrous lesions such as pleomorphic fibroma (PF), dermatofibroma, or angiofibroma is still controversial. High proliferating index of spindle cells in SF argues against the possibility of being a degenerating end product of another lesion. METHODS: We studied morphological features and immunoprofile of eight SFs, in comparison with four PFs, one collagenized dermatofibroma, two angiofibromas, and two periungual fibromas. Immunostains for CD34, CD31, O13 (CD99), Factor XIIIa, S-100, CD68 (KP-1), and MIB-1 were carried out using a labeled streptavidin-biotin method with DAKO-automated immunostainer. Paraffin blocks of two SFs were reprocessed for electron microscopic studies. Clinical data of all patients with SF were also reviewed. RESULTS: Spindle cells and pleomorphic cells in SF and PF showed diffuse immunoreactivity for CD34 and O13 but were negative for CD31, S-100, and CD68. Spindle cells in one dermatofibroma and one angiofibroma were positive for Factor XIIIa. Proliferating index (MIB-1) was very low in all cases of SF, contradicting some previous reports. CONCLUSIONS: SF is a fibrotic lesion with cells positive for CD34 and O13. It shares a common immunoprofile with PF but is distinct from dermatofibroma and other common spindle cell lesions of skin. O13 expression in SF has not been previously described.
Assuntos
Antígenos CD34/análise , Antígenos CD/análise , Moléculas de Adesão Celular/análise , Fibroma/imunologia , Fibroma/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Antígeno 12E7 , Angiofibroma/imunologia , Angiofibroma/patologia , Histiocitoma Fibroso Benigno/imunologia , Histiocitoma Fibroso Benigno/patologia , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem , Doenças da Unha/imunologia , Doenças da Unha/patologia , Esclerose , Coloração e RotulagemRESUMO
OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr +/- 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type I and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.
Assuntos
Adenoma de Células das Ilhotas Pancreáticas/enzimologia , Carcinoma de Células Acinares/enzimologia , Ilhotas Pancreáticas/enzimologia , Neoplasias Pancreáticas/enzimologia , Telomerase/fisiologia , Adenoma de Células das Ilhotas Pancreáticas/mortalidade , Adenoma de Células das Ilhotas Pancreáticas/patologia , Adulto , Idoso , Carcinoma de Células Acinares/mortalidade , Carcinoma de Células Acinares/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI). METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy. CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.
Assuntos
Doenças Funcionais do Colo/patologia , Pouchite/patologia , Proctocolectomia Restauradora/efeitos adversos , Adulto , Canal Anal/patologia , Canal Anal/cirurgia , Anastomose Cirúrgica/efeitos adversos , Doenças Funcionais do Colo/etiologia , Endoscopia Gastrointestinal , Feminino , Humanos , Íleo/patologia , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Pouchite/etiologia , SíndromeRESUMO
BACKGROUND: Barrett esophagus (BE)/Barrett adenocarcinoma and distal gastric intestinal metaplasia (IM)/adenocarcinoma are similar histologically, but they differ in their clinical presentation, epidemiology, and pathogenesis. Differentiating BE from gastric IM and Barrett adenocarcinoma from gastric adenocarcinoma is difficult, especially when IM is short or tumors are large and involve both sides of the esophagogastric junction. Previously, the authors identified unique cytokeratin (CK) immunoreactivity patterns that were associated strongly with BE and Barrett adenocarcinoma. The specificity of CK7 and CK20 (CK7/20) expression patterns in patients with IM-associated gastric adenocarcinoma, which is distinct epidemiologically from BE/Barrett adenocarcinoma, has not been evaluated. The objective of the current study was to evaluate the CK7/20 expression patterns in noncardia, IM-associated gastric adenocarcinoma in a Chinese population with a low risk for BE and esophageal adenocarcinoma and a high risk for Helicobacter pylori infection and gastric carcinoma. METHODS: Endoscopic biopsy specimens of gastric IM and adjacent tumor from 50 consecutive patients with advanced noncardia gastric carcinoma were immunostained for CK7 and CK20. Clinical and endoscopic features and H. pylori status were documented. Two gastrointestinal pathologists, blinded to clinical and endoscopic data, independently assessed CK7/20 immunohistochemistry. RESULTS: H. pylori infection was present in 43 of 50 patients (86%). In the area of IM, patchy CK7 staining was seen in 9 patients (18%), and diffuse CK20 staining was seen in all 50 patients (100%). The BE CK7/20 pattern characterized by CK7 staining in superficial and deep glands and the CK20 staining in surface epithelium was not seen in any of the 50 patients. Only one patient (2%) demonstrated a CK7 positive/CK20 negative immunophenotype characteristic of Barrett adenocarcinoma. The remaining 49 patients (98%) showed non-Barrett adenocarcinoma patterns of CK7/20 staining, i.e., a CK7 positive/CK20 positive pattern was seen in 33 patients (66%), a CK7 negative/CK20 positive pattern was seen in 12 patients (24%), and a CK7 negative/CK20 negative pattern was seen in 4 patients (8%). CONCLUSIONS: In a patient population without risk factors for the development of BE/esophageal adenocarcinoma, the CK7/20 pattern characteristic of BE was not present in gastric IM adjacent to adenocarcinoma, and the CK7/20 pattern characteristic of Barrett adenocarcinoma also was extremely rare. These results support the hypothesis that, despite the presence of intestinalized mucosa in both disorders, BE/Barrett adenocarcinoma and gastric IM/adenocarcinoma are two distinct clinical entities with unique demographic, clinical, and CK immunophenotypic findings. These results may have application to the evaluation of patients with IM and adenocarcinoma arising at the esophagogastric junction.
Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Biomarcadores Tumorais/análise , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Filamentos Intermediários/biossíntese , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Biópsia , Diagnóstico Diferencial , Endoscopia , Neoplasias Esofágicas/patologia , Feminino , Infecções por Helicobacter/complicações , Humanos , Proteínas de Filamentos Intermediários/análise , Intestinos/patologia , Queratina-20 , Masculino , Metaplasia , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn's disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores' diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.