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BACKGROUND: Gastrointestinal symptoms occur with deeply infiltrating endometriosis (DIE) of the rectum. AIMS: To explore the medium-term gastrointestinal functional outcomes after rectal disc resection for endometriosis. METHODS: All women undergoing laparoscopy for stage IV endometriosis at a tertiary referral hospital between November 2016 and January 2018 and had evidence of DIE of the rectum were included. Low anterior resection syndrome (LARS) score was measured using a validated questionnaire. RESULTS: Thirty-six women formed the cohort of the study. The mean age was 37 years (range 20-72 years). All women underwent a laparoscopic anterior rectal disc resection for DIE. The response rate was 100%. There was an increase in the percentage of patients having no LARS postoperatively compared to preoperatively (an increase of 78-83%). There was a reduction in LARS scores postoperatively observed in 18 patients (50%) and the prevalence of major LARS decreased postoperatively from 10% to 1%. Comparison of individual symptoms revealed a significant improvement in postoperative stool frequency scores (P = 0.02). Multivariate analysis using logistic regression analysis demonstrated that reduction in postoperative stool frequency scores remained an independent factor (P = 0.008). CONCLUSION: Rectal disc resection is feasible and safe, achieving observable improvements in stool frequency in patients with rectal DIE.
Assuntos
Defecação , Endometriose/cirurgia , Doenças Retais/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/fisiopatologia , Reto/cirurgia , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemAssuntos
Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/secundário , Apendicite/etiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Apendicite/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Acute perforated diverticulitis is frequently observed and spans a spectrum in the severity of its presentation. Emergency surgery is required in patients with generalized peritonitis; however, a large proportion of patients are clinically stable with localized peritonitis. This article aimed to examine this specific group of patients by reviewing the outcomes of their conservative management. METHODS: A systematic literature search was performed on the MEDLINE and PubMed databases. The management outcomes of patients undergoing non-operative treatment for acute perforated diverticulitis were synthesized and tabulated. RESULTS: Of 479 patients, 407 (85%) were successfully managed non-operatively. In total 70 (14.6%) patients failed non-operative treatment and underwent operative surgical management, and two (0.4%) died. Emergency surgery includes a Hartmann's operation (40%) and resection with anastomosis with or without stoma (24%), laparoscopic lavage (16%) and surgical drainage (20%). The success rate of conservative management was 94.0% and 71.4% for patients with pericolic and distant free air, respectively. Treatment failure was associated with a high volume of free air, distant free air and the presence of abscess. CONCLUSIONS: Conservative management is safe and successful in patients with acute perforated diverticulitis without generalized peritonitis. The early recognition of patients who show clinical signs of persistent perforation is important to ensure the success of this strategy.
Assuntos
Tratamento Conservador/métodos , Diverticulite/terapia , Perfuração Intestinal/terapia , Doença Aguda , Adulto , Idoso , Diverticulite/complicações , Feminino , Humanos , Perfuração Intestinal/complicações , Masculino , Pessoa de Meia-Idade , Peritonite/etiologia , Peritonite/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine cancer with treatments limited in efficacy for metastatic disease. New molecular targeted therapies have yet to improve patient outcomes. In contrast, established treatment regimens of adrenolytics and chemotherapy have demonstrated treatment benefit, although admittedly in a minority of patients. Identification of microRNAs (miRNAs) in patients responsive to adjuvant therapy may offer a means to sensitize patients with progressive disease to existing adjuvant regimens. MATERIALS AND METHODS: Samples from primary ACC tumors of 10 Stage IV patients were examined for differentially expressed miRNAs between a "sensitive" and "resistant" cohort. Candidate microRNAs were restored via transfection in two functional ACC cell lines. Gain of function and effects on apoptosis and cell cycle were assessed. RESULTS: microRNA-431 (miR-431) was underexpressed in patients with ACC with progressive disease undergoing adjuvant therapy. Restoration of miR-431 in vitro decreased the half maximal inhibitory concentrations of doxorubicin and mitotane, with markedly increased apoptosis. We found that a reversal of epithelial-mesenchymal transition underlies the action of miR-431 with doxorubicin treatment, with Zinc Finger E-Box Binding Homeobox 1 implicated as the molecular target of miR-431 in ACC. CONCLUSION: This is the first report of the potential of miRNA therapy to sensitize ACC to current established adjuvant therapy regimens, which may mitigate the resistance underlying treatment failure in patients with advanced ACC. Effective and well-studied methods of targeted miRNA delivery in existence hints at the imminent translatability of these findings. IMPLICATIONS FOR PRACTICE: Adrenocortical carcinoma (ACC) is a rare endocrine cancer with outcomes not improving despite extensive research and new targeted therapies. Mitotane and etoposide/doxorubicin/cisplatin chemotherapy is trial validated for improved recurrence-free survival. However, a minority of patients experience sustained benefit. Significant side effects exist for this regimen, with patients often unable to attain target drug doses shown to give survival benefit. This preclinical study examines the role of microRNAs in sensitizing ACC to doxorubicin or mitotane. This study offers an important bridge between new and existing cancer treatments, offering an imminently translatable approach to the treatment of adrenocortical carcinoma.
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Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Adolescente , Córtex Suprarrenal/patologia , Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Adrenalectomia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Biópsia , Linhagem Celular Tumoral , Quimioterapia Adjuvante/métodos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/agonistas , MicroRNAs/genética , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Adrenocortical carcinoma is a rare and heterogeneous malignancy with poor outcomes. Recent research has suggested that outcomes may be improved by centralization of care in specialist centres. We review our evolving 21-year experience in managing adrenocortical carcinoma with a view towards outcomes and lessons learnt. METHODS: A retrospective study of patients treated in our specialist endocrine surgical unit over 21 years was undertaken. RESULTS: Thirty-five patients were treated from diagnosis, 29 forming a primary study cohort. Additionally, seven patients were referred to us for quaternary care, forming a secondary study cohort. The European Network for the Study of Adrenal Tumours (ENSAT) stage and immunohistochemical marker Ki-67 index were strong prognostic indicators for survival. CONCLUSIONS: Early stage, complete resection and Ki-67 <10% are the best prognosticators for survival. Aggressive surgical resection at index operation and of recurrent oligometastatic disease along with multimodal adjuvant treatment has led to long-term survivors of patients with Stage 4 disease in our aggregate cohort.
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Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma Adrenocortical/cirurgia , Terapia Combinada/métodos , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Austrália/epidemiologia , Feminino , Humanos , Comunicação Interdisciplinar , Antígeno Ki-67/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Adrenal haemorrhage is a rare cause of adrenal crisis, which requires rapid diagnosis, prompt initiation of parenteral hydrocortisone and haemodynamic monitoring to avoid hypotensive crises. We herein describe a case of bilateral adrenal haemorrhage after hemicolectomy in a 93-year-old female with high-grade colonic adenocarcinoma. This patient's post-operative recovery was complicated by an acute hypotensive episode, hypoglycaemia and syncope, and subsequent computed tomography (CT) scan of the abdomen revealed bilateral adrenal haemorrhage. Given her labile blood pressure, intravenous hydrocortisone was commenced with rapid improvement of blood pressure, which had incompletely responded with fluids. A provisional diagnosis of hypocortisolism was made. Initial heparin-induced thrombocytopenic screen (HITTS) was positive, but platelet count and coagulation profile were both normal. The patient suffered a concurrent transient ischaemic attack with no neurological deficits. She was discharged on a reducing dose of oral steroids with normal serum cortisol levels at the time of discharge. She and her family were educated about lifelong steroids and the use of parenteral steroids should a hypoadrenal crisis eventuate. LEARNING POINTS: Adrenal haemorrhage is a rare cause of hypoadrenalism, and thus requires prompt diagnosis and management to prevent death from primary adrenocortical insufficiency.Mechanisms of adrenal haemorrhage include reduced adrenal vascular bed capillary resistance, adrenal vein thrombosis, catecholamine-related increased adrenal blood flow and adrenal vein spasm.Standard diagnostic assessment is a non-contrast CT abdomen.Intravenous hydrocortisone and intravenous substitution of fluids are the initial management.A formal diagnosis of primary adrenal insufficiency should never delay treatment, but should be made afterwards.
RESUMO
Adrenocortical carcinoma (ACC) has a poor prognosis with significant unmet clinical need due to late diagnosis, high rates of recurrence/metastasis and poor response to conventional treatment. Replacing tumor suppressor microRNAs (miRNAs) offer a novel therapy, however systemic delivery remains challenging. A number of miRNAs have been described to be under-expressed in ACC however it is not known if they form a part of ACC pathogenesis. Here we report that microRNA-7-5p (miR-7) reduces cell proliferation in vitro and induces G1 cell cycle arrest. Systemic miR-7 administration in a targeted, clinically safe delivery vesicle (EGFREDVTM nanocells) reduces ACC xenograft growth originating from both ACC cell lines and primary ACC cells. Mechanistically, miR-7 targets Raf-1 proto-oncogene serine/threonine kinase (RAF1) and mechanistic target of rapamycin (MTOR). Additionally, miR-7 therapy in vivo leads to inhibition of cyclin dependent kinase 1 (CDK1). In patient ACC samples, CDK1 is overexpressed and miR-7 expression inversely related. In summary, miR-7 inhibits multiple oncogenic pathways and reduces ACC growth when systemically delivered using EDVTM nanoparticles. This data is the first study in ACC investigating the possibility of miRNAs replacement as a novel therapy.
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Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/terapia , MicroRNAs/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Terapia Genética/métodos , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , MicroRNAs/administração & dosagem , Prognóstico , Proto-Oncogene Mas , RNA não Traduzido/genética , Distribuição Aleatória , Transfecção/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The aim of this study was to identify novel protein signatures that would predict clinical outcomes in a large cohort of patients with ACC based on data from previous gene expression microarray studies. MATERIALS AND METHODS: A tissue microarray was generated from the paraffin tissue blocks of 61 patients with clinical outcomes data. Selected protein biomarkers based on previous gene expression microarray profiling studies were selected, and immunohistochemistry staining was performed. Staining patterns were correlated with clinical outcomes, and a multivariate analysis was undertaken to identify potential biomarkers of prognosis. RESULTS: Median overall survival was 45 months, with a 5-year overall survival rate of 44%. Median disease-free survival was 58 months, with a 5-year disease-free survival rate of 44%. The proliferation marker Ki-67 and DNA topoisomerase TOP2A were associated with significantly poorer overall and disease-free survival. The results also showed strong correlation between the transcriptional repressor EZH2 and TOP2A expression, suggesting a novel role for EZH2 as an additional marker of prognosis. In contrast, increased expression of the BARD1 protein, with its ubiquitin ligase function, was associated with significantly improved overall and disease-free survival, which has yet to be documented for ACC. CONCLUSION: We present novel biomarkers that assist in determining prognosis for patients with ACC. Ki-67, TOP2A, and EZH2 were all significantly associated with poorer outcomes, whereas BARD1 was associated with improved overall survival. It is hoped that these biomarkers may help tailor additional therapy and be potential targets for directed therapy.
Assuntos
Carcinoma Adrenocortical/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Antígenos de Neoplasias/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose , Complexo Repressor Polycomb 2/genética , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Taxa de Sobrevida , Análise Serial de Tecidos , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
INTRODUCTION: Primary hyperaldosteronism (PA) is a common cause of secondary hypertension. Two recurrent mutations (G151R and L168R) in the potassium channel gene KCNJ5 have been identified that affect the Kir3.4 potassium channel found in the cells of the zona glomerulosa of the adrenal gland. The aim of this study was to determine the prevalence of KCNJ5 mutations in an Australian cohort of patients and to correlate these findings with clinical outcome data, in order to describe the clinical impact on patients who harbour this mutation. METHODS: Direct Sanger sequencing for KCNJ5 on DNA from adrenal tumour tissue of 83 patients with PA in a cohort study was undertaken and mutation status correlated with clinical outcome data. RESULTS: Seventy-one of 83 patients (86%) had adrenocortical adenomas and 12 patients (14%) had bilateral adrenal hyperplasia. A total of 34 (41%) patients were found to have heterozygous somatic mutations in KCNJ5, G151R and L168R. No germ line mutations were identified. Patients with mutations were predominately female (68% versus 49%) and significantly younger at presentation (48 versus 55 years). When correlated with clinical data, our results demonstrated that patients with KCNJ5 mutations were more likely to be cured following surgery without the requirement for ongoing medications. CONCLUSIONS: Our findings in a large Australian cohort show that patients with mutations in KCNJ5 present earlier with the signs and symptoms of PA benefit from surgical intervention. Moreover, our results highlight the importance of a thorough workup and management plan for younger patients who present with hypertension.
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Neoplasias do Córtex Suprarrenal/complicações , Hiperplasia Suprarrenal Congênita/complicações , Adrenalectomia , Adenoma Adrenocortical/complicações , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hiperaldosteronismo/genética , Mutação , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/cirurgia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/cirurgia , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos de Coortes , Feminino , Marcadores Genéticos , Heterozigoto , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy that carries a poor prognosis. There has yet to be a large Australian series that documents the characteristics of ACC and there are a paucity of data on management and the long-term outcomes. We sought to provide a unique insight into the management of ACC in Australia as well as to identify factors associated with prognosis and survival. METHODS: A multivariate analysis of a cohort of patients identified with ACC between 1998 and 2013 was undertaken. Recurrence-free survival (RFS) and overall survival (OS) were assessed as the main outcome measures and correlated with multiple clinical variables in order to identify prognostic markers. RESULTS: Of the 104 patients identified, a total of 98 patients with complete clinical and outcome data were included in the study. Median OS was 56 months, with the 5-year survival being 48 % (95 % confidence interval 36-59). On multivariate analysis, age ≥50 years, metastases at presentation, and evidence of extra-adrenal invasion were found to be statistically associated with reduced OS. RFS was analyzed in patients without metastases. On multivariate analysis, extra-adrenal invasion and no preoperative endocrine investigations were found to be statistically significant poor prognostic factors, with a non-significant trend for higher individual surgeon volume to be associated with improved resection margins and RFS. CONCLUSIONS: We present clinical outcomes and prognostic factors for patients with ACC in a landmark Australian series. We suggest that management in a specialized tertiary endocrine and/or surgical oncology unit is more likely to lead to improved outcomes.
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Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/terapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Neoplasias do Córtex Suprarrenal/patologia , Austrália , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause significant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopathologic factors, and serum thyroglobulin is the only commercially available marker for persistent or recurrent disease. The objective of this study was to determine microRNA (miRNA) expression in PTC and determine whether 1 or more miRNAs could be measured in plasma as a biomarker for recurrence. METHODS: Patients with recurrent PTC (Rc-PTC) and those without recurrence (NR-PTC) were retrospectively recruited for a comparison of their tumor miRNA profiles. Patients with either newly diagnosed PTC or multinodular goiter who were undergoing total thyroidectomy were prospectively recruited for an analysis of preoperative and postoperative circulating miRNA levels. Healthy volunteers were recruited as the control group. RESULTS: MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P = .014 and P = .038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the levels in plasma from healthy volunteers (P < .01 for both). Reductions of 2.7-fold and 5.1-fold were observed in the plasma levels of miR-222 and miR-146b, respectively, after total thyroidectomy (P = .03 for both). CONCLUSIONS: This study demonstrated that tumor levels of miR-222 and miR-146b are associated with PTC recurrence and that miR-222 and miR-146b levels in the circulation correspond to the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve patient stratification according to the risk of recurrence and as circulating biomarkers for PTC surveillance warrants further study.
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Biomarcadores Tumorais/genética , Carcinoma/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Carcinoma/patologia , Carcinoma Papilar , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Estudos Retrospectivos , Tireoglobulina/sangue , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodosRESUMO
Adrenal cortical carcinoma (ACC) is a rare cancer that poses a number of management challenges due to the limited number of effective systemic treatments. Complete surgical resection offers the best chance of long-term survival. However, despite complete resection, ACC is associated with high recurrence rates. This review will discuss the management of recurrent ACC in adults following complete surgical resection. Management should take place in a specialist center and treatment decisions must consider the individual tumor biology of each case of recurrence. Given the fact that ACC commonly recurs, management to prevent recurrence should be considered from initial diagnosis with the use of adjuvant mitotane. Close follow up with clinical examination and imaging is important for early detection of recurrent disease. Locoregional recurrence may be isolated, and repeat surgical resection should be considered along with mitotane. The use of radiotherapy in ACC remains controversial. Systemic recurrence most often involves liver, pulmonary, and bone metastasis and is usually managed with mitotane, with or without combination chemotherapy. There is a limited role for surgical resection in systemic recurrence in selected patients. In all patients with recurrent disease, control of excessive hormone production is an important part of management. Despite intensive management of recurrent ACC, treatment failure is common and the use of clinical trials and novel treatment is an important part of management.