Novel microbiome signatures for non-invasive diagnosis of adenoma recurrence after colonoscopic polypectomy.

BACKGROUND: We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer. AIM: To evaluate whether these markers are useful in detecting adenoma recurrence after polypectomy. METHODS: Subjects were enrolled in a polyp surveillance study from 2009 to 2019. Stool samples were collected before bowel preparation of index colonoscopy (baseline) and surveillance colonoscopy (follow-up). Fusobacterium nucleatum (Fn), Lachnoclostridium marker (m3), Clostridium hathewayi (Ch) and Bacteroides clarus were quantified in baseline and follow-up samples by quantitative polymerase chain reaction (qPCR) to correlate with adenoma recurrence. Recurrence was defined as new adenomas detected >6 months after polypectomy. Faecal immunochemical test (FIT) was performed for comparison. RESULTS: A total of 161 baseline and 104 follow-up samples were analysed. Among patients with adenoma recurrence, Fn and m3 increased (both P < 0.05) while Ch were unchanged in follow-up versus baseline samples. Among patients without recurrence, Fn and m3 were unchanged while Ch decreased (P < 0.05) in follow-up versus baseline samples. Logistic regression that included changes of m3, Fn and Ch at follow-up compared with baseline achieved an area under receiver operating characteristic curve (AUROC) of 0.95 (95%CI: 0.84-0.99) with 90.0% sensitivity and 87.0% specificity for detecting recurrent adenoma. Combination of m3, Fn and Ch at follow-up sample achieved AUROC of 0.74 (95%CI: 0.65-0.82) with 81.3% sensitivity and 55.4% specificity for detecting recurrent adenoma. FIT showed limited sensitivity (8.3%) in detecting recurrent adenomas. CONCLUSION: Our combinations of faecal microbiome gene markers can be potentially useful non-invasive tools for detecting adenoma recurrence.

Dual thyroid ectopia with submental thyroid excision using Sistrunk procedure: A case report.

INTRODUCTION AND IMPORTANCE: Having two or more sites of simultaneous ectopic thyroid tissue is a rare phenomenon. Thyroid ectopia should be considered in congenital hypothyroidism where no eutopic thyroid gland is found. CASE PRESENTATION: This case describes an incidental finding of dual ectopic thyroid tissue on computer tomography scan in an adult with known congenital hypothyroidism that was previously attributed to thyroid agenesis. The decision was made to proceed with a Sistrunk procedure to excise the ectopic submental thyroid as it became more noticeable after weight loss following bariatric surgery, and to monitor the remaining lingual thyroid with a combination of clinical symptomology, imaging and thyroid function studies given its challenging location. CLINICAL DISCUSSION: The literature on pathophysiology, imaging modalities, and common considerations for surgical extirpation is reviewed. CONCLUSION: The utility of thyroid scintigraphy may be limited in patients with known thyroid ectopia; other investigative modalities are helpful. The Sistrunk procedure was used to excise an ectopic thyroid, based on its embryological migration from the foramen caecum to the usual pretracheal position along the thyroglossal tract, and is a suitable technique for excision of submental thyroid tissue causing an unsightly mass and where thorough histopathological examination is required to exclude malignancy.

Improving Venous Thromboembolism Prophylaxis Administration in an Acute Surgical Unit.

OBJECTIVES: Venous thromboembolism (VTE) prophylaxis regimes frequently have a wide variation in application. Nepean acute surgical unit was established in 2006 as a novel model for emergency surgical care. As part of the model's rollout, there were several areas of clinical management targeted for improvement, one being VTE prophylaxis compliance. It was decided all patients older than 18 years treated for a variety of acute surgical conditions within the acute surgical unit should be administered routine VTE prophylaxis with heparin and compression stockings. A novel multifaceted intervention was implemented at the time to achieve this goal. The primary aim of this study was to determine VTE prophylaxis administration rates before and after this intervention. METHODS: A before-after study conducted as a retrospective review of medical records of all patients 18 years or older, having an appendicectomy in 3 periods: Before acute surgical unit (ASU) (November 2004 to October 2006), Early ASU (November 2006 to October 2008), and Established ASU (January 2012 to December 2013). Outcomes were mechanical and pharmacological VTE prophylaxis administration rates for each group. RESULTS: There were 1149 patients included in the study: Before ASU, 167; Early ASU, 375; and Established ASU, 607. There was a significant stepwise increase in parmacological VTE prophylaxis administration: Before ASU, 54.5%; Early ASU, 74.7%; and Established ASU, 96.9% (Before versus Early: odds ratio [OR], 2.46; 95% confidence interval [CI], 1.68-3.61; P < 0.001; Early versus Established: OR, 10.500; 95% CI, 6.29-17.53; P < 0.001). Mechanical VTE prophylaxis was significantly increased in the established group (Before versus Established: OR, 47.18; 95% CI, 25.61-86.91; P < 0.001). CONCLUSIONS: There was a significant increase in VTE prophylaxis administration after the implementation of our multifaceted intervention. Allocating a responsible provider dedicated to VTE prophylaxis prescription and compliance checking was a key component to this intervention.

microRNA-431 as a Chemosensitizer and Potentiator of Drug Activity in Adrenocortical Carcinoma.

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.

Treatment and management of adrenal cancer in a specialized Australian endocrine surgical unit: approaches, outcomes and lessons learnt.

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.

Delayed recurrent pleuropericardial effusions following atrial septal defect closure with Amplatzer septal occluder device: a case of postpericardiotomy syndrome?

The authors present the case of a 41-year-old woman, who presented with moderate pericardial effusion and bilateral pleural effusion 11 months following a secundum atrial septal defect closure with an Amplatzer septal occluder (ASO) device. The acute presentation responded well to diuretics and a short course of corticosteroid therapy. The patient, however, continued to experience pleuritic chest pain and a recurrence of pericardial effusion a month later. The patient showed significant symptomatic improvement with a 2-month course of down-titrating prednisolone. Six months later, the echocardiogram showed complete remission of pleural and pericardial effusion. The possibility of cardiac erosion following ASO implantation has been excluded. The aetiology of the reoccurrence of steroid-responsive pleuropericarditis remains unknown.

The Established Acute Surgical Unit: A reduction in nighttime appendicectomy without increased morbidity.

INTRODUCTION: Nighttime surgery for non-life threatening disease has been associated with poorer outcomes, but delaying surgery for acute appendicitis may also be detrimental. The aim was to assess the effect of the Acute Surgical Unit [ASU] model on nighttime surgery rates and outcomes for patients undergoing appendicectomy. METHOD: A retrospective review of medical records of patients having an appendicectomy. Primary outcomes were nighttime surgery rate, time from presentation to surgery, perforation rate, complication rate and length of stay. RESULTS: There was a large increase in workload: Pre ASU 278, Early ASU 553 and Est. ASU 923. There was a significant decrease in nighttime surgery rates: Pre ASU 46.9%, Early ASU 30.2% and Established ASU 28.3% (Pre vs. Early p < 0.001; Pre vs. Est. p < 0.001; Early vs. Est p = 0.004). When comparing the Pre ASU and Established ASU groups there was an increase in mean time from presentation to surgery (Pre 14.43 Hrs, Est. 18.65 Hrs; p = 0.001), an increase in perforation rate that was not significant (Pre 9.8%, Est. 14.2%; p = 0.05) and similar complication rates (Pre 8.66%, Est. 7.04%; p = 0.37). There was a significant decrease in length of stay between the Early and Established ASU groups (Pre 3.1 D, Est. 2.8D, p = 0.01). At our institution there was no statistically significant increase in complications for patients undergoing nighttime appendicectomy (Night 10.0%, Day 8.2%; p = 0.16). CONCLUSION: There was a significant decrease in nighttime surgery, without any difference in morbidity or length of stay for patients treated within the Established ASU (compared to Pre ASU group). LEVEL OF EVIDENCE: IIb.

Translational applications of microRNAs in cancer, and therapeutic implications.

The search for targeted novel therapies for cancer is ongoing. MicroRNAs (miRNAs) display a number of characteristics making them an attractive and realisable option. In this review, we explore these applications, ranging from diagnostics, prognostics, disease surveillance, to being a primary therapy or a tool to sensitise patients to treatment modalities such as chemotherapy and radiotherapy. We take a particular perspective towards miRNAs and their impact on rare cancers. Advancement in the delivery of miRNAs, from viral vectors and liposomal delivery to nanoparticle based, has led to a number of pre-clinical and clinical applications for microRNA cancer therapeutics. This is promising, especially in the setting of rare cancers.

Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child.

AIMS: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis. METHODS: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome. RESULTS: The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease. CONCLUSIONS: We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease.

Review of knee arthroscopy performed under local anesthesia.

Local anesthesia for knee arthroscopy is a well documented procedure with diagnostic and therapeutic role. Numerous therapeutic procedures including partial menisectomy, meniscus repair, abrasion chondroplasy, synovectomy, loose body removal can be performed safely and comfortably. Appropriate case selection, anesthetic strategy and technical expertise are the key to smooth and successful surgery.