Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas.

BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 µg/mL; adalimumab 9.1 vs 6.2 µg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 µg/mL; P < .05; adalimumab 9.8 vs 6.2 µg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.

Liver disease severity predicts carcinogenesis of dysplastic liver nodules in cirrhosis.

While dysplastic liver nodules in cirrhosis are pre-malignant, little is known about the predictors of hepatocarcinogenesis of these lesions. This was a retrospective observational study of subjects with cirrhosis who had at least one hypervascular, non-malignant intrahepatic nodule on imaging while undergoing outpatient management by a tertiary hepatology referral centre between Jan 2009 and Jan 2019. Clinical and biochemical parameters were collected. The primary endpoint was transformation to hepatocellular carcinoma (HCC) as determined by Liver Imaging Reporting and Data System. During the study period, 163 non-malignant hypervascular nodules were identified in 77 patients; 147 had at least 6 months of follow up imaging and 16 received upfront radiofrequency ablation upon detection. During a median follow up of 38.5 months (IQR 16.5-74.5), 25 (17%) of the 147 hypervascular nodules being monitored transformed to HCC. On multivariate analysis, Child-Pugh grade was found to be the only independent predictor of nodule transformation into HCC (p = 0.02). Those with Child-Pugh B and C liver disease had a 10.1 (95% CI 1.22-83.8; p = 0.03) and 32.6-fold (95% CI 2.3-467; p = 0.01) increased risk respectively for HCC transformation compared to Child-Pugh A subjects. This large, single centre study demonstrates that around 20% of dysplastic nodules in cirrhotic patients undergo hepatocarcinogenesis during follow up, and that Child Pugh grade is the only independent predictor of transformation to HCC. Additional prospective studies are warranted to better understand the risk profile of these nodules, and how best they should be managed.

Irreversible electroporation versus radiofrequency ablation for hepatocellular carcinoma: a single centre propensity-matched comparison.

BACKGROUND AND AIMS: Irreversible electroporation (IRE) is a relatively new non-thermal ablative method for unresectable hepatocellular carcinoma (HCC). We aimed to compare the longer-term efficacy of IRE to the standard thermal technique of radiofrequency ablation (RFA) in HCC. METHODS: All patients who underwent IRE or RFA for HCC in our centre were identified and demographic and clinical data were analysed up until 1st March, 2020. Local recurrence-free survival (LRFS) was compared between groups after propensity score matching for age, gender, Child-Pugh grade, BCLC stage, lesion size and alpha-fetoprotein (AFP) level. RESULTS: A total of 190 HCC ablations (31 IRE and 159 RFA) were identified. After propensity score matching, we compared 25 IRE procedures (76% males, median age 62.4 years, median tumour size 20 mm) to 96 RFA procedures (84.4% males, median age 64.3 years, median tumour size 18.5 mm). LRFS did not differ between groups, with a 1-, 2- and 5-year LRFS of 80.4% (95% CI 55.8-92.2), 69.1% (95% CI 43.3-84.9) and 44.9% (95% CI 18.9-68.1%), respectively for IRE and 84.8% (95% CI 75.2-90.9), 71.3% (95% CI 58.3-81.0) and 52.1% (95% CI 35.4-66.4%), respectively for RFA (p = .63). There were no major procedure-related complications or deaths in either group. CONCLUSIONS: Whilst IRE remains a relatively novel therapy for HCC cases where standard thermal ablation is contraindicated, the LRFS in our centre is comparable to that of RFA. IRE should therefore be considered as a treatment option in such cases when available before stage-migration to non-curative therapies such as transarterial chemoembolization (TACE).

Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation.

BACKGROUND: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD: Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS: Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION: Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.

Perianal sepsis in neutropaenic patients with haematological malignancies: the role of magnetic resonance imaging and surgery.

BACKGROUND: Perianal sepsis occurs in up to 10% of neutropaenic patients with haematological malignancy and is associated with significant morbidity and mortality. The management of this condition is challenging in neutropaenic patients due to its atypical pathophysiology. The aim of this study is to assess the role of magnetic resonance imaging (MRI) and surgery in neutropaenic patients with perianal sepsis. METHODS: A retrospective chart review was performed on all neutropenic patients with a haematological malignancy who had a diagnosis of perianal sepsis during the inpatient admission between 2008 and 2017. Patient characteristics, symptoms, haematological data, MRI result, surgical intervention, intraoperative findings and outcomes including recurrence and mortality were collected. RESULTS: Nineteen neutropaenic patients with haematological malignancy were treated for perianal sepsis, eight (42%) patients were managed conservatively and 11 (58%) were managed surgically. Nine patients underwent MRI, which identified a collection in 88% of cases despite severe neutropaenia. In patients with a collection identified on MRI prior to surgery, 80% had a drainable collection confirmed intraoperatively. Post-operative complications included two cases of sepsis from a presumed perianal source and one death. A total of 82% of patients experienced symptom resolution after surgery compared to 88% of patients managed conservatively. CONCLUSION: This study has demonstrated that MRI is a useful diagnostic tool in evaluating perianal sepsis in patients with haematological malignancy, even during periods of severe neutropenia. We found that both conservative and surgical management strategies lead to resolution of symptoms.

Congenital Insensitivity to Pain with Anhidrosis: A Case with Self-Inflicted Oral Ulcerations.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV, is a rare autosomal recessive condition. CIPA is caused by mutations in the NTRK1 gene, leading to the inability to feel pain and decreased or absent sweating (anhidrosis). The signs and symptoms of CIPA may not be easily diagnosed at birth, but repeated severe injuries or unintentional self-injurious behavior during infancy may prompt further investigation leading to a CIPA diagnosis. We present the case of an 18-month old child who was diagnosed with CIPA, after repeated visits to a hopsital's emergency department for serious tongue and finger biting, which prompted further investigation.

Ultrasound-based liver tracking utilizing a hybrid template/optical flow approach.

PURPOSE: With the ongoing shift toward reduced invasiveness in many surgical procedures, methods for tracking moving targets within the body become vital. Non-invasive treatment methods such as stereotactic radiation therapy and high intensity focused ultrasound, in particular, rely on the accurate localization of targets throughout treatment to ensure optimal treatment provision. This work aims at developing a robust, accurate and fast method for target tracking based on ultrasound images. METHODS: A method for tracking of targets in real-time ultrasound image data was developed, based on the combination of template matching, dense optical flow and image intensity information. A weighting map is generated from each of these approaches which are then normalized, weighted and combined, with the weighted mean position then calculated to predict the current position. The approach was evaluated on the Challenge for Liver Ultrasound Tracking 2015 dataset, consisting of a total of 24 training and 39 test datasets with a total of 53 and 85 annotated targets throughout the liver, respectively. RESULTS: The proposed method was implemented in MATLAB and achieved an accuracy of [Formula: see text] (95%: 1.91) mm and [Formula: see text] (95%: 1.85) mm on the training and test data, respectively. Tracking frequencies of between 8 and 36 fps (mean of 22 fps) were observed, largely dependent on the size of the region of interest. The achieved results represent an improvement in mean accuracy of approximately 0.3 mm over the reported methods in existing literature. CONCLUSIONS: This work describes an accurate and robust method for the tracking of points of interest within 2D ultrasound data, based on a combination of multi-template matching, dense optical flow and relative image intensity information.

A Rare Case of Gingival Cyst in a Child.

Gingival cysts, which are more frequently reported as gingival cysts of adults (GCA), are soft tissue cystic lesions of odontogenic origin that are infrequently seen, especially in children. These lesions usually appear as localized firm elevations on the facial gingiva in the anterior segment of the mandible. The purpose of this paper is to present a rare case of a gingival cyst discovered on the palatal aspect of the posterior maxilla in a four-year-old child. The lesion was treated with excisional biopsy.

Melanotic neuroectodermal tumour of infancy: a case report.

Melanotic neuroectodermal tumour of infancy is a rare benign pigmented tumour that typically appears in the first year of life. We report an atypical presentation of this tumour, associated with an erupted primary tooth in a 7-month-old boy. We discuss the clinical, radiographic and histologic features of this rare tumour, as well as its surgical management and the follow-up treatment plan.

Bilateral oral focal mucinosis on the palate of a 2-year-old child: a case report.

BACKGROUND: Oral focal mucinosis (OFM) is an uncommon benign oral lesion. The aetiology of the lesion is unknown. Histologically, it appears as a well-circumscribed myxomatous mass surrounded by denser, collagenous connective tissue. Most cases of OFM were found in adults. It is very unusual for young children to have OFM. CASE REPORT: A case of OFM in a 2-year-old child is reported. The patient was presented with non-painful bilateral enlargements on the palate. The overlying mucosa was smooth and not ulcerated and appeared in the same colour as the adjacent tissue. The histology of the lesion showed myxomatous mass indicative of OFM. Treatment consisted of surgically removing the lesions under general anaesthetic. CONCLUSION: Paediatric dentists should consider OFM in their differential diagnosis of soft tissue oral lesions in children.

Radiofrequency ablation versus resection for the treatment of early stage hepatocellular carcinoma: a multicenter Australian study.

OBJECTIVES: It remains unclear whether radiofrequency ablation (RFA) provides comparable outcomes to surgical resection (SR). We, therefore, compared survival outcomes of RFA to SR in patients with early stage and very early stage hepatocellular carcinoma (HCC). METHODS: A multicenter retrospective analysis was performed in patients from five academic hospitals with Barcelona Cancer of the Liver Clinic (BCLC) stages 0-A HCC having RFA or SR as primary therapy. RESULTS: From 2000-2010, 146 patients who received treatment with RFA (n = 96) or SR (n = 52) were identified. In BCLC A patients with ≤5 cm HCC, there was a trend of lower overall survival after RFA compared with SR (3- and 5-year survival: 62% and 37% vs. 66% and 62% respectively; p = 0.11). By multivariate analysis, RFA was an independent predictor of poor survival (hazard ratio = 2.26; 95% confidence interval: 1.02-5.03; p = 0.04). In ≤3 cm HCC (n = 109), the 3- and 5-year survivals in RFA and SR groups were 66% and 39%, and 69% and 59%, respectively, with no difference in the median survival (p = 0.41). Local recurrence was significantly higher after RFA compared to SR in HCC ≤5 cm (p = 0.006) with a trend of lower recurrence-free survival (p = 0.06) after RFA in HCC ≤3 cm. There were fewer major complications after RFA (2% vs. 8%). CONCLUSION: While SR is superior to RFA for the management of early stage BCLC A disease with ≤5 cm HCC, both appear effective as first-line treatment options for Western patients with small ≤3 cm tumors. Although safer than SR, RFA is associated with higher rates of tumor recurrence and local disease progression. Further prospective randomized controlled trials are warranted to compare these two modalities.

Investigation of the safety of irreversible electroporation in humans.

PURPOSE: A single-center prospective nonrandomized cohort study was performed to investigate the safety of irreversible electroporation (IRE) for tumor ablation in humans. MATERIALS AND METHODS: Thirty-eight volunteers with advanced malignancy of the liver, kidney, or lung (69 separate tumors) unresponsive to alternative treatment were subjected to IRE under general anesthesia. Clinical examination, biochemistry, and computed tomography (CT) scans of the treated organ were performed before, immediately after, and at 1 month and 3 months after the procedure. RESULTS: No mortalities occurred at 30 days. Transient ventricular arrhythmia occurred in four patients, and electrocardiographically (ECG) synchronized delivery was used subsequently in the remaining 30 patients, with two further arrhythmias (supraventricular tachycardia and atrial fibrillation). One patient developed obstruction of the upper ureter after IRE. One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension. There was no other evidence of adjacent organ damage related to the electroporation. Other adverse events were not directly related to IRE, but two patients developed temporary neurapraxia as a result of arm extension during a prolonged period of anesthesia. Although not a primary aim of this preliminary study, complete target tumor ablation verified by CT was achieved in 46 of the 69 tumors treated with IRE (66%). Most treatment failures occurred in renal and lung tumors. Biopsy in three patients showed coagulative necrosis in the regions treated by IRE. CONCLUSIONS: IRE appears to be safe for human clinical use provided ECG-synchronized delivery is used. Comparative evaluation with alternative ablative technologies is warranted.

Risk factors for colonic perforation after screening computed tomographic colonography: a multicentre analysis and review of the literature.

BACKGROUND: Computed tomographic (CT) colonography (or 'virtual' colonoscopy) has become an increasingly popular tool for colorectal cancer screening. Colonic perforation, an uncommon complication, is a risk that has not been widely reported. METHODS: A systematic review of the literature was undertaken to identify all reported risk factors for colonic perforation following CT colonography. In addition, a retrospective multicentre study was undertaken, evaluating all CT colonographies in 10 major metropolitan tertiary referral centres. All colonic perforations were assessed for risk factors. RESULTS: A range of 'patient'-related and 'procedure'-related risk factors were identified in the literature. Among 3458 CT colonographies, there were two cases of colonic perforation contributing to an incidence of perforation of 0.06%. There was no statistical correlation between the incidence of perforation and institutional experience (P = 0.66). Risk factors common to both cases and the literature included age, recent colonoscopy and manual colonic insufflation. Diverticular disease and recent colonic biopsy were also notable factors. CONCLUSION: There is a small but real risk of perforation following CT colonography. Patient selection and preventative procedural measures may reduce this risk. The importance of the consent process is emphasized.

Risk factors for early childhood caries in Canadian preschool children seeking care.

PURPOSE: The purpose of this study was to determine family characteristics, beliefs, and habits that contribute to early and severe caries in young children in Canada. METHODS: A survey was administered to: (1) parents of 139 children diagnosed with early childhood caries (ECC) in 5 pediatric dentistry practices in Canada over a 33-month period (group 1); and (2) parents of all normal referrals (carious and noncarious children) in one of the practices over a 3 month period (group 2). Group 2 prevented studying an exclusive or polarized population, and allowed direct comparison between children with decoy and without decoy. The survey responses were compared with caries rates in the children, determined by dental examination, to detect important correlations of family and child factors with the disease level. Chi-square and logistic regression analyses described the strength of the relationships. RESULTS: Parent responses provided information on: (1) demographics; (2) economic status; (3) birth order; (4) parental education; (5) payment methods; (6) feeding and weaning history; (7) fluoride history; (8) food habits; (9) hygiene; (10) behavior; and (11) medication use. Caries presence and severe caries was linked to: (1) leaving the bottle with a child while sleeping; (2) having problems brushing a child's teeth; (3) prolonged holding of liquids in the mouth; and (4) being Caucasian. The authors did find that bottle use in general and having a difficult child were protective influences against decay. CONCLUSIONS: The factors providing the most caries risk are: (1) being left with a bottle while sleeping; (2) parents having problems brushing the child's teeth; (3) holding liquids in the mouth for prolonged times; and (4) ethnicity.