Perianal Fistulizing Crohn's Disease-Associated Anorectal and Fistula Cancers: Systematic Review and Expert Consensus.

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Micro-enema immediately prior to prostate MRI: effects on rectal gas, image quality and PI-QUAL score.

PURPOSE: Our aim was to determine whether the administration of a micro-enema immediately prior to prostate MRI is associated with a reduction in rectal gas, gas related artifacts and an improvement in image quality and PI-QUAL score. METHOD: This retrospective analysis enrolled 171 patients who underwent multiparametric 3T prostate MRI at our institution between January 2021 and September 2022. 86 patients received a micro-enema, and a further 85 patients did not. Two fellowship trained abdominal radiologists were blinded and independently reviewed each prostate MRI, recording scores on a dedicated scoring sheet. The quality of T2 weighted (T2W), diffusion weighted (DWI), and dynamic contrast enhancement (DCE) images were assessed according to standardised scales supported in the literature. In addition, gas related artifacts and rectal gas level were examined. An independent-samples Mann-Whitney U and t-test were performed, comparing both the median and mean score between micro-enema and no micro-enema groups for each reader. Spearman's correlation was used to determine the strength of relationship between variables. A quadratic weighted Cohen's Kappa and percent agreement were used to assess inter-observer agreement. RESULTS: Image quality was improved in those who received the micro-enema compared to those who did not according to the visual grading scale on the DWI sequence for both readers (reader 1: median 4 vs. 4, p < 0.001, mean 4.27 vs. 3.92, p < 0.001; reader 2: median 5 vs. 4, p < 0.001, mean 4.74 vs. 4.14, p < 0.001). PI-QUAL score was significantly improved in the micro-enema group for reader 2 only (reader 1: median 4 vs. 4, p = 0.25, mean 3.99 vs. 4.08, p = 0.21; reader 2: median 5 vs. 5, p = 0.01, mean 4.95 vs. 4.78, p = 0.01). Visual grading score for both the T2W and DCE images was not significantly different. Rectal gas level was lower in patients who received the micro-enema for both readers (reader 1: median 2 vs. 4, p < 0.001, mean 2.12 vs. 3.60, p < 0.001; reader 2: median 1 vs. 2, p < 0.001, mean 1.37 vs. 2.48, p < 0.001), correlating with a lower score for gas-related artifacts (reader 1: median 1 vs. 2, p < 0.001, mean 1.50 vs. 1.92, p < 0.001; reader 2: median 1 vs. 1, p < 0.001, mean 1.16 vs. 1.71, p < 0.001) in this group. Correlation between rectal gas level and gas-related artifacts on DWI regardless of whether a micro-enema was given was strong (rs = 0.71, p < 0.001). Correlation was moderate to strong between rectal gas level and image quality on DWI (rs = -0.63, p < 0.001). There was only 1 (1.2%) borderline diagnostic or non-diagnostic DWI sequence in those who received the micro-enema, compared to 9 (10.6%) in those who did not (p = 0.009). Interobserver agreement was moderate for image quality on DWI, gas related artifacts and rectal gas level (weighted kappa values of 0.52, 0.49 and 0.53 respectively). CONCLUSIONS: The administration of a micro-enema immediately prior to prostate MRI is associated with a significant improvement in image quality on the DWI sequence compared to no bowel preparation. This is mediated through a reduction in rectal gas and gas related artifacts. Improvements in PI-QUAL score was mixed between readers.

Improving Hepatocellular Carcinoma Surveillance Outcomes in Patients with Cirrhosis after Hepatitis C Cure: A Modelling Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. METHODS: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. CONCLUSIONS: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy.

Auditory neuropathy in mice and humans with Friedreich ataxia.

OBJECTIVE: Recent studies have found that human Friedreich ataxia patients have dysfunction of transmission in the auditory neural pathways. Here, we characterize hearing deficits in a mouse model of Friedreich ataxia and compare these to a clinical population. METHODS: Sixteen mice with a C57BL/6 background were evaluated. Eight were YG8Pook/J animals (Friedreich ataxia phenotype) and eight wild-type mice served as controls. Auditory function was assessed between ages 6 and 12 months using otoacoustic emissions and auditory steady-state responses. At study end, motor deficit was assessed using Rotorod testing and inner ear tissue was examined. Thirty-seven individuals with Friedreich ataxia underwent auditory steady-state evoked potential assessment and response amplitudes were compared with functional hearing ability (speech perception-in-noise) and disease status was measured by the Friedreich Ataxia Rating Scale. RESULTS: The YG8Pook/J mice showed anatomic and functional abnormality. While otoacoustic emission responses from the cochlear hair cells were mildly affected, auditory steady-state responses showed exaggerated amplitude reductions as the animals aged with Friedreich ataxia mice showing a 50-60% decrease compared to controls who showed only a 20-25% reduction (F(2,94) = 17.90, p < 0.00). Furthermore, the YG8Pook/J mice had fewer surviving spiral ganglion neurons, indicating greater degeneration of the auditory nerve. Neuronal density was 20-25% lower depending on cochlear region (F(1, 30) = 45.02, p < 0.001). In human participants, auditory steady-state response amplitudes were correlated with both Consonant-Nucleus-Consonant word scores and Friedreich Ataxia Rating Scale score. INTERPRETATION: This study found degenerative changes in auditory structure and function in YG8Pook/J mice, indicating that auditory measures in these animals may provide a model for testing Friedreich ataxia treatments. In addition, auditory steady-state response findings in a clinical population suggested that these scalp-recorded potentials may serve as an objective biomarker for disease progress in affected individuals.

Elimination of oral contrast leads to faster scans in the workup of abdominal pain in the emergency setting without compromising diagnostic accuracy.

INTRODUCTION: The aim of this study was to study how the effect of eliminating oral contrast for computed tomography of the abdomen and pelvis (CTAP) in the workup of abdominal pain in the emergency department (ED) would affect the time from patient review to scan and time from review to discharge. METHODS: In this retrospective study, we analysed all ED presentations with abdominal pain to our university affiliated tertiary hospital before and after a protocol that eliminated oral contrast-enhanced CTAPs were implemented in September 2018. Two equivalent periods between September and November of 2017 and 2018 were analysed. Patients were excluded if they had a history of anatomy-altering gastrointestinal surgery, history of inflammatory bowel disease, trauma, suspicion of foreign body ingestion or suspected gastrointestinal bleeding. RESULTS: A total of 176 pre-protocol and 197 post-protocol patients were included in the study. We found that the elimination of oral contrast was associated with a decrease in mean time between ED review and scan by 110 min (379 vs. 269 min). We also found that the elimination of oral contrast did not significantly alter the pattern of radiological diagnoses seen between the two study periods, suggesting the absence of oral contrast does not affect diagnostic accuracy. CONCLUSION: Thus, eliminating the use of oral contrast in the workup of abdominal pain in the ED can lead to increased throughput and more timely patient care.

A case of a bleeding benign gastrocolic fistula in 2014.

INTRODUCTION: In the era of proton pump inhibitors in the treatment of peptic ulcer disease, the incidence of a gastrocolic fistula arising from unoperated gastric ulcers is extremely low. PRESENTATION OF CASE: We present the case of a 68-year old farmer who presented with melaena and was found to have a benign gastrocolic fistula in the setting of untreated peptic ulcer disease, chronic NSAID ingestion and heavy alcohol intake. The diagnosis was made by gastroscopy. En bloc surgery was undertaken due to the size of the fistula and concomitant significant bleeding of the ulcer which would not have made it amenable to medical management. DISCUSSION: The symptoms of a gastrocolic fistula are undifferentiated and the diagnosis can easily be missed in the setting of other complications such as bleeding or perforation of a hollow viscus. Barium enamas are the most accurate for the diagnosis but gastroscopy with biopsy is usually performed to rule out malignancy. The mainstay of treatment is usually surgical, though patients can be medically managed if he/she is not a surgical candidate. CONCLUSION: Benign gastrocolic fistulas are rare and its diagnosis is easily missed.

Prevalence of jugular bulb abnormalities and resultant inner ear dehiscence: a histopathologic and radiologic study.

OBJECTIVE: Jugular bulb abnormalities (JBA), including high-riding jugular bulb (HRJB) and jugular bulb diverticulum (JBD), can erode into the inner ear. In this study, the authors investigate the prevalence and consequences of JBA and their erosion into inner ear structures using temporal bone histopathology and computed tomography (CT). STUDY DESIGN: Cross-sectional study of temporal bone histopathology and radiology. SETTING: Academic medical center. SUBJECTS AND METHODS: In total, 1579 temporal bone specimens and 100 CT of the temporal bones (200 ears) were examined for JBA and any associated dehiscence of inner ear structures. Temporal bone specimens were examined for histological consequences of inner ear erosion. Jugular bulb dimensions were measured on axial CT scans and compared across groups. Accompanying demographic and clinical information were reviewed. RESULTS: High jugular bulbs were noted in 8.2% (130/1579) of temporal bone specimens and in 8.5% (17/200) of temporal bone CT. The prevalence of JBA increases during the first 4 decades of life and stabilizes thereafter. High-riding jugular bulbs eroded inner ear structures such as the vestibular aqueduct, vertical facial nerve, or posterior semicircular canal in 2.8% (44/1579) of cases histologically and 1.5% (3/200) radiologically. In most, jugular bulb-mediated inner ear dehiscence was clinically and radiologically silent. CONCLUSION: Jugular bulb abnormalities are common. They are present in 10% to 15% individuals and are primarily acquired by the fourth decade of life. In 1% to 3% of cases, the HRJB erodes into the inner ear and most frequently involves the vestibular aqueduct.

A clinical and histopathologic study of jugular bulb abnormalities.

OBJECTIVE: To further define the spectrum of clinical presentation and explore the histologic sequelae of jugular bulb abnormalities (JBAs). DESIGN: Retrospective review. SETTING: Academic medical center. PATIENTS: Thirty patients with radiologic evidence of inner ear dehiscence by JBA. MAIN OUTCOME MEASURE: Thirty patients with radiologic inner ear dehiscence by JBA and 1579 temporal bone specimens were evaluated for consequences from JBA. RESULTS: We found that JBA-associated inner ear dehiscence could be identified on computed tomography of the temporal bone but not on magnetic resonance imaging scan. Jugular bulb abnormalities eroded the vestibular aqueduct most often (in 25 patients), followed by the facial nerve (5 patients) and the posterior semicircular canal (4 patients). Half of the patients (15) were asymptomatic. Results from vestibular evoked myogenic potential (VEMP) tests were positive in 8 of 12 patients with inner ear dehiscence. Histologically, only 2 of 41 temporal bones with dehiscence of the vestibular aqueduct demonstrated endolymphatic hydrops. CONCLUSIONS: Jugular bulb abnormalities can erode into the vestibular aqueduct, facial nerve, and the posterior semicircular canal. While symptoms may include pulsatile tinnitus, vertigo, or conductive hearing loss, in contrast to earlier reports, half of the patients were asymptomatic. Dehiscence of vestibular aqueduct rarely leads to clinical or histologic hydrops. The VEMP testing was useful in confirming the presence of inner ear dehiscence due to JBAs. Because the natural history of JBAs is unknown, these patients should be followed closely to evaluate for progression of the JBA or development of symptoms.

Brain-derived neurotrophic factor modulates auditory function in the hearing cochlea.

Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced deafness and may be used in the future to improve the hearing of cochlear implant patients. It is increasingly common for patients with residual hearing to undergo cochlear implantation. However, the effect of neurotrophin treatment on acoustic hearing is not known. In this study, brain-derived neurotrophic factor (BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with BDNF, confirming that delivery to the cochlea was successful. The effects of BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after cannula placement. In contrast, ABR evaluation showed that BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving Ringer's solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies ≥16 kHz. BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following cochlear implantation.

Large jugular bulb abnormalities involving the middle ear.

OBJECTIVE: Jugular bulb abnormalities (JBA), such as jugular bulb diverticula (JBD) or large jugular bulbs, rarely present in the middle ear. We review a large series of temporal bone histopathologic specimens to determine their prevalence and present a series of cases of JB abnormalities involving the middle ear (JBME) that shed light on the probable mechanism for their development. PATIENTS: 1,579 unique temporal bone specimens and individuals with radiographically-diagnosed JBME. INTERVENTION: Histopathologic and clinical review of temporal bone specimens and patient presentations, radiographic findings, treatments and outcomes. MAIN OUTCOME MEASURE: Shared characteristics of JBME. RESULTS: There were 17 cases of JBME in 1,579 temporal bone (1.1%), of which, 15 involved the inferior mesotympanum below the level of the round window membrane (RWM), whereas 2 encroached upon the RWM or ossicles. In addition, 4 clinical cases of large JBME extending above RWM were encountered; these occurred in both sexes with ages spanning from young to old (7-66 yr). They presented with conductive hearing loss (n = 3), ear canal mass (n = 1), and intraoperative bleeding (n = 1). Radiologically, they had multiple diverticula of the JB on the side with JBME, with 1 patient demonstrating growth on serial imaging studies. All patients who underwent additional imaging had marked hypoplastic contralateral transverse sinus. CONCLUSION: JBME abnormalities are rare, present across age groups, and may demonstrate serial growth over time. They are usually associated with multiple other diverticula within the same JB. Our clinical series suggests that JBME's development and uniquely aggressive behavior results from contralateral transverse sinus outflow obstruction.