One-Year Outcomes of the ROBUST II Study Evaluating the Use of a Drug-Coated Balloon for Treatment of Urethral Stricture

Objective To report 1-year results of the ROBUST II study investigating the safety and efficacy of a paclitaxel-coated balloon for the treatment of recurrent urethral strictures. Methods Subjects were adult men with a single anterior urethral stricture ≤ 3 cm in length and at least 2 prior stricture treatments. After treatment with the Optilume urethral drug-coated balloon (DCB), subjects were followed through 1 year. The primary safety endpoint was the rate of treatment-related serious complications at 90 days post-procedure. Efficacy outcomes included symptomatic assessments, erectile function measured using the International Index of Erectile Function (IIEF), Qmax, and anatomic success. Results Sixteen men with an average of 4.1 prior dilations were treated with the DCB. Anatomic success was achieved at 6 months in 73%. Average IPSS improved from 18.4 to 6.0 at 1 year (P < 0.001). Qmax improved from 6.9 mL/sec to 20.8 mL/sec (P < 0.001). There was no change in IIEF. Four subjects received additional treatment within 1 year. There were no treatment-related serious complications. Conclusions Short-term follow-up of men with urethral stricture treated with the Optilume DCB showed durable anatomic results at 6 months and sustained symptomatic improvement through 1 year. Treatment with the device was safe.

Nasobiliary drainage: an effective treatment for pruritus in cholestatic liver disease

IntroductionNasobiliary drains (NBDs) have been successfully used to manage intrahepatic cholestasis, bile leaks and obstructive cholangitis. It allows external drainage of bile, bypassing the ileum where bile salts are reabsorbed. We assessed the utility of placement with effect on markers of cholestasis and patient symptoms.MethodsConsecutive patients undergoing NBD over 12 years for the management of pruritus were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and response to therapy.ResultsTwenty-three patients (14, 61% male) underwent 30 episodes of NBD. The median age was 26 years old (range 2–67 years old). A single procedure was carried out in 20. One patient each had two, three and five episodes of NBD. The most common aetiologies were hereditary cholestatic disease (n=17, 74%) and drug-induced cholestasis (n=5, 22%),NBD remained in situ for a median of 8 days (range 1–45 days). Significant improvement in bilirubin was seen at 7 days post-NBD (p=0.0324), maintained at day 30 (335 μmol/L vs 302 µmol/L vs 167 µmol/L). There was symptomatic improvement in pruritus in 20 (67%, p=0.0494) episodes. One patient underwent NBD during the first trimester of pregnancy after medical therapy failure with a good symptomatic response. The catheters were well tolerated in 27 (90%) of cases. Mild pancreatitis occurred in 4 (13%) cases.ConclusionNBD can be used to provide symptomatic improvement to patients with pruritus associated with cholestasis. It is well tolerated by patients. They can be used in pregnancy where medical management has failed.

The Erroneous Appearance of Silver Nitrate on CT Imaging in Patients with Severe Otitis Externa; A Case Series

Introduction Silver nitrate is commonly used within otolaryngology to treat granulation tissue in severe otitis externa. It appears radio-opaque on CT (computed tomography) imaging and therefore can mimic bony fragments and foreign bodies. This is particularly cumbersome when the phenomena correlates to the clinical complaint. Discussion We report two cases of 73-year-old and 75-year-old males who presented with chronic otalgia and discharge. Granulation tissue in the external auditory canal was identified and chemically cauterised with silver nitrate. Subsequent CT petrous bones demonstrated an unidentified foreign body in the canal with extensive soft tissue swelling giving an impression of a wick in situ and “minor bony erosion in the left external acoustic canal” respectively. An additional CT of a 57-year-old female who had been treated with silver nitrate for granulomatous tissue reported “multiple highly radiopaque foci in the external auditory canal, suggestive of foreign body”. Though relatively unknown, this phenomenon has been reported in literature. However, there are few reports of silver nitrate artefacts in CT images of the head no cases in the context of otitis externa. Our patients avoided further imaging or surgery following clarification with the radiologists and symptomatic improvement with long-term intravenous antibiotics. Conclusion Given the prevalence of CT imaging and cauterization in otolaryngology, we recommend contemporaneously documenting the use of silver nitrate and highlighting this on request forms to avoid alarming erroneous reports, unnecessary investigation and surgical procedures. We also recommend, where clinically acceptable, to use silver nitrate prior to imaging.

Use of long term aprepitant as a treatment for refractory nausea following oesophageal stent insertion – a case report

Background: Aprepitant, a substance P neurokinin-1 receptor antagonist, is licenced for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy. Case: A 33 year-old male with metastatic gastro-oesophageal cancer had multiple admissions for refractory nausea and vomiting following insertion of an oesophageal stent. Action: Mechanical issues with the stent, stent removal and central causes were excluded. Multiple anti-emetic agents were trialled in combination and with varying routes of administration without significant symptomatic improvement. Formulation: A trial of aprepitant was proposed as an off-licence therapy. Outcome: One hundred sixty-five milligrammes of aprepitant was given orally every 3 days and then up titrated to once daily with significant symptomatic improvement enabling the patient to tolerate an oral diet. The patient remained stable at 12 weeks and has been accepted into two clinical trials for potential further cancer treatment. Lessons: Aprepitant can be effective in refractory nausea and vomiting outside of emetogenic chemotherapy and safely used as a chronic treatment. The prevalence of refractory nausea and vomiting as a rare adverse outcome post-oesophageal stent insertion should be studied. What now? Further research of neurokinin-1 inhibitors for indications other than chemotherapy-induced nausea and vomiting is indicated.

654 Fragility of functional/symptomatic endpoints to assess the efficacy of drugs for pulmonary arterial hypertension

Aims Drugs for pulmonary arterial hypertension (PAH) have historically been evaluated for their efficacy in improving functional capacity and decreasing symptoms. However, these measures of treatment effect are approximate and subject to substantial variability, and therapeutic choices based on them may be aleatory. Methods and results We reviewed the articles reporting the results of phase 3 PAH randomized controlled trials (RCTs) and calculated the fragility index (FI) for the outcomes exploring functional capacity and symptoms. The FI corresponds to the number of events that need to be added to the arm with the smallest number of events to make a significant result non-significant: the lower the FI, the fragile the trial with respect to the endpoint examined. For RCTs with non-significant results, we calculated the FI as the number of events that need to be removed from the investigational drug (ID) group to reach a P-value &lt;0.05. When possible, we also computed the FI for PAH hospitalization. Data about the rate of functional/symptomatic improvement were available for 22 (63%) of 35 RCTs (Table). The ID was superior to placebo or comparator with P &lt; 0.05 in 10 (45%) of these 22 studies. The median FI was 2 [interquartile range (IQR): 6.5], with 4 RCTs having a FI = 1 and only 2 &gt; 10 (Table). For the 12 RCTs in which the effect of the ID was neutral (P &gt; 0.05), the median FI was 6 (IQR 4.25) (Table). The hospitalization FI was determined for 17 (77%) of the 22 RCTs and was overall higher than the one for the functional/symptomatic outcome (median 6, IQR 8). Conclusions Accessible information about the effects of PAH drugs on functional capacity and/or symptoms is published for 6 in 10 RCTs, in which very few events in one arm could have flipped the results from non-significant to significant or, more remarkably, from significant to non-significant. The evidence supporting the reduction of PAH hospitalizations as a treatment goal appears to be more robust.

Ustekinumab is effective for perianal fistulising Crohn's disease: a real-world experience and systematic review with meta-analysis

BackgroundPerianal Crohn’s disease (pCD) is a debilitating complication affecting up to 30% of Crohn’s disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied.AimTo determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review.MethodsA retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab.ResultsAt 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response.ConclusionUstekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.

Vulvar herpes zoster infection: a rare and challenging diagnosis

A 26-year-old woman under immunosuppression with infliximab due to Crohn’s disease was referred to the gynaecology emergency room with dispersed and coalescing vesicular lesions on the vulvar region extending to the right lower limb involving S2–S3 dermatome, associated with severe pain. Clinical history, physical examination and serological testing was consistent with herpes zoster infection. The patient was treated with valaciclovir for 14 days and cefradine for 7 days (due to the possibility of secondary bacterial infection). Significant symptomatic improvement was noted after 1 week. The 1-year follow-up was unremarkable. According to our knowledge and review of the literature, this is one of the few cases reported of vulvar herpes zoster, especially related to infliximab.

Treatment-induced sarcoidosis in a patient with metastatic clear cell ovarian cancer

Sarcoidosis is a granulomatous disease that commonly presents with lung or lymphatic system manifestations. Diagnosis is often delayed due to variable clinical presentation. This is a case of a patient with metastatic clear cell ovarian cancer who developed disease reoccurence after definitive treatment with surgery and adjuvant chemotherapy. She was treated with multiple lines of therapy, including investigational agents. During this time, she developed mediastinal lymphadenopathy and hypercalcaemia. Due to suspicion that her presentation was not a manifestation of her malignancy, she underwent two lymph node biopsies revealing granulomatous disease. She was initiated on prednisone for management of sarcoidosis, which led to radiologic, laboratory and symptomatic improvement. Although the precipitating factor for this patient’s sarcoidosis cannot be definitively determined, nivolumab is a possible culprit. This case highlights the importance of a broad differential diagnosis when a patient undergoing antineoplastic treatment develops mediastinal lymphadenopathy or hypercalcaemia.

Incidental diagnosis of Herlyn-Werner-Wunderlich Syndrome in a nulliparous woman: a case report in Bhutan

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital syndrome with features of uterus didelphys, ipsilateral absent kidney and obstructed hemivagina. Ultrasound findings of absent kidney or abnormalities in the kidney should alert the clinicians about the syndrome. Complications like endometriosis, infertility and pelvic inflammation occurs with late diagnosis.A 42-yearold nulliparious married woman who presented with right sided abdominal pain to the National Referral Hospital was diagnosed to have HWWS. The diagnosis was supported by ultrasound, CT and MRI findings. Patient was treated for endometriosis and had symptomatic improvement. The diagnosis of the syndrome is challenging as it is rare but clinicians should suspect the syndrome in women who present with infertility. Ultrasound scan is the basic investigation to screen the syndrome which is available in most hospitals.

Comparative evaluation of efficacy of muscle relaxant, vasodilator and combined intralesional steroid with hyalaronidase use in oral submucous fibrosis

Oral Sub Mucous Fibrosis (OSMF) is a disease , which predominately occurs in Indians and South East Asians. It is characterised by mucosal rigidity of varying intensity due to fibroelastic changes of the juxta-epithelial layer, resulting in a progressive inability to open mouth. The main concern in the condition is the management of trismus and burning sensation of oral mucosa. this study was conducted to compare various medical treatment protocol of OSMF, so as to arrive at definitive and effective protocol for the management of OSMF. 105 patients of OSMF attending the ENT OPD and satisfying the criteria for inclusion were enrolled for the study. The subjects were randomly divided into age sex matched into three study groups( Dexa with hyaluronidase , Oral vasodilator, Muscle relaxant) in which the relief in symptoms was noted. Lycopene was given in all patients. Group A, patients were given intralesional injection Dexamethasone with Hyaluronidase biweekly for five weeks and marked improvement was seen in cases of pain with spicy food 13 cases (76.47%), followed by decreased in mouth opening 9 cases (56.25%). In Group B, oral vasodilator Tablet Pentoxifylline 400 mg TDS was given and showed improvement in difficulty in protruding tongue in 9 cases (60%), pain with spicy food 8 cases (50%), decreased mouth opening 6 cases (37.5%), oral ulceration 3 cases (42.85%). In Group C with muscle relaxant Tablet Myosone 50 mg BD showed improvement pain with spicy food 8 cases (42.10%), decreased mouth opening 8 cases (42.10), difficulty in swallowing 3 cases (37.5%). As there is still paramount of controversy regarding the ethology of OSMF there is no definite treatment protocol. Patients which received intralesional dexamethasone and hyaluronidase along with oral lycopene showed better clinical and symptomatic improvement in comparison to others groups, which at present appears to the best option for OSMF.