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Benign biliary strictures (BBSs) may form from chronic inflammatory pancreaticobiliary pathologies, postoperative bile-duct injury, or at biliary anastomoses following liver transplantation. Treatment aims to relieve symptoms of biliary obstruction, maintain long-term drainage, and preserve liver function. Endoscopic therapy, including stricture dilatation and stenting, is effective in most cases and the first-line treatment of BBS. Radiological and surgical therapies are reserved for patients whose strictures are refractory to endoscopic interventions. Response to treatment is dependent upon the technique and accessories used, as well as stricture etiology. In this review, we discuss the various BBS etiologies and their management strategies.

Colorectal cancer (CRC) can be prevented by colonoscopy and polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions that have a high risk of progression to CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might contribute to adenoma recurrence, which occurs in 15% to 30% of patients who undergo surveillance. We aimed to determine the efficacy of adjuvant thermal ablation of the EMR mucosal defect margin in reducing polyp recurrence.We performed a prospective study of 390 patients with large laterally spreading colonic lesions (≥ 20 mm, n = 416) referred for EMR at 4 tertiary centers in Australia. After complete lesion excision by EMR, lesions were randomly assigned to thermal ablation of the post-EMR mucosal defect margin (n = 210) or no additional treatment (controls, n = 206). We performed surveillance colonoscopies with standardized photo documentation and biopsies of the scar after 5 to 6 months. Patient, procedure, and lesion characteristics were similar between the groups. The primary endpoint was detection of lesion recurrence at first surveillance colonoscopy.A significantly lower proportion of patients who received thermal ablation of the post-EMR mucosal defect margin had evidence of recurrence at first surveillance colonoscopy (10/192, 5.2%) than controls (37/176, 21.0%) (P .001). The relative risk of recurrence in the thermal ablation group was 0.25 compared with the control group (95% confidence interval 0.13-0.48). Rates of adverse events were similar between the groups.In a multicenter randomized trial, thermal ablation of the post-EMR mucosal defect margin significantly reduced polyp recurrence at first surveillance colonoscopy, compared with no additional treatment. Routine implementation of this simple and safe technique could increase the utility of EMR, decrease surveillance burdens, and reduce morbidity and mortality from CRC. ClinicalTrials.gov no: NCT01789749.

A 59-year-oldwoman presented with a 2-month history of malaise, abdominal distention and unintentional weight loss. She was initially managed as community acquired pneumonia with a suspicion of underlying chronic liver disease but she deteriorated rapidly into a multiorgan failure necessitating transfer to intensive care unit of a tertiary hospital. She was investigated with liver and bone marrow biopsy that confirmed the diagnosis of hepatosplenic T cell lymphoma. She was treated with cyclophosphamide, doxorubicin, vincristine, etoposide and prednisolone chemotherapy that was changed to salvage ifosfamide carboplatin etoposide (ICE) chemotherapy due to poor response with first-line chemotherapy and disease progression. Unfortunately, her disease progressed further and she opted for palliative management.

Symptomatic dysphagia is believed to be more common in the older population; however, the factors that predict age-related dysphagia are less well-understood. Here, we describe a questionnaire-based survey of swallowing dysfunction in a large, otherwise 'healthy' community dwelling older population in the UK in whom additional cognitive and depression related scores were evaluated. A postal survey using Sydney oropharyngeal dysphagia questionnaire was sent to 800 residences in the North of England that formed part of the University of Manchester Age and Cognitive Performance Longitudinal Study. This cohort was composed of older individuals (mean age 81 [range 69-98 years]) who are otherwise healthy with no history of previous neurological disease. The postal questionnaire is a validated self-report inventory measuring symptoms of oropharyngeal dysphagia covering a total of 17 domains of swallowing function. The maximal score obtainable is 1700, with a score of ?200 arbitrarily considered to indicate swallowing difficulty. Cognitive performance and depression scores utilized the telephone interview cognitive screen and the Geriatric Depression Scale. All data were analyzed in SPSS. Of the 800 questionnaires sent out, 637 where returned. Three were later discarded as unusable after follow-up telephone interviews of incomplete forms, giving a completed response rate of 79%. Females made up 77% of the total respondents. Of the population, 11.4% reported symptoms indicative of significant dysphagia. Unsurprisingly, dysphagia severity was directly correlated with subject age (r= 0.11, P= 0.007). When cognitive factors were taken into account, there was no correlation between memory, recall, and mental performance and dysphagia; however, depression was strongly and independently associated (P= 0.002) with dysphagia symptoms. Dysphagia symptoms are prevalent in older people, affecting nearly one in nine people who are otherwise living independently in the community. While cognitive factors such as memory recall do not seem to influence dysphagia symptoms, depression is associated with dysphagia, suggesting a potential interaction. This could relate to associations with quality of life or psychological factors.

Embryological development of the colon is complex and often unpredictable. This gives rise to variable colonic configurations during colonoscopy. An appreciation of normal colonic anatomy and three-dimensional spatial awareness of the estimated position of the colonoscope by the colonoscopist is important. Such understanding and awareness helps plan and institute specific maneuvers that are important for safe and complete examination, in addition to carrying out anatomically specific troubleshooting strategies in colonoscopy. This article is part of an expert video encyclopedia.

Background Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) can be effectively treated by single-session EMR, resulting in complete Barrett's excision (CBE). CBE provides accurate histology for staging and clinical confirmation of neoplasia eradication but is limited by a high risk of esophageal stricture formation. Objective To evaluate the effectiveness of prophylactic temporary esophageal stenting to prevent post-CBE stricture formation. Design and Setting Single-center, investigator-initiated feasibility study. Patients Circumferential, short-segment Barrett's esophagus (≤C3≤M5) with HGD or IMC. Intervention Single-stage CBE and insertion of a fully covered metal esophageal stent at 10 days that was removed at 8 weeks. Patients were followed for a minimum of 2 surveillance endoscopies. Main Outcome Measurement Symptomatic esophageal stricture formation. Results At the end of the follow-up period, 8 patients (57.1%) required esophageal dilation for symptomatic CBE-related (n = 7) or stent-related (n = 4) strictures. A median of 3 surveillance endoscopies were performed over a median endoscopic follow-up of 17 months (range 4-25 months). Single-stage CBE successfully eliminated Barrett's intestinal metaplasia and neoplasia in 71.4% and 92.9% of patients, respectively. Four patients were admitted to the hospital, and 4 patients had early stent removal because of pain or dysphagia. Limitations Single-center feasibility study. Conclusions In a prospective study evaluating prophylactic esophageal stent insertion after single-stage CBE, esophageal strictures formed in more than of half the study cohort, and stents were associated with significant morbidity. An alternative method to reduce stricture formation is required. (Clinical trial registration number: NCT01554280.)

The majority of patients of northern European descent with hereditary hemochromatosis are homozygous for the C282Y mutation in the HFE gene product. A significant proportion of patients with this genotype have elevated iron indices; however, most will not develop symptoms or organ damage. Age, gender and alcohol are the key factors known to influence this wide variation in clinical penetrance. The authors describe the three stages of disease ranging from only genetic abnormality to overt disease and review the other factors that modify the genotype–phenotype relationship. Algorithms for use in clinical practice are included to aid clinicians in diagnosis, risk stratification and treatment. Key Concepts: Mutations in the HFE gene are relatively common. The vast majority of patients with iron overload are homozygous for the C282Y mutation in the HFE gene product. Biochemical penetrance, that is, elevated iron stores are present in 70–91% of males and 30–60% of females who are C282Y homozygotes. End-organ damage is less common and occurs in approximately one-quarter of males and 1% of females. End-organ damage is extremely unlikely if serum ferritin is less than 1000 µg l−1. The principal modifiers of disease are gender, age and alcohol. The wide variation in expression of clinical disease is largely unexplained. Various genes have been shown to have variable modifying effects on disease penetrance. Phlebotomy is a safe and effective treatment that depletes iron stores, prevents end-organ damage and confers normal life expectancy. It is best initiated on discovery of elevated iron stores, that is, stage-II or stage-III disease. Keywords: hereditary hemochromatosis; genotype; phenotype; HFE; C282Y; clinical penetrance; iron overload; ferritin; phlebotomy; cirrhosis

Background Wide-field EMR (WF-EMR) of large colonic lesions exposes submucosal vessels, which may result in intraprocedural bleeding (IPB). Ongoing bleeding may obscure the endoscopic field, prolonging the procedure and reducing safety and accuracy. A number of potential interventions to control bleeding exist; however, they have inherent limitations. Safe, readily applicable, inexpensive, and effective therapy to control EMR-IPB has not yet been described. Objective To evaluate the safety and efficacy of the snare tip soft coagulation (STSC) technique to control IPB after WF-EMR of large colonic lesions. Design Single-center, prospective cohort study. Setting Tertiary care referral center. Patients A total of 196 patients undergoing wide-field colonic EMR for flat and sessile lesions 20 mm or larger. Interventions A standard inject-and-resect EMR technique was applied. IPB was defined as bleeding obscuring the endoscopic field that persisted for 60 seconds or longer. STSC was performed by using the tip of the polypectomy snare to apply soft coagulation (80 W) to sites of IPB. Main outcome measurements Immediate hemostasis, postprocedural bleeding, and other adverse events. Results A total of 198 lesions (mean size 41.5 mm, 64% in the right colon) were removed in 196 patients (mean age 68 years, 52.5% male). STSC alone achieved effective hemostasis in 40 of 44 cases of IPB (91%). In the remaining 4 cases, additional treatment with coagulating forceps or clips was required to achieve hemostasis. There were no immediate STSC-related adverse events. There was no statistically significant difference between the IPB and non-IPB groups in relation to the use of antiplatelet (P = .2) or anticoagulation agents (P = .4), postprocedural bleeding (P = .8) and adverse event rates (P = .7). Limitations Nonrandomized study. Conclusions STSC is a simple and efficient first-line technique for achieving hemostasis of IPB during WF-EMR in the colon. It succeeds in the majority of cases and appears to be safe.

Background Blue dyes such as indigo carmine have become a frequent component of the submucosal injectate for EMR. Confirmation of the correct resection plane and assessment of the resection defect are facilitated by the selective staining of the submucosal layer. Nonstained areas are more difficult to evaluate and may contain inadvertent muscularis propria (MP) injury. The use of topical submucosal chromoendoscopy (TSC) may allow rapid and accurate assessment of these unstained areas and visual recognition of MP injury. Objective To evaluate the utility of a novel technique in the assessment of nonstained areas within the post-EMR defect. Design Single-center prospective cohort study. Setting Academic, tertiary care referral center. Patients A total of 143 patients undergoing wide-field colonic EMR for sessile lesions 20 mm or larger. Interventions A standard inject-and-resect EMR technique was applied with indigo carmine blue dye in the injectate. Defects with areas of nonstaining were recorded and examined, and then irrigated with the submucosal injectate by using the blunt tip of the injection catheter. Main Outcome Measurements Detection of additional cases of MP injury by using TSC. Results A total of 147 EMRs were performed. Focal areas of defect nonstaining were seen in 25 of cases (17%), with no MP injury identified on initial examination. After TSC, 2 additional cases of MP injury were identified, and these were successfully managed endoscopically. Intraprocedural recognition of deep resection increased from 4 cases (2.8%) to 6 cases (4.1%), thereby avoiding potential delayed perforation in 2 patients. Limitations Single-center, nonrandomized study. Conclusions TSC is simple and effective and rapidly confirms the plane of resection and may improve detection of intraprocedural perforation.

Altered digestive anatomy creates unique challenges in endoscopic retrograde cholangiopancreatograghy (ERCP). The type of previous surgery acts as a guide for endoscope selection and technical approach. Endoscopic therapy is preferred to percutaneous radiologic technique as it is minimally invasive and less morbid. In this article, the authors present a series of selected cases demonstrating the different therapeutic aspects of ERCP in altered anatomy. This article is part of an expert video encyclopedia.

Introduction Animal studies, human brain imaging and more recently Transcranial Magnetic Stimulation (TMS) suggest a role for the cerebellum in human swallowing. Moreover, paired-pulse cerebellar-cortical TMS delivered in rapid succession (50–200 ms intervals) facilitates pharyngeal motor cortex excitability ( Jayasekeran et al., 2011 ). Objectives The aim of this study was to determine if longer trains of rTMS can induce long-lasting changes in pharyngeal cortical excitability that may prove to be therapeutically useful for dysphagia after stroke. Materials and methods In 17 healthy adults (6 female, age range 18–61 yrs), anatomical MR brain scans were acquired. Thereafter participants were intubated with an intraluminal catheter to record pharyngeal electromyography and underwent TMS cortical mapping with neuronavigation to co-localise pharyngeal motor representation bilaterally, hand motor cortex and the cerebellar site which evoked the largest pharyngeal motor response. Subjects were then randomised to receive one of 5 neuronavigated cerebellar rTMS interventions (Sham, 1 Hz, 5 Hz, 10 Hz and 20 Hz, at least 1 week apart) to the cerebellar site evoking the largest baseline pharyngeal responses to single-pulse cerebellar TMS. Bihemispheric pharyngeal cortical excitability (ipsilateral and contralateral cortex to cerebellum site) was measured at baseline and for up to 1 h post cerebellar rTMS intervention. Abductor pollicis brevis (APB) recordings were used as control. Interventional data were compared to sham using repeated measures ANOVA. Results Cerebellar rTMS was tolerated well and delivered at an average intensity of 55% of stimulator output. Compared to Sham, 10 Hz cerebellar rTMS increased pharyngeal cortical excitability ( F (1,16) = 8.3, ∗ p = 0.01), with maximal size and durational effects seen primarily in the contralateral pharyngeal cortex (+72%, ∗∗ p = 0.02, Fig. 1 ). By contrast, 1 Hz ( F (1,16) = 0.3, p = 0.60), 5 Hz ( F (1,16) = 0.5, p = 0.48), and 20 Hz rTMS ( F (1,16) = 1.3, p = 0.27) cerebellar conditioning did not significantly alter pharyngeal excitability compared to Sham. APB responses were not significantly different to sham after any intervention. Conclusions Our data show for the first time that high-frequency (10 Hz) cerebellar stimulation can produce long-lasting increases in human pharyngeal motor cortex excitability, with larger and longer-lasting effects of the intervention primarily seen in the contralateral projection. Hence 10 Hz cerebellar rTMS may play a therapeutic role in the treatment of dysphagia after hemispheric stroke.

Achalasia cardia is a primary esophageal motility disorder characterized by aperistalsis and incomplete or absent relaxation of the lower esophageal sphincter. Pneumatic dilatation is the first-line nonsurgical therapy for achalasia. The principle of this procedure is to weaken the lower esophageal sphincter by controlled tearing of esophageal muscle fibers generated by the radial force of the balloon. Demonstrated here is the technique of pneumatic balloon dilatation of the lower esophageal sphincter under fluoroscopic guidance. This article is part of an expert video encyclopedia.

Introduction: Human disease models can help to better understand the pathophysiology and systematically characterize its consequences. Upper esophageal sphincter (UES) dysphagia is a common sequela of a number of disorders including CVA, reflux disease and aging. Intrinsic disorders of the UES such as fibrosis and inflammation can result in its diminished distensibility and restrict its opening causing dysphagia. Aim: To characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restricted UES model in humans. Methods: We studied 15 patients (8 male, age 65±11 years) with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade simple device comprised of two components that could be comfortably worn around the neck: an elastic band and a cushion (5 X 3 X 2.5 CM). The cushion was placed horizontally at the center of the cricoid cartilage. By adjusting the elastic band, we selectively applied 0, 20, 30, 40 mmHg pressure perpendicular to the cricoid laryngeal structure inducing equivalent resistance against UES opening. In this model, the UES, in addition to relaxation, has to overcome the externally imparted pressure to open. Deglutitive pharyngeal and UES pressure phenomena were determined using high-resolution manometry, which recorded from entire pharynx, UES and proximal esophagus. We tested dry, 5 and 10ml swallows x 3. Results: Application of the external pressure band increased the length of the UES high pressure zone from 2.5 cm without the band to 3.1, 3.5 and 3.7 cm for 20, 30, 40mmHg cricoid restrictive pressure, respectively (p

Background Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry. Methods Healthy volunteers (n = 16, eight men, mean age = 32, range 19-57 years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter-stimulus intervals (ISIs) with the cortical response amplitudes being assessed. Key Results Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5 +/- 6.9 vs 42.8 +/- 5.9 mu V, P = 0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50-200 ms (P < 0.05), an effect not seen with sham or trigeminal nerve preconditioning. Conclusions & Inferences Posterior fossa stimulation excites the cerebellum and evokes direct motor responses within the pharynx. When conditioned with TMS, the cerebellum strongly facilitates the cortical swallowing motor pathways. This finding suggests that the cerebellum exerts a modulatory effect on human swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after neural damage.

Background & Aims Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. Methods First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. Results In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion ( F 7,70 = 2.7; P = .015) and was associated with improvement in swallowing behavior ( F 3,42 = 5; P = .02). After stroke, 1 PES treatment each day ( U = 8.0; P = .043) for 3 days ( U = 10.0) produced improved airway protection compared with controls ( P = .038). Active PES also reduced aspiration ( U = 54.0; P = .049), improved feeding status ( U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel–Cox log-rank test, P = 0.038). Conclusions This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.

Introduction Animal studies1 have suggested that the cerebellum plays an important role in the control of swallowing. Moreover human brain imaging studies have reported the activation of the cerebellum in the process of swallowing.2 In this study, we probed the interaction between cerebellum and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can be excited to induce pharyngeal activity, and also to elucidate if stimulation of the cerebellum can modulate cortical swallowing circuitry in the motor system. Methods Healthy volunteers (n=16, 8 males, mean age=32) underwent TMS measurements of pharyngeal EMG recorded from a swallowed intra luminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm where active or sham TMS conditioning pulses over the cerebellum were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at interstimulus intervals (ISIs) of 3, 5, 9, 20, 50, 100 and 200 ms allocated randomly, and the cortical responses were then assessed (compared to baseline and sham) for change in amplitude using T-tests. Results Stimulation of the cerebellum over the midline or either hemisphere evoked distinct EMG responses in the pharynx. There was a trend towards cerebellar hemispheric stimulation eliciting greater pharyngeal responses (mean amplitude 55.5±6.9 mV) than cerebellar midline stimulation (42.8±5.9 mV); p=0.08. Following active preconditioning cerebellar stimulation, the cortically evoked responses were facilitated with maximal effects at ISIs of 50–200 ms (p Conclusion This novel study demonstrates that cerebellar stimulation can evoke direct motor responses within the pharynx, and when excited with TMS, can modulate cortical swallowing motor pathways. These findings are in keeping with the animal literature suggesting a facilitatory role for the cerebellum in regulating swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after brain damage.