Metastatic melanoma: an unexpected cause of acute liver failure.

Acute liver failure secondary to metastatic melanoma is exceedingly rare with the literature limited to case reports. The disease itself presents with vague symptoms making diagnosis difficult without a high clinical suspicion. Further to this, the prognosis of acute liver failure secondary to metastatic melanoma is dismal. We present the case of a 59-year-old male with a distant history of previously excised cutaneous melanoma who presented to our institution with abdominal pain and liver enzyme derangement suggestive of acute hepatitis. Due to progressive derangement in liver function and cross-sectional imaging suggestive of an infiltrative cause, a left axillary lymph node was biopsied which demonstrated metastatic melanoma. The patient subsequently deteriorated into acute liver failure and despite acute treatment of his underlying metastatic melanoma died 17 days post initial presentation. This case highlights an uncommon cause of acute liver failure as well as the poor prognosis associated with acute liver failure secondary to metastatic melanoma.

Budesonide Orodispersible Tablet for the Treatment of Refractory Esophageal Lichen Planus.

Esophageal lichen planus is an uncommon but highly morbid condition where effective treatments are limited. Diagnosis may be challenging and requires a high degree of clinical suspicion considering endoscopic, histopathological, esophageal, and extraesophageal manifestations. We describe a severe case of esophageal lichen planus and recurrent esophageal stricture that was refractory to acid suppression, local and systemic steroid formulations, and dilatation. We present the first reported use of budesonide orodispersible tablet for this condition, including the excellent clinical, endoscopic, and histopathological response.

Assessing the diagnostic yield of achalasia using provocative testing in high-resolution esophageal manometry: Serial diagnostic study.

BACKGROUND: Chicago Classification v4.0 recommends that if achalasia is demonstrated with single water swallows (SWS); provocative testing is not required. We determine whether provocative testing in patients with suspected achalasia can change manometric findings and reproduce symptoms. METHODS: Between 2016 and 2022, 127 consecutive manometry studies of patients with achalasia were retrospectively analyzed. All patients underwent SWS, a solid meal (SM) and/or a rapid drink challenge (RDC). Demographic data, fluoroscopy, gastroscopy, and pre-and post-treatment Eckardt scores were collated. KEY RESULTS: Of 127 achalasia patients (50.6 ± 16.6 years and 54.6% male), all completed a SM and 116 (91.3%) completed RDC; overall 83 were naïve (65.4%) to previous therapy. 15.4% patients with normal integrated relaxation pressure (IRP) on SWS demonstrated obstruction with RDC. SM gave a different achalasia phenotype in 44.9% of patients (p ⟨ 0.001). Twelve patients with normal IRP during SWS had persistent/recurrent obstruction during provocative testing; 83.3% had previous achalasia therapy. None of 13 patients with Type III (TIII) achalasia with SWS exhibited a change in manometric findings with provocative testing. Impedance bolus heights were lower in patients with TIII achalasia and those with normal IRP with SWS. During the SM, symptoms were reproduced in 56.7% of patients. Forty-six of 103 patients (44.7%) underwent therapy based upon the final achalasia subtype which was defined by the provocative test result of the high-resolution manometry (HRM) study. All treatments were effective, regardless of the achalasia subtype. CONCLUSIONS AND INFERENCES: Manometric findings remain unchanged when TIII achalasia is diagnosed with SWS. In patients with normal IRP, Type I, or Type II achalasia during SWS, provocative testing can alter achalasia phenotype or uncover achalasia where diagnosis is unclear. Further, it can reproduce symptoms. Such findings can personalize and guide effective therapeutic decisions.

Empiric Esophageal Dilatation for Solid-Food Dysphagia: Presence of Mucosal Tear on Relook Endoscopy Predicts Symptomatic Response.

We hypothesized that a mucosal tear on relook endoscopy after empiric dilatation predicts symptomatic response. We evaluated symptomatic response (modified Ogilvie dysphagia score) after 161 consecutive esophageal dilatations. Comparing visible strictures, empiric dilatations with mucosal tear, and empiric dilatations without tear, baseline dysphagia scores were similar ( P = 0.34). Successful symptomatic response to dilatation occurred in 82% of visible strictures, 80% of those with tear, compared to only 37% of those with no tear ( P < 0.001). Patients with a mucosal tear after empiric dilatation have a superior symptomatic response to those without, and comparable to patients with visible strictures. We infer the tear represents disruption of an endoscopically inapparent stricture.

How to effectively use and interpret the barium swallow: Current role in esophageal dysphagia.

BACKGROUND: The barium swallow is a commonly performed investigation, though recent decades have seen major advances in other esophageal diagnostic modalities. PURPOSE: The purpose of this review is to clarify the rationale for components of the barium swallow protocol, provide guidance on interpretation of findings, and describe the current role of the barium swallow in the diagnostic paradigm for esophageal dysphagia in relation to other esophageal investigations. The barium swallow protocol, interpretation, and reporting terminology are subjective and non-standardized. Common reporting terminology and an approach to their interpretation are provided. A timed barium swallow (TBS) protocol provides more standardized assessment of esophageal emptying but does not evaluate peristalsis. Barium swallow may have higher sensitivity than endoscopy for detecting subtle strictures. Barium swallow has lower overall accuracy than high-resolution manometry for diagnosing achalasia but can help secure the diagnosis in cases of equivocal manometry. TBS has an established role in objective assessment of therapeutic response in achalasia and helps identify the cause of symptom relapse. Barium swallow has a role in the evaluating manometric esophagogastric junction outflow obstruction, in some cases helping to identify where it represents an achalasia-like syndrome. Barium swallow should be performed in dysphagia following bariatric or anti-reflux surgery, to assess for both structural and functional postsurgical abnormality. Barium swallow remains a useful investigation in esophageal dysphagia, though its role has evolved due to advancements in other diagnostics. Current evidence-based guidance regarding its strengths, weaknesses, and current role are described in this review.

How provocative tests in addition to wet swallows during high-resolution manometry can direct clinical management.

PURPOSE OF REVIEW: Provocative tests have been advocated to address limitations of high-resolution manometry (HRM) with wet swallows. We describe the commonly used provocative manometric manoeuvres [rapid drink challenge (RDC), multiple rapid swallows (MRS), solid swallows and the solid test meal (STM)], compare their diagnostic yield and accuracy to wet swallows, and outline their role in directing clinical management. RECENT FINDINGS: Provocative testing with RDC and STM identifies a proportion of achalasia cases missed by standard testing, and RDC can play a similar role to radiology in the evaluation of treatment response. In EGJOO, provocative testing with RDC and STM not only increase the diagnostic yield, but can also help differentiate between spurious cases and those representing true outflow obstruction likely to respond to achalasia-type therapies. MRS and STM can help determine the clinical relevance (or otherwise) of ineffective oesophageal motility, and in this setting, MRS may predict the likelihood of postfundoplication dysphagia. RDC and STM can help identify cases of postfundoplication dysphagia more likely to respond to dilatation. SUMMARY: Provocative testing has been shown to increase diagnostic yield of HRM, clarify inconclusive diagnoses, allows corroboration of dysmotility with patient symptoms and helps direct clinical management.

Barrett's esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett's in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett's with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett's by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett's is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.

Timed barium swallow: Esophageal stasis varies markedly across subtypes of esophagogastric junction obstruction.

BACKGROUND: Timed barium swallow (TBS) is a recommended ancillary investigation in evaluation of esophagogastric junction (EGJ) obstruction, yet there are little data comparing esophageal stasis across subtypes. METHODS: A retrospective cohort study was performed. All type III achalasia diagnosed between November 2016 and November 2020 were included, along with matched numbers of consecutive types I and II and conclusive EGJOO cases with concurrent TBS evaluation. Co-primary outcomes were TBS retention at 1 and 5 min. Secondary outcomes were symptoms and manometric metrics of EGJ function and peristaltic integrity. KEY RESULTS: One hundred patients were included (25 each of types I-III and conclusive EGJOO). TBS retention measured by height and width at 1 and 5 min differed significantly across the four subtypes (p < 0.0001 all comparisons), with esophageal stasis tending to be significantly greater for types I and II achalasia (88% and 84% with >5 cm column at 5 min) compared to type III and EGJOO (24% and 8% with >5 cm column; p < 0.0001). Eckardt symptom severity was similar across subtypes (p = 0.30). Magnitude of esophageal stasis and integrated relaxation pressure (IRP) were uncorrelated (R = 0.21). In EGJOO, the number of swallows with intact peristalsis inversely correlated with barium column height (R = -0.49) and those with disordered peristalsis were more likely to have any residual barium at 5 min compared to those without disordered peristalsis (43% vs. 0%; p = 0.02). CONCLUSIONS & INFERENCES: Timed barium swallow findings differed markedly with significantly less esophageal stasis in type III achalasia and EGJOO, despite similar symptom severity and no correlation between degree of emptying and IRP. Preservation of peristalsis may underlie this finding in EGJOO.

The Clinical Relevance of Manometric Esophagogastric Junction Outflow Obstruction Can Be Determined Using Rapid Drink Challenge and Solid Swallows.

INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO. METHODS: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated. RESULTS: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02). DISCUSSION: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol.

The timed barium swallow and its relationship to symptoms in achalasia: Analysis of surface area and emptying rate.

BACKGROUND: Timed barium swallow (TBS) is used to objectively measure response following achalasia therapy; however, findings can be discordant with symptoms. We hypothesized that measurement of surface area of the residual barium column would improve its utility in measuring outcome. METHODS: In a single-center cohort, achalasia patients undergoing therapy between September 2015-2016 who had TBS were included. Four metrics of emptying were studied: Post-therapy residual barium (a) absolute height and (b) surface area and percentage reduction in (c) residual height (%H) and (d) surface area (%SA) compared to pretherapy. Metrics were evaluated against symptom response (Eckardt score). KEY RESULTS: Twenty-four achalasics (median age 43 year; 13 males) were included; 14 received pneumatic dilatation, and 10 had peroral endoscopic myotomy. Treatment resulted in significant reduction in median Eckardt score (7 to 1; P = .03), mean residual barium column height (14.7 ± 8.7 to 7.9 ± 6.0 cm; P = .01) and surface area (52.7 ± 43.5 to 24.5 ± 23.6 cm2 ; P = .02). There were 4 (17%) initial non-responders (Eckardt > 3). % SA was best at discriminating between responders and non-responders (area under curve 0.85 ± 0.08; sensitivity 100%, specificity 80%). Concordance with symptomatic response following therapy was 83% when using 45% as the cutoff for surface area reduction compared to pretherapy. Eight patients whose static barium height was discordant with symptoms became concordant when % SA was used as a measure of response. CONCLUSIONS & INFERENCES: Change in barium surface area is a superior measure of esophageal emptying and better correlates with treatment response than the conventional 5-minute barium height in defining objective response to achalasia therapy.

Achalasia diagnosed despite normal integrated relaxation pressure responds favorably to therapy.

BACKGROUND: Achalasia diagnosis requires elevated integrated relaxation pressure (IRP; manometric marker of lower esophageal sphincter [LES] relaxation). Yet, some patients exhibit clinical features of achalasia despite normal IRP and have LES dysfunction demonstrable by other means. We hypothesized these patients to exhibit equivalent therapeutic response compared to standard achalasia patients. METHODS: Symptomatic achalasia-like cases, despite normal IRP, displayed evidence of impaired LES relaxation using rapid drink challenge (RDC), solid swallows during high-resolution manometry, and/or barium esophagogram; were treated with achalasia therapies and compared to standard achalasia patients with raised IRP. Outcomes included equivalence for short- and long-term symptom response and stasis on barium esophagogram. KEY RESULTS: Twenty-nine normal IRP achalasia cases (14 males, median age 50 year, median Eckardt 6, barium stasis 12 ± 7 cm) and 29 consecutive standard achalasia controls underwent therapy. Among cases, LES dysfunction was most often identified by RDC and/or barium esophagogram. Short-term symptomatic success was equivalent in cases vs controls (90% vs 93%; 95% CI for difference: -19% to 13%). Median short-term (1 vs 1; 95% CI for difference: 0-1) and long-term Eckardt scores (2 vs 1; 95% CI for difference: 0-2) were similar in cases and controls, respectively. Adequate clearance was observed in 67% of cases vs 81% of controls on post-therapy esophagogram. CONCLUSIONS AND INFERENCES: We described a subset of achalasia patients with normal IRP, but impaired LES relaxation identifiable only on additional provocative tests. These patients benefited from treatment, suggesting that such tests should be performed to increase the number of clinically relevant diagnoses.

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases.

BACKGROUND/AIMS: To examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort. METHODS: A prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD. RESULTS: Three hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77-3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049). CONCLUSIONS: In this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users.

Posterior Tibial Nerve Stimulation for the Treatment of Fecal Incontinence Following Obstetric Anal Sphincter Injury.

OBJECTIVES: Obstetric anal sphincter injuries (OASI) are a major risk factor for fecal incontinence (FI). Neuromodulation is often used as second-line therapy for FI, but evidence for its efficacy is conflicting. We aimed to evaluate the efficacy and predictive factors of posterior tibial nerve stimulation for obstetric anal sphincter injury-induced FI. MATERIALS AND METHODS: Consecutive females with FI related to past OASI who had not responded to first-line therapy and had received 8-12 weeks of posterior tibial nerve stimulation were included. Subjects aged more than 50 and/or having other causes of FI were excluded. Patients underwent anorectal physiology and endoanal ultrasound pretherapy. Symptom burden was evaluated pretherapy and posttherapy using Rockwood and Wexner scales. A Wexner score reduced to below 10 or halved was used to define responders. RESULTS: A total of 37 females (mean age 38 years, median parity 2) were included. About 17 (46%) had ultrasonographically visualized anal sphincter defects and 41% had a history of third or second-degree perineal tears. About 14 subjects (38%) were deemed responders. Compared with nonresponders, responders had lower baseline rectal distension thresholds and tended to have disrupted (59%) than intact sphincters (20%, p < 0.01). Responders demonstrated improvement in Rockwood score for depression and embarrassment, visual analogue score for bowel symptoms and stool consistency (median baseline Bristol score 5, to 3 posttherapy; p < 0.01). CONCLUSIONS: Of a well-defined cohort of females with FI secondary to OASI, 38% responded to posterior tibial nerve stimulation. Much of this improvement may relate to improvement in stool consistency.

Challenges in diagnosis of pancreatic cancer.

Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease.

Efficacy of Percutaneous Posterior Tibial Nerve Stimulation for the Management of Fecal Incontinence in Multiple Sclerosis: A Pilot Study.

BACKGROUND: Fecal incontinence is a debilitating and highly prevalent problem among multiple sclerosis patients. Conservative therapies often fail to provide benefit. Posterior tibial nerve stimulation is a minimally invasive neuromodulatory therapy with proven efficacy for fecal incontinence in non-neurological settings. OBJECTIVE: To evaluate the efficacy of posterior tibial nerve stimulation in treating multiple sclerosis-related fecal incontinence. METHODS: Consecutive multiple sclerosis patients with fecal incontinence that had failed conservative therapy received posterior tibial nerve stimulation between 2012 and 2015. All patients had previously undergone anorectal physiology tests and endoanal ultrasound. Patients whose Wexner incontinence score reduced below 10 post-therapy or halved from baseline were deemed responders. RESULTS: Thirty-three patients (25 female, median age 43 years) were included. Twenty-three (70%) had urge, 4 (12%) passive, and 9 (27%) mixed fecal incontinence. Twenty-six (79%) were classified as responders. The majority of subjects had relapsing-remitting multiple sclerosis (67%); those had a significantly higher response rate (95% vs. 67% and 50% in primary and secondary progressive respectively, P < 0.05). Responders tended to be more symptomatic at baseline and had greater improvements in bowel symptom scores and quality of life scores with therapy. CONCLUSION: Posterior tibial nerve stimulation demonstrates potential as an effective therapy for fecal incontinence in multiple sclerosis. These findings provide the basis for future more definitive controlled studies.

Achalasia: It Is Not All Black and White.

PURPOSE OF REVIEW: This review aims to shed light on subtleties of achalasia diagnosis, including potential pitfalls that may lead to errors. Optimal methods for assessment of disease severity and the relationship between achalasia and other motility disorders will also be reviewed with an emphasis on recent findings from the literature. RECENT FINDINGS: Adjunctive testing with viscous substances or larger water volumes should be used routinely as it improves the accuracy of achalasia diagnosis. Chronic opiate use can mimic achalasia. The timed barium swallow remains the best test for assessments of disease severity and prognostication, but the functional lumen-imaging probe, a newer tool which measures esophagogastric junction distensibility using impedance planimetry, is emerging as a potentially more powerful tool for these purposes. Functional esophagogastric junction outflow obstruction is possibly part of the achalasia spectrum. By addressing the potential pitfalls described, and through routine and standardized use of the diagnostic tools mentioned herein, the accuracy of diagnosis, severity assessment, and prognostication of achalasia can be improved.

Antispasmodic drugs in colonoscopy: a review of their pharmacology, safety and efficacy in improving polyp detection and related outcomes.

Antispasmodic drugs are cheap, effective and generally safe. They may improve outcomes in colonoscopy, however their use has not been consistent or widespread. This manuscript reviews the three most commonly used antispasmodics in colonoscopy, namely, hyoscine butylbromide (and related ammonium compounds), glucagon and peppermint oil. The pharmacology, action and safety of the agents, as well as the evidence for them improving colonoscopic outcomes will be discussed. In addition to polyp detection, other colonoscopic outcome endpoints of interest include cecal and ileal intubation, and patient comfort. The drugs studied were all found to be effective gastrointestinal antispasmodics with good safety profiles. There is insufficient evidence to conclude whether antispasmodics improve cecal intubation rate, predominantly because the baseline rates are already high. Antispasmodics probably have efficacy in reducing cecal intubation time especially in those with marked colonic spasm. Antispasmodics do not offer significant benefit in polyp detection or improving patient comfort during colonoscopy. Future studies should focus on inexperienced colonoscopists as well as those with marked colonic spasm, in whom the greatest benefit seems to lie.