Introduction

For many patients with restrictive and obstructive lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx (1,2). Which, if any patients, should be excluded from transplantation due to GER remains unclear.

Aims & Methods

Aim: To examine the changes in esophageal motor function (Chicago Classification v4.0) and association with GER following LTx in patients based on pre-LTx restrictive or obstructive lung disease.
Methods: High-resolution impedance esophageal manometry (HRIM) and 24hr impedance-pH (MII-pH) were performed in 57 respiratory patients (40 restrictive disease, 17 obstructive disease) before and after LTx (mean age 60 yrs (range 33-75 yrs), 39 males) between November 2016 and October 2022.

Results

Restrictive disease: Before LTx, 15 (38%) patients exhibited abnormal motility, with the majority presenting with either ineffective esophageal motility (IEM) (8, 53%) or esophagogastric junction outflow obstruction (EGJOO) (6, 40%). One patient had distal esophageal spasm and the rest (25, 63%) normal motility. Following LTx, approximately half of patients (21, 53%) retained the same diagnosis as pre-LTx. Patients with normal motility pre-LTx were more likely to retain the same diagnosis (i.e. normal) post-LTx (17/25, 68%) than those with an abnormal motility diagnoses (4/15, 27%)(p=0.021), particularly those with EGJOO(1/6, 17%)(p=0.059). Nine of 15 (60%) patients with abnormal motility pre-LTx changed to normal motility post-LTx.
Obstructive disease: Before LTx, 8 (47%) patients exhibited abnormal motility, with the majority exhibiting EGJOO (4, 50%). The rest exhibited either IEM (2, 25%), absent motility (1, 12.5%) or hypercontractility (1, 12.5%). Nine (53%) exhibited normal motility. Following LTx, about half (10, 59%) retained the same diagnoses, but patients with normal motility (5/9, 56%) were no more likely to retain the same diagnoses as those with abnormal motility (5/8, 63%). Only one of eight (12.5%) patients with abnormal motility changed to normal motility post-LTx, which is lower than that seen in patients with restrictive disease (p=0.07). Examination of the pH findings revealed that although acid exposure time (AET) was similar pre-LTx (restrictive 2.4(0.7-7.0) v obstructive 2.0(0.5-3.4); p=0.53), there was a decrease in AET in restrictive patients (1.7(0.3-3.5);p=0.05) but no change in patients with obstructive disease (3.7(0.6-10.1)p=0.31) post-LTx. Of note, mean nocturnal baseline impedance (5cm above the LES) was similar pre-LTx (1750(1139-2705)ohms v 1799(1058-2540)ohms) and increased in restrictive patients (2480(1511-4413)ohms; p=0.002) but not in those with obstructive disease (1732(1173-2293)ohms; p=0.82), mirroring changes in AET.

Conclusion

Patients with restrictive lung disease are more likely to retain a diagnosis of normal motility or change to normal motility post-LTx than patients with obstructive lung disease. This appears to associate with improved acid exposure time and mean nocturnal baseline impedance. Further data are required on long-term outcome.

References

1. Houghton LA, Lee AS, Badri H, DeVault KR, Smith JA. Respiratory disease and the oesophagus: reflux, reflexes and microaspiration. Nat Rev Gastroenterol Hepatol 2016; 13(8); 445-60
2. Chan WW, Ahuja N, Fisichella PM, Gavini S, Rangan V, Vela MF. Extraesophageal syndrome of gastroesophageal reflux: relationships with lung disease and transplantation outcome. Ann N Y Acad Sci 2020; 1482: 95-105

Clinical Case Summary

A 45-year-old man with medical history of hypertension, dyslipidaemia and maturity-onset diabetes of the young type 5 (MODY 5) complicated by retinopathy and nephropathy, under insulin, linagliptin, ramipril, and atorvastatin was referred to Hepatology in 2021, due to elevated liver enzymes spanning four years. The patient was asymptomatic, with no history of blood transfusions, risky behaviours or new medication. Physical examination was normal with a BMI of 24 kg/m². Initial laboratory results revealed AST 78 U/L, ALT 135 U/L, ALP 329 U/L, GGT 266 U/L, total bilirubin 0.8 mg/dL, and HbA1c 8.9%. Metabolic, autoimmune, and infectious causes were excluded due to normal blood tests. Abdominal ultrasound and CT scan displayed no pathological findings. Transient elastography showed normal results (elasticity of 5.1 kPa, controlled attenuation parameter of 169 dB/m with a low median IQR). Due to persistent elevated liver enzymes a liver biopsy was conducted revealing lobular hepatocytes with ballooning, glycogenotic nuclei, minimal steatosis (<1%), and focal minimal granulocytic perisinusoidal inflammation, devoid of fibrosis, iron deposits, or hyaline globules, excluding the most common causes. Biochemical abnormalities were therefore associated with MODY5.
Conclusion: Maturity-onset diabetes of the young (MODY) is a common type of monogenic diabetes with an autosomal dominant inheritance that leads to defects in pancreatic islet cell development. MODY 5 is a subset that accounts for less than 5% of the cases, being caused by a mutation in hepatocyte nuclear factor 1 β (HNF1β) gene, which is a transcription factor expressed in various organs. Involved in the regulation of the expression of liver enzymes, when mutated may result in biochemical abnormalities. There are few reported cases of MODY liver-associated disease, so it should be included in the differential diagnosis of persistently abnormal liver enzymes, particularly in diabetic young patients^1,2.

References

1. Veerareddy S, Reddy S, Barreto M, Vedherey N, Gopalareddy VV. Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5). ACG Case Rep J. 2023 Oct 3;10(10):e01150.
2. Bala V, Anania FA. Increased liver enzyme levels and HNF-1beta gene mutation. Clin Gastroenterol Hepatol. 2008 Dec;6(12):A26.

Introduction

Inflammatory bowel disease (IBD) shows significant variations in clinical presentation, prevalence, and epidemiology across the world. We hypothesized that these differences might be, in part, due to regional variations in gut microbiomes. To test this, we examined gut microbiota of IBD patients and healthy controls in Northen part of India, and compared our findings to Dutch patients and population.

Aims & Methods

We collected stool samples and clinical metadata from 226 IBD patients (198 ulcerative colitis, 28 Crohn’s disease) and 66 controls in Northern India. Metagenomic shotgun sequencing was employed to assess gut microbiota diversity, composition, and function. Associations between microbiome profiles and IBD subtypes, along with clinical parameters like medication usage, drug response, and disease activity, were investigated. We compared our findings to a Dutch cohort comprising 436 IBD patients and 903 controls, using a consistent analytical approach. Finally, we used machine learning approaches to evaluate the generalizability of Indian IBD signals to the Dutch population.

Results

Indian IBD patients exhibited reduced microbiome diversity and alterations in beta diversity (FDR < 0.05, replicated in the Dutch cohort). We identified 319 taxa and 71 biochemical pathways significantly altered in Indian patients (FDR < 0.05), with 39% of these signals replicated in the Dutch cohort (at FDR < 0.05). Shared dysbiosis patterns across Indian and Dutch IBD patients included expansion of opportunistic pathogens (e.g., Clostridium, Streptococcus, Lactobacilli genera) and oral bacteria (e.g., Streptococcus oralis, Bifidobacterium dentium), alongside reduction in butyrate producers (e.g., Faecalibacteria, Roseburia hominis, Blautia massiliensis). Furthermore, we identified unique pathobionts specific to the Indian cohort, including Scardovia and Oribacterium genera, Actinomyces dentalis and Klebsiella pneumoniae. Machine learning models trained on the Indian cohort exhibited high predictive accuracy within the Indian test set (Sensitivity 0.84, Specificity 0.95) and demonstrated generalizability to the Dutch cohort (Sensitivity 0.77, Specificity 0.69). Additionally, we found associations between medication use and gut microbiota independent of disease activity: Tofacitinib usage (by 26 UC patients) correlated with decreased Lactobacilliales and increased Clostridia, while Prednisolone and Azathioprine usage associated with reduced Roseburia and increased Streptococcus and Granulicatella.

Conclusion

IBD patients from Northern India exhibit gut dysbiosis patterns similar to European patients, alongside enrichment in India-specific pathobionts. Microbiome-based diagnostic models show generalizability across populations, demonstrating the potential utility of microbiota-based approaches in IBD diagnosis and management across diverse populations.

Introduction

Faecal incontinence (FI) is prevalent, being associated with a high biopsychosocial burden and considerable health costs. The pathophysiology of FI is varied and often multifactorial, representing a diagnostic and therapeutic challenge. Anorectal manometry is the first recommended diagnostic method, although its utility is debatable due to overlapping findings between healthy individuals and patients.

Aims & Methods

The aim of this study is to establish a relationship between FI clinical presentation, manometric findings, and imaging.
We prospectively included all patients undergoing high-resolution anorectal manometry, according to the London protocol, at a tertiary centre, who agreed to respond to a questionnaire to characterize their FI, between August 2021 and March 2023. Clinical records were consulted, in order to access demographic data and past imaging reports. Statistical analysis was performed using IBM SPSS Statistics version 26®.

Results

Forty-seven patients were included with a mean age of 63.5±11.6 years, 87.2% women, of whom 73.2% had an obstetric history. Depressive/anxious symptoms were described in 59.6%, previous perineal surgery in 38.3%, and concomitant urinary incontinence in 40.0%. Mean FI duration was 5.4±5.2 years, with 51.1% reporting daily complaints and a bowel movement median of 2.0 (IQR 3.0). Males tended to have more bowel movements than females (3.5 (IQR 5.0) vs 2.0 (IQR 2.0); p-value 0.03). FI for flatus and faeces was present in 57.4%, for faeces alone in 34.0%, and for flatus alone in 8.5%. Urgency FI was verified in 37.0%, passive FI in 37.0%, and mixed FI in 26.1%. Mean Wexner score was 10±5. Rectal examination revealed hypotonicity in 15.9%. Mean resting pressure on anorectal manometry was 55.9±22.5 mmHg, dyssynergy was identified in 16.7% and altered balloon expulsion in 19.5%. The mean value of first sensation, first urge to defecate, and maximum tolerated volume were within the normal range. Imaging was performed in 19 patients (40.4%), with external anal sphincter injury in 15.8% and internal sphincter injury in 10.5%. Mean thickness of the internal anal sphincter (IAS) was 2.3±1.0 cm. Patients with hypotonicity in rectal examination had lower anal resting pressure (35.7±16.0 mmHg vs 60.3±22.4 mmHg; p-value 0.09) and lower IAS thickness (1.6±0.8 mm vs 2.6±0.9 mm; p-value 0.07), although not statistically significant. Patients with depressive/anxious symptoms showed lower maximum incremental pressure (56.6±34.0 mmHg vs 81.2±46.2 mmHg; p-value 0.045), as well as females when compared to males (60.0±34.9 mmHg vs 108.7±53.2 mmHg; p-value 0.005). No other statistically significant results were found, especially correlating clinical findings with manometry or imaging.

Conclusion

Our study showed, as previously replicated, that clinical, manometric and imaging findings have low correlation in the assessment of FI, reflecting its pathophysiological complexity.

Introduction

Oesophageal leaks and fistulae are a major complication of upper gastrointestinal surgery leading to high rates of postoperative morbidity and mortality. Self-expanding metal stents (SEMS) are the endoscopic mainstay of treatment. Recently, endoscopic vacuum therapy (EVT) as emerged as a promising alternative. The present study intends to evaluate the success rate and safety of EVT versus SEMS in upper gastrointestinal tract surgical leaks/fistulae in a referral centre.

Aims & Methods

We included all patients undergoing EVT in 2022-2023 (n=5) versus all patients submitted to SEMS from 2014 to 2022 (n=39) due to upper gastrointestinal tract surgical leak/fistulae.

Results

There were no statistically significant differences regarding distribution by gender, age, benign vs malignant disease, time from complication diagnosis to endoscopic treatment, time from surgery to endoscopic treatment and leak size (p>0.05).
The success rate, defined as complete closure of the surgical leak/fistulae, was reached in all patients submitted to EVT and in 56.4% of patients with SEMS (p=0.14). Two patients undergoing EVT were previously submitted to unsuccessful SEMS treatment. The median number of endoscopic treatment sessions were significantly superior for EVT [4 (IQR:3) vs 2 (IQR:1); p<0.01].
Technique related complications, readmission and mortality rates were superior in SEMS vs EVT (76.9% vs 0%; 51.3% vs 20%; 35.9% vs 0%, respectively), although these differences were only statistically significant for complication rate (p<0.01). None of the deaths were related to stent placement.

Conclusion

Although with a higher number of treatment sessions, our experience showed that EVT is a safe and effective alternative to endoscopic stenting, with higher success rate (100% vs 56.4%) and lower complication, readmission, and mortality rates. Our data shows that EVT has the potential to become the new gold standard in the endoscopic treatment of oesophageal leaks and fistulae.