Introduction

Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD) with significant morbidity and mortality¹. Its pathogenesis and risk factors still need to be completely elucidated. Because of intestinal malabsorption, enteric hyperoxaluria is a critical pathogenic mechanism responsible for the development of NL in IBD patients². Growing evidence has highlighted the association between gut microbiota and NL, particularly emphasising the role of some oxalate-degrading bacteria, such as Oxalobacter formigenes, representing the mainstay of the so-called “gut-kidney axis”³. More recent studies also hypothesize the involvement of urinary microbiota⁴, but no data on IBD patients are currently available. Thus, our study aims to analyse the urinary lithogenic profile in IBD patients and its relationship with gut and urinary microbiota.

Aims & Methods

Consecutive adult patients with IBD were prospectively enrolled. The presence of ileoanal pouch, ileostomy, colostomy or short-bowel syndrome were exclusion criteria. Demographic and clinical data, including previous episodes of NL, were collected. Disease activity was evaluated using Harvey-Bradshaw index for Crohn’s disease (CD) and Mayo score for ulcerative colitis (UC). All patients underwent abdominal ultrasound for NL detection. Blood tests of kidney function (notably creatinine, blood urea nitrogen, creatinine clearance, and electrolytes) were also measured, together with a 24h-urine collection for lithogenic profile analysis, including calcium oxalate relative saturation ratio (RSRCaOx). In a subgroup of patients, urinary and faecal microbiota were also analysed through 16S rRNA sequencing.

Results

48 patients (52.1% men, mean age 42.6±17.4 years) were enrolled. Twenty-five patients were affected by CD and 23 by UC and 10 presented active disease at enrollement. NL was more frequent in CD than in UC (32% vs. 13%). In CD, 24-h urinary volume was lower and 24-h oxaluria was higher than in UC. Moreover, 24-h oxaluria was higher in patients with previous or present NL. Gut microbiota analysis was performed on 22 patients, stratified based on median RSRCaOx (higher or lower than the median). Significantly different β-diversity was observed between the two groups (p =0.025) and patients with an elevated RSRCaOx showed a higher relative abundance of Bacteroidetes and a lower abundance of Firmicutes (p value <0.05). No statistically significant difference was found in urinary microbiota composition between patients with high or low levels of RSRCaOx.

Conclusion

NL is more common in CD patients, who generally present lower urine volume and higher 24-h oxaluria than UC patients. Furthermore, NL is more frequent in IBD patients with higher oxaluria levels, confirming oxalate excretion's crucial role in NL pathogenesis. Again, our study reports an association between urinary stone development and Firmicutes/Bacteroidetes imbalance in the gut microbiota, suggesting possible further studies to identify patients at higher risk of NL.

References

1. Varda BK, McNabb-Baltar J, Sood A, et al. Urolithiasis and urinary tract infection among patients with inflammatory bowel disease: a review of US emergency department visits between 2006 and 2009. Urology. 2015;85(4):764-770. doi:10.1016/j.urology.2014.12.011
2. Witting C, Langman CB, Assimos D, et al. Pathophysiology and Treatment of Enteric Hyperoxaluria. Clin J Am Soc Nephrol. 2021;16(3):487-495. doi:10.2215/CJN.08000520
3. Ticinesi A, Milani C, Guerra A, et al. Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut. 2018;67(12):2097-2106. doi:10.1136/gutjnl-2017-315734
4. Xie J, Huang JS, Huang XJ, et al. Profiling the urinary microbiome in men with calcium-based kidney stones. BMC Microbiol. 2020;20(1):41. doi:10.1186/s12866-020-01734-6

Introduction

Gastro-esophageal reflux disease (GERD) is a multifactorial disease that manifests in patients with different degrees of anti-reflux barrier impairment. GERD significantly impacts quality of life despite the fact that symptom burden may not always correlate with disease severity. Precise pathophysiologic evaluation can identify patients with actionable GERD who may benefit from anti-reflux surgery or escalation of medical therapy. The Milan Score, a novel high-resolution manometry (HRM) metric, numerically quantifies the degree of anti-reflux barrier disruption¹. While the Milan Score has been proven to predict pathologic GERD, its ability to distinguish non-severe from severe GERD and to identify patients with a higher grade of anti-reflux barrier disruption requires further study.

Aims & Methods

A database of prospectively collected data from a cohort of patients undergoing HRM and pH-study for persistent GERD symptoms was queried. Using Lyon 2.0 consensus, pathologic GERD was defined as AET >6%, grade B-C-D esophagitis or Barrett’s esophagus on endoscopy. Severe reflux was defined as AET >12%, DeMeester score >50, grade C-D esophagitis or Barrett’s esophagus². Demographic, HRM and pH data were extracted, classified and compared between groups with varying GERD severity (no GERD, non-severe GERD, severe GERD). The Milan Score integrates the main manometric parameters related with the pathophysiology of GERD (ineffective esophageal motility, esophago-gastric junction (EGJ) contractile integral, EGJ morphology and straight leg raise maneuver response). In order to simplify the use of the Milan Score, risk rates have been classified into six categories, from extremely unlikely to extremely likely. A cumulative odds ordinal logistic regression was run to determine the independent effect of HRM variables on reflux severity. The ability of the Milan Score to predict severe reflux was assessed, as well as its association with the pH-study criteria proposed by Lyon 2.0 as adjunctive evidence for pathologic GERD (>80 reflux episodes, mean nocturnal baseline impedance (MNBI) <1500 W or positive reflux-symptom association).

Results

Among 603 patients enrolled (median age 49.9 years, median body mass index (BMI) 25.3 Kg/m², 50.5% males), 124 (20.6%) had non-severe and 142 (23.5%) had severe GERD. Non-severe and severe GERD patients had similar demographic and clinical characteristics, but were significantly different from the no-GERD group (Table). On univariate analysis, presence and size of hiatal hernia, Milan Score and Milan Score categories were significantly different among the groups (p <0.001). On ordinal logistic regression, hiatal hernia size and Milan Score category were found to be independent predictors of GERD severity (OR 1.28, 95% CI, 1.04-1.57, p=0.018 and OR 2.92, 95% CI, 2.47-4.45, p=<0.001 respectively). A significantly higher Milan Score (p <0.001) was found in patients with >80 reflux episodes, MNBI <1500 W, positive reflux-symptom association and any criteria of severe GERD.

Conclusion

Hiatal hernia size and Milan Score assessed at HRM are independent factors associated with severe GERD. The Milan Score is significantly higher in patients with pathologic adjunctive pH-impedance metrics and in patients with severe GERD.

References

1. Siboni S, Sozzi M, Kristo I et al. The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease. United European Gastroenterol J. 2024 Mar 27. doi: 10.1002/ueg2.12565. Epub ahead of print. PMID: 38536701.
2. Horvath KD, Jobe BA, Herron DM et al. Laparoscopic Toupet fundoplication is an inadequate procedure for patients with severe reflux disease. J Gastrointest Surg. 1999 Nov-Dec;3(6):583-91. doi: 10.1016/s1091-255x(99)80079-1. PMID: 10554364.

Clinical Case Summary

Amyloidosis is a systemic disease that results from the extracellular accumulation of a pathological protein - amyloid, which can be present with its light chain associated protein (AL) ^[1]. AL amyloidosis can be presented with two insoluble fibrils - the light chain immunoglobulin κ or λ. Acute liver failure with liver amyloidosis is reported extremely rarely ^[2]. Usually the symptoms of liver involvement are mild, but in rare cases acute liver failure can be noted. The characteristic clinical presentation of liver involvement is hepatomegaly, cholestasis, and jaundice ^[3].
We present a case of a 57 years old male patient admitted to Mikaelyan University Hospital, Yerevan, Armenia with jaundice, weakness, bloating and dyspnea. His past medical history is notable for bladder cancer, without distant metastasis. Upon admission, his ALP level was 722 U/L, GGT 779 U/L, ALT 37 U/L, AST 151 U/L, total bilirubin 229 umol/L, INR 2.17. Viral hepatitis serological markers were negative. Contrast computer tomography (figure 1) unveiled portal hypertension, ascites and hepatosplenomegaly with liver craniocaudal size 23 cm. A decision was made to perform a liver biopsy, which was complicated with bleeding. The liver histology(figure 2) showed positive Congo red staining and the к chain of AL amyloid was predominant to the λ chain. There was 0.25 g/L proteinuria. Serum and urine paraproteinemia tests were negative. An electrocardiogram revealed decreased voltage in all leads. Because of deteriorating condition, the patient was transferred to intensive care unit (ICU) where liver enzyme levels continued to rise, creatinine level was 430 umol/L, 24 h urine was 150 ml, total Ca level 2.9 mmol/L. Patient died 13 days after admission to the hospital.
This unusual case emphasizes that hematological diseases, like amyloidosis play an important role in liver injury, fibrosis and should be included in differential diagnosis of liver pathology.

References

1. Ueno H, Douhara A, Osaki Y, Koizumi A, Yorioka N, Ueda S, Tsutsumi M, Yoshiji H. Liver Biopsy-confirmed Primary Hepatic Amyloidosis with Only Jaundice As the Initial Symptom: An Autopsy Case Report. Intern Med. 2022 Oct 1;61(19):2877-2881. doi: 10.2169/internalmedicine.9189-21. Epub 2022 Feb 26. PMID: 35228432; PMCID: PMC9593147.
2. Kim HJ, Tomaszewski M, Lam EC, Xiong W, Moosavi S. Amyloidosis: A Rare Cause of Severe Cholestasis and Acute Liver Failure. ACG Case Rep J. 2020 Dec 4;7(12):e00479. doi: 10.14309/crj.0000000000000479. PMID: 34604435; PMCID: PMC8483873.
3. Premkumar M, Rangegowda D, Vyas T, Kulkarni A, Grover S, Mahiwall R, Sarin SK. Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure. ACG Case Rep J. 2017 Feb 15;4:e22. doi: 10.14309/crj.2017.22. PMID: 28286788; PMCID: PMC5340654.

Figure 1- CT scan of patients abdomen.
Figure 2- Liver biopsy, Congo red positive.

Introduction

EUS-guided portal pressure gradient measurement (EUS-PPGm) would be a useful procedure in patients with liver diseases (1). However, there is scarcely data on the clinical relevance of this EUS-guided procedure.

Aims & Methods

We report our experience on EUS-PPGm focus on safety, clinical relevant findings, technical drawbacks and how to overcome them.
We used a therapeutic echoendoscope and a 25G dedicated needle as previously reported (1, 2). To minimize the risk of infection, periprocedural antibiotherapy was administered and the working channel of the echoendoscope was flushed with povidone-iodine.

Results

EUS-PPGm was performed in 30 patients, median age 42±3 yo. Indications: assessment of NAFLD, 25 patients; idiopathic portal hypertension, 3 patients; evaluation for curative therapy in hepatocellular carcinoma (HCC), 2 patients. Anticoagulants were withdrawn in 4 patients. EUS-guided bilobar liver biopsies (EUS-BLB) were also immediately performed in 26 patients (87%) with a 19G needle. EUS-PPGm was successfully obtained in 25/30 patients (83%). EUS-PPGm was >5 mmHg in 14/25 cases (56%). In idiopathic portal hypertension 3/3 patients. In NAFLD 10/22 patients (45%) without endoscopic and/or ultrasonographic signs of portal hypertension and without liver fibrosis on EUS-BLB. Mean time to obtain EUS-PPGm was 21±2 minutes. Mean time for EUS-PPGm plus EUS-BLB was 45±2 minutes. Idiopathic portal hypertension was assessed by this procedure with the complementary information given by the EUS-BLB. In the 2 patients with HCC, one patient did not have reliable results and, in the other, EUS-PPGm was useful ruling out portal hypertension and the patient was referred to curative surgery that was successfully carried out.
Technical drawbacks: In 5 cases (17%) EUS-PPGm was not obtained due to non-reliable measurements in 4 cases probably due to excesive use of the elevator and up&down wheel of the echoendoscope and bending of the needle, that would be avoided. In the fifth case the EUS-PPGm was not performed for exacerbating breathing movements that precluded the procedure for safety concerns. We experienced difficulty in punctioning the hepatic and the portal vein in one and two cases, respectively, having to transverse these vessels and repositioning the needle in the lumen of these veins. In one case the 25G needle passed in close proximity to the hepatic artery. We think dedicated 25G needles have more flexibility and penetrability than larger caliber needles and, probably could lead for a safer and easier procedure and could be more accurate in the puncture of narrow vessels in liver cirrhosis (3).
Adverse events: A self-limited bleeding from the cardias was immediately observed after one EUS-PPGm in a patient with idiopathic portal hypertension. One mild epigastric pain 2 day after a combined procedure was observed. No other adverse events were registered one month later.

Conclusion

EUS-guided PPGm, even when combined with EUS-BLB, seems safe providing useful clinical information. Almost half of patients affected with NAFLD have portal hypertension diagnosed precociously in reversible stages providing a useful tool in precision Medicine, especially in the setting of obesity pandemic. Idiopathic portal hypertension was confirmed by this procedure with the complementary information provided by the EUS-BLB. In the patient with HCC, EUS-PPGm rule out portal hypertension and allowed for curative surgery. There are technical aspects related to the needle and the position of the echoendoscope that could be useful to know to improve the safety and accuracy of this procedure.

References

(1) Samarasena J, Chang KJ. Endo-hepatology: A new paradigm. Endosc Ultrasound. 72018. p. 219-22.
(2) Hashimoto R, Chang KJ. Endoscopic ultrasound guided hepatic interventions. Dig Endosc. 2021;33(1):54-65.
(3) Romero-Castro, R; Carmona-Soria, I; Jimenez-Garcia, VA; et al. Endoscopic ultrasound-guided portal pressure gradient measurement: Improving its safety overcoming technical drawbacks. Endoscopy (In press).

Disclosure

Rafael Romero-Castro is consultant to Cook Medical since February, 28th, 2023.

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce weight loss, and have been associated with an overall decreased risk of esophageal cancer. Obesity is strongly associated with esophageal adenocarcinoma and substantial weight loss may decrease the risk of this malignancy, whereas weight loss does not decrease the risk of esophageal squamous cell carcinoma. We examined the hypotheses that GLP-1RA treatment decreases the risk of esophageal adenocarcinoma.

Aims & Methods

This population-based case-control study included all cases of esophageal adenocarcinoma and esophageal squamous cell carcinoma in adults who had dispensed medication for type 2 diabetes in Denmark (2007-2020), Finland (2011-2018), Iceland (2009-2019), Norway (2007-2019), or Sweden (2007-2020). For each case participant, >10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from well-validated nationwide health-data registries with prospectively collected data. Multivariable logistic regression provided odds ratios (OR) for esophageal adenocarcinoma and esophageal squamous cell carcinoma with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, obesity, alcohol overconsumption, and tobacco smoking.

Results

This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with non-users (adjusted OR 1.3, 95% CI 1.1-1.5). However, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8).

Conclusion

Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. Confounding by indication may have been the most important, or even the sole, contributor to the decreased risk of esophageal squamous cell carcinoma observed, although anticarcinogenic mechanisms of GLP-1RAs other than weight loss cannot be ruled out.

Clinical Case Summary

Intestinal pseudo-obstruction (IPO) represents an unclarified dysmotility disorder featured by clinic-radiological signs of intestinal obstruction not associated with a well-identifiable organic gastroenterological disease. IPO may occur as a rare complication of autoimmune connectivopathies, including Systemic Lupus Erythematosus (SLE).
We present an SLE-affected 44-year-old man with a history of recurring nonspecific abdominal prokinetics not-responder sub-obstructive episodes.
The patient was admitted to our department for constipation, vomiting, and unintentional weight loss. Clinical examination revealed a family history of eosinophilic gastroenteritis (EG). SLE, diagnosed 5 years before with the onset of LSE-related hepatitis controlled by immunosuppressive therapy (prednisone 0.5 mg/kg/die/4 weeks; prednisone tapering + azathioprine 1 mg/kg/die/12 weeks). Except for LSE serology and malnutrition parameters, laboratory tests, including Systemic Sclerosis screening, presented no significant alterations. Radiologically, X-ray highlighted multiple air-fluid levels; contrast-enhanced CT showed fluid surrounding dilated loops, and fluid-filled ileal loops, without evidence of organic intrinsic/ab-extrinsic obstruction, perforation, or extraluminal gas.
In light of these findings, stenosing-pattern Crohn's disease (CD) and strictures-complicated EG were mainly suspected. Therefore, we confidently performed a colonoscopy with the histological examination resulting inconclusive for CD and EG. He was managed conservatively with nasogastric decompression, immunosuppressive therapy, and parenteral nutrition. Unfortunately, two weeks after, the worsening symptoms required a lifesaving right hemicolectomy with an ileostomy. Surgical histology showed an SLE fibro-inflammatory pattern, not-sparing the enteric plexus, suggestive of IPO.
IPO should be suspected in SLE patients presenting treated-unresponsive GI symptoms. Its early recognition is prognostically crucial.

References

• Downes TJ, Cheruvu MS, Karunaratne TB, De Giorgio R, Farmer AD. Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction. J Clin Gastroenterol. 2018 Jul;52(6):477-489. doi: 10.1097/MCG.0000000000001047. PMID: 29877952.
• Ohri AJ, Shah CG, Udani AH. Intestinal Pseudo-Obstruction - An Under-Recognized Presentation of Systemic Lupus Erythematosus. Indian J Nephrol. 2022 Sep-Oct;32(5):476-479. doi: 10.4103/ijn.IJN_494_20. Epub 2022 Aug 8. PMID: 36568587; PMCID: PMC9775609.
• Mok MY, Wong RW, Lau CS. Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation. Lupus. 2000;9(1):11-8. doi: 10.1177/096120330000900104. PMID: 10713642.