Clinical Case Summary

A 75-year-old female presented with severe fatigue for the last four days, denying evident gastrointestinal blood losses. Physical examination was unremarkable, except for mucocutaneous pallor. Laboratory evaluation revealed iron deficiency anemia with Hb 9.2g/dL, iron 18 ug/dL, ferritin 7.6 mg/dL and transferrin saturation 3%. She also reported a six-month history of intermittent upper quadrant abdominal pain and vomiting under investigation in an outpatient clinic.
Past medical history was notable for atrial fibrillation under anticoagulation with apixaban and two episodes of presumed colonic diverticular bleeding. She had recent upper and lower gastrointestinal endoscopic exams, which were remarkable only for colonic diverticulosis.
To proceed with the iron deficiency anemia etiologic investigation, a small bowel capsule was request, however the exam was incomplete due to capsule retention in a segment with multiple diverticula with friable mucosa. Capsule expulsion was later confirmed by the patient.
Abdominal computed tomography revealed herniation of intestinal loops through the fossa of Waldeyer associated with partial mesenteric torsion without upstream dilation, which were compatible with a right paraduodenal internal hernia. Within these herniated jejunal loops several small bowel diverticula were noted, the largest measuring 28mm.
The diagnosis of right paraduodenal hernia with acquired jejunal diverticulosis was made. Although these two rare entities have been described separately, exceptionally they can present in association, with left-sided hernias being more frequently described. Furthermore, to the authors’ knowledge, this is the first reported case diagnosed by capsule endoscopy.
Since the patient remained asymptomatic with good hematologic response for oral iron supplementation, surveillance was decided with a low threshold for surgical repair of paraduodenal hernia in case of symptomatic recurrence or difficult to control iron deficiency anemia.

References

Goodney PP, Pindyck F. Paraduodenal hernia and jejunal diverticulosis. Journal of Gastroenterology and Hepatology. 2004;19(2):229–31
Krishnamurthy S, Kelly MM, Rohrmann CA, Schuffler MD. Jejunal diverticulosis. A heterogenous disorder caused by a variety of abnormalities of smooth muscle or myenteric plexus. Gastroenterology. 1983;85(3):538–47
Martin LC, Merkle EM, Thompson WM. Review of internal hernias: Radiographic and clinical findings. American Journal of Roentgenology. 2006;186(3):703–17.

Clinical Case Summary

Biliary injury secondary to trauma is frequently associated with long-term complications. Liver transplantation is rarely indicated but might be the best therapeutic option in severe or intractable cases. There is limited data regarding the use of liver transplantation for biliary trauma and criteria for liver transplantation in the setting of secondary biliary cirrhosis are not well established.
A 14-year-old male was evacuated to Portugal due to biliary injury after abdominal trauma, after failure of cholecystectomy. A Roux-en-Y hepaticojejunostomy was initially performed without immediate complications. Four years later he presented with obstructive jaundice (total bilirubin of 22 mg/dL), pruritus and physical signs of chronic liver disease. A magnetic resonance cholangiopancreatography showed an anastomotic stricture with marked dilation of the intrahepatic biliary tree. Endoscopic resolution of the stricture was not feasible. A percutaneous transhepatic biliary drainage was performed with immediate efficacy, but the procedure failed to resolve cholestasis, with subsequent referral to a liver transplantation center. Abdominal imaging revealed a cirrhotic liver and dilation of the biliary tract. At the age of 19 years old, an orthotopic liver transplant was performed. Piggy-back technique was used along with a continuous hepaticojejunostomy. Two years post-transplant the patient is asymptomatic and with a markedly improved quality of life.
Management of extrahepatic biliary tree injury can be extremely demanding. Even after clinically successful treatment, the quality of life may be impaired. Some complicated cases culminate in refractory and intractable stenosis of the hepaticojejunostomy with secondary biliary cirrhosis. Timely referral to a tertiary center is essential. Liver transplantation is the last line of treatment, but an earlier referral for this treatment may be needed in order to improve outcomes in severe, complicated or intractable cases.

References

- Thomas MN, Stippel DL. Management of bile duct injuries [Management von Gallengangsverletzungen]. Chirurg 2020;91(1):18-22;
- Krawczyk M, Grat M, Adam R, et al. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry. Transplantation 2016;100(11):2372-2381;
- Coccolini F, Kobayashi L, Kluger Y, et al. Duodeno-pancreatic and extrahepatic biliary tree trauma: WSES-AAST guidelines. World J Emerg Surg 2019;14:56;
- Schreuder AM, Busch OR, Besselink MG, et al. Long-Term Impact of Iatrogenic Bile Duct Injury. Dig Surg 2020;37(1):10–21;
- LeBedis CA, Bates DDB, Soto JA. Iatrogenic, blunt, and penetrating trauma to the biliary tract. Abdom Radiology 2017;42(1):28-45;
- Romine MM, White J. Role of Transplant in Biliary Disease. Surg Clin North Am. 2019;99(2):387-401;
- Pereira R, Vo T, Slater K. Extrahepatic bile duct injury in blunt trauma: A systematic review. J Trauma Acute Care Surg 2019;86(5):896-901.Coccolini F, Coimbra R, Ordonez C, et al. Liver trauma: WSES 2020 guidelines. World J Emerg Surg 2020;15(1):24.

Introduction

During endoscopic submucosal dissection (ESD) of colorectal neoplasms, an interesting feature is occasionally detected in which the muscle layer under the tumour seems to be pulled upwards into the lesion in a triangle-shape. This feature is named muscle retracting sign (MR sign) and appears to indicate a potentially difficult ESD with high risk of incomplete and non-curative resection, although data about this subject is still scarce, without current studies in western countries. The aim of this study was to evaluate whether or not MR sign is associated with worst outcomes.

Aims & Methods

A retrospective analysis, using a prospectively collected database from 2 western centres, including all patients who underwent ESD for colorectal neoplasms with positivity for MR sign from July 2017 to January 2023 was performed. The presence of MR sign was determined by the endoscopist during the procedure. The results were evaluated in terms of complete, en bloc, R0 and curative resection rates, complications and local recurrence.

Results

In a total of 411 lesions treated by ESD, 26 presented MR sign (6.3%, mean size 62,3mm, range 20-180mm): 9 colonic and 17 rectal, corresponding to 26 patients (male 61.5%, mean age 70 years): 9 in colon and 17 in rectum. Morphologically and according to Paris classification, 13 were 0-Is (50%), 10 LST-G-M (38.5%), 1 0-Isp, 1 LST-G-N and 1 LST-NG-F. Technical success was achieved in 24 lesions (24/26, 92.3%) with 2 procedures aborted due to the perception of high perforation risk, both located in the colon (2/9, 22%). In the rectum, there was the need to perform intramuscular dissection in 3 procedures to complete the resection (3/17, 17.6%). Among resected lesions, en bloc and R0 resection rates were 100% and 66.7% (16/24). According to ESGE 2022 criteria, resection was considered curative in 66.7% (16/24), non-curative with high risk in 8.3% (2/24) and with local-risk recurrence in 25% (6/24). Intraprocedure complications were recorded in 2 resections (8%), both in the rectum and both perforations endoscopically managed. No recurrence was recorded in a mean follow-up time of 7 months (range 1-22 months).

Conclusion

This analysis show that MR sign is mostly present in large bulky protruding lesions and seems associated with a higher incomplete resection procedure rate in colon lesions but in rectum. Also, it seems associated with higher complication rate, namely perforations, and non-curative resection rates among resected lesions. Therefore, in the colon, an anticipated switch for surgery in clinically fit patients should be considered in the presence of this sign or even before initiating ESD when lesion morphology suggests its presence. To the authors’ best knowledge, this is the first study of the impact of the present of MRS in ESD in the West.

References

Toyonaga T, Tanaka S, Man-I M, East J, Ono W, Nishino E, et al. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection. Endosc Int Open. 2015;3(03):E246–51.
Suzuki N, Dhillon A, Seward E, Humphries A. CLIP MUSCLE PROTECTION (CLIMP) METHOD IN MUSCLE-RETRACTING SIGN DURING COLONIC ENDOSCOPIC SUBMUCOSAL DISSECTION. Gut. 2021;70(Suppl 1):A1–A262.

Disclosure

Toyonaga T, Tanaka S, Man-I M, East J, Ono W, Nishino E, et al. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection. Endosc Int Open. 2015;3(03):E246–51.

Introduction

Congenital Diarrhea and Enteropathies (CODEs) pose significant challenge for diagnosis and management. Genetic sequencing for children with CODEs has important implication in early diagnosis.

Aims & Methods

Among children with chronic diarrhea those suspected to have CODEs clinically and endoscopically during the period of March 2023 to Feb 2024 were included.
Clinical profile, endoscopic, histological and genetic analysis were studied in all children with suspected CODES.

Results

Total 15(n=15) cases were included. Overall male preponderance 80%(n=12) was noted. Age at onset ranged from 2days of life to 15months with mean age of 4months. Of them, 10(66%) children had watery diarrhea, 4(26%) children had bloody diarrhea and 1(6.6%) child had fatty diarrhea.
Endoscopic and histological yield in CODES children were found in 40%(n=4) and 30%(n=3) respectively in children with watery diarrhea, and in all children with fatty or bloody diarrhea.
Out of 10 children with watery diarrhea two children had syndromic facies, woolly hair and café-u-lait spots were diagnosed as Syndromic Diarrhea-Trichohepaticoenetric Syndrome(THES). 3 of them had protein losing enteropathy(PLE) with two among 3 showing normal endoscopy and biopsy,finally turned out to be enterokinase deficiency, while one child with endoscopically viewed whitish speckled mucosa with patchy vacuolated surface on histology had DGAT 1 mutation. Two children with watery diarrhoea had microvillous atrophy(MYO5B) and one with severe watery diarrhea had NEUROG3 mutation. Glucose galactose malabsorption (GGM), and Congenital Tufting Enteropathy (CTE) were seen in other two children. Among children with bloody diarrhea, two had proctocolitis on histology confirming Very Early Onset Inflammatory Bowel Disease(VEO-IBD) with genetic mutation showing CARMIL 2 and RIPK1 mutation. Two children with bloody diarrhoea suspected to have IBD had chronic colitis with thrombotic complications suggesting CD55 deficiency with Hyperactivation of complement, Angiopathic thrombosis, and PLE (CHAPLE syndrome). child with fatty diarrhoea with endoscopic findings suggestive of intestinal lymphangiectasia and histology of duodenal biopsy showing lipid droplets was clinically and genetically diagnosed Abetalipoproteinemia and started on fat free diet with MCT oil and vitamin A,D,E,K supplements. Genomic analysis are the final stand of diagnosing CODES due to the overlap of the clinical phenotypes and lack of appropriate biomarkers.Genetic Analysis had 100% yield when CODES were suspected. Overall mortality rate was 26%(n=4) in 1year follow-up in our study group.

Conclusion

Single gene disorders are common among CODEs patients. Early Genetic testing helps in accurate diagnosis and initiating appropriate therapy as endoscopy and histology has poor yield.

References

•Lee, Kun Song et al. “How to do in persistent diarrhea of children?: concepts and treatments of chronic diarrhea.” Pediatric gastroenterology, hepatology & nutrition vol. 15,4 (2012): 229-36. doi:10.5223/pghn.2012.15.4.229
•Thiagarajah, Jay R et al. “Advances in Evaluation of Chronic Diarrhea in Infants.” Gastroenterology vol. 154,8 (2018): 2045-2059.e6. doi:10.1053/j.gastro.2018.03.067
•Bourgeois, P., Esteve, C., Chaix, C., Beroud, C., Levy, N., THES Clinical Consortium, Fabre, A., Badens, C. Tricho-hepato-enteric syndrome mutation update: mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects. Hum. Mutat. 39: 774-789, 2018

Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.

Aims & Methods

We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described¹ cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status², use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.

Results

There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.

Conclusion

This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.

References

¹ Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
² https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio

Disclosure

An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.

Introduction

Therapeutic goals and clinical guidelines in Crohn’s disease (CD) have evolved to include endoscopic outcomes being a key prognostic parameter in disease management. STRIDE-II guidelines comprise of clinical and patient-reported outcome remission, along with biomarker normalization and endoscopic healing. While available publications have correlated achievement of endoscopic response with long-term outcomes, few if any have adjusted for clinical remission status. Moreover, most of the data comes from patients treated with immunomodulators and/or TNFs. The objective of this analysis was to assess the impact of endoscopic response at the end of maintenance and long-term outcomes while adjusting for clinical remission status at maintenance.

Aims & Methods

Data from two randomized clinical trials (GALAXI-1, NCT03466411 and IM-UNITI, NCT01369355) were pooled to assess the impact of endoscopic response at 1 year on long-term patient relevant outcomes including clinical response, clinical remission, quality of life as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), and risk for hospitalizations/surgeries. This post-hoc analysis assessed endoscopic response at the end of maintenance (~48 weeks) and patient relevant outcomes in the long-term extension (LTE) duration (~96 weeks). Patients without LTE outcome data and placebo treated patients were excluded. Multivariate analyses with trial as a random effect were conducted and adjusted for treatment arm during maintenance, clinical remission status at end of maintenance (EOM), and endoscopic response at EOM.

Results

A total of 461 patients had available endoscopy and clinical remission status at EOM (IM-UNITI, N=177; GALAXI-1, N=284). The number of patients with available LTE outcomes ranged from 290 (IBDQ remission) to 383 (clinical remission/clinical response). Endoscopic response at EOM was significantly associated with higher odds of LTE clinical remission and IBDQ remission with ORs of 1.91 and 1.99 respectively, with corresponding p values below 0.05. Endoscopic response at EOM was also associated with lower odds of LTE C-reactive Protein abnormality (OR=0.46, p<0.005), a marker of inflammation and disease activity. Lastly, a greater percentage of patients without endoscopic response at EOM experienced hospitalizations/surgeries though the difference was not significant due to low event counts (16% versus 9%, p=0.1237).

Conclusion

This analysis uses clinical data from robust trials and adjusted for patients’ clinical remission status at the end of maintenance to isolate the benefit of endoscopic response in predicting long-term outcomes. Endoscopic response is significantly associated with more patients reaching clinical remission and better quality of life. Further investigation in large datasets with longer follow-up is needed to better understand whether measures of endoscopic improvement are also good surrogates for reductions in hospitalizations and surgeries.

Disclosure

Janssen Global Services provided funding for this research and I am an employee of Janssen