Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

Microanatomical dissection; Mitochondrial disorders; MtDNA depletionDisección microanatómica; Trastornos mitocondriales; Agotamiento del ADNmtDissecció microanatòmica; Trastorns mitocondrials; Esgotament de l'ADNmtMitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.The work was supported by Ministero dell’Istruzione, dell’Università e della Ricerca-Dipartimenti eccellenti on the Project Personalized medicine. LC and VC are supported by the Italian Ministry of Health (Ricerca Corrente 2021 funding). RDG is supported by funds from the University of Ferrara

Evaluation of abdominal gas by plain abdominal radiographs

Abdominal CT imaging; Abdominal distension; Intestinal gasTAC abdominal; Distensión abdominal; Gas intestinalTAC abdominal; Distensió abdominal; Gas intestinalBackground Our aim was to determine the reliability of plain abdominal radiographs for the evaluation of abdominal gas content in patients with functional digestive symptoms. Methods Abdominal CT scan scout views, mimicking a conventional plain abdominal radiograph, were obtained from 30 patients both during episodes of abdominal distension and basal conditions. Physicians (n = 50) were instructed to rate the estimated volume of gas in the 60 images presented in random sequence using a scale graded from 0 to ≥600 ml. Key Results The gas volumes estimated in the scout views differed from those measured by CT by a median of 90 (95% CI 70–102) ml, and the misestimation was not related to the absolute volume in the image. The accuracy of the observers, measured by their mean misestimation, was not related to their specialty or the training status (misestimation by 96 (95% CI 85–104) ml in staff vs 78 (70–106) ml in residents; p = 0.297). The accuracy was independent of the order of presentation of the images. Gas volume measured by CT in the images obtained during episodes of abdominal distension differed by a median of 39 (95% CI 29–66) ml from those during basal conditions, and this difference was misestimated by a median of 107 (95% CI 94–119) ml. The accuracy of these estimations was not related to the absolute gas volumes (R = −0.352; p < 0.001) or the magnitude of the differences. Conclusions & Inferences Plain abdominal radiographs have limited value for the evaluation of abdominal gas volume in patients with functional gut disorders.This work was supported in part by the Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica, grant SAF 2016-76,648-R to F Azpiroz); Ciberehd is funded by the Instituto de Salud Carlos III. Dan M. Livovsky received support from the Israeli Medical Association and from Israeli Gastroenterological Association 2020 fellowship grants

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction

Constipation; Intestinal manometry; Intestinal neuropathyRestrenyiment; Manometria intestinal; Neuropatia intestinalEstreñimiento; Manometría intestinal; Neuropatía intestinalIntroduction Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. Methods Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. Results The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. Conclusion and Inference Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry.This work was supported by the Instituto de Salud Carlos III and co-financed by the European Union (FEDER/FSE) [PI17/01794]; Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica) [SAF 2016-76648-R]; Ciberehd is funded by the Instituto de Salud Carlos III. LA was supported by the Instituto de Salud Carlos III (CM20/00182)