Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study.

BACKGROUND: Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis. METHODS: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects. RESULTS: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted. CONCLUSION: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies. TRIAL NUMBER: NCT04243681.

Diagnosis of Hirschsprung's disease in children: Preliminary evaluation of a novel endoscopic technique for rectal biopsy.

BACKGROUND AND AIM: The diagnosis of Hirschsprung's disease (HD) relies on anorectal manometry and rectal biopsy. The role of endoscopic biopsy is uncertain for the diagnosis of HD in children. In this study, we evaluated the adequacy of biopsies procured by endoscopic mucosal resection (EMR) for the diagnosis of HD. METHODS: Consecutive children with suspected HD from January 2013 to January 2018 were enrolled in the study. EMR was performed using the standard band ligation device at a distance of about 3 cm from dentate line in rectum. All samples were assessed macroscopically and microscopically. An adequate sample was defined as those measuring >3 mm and including adequate submucosa. RESULTS: A total of 132 children underwent evaluation for constipation in the study period. Of these, 10 children (median age, 4.25 years) underwent EMR using the band ligation device for the evaluation of HD. EMR was performed with and without submucosal lifting injection in four and six children, respectively. All the samples were adequate macroscopically (>3 mm). Absence of ganglion cells was noted in six children. Of these, three children underwent full-thickness rectal biopsy followed by surgery. Three children did not undergo surgery. Ganglion cells were identified in four children, thereby excluding the diagnosis of HD. CONCLUSION: Rectal biopsy using EMR with a band ligation device is feasible, safe, and provides adequate sample for the evaluation of HD in children.