Introduction

Loop ileostomy has been reported to reduce the risk of leakage and reoperation in patients undergoing sphincter-preserving surgery. The structural and functional changes in the loop ileostomy may contribute to the development of ileus, such as decreased motility of smooth muscle and villous atrophy.

Aims & Methods

This study is to investigate the morphological, functional, and molecular changes of the distal limb after ileostomy and subsequent takedown.
Human ileum samples were obtained from patients who underwent diversion ileostomy after rectal cancer surgery and subsequently had ileostomy takedown. Samples were collected from the tips of the proximal and distal limbs. The whole layer of ileum was prepared for HE staining and the muscle layer which the mucosal layer was removed was prepared for motility measurement. The muscle strips (5x2 mm) were mounted to an isometric force transducer (Biopac Systems, Inc., Goleta, CA, USA) and suspended in 10 ml organ bath containing aerated (97% O₂ and 3% CO₂) and pre-warmed (36.5 ± 0.5°C) KRB solution. Amplitude (mN) and area under the curve (AUC) of contractions were measured and analyzed. To compare myogenic contraction and relaxation between the proximal and distal limbs of ileostomy, we administrated acetylcholine (ACh), potassium chloride (KCl) and sodium nitroprusside (SNP) in human ileal strips. Quantitative real-time polymerase chain reaction (qPCR) was performed for quantitative analysis of the expression of VAChT and NOS, cholinergic and nitrergic neuronal markers, and UCHL1 and MYH11, neuronal and smooth muscle cell marker, respectively.

Results

The height of the villi and the thickness of the mucosa, submucosa and muscle layer of the distal limb decreased significantly compared to those of the proximal limb. In the contractile responses to ACh and KCl, the amplitude and AUC of contractions in the distal limb were smaller than in the proximal limb in a dose-dependent manner. The relaxation response to the SNP in the distal limb was reduced compared to the proximal limb. Expressions of VAChT which is related with cholinergic neurotransmission, UCHL1 and MYH11 were not different in both proximal and distal limbs. However, expression of NOS1 which is related with nitrergic neurotransmission was increased significantly in the distal limb compared to the proximal limb. In addition, number of interstitial cells (ICC and PDGFRa⁺ cell) in muscle layer was not different in both proximal and distal limbs.

Conclusion

These results demonstrate that the distal limb which was not in use for a certain period of time after fecal diversion was morphologically atrophied and its motility was also impaired. Both myogenic contractile and relaxation responses were reduced in the distal limb of ileostomy although nitrergic neurons increased in the distal limb to compensate for the reduced relaxation response. These findings suggest that stimulating the distal limb can induce relaxation and may be a way to prevent ileus, which can occur after ileostomy takedown.

Introduction

Hemorrhoidal disease affects 2-7% of patients with inflammatory bowel disease (IBD) (1,2), but treatment recommendations are limited due to apparent higher morbidity in this subset of patients (3,4). Currently, there is limited data about hemorrhoidal disease treatment in IBD, there is even less information regarding non-surgical treatment.

Aims & Methods

The authors aim to evaluate the safety and efficacy of office-based procedures in hemorrhoidal disease in patients with IBD. This is a retrospective and Portuguese multicenter study (7 centers) that included patients with IBD who underwent office-based procedures for hemorrhoidal disease between July 2013 and July 2021. Data relating to IBD and hemorrhoidal disease were analyzed namely success, relapse, and complications. Success was defined as a significant improvement in symptoms after office-based procedures, without the need for additional treatment. Relapse was defined as a worsening of symptoms, requiring new office-based procedures/surgery.

Results

129 patients were included, 70% with ulcerative colitis; in Crohn's disease, 5.4% had a history of perianal disease. Only 62% of patients had endoscopic remission and 18% were on biologics. Regarding Goligher's classification, the majority had grade II (48%). 77 patients underwent rubber band ligation (RBL), 44 patients underwent polidocanol injection and 8 patients underwent both techniques, in a total of 304 procedures (median of 2(2) sessions/patient). The treatment was effective in 88% of patients, of which 14% relapsed, with an average follow-up time of 55.3±34.5 months. Of 304 procedures, 17 (5.6%) procedures were complicated, in a total of 16 patients (12.4%), 2 (0.65%) required invasive treatment, without cases of pelvic sepsis. Success, relapse, and complications were not associated with IBD (type, medication, or remission at the time of treatment) (p>0.05). Success was greater in patients with Goligher grades I and II (p=0.037). Complications were higher in patients undergoing RBL (p=0.030) and in patients with Goligher grade III (p=0.031).

Conclusion

This is the first study about office-based procedures for hemorrhoidal disease in IBD, showing similar efficacy to the general population, with a low rate of complications, and should therefore be recommended in these patients.

References

1. Eglinton TW, Barclay ML, Gearry RB, Frizelle FA. The spectrum of perianal Crohn's disease in a population-based cohort. Dis Colon Rectum. 2012 Jul;55(7):773-7.
2. Choi YS, Kim DS, Lee DH, Lee JB, Lee EJ, Lee SD, et al. Clinical Characteristics and Incidence of Perianal Diseases in Patients With Ulcerative Colitis. Ann Coloproctol. 2018 Jun;34(3):138-143.
3. Jeffery PJ, Parks AG, Ritchie JK. Treatment of haemorrhoids in patients with inflammatory bowel disease. Lancet. 1977 May 21;1(8021):1084-5.
4. D'Ugo S, Franceschilli L, Cadeddu F, Leccesi L, Blanco Gdel V, Calabrese E, et al. Medical and surgical treatment of haemorrhoids and anal fissure in Crohn's disease: a critical appraisal. BMC Gastroenterol. 2013 Mar 11;13:47

Introduction

Chronic constipation (CC) is a prodromal and severe symptom in up to the 80% of Parkinson's disease (PD) patients (PD/CC) often refractory to standard laxative treatments. The molecular mechanisms underlying PD/CC are still unclear, although changes of enteric nervous system and intestinal epithelial barrier (IEB) have been thought to play a pathogenetic role.

Aims & Methods

In this study, PD/CC and chronic constipated (CCs) patients were functionally characterized, and possible abnormalities to IEB and the key neuromodulator vasoactive intestinal polypeptide (VIP) were investigated. N=12 PD/CCs (2 females; age range: 51-80 yrs), 20 CCs (15 females; 27-78; yrs) and 23 controls (Ctrls; 11 females; 32-74yrs) were enrolled. PD was diagnosed according to the United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria, whereas CC was established following Rome IV criteria. Ctrls were otherwise asymptomatic subjects undergoing screening colonoscopy. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colonic mucosal / submucosal biopsies were obtained in all patients / subjects and tested for gene, protein expression and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1) and zonula occludens-1 (ZO-1) and VIP, by RT-qPCR, immunoblot and immunofluorescence staining.

Results

PD/CCs were clustered in two groups: a) patients with delayed TT and altered AM (60%); b) those with altered AM only (13%). The evaluation of IEB markers on mucosal specimens showed an increase of CLDN4 mRNA in PD/CCs (1.26 ± 0.26) vs. Ctrls (1.00 ± 0.19) and CCs (0.95 ± 0.33), whereas a trend to CLDN4 protein reduction in PD/CCs (0.88 ± 0.33) vs. Ctrls (0.96 ± 0.25) and CCs (1.02 ± 0.51) was observed. Moreover, the OCCL-1 transcript was significantly increased in PD/CCs (1.36 ± 0.36) vs. Ctrls (1.05 ± 0.33) and CCs (0.81 ± 0.18). ZO-1 mRNA relative levels were consistent with those of OCCL-1 showing a significant increase in PD/CCs (1.35 ± 0.38) vs. Ctrls (1.02± 0.27) and CCs (0.85 ± 0.24). Notably, both OCCL-1 and ZO-1 showed a tendency to be reduced in CCs vs. Ctrls. Immunofluorescence highlighted a decrease in OCCL-1 immunoreactivity (IR) in PD/CCs (score= 1.5) vs. CCs and Ctrls (score= 4). Conversely, ZO-1-IR displayed an intense pattern (score=4) in both Ctrls and PD/CCs, but it was decreased in CCs (score= 2). VIP mRNA levels resulted significantly greater in CCs (3.98 ± 3.93, p<0.05) vs. Ctrls (1.52 ± 1.55) and PD/CCs (0.86 ± 1.056), whereas a decreasing trend was observed in PD/CCs vs. Ctrls (p>0.05). Both immunofluorescence and immunoblot confirmed this tendency showing a 15% drop of the VIP protein (PD/CCs 0.86 ± 0.43 vs. Ctrls 1.01 ± 0.56, p>0.05).

Conclusion

Transit and anorectal dysfunctions in PD/CCs are associated with ZO-1, OCCL-1, CLDN-4 and VIP changes, hence suggesting that a leaky IEB contributes to submucosal neurochemical abnormalities underlying PD/CC. These findings suggest that the expression of the IEB markers are subject to both transcriptional and post-translational regulatory mechanisms, presumably distinct in CC and PD/CC.

References

1. Giancola F, Torresan F, Repossi R, Bianco F, Latorre R, Ioannou A, Guarino M, Volta U, Clavenzani P, Mazzoni M, Chiocchetti R, Bazzoli F, Travagli RA, Sternini C, De Giorgio R. Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation. Neurogastroenterol Motil. 2017 May;29(5):10.1111/nmo.12995.
2. Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, Heymann MF, Neunlist M, Derkinderen P. Structural alterations of the intestinal epithelial barrier in Parkinson's disease. Acta Neuropathol Commun. 2015 Mar 10;3:12.
3. Neunlist M, Toumi F, Oreschkova T, Denis M, Leborgne J, Laboisse CL, Galmiche JP, Jarry A. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G1028