Outcomes After Colonic Self-Expanding Metal Stent Insertion Without Fluoroscopy: A Surgeon-Led 10-Year Experience.

INTRODUCTION: Colonic self-expanding metal stents (SEMS) can be used to relieve malignant and benign large bowel obstruction (LBO) as a bridge to surgery (BTS) and for palliation. Guidelines suggest the use of fluoroscopic guidance for deployment. This may be difficult to obtain after hours and in certain centers. We aimed to determine the outcomes of stenting under endoscopic guidance alone. METHODS: All patients who underwent SEMS insertion in our tertiary referral center between August 2010 and June 2021 were identified from a prospectively maintained database. Patient demographics (age/gender), disease characteristics (benign versus malignant/location/stage), stenting intent (BTS versus palliative), and outcomes (technical success/stoma/time from stenting to resection/death/study end) were analyzed. RESULTS: Fifty-three (n = 39, 73.6% male) patients underwent SEMS insertion. Indications included colorectal carcinoma (n = 48, 90.6%), diverticular stricture (n = 3), and gynecological malignancy (n = 2). In five (9.4%) patients (four BTS and one palliative), SEMSs deployment was not completed because of the inability to pass the guidewire. All underwent emergency surgery. In the BTS cohort (n = 29, median 70.4 [range 40.3-91.8] years), 10 patients underwent neoadjuvant chemoradiotherapy. The permanent stoma rate was 20.7% (n = 6). There was no 30- or 90-d mortality. In the palliative cohort (n = 24, median age 77.1 [range 54.4-91.9]), 16 (66.7%) were deceased at the study end. The median time from stenting to death was 5.2 (2.3-7.9) months. CONCLUSIONS: SEMS placed under endoscopic visualization alone, palliatively and as a BTS, had acceptable stoma, morbidity, and mortality rates. These results show that SEMS insertion can be safely performed without fluoroscopy.

A fundamental change emerging in locally advanced rectal cancer management: a case report.

Treatment of locally advanced rectal cancer remains a challenge in colorectal surgery. It has had an evolving landscape over the past three decades. Implementation of total neoadjuvant therapy (TNT) as a novel approach to management has begun globally but long-term outcomes and data analysis to identify optimal schedules are eagerly awaited. We report a case of locally advanced rectal cancer management in a young male with a complete pathological response to TNT.

Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis.

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ - 0.460, p < 0.005) and B. wadsworthia (ρ - 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.

The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis.

Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL.

Binding of Helicobacter pylori to Human Gastric Mucins Correlates with Binding of TFF1.

Helicobacter pylori binds to the gastric mucin, MUC5AC, and to trefoil factor, TFF1, which has been shown to interact with gastric mucin. We examined the interactions of TFF1 and H. pylori with purified gastrointestinal mucins from different animal species and from humans printed on a microarray platform to investigate whether TFF1 may play a role in locating H. pylori in gastric mucus. TFF1 bound almost exclusively to human gastric mucins and did not interact with human colonic mucins. There was a strong correlation between binding of TFF1 and H. pylori to human gastric mucins, and between binding of both TFF1 and H. pylori to gastric mucins with that of Griffonia simplicifolia lectin-II, which is specific for terminal non-reducing α- or ß-linked N-acetyl-d-glucosamine. These results suggest that TFF1 may help to locate H. pylori in a discrete layer of gastric mucus and hence restrain their interactions with epithelial cells.

Deadly combination: Clostridium septicum and colorectal malignancy.

Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This case outlines an initial presentation of colonic malignancy as gas gangrene from C.septicum infection.A 69-year-old man presented with abdominal pain, vomiting and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed caecal thickening and subcutaneous emphysema overlying the left flank. Clinically, he became haemodynamically unstable. Examination revealed crepitus overlying the left flank in keeping with gas gangrene. The patient required immediate surgical debridement. Tissue specimens cultured C.septicum Following a complicated postoperative period, he was transferred to the plastic surgery team for further tissue debridement and reconstruction. A colonoscopy was later performed which was suspicious for malignancy. Colorectal multidisciplinary team discussion is awaited.

A Preliminary Study Examining the Binding Capacity of Akkermansia muciniphila and Desulfovibrio spp., to Colonic Mucin in Health and Ulcerative Colitis.

BACKGROUND: Akkermansia muciniphila and Desulfovibrio spp. are commensal microbes colonising the mucus gel layer of the colon. Both species have the capacity to utilise colonic mucin as a substrate. A. muciniphila degrades colonic mucin, while Desulfovibrio spp. metabolise the sulfate moiety of sulfated mucins. Altered abundances of these microorganisms have been reported in ulcerative colitis (UC). However their capacity to bind to human colonic mucin, and whether this binding capacity is affected by changes in mucin associated with UC, remain to be defined. METHODS: Mucin was isolated from resected colon from control patients undergoing resection for colonic cancer (n = 7) and patients undergoing resection for UC (n = 5). Isolated mucin was purified and printed onto mucin microarrays. Binding of reference strains and three clinical isolates of A. muciniphila and Desulfovibrio spp. to purified mucin was investigated. RESULTS: Both A. muciniphila and Desulfovibro spp. bound to mucin. The reference strain and all clinical isolates of A. muciniphila showed increased binding capacity for UC mucin (p < .005). The Desulfovibrio reference strain showed increased affinity for UC mucin. The mucin binding profiles of clinical isolates of Desulfovibrio spp. were specific to each isolate. Two isolates showed no difference in binding. One UC isolate bound with increased affinity to UC mucin (p < .005). CONCLUSION: These preliminary data suggest that differences exist in the mucin binding capacity of isolates of A. muciniphila and Desulfovibrio spp. This study highlights the mucin microarray platform as a means of studying the ability of bacteria to interact with colonic mucin in health and disease.

Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis.

The colonic mucus gel layer (MGL) is a critical component of the innate immune system acting as a physical barrier to microbes, luminal insults, and toxins. Mucins are the major component of the MGL. Selected microbes have the potential to interact with, bind to, and metabolize mucins. The tolerance of the host to the presence of these microbes is critical to maintaining MGL homeostasis. In disease states such as ulcerative colitis (UC), both the mucosa associated microbes and the constituent MGL mucins have been shown to be altered. Evidence is accumulating that implicates the potential for mucin degrading bacteria to negatively impact the MGL and its stasis. These effects appear more pronounced in UC.   This review is focused on the host-microbiome interactions within the setting of the MGL. Special focus is given to the mucolytic potential of microbes and their interactions in the setting of the colitic colon.