5-Hydroxytryptamine Enhances the Pacemaker Activity of Interstitial Cells of Cajal in Mouse Colon.

We examined the localization of the 5-hydroxytryptamine (5-HT) receptor and its effects on mouse colonic interstitial cells of Cajal (ICCs) using electrophysiological techniques. Treatment with 5-HT increased the pacemaker activity in colonic ICCs with depolarization of membrane potentials in a dose-dependent manner. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers blocked pacemaker activity and 5-HT-induced effects. Moreover, an adenylate cyclase inhibitor inhibited 5-HT-induced effects, and cell-permeable 8-bromo-cAMP increased the pacemaker activity. Various agonists of the 5-HT receptor subtype were working in colonic ICCs, including the 5-HT4 receptor. In small intestinal ICCs, 5-HT depolarized the membrane potentials transiently. Adenylate cyclase inhibitors or HCN blockers did not show any influence on 5-HT-induced effects. Anoctamin-1 (ANO1) or T-type Ca2+ channel blockers inhibited the pacemaker activity of colonic ICCs and blocked 5-HT-induced effects. A tyrosine protein kinase inhibitor inhibited pacemaker activity in colonic ICCs under controlled conditions but did not show any influence on 5-HT-induced effects. Among mitogen-activated protein kinase (MAPK) inhibitors, a p38 MAPK inhibitor inhibited 5-HT-induced effects on colonic ICCs. Thus, 5-HT's effect on pacemaker activity in small intestinal and colonic ICCs has excitatory but variable patterns. ANO1, T-type Ca2+, and HCN channels are involved in 5-HT-induced effects, and MAPKs are involved in 5-HT effects in colonic ICCs.

Toward less invasive coloproctology: The future is out there.

Medical care has undergone remarkable improvements over the past few decades. One of the most important innovative breakthroughs in modern medicine is the advent of minimally and less invasive treatments. The trend towards employing less invasive treatment has been vividly shown in the field of gastroenterology, particularly coloproctology. Parallel to foregut interventions, colorectal surgery has shifted towards a minimally invasive approach. Coloproctology, including both medical and surgical management of colorectal diseases, has undergone a remarkable paradigm shift. The treatment of both benign and malignant colorectal conditions has gradually transitioned towards more conservative and less invasive approaches. An interesting paradigm shift was the trend to avoid the need for radical resection of rectal cancer altogether in patients who showed complete response to neoadjuvant treatment. The trend of adopting less invasive approaches to treat various colorectal conditions does not seem to be stopping soon as further research on novel, more effective and safer methods is ongoing.

Argon plasma coagulation: an effective treatment for solitary rectal ulcer syndrome.

BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a very rare benign defecation disorder characterized by distinct clinical features and histological findings. Conventional measures are often shown to be ineffective for the treatment of ulcers. Argon plasma coagulation (APC) has recently been shown to be an effective treatment method for SRUS that is refractory to conventional therapy. OBJECTIVES: Determine the efficacy of APC treatment for patients suffering from SRUS. DESIGN: Prospective, single center. SETTINGS: Gastroenterology department at a military hospital in Pakistan. PATIENTS AND METHODS: This prospective study included patients with symptoms of rectal bleeding diagnosed with SRUS. Patients were recruited on the basis of clinical, sigmoidoscopic, and histological findings from September 2022 to March 2023. All patients had received conventional treatment initially and were assessed for persistence of symptoms. APC was performed only for those patients who were refractory to standard treatment. MAIN OUTCOME MEASURES: Effectiveness of APC for resistant SRUS. SAMPLE SIZE: 99 patients. RESULTS: The 99 patients diagnosed with SRUS had a median (minimum-maximum) age of patients was 20 (9-41) years. All the patients had undergone conventional treatment, which included the use of laxatives, drinking plenty of water and practicing biofeedback. After this standard treatment, 19 patients (19.19%) recovered fully. However, the remaining 80 patients did not show improvement and underwent APC sessions, out of which 61 patients (76.3%) achieved complete healing of ulcers, while the remaining 19 (23.8%) had no improvement at all. None of the patients reported post session complications. CONCLUSION: APC is an effective therapy with very promising results for rectal ulcer hemorrhage. It also helps with ulcer healing and alleviates clinical symptoms. However, further controlled investigations are required to consolidate the use of APC in SRUS patients. LIMITATIONS: Single centered.

Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis.

Objective: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis. Methods: We collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis. Results: The cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified. Conclusion: We comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.

Synthesis, characterization, and application of honey stabilized inulin nanoparticles as colon targeting drug delivery carrier.

Inulin (INU) is a versatile natural polysaccharide primarily derived from chicory roots. INU possesses the unique quality of evading digestion or fermentation in the early stages of the human digestive tract, instead reaching the lower colon directly. Exploiting on this distinctive attribute, INU finds application in the creation of targeted carrier systems for delivering drugs tailored to colon-related diseases. This study presents a novel method for synthesizing highly stable and non-aggregatory inulin nanoparticles (INU NPs) by ionotropic gelation method, using calcium chloride as crosslinker and natural honey as a stabilizing agent. Different formulation and process parameters were optimized for the synthesis of monodispersed INU NPs. These INU NPs efficiently encapsulated a hydrophilic drug irinotecan hydrochloride trihydrate (IHT) and drug loaded formulation (IINPs) demonstrated excellent colloidal and storage stabilities. Notably, these IINPs exhibited pH-dependent drug release, suggesting potential for colon-specific drug delivery. Anticancer activity of the NPs was found significantly higher in comparison to IHT through cytotoxicity and apoptosis studies against human colorectal carcinoma cells. Overall, this study revealed that the INU NPs synthesized by ionotropic gelation will be an efficient nanocarrier system for colon-targeted drug delivery due to their exceptional biocompatibility and stability in stomach and upper intestinal conditions.

Reading of small bowel capsule endoscopy after frame reduction using an artificial intelligence algorithm.

OBJECTIVES: Poorly visualized images that appear during small bowel capsule endoscopy (SBCE) can confuse the interpretation of small bowel lesions and increase the physician's workload. Using a validated artificial intelligence (AI) algorithm that can evaluate the mucosal visualization, we aimed to assess whether SBCE reading after the removal of poorly visualized images could affect the diagnosis of SBCE. METHODS: A study was conducted to analyze 90 SBCE cases in which a small bowel examination was completed. Two experienced endoscopists alternately performed two types of readings. They used the AI algorithm to remove poorly visualized images for the frame reduction reading (AI user group) and conducted whole frame reading without AI (AI non-user group) for the same patient. A poorly visualized image was defined as an image with < 50% mucosal visualization. The study outcomes were diagnostic concordance and reading time between the two groups. The SBCE diagnosis was classified as Crohn's disease, bleeding, polyp, angiodysplasia, and nonspecific finding. RESULTS: The final SBCE diagnoses between the two groups showed statistically significant diagnostic concordance (k = 0.954, p < 0.001). The mean number of lesion images was 3008.5 ± 9964.9 in the AI non-user group and 1401.7 ± 4811.3 in the AI user group. There were no cases in which lesions were completely removed. Compared with the AI non-user group (120.9 min), the reading time was reduced by 35.6% in the AI user group (77.9 min). CONCLUSIONS: SBCE reading after reducing poorly visualized frames using the AI algorithm did not have a negative effect on the final diagnosis. SBCE reading method integrated with frame reduction and mucosal visualization evaluation will help improve AI-assisted SBCE interpretation.

Density clustering-based automatic anatomical section recognition in colonoscopy video using deep learning.

Recognizing anatomical sections during colonoscopy is crucial for diagnosing colonic diseases and generating accurate reports. While recent studies have endeavored to identify anatomical regions of the colon using deep learning, the deformable anatomical characteristics of the colon pose challenges for establishing a reliable localization system. This study presents a system utilizing 100 colonoscopy videos, combining density clustering and deep learning. Cascaded CNN models are employed to estimate the appendix orifice (AO), flexures, and "outside of the body," sequentially. Subsequently, DBSCAN algorithm is applied to identify anatomical sections. Clustering-based analysis integrates clinical knowledge and context based on the anatomical section within the model. We address challenges posed by colonoscopy images through non-informative removal preprocessing. The image data is labeled by clinicians, and the system deduces section correspondence stochastically. The model categorizes the colon into three sections: right (cecum and ascending colon), middle (transverse colon), and left (descending colon, sigmoid colon, rectum). We estimated the appearance time of anatomical boundaries with an average error of 6.31 s for AO, 9.79 s for HF, 27.69 s for SF, and 3.26 s for outside of the body. The proposed method can facilitate future advancements towards AI-based automatic reporting, offering time-saving efficacy and standardization.

Inadvertent laparoscopic lavage of perforated colon cancer: a systematic review.

BACKGROUND: Although laparoscopic lavage for perforated diverticulitis with peritonitis has been grabbing the headlines, it is known that the clinical presentation of peritonitis can also be caused by an underlying perforated carcinoma. The aim of this study was to determine the incidence of patients undergoing inadvertent laparoscopic lavage of perforated colon cancer as well as the delay in cancer diagnosis. METHODS: The PubMed database was systematically searched to include all studies meeting inclusion criteria. Studies were screened through titles and abstracts with potentially eligible studies undergoing full-text screening. The primary endpoints of this meta-analysis were the rates of perforated colon cancer patients having undergone inadvertent laparoscopic lavage as well as the delay in cancer diagnosis. This was expressed in pooled rate % and 95% confidence intervals. RESULTS: Eleven studies (three randomized, two prospective, six retrospective) totaling 642 patients met inclusion criteria. Eight studies reported how patients were screened for cancer and the number of patients who completed follow-up. The pooled cancer rate was 3.4% (0.9%, 5.8%) with low heterogeneity (Isquare2 = 34.02%) in eight studies. Cancer rates were 8.2% (0%, 3%) (Isquare2 = 58.2%) and 1.7% (0%, 4.5%) (Isquare2 = 0%) in prospective and retrospective studies, respectively. Randomized trials reported a cancer rate of 7.2% (3.1%, 11.2%) with low among-study heterogeneity (Isquare2 = 0%) and a median delay to diagnosis of 2 (1.5-5) months. CONCLUSIONS: This systematic review found that 7% of patients undergoing laparoscopic lavage for peritonitis had perforated colon cancer with a delay to diagnosis of up to 5 months.

Rare Cause of Hematochezia in Children: Solitary Rectal Ulcer, Single Center Experience.

Background/Aims: Solitary rectal ulcer syndrome (SRUS) can be overlooked, diagnosed late, or misdiagnosed, particularly in childhood. This study reviewed the 13-year experience of the authors' institution to increase clinicians' awareness of SRUS in the presence of symptoms. This paper reports the endoscopic and histopathological findings in children presenting with hematochezia. Methods: The clinical and laboratory findings of 22 patients diagnosed with biopsy-proven SRUS in the authors' clinic between 2007 and 2020 were evaluated retrospectively. Results: The mean age at diagnosis was 12.5±2.6 years, and 59.1% of the patients were male. The median time of diagnosis was 24 months. A single ulcer lesion was found by colonoscopy in 18 patients (81.8%), two ulcers in two patients (9%), and more than two ulcers in two patients (9%). The pathology reports of all biopsies taken from the lesions were consistent with a solitary rectal ulcer. In the first stage, the treatment was started with toilet training, a high-fiber diet, and laxatives. In 11 patients (50%) who did not respond to the initial treatment, a 5-ASA enema was added. A glucocorticoid enema was added to treatment in five patients (22%) whose complaints did not regress despite this treatment. Clinical remission was achieved in five of the patients (18.1%). The time to diagnosis was significantly shorter in those in remission than those not in remission (p=0.04). Conclusions: This study is the first large series on Turkish children. An increased awareness of SRUS in children will increase the rate of early diagnosis and treatment, allowing remission in more patients.

Outcome of Transanal Endorectal Pull-Through in Patients with Hirschsprung's Disease.

BACKGROUND: Transanal endorectal pull-through (TERPT) has become one of the preferred treatments for Hirschsprung's disease (HD) in our setting. This report aims to evaluate the current outcome of TERPT in the setting. MATERIALS AND METHODS: A retrospective review of 71 children who had TERPT for histologically-confirmed HD in 11 years (2006-2017) in Nigeria. RESULTS: There were 48 boys and 23 girls; aged 3 days-12 years at initial presentation (median = 10 months). Three (4.2%) patients had associated anomalies (duodenal atresia; anorectal malformation and sensorineural deafness with hypopigmented skin patches each). Age at TERPT was 2 months to 15 years (median = 3 years), with surgery waiting time of 1 month-14.9 years (median = 18 months). Sixty-six (93.0%) patients had rectosigmoid, four (5.6%) patients had long segment and one (1.4%) had total colonic disease. Five (7.0%) patients with large megacolon and one (1.4%) with the total colonic disease had assisted abdominal resection of the colon at TERPT. Seventeen (23.9%) patients had post-operative complications, including post-operative enterocolitis 8 (11.3%); anastomotic dehiscence 3 (4.2%); retained aganglionic segment 2 (2.8%); anastomotic stenosis 2 (2.8%), resulting in prolonged hospital stay (P = 0.0001; range = 1-30 days; median = 5 days). The mortality rate was 4.2% (3) from malignant hyperthermia in one patient and in 2 patients, the cause of mortality was unclear. Patients were followed up for 3-6 years (median = 3.5 years). Bowel movement stabilised to 2-4 times daily by 6 weeks after surgery. CONCLUSION: TERPT is a safe treatment for HD in this setting with good short-term outcomes. Longer follow-up is necessary to further evaluate the long-term bowel movement outcomes.!

Are trauma victims with obesity lucky in penetrating trauma injuries?

BACKGROUND: We aimed to reveal the protective effect of body mass index (BMI) and subcutaneous adipose tissue thickness (SATT), together with scores covering the abdomen, in patients with penetrating abdominal trauma. METHODS: The data of 234 abdominal penetrating trauma patients over the age of 16 who applied to the emergency general sur-gery unit of Istanbul Medipol Hospital between 2017 and 2021 were analyzed retrospectively. Sex, age, types of penetrating injuries, BMI, need for blood transfusion and intensive care unit (ICU), mortality, Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Flint Colon Injury Score (FCIS) were recorded. RESULTS: The patients were divided into two groups: Gunshot Wound (GW) and Stab Wound (SW).While there was no significant difference in all parameters examined in all patients and GW patients in terms of BMI, a statistically significant difference was found in terms of blood transfusion need in SW patients (p=0.035). As a result of the Receiver Operating Characteristic curve analysis for the SATT variable, the cutoff value between mortality (p=0.866) and SATT (mm) values in all patients was 11 mm for all patients and 12 mm for GW patients. A significant difference was found in all patients and separately in GW and SW groups in terms of ICU and blood transfusion need, length of stay, ISS, PATI, and FCIS scores in non-operated patients (p<0.05). When all patients were examined, a statistically significant difference was found in terms of mortality (p=0.002). CONCLUSION: It is the first study to evaluate penetrating abdominal injuries with both BMI and SATT comprehensively and with all abdominal scores. A cutoff value to be determined for SATT with larger and multicenter studies can take its place as a parameter in the penetrating trauma algorithm.

Proximal protective diverting ostomy following colon anastomosis for penetrating trauma may not be protective: A matched cohort study.

INTRODUCTION: Despite the shift toward liberal primary anastomosis in penetrating colon injuries, some surgeons recommend a protective diverting ostomy (DO) proximal to the anastomosis. This study evaluates the effect of DO on outcomes in patients undergoing colon resection and anastomosis following penetrating trauma. METHODS: The TQIP database (2013-2018) was queried for penetrating colon injuries undergoing colectomy and anastomosis. Patients receiving DO were propensity matched to patients without diverting ostomy (woDO) (1:3). Outcomes were compared between groups. RESULTS: After matching, 89 DO patients were analyzed. The DO group had more surgical site infections (32 â€‹% vs. 21 â€‹%; p â€‹< â€‹0.05) and longer hospital stay (20 [13-27] vs. 15 [9-25]; p â€‹< â€‹0.05) compared to the woDO group. Mortality and unplanned operations were similar between groups. CONCLUSIONS: Diverting ostomy after colon resection and anastomosis is associated with increased infectious complications without decreasing unplanned operations or mortality. Its routine role in penetrating colon trauma needs reassessment.

Primary Repair Versus Resection for AAST Grade I and II Colon Injuries: Does the Type of Repair Matter?

INTRODUCTION: The management of traumatic colon injuries has evolved over the past two decades. Recent evidence suggests that primary repair or resection over colostomy may decrease morbidity and mortality. Data comparing patients undergoing primary repair versus resection are lacking. We sought to compare the outcomes of patients undergoing primary repair versus resection for low-grade colon injuries. METHODS: A retrospective review of all patients who presented with American Association for the Surgery of Trauma grade I and II traumatic colon injuries to our Level I trauma center between 2011 and 2021 was performed. Patients were further dichotomized based on whether they underwent primary repair or resection with anastomosis. Outcome measures included length of stay data, infectious complications, and mortality. RESULTS: A total of 120 patients met inclusion criteria. The majority of patients (76.7%) were male, and the average age was 35.6 ± 13.1 y. Most patients also underwent primary repair (80.8%). There were no statistically significant differences between the groups in arrival physiology or in injury severity score. Length of stay data including hospital length of stay, intensive care unit length of stay, and ventilator days were similar between groups. Postoperative complications including pneumonia, surgical site infections, fascial dehiscence, the development of enterocutaneous fistulas, and unplanned returns to the operating room were also all found to be similar between groups. The group who underwent resection with anastomosis did demonstrate a higher rate of intra-abdominal abscess development (3.1% versus 26.1%, P < 0001). Mortality between both groups was not found to be statistically significant (7.2% versus 4.3%, P = 0.4) CONCLUSIONS: For low-grade (American Association for the Surgery of Trauma I and II) traumatic colon injuries, patients undergoing primary repair demonstrated a decreased rate of intra-abdominal abscess development when compared to patients who underwent resection with anastomosis.

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.