Middle Colon Research Articles

Spatially restricted immune and microbiota-driven adaptation of the gut.

The intestine is characterized by an environment in which host requirements for nutrient and water absorption are consequently paired with the requirements to establish tolerance to the outside environment. To better understand how the intestine functions in health and disease, large efforts have been made to characterize the identity and composition of cells from different intestinal regions1-8. However, the robustness, nature of adaptability and extent of resilience of the transcriptional landscape and cellular underpinning of the intestine in space are still poorly understood. Here we generated an integrated resource of the spatial and cellular landscape of the murine intestine in the steady and perturbed states. Leveraging these data, we demonstrated that the spatial landscape of the intestine was robust to the influence of the microbiota and was adaptable in a spatially restricted manner. Deploying a model of spatiotemporal acute inflammation, we demonstrated that both robust and adaptable features of the landscape were resilient. Moreover, highlighting the physiological relevance and value of our dataset, we identified a region of the middle colon characterized by an immune-driven multicellular spatial adaptation of structural cells to the microbiota. Our results demonstrate that intestinal regionalization is characterized by robust and resilient structural cell states and that the intestine can adapt to environmental stress in a spatially controlled manner through the crosstalk between immunity and structural cell homeostasis.

Surgical maneuvers for long-segment Hirschsprung pull-through in unique patients.

Patients with Hirschsprung disease affecting the splenic flexure or more proximal segments present a surgical challenge. Mobilizing the transverse colon to the pelvis during a pull-through may obstruct the distal ileum, or the length may be insufficient to reach the lower pelvis. This retrospective study aimed to describe two surgical techniques that facilitate mobilization of the transverse colon and their outcome. We included patients operated on between April 2017 and April 2024 and analyzed sex, comorbidities, type of pull- through,age at pull-through, history ofprevious surgeries, cause of the proximal transverse colon pull-through, technique used (Deloyers or Turnbull), complications, postoperative outcomeand follow-up. The first technique used was the maneuver described by Turnbull. This operation creates a mesenteric defect and mobilizes the colon into this mesenteric window at the distal ileum level. The second technique was described by Deloyers and involves a 180-degree rotation of the right colon by dissecting the right colon attachment and the hepatocolic ligament. The cecum and the ileocecal valve are placed in the right upper quadrant, and the distal colon is mobilized into the pelvis. We included 13 patients, 12 boys and 1 girl. Eight patients had previous surgeries in another hospital: five had an initial transverse colostomy, and three had an ileostomy. The remaining five had the initial operation in our hospital: two had an ileostomy, two had a colostomy, and one had a primary pull-through. The median age at pull-through was 16months (4-59months). We used the Turnbull technique in four patients whose aganglionosis was limited to the middle transverse colon. The Deloyers technique was used in the remaining patients, with ganglion cells in the proximal transverse colon. We left a protective ileostomy in five patients. The median follow-up was 4.5years (3months to 10years). The stoma takedown is pending in one patient. The Turnbull and Deloyers techniques were helpful in patients with aganglionosis affecting the transverse colon.

Finite Element Analysis of Bilateral Double Rod Constructs in Thoracolumbar Fractures.

To evaluate bilateral double rod contructs in thoracolumbar fractures in a Finite Element model MATERIAL and METHODS: A computed tomography of a 35-year old male have been chosen to create a vertebra model and 1/3 of the T12 was removed to create the burst fracture model. In model A, transpedicular polyaxial screws were inserted two levels above and two levels below the burst fracture. On each side the screws were connected with a single rod. In model B, the screws were connected with two rods on each side attached to two lateral connectors. A uniform 150 N axial load and 10 N/m torque was applied on the superior T10. ROM and von Mises stress nephrograms revealed that the bilateral double-rod construct is being the most rigid and that the force on the pedicle screws were significantly lower compared to model A. We believe that bilateral double-rod constructs for the stabilization of thoracolumbar fractures have a decreased load on pedicle screws and rods compared to the classic bilateral single rod stabilization system and can lower the risk of implant failure and the risk for secondary complications and revision surgery.

Nitric oxide and ion channels mediate L-cysteine-induced inhibition of colonic smooth muscle contraction.

Previous studies have suggested that L-cysteine regulates gut motility through hydrogen sulfide. However, the mechanisms involved in the L-cysteine-induced response have not been extensively studied. This study aimed to investigate the underlying mechanisms of action of L-cysteine on spontaneous contraction of rat colon. Longitudinal and circular muscle strips from rat middle colon were prepared to measure the spontaneous contractile activities of colon in an organ bath system. Whole-cell voltage-clamp techniques were applied to record the currents of L-type voltage-dependent Ca2+ channels (VDCCs) and voltage-gated K+ channels (Kv) in isolated smooth muscle cells (SMCs) from colon. L-cysteine inhibited the spontaneous contraction of longitudinal and circular muscle strips from the rat colon in a concentration-dependent manner. The inhibition induced by L-cysteine was significantly decreased by inhibitors of H2S synthesis (p < 0.05). Furthermore, the suppression induced by L-cysteine was partially attenuated by tetrodotoxin, L-NNA and glibenclamide (p < 0.05). Whole-cell voltage-clamp recordings showed that L-cysteine caused a remarkable reduction in the peak currents of VDCCs and significantly increased the membrane currents of Kv channels in isolated SMCs (p < 0.05). We concluded that L-cysteine inhibits the contractile activities of smooth muscle strips from the rat colon. The relaxation in response to L-cysteine may be in part mediated by a nitrergic pathway and by inhibiting the VDCCs in combination with a direct activation of the KV channels and KATP channels.

Application of robotic (or laparoscopic) surgery combined with colonoscopy in T1 stage colorectal cancer surgery: 13 cases

Objective: To investigate the feasibility and safety of a robotic surgical system (or laparoscopy) in combination with colonoscopy (combined) for the treatment of stage T1N0M0 colorectal cancer. Methods: This was a descriptive case series. Indications for combined dual-scope surgery in this study were as follows: (1) preoperative colonoscopic examination of lesions in the middle and upper rectum and colon with pathologically confirmed high-grade intraepithelial neoplasia, intramucosal adenocarcinoma, or adenocarcinoma; (2) no distant or local lymph node metastases; and (3) endoscopic ultrasound and magnetic resonance imaging evidence of tumor invasion of the mucosal or submucosal, but not the muscular, layer (i.e., T1). The clinical data of 13 patients with stage T1 colorectal cancer who had undergone dual-scope combined resection using a robotic surgery system or laparoscope-assisted combined colonoscopy surgery at the First Affiliated Hospital of Zhengzhou University from April to October 2022 were retrospectively collected, including 6 males and 7 females, with a median age of 59 (48~88) years old. The tumors were located in the upper and middle rectum in six patients, in the sigmoid colon in three, and in the ascending colon in four. The median maximum diameter of the tumors was 3.0 (1.8-5.0) cm. The surgery was performed by a robotic surgery system (or laparoscopy) with peritumoral D1 lymph node dissection at the first station in the tumor area. The tumors were resected under direct vision and the defects in the intestinal wall were using a robotic surgery system (or laparoscopy). A robotic surgery system was combined with colonoscopy in eight cases and laparoscopy combined with colonoscopy in the remaining five. Studied variables includes surgical and pathological features, postoperative factors, and outcomes. Results: Surgery was successful in all 13 patients with no need for conversion to open surgery or intraoperative blood transfusion. The median operating time was 85 (60-120) minutes, median intraoperative bleeding 3 (2-5) mL, median number of lymph nodes harvested 3 (1-5), and the median circumferential resection margin 0.8 (0.5-1.0) cm. Postoperative pathological examination showed lymph node metastasis in one patient, who therefore underwent additional radical surgery. The median postoperative time to ambulation was 1 (1-2) days. The urinary catheters of all patients were removed 1 day after surgery and the median length of stay was 4 (3-5) days. No abdominal infection, anastomotic leakage or bleeding occurred in any of the study patients. The median follow-up time was 10 (6-12) months, during which no tumor recurrence or metastasis was found, and the quality of life was satisfactory. Conclusions: The combination of two minimally invasive platforms, a robotic surgery system (or laparoscopy) and colonoscopy, is safe and feasible for resection of stage T1 colorectal cancer and has a good short-term prognosis.

Comparison of survival outcomes between laparoscopic and open colectomy for transverse colon cancer: a systematic review and meta-analysis.

This study aimed to compare laparoscopic with open resection for transverse colon cancer (TCC) regarding long-term survival outcomes. Systematic literature search was performed on PubMed, Ovid, and Cochrane Library for studies comparing laparoscopic with open resection for TCC. The last search was performed on October 7, 2022. Oncological and survival outcomes were collected and analyzed. This meta-analysis was performed using Review Manager Software (v 5.3). This study included fifteen studies published between 2014 and 2022 with 2556 patients in total. When compared with the laparoscopic group, the open group had significantly more tumors locating on middle transverse colon (P = 0.006, OR = 0.67, 95%CI [0.50, 0.89], I2 = 12%) and more patients received transverse colectomy (P = 0.03, OR = 0.66, 95%CI [0.46, 0.96], I2 = 53%) as results. Comparable tumor stage (P = 0.13, OR = 0.81, 95%CI [0.62, 1.06], I2 = 55%) and number of lymph node harvested (P = 0.22, WMD = -0.81, 95%CI [-2.09, 0.47], I2 = 73%) were observed between the two groups. As for survival outcomes, no significant difference was observed between the two groups for 5-year disease-free survival (DFS; P = 0.61, OR = 0.93, 95%CI [0.72, 1.21], I2 = 0%), 5-year overall survival (OS; P = 0.83, OR = 0.97, 95%CI [0.71, 1.32], I2 = 0%), 3-year DFS (P = 0.97, OR = 0.96, 95%CI [0.69, 1.32], I2 = 0%), and 3-year OS (P = 0.67, OR = 0.92, 95%CI [0.63, 1.35], I2 = 0%). In the subgroup analysis according to tumor stage, the results did not change. Current evidence based on studies demonstrated that laparoscopic procedure could be safely performed for TCC, and it would not affect the long-term survival. Randomized clinical trials with a larger sample size are warranted in the future for further investigation.

Spontaneous regression of advanced transverse colon cancer with deficient mismatch repair: a case report

BackgroundSpontaneous regression (SR) of cancer occurs in 1 in 60,000–100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer.Case presentationA 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0–IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR.ConclusionThis study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

P029 Histopathological characterization of a chronic DSS-induced mouse model of IBD with intestinal fibrosis

Abstract Background Inflammatory bowel disease (IBD) comprises a group of intestinal disorders, including ulcerative colitis and Crohn's disease. Intestinal fibrosis, as result of chronic inflammation, is a common complication in IBD. High treatment failure rates associated with existing interventions indicate a high unmet need for more effective drugs to improve the management and outcomes of IBD. Consequently, translational animal models of IBD demonstrating chronic, progressive colonic fibrosis are important tools in preclinical drug discovery for IBD. The aim of the present study was to characterize intestinal histopathology in a chronic DSS-induced mouse model of IBD. Methods Ten-weeks-old male C57BL/6JRj mice were randomized into study groups based on body weight and received 3 cycles of DSS (2.5 % w/v) in the drinking water (DSS-IBD) or normal water (CTRL). Terminal endpoints included colon morphometry and quantitative histological markers of inflammation and fibrosis assessed in proximal, middle and distal colonic segments. Using RNA sequencing, transcriptome signatures were profiled in the middle colon segment. Results Compared to healthy controls, the chronic DSS-IBD mouse model demonstrated hallmarks of IBD, including mild-to-moderate weight loss and colonic hypertrophy. Histopathological analysis indicated increased deposition of inflammatory (CD45 and CD11b), fibrogenesis (alpha-smooth muscle actin) and fibrosis markers (collagen 1a1, Picrosirius red) in the middle and distal colon. Severe fibrosis was observed throughout all layers of the middle colon. Histological findings were supported by significantly upregulated gene expression markers of inflammation and fibrosis. Conclusion The DSS-IBD mouse is a translational preclinical model suitable for testing novel drug therapies for IBD with intestinal fibrosis.

Gunshot injury to the colon by expanding bullets in combat patients wounded in hybrid period of the Russian-Ukrainian war during 2014–2020

BackgroundA gunshot wound to the colon is a frequent injury in armed conflicts. An example of a high-energy modern weapon is hollow-point bullets, which is associated with increased tissue damage and lethal outcome. The aim of this study was to evaluate gunshot injuries to the colon in combat patients and to assess the difference in clinical features of patients with colon injuries by hollow-point versus shape-stable bullets.Patients and methodsAnalyses of clinical data were performed on 374 male soldiers from the Armed Forces of Ukraine with gunshot abdominal wounds with injury to the colon in East Ukraine between 2014 and 2020. Out of 374 injured, 112 (29.9%) patients were diagnosed with penetrating gunshot bullet wounds: 69/112 (61.6%) were injured by shape-stable bullets, and the hollow-point bullets injured 43/112 (38.4%) patients.ResultsMore severe hemorrhagic shock stages were in patients injured by hollow-point bullets: shock stages III-IV was in 25 (58.1%) patients injured by the hollow-point bullets vs. 17 (24.6%) patients injured by shape-stable bullets (p = 0.0004). Left colon parts were more frequently injured as compared to the right colon side or transverse colon: 21 (48.8%) patients were injured by the hollow-point bullets (p < 0.0001), and 41 (59.4%) patients were injured by the shape-stable bullets (p = 0.032). A significant difference was identified for the frequent injury to the middle colon within the entire cohort (p = 0.023). Patients injured by the hollow-point bullets demonstrated a higher frequency of 3–5 areas of colon gunshot defects, which was detected in 18 (41.8%) patients injured by hollow-point bullets and none with shape-stable bullets injury (p = 0.0001). Colon Injury Scale (CIS) IV was detected in 7 (16.3%) patients injured by the hollow-point bullets as compared to 2 (2.9%) patients injured by shape-stable bullets (p = 0.011). Colostomy was performed in 14 (69%) patients injured by shape-stable bullets and in 12 (27.9%) patients injured by hollow-point bullets (p > 0.05). 15 (35%) patients died after injury by the hollow-point bullet, whereas 9 (13%) patients after damage by the shape-stable bullets (p = 0.0089).ConclusionsAll patients should be suspected to have an injury by bullet with expanding properties in case of penetrating abdominal injury (absent of outlet wound) and careful revision of the abdomen must be performed to identify possible multiorgan injury as well as multiple gunshot defects of the intestine.

HISTOPATHOLOGICAL CHARACTERIZATION OF A CHRONIC DSS-INDUCED MOUSE MODEL OF IBD WITH INTESTINAL FIBROSIS

Abstract RATIONALE Inflammatory bowel disease (IBD) comprises a group of intestinal disorders, including ulcerative colitis and Crohn's disease. Intestinal fibrosis, as result of chronic inflammation, is a common complication in IBD. High treatment failure rates associated with existing interventions indicate a high unmet need for more effective drugs to improve the management and outcomes of IBD. Consequently, translational animal models of IBD demonstrating chronic, progressive colonic fibrosis are important tools in preclinical drug discovery for IBD. The aim of the present study was to characterize intestinal histopathology in a chronic DSS-induced mouse model of IBD. METHODS Ten-weeks-old male C57BL/6JRj mice were randomized into study groups based on body weight and received 3 cycles of DSS (2.5 % w/v) in the drinking water (DSS-IBD) or normal water (CTRL). Terminal endpoints included colon morphometry and quantitative histological markers of inflammation and fibrosis assessed in proximal, middle and distal colonic segments. Using RNA sequencing, transcriptome signatures were profiled in the middle colon segment. RESULTS Compared to healthy controls, the chronic DSS-IBD mouse model demonstrated hallmarks of IBD, including mild-to-moderate weight loss and colonic hypertrophy. Histopathological analysis indicated increased deposition of inflammatory (CD45 and CD11b), fibrogenesis (alpha-smooth muscle actin) and fibrosis markers (collagen 1a1, Picrosirius red) in the middle and distal colon. Severe fibrosis was observed throughout all layers of the middle colon. Histological findings were supported by significantly upregulated gene expression markers of inflammation and fibrosis. CONCLUSIONS The DSS-IBD mouse is a translational preclinical model suitable for testing novel drug therapies for IBD with intestinal fibrosis.

Anatomic location of colorectal cancer presents a new paradigm for its prognosis in African American patients.

Among all racial groups in the U.S., African Americans (AA) have the highest incidence of and mortality from colorectal cancer (CRC). Although socioeconomic factors, as the major contributors to racial disparity of CRC, have been widely investigated, there is a dearth of information germane to understanding its biological basis. To better elucidate the clinicopathologic features we extracted demographic, clinical, pathologic and molecular features of 500 consecutive cases of CRC diagnosed at our institution which has an AA-predominant patient population (75% of all patients). We compared data from our AA patients with those of white patients both from our institution and from SEER and the published literature for meaningful comparison. AA patients were more likely to be at an advanced disease stage (25.9% vs. 20.8%, p = 0.041), have low grade tumors (89.2% vs. 77.5%, p<0.001) in cecum (18.7% vs. 16.2%, p<0.001) and <60-years-old than white patients (31.8% vs. 26.3%, p = 0.015). The frequency of KRAS mutation was higher in AA patients than in white patients (56.8% vs. 20.7%, p<0.001). Amongst subtypes of KRAS tested in CRC, codon 12 mutation is more common in AA than white patients (85.2% vs. 68.9%, p = 0.020). Compared with other racial groups, we found AA patients to have worse disease-free survival (HR = 3.682, p = 0.035). Also, AA patients with CRC in distal (sigmoid and rectum) or proximal (cecum) colon have worse overall survival than those with CRC in middle colon (HR = 2.926, p = 0.014), a finding not observed in white patients. In both racial groups, advanced stage, perforation, and hypertension were independent prognostic factors for overall survival (p<0.05). Similarly, low body-mass index at presentation, mucinous adenocarcinoma, lymphovascular invasion, perineural invasion and KRAS mutations were independent factors significantly associated with poor disease-free survival. Collectively, our data provide new insights into the roles of clinicopathologic features, especially anatomic distribution, in predicting outcomes of CRC in AA population.

Effect and Prognosis Factors of Combining Laparoscopic Radical Resection of Colon Adenocarcinoma with Docetaxel Therapy in Treating Middle and Advanced Colon Adenocarcinoma.

Objective The aim of the study is to explore the clinical efficacy and prognosis factors of joint application of laparoscopic radical resection of colon adenocarcinoma (COAD) and docetaxel therapy in treating COAD of middle and advanced stages. Methods The clinical data of 103 COAD patients of middle and advanced stages treated in our hospital from July 2016 to July 2018 were selected for the retrospective analysis, all patients received the treatment scheme of combining laparoscopic radical resection of COAD with docetaxel therapy for the observation of short-term efficacy, follow-up was conducted to record their 3-year survival, and relevant factors affecting patient prognosis were analyzed by the logistic regression model. Results After treatment, the total remission rate of patients was 75.73% (78/103), the total incidence rate of adverse reactions was 16.50% (17/103); patients' level values of various serum tumor markers after treatment were significantly lower than those before treatment (P < 0.001); according to the univariate analysis results, for COAD patients with different tumor diameters, differentiated degrees, TNM stages, perineural invasion degrees, pathological types, and depths of invasion, their modality rates were statistically different (P < 0.05); and the logistic regression analysis showed that tumor diameter ≥5 cm, poor differentiation, TNM stage IV, perineural invasion, pathologically signet-ring cell carcinoma, and T3-invasion were the independent risk factors affecting patient prognosis (P < 0.05). Conclusion Combining laparoscopic radical resection of COAD with docetaxel therapy in treating COAD of middle and advanced stages achieves affirmed short-term efficacy, which can reduce patients' level of serum tumor markers and ensure high safety and good survival prognosis. Tumor diameter, differentiated degree, TNM stage, perineural invasion, pathological type, and T3-invasion are the relevant factors affecting the prognosis of middle and advanced COAD.

Wheat Amylase Trypsin Inhibitors Aggravate Intestinal Inflammation Associated with Celiac Disease Mediated by Gliadin in BALB/c Mice.

Celiac disease (CD) is an autoimmune intestinal disorder caused by the ingestion of gluten in people who carry the susceptible gene. In current celiac disease research, wheat gluten is often the main target of attention, neglecting the role played by non-gluten proteins. This study aimed to describe the effects of wheat amylase trypsin inhibitors (ATI, non-gluten proteins) and gliadin in BALB/c mice while exploring the further role of relevant adjuvants (cholera toxin, polyinosinic: polycytidylic acid and dextran sulfate sodium) intervention. An ex vivo splenocyte and intestinal tissue were collected for analysis of the inflammatory profile. The consumption of gliadin and ATI caused intestinal inflammation in mice. Moreover, the histopathology staining of four intestinal sections (duodenum, jejunum, terminal ileum, and middle colon) indicated that adjuvants, especially polyinosinic: polycytidylic acid, enhanced the villi damage and crypt hyperplasia in co-stimulation with ATI and gliadin murine model. Immunohistochemical results showed that tissue transglutaminase and IL-15 expression were significantly increased in the jejunal tissue of mice treated with ATI and gliadin. Similarly, the expression of inflammatory factors (TNF-α, IL-1β, IL-4, IL-13) and Th1/Th2 balance also showed that the inflammation response was significantly increased after co-stimulation with ATI and gliadin. This study provided new evidence for the role of wheat amylase trypsin inhibitors in the pathogenesis of celiac disease.

METHYLTRANSFERASE SMYD2 MODULATES THERAPEUTIC EFFECTS OF EPIDERMAL GROWTH FACTOR IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Inflammatory bowel disease (IBD) is a chronic and remitting inflammatory disorder of the gastrointestinal tract. A prior clinical trial demonstrated the ability of epidermal growth factor receptor (EGFR) ligand EGF to induce and maintain remission in ulcerative colitis. As a protein lysine methyltransferase, SET and MYND domain-containing protein 2 (SMYD2) regulates various cellular functions, including chromatin remodeling and tumorigenesis. A bioinformatic study has shown that EGFR might be a candidate for SMYD2-mediated methylation. In this research, we aimed to investigate whether SMYD2 depletion could synergize with EGFR-activating treatment to promote intestinal goblet cell regeneration in IBD. METHODS SMYD2 flox C57BL/6 (SMYD2fl/fl) and intestine epithelial cell-specific conditional knockout of SMYD2 (SMYD2ΔIEC) male mice (8 to10-week old) were given 3 cycles of DSS treatment, each cycle including 5 days of 2% DSS in drinking water followed by 16 days of normal drinking water. EGF (50 μg/kg/day) was administered via intraperitoneal injection once per day for 6 days during the third cycle of DSS treatment (from day 42 to 47 along with DSS administration). The disease activity index (DAI), including body weight loss, stool consistency and colorectal bleeding, was monitored and calculated daily. Histologic scoring was used to evaluate the extent of histopathologic change in middle colon tissue. Goblet cell differentiation and maturation was analyzed via Alcian Blue/periodic acid-Schiff (AB/PAS) staining and immunostaining. RESULTS EGF treatment significantly increased the number of goblet cells (AB/PAS staining positive cells) in both SMYD2fl/fl and SMYD2ΔIEC mice. However, in SMYD2ΔIEC mice, more mature goblet cells were observed. In contrast, in SMYD2fl/fl mice, most goblet cells were accumulated at the lower half of colon crypts with small mucin particles. As compared with SMYD2fl/fl mice receiving EGF treatment, SMYD2 depletion combined with EGF injection (6 days) failed to significantly improve body weight loss and DAI scoring during DSS treatment, as well as histologic scoring (including inflammatory cell infiltration and epithelial tissue damage). Immunostaining of goblet cell differentiation markers (including ATOH1, SPDEF and KLF4) revealed no significant difference between SMYD2fl/fl and SMYD2ΔIEC mice. CONCLUSION SMYD2 depletion combined with EGF treatment could promote goblet cell expansion and maturation in mouse DSS-induced chronic colitis. However, the mechanism by which SMYD2 depletion facilitates goblet cell maturation needs further investigation.

Contrast Enhanced Ultrasound Molecular Imaging of Spontaneous Chronic Inflammatory Bowel Disease in an Interleukin-2 Receptor α-/- Transgenic Mouse Model Using Targeted Microbubbles.

Inflammatory bowel disease (IBD) is a lifelong inflammatory disorder with relapsing–remission cycles, which is currently diagnosed by clinical symptoms and signs, along with laboratory and imaging findings. However, such clinical findings are not parallel to the disease activity of IBD and are difficult to use in treatment monitoring. Therefore, non-invasive quantitative imaging tools are required for the multiple follow-up exams of IBD patients in order to monitor the disease activity and determine treatment regimens. In this study, we evaluated a dual P- and E-selectin-targeted microbubble (MBSelectin) in an interleukin-2 receptor α deficient (IL-2Rα−/−) spontaneous chronic IBD mouse model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI). We used IL-2Rα−/− (male and female on a C57BL/6 genetic background; n = 39) and C57BL/6 wild-type (negative control; n = 6) mice for the study. USMI of the proximal, middle, and distal colon was performed with MBSelectin using a small animal scanner (Vevo 2100) up to six times in each IL-2Rα−/− mouse between 6–30 weeks of age. USMI signals were compared between IL-2Rα−/− vs. wild-type mice, and sexes in three colonic locations. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E-stained sections and for selectin expression by immunofluorescence staining. We successfully detected spontaneous chronic colitis in IL-2Rα−/− mice between 6–30 weeks (onset at 6–14 weeks) compared to wild-type mice. Both male and female IL-2Rα−/− mice were equally (p = 0.996) affected with the disease, and there was no significant (p > 0.05) difference in USMI signals of colitis between the proximal, middle, and distal colon. We observed the fluctuating USMI signals in IL-2Rα−/− mice between 6–30 weeks, which might suggest a resemblance of the remission-flare pattern of human IBD. The ex vivo H&E and immunostaining further confirmed the inflammatory changes, and the high expression of P- and E-selectin in the colon. The results of this study highlight the IL-2Rα−/− mice as a chronic colitis model and are suitable for the long-term assessment of treatment response using a dual P- and E-selectin-targeted USMI.

Chronic Evolution of a Covered Perforation of Middle Third Transverse Colon by a Toothpick: A Case Report

Background: Foreign bodies (FBs) ingestion is generally rare but they can cause often bowel perforation if they have a sharp form and the patient did not manage to eliminate it naturally in the stools. Sometimes they can pierce the digestive tube wall leading to acute complications. Among the numerous cases of ingestion of FBs presented in the literature, the current case of transverse colon perforation, with chronic evolution, epiploic and pelvic abscess, submesocolic perivisceritis represents a particular one. Case Presentation: We present a case of a 59-year-old female patient, reported episodes of transitory melena in the past 6 months and chronic pain in the right iliac fossa, chronic anemia after ingesting a toothpick. The patient complained of chronic pain in the right iliac fossa, melena, intestinal transit disorders et impaired digestive tolerance. Computerized Tomography (CT) scan suggested peritonitis with pelvic adhesions and possible covered perforation in the right iliac fossa. Surgery started as an exploratory laparotomy to define the final diagnosis since a tumoral pathology couldn’t be eliminated. Colic perforation by a toothpick was found, followed by colporrhaphy and a biosynthetic patch on the great omentum. Conclusion: This paper presents the case of a patient with a sharp foreign body (toothpick) positioned in the transverse colon. The toothpick was ingested a few months ago and had a subtle chronic evolution causing colon perforation, covered peritonitis, intra-abdominal abscess, and chronic anemia because of recurrent episodes of melena. The treatment of choice was surgery with good postoperative evolution.

Changes and Prognostic Value of lncRNA CASC9 in Patients with Advanced Colon Cancer after Chemotherapy.

Objective Colon cancer (CC) shows a gradual increasing incidence in recent years, and chemotherapy is a frequently adopted treatment for patients with middle or advanced colon cancer (ACC), but it lacks prognostic markers after CC. Methods The changes of lncRNA CASC9 in 58 patients with CC were determined using a real-time quantitative PCR (qRT-PCR) assay before and after chemotherapy, and the correlation of serum lncRNA CASC9 with efficacy of FOLFOX4 regimen (oxaliplatin + calcium folinate + fluorouracil) was analyzed. The patients were followed up to understand the association of lncRNA CASC9 with overall survival (OS) and progression-free survival (PFS). Results Patients with CC showed notably higher lncRNA CASC9 expression than controls, and lncRNA CASC9 presented an association with the clinical stage of the patients. In addition, lncRNA CASC9 demonstrated a clinical value in predicting efficacy on patients and acted as one independent prognostic factor for PFS in patients with ACC. Conclusions With increased expression of serum lncRNA CASC9, patients with ACC suffered an unfavorable chemotherapy effect. In addition, serum lncRNA CASC9 is a promising sensitive indicator for prediction of ACC and is related to the clinical efficacy and prognosis of patients.

Surgical glance at pancreatic arterial anatomy

Aim. Study of anatomical variations of the pancreatic neck blood supply, which may affect the results of pancreaticoduodenectomy.Material and methods. Anatomic characteristics of arterial blood supply of pancreas were studied in 42 autopsied cases, who died from diseases not associated with abdominal organs failure. Clinical part of our study included 62 patients. Arterial anatomy was examined during early arterial phase of computer tomography. Options of the origin of the dorsa pancreatic artery were noted. All patients had “soft” pancreas confirmed by morphological examination and computer tomography. Main group included 20 patients. Dissection of the pancreas during pancreatoduodenectomy in this group were performed 10–15 mm left of portal vein confluence. Control (retrospective) group included 42 patients performed standard procedure, when pancreas was dissected above the portal vein confluence.Results. It was found that the neck of pancreas was supplied from dorsal pancreatic artery, found in all specimens. In 76% of cases it was a branch of splenic artery, in other cases – a branch of superior mesenteric artery. CT scan revealed the dorsal pancreatic artery in 54 (87.1%) people, in 8 patients the artery could not be identified. The dorsal pancreatic artery was a branch of the splenic artery in 64.8% of cases. In other cases it was a branch of the superior mesenteric artery, common hepatic artery, gastroduodenal artery and middle colon artery. If the dorsal pancreatic artery was a branch of the superior mesenteric, common hepatic, gastroduodenal artery, it was transected during lymphadenectomy. This led to higher frequency of postoperative pancreatic fistula.Conclusion. Localization of dorsal pancreatic artery must be taken into account during the pancreatoduodenectomy. That allows to decrease probability of postoperative pancreatic fistula.

Unique Neural Circuit Connectivity of Mouse Proximal, Middle, and Distal Colon Defines Regional Colonic Motor Patterns.

Background & AimsColonic motor patterns have been described by a number of different groups, but the neural connectivity and ganglion architecture supporting patterned motor activity have not been elucidated. Our goals were to describe quantitatively, by region, the structural architecture of the mouse enteric nervous system and use functional calcium imaging, pharmacology, and electrical stimulation to show regional underpinnings of different motor patterns.MethodsExcised colon segments from mice expressing the calcium indicator GCaMP6f or GCaMP6s were used to examine spontaneous and evoked (pharmacologic or electrical) changes in GCaMP-mediated fluorescence and coupled with assessment of colonic motor activity, immunohistochemistry, and confocal imaging. Three-dimensional image reconstruction and statistical methods were used to describe quantitatively mouse colon myenteric ganglion structure, neural and vascular network patterning, and neural connectivity.ResultsIn intact colon, regionally specific myenteric ganglion size, architecture, and neural circuit connectivity patterns along with neurotransmitter-receptor expression underlie colonic motor patterns that define functional differences along the colon. Region-specific effects on spontaneous, evoked, and chemically induced neural activity contribute to regional motor patterns, as does intraganglionic functional connectivity. We provide direct evidence of neural circuit structural and functional regional differences that have only been inferred in previous investigations. We include regional comparisons between quantitative measures in mouse and human colon that represent an important advance in showing the usefulness and relevance of the mouse system for translation to the human colon.ConclusionsThere are several neural mechanisms dependent on myenteric ganglion architecture and functional connectivity that underlie neurogenic control of patterned motor function in the mouse colon.

Protective effect of Callistemon citrinus on oxidative stress in rats with 1,2-dimethylhydrazine-induced colon cancer

Callistemon citrinus has terpenes effective in inducing antioxidant enzymes, an important mechanism involved in cancer chemoprevention. This study investigated the chemopreventive efficacy of herbal preparation of C. citrinus leaves against the oxidative stress produced during the colorectal cancer (CRC) in male Wistar rats. The amelioration of toxicity in a model of CRC induced with 1,2-dimethylhydrazine (DMH) was determined by assessing antioxidant enzymes, phase II enzymes activities and lipid peroxidation (LPO) products after 22 weeks of treatment. C. citrinus was administered at a daily oral dose of 250 mg/kg. The activities in proximal, middle and distal colon, liver, kidney and heart were determined. C. citrinus showed a strong antioxidant activity that correlated with the high content of phenolics and terpenoids. DMH treated animals showed a decrease of the enzymes activity in most tissues and the level of reduced glutathione (GSH). Conversely, the levels of lipid peroxidation products were increased. Macroscopic examination revealed the protective effect of C. citrinus in damaged organs caused by DMH. Moreover, histopathological examination of the liver displayed normal structure in the C. citrinus-treated group, unlike the DMH-treated group. C. citrinus supplementation significantly maintained or increased the antioxidant enzyme activities, whereas lipid peroxidation products levels were reduced to values similar to the level of control group. The ability of C. citrinus to induce the antioxidant system reduced the damage of oxidative stress, which makes this plant a good candidate to be used as a prevention agent in treatment of diseases such as colorectal cancer.