The middle colic artery usually arises from the superior mesenteric artery, but in rare cases it may arise from the coeliac trunk or its branches. The aim of this study was to investigate variant origins of the middle colic artery on computed tomography and anatomical dissection. Variant middle colic arteries were identified on computed tomography as part of an ongoing study investigating anatomical variations of vessels of the upper abdomen. Three-dimensional reconstructions were made to demonstrate the variant findings. Cadaveric dissections were performed as part of a routine dissection course. We report five cases of rare variant origins of the middle colic artery arising from the coeliac axis. Among these sites of origin were the coeliac trunk, the gastrosplenic trunk, the splenic artery, and the common hepatic artery. Four cases were identified on multi-detector computed tomography and one in a cadaver. In all cases, the vessels passed posterior to the body of the pancreas before entering the transverse mesocolon. Knowledge of middle colic artery variations is important to prevent inadvertent injury in digestive surgery, especially in the hepatopancreatic area. Variant origins of the middle colic artery are rare, and their knowledge is crucial to prevent unnecessary iatrogenic injury during abdominal surgery.
Both aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) belong among key regulators of xenobiotic metabolism in the intestinal tissue. AhR in particular is activated by a wide range of environmental and dietary carcinogens. The data accumulated over the last two decades suggest that both of these transcriptional regulators play a much wider role in the maintenance of gut homeostasis, and that both transcription factors may affect processes linked with intestinal tumorigenesis. Intestinal epithelium is continuously exposed to a wide range of AhR, PXR and dual AhR/PXR ligands formed by intestinal microbiota or originating from diet. Current evidence suggests that specific ligands of both AhR and PXR can protect intestinal epithelium against inflammation and assist in the maintenance of epithelial barrier integrity. AhR, and to a lesser extent also PXR, have been shown to play a protective role against inflammation-induced colon cancer, or, in mouse models employing overactivation of Wnt/β-catenin signaling. In contrast, other evidence suggests that both receptors may contribute to modulation of transformed colon cell behavior, with a potential to promote cancer progression and/or chemoresistance. The review focuses on both overlapping and separate roles of the two receptors in these processes, and on possible implications of their activity within the context of intestinal tissue.
- MeSH
- karcinogeneze genetika metabolismus MeSH
- kolon metabolismus MeSH
- myši MeSH
- pregnanový X receptor metabolismus MeSH
- receptory aromatických uhlovodíků * genetika metabolismus MeSH
- steroidní receptory * metabolismus MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
There is an urgent need to develop therapeutics for inflammatory bowel disease (IBD) because up to 40% of patients with moderate-to-severe IBD are not adequately controlled with existing drugs. Glutamate carboxypeptidase II (GCPII) has emerged as a promising therapeutic target. This enzyme is minimally expressed in normal ileum and colon, but it is markedly up-regulated in biopsies from patients with IBD and preclinical colitis models. Here, we generated a class of GCPII inhibitors designed to be gut-restricted for oral administration, and we interrogated efficacy and mechanism using in vitro and in vivo models. The lead inhibitor, (S)-IBD3540, was potent (half maximal inhibitory concentration = 4 nanomolar), selective, gut-restricted (AUCcolon/plasma > 50 in mice with colitis), and efficacious in acute and chronic rodent colitis models. In dextran sulfate sodium-induced colitis, oral (S)-IBD3540 inhibited >75% of colon GCPII activity, dose-dependently improved gross and histologic disease, and markedly attenuated monocytic inflammation. In spontaneous colitis in interleukin-10 (IL-10) knockout mice, once-daily oral (S)-IBD3540 initiated after disease onset improved disease, normalized colon histology, and attenuated inflammation as evidenced by reduced fecal lipocalin 2 and colon pro-inflammatory cytokines/chemokines, including tumor necrosis factor-α and IL-17. Using primary human colon epithelial air-liquid interface monolayers to interrogate the mechanism, we further found that (S)-IBD3540 protected against submersion-induced oxidative stress injury by decreasing barrier permeability, normalizing tight junction protein expression, and reducing procaspase-3 activation. Together, this work demonstrated that local inhibition of dysregulated gastrointestinal GCPII using the gut-restricted, orally active, small-molecule (S)-IBD3540 is a promising approach for IBD treatment.
- MeSH
- cytokiny metabolismus MeSH
- glutamátkarboxypeptidasa II * antagonisté a inhibitory MeSH
- idiopatické střevní záněty * farmakoterapie patologie MeSH
- kolitida * farmakoterapie metabolismus MeSH
- kolon patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND & AIMS: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. METHODS: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. RESULTS: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). CONCLUSIONS: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. CLINICALTRIALS: gov number: NCT03107793.
- MeSH
- biologické přípravky * MeSH
- Crohnova nemoc * diagnostické zobrazování farmakoterapie MeSH
- dospělí MeSH
- indukce remise MeSH
- kolon MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- ustekinumab terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
Anastomotický leak je v kolorektální chirurgii závažnou komplikací. Problematikou poruch hojení střevní anastomózy se zabývá řada experimentálních prací zejména ve smyslu aplikovaného výzkumu. Design zvířecích modelů je přitom různorodý a výsledky jednotlivých prací jsou těžko porovnatelné. Tato práce pojednává souhrnně o hlavních bodech problematiky plánování zvířecích modelů střevních anastomóz, které jsou jednotlivě rozebrány. Hlavní částí textu je popis modelu defektní střevní anastomózy prasete. Anastomóza je v modelu konstruována s lokalizovanou protruzí sliznice. Zvířata jsou pooperačně sledována 3 týdny, monitorovány jsou jak klinický stav, tak změny vitálních hodnot, laboratorních parametrů, je prováděno v definovaných bodech CT vyšetření. Na konci observačního období jsou odebrány vzorky, hodnocen makroskopický nález v dutině břišní, skórování adhezí, známky leaku či poruch pasáže. Histologicky jsou preparáty hodnoceny jak standardními metodami analyzujícími vaskularitu, zánětlivou infiltraci a podíl kolagenu, tak metodami vyvinutými de novo pro potřeby experimentu, jako je analýza integrity střevní stěny v místě slizniční protruze. Experimentálního modelu si ceníme pro možnost systematické a podrobné analýzy stavu zhojení anastomózy v kombinaci s podrobným observačním protokolem, jež vytvářejí klinicky relevantní výsledky.
Anastomotic leak is a serious complication in colorectal surgery. The problem of intestinal anastomosis healing disorders is dealt with by a number of experimental studies, especially in applied research. The design of animal models is diverse and the results of individual studies are difficult to compare. This paper summarizes the main issues of planning animal models of intestinal anastomoses, which are discussed individually. The main part of the text is a description of the defective intestinal anastomosis model of the pig. The anastomosis is constructed in the model with a localized mucosal protrusion. The animals are monitored for 3 weeks postoperatively, the clinical condition and changes in vital values and laboratory parameters are monitored, and CT examinations are performed at defined points. At the end of the observation period, samples are taken, macroscopic findings in the abdominal cavity are evaluated, adhesions are scored, and signs of leakage or passage disorders are assessed. The preparations are evaluated histologically both by standard methods analyzing vascularity, inflammatory infiltration and the proportion of collagen, and by methods developed de novo for the needs of the experiment, such as the analysis of the integrity of the intestinal wall at the site of the mucosal protrusion. We value the experimental model for the possibility of a systematic and detailed analysis of the healing state of the anastomosis in combination with a detailed observation protocol, which produces clinically relevant results.
Calcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.
- MeSH
- blokátory kalciových kanálů MeSH
- kardiovaskulární nemoci * MeSH
- kolon MeSH
- lidé MeSH
- nádory rekta * MeSH
- nežádoucí účinky léčiv * MeSH
- sekundární malignity * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Kolorektální trauma se v soudobých válečných konfliktech vyskytuje v 5–10 %. Nejčastější příčinou je střelné nebo střepinové poranění, kontuzně-lacerační mechanismus je ve válečné zóně ojedinělý. I přes moderní léčebné postupy je ale zatíženo vysokou mírou morbidity, zejména pokud není včas diagnostikováno a léčeno. Management chirurgické léčby upřesňují jednoduchá skórovací schémata – colon injury scale, rectal injury scale a Flintův skórovací systém. Resekční výkony tračníku s primární nebo odloženou anastomózou nemají vyšší riziko komplikovaného hojení a v dnešní době jsou upřednostňovány před konstrukcí terminálních stomií. Ty jsou indikovány při závažné oběhové nestabilitě při hemoragicko-traumatickém nebo septickém šoku s pokročilou difuzní peritonitidou. K traumatu intraperitoneálního segmentu rekta se přistupuje stejně jako k tračníku. Poranění extraperitoneálního rekta bez devastace měkkých tkání může být ošetřeno transanální suturou nebo i bez ní. Naopak devastující poranění rekta spolu s měkkými tkáněmi pánve se mají primárně zajistit derivační stomií a odloženou rekonstrukcí. Presakrální drenáž nebo laváž rekta již nejsou doporučovány.
The rate of colorectal trauma is 5–10 % in modern war conflicts. The most common causes include gunshots or shrapnel injuries; the contusion-laceration mechanism occurs in sporadic cases in the war zone. Despite modern surgical procedures, however, it is associated with a high rate of morbidity, especially if it is not diagnosed and treated in time. Surgical management is specified by simple scoring schemes – the colon injury scale, rectal injury scale and the Flint grading system. Colonic resection with primary or delayed anastomosis is not associated with a higher risk of complicated healing and is nowadays preferred over the construction of terminal stomas. These are indicated only for cases with severe hemodynamic instability in traumatic-hemorrhagic or septic shock with severe diffuse peritonitis. Trauma to the intraperitoneal segment of the rectum is treated in the same way as trauma to the colon. An extraperitoneal rectal injury without soft tissue devastation can be treated with or without a transanal suture. On the contrary, devastating injuries to the rectum including the pelvic soft tissues should be primarily controlled with a stoma with delayed reconstruction. Presacral drainage or rectal stump lavage are no longer recommended.
- MeSH
- anastomóza chirurgická MeSH
- kolon chirurgie diagnostické zobrazování zranění MeSH
- lidé MeSH
- penetrující rány * chirurgie diagnostické zobrazování MeSH
- poranění břicha chirurgie diagnostické zobrazování MeSH
- rektum chirurgie diagnostické zobrazování zranění MeSH
- válečná poranění * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Modulation of gut microbiome composition seems to be a promising therapeutic strategy for a wide range of pathologic states. However, these microbiota-targeted interventions may affect production of microbial metabolites, circulating factors in the gut-liver axis influencing hepatic drug metabolism with possible clinical relevance. Butyrate, a short-chain fatty acid produced through microbial fermentation of dietary fibers in the colon, has well established anti-inflammatory role in the intestine, while the effect of butyrate on the liver is unknown. In this study, we have evaluated the effect of butyrate on hepatic AhR activity and AhR-regulated gene expression. We have showed that AhR and its target genes were upregulated by butyrate in dose-dependent manner in HepG2-C3 as well as in primary human hepatocytes. The involvement of AhR has been proved using specific AhR antagonists and siRNA-mediated AhR silencing. Experiments with AhR reporter cells have shown that butyrate regulates the expression of AhR target genes by modulating the AhR activity. Our results suggest also epigenetic action by butyrate on AhR and its repressor (AHRR) presumably through mechanisms based on HDAC inhibition in the liver. Our results demonstrate that butyrate may influence the drug-metabolizing ability of liver enzymes e.g., through the interaction with AhR-dependent pathways.
1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.
- MeSH
- gastrointestinální endoskopie * MeSH
- kolon diagnostické zobrazování MeSH
- lidé MeSH
- prekancerózy * MeSH
- rektum diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
