Clinical Utility of Laser Speckle Contrast Imaging and Real-Time Quantification of Bowel Perfusion in Minimally Invasive Left-Sided Colorectal Resections.

BACKGROUND: Left-sided colorectal surgery demonstrates high anastomotic leak rates, with tissue ischemia thought to influence outcomes. Indocyanine green is commonly used for perfusion assessment, but evidence remains mixed for whether it reduces colorectal anastomotic leaks. Laser speckle contrast imaging provides dye-free perfusion assessment in real-time through perfusion heat maps and quantification. OBJECTIVE: This study investigates the efficacy of advanced visualization (indocyanine green versus laser speckle contrast imaging), perfusion assessment, and utility of laser speckle perfusion quantification in determining ischemic margins. DESIGN: Prospective intervention group using advanced visualization with case-matched, retrospective control group. SETTINGS: Single academic medical center. PATIENTS: Forty adult patients undergoing elective, minimally invasive, left-sided colorectal surgery. INTERVENTIONS: Intraoperative perfusion assessment using white light imaging and advanced visualization at 3 time points: T1-proximal colon after devascularization, before transection, T2-proximal/distal colon before anastomosis, and T3-completed anastomosis. MAIN OUTCOME MEASURES: Intraoperative indication of ischemic line of demarcation before resection under each visualization method, surgical decision change using advanced visualization, post hoc laser speckle perfusion quantification of colorectal tissue, and 30-day postoperative outcomes. RESULTS: Advanced visualization changed surgical decision-making in 17.5% of cases. For cases in which surgeons changed a decision, the average discordance between the line of demarcation in white light imaging and advanced visualization was 3.7 cm, compared to 0.41 cm ( p = 0.01) for cases without decision changes. There was no statistical difference between the line of ischemic demarcation using laser speckle versus indocyanine green ( p = 0.16). Laser speckle quantified lower perfusion values for tissues beyond the line of ischemic demarcation while suggesting an additional 1 cm of perfused tissue beyond this line. One (2.5%) anastomotic leak occurred in the intervention group. LIMITATIONS: This study was not powered to detect differences in anastomotic leak rates. CONCLUSIONS: Advanced visualization using laser speckle and indocyanine green provides valuable perfusion information that impacts surgical decision-making in minimally invasive left-sided colorectal surgeries. See Video Abstract . UTILIDAD CLNICA DE LAS IMGENES DE CONTRASTE MOTEADO CON LSER Y LA CUANTIFICACIN EN TIEMPO REAL DE LA PERFUSIN INTESTINAL EN RESECCIONES COLORRECTALES DEL LADO IZQUIERDO MNIMAMENTE INVASIVAS: ANTECEDENTES:La cirugía colorrectal del lado izquierdo demuestra altas tasas de fuga anastomótica, y se cree que la isquemia tisular influye en los resultados. El verde de indocianina se utiliza habitualmente para evaluar la perfusión, pero la evidencia sobre si reduce las fugas anastomóticas colorrectales sigue siendo contradictoria. Las imágenes de contraste moteado con láser proporcionan una evaluación de la perfusión sin colorantes en tiempo real a través de mapas de calor de perfusión y cuantificación.OBJETIVO:Este estudio investiga la eficacia de la evaluación de la perfusión mediante visualización avanzada (verde de indocianina versus imágenes de contraste moteado con láser) y la utilidad de la cuantificación de la perfusión con moteado láser para determinar los márgenes isquémicos.DISEÑO:Grupo de intervención prospectivo que utiliza visualización avanzada con un grupo de control retrospectivo de casos emparejados.LUGARES:Centro médico académico único.PACIENTES:Cuarenta pacientes adultos sometidos a cirugía colorrectal electiva, mínimamente invasiva, del lado izquierdo.INTERVENCIONES:Evaluación de la perfusión intraoperatoria mediante imágenes con luz blanca y visualización avanzada en tres puntos temporales: T1-colon proximal después de la devascularización, antes de la transección; T2-colon proximal/distal antes de la anastomosis; y T3-anastomosis completa.PRINCIPALES MEDIDAS DE VALORACIÓN:Indicación intraoperatoria de la línea de demarcación isquémica antes de la resección bajo cada método de visualización, cambio de decisión quirúrgica mediante visualización avanzada, cuantificación post-hoc de la perfusión con láser moteado del tejido colorrectal y resultados posoperatorios a los 30 días.RESULTADOS:La visualización avanzada cambió la toma de decisiones quirúrgicas en el 17,5% de los casos. Para los casos en los que los cirujanos cambiaron una decisión, la discordancia promedio entre la línea de demarcación en las imágenes con luz blanca y la visualización avanzada fue de 3,7 cm, en comparación con 0,41 cm (p = 0,01) para los casos sin cambios de decisión. No hubo diferencias estadísticas entre la línea de demarcación isquémica utilizando láser moteado versus verde de indocianina (p = 0,16). El moteado con láser cuantificó valores de perfusión más bajos para los tejidos más allá de la línea de demarcación isquémica y al mismo tiempo sugirió 1 cm adicional de tejido perfundido más allá de esta línea. Se produjo una fuga anastomótica (2,5%) en el grupo de intervención.LIMITACIONES:Este estudio no tuvo el poder estadístico suficiente para detectar diferencias en las tasas de fuga anastomótica.CONCLUSIONES:La visualización avanzada utilizando moteado láser y verde de indocianina proporciona información valiosa sobre la perfusión que impacta la toma de decisiones quirúrgicas en cirugías colorrectales mínimamente invasivas del lado izquierdo. (Traducción-Dr. Ingrid Melo).

Discontinuity of marginal artery at splenic flexure and rectosigmoid junction: A systematic review and meta-analysis.

AIM: The aim of this study was to provide comprehensive evidence-based assessment of the discontinuity of the marginal artery at the splenic flexure (SF) and the rectosigmoid junction (RSJ). METHOD: A systematic review was conducted of literature published to 26 December 2022 in the electronic databases PubMed, SCOPUS and Web of Science to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using the Metafor package in R. The primary outcomes were the pooled PPEs of the marginal artery at the SF and the RSJ. The secondary outcome was the size of vascular anastomoses. RESULTS: A total of 21 studies (n = 2,864 patients) were included. The marginal artery was present at the splenic flexure in 82% (95% CI: 62-95) of patients. Approximately 81% (95% CI: 63-94%) of patients had a large macroscopic anastomosis, while the remainder (19%) had small bridging ramifications forming the vessel. The marginal artery was present at the RSJ in 82% (95% CI: 70-91%) of patients. CONCLUSION: The marginal artery may be absent at the SF and the RSJ in up to 18% of individuals, which may confer a higher risk of ischaemic colitis. As a result of high interstudy heterogeneity noted in our analysis, further well-powered studies to clarify the prevalence of the marginal artery at the SF and the RSJ, as well as its relationship with other complementary colonic collaterals (intermediate and central mesenteric), are warranted.

Cadaveric and CT angiography study of vessels around the transverse colon mesentery.

BACKGROUND: Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse colon. Although the vessels of the right colon have been investigated, middle colic artery (MCA) variation and the relationship with vessels around the transvers colon are unknown. We investigated variation of the MCA using computed tomography angiography (CTA) and cadaver specimen and the relationship between the superior mesenteric vein (SMV) and MCA using CTA. The classification of vessels around the transverse colon may lead to safer and reliable surgery. METHODS: This study included 505 consecutive patients who underwent CTA in our institution from 2014 to 2020 and 44 cadaver specimens. Vascular anatomical classifications and relationships were analyzed using CT images. RESULTS: The MCA was defined as the arteries arising from the superior mesenteric artery (SMA) that flowed into the transverse colon at the distal ends. The classifications were as follows: type I, branching right and left from common trunk; type II, the right and left branches bifurcated separately from the SMA; and type III, the MCA branched from a vessel other than the SMA. Type II was subclassified into two subtypes, type IIa with one left branch and type IIb with two or more left branches from SMA. In the CTA and cadaver studies, respectively, the classifications were as follows: type I, n = 290 and n = 31; type IIa, n = 211 and n = 13; type IIb, n = 3 and n = 0; and type III, n = 1 and n = 0. We classified the relationship between the MCA and left side of the SMV into three types: type A, a common trunk runs along the left edge of the SMV (n = 173; 59.7%); type B, a right branch of the MCA runs along the left edge of the SMV (n = 116; 40.0%); and type C, the MCA runs dorsal of the SMV (n = 1; 0.3%). CONCLUSIONS: This study revealed that The MCA branching classifications and relationship between the SMV and MCA. Preoperative CT angiography may be able to reliably identify vessel variation, which may be useful in clinical practice.

Arterial branching pattern of the cranial mesenteric artery in the degu (Octodon degus).

BACKGROUND: The cranial mesenteric artery exhibits a species-specific ramification pattern that adapts to the morphology of the intestinal tract. The degu is a strictly herbivorous rodent with a well-developed large intestine with a spiral loop in the ascending colon; therefore, the cranial mesenteric artery likely demonstrates a degu-specific ramification pattern. Thus, we traced the cranial mesenteric artery to establish the detailed ramification pattern of the branches. METHODS: Eighteen male degus were injected with 0.3-0.8 ml of a latex mixture and water at a 1:1 ratio in conjunction with red acrylic paint coloring using a catheter inserted into the thoracic aorta. The cranial mesenteric artery was traced using a surgical microscope and photographed using a digital camera. RESULTS: The arteries emerging from the cranial mesenteric artery exhibited frequent variations in number, distribution area, anastomosis pattern, and branching order. In the most frequent cases (22%), the cranial mesenteric artery sequentially gave rise to caudal pancreaticoduodenal, middle colic, right colic, jejunal, and ileocolic arteries. The right and middle colic arteries exhibited four different ramification patterns. In the most common cases (67%), the middle and right colic arteries emerged independently from the cranial mesenteric artery. The former was distributed to the transverse and descending colon, whereas the latter sent branches to the spiral loop of the ascending colon. CONCLUSIONS: The complex ramification pattern of the right colic artery in the degu may be an adaptation to the characteristic running pattern of the ascending colon. Thus, we present the first comprehensive report of the arterial branching pattern of the cranial mesenteric artery in the degu.

Widespread mesenteric phlebosclerosis presenting as intestinal obstruction due to stenosis of the right-sided colon.

Mesenteric phlebosclerosis is a rare form of intestinal ischemia characterized by thickening of the right-sided colon and calcification of the mesenteric vein. We describe the case of a 58-year-old woman admitted to our hospital because of abdominal pain and distension. An abdominal computed tomography study revealed remarkable dilatation and fluid collection of the small intestine compatible with intestinal obstruction, which was considered to be the result of stenosis of the ascending colon. The thickened wall of the cecum and ascending colon was associated with calcification of the colonic wall and mesenteric veins. Colonoscopy showed dark purple discoloration of the edematous mucosa from the splenic flexure through the hepatic flexure, at which point the colonoscope could not be advanced further because of stenosis of the ascending colon. Over 10 years previously, the patient had taken an herbal medicine containing gardenia fruit, which can cause mesenteric phlebosclerosis. An extensive colonic resection was performed after intestinal decompression. This case highlights extensive mesenteric phlebosclerosis causing intestinal obstruction from the cecum through the proximal portion of the sigmoid colon, which was treated with extensive colonic resection.

Mesenteric occlusive disease of the inferior mesenteric artery is associated with anastomotic leak after left-sided colon and rectal cancer surgery: a retrospective cohort study.

PURPOSE: Anastomotic leak (AL) is a serious complication following colorectal surgery. Atherosclerosis causes inadequate anastomotic perfusion and is suggested to be a risk factor for AL. The aim of this study was to investigate the association of mesenteric occlusive disease on preoperative computed tomography (CT) scan with AL after left-sided colon or rectal cancer surgery. METHODS: This was a retrospective, multicenter cohort study including 1273 patients that underwent left-sided or rectal cancer resection between 2009 and 2018 from three hospitals in the Netherlands. AL patients were 1:1 matched with non-leak patients and preoperative contrast-enhanced CT-scans were retrospectively analyzed for mesenteric atherosclerotic lesions. The main outcome measure was the presence of mesenteric occlusive disease on the preoperative CT-scan. RESULTS: Anastomotic leak developed in 6% of 1273 patients (N = 76). Low anterior resection and stage I-III disease were statistically significant associated with AL (p = 0.01, p = 0.04). No other statistically significant differences in patient characteristics between AL and non-leak patients were found. A clinically significant stenosis (≥ 70-100%) of the inferior mesenteric artery was statistically significant more frequent present in AL patients, compared to non-leak patients (p < 0.01). No statistically significant differences in the presence of mesenteric occlusive disease of the celiac artery and superior mesenteric artery between AL patients and non-leak patients were found. CONCLUSION: Mesenteric occlusive disease of the IMA on preoperative CT-scan is associated with AL after left-sided colon or rectal resection for cancer. Preoperative identification of high-risk patients with a preoperative CT-scan of the mesenteric vasculature might be useful to reduce the risk of AL.

Influence of perioperative risk factors on the development of transmural colonic ischemia after open repair of ruptured abdominal aortic aneurysm.

BACKGROUND: Development of colonic ischemia (CI) after ruptured abdominal aortic aneurysm (RAAA) treatment is a lethal complication with perioperative mortality reported to be high as 50%. Therefore, the main goal of this study was to identify pre-, intra- and postoperative risk factors associated with CI in patients undergoing open repair (OR) due to RAAA, that might help to select patients who are more prone to develop CI. METHODS: This was a single-center prospective cohort study on patients with RAAA undergoing OR between January 1st 2018 and July 1st 2019, at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia. During this period 89 patients were treated due to RAAA and all were included in the study. The primary endpoint was grade III CI, or transmural necrosis, diagnosed by laparotomy. RESULTS: Out of 89 patients operated due to RAAA, CI was diagnosed in 14 (15.73%). During the operation, patients with CI had a longer duration of hypotension (42.86±35.82 vs. 24.13±23.48, P=0.021) and more common significant hypotension (54.54% vs. 14.66%, P=0.024). In the postoperative course, patients with CI had more common signs of abdominal compartment syndrome (71.42% vs. 25.33%, P=0.001) and higher mortality rate (78.57% vs 29.33%, P=0.001). The univariate regression model showed that one of the most significant factors that were associated with CI were age higher than 75 years, significant hypotension lasting more than one hour, organ lesion, development of abdominal compartment syndrome and higher potassium values on third and fourth quartile. CONCLUSIONS: Grade III colon ischemia (transmural) remains the important cause of mortality after ruptured abdominal aortic aneurysm repair. We identified pre- and intraoperative and postoperative risk factors that could improve the selection of patients for primary open abdomen treatment or early exploratory laparotomy in order to prevent or timely diagnose colon ischemia.

[Laparoscopic Right-Sided Colon Cancer Surgery Using Pancreas/Duodenum 3DCT(PDCT)].

BACKGROUND AND PURPOSE: The right colic artery(RCA)and gastrocolic trunk(GCT)traverse around the pancreas and duodenum and branch divergently, thus, complicating right-sided colon cancer surgery. The usefulness of pancreatic/duodenum 3DCT imaging(pancreas/duodenum CT: PDCT)for laparoscopic right-sided colon cancer surgery was investigated. PATIENT AND METHOD: The patient was a woman, in her 80's with 2 sites of ascending colon cancer:(1)A-C, cT4b(retroperitoneum) N2aM0, Stage Ⅲc;(2)A, cT3N1bM0, Stage Ⅲb. A radical surgery was planned. Contrast-enhanced CT colonography( CTC)was performed preoperatively, and 3 3DCT images(CTC, arteriovenous 3DCT, and PDCT)were created using Workstation: Ziostation 2®(Ziosoft). These 3DCT images were combined and used for preoperative simulation and intraoperative navigation. RESULT: Composite images of CTC and arterial 3DCT identified the dominance of ileocolic artery(ICA)and RCA. In addition, a composite venous 3DCT image confirmed the branching and course of ileocolic vein(ICV)and right colic vein(RCV). Composite images of PDCT and arteriovenous 3DCT showed that the RCA branched from the superior mesenteric artery at the level of the third part of duodenum and ran ventral to the pancreatic head, while the RCV branched from the GCT in front of the pancreatic head, with the right gastroepiploic vein(RGEV). A laparoscopic combined ileal and retroperitoneal resection and D3 lymph node dissection with ICA/V and RCA/V root dissection were planned. Surgical simulation facilitated the identification of ICA/V and RCA/V and surgical procedure. The operative time was 310 minutes, and blood loss was 90 mL. Histopathological examination confirmed the diagnosis of(1)pT3(SS)N1bM0, Stage Ⅲb and(2)pT3 (SS)N1aM0, Stage Ⅲb. The patient was discharged 10 days post-surgery, without any complications. Currently, there is no apparent recurrence at 1-year follow-up. CONCLUSION: PDCT clarified the location of the RCA and GCT in relation to the pancreas and duodenum and complemented the laparoscopic right-sided colon cancer surgery.

Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis.

Introduction: In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H2S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis. Methods: In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g â€¢ kg-1 i.p., 2: glibenclamide (GL) 5 mg • kg-1 i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO2) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn's multiple comparison test (mitochondria). p < 0.05 was considered significant. Results: STS increased µHbO2 (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO2 and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO2 and µflow (µHbO2 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO2 and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO2 or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered. Conclusion: The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.

Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder for many people associated with poor health. Although there are some clinical drugs for IBD treatment, the development of effective therapeutics on IBD patients has always been necessary. Here, we show that externalized phosphatidylserine (PS) is observed on the surface of colonic capillaries. Annexin A5 (ANXA5) with high affinity for PS has a good targeting to the colon and effectively alleviates experimental colitis. In contrast, ANXA5 mutant (A5m) lacking the PS-binding ability, has no accumulation in the colon and no therapeutic effects on colitis. Mechanistic investigations indicate that ANXA5 reduces the inflammatory cell infiltration by inhibiting endothelial cell activation dependent on PS-binding ability. With the increasing of PS exposure on activated HUVECs (human umbilical vein endothelial cells), ANXA5 binding induces the internalization of TLR4 via PS-dependent endocytosis. We provide new insights on the molecular mechanism of ANXA5 for its anti-inflammatory effect. Our data suggest that PS-externalization is a potential target of ANXA5 aiming at targeted drug delivery (TDD) for IBD treatment.

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

BACKGROUND: Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. OBJECTIVE: We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. DESIGN: We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. SETTINGS: This was a multicenter trial. PATIENTS: Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge. INTERVENTION: Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. MAIN OUTCOME MEASURES: Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. RESULTS: This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34). LIMITATIONS: The predetermined sample size to adequately reduce the risk of type II error was not achieved. CONCLUSIONS: Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560. VALORACIN DE LA IRRIGACIN DE LADO IZQUIERDO/RESECCIN ANTERIOR BAJA PILAR III UN ESTUDIO ALEATORIZADO, CONTROLADO, PARALELO Y MULTICNTRICO QUE EVALA LOS RESULTADOS DE LA IRRIGACIN CON PINPOINT IMGENES DE FLUORESCENCIA CERCANA AL INFRARROJO EN LA RESECCIN ANTERIOR BAJA: ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).

An organoid-based organ-repurposing approach to treat short bowel syndrome.

The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment.

Intraoperative perfusion assessment of the proximal colon by a visual grading system for safe anastomosis after resection in left-sided colorectal cancer patients.

We aimed to evaluate the clinical feasibility of a new visual grading system. We included 50 patients who underwent resection of primary colorectal cancer. Before anastomosis, the marginal vessel was cut and the perfusion status was assessed by a visual grading system. The visual grading system is comprised of five grades according to the bleeding from the marginal vessel and is categorized into 4 groups: good (grade A and B), moderate (grade C), poor (grade D) and none (grade E). Colorectal anastomosis was performed only in the good and moderate groups. We compared postoperative outcomes between the good and moderate groups and analysed the factors affecting the perfusion grade. Among the patients, 48% were grade A, 12% were grade B, and 40% were grade C. There was no anastomotic leakage. Only one patient with grade C showed ischemic colitis and needed reoperation. Age was the only factor correlated with perfusion grade in multivariate analysis (OR 1.080, 95% CI 1.006-1.159, p = 0.034). The perfusion grades were significantly different between > 65 and < 65 year-old patients (> 65, A 29.2% B 12.5% C 58.3% vs. < 65, A 65.4% B 11.5% C 23.1%, p = 0.006). Our intraoperative perfusion assessment that uses a cutting method and a visual grading system is simple and useful for performing a safe anastomosis after colorectal resection. If the perfusion grade is better than grade C, an anastomosis can be performed safely. Age was found to be an important factor affecting the perfusion grade.

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability.

BACKGROUND & AIMS: Increased vascular permeability (VP) has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). However, the pathological causes of increased intestinal VP in IBD remain largely unknown. METHOD: Fibrinogen level was measured in dextran sulphate sodium (DSS)-induced colitis and patients with ulcerative colitis. Gly-Pro-Arg-Pro acetate (GPRP), an Fg inhibitor, was used to detect the effect of Fg inhibition on the pathogenesis of DSS-induced colitis, as indicated by tissue damage, cytokine release and inflammatory cell infiltration. Miles assay was used to detect vascular permeability. RESULTS: Through tandem mass tag-based quantitative proteomics, fibrinogen (Fg) was found to be upregulated in the colon of DSS-treated mice, which was consistent with increased Fg level in colon sample of patients with ulcerative colitis. Gly-Pro-Arg-Pro acetate (GPRP), an Fg inhibitor, significantly alleviated DSS-induced colitis as indicated by improvement of body weight loss and mortality. GPRP decreased colonic inflammation and VP in DSS-treated mice. In vivo, Fg enhanced VP as indicated by Miles assay, which was significantly inhibited by GRPR, AKT (serine/threonine kinase 1) inhibitors and low doses of Jasplakinolide which induced actin polymerization, while was dramatically enhanced by Cytochalasin D (an actin polymerization inhibitor). Moreover, activation of AKT was found in vessels of DSS-treated mice. In vitro, Fg induced activation of AKT and depolymerization of microfilament and promoted cell-to-cell disaggregation. Furthermore, inhibition of AKT decreased Fg-induced microfilament depolymerization. CONCLUSIONS: Our findings highlight the importance of Fg in regulating colitis by modulation of VP via activating AKT and subsequent depolymerization of microfilament and suggest Fg as an attractive target for anti-colitis treatment.

Therapeutic Opportunities for Intestinal Angioectasia- Targeting PPARγ and Oxidative Stress.

Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment. Using data from the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), we analyzed 12 million patient reports to identify drugs inversely correlated with gastrointestinal bleeding and potentially limiting AEC severity. FAERS analysis revealed that drugs used in patients with diabetes and those targeting PPARγ-related mechanisms were associated with decreased AEC phenotypes (P < 0.0001). Electronic health records (EHRs) at University of Cincinnati Hospital were analyzed to validate FAERS analysis. EHR data showed a 5.6% decrease in risk of AEC and associated phenotypes in patients on PPARγ agonists. Murine knockout models of AEC phenotypes were used to construct a gene-regulatory network of candidate drug targets and pathways, which revealed that wound healing, vasculature development and regulation of oxidative stress were impacted in AEC pathophysiology. Human colonic tissue was examined for expression differences across key pathway proteins, PPARγ, HIF1α, VEGF, and TGFß1. In vitro analysis of human AEC tissues showed lower expression of PPARγ and TGFß1 compared with controls (0.55 ± 0.07 and 0.49 ± 0.05). National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) RNA-Seq data was analyzed to substantiate human tissue findings. This integrative discovery approach showing altered expression of key genes involved in oxidative stress and injury repair mechanisms presents novel insight into AEC etiology, which will improve targeted mechanistic studies and more optimal medical therapy for AEC.