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.

Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and includes epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS. METHODS: Seventy-eight healthy subjects (controls) and 223 patients with IBS were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate in vivo permeability. Immunohistochemistry, western blot, and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin. Caco-2 or human umbilical vein endothelial cell monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data. RESULTS: The intestinal epithelial barrier was compromised in patients with IBS throughout the gastrointestinal tract. IBS-soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in human umbilical vein endothelial cell monolayers through the activation of protease-activated receptor-2 and histone deacetylase 11, resulting in vascular endothelial cadherin downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of patients with IBS. CONCLUSIONS: Epithelial and vascular barriers are compromised in patients with IBS and contribute to clinical manifestations.

A novel artificial intelligence-assisted "vascular healing" diagnosis for prediction of future clinical relapse in patients with ulcerative colitis: a prospective cohort study (with video).

BACKGROUND AND AIMS: Image-enhanced endoscopy has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)-assisted image-enhanced endoscopy may help nonexperts provide objective accurate predictions with the use of optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose "vascular-healing" and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC. METHODS: This open-label prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histologic assessment were recorded for 6 colorectal segments from each patient. Patients were followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2 RESULTS: The clinical relapse rate was significantly higher in the AI-based vascular-active group (23.9% [16/67]) compared with the AI-based vascular-healing group (3.0% [1/33)]; P = .01). In a subanalysis predicting clinical relapse in patients with MES ≤1, the area under the receiver operating characteristic curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65). CONCLUSIONS: AI-based vascular-healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable.

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).

Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender.

INTRODUCTION: Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation. METHODS: Patients undergoing elective colorectal resection had colonic ICGFA both immediately after operative commencement prior to any dissection and again, as usual, just before anastomotic construction. Video recordings of both ICGFA acquisitions were blindly quantified post hoc across selected colonic regions of interest (ROIs) using tracking-quantification software and computationally compared with satisfactory perfusion assumed in second time-point ROIs, demonstrating 85% agreement with baseline ICGFA. ROI quantification outputs detailing projected perfusion sufficiency-insufficiency zones were compared to the actual surgeon-selected transection/anastomotic construction site for left/right-sided resections, respectively. Anastomotic outcomes were recorded, and tissue lactate was also measured in the devascularised colonic segment in a subgroup of patients. The novel perfusion zone projections were developed as full-screen recommendations via overlay heatmaps. RESULTS: No patient suffered intra- or early postoperative anastomotic complications. Following computational development (n = 14) the software recommended zone (ROI) contained the expert surgical site of transection in almost all cases (Jaccard similarity index 0.91) of the nine patient validation series. Previously published ICGFA time-series milestone descriptors correlated moderately well, but lactate measurements did not. High resolution augmented reality heatmaps presenting recommendations from all pixels of the bowel ICGFA were generated for all cases. CONCLUSIONS: By benchmarking to the patient's own baseline perfusion, this novel QICGFA method could allow the deployment of algorithmic personalised NIR bowel transection point recommendation in a way fitting existing clinical workflow.

Regional Heterogeneity in Intestinal Epithelial Barrier Permeability and Mesenteric Perfusion After Thoracic Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) disrupts intestinal barrier function, thereby increasing antigen permeation and leading to poor outcomes. Despite the intestinal tract's anatomic and physiologic heterogeneity, studies following SCI have not comprehensively addressed intestinal pathophysiology with regional specificity. AIMS AND METHODS: We used an experimental model of high thoracic SCI to investigate (1) regional mucosal oxidative stress using dihydroethidium labeling; (2) regional paracellular permeability to small- and large-molecular probes via Ussing chamber; (3) regional intestinal tight junction (TJ) protein expression; and (4) hindgut perfusion via the caudal mesenteric artery. RESULTS: Dihydroethidium staining was significantly elevated within duodenal mucosa at 3-day post-SCI. Molar flux of [14C]-urea was significantly elevated in duodenum and proximal colon at 3-day post-SCI, while molar flux of [3H]-inulin was significantly elevated only in duodenum at 3-day post-SCI. Barrier permeability was mirrored by a significant increase in the expression of pore-forming TJ protein claudin-2 in duodenum and proximal colon at 3-day post-SCI. Claudin-2 expression remained significantly elevated in proximal colon at 3-week post-SCI. Expression of the barrier-forming TJ protein occludin was significantly reduced in duodenum at 3-day post-SCI. Caudal mesenteric artery flow was unchanged by SCI at 3 days or 3 weeks despite significant reductions in mean arterial pressure. CONCLUSION: These data show that T3-SCI provokes elevated mucosal oxidative stress, altered expression of TJ proteins, and elevated intestinal barrier permeability in the proximal intestine. In contrast, mucosal oxidative stress and intestinal barrier permeability were unchanged in the hindgut after SCI. This regional heterogeneity may result from differential sensitivity to reduced mesenteric perfusion, though further studies are required to establish a causal link. Understanding regional differences in intestinal pathophysiology is essential for developing effective treatments and standards of care for individuals with SCI.

Epiploic steal: is this concept the key to reducing colorectal anastomotic leak rates?

PURPOSE: Ensuring optimal colonic perfusion is a critical step in every colorectal anastomosis. The aim of this study is to describe the concept of epiploic steal. METHODS: A literature review was performed to identify studies evaluating anastomotic blood supply. The fundamental principle of epiploic steal is outlined. RESULTS: Epiploic steal has not been previously evaluated in the literature, and likely has a negative effect on colonic blood supply. Resection of colonic epiploicae may improve perfusion at the distal most lengths of a mobilised colonic conduit where the anastomosis requires it. CONCLUSION: This novel concept has the potential to change practice and reduce colorectal anastomotic leak rates. Further clinical studies are required.

Feasibility of middle colic artery as a landmark for superior mesenteric artery - first approach in laparoscopic pancreatoduodenectomy: a prospective study.

BACKGROUND: SMA-first approach in pancreatoduodenectomy (PD) has been widely applied in open surgery as well as laparoscopy. Finding the superior mesenteric artery (SMA), inferior pancreatoduodenal artery (IPDA), first jejunal artery (J1A) has become a great challenge in laparoscopic PD (LPD). Meanwhile, exposing the midde colic artery (MCA) might be a feasible approach to determine SMA, IPDA, and J1A. Our study aims to find the anatomical correlation between MCA and SMA, IPDA, J1A, especially in SMA-first approach LPD from the left. METHODS: Uncontrolled clinical trial with 33 patients undergoing LPD had preoperative contrast abdominal CT scan to analyze the anatomical relevance between MCA and SMA, J1A, IPDA. The operation was performed starting with exposing MCA in advance to find SMA, J1A and IPDA. The data was analyzed by SPSS 25.0. RESULTS: 90.9% of MCA started at 12-3 o'clock from SMA, the mean distance from the SMA root to the MCA and J1A was 56.4 mm and 37.4 mm, respectively. The distance between SMA and J1A was 19 mm. 72.7% J1A started at 9-12 o'clock, 69.7% J1A and IPDA had a common trunk. 78.8% IPDA started at 3-6 o'clock. 100% of the cases had J1A controlled intraoperatively, 81.8% for IPDA when approached from the left, 3% had MCA injury. The mean time to approach from the left was 98 min, median blood loss was 100 ml. CONCLUSION: Exposing MCA first helps determine SMA, J1A and IPDA safely, efficiently and faciliates SMA-first approach LPD from the left and complete dissection of the mesopancreas and lymph nodes.

A novel technique for NO.253 lymph node dissection and left colic artery preservation to avoid potential postoperative internal hernia in laparoscopic radical resection for rectal cancer.

BACKGROUND: The preservation of the left colic artery (LCA) has emerged as a preferred approach in laparoscopic radical resection for rectal cancer. However, preserving the LCA while simultaneously dissecting the NO.253 lymph node can create a mesenteric defect between the inferior mesenteric artery (IMA), the LCA, and the inferior mesenteric vein (IMV). This defect could act as a potential "hernia ring," increasing the risk of developing an internal hernia after surgery. The objective of this study was to introduce a novel technique designed to mitigate the risk of internal hernia by filling mesenteric defects with autologous tissue. METHODS: This new technique was performed on eighteen patients with rectal cancer between January 2022 and June 2022. First of all, dissected the lymphatic fatty tissue on the main trunk of IMA from its origin until the LCA and sigmoid artery (SA) or superior rectal artery (SRA) were exposed and then NO.253 lymph node was dissected between the IMA, LCA and IMV. Next, the SRA or SRA and IMV were sequentially ligated and cut off at an appropriate location away from the "hernia ring" to preserve the connective tissue between the "hernia ring" and retroperitoneum. Finally, after mobilization of distal sigmoid, on the lateral side of IMV, the descending colon was mobilized cephalad. Patients'preoperative baseline characteristics and intraoperative, postoperative complications were examined. RESULTS: All patients' potential "hernia rings" were closed successfully with our new technique. The median operative time was 195 min, and the median intraoperative blood loss was 55 ml (interquartile range 30-90). The total harvested lymph nodes was 13.0(range12-19). The median times to first flatus and liquid diet intake were both 3.0 days. The median number of postoperative hospital days was 8.0 days. One patient had an injury to marginal arterial arch, and after mobolization of splenic region, tension-free anastomosis was achieved. No other severe postoperative complications such as abdominal infection, anastomotic leakage, or bleeding were observed. CONCLUSIONS: This technique is both safe and effective for filling the mesenteric defect, potentially reducing the risk of internal hernia following laparoscopic NO.253 lymph node dissection and preservation of the left colic artery in rectal cancer surgeries.

Vascular-oriented D3 lymph node dissection with left colic artery preservation for distal sigmoid colon cancer: a variety of techniques.

BACKGROUND: One of the approaches to distal sigmoid colon cancer surgical treatment is segmental colonic resection with vascular preservation of left colic artery (LCA). D3 lymph node dissection may technically vary according to different vascular anatomy. This study aims to show the approaches to D3 lymph node dissection with LCA preservation for distal sigmoid colon cancer according to different patterns of inferior mesenteric artery (IMA) branching. METHODS: CT angiography with 3D reconstruction was routinely performed to identify the IMA branching pattern. Laparoscopic distal sigmoid colon resection with D3 lymph node dissection and left colic artery preservation in standardized fashion was performed in all cases. Data, including clinical, intraoperative, and short-term surgical outcomes, is presented as median numbers (Me) and interquartile range (IQR). RESULTS: Twenty-six patients with distal sigmoid colon cancer were treated with laparoscopic distal sigmoid colon resection. The approach to D3 lymph node dissection varied according to different anatomical variations. There was one conversion (3.8%) and one anastomotic leakage (3.8%) in patients with high BMI. At the same time, there was a high apical lymph node count (Me 3 (IQR 2-5), min-max 0-10) due to the skeletonization of the IMA. CONCLUSIONS: The technical aspects of D3 lymph node dissection with left colic artery preservation may vary in different types of LCA and sigmoid artery branching patterns regardless of the standardized anatomical landmarks. The anatomical features should be considered when performing vascular-sparing lymph node dissection.

Effects of Local Vasodilators and the Autonomic Nervous System on Microcirculation and Mitochondrial Function in Septic Rats.

Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (-13.1%*) and Ilo (-10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: -4.0%, non-significant; Ilo + carbachol: -1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (-10.5%*) or in combination with NG (-17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition.

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.

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.

[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.

Surveillance to detect colonic ischemia with extraluminal pH measurement after open surgery for abdominal aortic aneurysm.

OBJECTIVE: Colonic ischemia (CI) is a life-threatening complication after aortic surgery. Postoperative surveillance of colonic perfusion might be warranted. The aim of the present study was to evaluate the safety and feasibility of postoperative extraluminal pH measurement (pHe) using colonic tonometry after open abdominal aortic aneurysm (AAA) repair. METHODS: Before closing the abdomen after open AAA repair, a tonometric catheter was placed transabdominally in contact with the sigmoid colon serosa, similar to a drainage catheter. Extraluminal partial pressure of carbon dioxide was measured postoperatively and combined with arterial blood gas analysis to calculate the pHe. The measurements were repeated every 4 hours with simultaneous intra-abdominal pressure measurements. The threshold for colonic malperfusion was set at pHe <7.2. RESULTS: A total of 27 patients were monitored, 12 had undergone surgery for ruptured AAAs and 15 for intact AAAs. Of the 27 patients, 4 developed clinically significant CI requiring surgery. All four cases were preceded by a prolonged (>5 hours) pHe <7.2 indicating malperfusion. A fifth patient, who, during monitoring, had had the lowest pHe of 7.21, developed mild CI with the onset after completion of monitoring, which was successfully managed conservatively. Seven patients who had had brief durations (<5 hours) of pHe <7.2 did not develop clinical signs of CI or any related adverse events. CONCLUSIONS: Measurements of pHe using colonic tonometry indicated malperfusion in all four patients who had developed clinically significant CI. A shorter duration of low pHe was well tolerated without any signs of CI. Measurement of pHe was safe and reliable for the surveillance of colonic perfusion after open aortic surgery, indicating a promising technique. However, larger studies are needed.

Dendritic cell vaccine therapy for colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States despite an array of available treatment options. Current standard-of-care interventions for this malignancy include surgical resection, chemotherapy, and targeted therapies depending on the disease stage. Specifically, infusion of anti-vascular endothelial growth factor agents in combination with chemotherapy was an important development in improving the survival of patients with advanced colorectal cancer, while also helping give rise to other forms of anti-angiogenic therapies. Yet, one approach by which tumor angiogenesis may be further disrupted is through the administration of a dendritic cell (DC) vaccine targeting tumor-derived blood vessels, leading to cytotoxic immune responses that decrease tumor growth and synergize with other systemic therapies. Early generations of such vaccines exhibited protection against various forms of cancer in pre-clinical models, but clinical results have historically been disappointing. Sipuleucel-T (Provenge®) was the first, and to-date, only dendritic cell-based therapy to receive FDA approval after significantly increasing overall survival in prostate cancer patients. The unparalleled success of Sipuleucel-T has helped revitalize the clinical development of dendritic cell vaccines, which will be examined in this review. We also highlight the promise of these vaccines to instill anti-angiogenic immunity for individuals with advanced colorectal cancer.

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).

Nationwide Study to Predict Colonic Ischemia after Abdominal Aortic Aneurysm Repair in The Netherlands.

BACKGROUND: Colonic ischemia remains a severe complication after abdominal aortic aneurysm (AAA) repair and is associated with a high mortality. With open repair being one of the main risk factors of colonic ischemia, deciding between endovascular or open aneurysm repair should be based on tailor-made medicine. This study aims to identify high-risk patients of colonic ischemia, a risk that can be taken into account while deciding on AAA treatment strategy. METHODS: A nationwide population-based cohort study of 9,433 patients who underwent an AAA operation between 2014 and 2016 was conducted. Potential risk factors were determined by reviewing prior studies and univariate analysis. With logistic regression analysis, independent predictors of intestinal ischemia were established. These variables were used to form a prediction model. RESULTS: Intestinal ischemia occurred in 267 patients (2.8%). Occurrence of intestinal ischemia was seen significantly more in open repair versus endovascular aneurysm repair (7.6% vs. 0.9%; P < 0.001). This difference remained significant after stratification by urgency of the procedure, in both intact open (4.2% vs. 0.4%; P < 0.001) and ruptured open repair (15.0% vs. 6.2%); P < 0.001). Rupture of the AAA was the most important predictor of developing intestinal ischemia (odds ratio [OR], 5.9, 95% confidence interval [CI] 4.4-8.0), followed by having a suprarenal AAA (OR 3.4; CI 1.1-10.6). Associated procedural factors were open repair (OR 2.8; 95% CI 1.9-4.2), blood loss >1L (OR 3.6; 95% CI 1.7-7.5), and prolonged operating time (OR 2.0; 95% CI 1.4-2.8). Patient characteristics included having peripheral arterial disease (OR 2.4; 95% CI 1.3-4.4), female gender (OR 1.7; 95% CI 1.2-2.4), renal insufficiency (OR 1.7; 1.3-2.2), and pulmonary history (OR 1.6; 95% CI 1.2-2.2). Age <68 years proved to be a protective factor (OR 0.5; 95% CI 0.4-0.8). Associated mortality was higher in patients with intestinal ischemia versus patients without (50.6% vs. 5.1%, P < 0.001). Each predictor was given a score between 1 and 4. Patients with a score of ≥10 proved to be at high risk. A prediction model with an excellent AUC = 0.873 (95% CI 0.855-0.892) could be formed. CONCLUSIONS: One of the main risk factors is open repair. Several other risk factors can contribute to developing colonic ischemia after AAA repair. The proposed prediction model can be used to identify patients at high risk for developing colonic ischemia. With the current trend in AAA repair leaning toward open repair for better long-term results, our prediction model allows a better informed decision can be made in AAA treatment strategy.