IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Metaverse and Telementoring: From Surgery to Workshop.

BACKGROUND: The Coronavirus 2019 (COVID-19) pandemic has favored the growth of telemedicine systems and in this context the idea of Metaverse was born and developed. A 3D reality in which people can interact with each other through digital reproductions of themselves. Metaverse has already been tested in numerous medical fields due to its ability to combine visual and auditory information with tactile sensations. The purpose of this study is to highlight its potential also in its ability to be used as a telementoring place where the skills and knowledge of surgeons from all over the world can be combined. MATERIAL AND METHODS: The first HPB Surgery Workshop was held at the "Metaverse Surgical Hospital, USA". During the workshop, surgeons located in various parts of the world reported on hepatic, pancreatic and biliary tract surgery and remotely supported the execution of a robotic liver resection. RESULTS: The Metaverse gave the opportunity for surgeons to meet and discuss HPB pathologies and its surgical strategies and for surgeons in training to interface with experts by participating in a moment of advanced training. CONCLUSION: In the Metaverse, telementoring can be used at very low cost to improve clinical and surgical practice.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

BACKGROUND: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. METHODS: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series. RESULTS: In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8ß expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. CONCLUSION: Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

New Robotic Platforms in General Surgery: What's the Current Clinical Scenario?

Background and Objectives: Robotic surgery has been widely adopted in general surgery worldwide but access to this technology is still limited to a few hospitals. With the recent introduction of new robotic platforms, several studies reported the feasibility of different surgical procedures. The aim of this systematic review is to highlight the current clinical practice with the new robotic platforms in general surgery. Materials and Methods: A grey literature search was performed on the Internet to identify the available robotic systems. A PRISMA compliant systematic review was conducted for all English articles up to 10 February 2023 searching the following databases: MEDLINE, EMBASE, and Cochrane Library. Clinical outcomes, training process, operating surgeon background, cost-analysis, and specific registries were evaluated. Results: A total of 103 studies were included for qualitative synthesis after the full-text screening. Of the fifteen robotic platforms identified, only seven were adopted in a clinical environment. Out of 4053 patients, 2819 were operated on with a new robotic device. Hepatopancreatobiliary surgery specialty performed the majority of procedures, and the most performed procedure was cholecystectomy. Globally, 109 emergency surgeries were reported. Concerning the training process, only 45 papers reported the background of the operating surgeon, and only 28 papers described the training process on the surgical platform. Only one cost-analysis compared a new robot to the existing reference. Two manufacturers promoted a specific registry to collect clinical outcomes. Conclusions: This systematic review highlights the feasibility of most surgical procedures in general surgery using the new robotic platforms. Adoption of these new devices in general surgery is constantly growing with the extension of regulatory approvals. Standardization of the training process and the assessment of skills' transferability is still lacking. Further studies are required to better understand the real clinical and economical benefit.

Rectal Sparing Approach After Neoadjuvant Therapy in Patients with Rectal Cancer: The Preliminary Results of the ReSARCh Trial.

BACKGROUND: Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS: Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS: From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS: LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.

Robotic oncologic colorectal surgery with a new robotic platform (CMR Versius): hope or hype? A preliminary experience from a full-robotic case-series.

BACKGROUND: The present case-series describes the first full-robotic colorectal resections performed with the new CMR Versius platform (Cambridge Medical Robotics Surgical, 1 Evolution Business Park, Cambridge, United Kingdom) by an experienced robotic surgeon. METHODS: In a period between July 2020 and December 2020, patients aged 18 years or older, who were diagnosed with colorectal cancer and were fit for minimally invasive surgery, underwent robotic colorectal resection with CMR Versius robotic platform at "Casa di Cura Cobellis" in Vallo della Lucania,Salerno, Italy. Three right colectomies, 2 sigmoid colectomies and 1 anterior rectal resection were performed. All the procedures were planned as fully robotic. Surgical data were retrospectively reviewed from a prospectively collected database. RESULTS: Four patients were male and 2 patients were female with a median (range) age of 66 (47-72) years. One covering ileostomy was created. Full robotic splenic flexure mobilization was performed. No additional laparoscopic gestures or procedures were performed in this series except for clipping and stapling which were performed by the assistant surgeon due to the absence of robotic dedicated instruments. Two ileocolic anastomoses, planned as robotic-sewn, were performed extracorporeally. One Clavien-Dindo II complication occurred due to a postoperative blood transfusion. Median total operative time was 160 (145-294) min for right colectomies, 246 (191-300) min for sigmoid colectomies and 250 min for the anterior rectal resection. CONCLUSIONS: The present series confirms the feasibility of full-robotic colorectal resections while highlighting the strengths and the limitations of the CMR Versius platform in colorectal surgery. New devices will need more clinical development to be comparable to the current standard.

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Effects of Warmed and Humidified CO2 Surgical Site Insufflation in a Novel Experimental Model of Magnetic Compression Colonic Anastomosis.

Background. Pneumoperitoneum insufflation with warmed and humidified carbon dioxide (WH-CO2) can prevent heat loss and increase tissue oxygenation. We evaluated the impact of localized WH-CO2 insufflation on the anastomotic healing process. Methods. Sixty male Wistar rats were randomized: Group 1 (control, n = 12), Group 2 (cold and dry CO2, CD-CO2, n = 24), and Group 3 (WH-CO2, n = 24). A magnetic compression side-to-side colonic anastomosis was performed under 60-minute local abdominal CO2 flow insufflation. Animal temperature was recorded. IL-1, IL-6, and CRP levels were assessed before and after insufflation and on postoperative day (POD) 7 and POD 10. Endoscopic follow-up was performed on POD 7 and POD 10. A burst pressure (BP) test of the specimen was performed on POD 10, and histopathological analysis was then performed. Metabolomics of the anastomotic site was determined. Results. Seven rats (5 CD-CO2 group, 1 WH-CO2 group, and 1 control group) died during the survival period. Necropsies revealed intestinal occlusions (n = 2). One additional rat from the CD-CO2 group was sacrificed on POD 7 due to intestinal perforation. The postoperative course was uneventful in the remaining cases. There was no difference in BP among the groups. Thermal monitoring confirmed that WH-CO2 insufflation was effective to reduce heat loss. IL-1 levels were statistically and significantly lower on POD 10 in the WH-CO2 group than the CD-CO2 group but not lower than the control group. CRP levels, histopathology, and metabolomics did not show any difference between the 3 groups. Conclusions. WH-CO2 was effective to preserve core temperature. However, it did not improve anastomotic healing.

Robotic infrahepatic vena cava clamping and Pringle manoeuvre for major hepatectomy: A safe and bloodless procedure - First technical report.

Mini-invasive approaches in hepatic surgery are associated with a significant decrease in the incidence of post-operative morbidity and liver failure. Intraoperative blood loss represents the major intraoperative accident during hepatectomy. Infrahepatic inferior vena cava clamping is an emerging technical trick which guarantees a lower intraoperative blood loss and transfusion rates during liver surgery. Herein, we present the first report of infrahepatic caval clamping during robotic hepatectomy at our centre, highlighting some technical tips and tricks.

Human amniotic fluid stem cells attract osteoprogenitor cells in bone healing.

Current treatments of large bone defects are based on autologous or allogenic bone transplantation. Human amniotic fluid stem cells (hAFSCs) were evaluated for their potential in bone regenerative medicine. In this study, hAFSCs were transduced with lentiviral vector harboring red fluorescent protein to investigate their role in the regeneration of critical-size bone defects in calvarial mouse model. To distinguish donor versus recipient cells, a transgenic mouse model carrying GFP fluorescent reporter was used as recipient to follow the fate of hAFSCs transplanted in vivo into Healos® scaffold. Our results showed that transduced hAFSCs can be tracked in vivo directly at the site of transplantation. The presence of GFP positive cells in the scaffold at 3 and 6 weeks after transplantation indicates that donor hAFSCs can recruit host cells during the repair process. These observations help clarify the role of hAFSCs in bone tissue repair.

Rat bone healing induced by natural nanocrystalline carbonated hydroxyapatite in combination with human amniotic fluid stem cells (AFSCs).

The present study was aimed at identifying a new scaffold/stem cell combination useful to treat large bone defects. Human amniotic fluid stem cells (AFSCs) were expanded in vitro, labeled with a fluorescent cell-permeable dye (PKH26) and transplanted in vivo in a femoral injured rat model. The femoral defect was left untreated (control rats) or filled with hydroxyapatite (HA; natural nanocrystalline carbonated hydroxyapatite-Orthoss®) scaffold alone or loaded with PKH26-labeled AFSCs. All animals were killed 3 weeks after implantation. Both gross anatomy and histological observations revealed a major bone regenerative response in rat specimens treated with HA scaffold, alone or supplemented with AFSCs. Samples injected with HA plus AFSCs displayed the presence of abundant fibrotic tissue, the formation of periosteal woven bone, and an increased presence of blood vessels in the bone marrow, with still fluorescent AFSCs in close proximity. These observations provide evidence that natural HA plus AFSCs represents a promising alternative therapeutic strategy to autologous bone grafting procedures.

Colonic J-Pouch or Straight Colorectal Reconstruction After Low Anterior Resection For Rectal Cancer: Impact on Quality of Life and Bowel Function: A Multicenter Prospective Randomized Study.

BACKGROUND: Patient-reported outcomes associated with different bowel reconstruction techniques following anterior resection for rectal cancer are still a matter of debate. OBJECTIVE: This study aimed to assess quality of life and bowel function in patients who underwent colonic J-pouch or straight colorectal anastomosis reconstruction after low anterior resection. DESIGN: Bowel function and quality of life were assessed within a multicenter randomized trial. Questionnaires were administered before the surgery (baseline) and at 6, 12, and 24 months after surgery. SETTINGS: Patients were enrolled by 19 centers. The enrollment started in October 2009 and was stopped in February 2016. The study was registered at www.clinicaltrials.gov (Identifier: NCT01110798). PATIENTS: Patients who underwent low anterior resection for primary mid-low rectal cancer and who were randomly assigned in a 1:1 ratio to receive either stapled colonic J-pouch or straight colorectal anastomosis were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and bowel function. RESULTS: Of the 379 patients who were evaluable, 312 (82.3%) completed the baseline, 259 (68.3%) the 6-month, 242 (63.9%) the 12-month, and 199 (52.5%) the 24-month assessment. Bowel functioning and quality of life did not significantly differ between arms for almost all domains. The total bowel function score, the urgency, and the stool fractionation scores significantly worsened after surgery and remained impaired over time in both arms (p < 0.0032), whereas constipation improved after surgery but recovered to baseline levels from 1 year onward (p < 0.0036). All patients showed a significant and continuous improvement in emotional functioning (p < 0.0013) and future perspective (p < 0.0001) from baseline to the end of the study. LIMITATIONS: Limitations of the study include missing data, which increased over time; the possibility that some treatments have slightly changed since the study was conducted; and investigators not blind to treatment allocation. CONCLUSION: The findings of this study do not support the routine use of colonic J-pouch reconstruction in patients with rectal cancer who undergo a low anterior resection. See Video Abstract at http://links.lww.com/DCR/B328. BOLSA J COLÓNICA O RECONSTRUCCIÓN COLORRECTAL RECTA DESPUÉS DE RESECCIÓN ANTERIOR BAJA PARA CÁNCER RECTAL: IMPACTO EN LA CALIDAD DE VIDA Y LA FUNCIÓN INTESTINAL: UN ESTUDIO ALEATORIZADO PROSPECTIVO MULTICÉNTRICO: Los resultados informados por el paciente asociados con diferentes técnicas de reconstrucción intestinal después de la resección anterior para el cáncer de recto aún son tema de debate.Evaluar la calidad de vida y la función intestinal en pacientes que se sometieron a una bolsa en J colónica o reconstrucción de anastomosis colorrectal recta después de una resección anterior baja.La función intestinal y la calidad de vida se evaluaron en un ensayo aleatorizado multicéntrico. Los cuestionarios se administraron antes de la cirugía (basal) y a los 6, 12 y 24 meses después de la cirugía.Los pacientes fueron incluidos en 19 centros. La inscripción comenzó en Octubre de 2009 y se detuvo en Febrero de 2016. El estudio se registró en www.clinicaltrials.gov (Identificador: NCT01110798).Pacientes que se sometieron a resección anterior baja por cáncer rectal primario medio-bajo y que fueron aleatorizados en una proporción de 1: 1 para recibir bolsa J colónica con grapas o anastomosis colorrectal recta.calidad de vida y función intestinal.De los 379 pacientes que fueron evaluables, 312 (82.3%) completaron la evaluación inicial, 259 (68.3%) a los 6 meses, 242 (63.9%) a los 12 meses y 199 (52.5%) a los 24 meses. . El funcionamiento intestinal y la calidad de vida no difirieron significativamente entre los dos grupos en casi todos los dominios. La puntuación total de la función intestinal, la urgencia y las puntuaciones de fraccionamiento de las heces empeoraron significativamente después de la cirugía y continuaron con el tiempo extra en ambos grupos (p <0.0032), mientras que el estreñimiento mejoró después de la cirugía pero se recuperó a los niveles basales a partir de 1 año en adelante (p <0.0036). Todos los pacientes mostraron una mejora significativa y continua en el funcionamiento emocional (p <0.0013) y la perspectiva futura (<0.0001) desde el inicio hasta el final del estudio.Datos faltantes, que aumentaron con el tiempo; la posibilidad de que algunos tratamientos hayan cambiado ligeramente desde que se realizó el estudio; investigadores no cegados a la asignación del tratamiento.Los hallazgos de este estudio no respaldan el uso rutinario de la reconstrucción de la bolsa J colónica en pacientes con cáncer rectal que se someten a una resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B328. (Traducción-Dr. Yesenia Rojas-Khalil).

Impact of laparoscopic approach on the short-term outcomes of elderly patients with colorectal cancer: a nationwide Italian experience.

INTRODUCTION: The laparoscopic approach is increasingly adopted in colorectal cancer surgery; however, its role in elderly patients is controversial. We sought to examine the relationship between age and short-term outcomes following laparoscopic surgery for colorectal cancer (CRC). METHODS: Data of patients 65 + years old who underwent laparoscopic surgery for CRC between 2002 and 2014 were retrieved from the administrative National Italian Hospital Discharge Dataset. Patients were divided into three age categories (65-74, 75-84, and 85 +). The impact of age on length of stay, 30-day readmission, in-hospital mortality, and postoperative complications was evaluated. RESULTS: During the study period, 47,704 patients underwent laparoscopic surgery for CRC. The median postoperative length of stay was 9 days, and 30-day readmission and in-hospital mortality were 4.4% and 0.9%, respectively. Age was found to be an independent risk factor of prolonged length of stay and increased in-hospital mortality. With respect to patients in 65-74 years age category, patients aged 75-84 years and those aged 85 + years had a higher risk of complications (OR 1.43, 95% CI 1.36-1.50, and OR 2.00, 95% CI 1.83-2.17, respectively). However, no statistically significant association was found between age and anastomotic leakage or surgical site infection (p = 0.29, and p = 0.58, respectively). CONCLUSIONS: In patients with CRC who underwent laparoscopic surgery, age was found to be an independent risk factor for prolonged length of stay, in-hospital mortality, and global postoperative complications. These findings should be considered when planning laparoscopic surgery in elderly patients.

Fluorescence lymphangiography-guided full-thickness oncologic gastric resection.

BACKGROUND: We aimed to assess the feasibility of a novel hybrid endoscopic/laparoscopic non-exposed, full-thickness, single-wall gastric resection technique guided by a fluorescence lymphangiography to identify the lymphatic pathway and the sentinel node basin. METHODS: Eight large white pigs (4 acute and 4 survival models) were included. Indocyanine green was injected submucosally around a pseudo-tumor at four points (1 ml, 0.1 mg/ml). The lymphatic spreading pathway was identified by the means of near-infrared (NIR) laparoscopic camera, and the resection line was planned outside of the fluorescent signals, to include all the potential lymphatic channels. Lymph node (LN) dissection was performed at greater curvature side and the infrapyloric area preserving the infragastric artery for all pigs. At the lesser curvature, 3-4 branches of the gastric artery were preserved in all acute and in two survival (group A), while in the remaining animals, 1-2 branches were preserved (group B). Perfusion of the remaining stomach was examined by NIR angiography. The gastric motility and function were evaluated by the means of a dynamic MRI immediately after the procedure and repeated after 1 week in surviving animals. RESULTS: The hybrid full-thickness resection with bilateral sentinel LN basin dissection were successfully performed with no intra-operative or post-operative complications. The removed specimen was including all the area with florescent signal. The remaining stomach demonstrated a good perfusion at the NIR angiography. The dynamic MRI revealed a preserved emptying function in the acute animals and in the group A, and a loss of function in the group B. CONCLUSIONS: Fluorescence-lymphangiography guided hybrid resection was feasible to remove a relatively large part of the stomach including the lymphatic spreading pathway and sentinel basin. The extent of dissection in the lesser curvature side can affect the post-operative function and further researches are warranted to optimize the concept.

Gastrointestinal Hormones Manipulation to Counteract Metabolic Syndrome Using Duodenal Targeted Embolization.

PURPOSE: Targeted embolization of gastrointestinal (GI) arteries can modify hormonal production. We aimed to evaluate the impact of the embolization of the gastroduodenal artery (GDA) on the activity of foregut mucosa. METHODS: The GDA's duodenal branch was embolized in 12 Yucatan pigs using 100-300 µm (group A; n = 4) or 300-500 µm (group B; n = 4) microspheres, followed by coiling of the branch. In 4 animals (sham), only saline was injected. The levels of GI hormones (ghrelin, glucose-dependent insulinotropic peptide [GIP], glucagon-like peptide-1 [GLP-1], insulin, peptide YY [PYY], leptin) and the gene expression of sodium-glucose-linked transporter-1 (SGLT-1) and glucose transporter-2 (GLUT-2) were assessed before (T0), 1 hour (T1), 1 month (T2), 3 months (T3), and 6 months (T4) after embolization. RESULTS: In group A, a segmental duodenal stenosis occurred in all cases, which required balloon dilatation. There was a significant drop in the baseline glycemia in group A at T1 and T4 versus sham. Ghrelin was reduced in group A versus baseline and versus group B at T2 and T3 and versus sham at T1 and T3. Insulin was significantly lower in group A versus B at T1 and at T4 but not versus sham. SGLT-1 expression increased in B and sham at T4, while it remained stable in group A. GLUT-2 expression increased in sham at T4 but not in A or B. CONCLUSIONS: GDA embolization induced a decrease in ghrelin production and influenced expression of glucose carriers in the foregut mucosa.

Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model.

BACKGROUND: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. METHODS: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). RESULTS: The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. CONCLUSIONS: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.