The impact of preoperative nutritional status on postoperative outcomes: an insight from Geriatric Nutritional Risk Index in elderly pancreaticoduodenectomy patients.

BACKGROUND: Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD. MATERIALS AND METHODS: This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS). RESULTS: Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002). CONCLUSIONS: Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.

Near-infrared cholangiography can increase the chance of success in laparoscopic approaches to common bile duct stones, even with previous abdominal surgery.

BACKGROUND: The treatment of common bile duct (CBD) stones with minimally invasive surgery (MIS) is more technical demanding than laparoscopic cholecystectomy (LC), especially in patients with history of previous abdominal surgery, cholangitis or cholecystitis. Near-infrared (NIR) cholangiography via systemic or biliary tree administration of indocyanine green (ICG), which enhances the visualization of the biliary tree anatomy, may increase the reassurance of CBD localization. The aim of this study was to identify the benefit of near-infrared cholangiography for laparoscopic common bile duct exploration (LCBDE). METHODS: Three groups of CBD stone patients were included in this retrospective study depending on the surgical methods: 1) open choledocholithotomy (OCC), 2) laparoscopic choledocholithotomy (LCC), and 3) near-infrared cholangiography-assisted laparoscopic choledocholithotomy (NIR-CC). For the NIR-CC group, either 3 ml (concentration: 2.5 mg/mL) of ICG were intravenously administered or 10 ml (concentration: 0.125 mg/mL) of ICG were injected directly into the biliary tree. The enhancement rate of the cystic duct (CD), CBD, the upper and lower margin of the CBD were compared using white light image. RESULTS: A total of 187 patients with a mean age of 68.3 years were included (OCC, n = 56; LCC, n = 110; NIR-CC, n = 21). The rate of previous abdominal surgery was significantly lower in the LCC group. The conversion rate was similar between the LCC and the NIR CC groups (p = 0.746). The postoperative hospital stay was significantly longer in the OCC group. No differences in morbidity and mortality were found between the three groups. In the NIR-CC group, the localization of CBD was as high as 85% compared to 24% with white light imaging. CONCLUSIONS: Near-infrared cholangiography helps increase the chance of success in minimally invasive approaches to CBD stones even in patients with previous abdominal surgeries, without increasing the rate of conversion.

Short-term outcomes after minimally invasive versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: To date, the evidence on the safety and benefits of minimally invasive pancreatoduodenectomy (MIPD) in elderly patients is still controversy. This study aim to compare the risk and benefit between MIPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: From 2016 to 2020, we retrospective enrolled 26 patients underwent MIPD and other 119 patients underwent OPD. We firstly compared the baseline characteristics, 90-day mortality and short-term surgical outcomes of MIPD and OPD. Propensity score matching was applied for old age patient (≥ 65-year-old vs. < 65-year-old) for detail safety and feasibility analysis. RESULTS: Patients received MIPD is significantly older, had poor performance status, less lymph node harvest, longer operation time, less postoperative hospital stay (POHS) and earlier drain removal. After 1:2 propensity score matching analysis, elderly patients in MIPD group had significantly poor performance status (P = 0.042) compared to OPD group. Patients receiving MIPD had significantly shorter POHS (18 vs. 25 days, P = 0.028), earlier drain removal (16 vs. 21 days, P = 0.012) and smaller delay gastric empty rate (5.9 vs. 32.4% P = 0.036). There was no 90-day mortality (0% vs. 11.8%, P = 0.186) and pulmonary complications (0% vs. 17.6%, P = 0.075) in MIPD group, and the major complication rate is comparable to OPD group (17.6% vs. 29.4%, P = 0.290). CONCLUSION: For elderly patients, MIPD is a feasible and safe option even in patients with inferior preoperative performance status. MIPD might also provide potential advantage for elderly patients in minimizing pulmonary complication and overall mortality over OPD.

Super-Selective Intra-Arterial Indocyanine Green Administration for Near-Infrared Fluorescence-Based Positive Staining of Hepatic Segmentation: A Feasibility Study.

BACKGROUND: Despite the increasing number of laparoscopic hepatic procedures for the resection of hepatocellular carcinoma (HCC), intraoperative tumor localization and demarcation remains challenging in comparison to open surgery. In this study, we evaluated the feasibility of positive liver segment staining through the super-selective intra-arterial indocyanine green (ICG) administration. METHODS: Eight patients presenting with a single HCC underwent an interventional vascular procedure followed by laparoscopic surgery. A microcatheter was advanced into the hepatic artery branches perfusing the HCC followed by digital subtraction angiography and angiography computed tomography (angio-CT). Patients were then transferred to the operating room, and a laparoscopic hepatectomy was performed under ultrasound guidance. A 5 mL bolus of ICG with a concentration of .125 mg/mL was injected through the microcatheter, and a near-infrared laparoscope was used to detect the fluorescence signal to assess the correspondence between the fluorescence-based demarcation and the intraoperative ultrasound-based demarcation. RESULTS: The duration for the angiography procedure was 32.7 +/- 5.3 min, and it took 242 +/- 118 min from the end of angiography procedure until the start of the surgical procedure. In all cases, the fluorescent liver segment was corresponding to the angio-CT findings. In 6/8 cases, fluorescence imaging was considered helpful in the identification of the resection line. In 3 patients, the resection line was changed according to the positively stained liver segment. CONCLUSION: We successfully demonstrated the feasibility of the super-selective intra-arterial ICG administration for fluorescence-based positive staining of hepatic segmentation during laparoscopic surgery for HCC (NCT04266548).

The GAMMA concept (gastrointestinal activity manipulation to modulate appetite) preliminary proofs of the concept of local vibrational gastric mechanical stimulation.

BACKGROUND: Mechanical stimulation of the stretch receptors of the gastric wall can simulate the presence of indigested food leading to reduced food intake. We report the preliminary experimental results of an innovative concept of localized mechanical gastric stimulation. METHODS: In a first survival study, a biocompatible bulking agent was injected either in the greater curvature (n = 8) or in the cardia wall (n = 8) of Wistar rats. Six animals served as sham. Changes of bulking volume, leptin levels and weight gain were monitored for 3 months. In a second acute study, a micro-motor (n = 10; MM) or a size-paired inactive device (n = 10; ID) where applied on the cardia, while 10 additional rats served as sham. Serum ghrelin and leptin were measured at baseline and every hour (T0-T1-T2-T3), during 3 h. In a third study, 24 implants of various shapes and sizes were introduced into the gastric subserosa of 6 Yucatan pigs. Monthly CT scans and gastroscopies were done for 6 months. RESULTS: Weight gain in the CW group was significant lower after 2 weeks and 3 months when compared to the shame and GC (p = 0.01/p = 0.01 and p = 0.048/p = 0.038 respectively). Significant lower increase of leptin production occurred at 2 weeks (p = 0.01) and 3 months (p = 0.008) in CW vs. SG. In the MM group significant reduction of the serum ghrelin was seen after 3 h. Leptin was significantly increased in both MM and ID groups after 3 h, while it was significantly reduced in sham rats. The global device retention was 43.5%. Devices with lower profile and with a biocompatible coating remained more likely in place without complications. CONCLUSIONS: Gastric mechanical stimulation induced a reduced weight gain and hormonal changes. Low profile and coated devices inserted within the gastric wall are more likely to be integrated.

Serum asprosin levels and bariatric surgery outcomes in obese adults.

BACKGROUND/OBJECTIVES: Asprosin is a novel fasting-induced glucogenic and orexigenic protein hormone. The clinical function of asprosin in obesity is currently unknown. This study investigated the association between asprosin abundance and the outcome of bariatric surgery. SUBJECTS/METHODS: Patients with body mass index more than 35 kg/m2 were recruited for the Obesity and Clock for Elegant Aging Registry in 2011-2016. Body weight changes, blood sugar, and asprosin were assessed in 117 patients receiving bariatric surgery and 57 non-obese subjects as normal control. Primary outcomes of excess weight loss percentage at 6 months after bariatric surgery were determined at follow-up. RESULTS: Asprosin levels were significantly higher in obese patients than in non-obese subjects (2360 ± 5094 vs. 307 ± 832 ng/ml, p < 0.0001). Multivariate analyses showed a significant association of asprosin abundance with excess body weight loss percentage at 6 months after surgery (p < 0.0001). After adjusted for age, sex, smoking, HbA1c, cholesterol, and triglyceride, serum asprosin level was the only independent predictor of 6 months excess weight loss percentage after bariatric surgery. Asprosin levels decreased significantly 6 months after bariatric surgery (162.2 ± 169.1 ng/ml). Furthermore, there was no association between asprosin and serum glucose levels in our study. CONCLUSION: This study provides novel evidence that higher asprosin concentrations before bariatric surgery were associated with the weight reduction magnitude at 6 months after surgery. Further studies are warranted to investigate whether asprosin has direct functions to modulate body weight regulation in humans after bariatric surgery.

Elevated heme impairs macrophage phagocytosis in endometriosis.

Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22 µmol/L, 95% confidence interval (CI): 12.54-16.71), compared with the EMS-free group (9.517 µmol/L, 95% CI: 8.891-10.1053). This abnormal accumulation was not associated with the color of PF, phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophages (pMφs) was observed in the EMS group. Consistently, a high-concentration (30 µmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low-concentration (10 µmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) and the CD14+ peripheral monocytes (CD14+ Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pMφs in EMS.

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.

Image-guided video-assisted thoracoscopic small lung tumor resection using near-infrared marking.

BACKGROUND: Localization of non-visible, non-palpable small pulmonary nodules during video-assisted thoracoscopic surgery (VATS) remains challenging. We sought to investigate the feasibility and safety of image-guided video-assisted thoracoscopic surgery (iVATS) with near-infrared (NIR) marking in a hybrid operating room (OR). METHODS: Both localization and surgery were performed by a single team of thoracic surgeons. Diluted indocyanine green (ICG; quantity: 0.3-0.5 mL; dye concentration: 0.125 mg/mL) was injected percutaneously to pinpoint the tumor's location under cone beam computed tomography (CBCT) guidance using a laser-guided navigation system. Real-time fluorescence images were intraoperatively obtained using a NIR thoracoscopic camera to guide subsequent resection. RESULTS: Between March and December 2017, 26 patients underwent NIR marking of small pulmonary nodules for iVATS. The median tumor size was 7 mm (interquartile range [IQR] 5.3-10.8 mm), whereas their median distance from the pleural surface was 5 mm (IQR 0.3-10.5 mm). Seven nodules (35%) were solid, whereas 17 (65%) were ground-glass opacities. All lesions were identifiable on intraoperative CBCT. The median time required for NIR localization was 13 min. An NIR(+) "tattoo" was identified in all cases, and no intraoperative conversion to thoracotomy occurred. The final pathological diagnoses were primary lung cancer (n = 11), metastatic cancer (n = 6), and benign lung tumor (n = 9). Adverse events were not observed, and the median length of post-operative stay was 4 days (IQR 3-4 days). CONCLUSIONS: Our data show that iVATS with NIR marking is useful, has no adverse effects, and can successfully localize difficult-to-identify small pulmonary nodules.

Near-infrared cholecystocholangiography with direct intragallbladder indocyanine green injection: preliminary clinical results.

BACKGROUND: Near-infrared (NIR) fluorescence cholangiography by systemic administration of indocyanine green (ICG) enhances the visualization of the biliary tree anatomy. However, the simultaneous enhancement of liver parenchyma can disturb the visualization of critical details. We herein proposed a new technique of NIR cholecystocholangiography by intragallbladder ICG injection to increase the safety during laparoscopic cholecystectomy. METHODS: A total of 46 patients scheduled for laparoscopic cholecystectomy for symptomatic lithiasis (n = 21) or cholecystitis (n = 25) were enrolled. A fluorescence cholangiography by direct gallbladder injection of ICG was performed in all cases. Of them, the ICG was injected through a previously placed percutaneous transhepatic gallbladder drainage catheter (n = 18) or by intraoperative, percutaneous needle puncture of the gallbladder (n = 28). Visualization of biliary structures, including the cystic duct (CD), the common bile and hepatic ducts (CBD and CHD), the gallbladder neck, and the Hartmann's pouch (HP), was performed using White Light (served as control modality) and by NIR enhancement. RESULTS: Cholecystocholangiography provided a significantly higher rate of visualization of the CD in case of cholecystitis with mild adhesions, and an improved visualization of the HP, CBD, and CHD in case of severe inflammation, when compared to White Light observation. There were no benefits of NIR in case of non-inflamed lithiasis. CONCLUSIONS: Clinical translation of NIR cholecystocholangiography has been successful with a noise-free visualization of biliary anatomy. It can be considered in difficult cases to increase the safety of laparoscopic cholecystectomy.

Impact of valve-less vs. standard insufflation on pneumoperitoneum volume, inflammation, and peritoneal physiology in a laparoscopic sigmoid resection experimental model.

BACKGROUND: Standard insufflators compensate for intra-abdominal pressure variations with pressure spikes. Our aim was to evaluate the impact of a stable, low-pressure pneumoperitoneum induced by a valve-less insufflator, on working space, hemodynamics, inflammation, and peritoneal physiology, in a model of laparoscopic sigmoid resection. MATERIALS AND METHODS: Twelve pigs (47 ± 3.3 kg) were equipped for invasive hemodynamic monitoring and randomly assigned to Standard (n = 6) vs. valve-less (n = 6) insufflation. Animals were positioned in a 30° Trendelenburg on a CT scan bed. A low-pressure pneumoperitoneum (8 mmHg) was started and duration was set for 180 min. Abdominal CT scans were performed, under neuromuscular blockade, before, immediately after, and 1 and 3 h after insufflation. Pneumoperitoneum volumes were calculated on 3D reconstructed CT scans. After creation of a mesenteric window, capillary blood was obtained by puncturing the sigmoid serosa and local lactatemia (mmol/L) was measured using a handheld analyzer. Surgical resection was performed according to the level of lactates, in order to standardize bowel stump perfusion. IL-1 and IL-6 (ng/mL) were measured repeatedly. The peritoneum was sampled close to the surgical site and distantly for the oxygraphic assessment of mitochondrial respiration. A pathologist applied a semi-quantitative score to evaluate the anastomosis. RESULTS: Mean arterial pressure, pulse, body temperature, oximetry, systemic lactatemia, and local lactates were similar. IL-6 was lower in the valve-less group, reaching a statistically significant difference after 3 h of insufflation (64.85 ± 32.5 vs. 133.95 ± 59.73; p = 0.038) and 48 h (77.53 ± 68.4 vs. 190.74 ± 140.79; p = 0.029). Peritoneal mitochondrial respiration was significantly increased after the survival period, with no difference among the groups. The anastomoses in the valve-less group demonstrated a lower acute (p = 0.04) inflammatory infiltration. The mean anterior posterior thickness was slightly, yet significantly higher in the valve-less group, on all post-insufflation CT scans. CONCLUSIONS: Valve-less insufflation achieved a slightly higher working space and a lower systemic and localized inflammatory response in this experimental setting.

Does a Higher Cutoff Value of Lymph Node Retrieval Substantially Improve Survival in Patients With Advanced Gastric Cancer?-Time to Embrace a New Digit.

BACKGROUND: The present study assessed the impact of the retrieval of >25 lymph nodes (LNs) on the survival outcome of patients with advanced gastric cancer after curative-intent gastrectomy. PATIENTS AND METHODS: A total of 5,386 patients who had undergone curative gastrectomy for gastric cancer from 1994 to 2011 were enrolled. The clinicopathological parameters and overall survival (OS) were analyzed according to the number of LNs examined (≤15, n = 916; 16-25, n = 1,458; and >25, n = 3,012). RESULTS: The percentage of patients with >25 LNs retrieved increased from 1994 to 2011. Patients in the LN >25 group were more likely to have undergone total gastrectomy and to have a larger tumor size, poorer tumor differentiation, and advanced T and N stages. Hospital mortality among the LN ≤15, LN 16-25, and LN >25 groups was 6.1%, 2.7%, and 1.7%, respectively (p < .0001). The LN >25 group consistently exhibited the most favorable OS, in particular, with stage II disease (p = .011) when OS was stratified according to tumor stage. Similarly, the LN >25 group had significantly better OS in all nodal stages (from N1 to N3b). The discrimination power of the lymph node ratio (LNR) for the LN ≤15, LN 16-25, and LN >25 groups was 483, 766, and 1,560, respectively. Multivariate analysis demonstrated that the LNR was the most important prognostic factor in the LN >25 group. CONCLUSION: Retrieving more than 25 lymph nodes during curative-intent gastrectomy substantially improved survival and survival stratification of advanced gastric cancer without compromising patient safety. The Oncologist 2017;22:97-106Implications for Practice: D2 lymph node (LN) dissection is currently the standard of surgical management of gastric cancer, which is rarely audited by a third party. The present study, one of the largest surgical series worldwide, has shown that the traditionally recognized retrieval of ≥16 LNs during curative-intent gastrectomy might not be adequate in regions in which locally advanced gastric cancers predominate. The presented data show that retrieval of >25 LNs, which more greatly mimics D2 dissection, improves long-term outcomes and survival stratification without compromising patient safety.

Comprehensive profiling of virus microRNAs of Epstein-Barr virus-associated gastric carcinoma: highlighting the interactions of ebv-Bart9 and host tumor cells.

BACKGROUND AND AIM: Epstein-Barr virus (EBV) is suggested to actively utilize its ebv-microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. A systemic profiling of ebv-miRNAs expressed in EBV-associated gastric carcinoma (EBVa GC) helps understand its epigenetic regulation of carcinogenesis. METHODS: A total of 1039 patients with gastric cancer were screened for EBVa GC using EBV-encoded RNAs in situ hybridization. A comprehensive profiling of ebv-miRNAs expressed in EBVa GC was constructed using stem-loop quantitative polymerase chain reaction. Functional assay of specific ebv-miRNA was conducted. Expression of epithelial-to-mesenchymal transition (EMT) markers among EBVa GC and non-EBVa GC was compared. RESULTS: The prevalence of EBVa GC was 5.0% (52 out of 1039) in our series. The most abundant ebv-miRNAs of EBVa GC were Bart4, followed by Bart11, Bart2, Bart6, Bart9, and Bart18, in the decreasing order. Of them, Bart9 exhibited the same seed sequence as to hsa miR-200a and miR-141. Expression of E-cadherin of EBV-positive SNU-719 was increased after BART9 knockdown. Depleting endogenous Bart9 of SNU-719 induced a surged expression of miR-200a and miR-141, accompanied by decreased proliferative and invasive ability. Expression of mesenchymal markers in EBVa GC was increased compared with those of non-EBVa GC, albeit the two cohorts exhibited a comparable long-term survival. CONCLUSIONS: We constructed a comprehensive profiling of ebv-miRNAs in EBVa GC. BART9 plays an important role during carcinogenesis through EMT. Inherent mesenchymal phenotype of EBVa GC represents a unique virus-induced morphology and microenvironment rather than being able to predict the prognosis.

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

BACKGROUND: Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). MATERIALS AND METHODS: Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego®, multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). RESULTS: Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. CONCLUSIONS: Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Precision real-time evaluation of bowel perfusion: accuracy of confocal endomicroscopy assessment of stoma in a controlled hemorrhagic shock model.

BACKGROUND AND AIMS: Confocal laser endomicroscopy (CLE) can provide real-time evaluation of bowel perfusion. We aimed to evaluate CLE perfusion imaging in a hemorrhagic shock model. MATERIALS AND METHODS: Five pigs were equipped to ensure hemodynamic monitoring. Three ileostomies per animal (total n = 15) were randomly created (T0). Blood was withdrawn targeting a mean arterial pressure of 40 mmHg (shock phase, T1), for 90 min. Infusion of Ringer's lactate was started and continued for 90 min (T2). At the different time points: (a) stomas' mucosa was scanned with CLE; (b) capillary lactates were measured on blood obtained by puncturing stomas' mucosa; and (c) full-thickness stomas' biopsies were sampled for histology, mitochondrial respiratory rate (V 0 = basal and V ADP = respiratory rate in excess of adenosine diphosphate), and levels of superoxide anion evaluation. Functional capillary density (FCD) was measured using ad hoc software. RESULTS: Confocal scanning provided consistent and specific imaging of bowel hypoperfusion at T1: vascular hyperpermeability (blurred and enlarged capillaries) and edema (enhanced visualization of the brush border due to increased intercellular spaces and fluorescein leakage). At the end of T2, there was an improved capillary flow. FCD-A index expressed statistically significant correlation with (1) stoma capillary lactates (p = 0.023); (2) systemic capillary lactates (p = 0.031); (3) inflammation pathology score (p = 0.048); (4) central venous pressure (p = 0.0043); and (5) pulmonary artery pressure (p = 0.01). Stoma capillary lactates (mmol/L) were significantly increased at T1 (8.81 ± 4.23; p < 0.0001) and at T2 (4.77 ± 3.13; p < 0.01) when compared to T0 inclusion values (1.86 ± 0.56). V 0 and V ADP (pmol O2/min/mg tissue) were both significantly decreased at T1 versus T0 (p < 0.007 and p < 0.01, respectively) and recovered by the end of reanimation (T2 vs. T0, p = n.s.). Mean O 2·- production (µmol/min/mg/dry tissue) increased at T1 and significantly decreased at T2. CONCLUSIONS: Confocal laser endomicroscopy (CLE) imaging could identify morphological signs congruent with biochemical markers of bowel perfusion and could be useful for assessment of stomas.

The feasibility of laparoscopic pancreaticoduodenectomy-a stepwise procedure and learning curve.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) has been proven feasible and safe. The artery-first approach emerged as a standard procedure in pancreatic surgery. In this manuscript, we describe both our stepwise, artery-first technique for LPD and methods for accumulating experience during the initial learning stage. METHOD: This is a retrospective review of 12 patients who underwent LPD between 2012 and 2015. We classified the first five patients as the early group and the remaining seven as the late group. Here, we present our stepwise procedure for LPD, along with the perioperative results and postoperative prognoses for the two groups. RESULTS: The mean operative time for the 12 patients undergoing LPD was 408.3 ± 97.5 min. The average blood loss was 146.7 ± 90.2 mL. The dissection time (TD) was significantly shorter in the late group compared with the early group (140 vs. 200 min, respectively; p = 0.006). However, there was no difference in the reconstruction time (TR) between the two groups (220 vs. 200 min; p = 0.807). CONCLUSION: Artery-first LPD is a feasible procedure for selected patients and has acceptable results. Using this stepwise procedure, the operative time could be reduced, mainly by reducing the time required for dissection.

Confocal Imaging and Tissue-Specific Fluorescent Probes for Real-Time In Vivo Immunohistochemistry. Proof of the Concept in a Gastric Lymph Node Metastasis Model.

BACKGROUND: Tumor-specific fluorescent antibodies, which can be recognized at a cellular or tissue level using optical imaging such as confocal laser endomicroscopy (CLE), could provide a means for rapid and accurate tumor diagnosis and staging. The aim of this study was to evaluate the ability of CLE to detect the presence of tagged cells within lymph nodes in an original simulated metastatic model. MATERIALS AND METHODS: A solution of indocyanine green containing a suspension of porcine hepatocytes, marked with carboxy-fluorescein-succinimidyl-ester (CFSE), was injected endoscopically in the gastric submucosa of 10 pigs. Fluorescence lymphography using a near-infrared laparoscope was used to identify sentinel and secondary drainage nodes. Additionally, a nonfluorescent gastric and a mesenteric node were identified. Every 5-10 min, those nodes were scanned using probe-based or needle-based CLE (pCLE or nCLE). Immunohistochemistry (IHC) using anti-cytokeratin 18 antibodies was subsequently performed to confirm the presence of hepatocytes in the lymph nodes. RESULTS: A total of 36 lymph nodes were analyzed with both CLE probes. Hepatocyte penetration in lymph nodes, as assessed by repeated CLE scanning, took 10-40 min after submucosal injection. Concordance between CLE and IHC was 84 and 72 % for pCLE and nCLE, respectively. False negatives were partly due to incomplete CFSE labeling of hepatocytes, which could not be recognized by CLE, but were detected with IHC. CONCLUSIONS: Real-time CLE analysis effectively recognized the presence in perigastric nodes of marked hepatic cells that had been injected endoscopically in the stomach. Validation studies on tumor-bearing animals using tumor-specific antibodies should be performed.

Real-time fluorescence angiography by intra-arterial indocyanine green injection to identify obscure gastrointestinal bleeding territory: proof of concept in the porcine model.

BACKGROUND: Despite intensive preoperative localization workouts, intraoperative localization of the bleeding source in case of obscure gastrointestinal bleeding (OGIB) can be cumbersome and time-consuming. Our aim was to assess the feasibility of image-guided laparoscopic identification of the small bowel loop containing the bleeding source with and without near-infrared angiographic enhancement. MATERIALS AND METHODS: Angiography of superior mesenteric artery (SMA) branches was performed in 11 pigs using a right femoral artery approach, followed by a three-port laparoscopy, using a near-infrared-equipped laparoscope. Two pigs were used to identify the optimal intra-arterial indocyanine green (ICG) dose. Eight pigs were divided into two groups: ICG near-infrared angiography-assisted laparoscopy (n = 4) and fluoroscopic-assisted laparoscopy (n = 4). Finally, in one pig, a novel OGIB model was created and used to evaluate the ICG enhancement pattern in the presence of active bleeding. RESULTS: Mean time to identify the fluorescence signal from the small bowel segment fed by the catheterized SMA branch was 13.75 ± 7.8 s, which was statistically significantly shorter than the time required to identify the tip of the catheter by fluoroscopic guidance, i.e., 243.25 ± 107 s (p = 0.02). CONCLUSIONS: Near-infrared fluorescence angiography using intra-arterial ICG injection provides a fast image-guided intraoperative localization of the small bowel loop fed by the arterial territory identified as bleeding by digital subtraction angiography and could help target the bleeding source during OGIB surgery.

Novel method for hybrid endo-laparoscopic full-thickness gastric resection using laparoscopic transgastric suture passer device.

BACKGROUND: Current surgical methods for partial gastric full-thickness resections (FTRs) are limited by long operative times and risk of gastric content spillage, especially for lesions located at the posterior wall. We propose a simplified hybrid approach to FTR with reduced risk of spillage. METHODS: Resection margins were marked by endoscopic electrocautery to simulate a gastric lesion in the upper third of the posterior wall in eight pigs. A custom-made laparoscopic "suture passer" was made of a sharpened bendable dissecting forceps. Full-thickness sutures were alternatively passed from the serosa side with the suture passer through the gastric wall and grabbed endoluminally using an endoscopic grasper and vice versa. These transgastric sutures formed either a purse string (PS; n = 4) or a continuous horizontal mattress (HM; n = 4). Sutures were then fastened from the laparoscopic side, resulting in external outpouching of the lesion. The pouch was transected using 45-mm linear staplers. Operative time, resection margins, and number of staplers were evaluated. RESULTS: The combined approach allowed one to precisely place the sutures around the pseudo lesions, despite the inflated stomach, and it included all target markings. PS and HM methods were similar regarding time for transgastric suture (780 s ± 219.1 s vs. 765 s ± 179.2 s, p = .885), resection margins (1.3 ± 1.0 cm vs. 0.8 ± 0.6 cm, p = .248), and number of staplers (3.8 ± 1.0 vs 3.3 ± 0.5, p = .405). Stapling time (600 s ± 189.7 s vs. 330 s ± 24.5 s, p = .028) was significantly shorter in the HM technique. CONCLUSION: FTR with laparo-endoscopic transgastric suture application was feasible in the animal model. This technique allows one to achieve accurate resection margins with minimal risk of spillage.

Near-infrared cholecysto-cholangiography with indocyanine green may secure cholecystectomy in difficult clinical situations: proof of the concept in a porcine model.

BACKGROUND: Biliary injuries remain a major concern in laparoscopic cholecystectomy. New intraoperative guidance modalities, including near-infrared fluorescence cholangiography, are under evaluation. Initial results showed limitations in visualizing the biliary tree in specific clinical situations. The aim of this study was to examine the feasibility and potentiality of fluorescence cholecysto-cholangiography performed with a direct injection of indocyanine green (ICG) in the gallbladder and to compare it to systemic injection in such situations. MATERIALS AND METHODS: Seven pigs were included in this non-survival study. In two pigs, the gallbladder was punctured by a percutaneous needle, and 1 mL of ICG in different concentrations (0.001, 0.01, 0.1, and 1 mg/mL) was sequentially injected. Visibility and pattern of the fluorescent signal around Calot's triangle were examined and compared with those of two control pigs receiving 2.5 mg of intravenous ICG, 30 min prior to the operation. Different scenarios of cholecystitis were modeled using an injection of a mixture of blood and agarose gel around Calot's triangle area in the remaining three pigs, and the applicability of direct intragallbladder injection methods was evaluated. RESULTS: The fluorescent signal was identified immediately after intragallbladder injection, and the cystic duct became visible by 0.1 and 1 mg/mL of ICG. The whole cystic duct and the infundibulum of the gallbladder were clearly enhanced by intragallbladder ICG injection, but not by systemic injection. In the cholecystitis models, the cystic duct could be identified only after partial dissection, and fluorescence visualization of the gallbladder infundibulum provided crucial information to find the correct starting point of dissection. CONCLUSIONS: Fluorescence cholecysto-cholangiography through direct intragallbladder ICG injection could rapidly provide an adequate visualization of gallbladder neck and cystic duct and might be a valid option to increase the safety of cholecystectomy in case of cholecystitis.