Comparing the effects of continuous positive airway pressure via mask or helmet interface on oxygenation and pulmonary complications after major abdominal surgery: a randomized trial.

The risk of pulmonary complications is high after major abdominal surgery but may be reduced by prophylactic postoperative noninvasive ventilation using continuous positive airway pressure (CPAP). This study compared the effects of intermittent mask CPAP (ICPAP) and continuous helmet CPAP (HCPAP) on oxygenation and the risk of pulmonary complications following major abdominal surgery. Patients undergoing open abdominal aortic aneurysm repair or pancreaticoduodenectomy were randomized (1:1) to either postoperative ICPAP or HCPAP. Oxygenation was evaluated as the partial pressure of oxygen in arterial blood fraction of inspired oxygen ratio (PaO2/FIO2) at 6 h, 12 h, and 18 h postoperatively. Pulmonary complications were defined as X-ray verified pneumonia/atelectasis, clinical signs of pneumonia, or supplementary oxygen beyond postoperative day 3. Patient-reported comfort during CPAP treatment was also evaluated. In total, 96 patients (ICPAP, n = 48; HCPAP, n = 48) were included, and the type of surgical procedure were evenly distributed between the groups. Oxygenation did not differ between the groups by 6 h, 12 h, or 18 h postoperatively (p = 0.1, 0.08, and 0.67, respectively). Nor was there any difference in X-ray verified pneumonia/atelectasis (p = 0.40) or supplementary oxygen beyond postoperative day 3 (p = 0.53). Clinical signs of pneumonia tended to be more frequent in the ICPAP group (p = 0.06), yet the difference was not statistically significant. Comfort scores were similar in both groups (p = 0.43), although a sensation of claustrophobia during treatment was only experienced in the HCPAP group (11% vs. 0%, p = 0.03). Compared with ICPAP, using HCPAP was associated with similar oxygenation (i.e., PaO2/FIO2 ratio) and a similar risk of pulmonary complications. However, HCPAP treatment was associated with a higher sensation of claustrophobia.

Intraoperative near-infrared lymphography with indocyanine green may aid lymph node dissection during robot-assisted resection of gastroesophageal junction cancer.

BACKGROUND: Adequate lymphadenectomy during gastroesophageal junction (GEJ) cancer resection is essential, because lymph node (LN) metastasis correlates with increased recurrence risk. Fluorescence lymphography with indocyanine green (ICG) has been used for LN mapping in several surgical specialties; however, reports on GEJ cancer are lacking. Therefore, we investigated whether intraoperative ICG lymphography could facilitate LN harvest during robot-assisted resection of GEJ cancer. METHODS: Patients scheduled for robot-assisted resection of GEJ cancer were included, and outcomes were compared with historical controls. After intraoperative endoscopic submucosal ICG injection, standard D1 + LN dissection was performed under white light. Then, near-infrared (NIR) fluorescence imaging was activated, and each LN dissection area was re-examined. Any tissue within the D1 + field exhibiting distinctly increased ICG fluorescence compared with background tissue was dissected and sent for pathology review. RESULTS: We included 70 patients between June 2020 and October 2021. Three cases were aborted due to disseminated disease, and two were converted to open resection and excluded from the analysis. Additional tissue was dissected after NIR review in 34 of 65 (52%) patients. We dissected 43 fluorescent tissue samples, and after pathology review, 30 were confirmed LNs; none were metastatic. The median number of LNs harvested per patient (34, interquartile range [IQR] = 26-44) was not significantly different from that harvested from historical controls (32, IQR = 24-45; p = 0.92), nor were there any differences between these two groups in the duration of surgery, intraoperative blood loss, or comprehensive complication scores (p = 0.12, p = 0.46, and p = 0.41, respectively). CONCLUSIONS: Intraoperative NIR lymphography with ICG may aid LN detection during robot-assisted resection of GEJ cancer without increasing surgical risk. Although NIR lymphography may facilitate LN dissection, none of the LN removed after the NIR review was metastatic. Hence, it remains uncertain whether NIR lymphography will improve oncological outcomes.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BACKGROUND: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. METHODS: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. RESULTS: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (-9% [95% CI -3.2 to -15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r = .352 [95% CI 0.031-0.674], p < .001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. CONCLUSION: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.

Evaluation of the systemic inflammatory response, endothelial cell dysfunction, and postoperative morbidity in patients, receiving perioperative corticosteroid, developing severe mesenteric traction syndrome - an exploratory study.

OBJECTIVE: To determine whether a severe mesenteric traction syndrome (MTS) leads to increased surgical stress, endothelial dysfunction, and postoperative morbidity in a cohort in which all patients received a single dose of methylprednisolone. INTRODUCTION: Preoperatively administered corticosteroids lower the incidence of severe MTS and may also attenuate surgical stress and endothelial damage associated with the development of severe MTS, ultimately lowering the postoperative morbidity. METHODS: This exploratory study analyzed prospectively collected data from 45 patients all receiving 125 mg methylprednisolone. No control group was included. The severity of MTS was graded intraoperatively, and postoperative morbidity was assessed blinded. Blood samples for plasma prostacyclin (PGI2), IL6 and endothelial damage (Syndecan-1, sVEGRF1 and sThrombomodulin) biomarkers were obtained at predefined time points. RESULTS: Patients undergoing either open liver surgery (n = 23) or Whipple's procedure (n = 22) were included. No differences were found in postoperative morbidity between patients developing and not developing severe MTS. Surgery led to significantly increased plasma levels of biomarkers indicative of surgical stress and endothelial damage. Further, patients developing severe MTS had increased levels of PGI2 (p = 0.05) and lower systemic vascular resistance (p < 0.05) 15 min into surgery. However, when comparing the biomarkers of surgical stress, endothelial damage no differences between patients with and without severe MTS were identified. CONCLUSION: This exploratory study found that surgery was associated with a pro-inflammatory response and damage to the endothelium. However, no differences were found between patients developing severe MTS and patients developing moderate/no MTS in biomarkers of surgical stress, endothelial damage, or postoperative morbidity. Corticosteroids may therefore attenuate the endothelial damage in patients developing severe MTS. However, as this was an exploratory study, these findings must be confirmed in future randomized controlled studies.

Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography.

PURPOSE: Indocyanine green (ICG) and sodium fluorescein (SF) are fluorescent dyes used for sentinel lymph node mapping. In oncological gastric surgery, ICG lymphography has increased the number of resected lymph nodes. However, the optimal time to administer ICG is unclear, and both preoperative and intraoperative injections have been practised. As dye spillage will diminish lymphogram visibility, a second dye with different excitation and emission spectra may present a clinical alternative. We measured the time until maximum ICG fluorescence of gastric sentinel lymph nodes and investigated the feasibility of combined lymphography with two fluorescent dyes: ICG and SF. METHODS: Ten Danish Landrace/Yorkshire pigs were used in this study. After completion of the laparoscopic setup, ICG and then SF were endoscopically injected into the gastric submucosa. Lymphograms for both dyes were recorded, and the time until maximum ICG sentinel lymph node fluorescence was determined. RESULTS: The mean time until maximum ICG fluorescence of gastric sentinel lymph nodes was 50 s (± 12.5), and the fluorescent signal then remained stable until the end of the recorded period (45 min). A lymphogram showing both ICG and SF was acquired for eight of the ten pigs. CONCLUSIONS: Because of the short time until maximum ICG fluorescence of sentinel lymph nodes, intraoperative injections could be a sufficient alternative to preoperative injections for oncological gastric surgery. Combined ICG and SF lymphography was feasible and resulted in clear lymphograms with no interference between the two dyes. The ability to use multiple dyes during a surgical procedure offers the exciting prospect of simultaneously assessing perfusion and performing fluorescence lymphography.

Mesenteric traction syndrome in pigs: A single-blinded, randomized controlled trial.

Background: Mesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications. A triad of hypotension, tachycardia, and facial flushing seems provoked by prostacyclin (PGI2) release from the gut in response to mesenteric traction. The administration of nonsteroidal anti-inflammatory drugs (NSAID) inhibits PGI2 release, stabilizing the hemodynamic response. Here, we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo treatment. Materials and Methods: Twenty pigs were allocated to either ketorolac or placebo treatment. Five minutes of manual mesenteric traction was applied. Plasma 6-keto-PGF1α, a stable metabolite of PGI2, hemodynamic variables, and regional blood flow (laser speckle contrast imaging) to the liver, stomach, small intestine, upper lip, and snout (laser Doppler flowmetry) were recorded prior to traction and 5 and 30 minutes thereafter. Results: Both groups of pigs presented a decrease in systemic vascular resistance (P = .01), mean arterial blood pressure (P = .001), and blood flow in the gastric antrum (P = .002). Plasma 6-keto-PGF1α did not increase in either group (P = .195), and cardiac output, heart rate, central venous pressure, and blood flow to the liver, small intestine, upper lip, and snout remained unchanged. Conclusion: Mesenteric traction resulted in cardiovascular depression, including reduced blood flow in the gastric antrum. Plasma 6-keto-PGF1α did not increase, and ketorolac administration did not alter the response to mesenteric traction. Furthers studies are needed to identify which substance is responsible for eliciting the cardiovascular response to mesenteric traction in pigs.

Hypotension Associated with MTS is Aggravated by Early Activation of TEA During Open Esophagectomy.

OBJECTIVE: A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI2)-induced vasodilation and identified by facial flushing, tachycardia, and hypotension during abdominal surgery. We evaluated whether thoracic epidural anesthesia (TEA) influences the incidence of MTS. DESIGN: Randomized, blinded controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Fifty patients undergoing open esophagectomy. INTERVENTIONS: Patients were randomized to either early (EA, after induction of general anesthesia) or late activation of TEA (LA, after re-established gastric continuity). Plasma 6-keto-PGF1α, a stable metabolite of PGI2 and interleukine-6 (IL6) were measured in plasma during surgery along with hemodynamic variables and MTS graded according to facial flushing together with plasma C-reactive protein on the third post-operative day. RESULTS: Forty-five patients met the inclusion criteria. Development of MTS tended to be more prevalent with EA (n=13/25 [52%]) than with LA TEA (n=5/20 [25%], p=0.08). For patients who developed MTS, there was a transient increase in plasma 6-keto-PGF1α by 15 min of surgery and plasma IL6 (p<0.001) as C-reactive protein (P<0.009) increased. EA TEA influenced the amount of phenylephrine needed to maintain mean arterial pressure >60 mmHg in patients who developed MTS (0.16 [0.016-0.019] mg/min vs MTS and LA TEA 0.000 [0.000-0.005] mg/min, p<0.001). CONCLUSION: The incidence of MTS is not prevented by TEA in patients undergoing open esophagectomy. On the contrary, the risk of hypotension is increased in patients exposed to TEA during surgery, and the results suggest that it is advantageous to delay activation of TEA. Also, MTS seems to be associated with a systemic inflammatory response, maybe explaining the aggravated post-operative outcome.

Severe mesenteric traction syndrome is associated with increased systemic inflammatory response, endothelial dysfunction, and major postoperative morbidity.

This study aimed to determine if mesenteric traction syndrome (MTS) triggers increased systemic inflammation and endothelial cell dysfunction. Patients developing severe MTS had pronounced early IL6 elevations followed by endothelial cell damage. Furthermore, these processes were associated with increased postoperative morbidity. OBJECTIVE: To determine whether mesenteric traction syndrome (MTS) leads to increased systemic inflammation and dysfunction of the glycocalyx and endothelial cell and whether this correlates with the degree of postoperative morbidity. INTRODUCTION: Severe MTS is associated with increased postoperative morbidity following major gastrointestinal surgery, but the pathophysiological mechanism has not been previously explored. Systemic inflammatory response and impaired glycocalyx and endothelial cells may be responsible for the development of symptoms. METHODS: The study analyzed prospectively collected data from two cohorts (n = 67). The severity of the MTS response was graded intraoperatively and blood samples for PGI2, catecholamines, IL6, and endothelial biomarkers obtained at predefined time points. RESULTS: Patients undergoing either esophagectomy (n = 45) or gastrectomy (n = 22) were included. Surgery led to significantly increased plasma concentrations of all biomarkers. Yet, patients who developed severe MTS had higher baseline epinephrine levels (p < 0.05) and higher levels of PGI2 (p < 0.05), Syndecan-1 (p < 0.001), and sVEGFR1 (p < 0.001). Peak values of IL6, Syndecan-1, sVEGFR1, and sTM all correlated to peak PGI2. Lastly, patients with high postoperative morbidity had higher baseline epinephrine (p = 0.009) and developed higher plasma IL6 (p = 0.007) and sTM (p = 0.022). CONCLUSION: The development of severe MTS during upper gastrointestinal surgery is associated with preoperative elevated plasma epinephrine and further a more pronounced proinflammatory response and damage to the vascular endothelium. The increased postoperative morbidity seen in patients with severe MTS may thus, in part, be explained by an inherent susceptibility towards an inappropriate secretion of PGI2, which leads to an increased surgical stress response and endothelial damage. These findings must be confirmed in a new prospective cohort.

Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist.

OBJECTIVES: Obesity is a complex disease associated with a high risk of comorbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling. An attractive alternative is to pharmacologically mimic the effects of bariatric surgery by targeting several gut hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed in the gastrointestinal tract has been shown to mediate ghrelin signaling and control appetite, food intake, and energy homeostasis, but the broader effect on gut hormones is largely unknown. A potent and efficacious GPR39 agonist (Cpd1324) was recently discovered, but the in vivo function was not addressed. Herein we studied the efficacy of the GPR39 agonist, Cpd1324, on metabolism and gut hormone secretion. METHODS: Body weight, food intake, and energy expenditure in GPR39 agonist-treated mice and GPR39 KO mice were studied in calorimetric cages. Plasma ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels were measured. Organoids generated from murine and human small intestine and mouse colon were used to study GLP-1 and PYY release. Upon GPR39 agonist administration, dynamic changes in intracellular GLP-1 content were studied via immunostaining and changes in ion transport across colonic mucosa were monitored in Ussing chambers. The G protein activation underlying GPR39-mediated selective release of gut hormones was studied using bioluminescence resonance energy transfer biosensors. RESULTS: The GPR39 KO mice displayed a significantly increased food intake without corresponding increases in respiratory exchange ratios or energy expenditure. Oral administration of a GPR39 agonist induced an acute decrease in food intake and subsequent weight loss in high-fat diet (HFD)-fed mice without affecting their energy expenditure. The tool compound, Cpd1324, increased GLP-1 secretion in the mice as well as in mouse and human intestinal organoids, but not in GPR39 KO mouse organoids. In contrast, the GPR39 agonist had no effect on PYY or GIP secretion. Transepithelial ion transport was acutely affected by GPR39 agonism in a GLP-1- and calcitonin gene-related peptide (CGRP)-dependent manner. Analysis of Cpd1324 signaling properties showed activation of Gαq and Gαi/o signaling pathways in L cells, but not Gαs signaling. CONCLUSIONS: The GPR39 agonist described in this study can potentially be used by oral administration as a weight-lowering agent due to its stimulatory effect on GLP-1 secretion, which is most likely mediated through a unique activation of Gα subunits. Thus, GPR39 agonism may represent a novel approach to effectively treat obesity through selective modulation of gastrointestinal hormonal axes.

Quantitative fluorescence angiography detects dynamic changes in gastric perfusion.

INTRODUCTION: The use of Indocyanine green (ICG) fluorescence angiography (ICG-FA) is an applied method to assess visceral perfusion during surgical procedures worldwide. Further development has entailed quantification of the fluorescence signal; however, whether quantified ICG-FA can detect intraoperative changes in perfusion after hemorrhage has not been investigated previously. In this study, we investigated whether a quantification method, developed and validated in our department (q-ICG), could detect changes in gastric perfusion induced by hemorrhage and resuscitation. METHODS: Ten pigs were included in the study. Specific regions of interest of the stomach were chosen, and three q-ICG measurements of gastric perfusion obtained: 20 min after completion of the laparoscopic setup (baseline), after reducing the circulating blood volume by 30%, and after reinfusion of the withdrawn blood volume. Hemodynamic variables were recorded, and blood samples were collected every 10 min during the procedure. RESULTS: The reduction in blood volume generated decreased gastric perfusion (q-ICG) from baseline (p = 0.023), and gastric perfusion subsequently increased (p < 0.001) after the reintroduction of the withdrawn blood volume. Cardiac output (CO) and mean arterial blood pressure (MAP) shifted correspondingly and the gastric perfusion correlated to CO (r = 0.575, p = 0.001) and MAP (r = 0.436, p = 0.018). CONCLUSION: We present a novel study showing that the q-ICG method can detect dynamic changes in local tissue perfusion induced by hemorrhage and resuscitation. As regional gastrointestinal perfusion may be significantly reduced, while hemodynamic variables such as MAP or heart rate remain stable, q-ICG may provide an objective, non-invasive method for detecting regional early ischemia, strengthening surgical decision making.

The Incidence of Free Peritoneal Tumor Cells before and after Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer.

CONTEXT: The utility of peritoneal washing cytology in patients with gastroesophageal junction cancer has not been thoroughly evaluated. AIMS: The study aimed to determine the incidence of free peritoneal tumor cells by peritoneal washing cytology before and after neoadjuvant chemotherapy using conventional cytopathological methods and immunohistochemical staining for the analysis of peritoneal washings. SETTINGS AND DESIGN: A prospective study conducted at a single tertiary referral hospital. MATERIALS AND METHODS: Patients with gastroesophageal junction cancer and without suspicion of intra- or extraabdominal metastases before the staging laparoscopy were prospectively and consecutively enrolled. Peritoneal washing cytology was performed at staging laparoscopy (primary cytology) and after neoadjuvant chemotherapy during robot-assisted or open resection (secondary cytology). Peritoneal fluid samples were analyzed by conventional cytology and an immunohistochemical panel. RESULTS: Overall, 81 patients met the primary inclusion criteria. During primary cytology, positive cytology without overt metastases (C1M0) was detected in three patients (3.8%) while five patients (6.3%) had overt intra-abdominal metastases but negative cytology (C0M1). None of the patients with C1M0 underwent surgery due to extra-abdominal (n = 1) or intra-abdominal metastases (n = 2), and the overall survival was 4, 7, and 14 months. During secondary cytology, no patients with free peritoneal tumor cells were identified, but seven patients were classified as C0M1 (10.9%). CONCLUSIONS: The incidence of C1M0 was 3.8% and 0% before and after neoadjuvant chemotherapy, respectively in patients with gastroesophageal junction cancer. Free peritoneal tumor cells were not identified in several patients with intra-abdominal metastases suggesting that peritoneal washing cytology with conventional cytology and immunohistochemical staining lack sensitivity.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Laparoscopy to Assist Surgical Decisions Related to Necrotizing Enterocolitis in Preterm Neonates.

Aim of the Study: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that mainly affects preterm infants. Despite advancements in neonatal care, mortality of NEC remains high and controversies exist regarding the most appropriate time for surgical intervention and challenging of diagnosing NEC. Using a pig model of NEC, we aimed to examine if laparoscopy is feasible for diagnosis of NEC. Methods: Preterm caesarean-delivered piglets (n = 42) were fed with increasing amounts of infant formula up to 5 days to induce NEC. On days 3-5, we examined the intestine by laparoscopy under general anesthesia. The bowel was examined by tilting the pigs from supine position to the left and right side. Macroscopic NEC lesions were identified and graded according to a macroscopic scoring system, then a laparotomy was performed to rule out any organ injury and missed NEC lesions. Results: Visible NEC lesions (scores 4-6) were found in 26% (11/42) of the piglets. A positive predictive value of 100% was found for laparoscopy as a diagnostic marker of NEC in both colon and the small intestine. One piglet had a higher NEC score in the small intestine found at laparotomy, than at laparoscopy, resulting in a sensitivity of 67%, and a specificity of 100% for the small intestine. Conversely, both the sensitivity and specificity for colon was 100%. Acceptable levels of agreement was found, with minimal proportional bias in both colon and the small intestine for laparoscopy and laparotomy. Ultrasound examination had a lower sensitivity of 67% and specificity of 63%. All piglets were respiratory and circulatory stable during the procedure. Conclusions: In preterm piglets, laparoscopy is a feasible tool to diagnose NEC with a high positive predictive value and a high specificity.

Effect of hypotensive hypovolemia and thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume in pigs: a blinded, randomized controlled trial.

PURPOSE: Changes in plasma pro-atrial natriuretic peptide (proANP) may indicate deviations in the central blood volume (CBV). We evaluated the plasma proANP response to hypotensive hypovolemia under the influence of thoracic epidural anesthesia (TEA) in pigs. We hypothesized that plasma proANP would decrease in response to hypotensive hypovolemia and that TEA would aggravate the proANP response, reflecting a further decrease in CBV. DESIGN: Randomized, blinded, controlled trial. SETTING: A university-affiliated experimental facility. PARTICIPANTS: Twenty pigs randomized to administration of saline (placebo) or bupivacaine with morphine (TEA) in the epidural space at Th8-Th10. INTERVENTIONS: Relative hypovolemia was established by an inflatable Foley catheter positioned in the inferior caval vein just below the heart (caval obstruction), and hemorrhage-induced hypovolemia was by withdrawal of blood from the femoral artery, both aiming at a mean arterial pressure (MAP) of 50-60 mmHg. Hemodynamic variables and plasma proANP were determined before and after the interventions. RESULTS: Caval obstruction and withdrawal of blood reduced MAP to 50-60 mmHg. Accordingly, cardiac output, central venous pressure, and mixed venous oxygen saturation decreased (p<0.05). Yet, plasma proANP was stable after both caval obstruction (TEA: 72 [63-78] to 80 pmol/L [72-85], p=0.09 and placebo: 64 [58-76] to 69 pmol/L [57-81], p=0.06) and withdrawal of blood (TEA: 74 [73-83] to 79 pmol/L [77-87], p=0.07 and placebo: 64 [56-77] to 67 pmol/L [58-78], p=0.15). CONCLUSION: Plasma proANP was stable in response to relative and hemorrhage-induced hypovolemia to a MAP of 50-60 mmHg, and the response was independent of TEA. The findings suggest that alterations in plasma proANP do not follow deviations in CBV during hypotensive hypovolemia in pigs.

Laser speckle contrast imaging and quantitative fluorescence angiography for perfusion assessment.

PURPOSE: Indocyanine green fluorescence angiography (ICG-FA) is an established technique for assessment of intestinal perfusion during gastrointestinal surgery, whereas quantitative ICG-FA (q-ICG) and laser speckle contrast imaging (LSCI) are relatively unproven. The study aimed to investigate whether the techniques could be applied interchangeably for perfusion assessment. METHODS: Nineteen pigs underwent laparotomy, two minor resections of the small bowel, and anastomoses. Additionally, seven pigs had parts of their stomach and small intestine de-vascularized. Data was also collected from an in vivo model (inferior caval vein measurements in two additional pigs) and an ex vivo flow model, allowing for standardization of experimental flow, distance, and angulation. Q-ICG and LSCI were performed, so that regions of interest were matched between the two modalities in the analyses, ensuring coverage of the same tissue. RESULTS: The overall correlation of q-ICG and LSCI evaluated in the porcine model was modest (rho = 0.45, p < 0.001), but high in tissue with low perfusion (rho = 0.74, p < 0.001). Flux values obtained by LSCI from the ex vivo flow model revealed a decreasing flux with linearly increasing distance as well as angulation to the model. The Q-ICG perfusion values obtained varied slightly with increasing distance as well as angulation to the model. CONCLUSIONS: Q-ICG and LSCI cannot be used interchangeably but may supplement each other. LSCI is profoundly affected by angulation and distance. In comparison, q-ICG is minimally affected by changing experimental conditions and is more readily applicable in minimally invasive surgery.

Effect of early versus delayed activation of thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume during esophagectomy.

BACKGROUND AND OBJECTIVES: A side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects plasma pro-atrial natriuretic peptide (proANP) reflecting deviations in the central blood volume (CBV). We hypothesized that EA TEA would reduce plasma proANP, thus reflecting a decrease in CBV. METHODS: A randomized, controlled, single-blinded trial was conducted. Patients undergoing open esophagectomy were randomized to EA (n=25, after induction of general anesthesia) or LA TEA (n=25, after re-established gastric continuity) with the epidural catheter placed at the interspaces Th7-8 or Th8-9. Plasma proANP was determined repetitively along with hemodynamic variables and administration of fluid/vasopressors as postoperative complications were noted. RESULTS: With EA TEA, plasma proANP decreased following induction of anesthesia to the end of surgery (13%; 113±68 to 99±49 pmol/L; p=0.026), but that was not the case in the LA group (3%; 97±44 to 94±49 pmol/L; p=0.565) despite equal fluid balance (+1584±582 vs +1560±563 mL; p=0.888). Accordingly, the EA group required excessive treatment with vasopressors to maintain MAP >60 mm Hg during surgery (2.7±2 vs 1.6±1.4 ephedrine boluses; p=0.033 and infusion of phenylephrine for 216±86 vs 58±91 min; p<0.001). Plasma proANP and fluid balance were correlated only for EA patients (r=0.44; 95% CI 0.04 to 0.91; p=0.033). CONCLUSIONS: EA TEA reduces plasma proANP indicating that CBV becomes affected. Based on a correlation between plasma proANP and fluid balance, a 2000 mL volume surplus of lactated Ringer's solution is required to maintain plasma proANP stable during open esophagectomy. TRIAL REGISTRATION NUMBER: 2014-002036-14 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-002036-14).

Laser speckle contrast imaging for quantitative assessment of facial flushing during mesenteric traction syndrome in upper gastrointestinal surgery.

The mesenteric traction syndrome (MTS) is associated with prostacyclin (PGI2) facilitated systemic vasodilatation during surgery and is identified by facial flushing. We hypothesized that severe facial flushing would be related to the highest concentrations of plasma PGI2 and accordingly to the highest levels of skin blood flow measured by laser speckle contrast imaging (LSCI). Patients scheduled for major upper abdominal surgery were consecutively included. Within the first hour of the procedure, facial flushing was scored according to a standardized scale, and skin blood flow (LSPU) was continuously measured on the forehead and the cheeks by LSCI. Arterial blood samples for 6-keto-PGF1α (stable metabolite of PGI2) and hemodynamic variables were obtained at defined time points. Overall, 66 patients were included. After 15 min of surgery, patients with severe flushing demonstrated the highest plasma 6-keto-PGF1α concentration and the most significant decrease in systemic vascular resistance. Accordingly, the skin blood flow on the forehead (238 [201-372] to 562 LSPU [433-729]) and the cheeks (341 [239-355] to 624 LSPU [468-917]) increased and were significantly higher than for patients with moderate or no flushing (both, P = 0.04). A cut-off value for skin blood flow could be defined for both the cheeks and the forehead for patients with severe flushing vs. no flushing (425/456 LSPU, sensitivity 75/76% and specificity 80/85%). MTS is linked to an increase in facial skin blood flow during upper gastrointestinal surgery. By applying LSCI, it is possible to quantitatively register facial blood flow, and thereby provide an objective tool for intraoperative verification of MTS.

Synchronous and metachronous liver metastases in patients with colorectal cancer.

INTRODUCTION: Liver metastases are the most common complication to colorectal cancer, and the presence of metastatic disease severely impacts the overall prognosis of the disease. Since the diagnostic work-up of metastasised colorectal cancer has undergone tremendous changes in past decades, an impact on the incidence of metastatic disease is anticipated. The aim of this study was to evaluate the incidence and prognosis of liver metastasis in patients with colorectal cancer. METHODS: From 1 January 2005 to 31 December 2011, all patients with a primary diagnosis of colorectal cancer were identified. Data on metastatic dissemination to the liver were collected from medical charts. Patients were followed until death or the end of the study period (31 December 2016). RESULTS: Among the total study population of 1,672 patients, 23.6% of patients were diagnosed with liver metastases. The incidence of synchronous and metachronous metastases was 16% and 7.7%, respectively. Patients with synchronous and metachronous metastases had a median survival of ten (95% confidence interval (CI): 7.5-12.5) and 43 (95% CI: 35.8-50.2) months, respectively, compared with a median survival of 86 (95% CI: 73.5-98.5) months for patients without liver metastases. CONCLUSIONS: The incidence of synchronous metastases has remained high despite improved diagnostic technology. Patient survival remains significantly lower when metastatic disease is present, even though treatment options for liver metastases have improved. FUNDING: none. TRIAL REGISTRATION: not relevant.

Quantitative perfusion assessment of intestinal anastomoses in pigs treated with glucagon-like peptide 2.

PURPOSE: Despite exhaustive research and improvement of techniques, anastomotic leakage remains a frequent complication in gastrointestinal surgery. As leakage is associated with poor perfusion, reliable objective methods to assess anastomotic perfusion are highly demanded. In addition, such methods enable evaluation of interventions that may improve anastomotic perfusion. Glucagon-like peptide 2 (GLP-2) is an enteroendocrine hormone that regulates mid-gut perfusion. In the present study, we aimed to explore if quantitative perfusion assessment with indocyanine green (q-ICG) could detect an increase in porcine anastomotic perfusion after treatment with GLP-2. METHODS: Nineteen pigs had two small bowel resections followed by anastomosis. Blinded to all investigators, animals were randomized to receive GLP-2 or placebo. Anastomotic perfusion was assessed at baseline, 30 min after injection of GLP-2/placebo, and after 5 days of treatment. Anastomotic strength and healing were evaluated by bursting pressure and histology. RESULTS: Q-ICG detected a significantly higher increase in anastomotic perfusion (p < 0.05) in animals treated with GLP-2, compared with placebo. No significant differences in anastomotic strength or healing were found. CONCLUSIONS: Q-ICG is a promising tool for perfusion assessment in gastrointestinal surgery and opens new opportunities in research of factors that may influence anastomotic healing, but further research is warranted to evaluate the effects of GLP-2 on anastomotic healing.