Assessing the benefits of repeated esophagogastroduodenoscopy at a specialized center before gastric and esophageal cancer surgery.

BACKGROUND: The surgical treatment of gastric and esophageal cancer in Denmark is centralized in four specialized esophagogastric cancer (EGC) centers. Patients are referred after an esophagogastroduodenoscopy (EGD) at a secondary healthcare facility. The EGD is repeated at the specialized EGC center before determining a surgical treatment strategy. This multicenter retrospective study aimed to investigate the quality of EGDs performed at a secondary healthcare facility and evaluate the clinical value of repeated EGD at a specialized center when determining the surgical treatment strategy. METHODS: Patients from three of the four centers, who underwent esophagectomy or gastrectomy with curative intent from 1 June 2016 to 1 May 2021, were included. EGD reports from the referral facilities and EGC centers were compared based on a predefined checklist. Furthermore, endoscopist experience, the time between examinations, and histology were registered. Finally, it was assessed whether the specialized EGD led to any substantial changes in surgical treatment. Baseline characteristics and differences in EGD reports were described and McNemar's chi-square test was performed. A logistic regression analysis was conducted to identify risk factors for a change in surgical strategy. RESULTS: The study included 953 patients who underwent both an initial EGD and EGD at referral to a specialized center. In 644 cases (68%), the information from the initial EGD was considered insufficient concerning preoperative tumor information. In 113 (12%) cases, the findings in the specialized EGD would lead to a significant alteration in the surgical strategy compared with the primary EGD. CONCLUSION: The findings suggest that repeated EGD at a specialized center is of clinical value and helps ensure proper surgical treatment for patients undergoing curative surgery for gastroesophageal cancer.

Western European Variation in the Organization of Esophageal Cancer Surgical Care.

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe.

Excessive Oxygen Administration in High-Risk Patients Admitted to Medical and Surgical Wards Monitored by Wireless Pulse Oximeter.

The monitoring of oxygen therapy when patients are admitted to medical and surgical wards could be important because exposure to excessive oxygen administration (EOA) may have fatal consequences. We aimed to investigate the association between EOA, monitored by wireless pulse oximeter, and nonfatal serious adverse events (SAEs) and mortality within 30 days. We included patients in the Capital Region of Copenhagen between 2017 and 2018. Patients were hospitalized due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) or after major elective abdominal cancer surgery, and all were treated with oxygen supply. Patients were divided into groups by their exposure to EOA: no exposure, exposure for 1-59 min or exposure over 60 min. The primary outcome was SAEs or mortality within 30 days. We retrieved data from 567 patients for a total of 43,833 h, of whom, 63% were not exposed to EOA, 26% had EOA for 1-59 min and 11% had EOA for ≥60 min. Nonfatal SAEs or mortality within 30 days developed in 24%, 12% and 22%, respectively, and the adjusted odds ratio for this was 0.98 (95% CI, 0.96-1.01) for every 10 min. increase in EOA, without any subgroup effects. In conclusion, we did not observe higher frequencies of nonfatal SAEs or mortality within 30 days in patients exposed to excessive oxygen administration.

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.

BACKGROUND: The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently). METHODS: Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m2 epirubicin on day 1 plus intravenous 60 mg/m2 cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m2 fluorouracil daily or oral 625 mg/m2 capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m2 fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 50 mg/m2 docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41·4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m2 paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452. FINDINGS: Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38·8 months (IQR 16·3-55·1), median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82). Median disease-free survival was 32·4 months (95% CI 22·8-64·8) in the perioperative chemotherapy group and 24·0 months (18·0-40·8) in the trimodality therapy group [hazard ratio 0·89 [95% CI 0·68-1·17]; log-rank p=0·41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1·35 [95% CI 0·63-2·91], p=0·44). Pathological complete response (odds ratio 0·33 [95% CI 0·14-0·81], p=0·012), major pathological response (0·21 [0·12-0·38], p<0·0001), and R0 rates (0·21 [0·08-0·53], p=0·0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years. INTERPRETATION: Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise. FUNDING: Health Research Board, Cancer Research UK, Irish Cancer Society, Oesophageal Cancer Fund, and French National Cancer Institute.

Mesenteric traction syndrome - Incidence, impact, and treatment: A systematic scoping review of the literature.

BACKGROUND: Mesenteric traction syndrome (MTS) is commonly seen during major abdominal surgery and is characterised by facial flushing, hypotension, and tachycardia 15 min into surgery. MTS also impacts the postoperative course, as severe MTS has been associated with increased postoperative morbidity. However, despite MTS being common and severe MTS causing increased postoperative morbidity, the gaps in the literature are not clearly defined. We aimed to examine the diagnostic criteria, incidence, intraoperative and postoperative impact, and potential preventative measures of MTS while highlighting potential gaps in the literature. METHODS: We followed the Prisma guidelines and performed a systematic literature search. We included only human studies examining MTS. All hits were screened for title and abstract, followed by a full-text review by at least two authors for determining eligibility for inclusion. Data were extracted and risk of bias was assessed by two independent reviewers. RESULTS: A total of 37 studies, comprising 1102 patients were included in the review. The combined incidence of MTS during open abdominal surgery was found to be 76%, with 35% developing severe MTS. It was found that the development of MTS was associated with marked haemodynamic changes. It was also found that several different subjective diagnostic criteria exist and that severe MTS was associated with increased postoperative morbidity. Furthermore, several preventative measures for protecting against MTS have been examined, but only on the incidence of MTS and not on the postoperative course. CONCLUSION: MTS occurs in 76% of patients undergoing major abdominal surgery and is associated with deleterious haemodynamic effects, which are more pronounced in patients developing severe MTS. Severe MTS is also associated with a worse postoperative outcome. However, gaps are still present in the current literature on MTS.

Continuous Glucose Monitoring Reveals Perioperative Hypoglycemia in Most Patients With Diabetes Undergoing Major Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols. SUMMARY BACKGROUND DATA: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions. METHODS: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001. RESULTS: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses. CONCLUSIONS: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management.

Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial.

BACKGROUND: The proadaptive effects of glucagon-like peptide-2 (GLP-2) include stimulation of intestinal mucosal growth as well as intestinal blood flow and angiogenesis. We have recently reported that daily subcutaneous injections of glepaglutide, a long-acting GLP-2 analog, improved intestinal absorptive function in patients with short bowel syndrome (SBS). As secondary and exploratory end points, the effects of glepaglutide on intestinal morphology and perfusion are reported. METHODS: The following assessments were done in 18 patients with SBS in a randomized, crossover, dose-finding, phase 2 trial before and after three weeks of treatment with glepaglutide: plasma citrulline and mucosa biopsies to assess changes in (1) intestinal morphology by immunohistochemistry and (2) gene expressions associated with absorption, proliferation, and markers of tight-junction integrity by quantitative polymerase chain reaction. Intestinal perfusion was assessed in stoma nipples by laser speckle contrast imaging and quantitative fluorescence angiography with indocyanine green. RESULTS: In the 1- and 10-mg dose groups, glepaglutide significantly increased plasma citrulline by 15.3 µmol/L (P = 0.001) and 15.6 µmol/L (P = 0.001), respectively. Trends toward an increase in villus height, crypt depth, and epithelium height were seen in the same groups. No significant changes were seen in gene expressions or intestinal perfusion. CONCLUSION: The increase in plasma citrulline and the morphological improvements may partly account for improvement in the intestinal absorptive function. However, the finding of a stability in perfusion after three weeks of treatment with glepaglutide may have been preceded by a more profound acute-phase increase in intestinal perfusion at treatment initiation.

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.

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.

Wireless Single-Lead ECG Monitoring to Detect New-Onset Postoperative Atrial Fibrillation in Patients After Major Noncardiac Surgery: A Prospective Observational Study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is associated with several cardiovascular complications and higher mortality. Several pathophysiological processes such as hypoxia can trigger POAF, but these are sparsely elucidated, and POAF is often asymptomatic. In patients undergoing major gastrointestinal cancer surgery, we aimed to describe the frequency of POAF as automatically estimated and detected via wireless repeated sampling monitoring and secondarily to describe the association between preceding vital sign deviations and POAF. METHOD: Patients ≥60 years of age undergoing major gastrointestinal cancer surgery were continuously monitored for up to 4 days postoperatively. Electrocardiograms were obtained every minute throughout the monitoring period. Clinical staff were blinded to all measurements. As for the primary outcome, POAF was defined as 30 consecutive minutes or more detected by a purpose-built computerized algorithm and validated by cardiologists. The primary exposure variable was any episode of peripheral oxygen saturation (Spo2) <85% for >5 consecutive minutes before POAF. RESULTS: A total of 30,145 hours of monitoring was performed in 398 patients, with a median of 92 hours per patient (interquartile range [IQR], 54-96). POAF was detected in 26 patients (6.5%; 95% confidence interval [CI], 4.5-9.4) compared with 14 (3.5%; 95% CI, 1.94-5.83) discovered by clinical staff in the monitoring period. POAF was followed by 9.4 days hospitalization (IQR, 6.5-16) versus 6.5 days (IQR, 2.5-11) in patients without POAF. Preceding episodes of Spo2 <85% for >5 minutes (OR, 1.02; 95% CI, 0.24-4.00; P = .98) or other vital sign deviations were not significantly associated with POAF. CONCLUSIONS: New-onset POAF occurred in 6.5% (95% CI, 4.5-9.4) of patients after major gastrointestinal cancer surgery, and 1 in 3 cases was not detected by the clinical staff (35%; 95% CI, 17-56). POAF was not preceded by vital sign deviations.

Continuous monitoring of vital sign abnormalities; association to clinical complications in 500 postoperative patients.

BACKGROUND: Patients undergoing major surgery are at risk of complications, so-called serious adverse events (SAE). Continuous monitoring may detect deteriorating patients by recording abnormal vital signs. We aimed to assess the association between abnormal vital signs inspired by Early Warning Score thresholds and subsequent SAEs in patients undergoing major abdominal surgery. METHODS: Prospective observational cohort study continuously monitoring heart rate, respiratory rate, peripheral oxygen saturation, and blood pressure for up to 96 h in 500 postoperative patients admitted to the general ward. Exposure variables were vital sign abnormalities, primary outcome was any serious adverse event occurring within 30 postoperative days. The primary analysis investigated the association between exposure variables per 24 h and subsequent serious adverse events. RESULTS: Serious adverse events occurred in 37% of patients, with 38% occurring during monitoring. Among patients with SAE during monitoring, the median duration of vital sign abnormalities was 272 min (IQR 110-447), compared to 259 min (IQR 153-394) in patients with SAE after monitoring and 261 min (IQR 132-468) in the patients without any SAE (p = .62 for all three group comparisons). Episodes of heart rate ≥110 bpm occurred in 16%, 7.1%, and 3.9% of patients in the time before SAE during monitoring, after monitoring, and without SAE, respectively (p < .002). Patients with SAE after monitoring experienced more episodes of hypotension ≤90 mm Hg/24 h (p = .001). CONCLUSION: Overall duration of vital sign abnormalities at current thresholds were not significantly associated with subsequent serious adverse events, but more patients with tachycardia and hypotension had subsequent serious adverse events. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03491137.

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

OBJECTIVE: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

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.

Assessment of sarcopenia in patients with upper gastrointestinal tumors: Prevalence and agreement between computed tomography and dual-energy x-ray absorptiometry.

BACKGROUND & AIMS: Sarcopenia is associated with an increased risk of complications to treatment and lower survival rates in patients with cancer, but there is a lack of agreement on cut-off values and assessment methods. We aimed to investigate the prevalence of sarcopenia assessed by dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) as well as the agreement between the methods for identification of sarcopenia. METHODS: This cross-sectional study pooled data from two studies including patients scheduled for surgery for gastrointestinal tumors. We assessed sarcopenia using two different cut-off values derived from healthy young adults for DXA and two for CT. Additionally, we used one of the most widely applied cut-off values for CT assessed sarcopenia derived from obese cancer patients. The agreement between DXA and CT was evaluated using Cohen's kappa. The mean difference and range of agreement between DXA and CT for estimating total and appendicular lean soft tissue were assessed using Bland-Altman plots. RESULTS: In total, 131 patients were included. With DXA the prevalence of sarcopenia was 11.5% and 19.1%. Using CT, the prevalence of sarcopenia was 3.8% and 26.7% using cut-off values from healthy young adults and 64.1% using the widely applied cut-off value. The agreement between DXA and CT in identifying sarcopenia was poor, with Cohen's kappa values ranging from 0.05 to 0.39. The mean difference for estimated total lean soft tissue was 1.4 kg, with 95% limits of agreement from -8.6 to 11.5 kg. For appendicular lean soft tissue, the ratio between DXA and CT was 1.15, with 95% limits of agreement from 0.92 to 1.44. CONCLUSIONS: The prevalence of sarcopenia defined using DXA and CT varied substantially, and the agreement between the two modalities is poor.

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.

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.

Quantification of fluorescence angiography: Toward a reliable intraoperative assessment of tissue perfusion - A narrative review.

BACKGROUND: Accurate intraoperative assessments of tissue perfusion are essential in all forms of surgery. As traditional methods of perfusion assessments are not available during minimally invasive surgery, novel methods are required. Here, fluorescence angiography with indocyanine green has shown promising results. However, to secure objective and reproducible assessments, quantification of the fluorescent signal is essential (Q-ICG). This narrative review aims to provide an overview of the current status and applicability of Q-ICG for intraoperative perfusion assessment. RESULTS: Both commercial and custom Q-ICG software solutions are available for intraoperative use; however, most studies on Q-ICG have performed post-operative analyses. Q-ICG can be divided into inflow parameters (ttp, t0, slope, and T1/2max) and intensity parameters (Fmax, PI, and DR). The intensity parameters appear unreliable in clinical settings. In comparison, inflow parameters, mainly slope, and T1/2max have had superior clinical performance. CONCLUSION: Intraoperative Q-ICG is clinically available; however, only feasibility studies have been performed, rendering an excellent usability score. Q-ICG in a post-operative setting could detect changes in perfusion following a range of interventions and reflect clinical endpoints, but only if based on inflow parameters. Thus, future studies should include the methodology outlined in this review, emphasizing the use of inflow parameters (slope or T1/2max), a mass-adjusted ICG dosing, and a fixed camera position.

Optimizing quantitative fluorescence angiography for visceral perfusion assessment.

BACKGROUND: Compromised tissue perfusion is a significant risk factor for anastomotic leakage after intestinal resection, leading to prolonged hospitalization, risk of recurrence after oncologic resection, and reduced survival. Thus, a tool reducing the risk of leakage is highly warranted. Quantitative indocyanine green angiography (Q-ICG) is a new method that provides surgeons with an objective evaluation of tissue perfusion. In this systematic review, we aimed to determine the optimal methodology for performing Q-ICG. METHOD: A comprehensive search of the literature was performed following the PRISMA guidelines. The following databases were searched: PubMed, Embase, Scopus, and Cochrane. We included all clinical studies that performed Q-ICG to assess visceral perfusion during gastrointestinal surgery. Bias assessment was performed with the Newcastle Ottawa Scale. RESULTS: A total of 1216 studies were screened, and finally, 13 studies were included. The studies found that intensity parameters (maximum intensity and relative maximum intensity) could not identify patients with anastomotic leakage. In contrast, the inflow parameters (time-to-peak, slope, and t1/2max) were significantly associated with anastomotic leakage. Only two studies performed intraoperative Q-ICG while the rest performed Q-ICG retrospectively based on video recordings. Studies were heterogeneous in design, Q-ICG parameters, and patient populations. No randomized studies were found, and the level of evidence was generally found to be low to moderate. CONCLUSION: The results, while heterogenous, all seem to point in the same direction. Fluorescence intensity parameters are unstable and do not reflect clinical endpoints. Instead, inflow parameters are resilient in a clinical setting and superior at reflecting clinical endpoints.