Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish ...safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.
Abstract
Background and study aims
Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a ...chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug’s cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer.
Patients and methods
In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin. All side effects and adverse events (AEs) were registered and the patients were later evaluated with gastroscopy and 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).
Results
Treatment were well tolerated, main AEs being nausea, vomiting, oral thrush, pneumonia, retrosternal pain, fever, and hoarseness. No serious complications were observed. Five patients had a visual tumor response confirmed by gastroscopy. In two cases, these findings were confirmed with 18F-FDG PET/MRI as it revealed a reduction of total tumor mass.
Conclusion
Electrochemotherapy in patients with advanced esophageal cancer was conducted without major safety concerns. This study paves the way for larger studies, which may further elucidate response rates for and side effects of this new treatment.
Isolated tumor cells (ITC) are tumor cells identified in the regional lymph nodes of patients with adeno- or squamous cell carcinoma of the esophagogastric junction (EGJ) or the esophagus. The ...current staging guidelines for these cancers do not assign any prognostic relevance to ITC, but their role remains debatable. We evaluated current literature to provide an overview of the prognostic relevance of ITC in regional lymph nodes of patients diagnosed with node negative cancer of the esophagus and EGJ.
A systematic search of several databases according to PRISMA guidelines. Three main criteria for inclusion were selected: 1. The studies had to include a group of patients with histopathologically identified ITC as defined by the Union for International Cancer Control Tumor, Node, Metastasis-classification 8th edition. 2. The studies had to include a group of patients classified as pN0. 3. The studies had to present the survival rate of patients with pN0, ITC.
A total of five studies met the inclusion criteria. Combined, the studies included 434 pN0-patients of which 88 patients had ITC when evaluating the lymph nodes more extensively. The rate of ITC varied from 8% to 56% between studies. Significant differences in surgical techniques, neoadjuvant treatment and histological subtypes were observed. Three studies found a significant prognostic impact of ITC while one did not, and one had conflicting results. The largest difference in 5-year-survival was 33% for patients with ITC compared with 60% without ITC.
Although, the results were conflicting, ITC appeared to be a negative prognostic factor in esophageal and EGJ cancer. However, heterogeneity between the studies did not allow for a definitive conclusion.
Objective
The objective of this study is to investigate the impact of ketorolac and other nonsteroidal anti-inflammatory drugs on anastomotic leakage after surgery for gastro-esophageal-junction ...cancer.
Summary Background Data
Within the last two decades, the incidence of gastro-esophageal-junction cancer has increased in the western world and surgery is the curative treatment modality of choice. Anastomotic leakage is a feared complication of gastro-esophageal surgery, as it increases recurrence, morbidity, and mortality. Nonsteroidal anti-inflammatory drugs are widely used for postoperative pain relief. Nonsteroidal anti-inflammatory drugs have, however, in colorectal surgery, been shown to increase the risk of anastomotic leakage.
Method
In a historical cohort study, we investigated the impact of nonsteroidal anti-inflammatory drugs on anastomotic leakage in 557 patients undergoing surgery for gastro-esophageal-junction cancer. Data were collected from a prospective maintained database, the Danish National Patient Registry, and patient medical records. Data were analyzed using univariate and multivariate statistical models and were stratified for theoretical confounders.
Results
In univariate analysis, we did not observe any difference in age, gender, tobacco exposure, or comorbidity status between patients experiencing anastomotic leakage and those without. In multivariate analysis, gender, histology, and type of anastomosis proved to affect odds ratios for anastomotic leakage. After adjustment for possible confounders, we found an odds ratio of 6.05 (95% confidence interval 2.71; 13.5) for ketorolac use and of 5.24 (95% confidence interval 1.85; 14.8) for use of other nonsteroidal anti-inflammatory drugs for anastomotic leakage during the first seven postoperative days.
Conclusion
In the present study, we found a strong association between the postoperative use of ketorolac and other nonsteroidal anti-inflammatory drugs and the risk for anastomotic leakage after surgery for gastro-esophageal-junction cancers.
Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients ...were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic examinations showed a similar wart-like, white, irregular mucosa in both cases. The diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy. This cancer type has a relatively good prognosis when the diagnosis is finally obtained. Both our patients presented with dysphagia, weight loss, and an endoscopically malignant tumor, but surgery was not performed until after 9 and 10 months, respectively, and then in order to get a diagnosis. At the last follow-up, both patients were without any recurrence of the disease.
Microvascular blood flow is essential for healing and predicts surgical outcome. The aim of the current study was to investigate the relation between fluxes measured with the laser speckle contrast ...imaging (LSCI) technique and changes in absolute blood flow. In addition, we studied the reproducibility of the LSCI technique when assessing the intra-abdominal microcirculation of the pig.
During trial 1, a fish gill arch was mechanically perfused with heparinized fish blood under controlled stepwise-altered flow rates alongside mechanically induced movement artefacts. The microcirculation of the fish gill was simultaneously assessed with the LSCI technique. In trial 2, microcirculation was measured in the stomach, liver, and small intestine of 10 pigs by two observers.
A linear correlation was observed between flux and volumetric flow. During conditions of no volumetric flow, the high recording speed with the LSCI technique registered the movement artefacts as flow signals. The LSCI measurements showed good correlation and agreement between the two observers when assessing microcirculation in the stomach, liver, and small intestine (r2 = 0.857, 0.956, and 0.946; coefficients of variation = 6.0, 3.2, and 6.4%, respectively).
Due to the non-contact and real-time assessment over large areas, LSCI is a promising technique for the intraoperative assessment of intra-abdominal microcirculation. A linear correlation between flux and volumetric flow was found, in accordance with previous experimental studies. However, movement artefacts affect flux measurements, and the choice of the sampling speed must be made with care, depending on the given setting.
In this case report two patients, having severe intra-abdominal injuries after cardiopulmonary resuscitation (CPR) with the LUCAS system, are presented. They both underwent surgical intervention. ...Severe intra-abdominal injuries following manual CPR are rare, but little is known about the incidence of these injuries associated with mechanical CPR. We have reviewed the literature on clinical outcome and adverse events after out-of-hospital cardiac arrest with LUCAS CPR and manual CPR, and our conclusion is, that more research is needed to establish the safety of mechanical chest compression systems.
Single-operator cholangioscopy (SOC) is increasingly used for evaluation of the biliary tree following endoscopic retrograde cholangiopancreaticography (ERCP). This study aimed to determine the ...visual and histological success rates of SOC at a single Danish tertiary referral centre.
All patients undergoing SOC between 2008 and 2015 were retrospectively included from a prospectively maintained database. Patient characteristics and proced-ure-related variables were obtained from medical records. A visual and a histological success rate were determined according to predefined criteria.
In total, 54 patients underwent SOC, most often due to suspicion of malignancy (n = 53; 98%). In one case, access to the common bile duct failed, and in six cases malignant disease was missed. Thus, the cholangioscopies were successful in 47 of 54 procedures corresponding to a visual success rate of 87%. Nine patients (17%) had a mean of 1.3 ± 1.0 SOC-guided biopsies taken. The extracted tissue was inadequate for histological evaluation in seven of nine cases, corres-pond-ing to a histological success rate of 22% (two out of nine tissue samples were eligible for histological diagnosis).
Considering the reasonable visual success rate, SOC seems to be a useful extension of ERCP during diagnostic work-up for detection of malignant disease in the biliary tree. However, one biopsy per patient is insufficient for histological verification of common bile duct malignancy.
The Danish Health Authority (3-3013-1299/1) and The Danish Data Protection Agency (RH-2015-229).
none.
Esophageal and gastric lesions are effectively managed with minimally invasive upper endoscopic procedures such as endoscopic mucosa resection (EMR) and endoscopic submucosal dissection (ESD), ...offering patients alternatives to invasive interventions. While ESD is well established in Eastern Asia, its adoption in Denmark for superficial esophageal cancer is recent. This study presents real-world data on the feasibility, safety, and hospitalization duration associated with ESD and EMR for esophageal and gastric lesions.
A retrospective analysis was conducted on patients who underwent ESD or EMR at a specialized center in Denmark from October 2016 to June 2022. Data on treatment, indication, lesion location, hospitalization duration, procedure duration, specimen size, complications, recurrence, and one-year overall survival were collected. Statistical comparisons utilized the Mann–Whitney U test, independent sample median test, and chi-squared test.
The study included 130 patients (144 procedures): 72 underwent ESD and 58 underwent EMR. Compared with EMR, ESD resulted in greater percentages of en bloc and R0 resections (98.8% vs. 64.1%, p < 0.001; and 83.9% vs. 23.8%, p < 0.001), greater complication rates (28.7% vs. 3.1%, p < 0.001) and longer procedure times (119.5 min vs. 37.0 min, p < 0.001). The ESD procedure time significantly decreased over time (p = 0.01). The local recurrence rates were 14.5% for ESD and 23.8% for EMR (p = 0.767). The one-year overall survival rates were similar between the groups (95.8% vs. 94.8%, p = 0.553).
Both ESD and EMR are safe and viable for treating esophageal and gastric lesions. ESD offers advantages but requires more time and skill. These findings support the literature, emphasizing the importance of considering patient-specific factors and surgeon proficiency in selecting the appropriate procedure.
A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI
)-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.
Randomized, blinded controlled trial.
Single-center university hospital.
Fifty patients undergoing open esophagectomy.
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-PGF
, a stable metabolite of PGI
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.
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-PGF
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).
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.
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