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.

New technology for data-driven improvement of effectiveness, quality, and safety in the operating room.

With a synchronised data capture and analysis platform, comprehensive data can be collected from the operating room (OR), like in most high-risk industries. This review summarises the various benefits from capturing data from every procedure in the OR. From every surgery there are millions of data which, when synchronised and analysed, can help us to identify, understand and mitigate safety threats. Data can be used to increase efficiency, to identify and predict adverse events, and to increase the quality of teaching in the OR. The rapid advances in modern technology and the introduction of high-reliability culture in healthcare will result in more data-driven, precise, and safer surgical care.

Calcium electroporation of esophageal cancer induces gene expression changes: a sub-study of a phase I clinical trial.

PURPOSE: In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment. METHODS: In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples. RESULTS: Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased. CONCLUSION: This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.

Palliative Treatment of Esophageal Cancer Using Calcium Electroporation.

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.

Palliation of dysphagia in patients with non-curable esophageal cancer - a retrospective Danish study from a highly specialized center.

PURPOSE: A majority of the patients with esophageal cancer (EC) suffer from dysphagia. Several endoscopic treatment options are available such as stent placement, argon plasma coagulation, and esophageal dilatation. This study aimed to map the use of endoscopic dysphagia relieving interventions and secondly investigate possible impact on survival. METHODS: Data was collected at the Dept. of Surgery & Transplantation, Rigshospitalet, Denmark. Patients with non-curable EC referred from 2016 to 2019 were included. Type of dysphagia treatment, complications and the need for repeated treatments, and survival were registered. RESULTS: In the study, 601 patients were included. Forty-five percent were treated with an endoscopic procedure due to dysphagia (82% had a stent placed). The median time from diagnosis to intervention was 24 days. The overall complication rate was 35% (38% in the stent group and 20% in the non-stent group, p = 0.03) and 13% of the patients were readmitted due to a complication. After 26% of the procedures, a repeated treatment was required. Patients having an endoscopic intervention had a worsened survival prognosis compared with the patients in the non-intervention group (HR: 2.17, 95% CI: 1.80-2.61, p < 0.001). In the sub analysis where only patients who had an intervention was included, a survival difference in favor of the non-stent group was found (HR: 0.61, 95% CI: 0.43-0.86, p = 0.005). CONCLUSION: In this cohort, the incidence of endoscopic procedures was high, complication rates were considerable, and many the patients required a second treatment. A survival difference was seen, where the patients who had a stent placed seemed to have the worst survival outcomes. However, the causal relationship is yet to be determined why the results must be interpreted carefully. New interventions and tailored approaches that may positively affect functional and long-term oncological outcomes are highly warranted and this should preferably be investigated in randomized clinical trials.

Morbidity and mortality after liver surgery for colorectal liver metastases: a cohort study in a high-volume fast-track programme.

BACKGROUND: For colorectal liver metastases, surgery is a high-risk procedure due to perioperative morbidity. The objective was to assess severity of complications after fast-track liver surgery for colorectal liver metastases and their impact on morbidity and mortality. METHODS: All patients were treated according to the same fast-track programme. Complications were graded according to the Clavien-Dindo classification for patients undergoing surgery from 2013 to 2015. Correlation between complications and length of stay was analysed by multivariate linear regression. RESULTS: 564 patient cases were included of which three patients died within 3 months (0.53%, 95% CI: 0.17-1.64%). Complications were common with Grade ≤ 2 in 167 patients (30%) and ≥ Grade 3a in 93 (16%). Patients without complications had a mean length of stay of 4.1 days, which increased with complications: 1.4 days (95% CI: 1.3-1.5) for Grade 2, 1.7 days (1.5-2.0) for Grade 3a, 2.3 days (1.7-3.0) for Grade 3b, 2.6 days (1.6-4.2) for Grade 4a, and 2.9 days (2.8-3.1) for Grade 4b. Following were associated with increased length of stay: complication severity grade, liver insufficiency, ascites, biliary, cardiopulmonary, and infectious complications. CONCLUSIONS: Complications after liver surgery for colorectal liver metastases, in a fast track setting, were associated with low mortality, and even severe complications only prolonged length of stay to a minor degree.

Exercise-mediated improvement of depression in patients with gastro-esophageal junction cancer is linked to kynurenine metabolism.

Background: Exercise may improve depression in cancer patients, yet the molecular mechanism behind this protection is poorly understood. Here, we aimed to explore the link between exercise and regulation of kynurenine (Kyn) metabolism and inflammation in patients with operable gastro-esophageal junction (GEJ) cancer patients, who improved significantly in depression score with exercise training. Material and Methods: Fifty GEJ cancer patients were allocated to 12 weeks of supervised training twice weekly including interval-based aerobic exercise and resistance training, or standard care. Depression score was evaluated by HADS, and blood samples and muscle biopsies were collected for determination of Kyn metabolism and inflammation across the intervention. Results: Depression scores decreased by -1.3 points in the exercise group (p < 0.01), whereas no changes were observed in the control group. Plasma 3-hydroxykynurenine (HK), a Kyn metabolite giving rise to other neurotoxic metabolites, increased by 48% (p <0.001) in the control group, while exercise training attenuated this accumulation. The production of HK is induced by inflammation, and while we observed no differences in systemic pro-inflammatory cytokines, exercise training ameliorated the treatment-induced intramuscular inflammation. Moreover, exercise has been suggested to convert Kyn to the neuroprotective metabolite, kynurenic acid (KA), but despite marked functional and muscular exercise-mediated adaptations, we did not observe any enhancement of KA production and related enzyme expression in the muscles of GEJ cancer patients. Conclusion: Exercise training reduced symptoms of depression in patients with GEJ cancer, and this effect was associated with an exercise-dependent attenuation of the inflammation-induced conversion of Kyn to neurotoxic metabolites.

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.

Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study.

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.

Verrucous Squamous Cell Cancer in the Esophagus: An Obscure Diagnosis.

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.