Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery.

BACKGROUND: Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques. METHODS: Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure. RESULTS: 35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively. CONCLUSION: EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.

Impact of Endoscopic Vacuum Therapy with Low Negative Pressure for Esophageal Perforations and Postoperative Anastomotic Esophageal Leaks.

INTRODUCTION: Management of esophageal anastomotic leaks (AL) and esophageal perforations (EP) remains difficult and often requires an interdisciplinary treatment modality. For primary endoscopic management, self-expanding metallic stent (SEMS) placement is often considered first-line therapy. Recently, endoscopic vacuum therapy (EVT) has emerged as an alternative or adjunct for management of these conditions. So far, data for EVT in the upper gastrointestinal-tract is restricted to single centre, non-randomized trials. No studies on optimal negative pressure application during EVT exist. The aim of our study is to describe our centre's experience with low negative pressure (LNP) EVT for these indications over the past 5-years. PATIENTS AND METHODS: Between January 2014 and December 2018, 30 patients were endoscopically treated for AL (n = 23) or EP (n = 7). All patients were primarily treated with EVT and LNP between -20 and -50 mm Hg. Additional endoscopic treatment was added when EVT failed. Procedural and peri-procedural data, as well as clinical outcomes including morbidity and mortality, were analysed. RESULTS: Clinical successful endoscopic treatment of EP and AL was achieved in 83.3% (n = 25/30), with 73.3% success using EVT alone (n = 22/30). Mean treatment duration until leak closure was 16.1 days (range 2-58 days). Additional treatment modalities for complete leak resolution was necessary in 10% (n = 3/30), including SEMS placement and fibrin glue injection. Mean hospital stay for patients with EP was shorter with 33.7 days compared to AL with 54.4 days (p = 0.08). Estimated preoperative 10-year overall survival (Charlson comorbidity score) was 39.4% in patients with AL and 59.9% in patients with EP (p = 0.26). A mean of 5.1 EVT changes (range 1-12) was needed in EP and 3.6 changes (range 1-13) in AL to achieve complete closure, switch to other treatment modality, or reach endoscopic failure (p = 0.38). CONCLUSION: LNP EVT enables effective minimally - invasive endoluminal leak closure from anastomotic esophageal leaks and EP in high-morbid patients. In this study, EVT was combined with other endoscopic treatment options such as SEMS placement or fibrin glue injection in order to achieve leak or perforation closure in the vast majority of patients (83.3%). Low aspiration pressures led to slower but still sufficient clinical results.

Neoadjuvant Therapy in Rectal Cancer - Biobanking of Preoperative Tumor Biopsies.

Translational research relies on high-quality biospecimens. In patients with rectal cancer treated preoperatively with radiochemotherapy tissue based analyses are challenging. To assess quality challenges we analyzed tissue samples taken over the last years in a multicenter setting. We retrospectively evaluated overall 197 patients of the CAO/ARO/AIO-94- and 04-trial with locally advanced rectal cancer that were biopsied preoperatively at the University Medical Center Goettingen as well as in 10 cooperating hospitals in Germany. The cellular content of tumor, mucosa, stroma, necrosis and the amount of isolated DNA and RNA as well as the RNA integrity number (RIN) as quality parameters were evaluated. A high RNA yield (p = 2.75e-07) and the content of tumor (p = 0.004) is significantly associated to high RIN-values, whereas a high content of mucosa (p = 0.07) shows a trend and a high amount of necrosis (p = 0.01) is significantly associated with RNA of poor quality. Correlating biopsies from Goettingen and the cooperating centers showed comparable tumor content results. By taking small sized biopsies we could assess a clear correlation between a good RNA quality and a high amount of RNA and tumor cells. These results also indicate that specimens collected at different centers are of comparable quality.

CpG island methylator phenotype infers a poor disease-free survival in locally advanced rectal cancer.

BACKGROUND: Locally advanced rectal cancers are treated with preoperative radiochemotherapy (RCT). However, subsets of patients have no benefit from preoperative treatment. Since epigenetic modifications, including DNA methylation, may influence response to neoadjuvant treatment we studied the CpG island methylator phenotype (CIMP) in patients who received a 5-fluouracil based RCT. METHODS: One hundred fifty patients with locally advanced rectal cancer, treated within a phase III clinical trial (CAO/ARO/AIO-94 and -04), were included in this analysis. CIMP was assessed by methylation specific PCR (MSP) using RUNX3, SOCS1, NEUROG1, IGF2, and CACNA1G as a marker panel. Loss of mismatch repair gene (MMR) expression was assessed by immunohistochemistry for a subset of patients. KRAS and BRAF mutation status were assessed using Sanger sequencing. RESULTS: The CIMP status could be established in all 150 patients. Fifteen (10%) revealed CIMP positivity (≥3 methylated promoters), whereas 135 patients (90%) where classified as CIMP negative. Analysis for MMR status did not reveal any microsatellite instability (MSI). A single mutation of the BRAF gene (D594G) was detected. The KRAS gene (exon 1, 2, and 3) was mutated in 65 tumors (43%) but was not correlated to a specific CIMP status. Three- and 5-year disease-free survival was notably worse in CIMP positive patients (56% and 0% vs 80% and 75%; P < .01) suggesting an increased likelihood of poor clinical outcome (HR 5.5; 95%CI: [2.1, 13.9]). CONCLUSION: CIMP positivity, defined by methylation of at least 3 specific gene promoters, is an infrequent event in locally advanced rectal cancer. However, it increases the likelihood of distant metastases. Therefore, the CIMP status may be included as a molecular marker for the identification of high-risk patients and might contribute to individual treatment stratification.