Oligometastatic disease and visceral resections in advanced malignant melanoma: a propensity-matched analysis.

PURPOSE: Malignant melanoma is among the tumours with the highest increase in incidence of solid tumours in Germany. While most patients are diagnosed at an early stage and show a good prognosis, advanced stages of malignant melanoma are accompanied with a poor prognosis and limited treatment options. Comparable to other tumour entities, the resection of visceral metastases could lead to a better prognosis. Supplementary, the subgroup of oligometastatic patients might benefit from surgical therapy to a greater extent. METHODS: This retrospective study analysed 351 patients treated between 2006 and 2017 at the University Hospital of Cologne. A total of 121 patients showed visceral metastases, with which we compared patients with a diffuse tumour spread to patients in an oligometastatic state. Furthermore, we evaluated the effect of visceral resection of oligometastatic, malignant melanoma. RESULTS: Our analysis showed that patients with an oligometastatic malignant melanoma had a significantly better prognosis than patients with a diffuse pattern of metastases, if they showed visceral metastases. Furthermore, the resection of visceral metastases leads to a significant gain in median overall survival time (13.6 vs. 34.2 months) and in progression-free survival (9.6 vs. 3.8 months). CONCLUSION: The resection of visceral metastases is a rational treatment option in advanced malignant melanoma. Although our study is limited by a small cohort of patients (n = 18), we believe that the resection of visceral metastases will be fundamental in the treatment of malignant melanoma. In particular, patients in an oligometastatic stage could be an eligible group for surgical treatment.

[New techniques and training methods for robot-assisted surgery and cost-benefit analysis of Ivor Lewis esophagectomy]. / Neue Techniken und Trainingsmethoden für die roboterassistierte Chirurgie und Kosten-Nutzen-Bewertung anhand der Ivor-Lewis-Ösophagektomie.

INTRODUCTION: Robotic surgery was introduced into general surgery more than 20 years ago. Shortly afterwards, Horgan performed the first robotic-assisted esophagectomy in 2003 in Chicago. The aim of this manuscript is to elucidate new developments and training methods in robotic surgery with a cost-benefit analysis for robotic-assisted Ivor Lewis esophagectomy. METHODS: Systematic literature search regarding new technology and training methods for robotic surgery and cost analysis of intraoperative materials for hybrid and robotic-assisted Ivor Lewis esophagectomy. RESULTS: Robotic-assisted esophageal surgery is complex and involves an extensive learning curve, which can be shortened with modern teaching methods. New robotic systems aim at the use of image-guided surgery and artificial intelligence. Robotic-assisted surgery of esophageal cancer is significantly more expensive that surgery without this technology. CONCLUSION: Oncological short-term and long-term benefits need to be further evaluated to support the higher cost of robotic esophageal cancer surgery.

The economic burden of endoscopic treatment for anastomotic leaks following oncological Ivor Lewis esophagectomy.

BACKGROUND: Complications after surgery for esophageal cancer are associated with significant resource utilization. The aim of this study was to analyze the economic burden of two frequently used endoscopic treatments for anastomotic leak management after esophageal surgery: Treatment with a Self-expanding Metal Stent (SEMS) and Endoscopic Vacuum Therapy (EVT). MATERIALS AND METHODS: Between January 2012 and December 2016, we identified 60 German-Diagnosis Related Group (G-DRG) cases of patients who received a SEMS and / or EVT for esophageal anastomotic leaks. Direct costs per case were analyzed according to the Institute for Remuneration System in Hospitals (InEK) cost-accounting approach by comparing DRG payments on the case level, including all extra fees per DRG catalogue. RESULTS: In total, 60 DRG cases were identified. Of these, 15 patients were excluded because they received a combination of SEMS and EVT. Another 6 cases could not be included due to incomplete DRG data. Finally, N = 39 DRG cases were analyzed from a profit-center perspective. A further analysis of the most frequent DRG code -G03- including InEK cost accounting, revealed almost twice the deficit for the EVT group (N = 13 cases, € - 9.282 per average case) compared to that for the SEMS group (N = 9 cases, € - 5.156 per average case). CONCLUSION: Endoscopic treatments with SEMS and EVT for anastomotic leaks following oncological Ivor Lewis esophagectomies are not cost-efficient for German hospitals. Due to longer hospitalization and insufficient reimbursements, EVT is twice as costly as SEMS treatment. An adequate DRG cost compensation is needed for SEMS and EVT.

Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival.

BACKGROUND: Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown. METHODS: In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters. RESULTS: Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis. CONCLUSIONS: All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma.

Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted next-generation sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumor-draining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.

Validation of 2-mm tissue microarray technology in gastric cancer. Agreement of 2-mm TMAs and full sections for Glut-1 and Hif-1 alpha.

BACKGROUND/AIM: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue. MATERIALS AND METHODS: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment. RESULTS: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides. CONCLUSION: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.

Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats.

Mesenchymal stem cell (MSC) therapy is a promising approach for regaining muscle function after trauma. Prior to clinical application, the ideal time of transplantation has to be determined. We investigated the effects of immediate and delayed transplantation. Sprague-Dawley rats received a crush trauma to the left soleus muscle. Treatment groups were transplanted locally with 2 × 10(6) autologous MSCs, either immediately or 7 days after trauma. Saline was used as sham therapy. Contraction force tests and histological analyses were performed 4 weeks after injury. GFP-labelled MSCs were followed after transplantation. The traumatized soleus muscles of the sham group displayed a reduction of twitch forces to 36 ± 17% and of tetanic forces to 29 ± 11% of the non-injured right control side, respectively. Delayed MSC transplantation resulted in a significant improvement of contraction maxima in both stimulation modes (twitch, p = 0.011; tetany, p = 0.014). Immediate transplantation showed a significant increase in twitch forces to 59 ± 17% (p = 0.043). There was no significant difference in contraction forces between muscles treated by immediate and delayed cell transplantation. We were able to identify MSCs in the interstitium of the injured muscles up to 4 weeks after transplantation. Despite the fundamental differences of the local environment, which MSCs encounter after transplantation, similar results could be obtained with respect to functional muscle regeneration. We believe that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways. Our data suggest a large time window of the therapeutical measures.