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This study analyses the effects of vagotomy on tumor growth and survival in a murine, pancreatic cancer model in wild-type and TNFα-knockout (−/−) mice.Throughout many operative procedures in the upper gastrointestinal tract the partial or complete transection of the vagus nerve or its local nerve fibers is unavoidable. Thereby its anti-inflammatory effects in residual tumor tissue may get lost. This effect may be mediated by tumor-associated macrophages (TAM) secreting TNFα.In an orthotopic murine pancreatic cancer model subdiaphragmatic vagotomy versus sham surgery was performed. The impact on tumor growth was monitored in wild type and TNFα −/− mice using MRI. TAMs as well as expression levels of TNFα were analyzed using immunohistochemistry. The role of TNFα on tumor growth and migration was examined in vitro. Vagotomised mice showed increased tumor growth with macroscopic features of invasive growth and had a shorter survival time. The loss of vagal modulation led to significantly increased TNFα levels in tumors and considerably elevated numbers of TAMs. In vitro TNFα significantly stimulated growth (p < 0.05) and migration (p < 0.05) of pancreatic cancer cells. TNFα −/− mice survived significantly longer after tumor implantation (p < 0.05), with vagotomy not affecting the prognosis of these animals (p > 0.05).Vagotomy can increase tumor growth and worsen survival in a murine pancreatic cancer model mediated through TAMs and TNFα. Hence, the suppression of TAMs and the modulation of TNFα dependent pathways could offer new perspectives in immunotherapies of pancreatic cancer patients especially with remaining vital tumor cells and lost vagal modulation.

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Pancreatic cancer is known for its tumor microenvironment (TME), which is rich in stromal and immune cells supporting cancer growth and therapy resistance. In particular, tumor-associated macrophages (TAMs) are known for their angiogenesis- and metastasis-promoting properties, which lead to the failure of conventional therapies for pancreatic cancer. Hence, treatment options targeting TAMs are needed. The C-C chemokine receptor type 4 (CCR4) is critical for immune cell recruitment into the TME, and in this paper we explore the effects of its genetic or immunotherapeutic blockade in pancreatic-cancer-bearing mice. Murine PDA6606 pancreatic cancer cells and murine peritoneal macrophages were used for in vitro migration assays. In vivo, a syngeneic, orthotropic pancreatic cancer model was established. Tumor growth and survival were monitored under prophylactic and therapeutic application of a CCR4 antagonist (AF-399/420/18025) in wildtype (CCR4wt) and CCR4-knockout (CCR4−/−) mice. Immune infiltration was monitored in tumor tissue sections and via flow cytometry of lysed tumors. PDA6606 cells induced less migration in CCR4−/− than in CCR4wt macrophages in vitro. Pancreatic TAM infiltration was higher, and survival was reduced in CCR4wt mice compared to CCR4−/− mice. Antagonizing CCR4 in wildtype mice revealed similar results as in CCR4−/− mice without antagonization. Prophylactic CCR4 antagonist application in wildtype mice was more efficient than therapeutic antagonization. CCR4 seems to be critically involved in TAM generation and tumor progression in pancreatic cancer. CCR4 blockade may help prolong the relapse-free period after curative surgery in pancreatic cancer and improve prognosis.

Background: Both laryngeal mask airway I-gel and Supreme have been available for clinical use, but there was no comparison between two devices. This study was designed to compare the efficacy and complications of the laryngeal mask airway I-gel and Supreme in children undergoing general anesthesia for lower abdominal surgery. Methods: One hundred and twenty children were randomly assigned to either the I-gel or the Supreme group (60 children in each group). All patients of the two groups received the same protocol of general anesthesia. Evaluation criteria included successful mask insertion rate, ease of insertion, insertion time, and number of adjustments needed during anesthesia maintenace and postoperative complications. Results: There were no differences in the demographic data between the two groups. The success rate of insertion in the first attempt of the I-gel group was 94.8% and the Supreme group (98.3%) (p>0.05). According to ease of placement, grade 1 (very easy) ratios of Supreme, and I-gel were 40% and 3.3%, respectively (p<0.01). The insertion time of the I-gel was longer than that of Supreme (p < 0.05). The rate of airway manipulations during anesthesia maintenance of Supreme, and I-gel group were 5% and 11.7%, respectively (p > 0.05). The most common complication was cough, with the rate of 17% in I-gel group and 5% in Supreme group (p<0.05). There were no differences in other complications between both groups. Conclusions: Both I-gel and Supreme provided a satisfactory airway during general anesthesia in children. Insertion of Supreme was significantly easier and more rapid than insertion of I-gel, and the incidence of cough after surgery was significantly lower with Supreme than I-gel. Key words: Laryngeal mask airway, I-gel, Supreme, children