Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

Primary pneumococcal peritonitis with a fulminant course.

INTRODUCTION: Primary peritonitis is an inflammation of the peritoneal cavity in the absence of a localized intra-abdominal source. It is included in the differential diagnosis of acute abdomen and can be potentially life-threatening. Pneumococci were a frequent pathogen causing primary peritonitis especially in the preantibiotic era. Nowadays, they act as an uncommon primary pathogen. Pneumococcal peritonitis in adults is more frequently seen in cases of liver cirrhosis with ascites and other pre-existing conditions. Primary pneumococcal peritonitis is uncommon in healthy individuals and therefore its diagnosis is difficult. Secondary peritonitis has to be excluded. CASE REPORT: A 36-year-old woman was admitted to our surgery department with symptoms of severe sepsis. She reported a sudden onset of diffuse abdominal pain and was eight weeks after delivery per vias naturales. A computed tomography scan of the abdomen with intravenous contrast has not demonstrated any pathology explaining the condition of our patient. Empiric anti-microbial therapy with broad-spectrum antibiotics was commenced and a laparotomy was performed, which also did not reveal any source of infection. Purulent odorless fluid was found in the peritoneal cavity. Peritoneal lavage with an antiseptic was performed. Cultures from peritoneal fluid demonstrated a monobacterial growth of Streptococcus pneumoniae. The condition of our patient improved after continued adequate antibiotic therapy and lavage. CONCLUSION: Primary pneumococcal peritonitis is difficult to diagnose in healthy individuals, since it is mimicking secondary peritonitis that has to be excluded. A clinical diagnose without surgical intervention is impossible in most cases. Surgical treatment has an important role in both the diagnosis and management of primary pneumococcal peritonitis, same as adequate antibiotic therapy. Primary peritonitis should be a part of the differential diagnosis of patients presenting with acute abdominal pain.

Clinical and prognostic significance of detecting CEA, EGFR, LunX, c-met and EpCAM mRNA-positive cells in the peripheral blood, tumor-draining blood and bone marrow of non-small cell lung cancer patients.

Background: Surgical treatment of early-stage non-small cell lung cancer (NSCLC) yields highest expectations for recovery. However, the frequency of further disease progression remains high since micro-metastatic disease may be undetected by conventional diagnostic methods. We test the presence and prognostic impact of circulating tumor cells (CTCs) in peripheral blood (PB), tumor-draining pulmonary blood (TDB) and bone marrow (BM) samples from NSCLC patients. Methods: The presence of circulating/disseminated tumor cells (CTCs/DTCs) was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis in PB, TDB and BM samples before surgery in 119 stage IA-IIIA NSCLC patients (Clinical Trial NS10285). Results: NSCLC patients with the presence of carcinoembryonic antigen (CEA) mRNA-positive CTCs/DTCs in TDB and BM had significantly shorter cancer-specific survival (CSS) (P<0.013, resp. P<0.038). Patients with the presence of epithelial cellular adhesion molecule (EpCAM) mRNA-positive CTCs in TDB samples had significantly shorter CSS and disease-free survival (DFS) (P<0.031, resp. P<0.045). A multivariate analysis identified the presence of CEA mRNA-positive CTCs in the PB as an independent negative prognostic factor for DFS (P<0.005). No significant correlation of CTCs/DTCs presence and other prognostic factors was found. Conclusions: In NSCLC patients undergoing radical surgery, the presence of CEA and EpCAM mRNA-positive CTCs/DTCs is associated with poorer survival.