Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study.

Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.

miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression.

BACKGROUND: The ability to metastasize is one of the most important characteristics of neoplastic cells. An imbalance between the action of some matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs drives the invasion process. Some studies have suggested that MMP-2 is involved in metastasis, while other studies have reported that collagen production by cancer cells might also contribute to motility. However, decreased expression of microRNA-29b (miR-29b), which may control MMP-2 and collagen gene expression, has been shown in prostate cancer (PCa). The objectives of the present study were to clarify whether MMP-2 as well as collagens I and III (encoded by COL1A1 and COL3A1, respectively) are controlled by miR-29b and to determine whether metastasis is altered by this relationship. METHODS: PCa DU145 and PC-3 cells were transfected with 100 µL of OPTI-MEM I containing 100 nmol of miR-29b (or its inhibitor) along with 1.5 µL of lipofectamine. Positive and negative controls were prepared using the same protocol. MMP-2, COL1A1 and COL3A1 messenger RNA (mRNA) levels were evaluated via real-time polymerase chain reaction (qRT-PCR). For qRT-PCR, 6 × 104 cells were used. Invasion studies were conducted with Matrigel assays, which simulate invasion of the extracellular matrix by neoplastic cells. After transfection of 3 × 104 cells, invasion was allowed to proceed for 48 h. Invasive cells were counted under an optical microscope. Each experiment was performed in triplicate. RESULTS: MMP-2 mRNA was not expressed in DU145 cells after transfection with miR-29b. After transfection of cells with the miR-29b inhibitor, COL1A1 (p = 0.02) and COL3A1 (p = 0.06) mRNA expression was increased in DU145 cells, and a large number of transfected DU145 and PC3 cells invaded the Matrigel membrane. CONCLUSIONS: In vitro studies showed that reducing the amount of miR-29b may lead to higher PCa cell invasion via a process that is independent of MMP-2. Collagen expression, controlled by miR-29b, may facilitate this motility process. Thus, the present study suggests that collagen production plays an active role in metastasis control and restoration of miR-29b levels may decrease metastasis. Altogether, these findings support further exploration of drug therapy targeting this aspect of the metastasis circuit.

Comparison of the learning curves and frustration level in performing laparoscopic and robotic training skills by experts and novices.

INTRODUCTION: Robotic assistance may provide for distinct technical advantages over conventional laparoscopic technique. The goals of this study were (1) to objectively evaluate the difference in the learning curves by novice and expert surgeons in performing fundamental laparoscopic skills using conventional laparoscopic surgery (CLS) and robotic-assisted laparoscopic surgery (RALS) and (2) to evaluate the surgeons' frustration level in performing these tasks. METHODS: Twelve experienced and 31 novices in laparoscopy were prospectively evaluated in performing three standardized laparoscopic tasks in five consecutive, weekly training sessions. Analysis of the learning curves was based on the magnitude, rate, and quickness in performance improvement. The participant's frustration and mood were also evaluated during and after every session. RESULTS: For the novice participants, RALS allowed for shorter time to task completion and greater accuracy. However, significant and rapid improvement in performance as measured by magnitude, rate, and quickness at each session was also seen with CLS. For the experienced surgeons, RALS only provided a slight improvement in performance. For all participants, the use of RALS was associated with less number of sessions in which they felt frustrated, less number of frustration episodes during a session, lower frustration score during and after the session, and higher good mood score. CONCLUSION: The advantages of RALS may be of most benefit when doing more complex tasks and by less experienced surgeons. RALS should not be used as a replacement for CLS but rather in specific situations in which it has the greatest advantages.

Validation of the pediatric surgical risk assessment scoring system.

BACKGROUND: Within the adult population, there exist numerous validated risk stratification tools aimed at predicting postoperative outcomes using preoperative and intraoperative parameters. However, similar tools for the pediatric population are scarce. We previously developed and reported on a scoring system to predict postoperative complications in children undergoing surgery at Boston Children's Hospital. The objective of this study was to validate our scoring system to determine its effectiveness in identifying children at risk for major complications or death within 30 days following surgery. STUDY DESIGN: A computer program randomly selected 2015 out of 11,734 patients who underwent surgery at our institution in 2009. The severity of the complications was graded based on the Clavien classification system, with major complications being a grade III or higher. The Preoperative Complication Score (PCS) and the Overall Complication Score (OCS) were calculated for all patients, and Receiver Operating Characteristic (ROC) curves were generated for each scoring system. RESULTS: The overall incidence of major complications was 3.9% (79 patients). Proportionally, cardiac surgery had the highest percentage of major complications (20% of the performed surgeries). Both PCS and OCS demonstrated excellent correlation with postoperative outcomes with c-statistic values of 0.740 (CI 0.682-0.800, p < 0.001) and 0.767 (CI 0.712-0.822, p < 0.001) respectively. CONCLUSIONS: We determined that both the PCS and OCS are effective in identifying children at risk for major complications and death following surgery. Further studies will be needed to determine if these scoring systems are applicable to children undergoing surgery at other institutions and if the use of the scoring systems would result in improved clinical outcomes and reduced costs.