Direct Cytotoxic and Indirect, Immune-Mediated Effects of Local Anesthetics Against Cancer

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.

Precise Anti-Tumor Effect of a Metallopolysaccharide-Based Nanotheranostic: Turning Phototherapy into Programmed Chemotherapy

Phototheranostic, a regional-focused treatment, can endow cancer theranostic with low damage due to its spatial precision. However, precise elimination of residual cancer cells in laser-focused field and in non-laser-focused field...

Clinical significance of additional gastrectomy after non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective single-center study

Purpose: Additional surgery is recommended for patients after a non-curative endoscopic submucosal dissection (ESD) to prevent residual cancer (RC) or lymph node metastasis (LNM). We aimed to evaluate the clinicopathologic characteristics of patients who underwent an additional gastrectomy after a non-curative ESD procedure and identify the risk factors of RC and LNM.Methods: We retrospectively assessed the clinicopathological factors of 73 patients who underwent additional gastrectomy following a non-curative ESD between January 2009 and December 2019 at our center.Results: RC and LNM rates after additional gastrectomy were 9.6% and 8.2%, respectively. Invasion deeper than 500 μm (P = 0.045), positive horizontal resection margin (P < 0.001), and positive ESD margin (P = 0.001) were identified as statistically significant factors in univariate analysis for RC, but not in multivariate analysis. Lymphatic invasion was the only risk factor found to be significant in both univariate and multivariate analyses (P = 0.005 and P = 0.012).Conclusion: Additional gastrectomy is necessary to prevent RC or LNM after non-curative ESD. Lymphatic invasion was also associated with LNM in patients who underwent an additional gastrectomy after a non-curative ESD, and in such cases, active treatment is required.

Successful treatment of bepridil-induced intraoperative torsades de pointes by isoproterenol infusion

Background Several types of antiarrhythmic drugs are known to induce QT prolongation and torsades de pointes. Case presentation An 84-year-old man was scheduled for open gastrectomy for residual cancer. He had been prescribed bepridil for atrial fibrillation that converted to sinus rhythm with prolonged QT interval in the operating room. After the surgery was initiated under general and epidural anesthesia, the patient’s heart rate decreased to 50/min and multifocal premature ventricular contractions appeared, followed by several episodes of torsades de pointes, each lasting for 5 to 15 s. Infusion of isoproterenol was started (0.01 μg/kg/min), and the heart rate was maintained at around 80/min. Premature ventricular contractions disappeared, and torsades de pointes did not recur during the surgery. The operation was completed uneventfully. The serum bepridil concentration was found to be extremely high postoperatively. Conclusions Bepridil-induced intraoperative episodes of torsades de pointes were successfully treated by increasing the heart rate with isoproterenol.

Personalized analysis of minimal residual cancer cells in peritoneal lavage fluid predicts peritoneal dissemination of gastric cancer

Peritoneal dissemination (PD) is a major type of gastric cancer (GC) recurrence and leads to rapid death. Current approaches cannot precisely determine which patients are at high risk of PD to provide early intervention. In this study, we developed a technology to detect minimal residual cancer cells in peritoneal lavage fluid (PLF) samples with a personalized assay profiling tumor-specific mutations. In a prospective cohort of 104 GC patients, the technology detected all the cases that developed PD with 100% sensitivity and 85% specificity. The minimal residual cancer cells in PLF were associated with a significantly increased risk of PD (HR = 145.13; 95% CI 20.20–18,435.79; p < 0.001), which was the strongest independent predictor over pathologic diagnosis and cytological diagnosis. In pathologically high-risk (pT4) patients, the PLF mutation profiling model exhibited a greater specificity of 91% and a positive predictive value of 88% while retaining a sensitivity of 100%. This approach may help in the postsurgical management of GC patients by detecting PD far before metastatic lesions grow to a significant size detectable by conventional methods such as MRI and CT scanning.

Validation of the Residual Cancer Burden Index as a prognostic tool in women with locally advanced breast cancer treated with neoadjuvant chemotherapy

AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of São Paulo.MethodsWe analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors.Results347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showed a statistically significant better prognosis for the RCB 0 (pCR) subgroup compared with RCB 1, 2 and 3 (log rank p=0.01). In a multivariate analysis, only the RCB classification showed a statistically significant correlation with DFS (RCB 1, HR 6.9, CI 1.9 to 25.4, p=0.004; RCB 2, HR 4.2, CI 1.6 to 10.8, p=0.03; and RCB 3, HR 7.6, CI 2.76 to 20.8, p=0.00).ConclusionWe demonstrated a positive and significant relationship between the RCB index and the risk of relapse and death.

Extending treatment criteria for Barrett’s neoplasia: results of a nationwide cohort of 138 ESDs

Objective The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett’s esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed inNL. Design We retrospectively assessed ESD outcomes in NL, where treatment for BE neoplasia is centralized in 9 expert centers with jointly trained endoscopists and pathologists, and treatment/follow-up data collected in a joint database. ESD is restricted for selected cases. Results During median 121 minutes (p25-p75 90-180), 130 complete ESDs were performed with 97% (126/130) removed en-bloc. Pathology was HGD (5%), T1a-EAC (43%) or T1b-EAC (52%; 19%sm1, 33%≥sm2). The combined en-bloc and R0 rate was 87% [95%-CI 77-94%] for HGD/T1a-EAC and 49% [37-62%] for T1b-EAC. Upon R1 resection, 29% had residual cancer, in all cases detected at first follow-up endoscopy, while the remaining 71% had no residual cancer in esophagectomy specimen (n=6) or during median 9 months endoscopic FU (p25-p75 4-22) (n=18). Upon R0 resection, local recurrence rate during median 17 months (8-30) was 0% [0-5%]. Adverse events: 1% perforation [0-4%], 3% post-procedural bleeding [1-7%], 13% strictures [8-20%]. Conclusion In expert hands, ESD is safe and allows for removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter is, however, associated with a positive deep resection margin in half of the patients, yet only one third had actual persisting neoplasia at endoscopic FU. To better stratify R1-patients with an indication for additional surgery, repeat endoscopy after healing of the ESD wound may help in predicting residual cancer.