Postoperative Cancer Recurrence Research Articles

AB014. SOH23ABS_149. Exploring neutrophil-lymphocyte ratio as a predictor of postoperative breast cancer recurrence

Background: Neutrophil-lymphocyte ratio (NLR) is an emerging prognostic biomarker with potential utility in solid malignancies. Routine inclusion of the full blood count in preoperative workup and postoperative course positions NLR as a cost-effective adjunct in surveillance. This project explores associations between preoperative NLR and breast cancer recurrence.

Exploring neutrophil-lymphocyte ratio as a predictor of postoperative breast cancer recurrence

Exploring neutrophil-lymphocyte ratio as a predictor of postoperative breast cancer recurrence

Metabolic Syndrome and Clinical Outcomes of Patients with Gastric Cancer: A Meta-Analysis.

Metabolic syndrome (MetS) is suggested to participate in the pathogenesis and progress of some cancers via inducing low-grade systemic inflammation. However, the influence of MetS on patients with gastric cancer (GC) remains not fully determined. A systematic review and meta-analysis was therefore performed to evaluate the influence of MetS on clinical outcomes of patients with GC. A search of PubMed, Embase, Web of Science, Wanfang, and CNKI retrieved relevant cohort studies from the inception of the databases to October 11, 2022. We pooled the results using a random-effects model that incorporates heterogeneity. In the meta-analysis, 6649 patients with GC were included, and all of them received gastrectomy. A total of 1248 (18.8%) patients had MetS at baseline. Pooled results showed that MetS was associated with higher risks of postoperative complications [risk ratio (RR): 2.41, 95% confidence interval (CI): 1.85 to 3.14, p<0.001; I2=55%], overall mortality (RR: 1.73, 95% CI: 1.85 to 3.14, p<0.001; I2=77%), and recurrence of GC (RR: 2.00, 95% CI: 1.10 to 3.63, p=0.02; I2=39%). Subgroup analyses showed similar results in prospective and retrospective cohort studies and in studies with MetS diagnosed with the Chinese Diabetes Society criteria and the National Cholesterol Education Program Adult Treatment Panel III criteria (p for subgroup difference all>0.05). In patients with GC after gastrectomy, MetS may be a predictor of high incidence of postoperative complications, cancer recurrence, and overall mortality.

Do Certain Anaesthetic Drugs Affect Postoperative Cancer Recurrence Rates? Implications for Drug Discovery

Recurrence of cancer after primary tumour resection is a leading cause of cancer-related mortality. Preclinical research indicates that surgery induces a stress response that inhibits cell-mediated immunity as a possible basis for risk of recurrence. Other preclinical evidence suggests that, conversely, propofol and local anaesthetics diminish the effects of the surgical stress response and so could directly inhibit cancer progression, and this is supported by several retrospective cohort studies and meta-analyses. However, the first large-scale randomised clinical trial (RCT), comparing recurrence after mastectomy in patients anaesthetised with either propofol/local anaesthetic or sevoflurane/opioids, concluded that recurrence was not significantly improved in the propofol/local anaesthetic group (p = 0.84). Other cancers may prove more responsive and results from a number of ongoing RCTs, encompassing several cancer types, are currently awaited. These trials should establish whether choice of anaesthetic technique is an important determinant of cancer recurrence risk.

The implication of gut microbiota in recovery from gastrointestinal surgery.

Recovery from gastrointestinal (GI) surgery is often interrupted by the unpredictable occurrence of postoperative complications, including infections, anastomotic leak, GI dysmotility, malabsorption, cancer development, and cancer recurrence, in which the implication of gut microbiota is beginning to emerge. Gut microbiota can be imbalanced before surgery due to the underlying disease and its treatment. The immediate preparations for GI surgery, including fasting, mechanical bowel cleaning, and antibiotic intervention, disrupt gut microbiota. Surgical removal of GI segments also perturbs gut microbiota due to GI tract reconstruction and epithelial barrier destruction. In return, the altered gut microbiota contributes to the occurrence of postoperative complications. Therefore, understanding how to balance the gut microbiota during the perioperative period is important for surgeons. We aim to overview the current knowledge to investigate the role of gut microbiota in recovery from GI surgery, focusing on the crosstalk between gut microbiota and host in the pathogenesis of postoperative complications. A comprehensive understanding of the postoperative response of the GI tract to the altered gut microbiota provides valuable cues for surgeons to preserve the beneficial functions and suppress the adverse effects of gut microbiota, which will help to enhance recovery from GI surgery.

A Local Strategy Toward Concurrent Chemoradiotherapy Based on Fibrin Gel for Postsurgical Cancer Treatment

Postoperative cancer recurrence and metastasis have always been huge challenges in cancer therapy. The concurrent cisplatin (CDDP)-based chemoradiotherapy regimen is a standard therapeutic strategy in some cancer treatments after surgical resection. However, severe side effects and unsatisfactory local tumor concentrations of CDDP have hampered the application of this concurrent chemoradiotherapy. Therefore, a superior option that can enhance CDDP-based chemoradiotherapy efficacy with milder concurrent therapy-related toxicity is highly desirable. We developed a platform based on fibrin gel (Fgel) loaded with CDDP to be implanted into the tumor bed after surgery combined with concurrent radiation therapy for the prevention of postoperative local cancer recurrence and distant metastasis. The postoperative subcutaneous tumor mouse models established by incomplete resection of primary tumors were used to evaluate the therapeutic advantages of this chemoradiotherapy regimen for postsurgical treatment. The local and sustained release of CDDP from Fgel could enhance the antitumor efficacy of radiation therapy in the residual tumor with lower systemic toxicity. The therapeutic benefits of this approach are demonstrated in breast cancer, anaplastic thyroid carcinoma, and osteosarcoma mouse models. Our work offers a general platform for concurrent chemoradiotherapy to prevent postoperative cancer recurrence and metastasis.

Implantable 3D Printed Hydrogel Scaffolds Loading Copper-Doxorubicin Complexes for Postoperative Chemo/Chemodynamic Therapy

Biomaterial-based implants hold great potential for postoperative cancer treatment due to the enhanced drug dosage at the disease site and decreased systemic toxicity. However, the elaborate design of implants to avoid complicated chemical modification and burst release remains challenging. Herein, we report a three-dimensional (3D) printed hydrogel scaffold to enable sustained release of drugs for postoperative synergistic cancer therapy. The hydrogel scaffold is composed of Pluronic F127 and sodium alginate (SA) as well as doxorubicin (DOX) and copper ions (F127-SA/Cu-DOX hydrogel scaffold). Benefiting from the coordination of Cu(II) with both SA and DOX, burst release of DOX can be overcome, and prolonged release time can be achieved. The therapeutic efficiency can be adjusted by altering the amount of DOX and Cu(II) in the scaffolds. Moreover, apoptosis and ferroptosis of cancer cells can be induced through the combination of chemotherapy and chemodynamic therapy. In addition, DOX supplies excess hydrogen peroxide to enhance the efficiency of Cu-based chemodynamic therapy. When implanted in the resection site, hydrogel scaffolds effectively inhibit tumor growth. Overall, this study may offer a new strategy for fabricating local implants with synergistic therapeutic performance for preventing postoperative cancer recurrence.

Dose-response relationship between epidural bupivacaine dose and mortality risk after surgical resection of nonsmall-cell lung cancer.

Preclinical studies have shown that local anesthetics may modify the growth and invasion of cancer cells. However, few clinical studies have evaluated their impact on cancer outcomes after tumor resection. In this single-center cohort study, patients who underwent surgical resection of stage IA through IIIB nonsmall-cell lung cancer and used patient-controlled epidural analgesia from 2005 to 2015 were recruited and followed until May 2017. Data of the epidural bupivacaine dose for each patient were obtained from infusion pump machines. Proportional hazards regression models were used to analyze the associations between bupivacaine dose with postoperative cancer recurrence and all-cause mortality. A total of 464 patients were analyzed. Among these patients, the mean bupivacaine dose was 352 mg (± standard deviation 74 mg). After adjusting for important clinical and pathological covariates, a significant dose-response relationship was observed between epidural bupivacaine dose and all-cause mortality (adjusted hazard ratio: 1.008, 95% confidence interval: 1.001-1.016, p = 0.029). The association between bupivacaine dose and cancer recurrence were not significant (adjusted hazard ratio: 1.000, 95% confidence interval: 0.997-1.002, p = 0.771). Age, sex, body mass index, mean daily maximum pain score, and pathological perineural infiltration were independently associated with bupivacaine dose. A dose-dependent association was found between epidural bupivacaine dose and long-term mortality among patients following surgical resection of nonsmall-cell lung cancer. Our findings do not support the hypothetical anticancer benefits of local anesthetics. More studies are needed to elucidate the role of local anesthetics in cancer treatment.

EP16.02-021 The Expression of CEACAMs and Serum CEA Levels as Biomarkers of Postoperative Cancer Recurrence in Non-small Cell Lung Cancer

The serum carcinoembryonic antigen (CEA) levels have been used as biomarkers and as a diagnostic tool for non-small cell lung cancer (NSCLC). However, no study has been conducted to compare the gene expression of CEA-related cell adhesion molecules (CEACAMs) in surgically resected cancer specimens matching CEA levels.

The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5h or propofol (20μgg-1; ip injection) with or without 4μgg-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

Unified Therapeutic‐Prophylactic Vaccine Demonstrated with a Postoperative Filler Gel to Prevent Tumor Recurrence and Metastasis

AbstractAlthough surgical resection is currently the first choice of clinical treatment for most solid tumors, postoperative cancer recurrence and metastasis are the main causes of mortality. Herein, the authors aim to enable immunotherapy consistent with surgery. To this end, the term “therapeutic‐prophylactic vaccine (TPV)” is suggested, and a TPV‐gel is developed as a filler after resection of ≈90% tumor to eradicate residue tumor (therapeutic) and prevent recurrence and metastasis (prophylactic). The TPV‐gel is made of the matrix of blends of two poly(d,l‐lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(d,l‐lactide‐co‐glycolide) block copolymers and the bioactive substances of inorganic calcium salt and organic R837. The aqueous system of polymeric block blends undergoes a sol‐gel transition upon heating and thus leads to an injectable hydrogel filling the resection site; loading of CaCl2 and CaCO3 results in the release of calcium ions out of the TPV‐gel, which induces immunogenic cell death of the residual tumor cells; R837, an immune adjuvant, is dispersed in the TPV‐gel as microcrystal and can be released to awaken immune responses. The therapeutic and prophylactic efficacy of this TPV‐gel is confirmed in vitro and in vivo using a postoperative breast 4T1 mice model.

The Role of NMP22 and CSTB Levels in Predicting Postoperative Recurrence of Bladder Cancer

Objective To investigate the value of preoperative urinary nuclear matrix protein 22 (NMP22) and Cystatin B (CSTB) expressions in evaluating the postoperative recurrence of bladder cancer. Methods The clinical case data of 102 patients with bladder cancer who underwent surgical treatment from January 2017 to January 2022 were collected, and the patients were divided into a recurrence group (n = 54) and nonrecurrence group (n = 48) according to whether the patients recurred after surgery, and the preoperative NMP22 and CSTB expression levels between the two groups were compared. Receiver operating curve (ROC) was used to analyze the evaluation value of preoperative NMP22 and CSTB expression in patients with bladder cancer postoperative recurrence. Logistic multivariate regression method was used to analyze the correlation between preoperative NMP22 and CSTB expression and postoperative bladder cancer recurrence. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of NMP22 and CSTB single detection and combined detection were evaluated for postoperative recurrence of bladder cancer. Results The preoperative expression levels of NMP22 and CSTB in the recurrence group were significantly higher than those in the nonrecurrence group (P < 0.05). The results of ROC curve analysis showed that the AUC of preoperative NMP22 and CSTB expression levels to assess postoperative recurrence of bladder cancer was 0.696 and 0.659, respectively (P < 0.05). Logistic multivariate regression analysis showed that preoperative NMP22 and CSTB overexpression was an independent risk factor for postoperative recurrence of bladder cancer (OR = 1.042, 2.307, P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of preoperative NMP22 combined with CSTB in evaluating bladder cancer recurrence after surgery were higher than those of preoperative NMP22 and CSTB alone, and the differences were statistically significant (P < 0.05). Conclusion Preoperative NMP22 and CSTB conveying is hardly interrelated to postoperative recurrence of bladder carcinoma and has certain appraisal worth for postoperative recurrence of bladder carcinoma, and the combined testing of the two has a taller appraisal worth. NMP22 combined with CSTB detection will help to detect postoperative recurrence of bladder cancer and formulate effective treatment measures in time.

Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study

ObjectiveGastric-type mucinous carcinoma (GAS) is a novel variant of uterine cervix mucinous carcinoma. GAS is a distinct entity that can be distinguished from typical endocervical adenocarcinoma (UEA). In Japan, postoperative adjuvant therapy for cervical cancer includes not only radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) but also chemotherapy in many cases. However, no previous studies have analyzed adjuvant therapy for GAS. In the present study, we investigated the efficacy of adjuvant therapy for GAS. MethodsThis was a preplanned secondary analysis of a dataset from previous nationwide, retrospective, observational study. The study population comprised women with stage I–II GAS who underwent surgery. Progression-free survival (PFS) and overall survival (OS) were compared among patients who did and did not receive adjuvant therapy using the Kaplan–Meier method. ResultsData were analyzed for a total of 102 enrolled patients, who were classified as low- (17 patients), intermediate- (37 patients), or high risk (48 patients) based on the risk of postoperative cervical cancer recurrence. In the intermediate-risk group, median survival could not be assessed due to a lack of sufficient events, but the no-adjuvant and RT groups tended to exhibit better prognoses. In contrast, within the high-risk group, patients in the RT subgroup exhibited a trend towards better PFS and OS than those in the CCRT and chemotherapy groups. ConclusionsThe prognosis of GAS was confirmed to be poor, even in cases of early-stage cancer and following surgical resection. Chemotherapy strategies, including CCRT as postoperative adjuvant therapy, tend to have a poor prognosis.

Effect of epidural analgesia on cancer outcomes after gastric cancer resection: a single-centre cohort study in Taiwan

ObjectiveTo investigate the influence of epidural anaesthesia and analgesia (EA) on cancer recurrence and overall survival after surgery for gastric cancer.Study design and settingA retrospective study which involved patients with...

The Influence of Analgesic Modalities on Postoperative Cancer Recurrence.

The potential for cancer cells to grow and to metastasize depends on complex interactions between inflammatory signals and pathways, immune cells, and elements of the stromal tissue in which they invade. Related to the nature of many cancers, the probability of recurrence can potentially be quite high for some patients. Immunology, lifestyle modifications, timing of disease, genetics, age, gender, and race are only a handful of ways the likelihood of cancer recurrence can be influenced. The quantity, or density, of certain immunological cells or factors, plays a role in the propagation of cancer cells. Opioids are often used in cancer patients for acute postoperative and chronic pain management. While they can produce significant pain relief, the type of analgesic utilized is important, as it may influence cancer propagation. In this regard, certain opioids have been found to increase T regulatory cells while suppressing NK cell function. Morphine may promote tumor neovascularization and expansion. Fentanyl administration significantly diminishes NK-cells and CD8+ cytotoxic T-cells. In a recent meta-analysis, propofol-based anesthesia improved both cancer-free survival and overall survival. COX inhibitors have also shown promise in persevering cancer immune function, as in literature involving ketorolac and celecoxib. In summary, inhaled anesthesia and opioids may contribute to a pro-tumor metastasis environment also known as cancer propagation; whereas propofol and COX inhibitors may provide a better alternative to reduce cancer recurrence and propagation.

RNA-seq analysis of peripheral blood dendritic cells maturated by dezocine in patients with lung cancer

Surgical resection is the most common and effective option for the clinical treatment of lung cancer. Postoperative pain may activate surgically induced stress response, leading to a decrease in human immune function. However, conventional analgesics such as morphine and its derivatives have been reported to have immunosuppressive side effects. In the critical period after surgery, the immunosuppressive effect of analgesics on patients with lung cancer could promote postoperative cancer recurrence and metastasis. Therefore, it will be an ideal scenario for postoperative pain management to maximize pain relief while minimizing immunosuppression side effects. In this study, we found that a novel mixed agonist-antagonist opioid analgesic, dezocine, significantly promoted the morphological maturation of dendritic cells (DCs), and increase the expression of DCs-related surface markers in postoperative peripheral blood of patients with lung cancer. Furthermore, dezocine-matured DCs increased the general immune response by promoting the secretion of IL-12 and IL-6 cytokines and enhancing the proliferation and cytotoxicity of CD8+ T cells. Then genome-wide transcriptomic profiling analyses were performed to identify the specific gene expression of dezocine-matured DCs. The results of transcriptomic analysis as well as in vitro validation showed that the upregulation of CXCL10, CD3G, and GRB2 were significantly associated with dezocine-induced DCs maturation. Overall, our data showed that dezocine might exhibit unique properties by acting as an immunostimulant, which provides new evidence for its application in postoperative pain management of patients with lung cancer.

Durable complete response to combination nivolumab and ipilimumab in metastatic renal cell carcinoma

Immune checkpoint inhibitors, which promote or suppress the anti-tumor immune response, are becoming the mainstay of cancer treatment. In 2018, CheckMate 214 study showed a higher response rate with ipilimumab and nivolumab combination therapy compared to conventional therapy for advanced renal cell carcinoma. We report a case of complete response and durable response for two years to ipilimumab and nivolumab combination therapy in a patient with postoperative renal cancer recurrence that caused immune-related adverse events such as interstitial pneumonia and hepatotoxicity.

Local delivery of biocompatible lentinan/chitosan composite for prolonged inhibition of postoperative breast cancer recurrence

Postsurgical localized chemotherapy for breast cancer recurrence (BCR) still faces many problems which dampen researchers' enthusiasm and discounted prognosis. Simple strategies with controllable toxicities are expected to address these hurdles. Lentinan (LNT) has excellent biocompatibility and notable antitumor activity but rather low bioavailability after intravenous or oral administration. Here, a sponge-like LNT/chitosan composite (LNT/CS sponge) was prepared for efficient local delivery to prevent postoperative BCR. The obtained sponges exhibit uniform porosity and sustained release of LNT in vitro and in vivo. Furthermore, the sponges were implanted and showed significant reduction of postsurgical recurrence and suppression of long-term tumor regrowth with favorable biocompatibility in a subcutaneous postsurgical recurrence mouse model. Subsequent studies revealed that LNT can restrain the stemness of breast cancer cells, which may account for the long-term inhibition of tumor relapse. Therefore, LNT/CS sponge has a great potential as a promising alternative for postsurgical BCR.

Effect of Radiofrequency Ablation with Interventional Therapy of Hepatic Artery on the Recurrence of Primary Liver Cancer and the Analysis of Influencing Factors.

Background The probability of liver cancer recurring in patients after surgery is a serious threat to liver cancer patients. Radiofrequency ablation is widely employed in liver cancer cases. We explored the therapeutic effects and influencing factors of radiofrequency ablation combined with hepatic artery intervention in patients with recurrence of primary liver cancer surgery. Methods 90 patients with primary liver cancer postoperative recurrence admitted to our hospital from January 2014 to February 2017 were selected as the research objects. The patients were randomly divided into the control group (n = 45) and combined treatment group (n = 45). The combined treatment group received radiofrequency ablation combined with hepatic artery interventional therapy, and the control group received hepatic artery interventional therapy. The short-term efficacy, AFP levels before and after treatment, and long-term survival results of the two groups were compared. Single-factor and multifactor analyses of the clinical information of the combined treatment group were carried out to find out the factors affecting the therapeutic effect of radiofrequency ablation combined with hepatic artery intervention on patients with recurrence of primary liver cancer. Results The total effective rate of short-term curative effect of the combined treatment group was higher than the control group, and there was a statistically significant difference existing (P < 0.05). After treatment, two groups of patients' AFP levels were greatly lower than before treatment, the AFP levels of the combined treatment group were significantly lower than the control group, and there was a statistically significant difference (P < 0.05). The survival rates of patients in the combined treatment group at the sixth month, the first year, and the second year after treatment were significantly higher than those of the control group, and there was a statistically significant difference (P < 0.05). The univariate results showed that, in the combined treatment group, there were statistically significant differences between the effective group and the ineffective group in tumor diameter, intact capsule, liver cirrhosis, intrahepatic spread, and tumor adjacent to large blood vessels (P < 0.05). The outcomes of multivariate analysis indicated that tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels were risk factors for ineffective recurrence of patients with primary liver cancer after radiofrequency ablation combined with hepatic artery intervention (P < 0.05). Discussion. Tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels are risk factors for the ineffectiveness of radiofrequency ablation combined with hepatic artery interventional therapy for patients with recurrence of primary liver cancer. It is necessary to increase the range of radiofrequency treatment, increase the temperature of the radiofrequency needle, and strengthen postoperative follow-up interventions based on the specific conditions of the patient's tumor.

Effect of epidural analgesia on long-term outcomes after curative surgery for pancreatic cancer: A single-center cohort study in Taiwan.

Whether epidural anesthesia and analgesia (EA) improves long-term outcomes after pancreatic cancer surgery remains controversial. We conducted this retrospective cohort study to investigate the influence of EA on cancer recurrence and overall survival after surgery for pancreatic cancer. We conducted an electronic medical chart review of patients with pancreatic cancer who underwent curative resection at our hospital from 2008 to 2017 and were followed up until December 2019. Patient demographics, anesthetic and surgical characteristics, and pathologic features were also collected. The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW) based on propensity scores to balance unequal distributions of observed covariates. For sensitivity analysis, multivariable regression modeling and quintile-stratified propensity adjustments were also used. Among the 252 included patients, the median follow-up period was 15.9 months (interquartile range 6.8-28.2 months), and 88 (35%) received EA after pancreatic cancer surgery. EA was not associated with greater cancer recurrence (IPTW adjusted HR: 0.98; 95% CI, 0.78%-1.24%; p = 0.87) or all-cause mortality (IPTW adjusted HR: 1.02; 95% CI, 0.82%-1.27%; p = 0.85) after pancreatic cancer resection. In sensitivity analysis, both the multivariable and stratified Cox regression analyses failed to demonstrate significant effects of EA on cancer recurrence and survival after surgery. There were no significant associations between EA and cancer recurrence and overall survival after curative surgery for pancreatic cancer. Prospective studies should be considered to elucidate the relationship between EA and cancer outcomes after pancreatic cancer surgery.