Postoperative Tumor Research Articles

Initial ablation ratio predicts the recurrence of low-risk papillary thyroid microcarcinomas treated with microwave ablation: a 5-year, single-institution cohort study.

To assess the long-term efficacy and safety of microwave ablation (MWA) in treating low-risk papillary thyroid microcarcinomas (PTMC) and to identify predictive factors for the postoperative local tumor progression of PTMC. A total of 154 low-risk PTMC patients treated with MWA who were followed up for at least 3 months were retrospectively recruited. Ultrasonography was performed after MWA to assess the local tumor progression. Adverse events associated with MWA were recorded. The ablated volume (Va) and initial ablation ratio (IAR) were measured to assess their influences on the recurrence risk of PTMC. The mean tumor volume of PTMC before MWA was 0.071 (0.039, 0.121) cm3, with a maximum diameter of 0.60 ± 0.18 cm. All PTMC patients were followed up for 6 (3, 18) months. Va increased immediately after MWA, then gradually decreased over time, till significantly smaller at 12 months than that before MWA (P < 0.05). The median volume reduction ratio at 24 months reached 100%, which was maintained during a 60-month follow-up. A total of 7 (4.55%) cases of local tumor progression were recorded during the follow-up. Kaplan-Meier survival analysis revealed that the rate of local tumor progression was significantly lower in PTMC patients with a maximum tumor diameter < 0.70 cm than in those with ≥0.70 cm (P = 0.031). A significant better prognosis was achieved in PTMC patients with IAR ≥ 15 than in those with IAR < 15 (P = 0.015). Sex, age (<55 years) and preoperative thyroid-stimulating hormone (>2.0 mU/L) of PTMC patients were not correlated with local tumor progression. MWA is an effective therapeutic strategy for low-risk PTMC with high safety. The maximum tumor diameter and IAR are predictive factors for the local tumor progression of PTMC after MWA.

An adhesive hydrogel implant combining chemotherapy and tumor microenvironment remodeling for preventing postoperative recurrence and metastasis of breast cancer

Postoperative tumor microenvironments, such as cancer-associated adipocytes and angiogenesis, severely affect the recurrence and metastasis of residual tumor cells. Efficiently killing residual tumor cells and simultaneously blocking the function of cancer-associated adipocytes and inhibiting angiogenesis might be a promising strategy to prevent postoperative tumor recurrence and metastasis. Here, a bio-adhesive hydrogels grafting dopamine and 3-aminobenzeneboronic acid onto hyaluronic acid were facilely developed to load anticancer drug doxorubicin and metformin (DOX/Met@HDP) for postoperative in-situ treatment in breast cancer. After implantation into the tumor surgical cavity, DOX/Met@HDP persistently retains drugs at the tumor resection sites and releases drugs in a tumor acidic microenvironment-controlled manner. The released doxorubicin efficiently kills residual tumor cells, while the released metformin inhibits adipocyte function to abrogate the adipocyte-promoted proliferation and migration of tumor cells and suppresses tumor angiogenesis, resulting in the significant inhibition of postoperative tumor recurrence and metastasis. Our results demonstrate that DOX/Met@HDP is a potential implant for improving the prognosis of breast cancer patients undergoing surgery.

Association between immunohistochemical markers and tumor progression following resection of spinal chordomas: a multicenter study.

Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression. The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split. Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role. These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

Brain metastasis resection: the impact of fluorescence guidance (MetResect study).

Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection. Analyzing their institution's prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences. In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival. Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Application of the Robotic-Assisted Digital Exoscope for Resection of Posterior Fossa Tumors in Adults: A Series of 45 Cases.

Complete safe resection is the goal when pursuing surgical treatment for posterior fossa (PF) tumors. Efforts have led to the development of the exoscope that delineates tumors from non-neoplastic brain. This investigation aims to assess patient outcomes where PF tumor resection is performed with the exoscope by a retromastoid or suboccipital approach. A retrospective analysis was conducted for patients with PF tumors who underwent exoscope resection from 2017 to 2022. Patient demographics, clinical, operative, and outcome findings were collected. Extent of resection studies were also performed. Associations between perioperative data, discharge disposition, progression-free survival (PFS), and overall survival (OS) were evaluated. A total of 45 patients (22 male patients) with a median age of 57 years were assessed. Eighteen (40%) and 27 patients (60%) were diagnosed with malignant and benign tumors, respectively. Tumor neurovascular involvement was found in 28 patients (62%). Twenty-four (53%) and 20 (44%) tumors formed in the cerebellum and cerebellopontine angle cistern, respectively. One tumor (2%) was found in the cervicomedullary junction. The mean extent of resection was 96.7% for benign and malignant tumors. The PFS and OS rate at 6 months (PFS6, OS6) was 89.7% and 95.5%, respectively. Neurological complications included sensory loss and motor deficit, with 11 patients reporting no postoperative symptoms. Of the neurological complications, 14 were temporary and 9 were permanent. The exoscope is an effective intraoperative visualization tool for delineating PF tumors. In our series, we achieved low postoperative tumor volumes and a high gross total resection rate.

Tailored magnetic resonance fingerprinting of post-operative pediatric brain tumor patients

PurposeBrain and spinal cord tumors are the second most common cancer in children and account for one out of four cancers diagnosed. However, the long acquisition times associated with acquiring both data types prohibit using quantitative MR (qMR) in pediatric imaging protocols. This study aims to demonstrate the tailored magnetic resonance fingerprinting's (TMRF) ability to simultaneously provide quantitative maps (T1, T2) and multi-contrast qualitative images (T1 weighted, T1 FLAIR, T2 weighted) rapidly in pediatric brain tumor patients. MethodsIn this work, we imaged five pediatric patients with brain tumors (resected/residual) using TMRF at 3 T. We compared the TMRF-derived T2 weighted images with those from the vendor-supplied sequence (as the gold standard, GS) for healthy and pathological tissue signal intensities. The relaxometric maps from TMRF were subjected to a region of interest (ROI) analysis to differentiate between healthy and pathological tissues. We performed the Wilcoxon rank sum test to check for significant differences between the two tissue types. ResultsWe found significant differences (p < 0.05) in both T1 and T2 ROI values between the two tissue types. A strong correlation was found between the TMRF-based T2 weighted and GS signal intensities for the healthy (correlation coefficient, r = 0.99) and pathological tissues (r = 0.88). ConclusionThe TMRF implementation provides the two relaxometric maps and can potentially save ~2 min if it replaces the T2-weighted imaging in the current protocol.

Emergency exploratory laparotomy and radical gastrectomy in patients with gastric cancer combined with acute upper gastrointestinal bleeding.

Gastric cancer (GC) is a prevalent malignant tumor worldwide and ranks as the fourth leading cause of cancer-related mortality. Upper gastrointestinal bleeding (UGIB) is a frequent complication of GC. Radical gastrectomy and palliative therapy are widely used surgical procedures in the clinical management of GC. This study intends to probe the clinical efficacy and safety of radical gastrectomy and palliative therapy on the basis of exploratory laparotomy in patients with GC combined with UGIB, hoping to provide valuable information to aid patients in selecting the appropriate surgical intervention. To investigate the clinical efficacy and safety of exploratory laparotomy + radical gastrectomy and palliative therapy in patients with GC and UGIB combined. A total of 89 GC patients admitted to the First Affiliated Hospital of the University of South China between July 2018 and July 2020 were selected as participants for this study. The 89 patients were divided into two groups: radical resection group (n = 46) treated with exploratory laparotomy + radical gastrectomy and Palliative group (n = 43) treated with palliative therapy. The study compared several variables between the two groups, including surgical duration, intraoperative blood transfusion volume, postoperative anal exhaust time, off-bed activity time, length of hospitalization, and incidence of complications such as duodenal stump rupture, anastomotic obstruction, and postoperative incision. Additionally, postoperative immune function indicators (including CD3+, CD4+, CD8+, CD4+/CD8+, and CD3+/HLADR+), immunoglobulin (IgG and IgM), tumor markers (CEA, CA199, and CA125), and inflammatory factors (IL-6, IL-17, and TNF-α) were assessed. The surgical efficacy and postoperative quality of life recovery were also evaluated. The patients were monitored for survival and tumor recurrence at 6 mo, 1 year, and 2 years post-surgery. The results indicated that the duration of operation time and postoperative hospitalization did not differ between the two surgical procedures. However, patients in the radical resection group exhibited shorter intraoperative blood loss, anus exhaust time, off-bed activity time, and inpatient activity time than those in the Palliative group. Although there was no substantial difference in the occurrence of postoperative complications, such as duodenal stump rupture and anastomotic obstruction, between the radical resection group and Palliative group (P > 0.05), the radical resection group exhibited higher postoperative immune function indicators (including CD3+, CD4+, CD8+, etc.) and immunoglobulin levels (IgG, IgM) than the Palliative group, while tumor markers and inflammatory factors levels were lower than those in the radical resection group. Additionally, surgical efficacy, postoperative quality of life, and postoperative survival rates were higher in patients who underwent radical gastrectomy than in those who underwent palliative therapy. Moreover, the probability of postoperative tumor recurrence was lower in the radical gastrectomy group compared to the palliative therapy group, and these differences were all statistically significant (P < 0.05). Compared to palliative therapy, exploratory laparotomy + radical gastrectomy can improve immune function, reduce the levels of tumor markers and inflammatory factors, improve surgical efficacy, promote postoperative quality of life recovery, enhance survival rates, and attenuate the probability of tumor recurrence.

Enrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence

Postoperative tumor recurrence and metastases often lead to cancer treatment failure. Here, we develop a local embedded photodynamic immunomodulatory DNA hydrogel for early warning and inhibition of postoperative tumor recurrence. The DNA hydrogel contains PDL1 aptamers that capture and enrich in situ relapsed tumor cells, increasing local ATP concentration to provide a timely warning signal. When a positive signal is detected, local laser irradiation is performed to trigger photodynamic therapy to kill captured tumor cells and release tumor-associated antigens (TAA). In addition, reactive oxygen species break DNA strands in the hydrogel to release encoded PDL1 aptamer and CpG, which together with TAA promote sufficient systemic antitumor immunotherapy. In a murine model where tumor cells are injected at the surgical site to mimic tumor recurrence, we find that the hydrogel system enables timely detection of tumor recurrence by enriching relapsed tumor cells to increase local ATP concentrations. As a result, a significant inhibitory effect of approximately 88.1% on recurrent tumors and effectively suppressing metastasis, offering a promising avenue for timely and effective treatment of postoperative tumor recurrence.

Mussel-inspired “plug-and-play” hydrogel glue for postoperative tumor recurrence and wound infection inhibition

Currently, clinical tumor resection is faced with two options: open and minimally invasive surgery. Open surgery is easy to completely remove the lesion but is prone to infection, while minimally invasive surgery recovers faster but may cause tumor recurrence. To fill the shortcomings of the two surgical modes and make the choice for tumor resection more effortlessly, we developed a postoperative black phosphorus-Ag nanocomposites-loaded dopamine-modified hyaluronic acid-Pluronic® F127 (BP-Ag@HA-DA-Plu) hydrogel implantation system that can prevent tumor recurrence and wound infection simultaneously. Experiments have shown that the hydrogel system combined with 808 nm near-infrared (NIR) irradiation has excellent anti-tumor, antibacterial, and wound healing abilities. Additionally, unlike existing surgical hydrogel products that require inconvenient in-situ cross-linking, the BP-Ag@HA-DA-Plu hydrogel system offers “plug-and-play” functionality during surgery due to its thermo-responsiveness, injectability, and adhesion, thereby greatly improving the efficiency of surgery.

Does tumor rupture during robot-assisted partial nephrectomy have an impact on mid-term tumor recurrences?

Intraoperative kidney tumor rupture (TR) can occur during robot-assisted partial nephrectomy (RAPN) in daily clinical practice, but there are no solid guidelines on the management and implications of it. The purpose of the study was to investigate the impact of TR on tumor recurrences, what a surgeon should do if this adverse event occurs, and how to avoid it. We retrospectively analyzed the first 100 patients who underwent RAPN at University Medical Centre Ljubljana, between 2018 and 2021. Patients were stratified into 2 groups (TR and no-TR) and were compared according to patient, tumor, pathologic, perioperative and postoperative characteristics and tumor recurrences, using the Mann-Whitney U test and chi-squared test. Of the 100 patients, 14 had TR (14%); this occurred in tumors with higher RENAL nephrometry scores (P = 0.028) and mostly with papillary renal cell carcinomas (P = 0.043). Median warm ischemia time was longer for the TR group (22 vs. 15 min, P = 0.026). In terms of studied outcomes, there were no cases of local or distant recurrence after a median observation time of 39 months (interquartile range, 31-47 months) in both groups. We observed positive surgical margins on the final oncologic report in one case in the no-TR group. Tumor rupture during RAPN seems to be of no mid-term oncologic importance. According to presented results, we would recommend surgeons to proceed with tumor resection if this event occurs and abstain from conversion to radical nephrectomy or open partial nephrectomy. However, more similar cases should be studied to make more solid conclusions.

High-intensity focused ultrasound versus transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis

Purpose The application of high-intensity focused ultrasound (HIFU) in hepatocellular carcinoma (HCC) was promising. However, whether the effect of HIFU is comparable with that of transarterial chemoembolization (TACE) has not been determined. Materials and methods PubMed, Embase, Cochrane Library, Web of Science, WanFang Data, CqVip, CNKI, and CBM databases were searched for randomized controlled trials (RCTs), cohort studies, and case-control studies. The methodological quality of each study was evaluated. When there is no statistical heterogeneity, the fixed effect model would be used to merge data. Otherwise, the random effect model would be utilized. Sensitivity analyses were conducted by excluding one study each time. Subgroup analyses were conducted based on age, sex, tumor number, relative number of the patients with Child-Pugh C grade in each group, the percentage of patients with Child-Pugh C grade in the whole study, and tumor load. Publication bias was evaluated by Egger’s test and Begg’s test. Results Six cohort studies including 188 patients from HIFU group and 224 patients from TACE group were obtained for further analysis. The meta-analysis suggested HIFU and TACE showed no differences in postoperative 1-year overall survival (OS) rate, tumor response (including complete response, partial response, stable disease, and progressive disease), and postoperative complications. Moreover, compared with TACE, HIFU showed higher postoperative 6-month and 2-year OS rates. Subgroup analyses, meta regression analysis and sensitivity analyses indicated the findings above were reliable. Additionally, no potential publication bias was detected. Conclusion For HCC, when compared with TACE, HIFU might show comparable safety but better effect. Considering the limitations of current studies, more well-designed studies are needed to validate our conclusion.

Golden Buckwheat Extract-Loaded Injectable Hydrogel for Efficient Postsurgical Prevention of Local Tumor Recurrence Caused by Residual Tumor Cells.

To prevent local tumor recurrence caused by possible residual cancer cells after surgery, avoid toxicity of systemic chemotherapy and protect the fragile immune system of postsurgical patients, an increasing amount of attention has been paid to local anti-cancer drug delivery systems. In this paper, golden buckwheat was first applied to prevent post-operative tumor recurrence, which is a Chinese herb and possesses anti-tumor activity. Golden buckwheat extract-loaded gellan gum injectable hydrogels were fabricated via Ca2+ crosslinking for localized chemotherapy. Blank and/or drug-loaded hydrogels were characterized via FT-IR, TG, SEM, density functional theory, drug release and rheology studies to explore the interaction among gellan gum, Ca2+ and golden buckwheat extract (GBE). Blank hydrogels were non-toxic to NIH3T3 cells. Of significance, GBE and GBE-loaded hydrogel inhibited the proliferation of tumor cells (up to 90% inhibition rate in HepG2 cells). In vitro hemolysis assay showed that blank hydrogel and GBE-loaded hydrogel had good blood compatibility. When GBE-loaded hydrogel was applied to the incompletely resected tumor of mice bearing B16 tumor xenografts, it showed inhibition of tumor growth in vivo and induced the apoptosis of tumor cells. Taken together, gellan gum injectable hydrogel containing GBE is a potential local anticancer drug delivery system for the prevention of postsurgical tumor recurrence.

Electrospun fibers integrating enzyme-functionalized metal-organic frameworks for postoperative tumor recurrence inhibition and simultaneously wound tissue healing

The tumor recurrence and infected wound tissue defect are the major clinical challenges after the surgical treatment of primary chest wall cancer. Herein, to address the above issues, blending electrospinning was applied to incorporate glucose oxidase (GOx) loaded Zn/Cu-based bimetallic zeolitic imidazolate frameworks (GOx/BMOFs) into polyurethane (PU) fibers, which were designed for effective cancer therapy with improved wound healing. The release of Cu2+ and GOx could accomplish the conversion from Cu2+ to Cu+ through the glutathione (GSH) depletion and provide additional H2O2 from glucose by GOx catalysis, respectively, which further underwent the Fenton-like reaction to produce toxic hydroxyl radical (OH). The tumor cells (human fibrosarcoma cells) could be effectively killed in vitro and in vivo through the synergistic chemodynamic therapy and starvation therapy. Moreover, the electrospun fiber platform could support the adhesion and proliferation of wound tissue cells, and also show the antibacterial ability owing to the functional agents in the fibers, thereby accelerating the infected wound repair in vivo. This work may offer a reliable and effective fiber biomaterial for localized chest wall tumor therapy and simultaneous tissue regeneration.

Prognosis of Concurrent Versus Sequential Chemo-Radiotherapy Induction Followed by Surgical Resection in Patients with Advanced Thymic Epithelial Tumors: A Retrospective Study.

This study aimed to evaluate the prognosis of concurrent chemo-radiotherapy (CCRT) versus sequential chemo-radiotherapy (SCRT) induction followed by surgical resection in patients with advanced thymic epithelial tumors (TETs). This retrospective study included patients with advanced TETs who underwent CCRT or SCRT induction followed by surgical resection at the Second General Hospital of Guangdong Province between January 2008 and December 2019. The primary outcomes were induction response rate and surgical complete resection rate. The secondary outcomes were surgery combined resection, post-induction T staging, postoperative TNM staging, postoperative pathological tumor regression grade, progression-free survival (PFS) and overall survival (OS), and adverse events (AEs). A total of 31 patients were included, 15 of whom received CCRT and the other 16 SCRT. The induction response rates were 80.0 and 62.5%, respectively, the post-induction step-down rates were 46.7 and 31.3%, respectively, and the post-induction R0 resection rates were 80.0 and 68.8%, respectively, without significant differences between CCRT and SCRT groups (all P > 0.05). The 5-year OS rate was 64.2 and 51.6%, respectively, and PFS was 42.3 and 21.4%, respectively, without significant differences between CCRT and SCRT groups (both P > 0.05). AEs in the hematologic system were significantly higher with CCRT compared with SCRT (P = 0.009). Patients with advanced TETs might have a good prognosis with both CCRT and SCRT induction therapy, while SCRT induction may result in a lower probability of AEs in the hematologic system.

Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

RWTC-MBTA: autologous vaccine prevents metastases via antitumor immune responses

BackgroundAutologous tumor cell-based vaccines (ATVs) aim to prevent and treat tumor metastasis by activating patient-specific tumor antigens to induce immune memory. However, their clinical efficacy is limited. Mannan-BAM (MB), a pathogen-associated molecular pattern (PAMP), can coordinate an innate immune response that recognizes and eliminates mannan-BAM-labeled tumor cells. TLR agonists and anti-CD40 antibodies (TA) can enhance the immune response by activating antigen-presenting cells (APCs) to present tumor antigens to the adaptive immune system. In this study, we investigated the efficacy and mechanism of action of rWTC-MBTA, an autologous whole tumor cell vaccine consisting of irradiated tumor cells (rWTC) pulsed with mannan-BAM, TLR agonists, and anti-CD40 antibody (MBTA), in preventing tumor metastasis in multiple animal models.MethodsThe efficacy of the rWTC-MBTA vaccine was evaluated in mice using breast (4T1) and melanoma (B16-F10) tumor models via subcutaneous and intravenous injection of tumor cells to induce metastasis. The vaccine’s effect was also assessed in a postoperative breast tumor model (4T1) and tested in autologous and allogeneic syngeneic breast tumor models (4T1 and EMT6). Mechanistic investigations included immunohistochemistry, immunophenotyping analysis, ELISA, tumor-specific cytotoxicity testing, and T-cell depletion experiments. Biochemistry testing and histopathology of major tissues in vaccinated mice were also evaluated for potential systemic toxicity of the vaccine.ResultsThe rWTC-MBTA vaccine effectively prevented metastasis and inhibited tumor growth in breast tumor and melanoma metastatic animal models. It also prevented tumor metastasis and prolonged survival in the postoperative breast tumor animal model. Cross-vaccination experiments revealed that the rWTC-MBTA vaccine prevented autologous tumor growth, but not allogeneic tumor growth. Mechanistic data demonstrated that the vaccine increased the percentage of antigen-presenting cells, induced effector and central memory cells, and enhanced CD4+ and CD8+ T-cell responses. T-cells obtained from mice that were vaccinated displayed tumor-specific cytotoxicity, as shown by enhanced tumor cell killing in co-culture experiments, accompanied by increased levels of Granzyme B, TNF-α, IFN-γ, and CD107a in T-cells. T-cell depletion experiments showed that the vaccine’s antitumor efficacy depended on T-cells, especially CD4+ T-cells. Biochemistry testing and histopathology of major tissues in vaccinated mice revealed negligible systemic toxicity of the vaccine.ConclusionThe rWTC-MBTA vaccine demonstrated efficacy in multiple animal models through T-cell mediated cytotoxicity and has potential as a therapeutic option for preventing and treating tumor metastasis with minimal systemic toxicity.

Long-term Recurrence Rates of Low-risk Non–muscle-invasive Bladder Cancer—How Long Is Cystoscopic Surveillance Necessary?

BackgroundWhile low-risk non–muscle-invasive bladder cancer (LR-NMIBC) has a low propensity to progress, the risk of recurrence remains high (50% within 4 yr). Guidelines recommend cystoscopic surveillance after resection, but the necessary duration of follow-up is debated. ObjectiveTo determine the risk of recurrence beyond 5 yr after diagnosis in patients with LR-NMIBC, and to identify risk factors of recurrence. Design, setting, and participantsIn this multicenter retrospective observational study, patients who received their first transurethral bladder tumor resection before 2016 for LR-NMIBC were included. Low risk was defined as a primary, solitary, low grade, Ta bladder tumor measuring <3 cm. Outcome measurements and statistical analysisThe primary endpoint was determination of the recurrence rates at 1, 2, and 5 yr. The secondary endpoints included overall recurrence-free survival (RFS) and high-risk RFS. A univariate analysis and multivariable logistic regression were performed to assess the risk factors for recurrence over the study period. Results and limitationsThe median age of the 577 patients was 70.9 yr, and 126 (21.8%) patients were female. The median follow-up was 69.6 (interquartile range: 58.4) mo, and recurrence was observed in 236 (40.9%) patients. The 1-, 2-, and 5-yr RFS rates were 81.6% (95% confidence interval 78.4–84.9), 72.4% (68.7–76.3), and 59.2% (55–63.8), respectively. Recurrence after 5 yr was observed in 13.1% (28/213). High-risk recurrence, defined as the first recurrence of a high-grade and/or ≥T1 tumor, occurred in 6.2% (36/579) overall and 2.8% (6/213) after 5 yr. The lack of a single postoperative dose of chemotherapy and tumor size >2 cm were prognostic factors of recurrence. ConclusionsThe risk of recurrence in patients with LR-NMIBC decreases progressively after the 1st year and remains low beyond 5 yr. Discontinuation of endoscopic surveillance after 5 yr in patients with LR-NMIBC can be discussed. Treatment with postoperative chemotherapy and tumor size <2 cm may be relevant variables to identify patients who will benefit from cystoscopic follow-up as short as 12 mo. Patient summaryIn this study, we observed that 13% of patients who did not have a recurrence during the first 5 yr following the diagnosis of low-risk non–muscle-invasive bladder cancer will recur after this time point. Discontinuation of cystoscopic surveillance can be discussed after 5 yr in these patients.

Survival of small-cell lung cancer patients after surgery: a single-center retrospective cohort study.

This study summarized and analyzed the clinical characteristics and prognosis of small-cell lung cancer (SCLC) patients after surgical treatment. The clinical data of 130 patients (99 males and 31 females) with SCLC treated by surgery and confirmed by postoperative pathological examination at Peking Union Medical College Hospital from April 2004 to April 2019 were retrospectively analyzed. Clinical characteristics, surgery, pathological stage, and perioperative treatment were summarized. Kaplan-Meier survival curve and Cox regression analysis were performed. Pathological examination revealed that 36 (27.69%) patients had stage I SCLC, 22 (16.92%) patients had stage II SCLC, 65 (50.00%) patients had stage III SCLC, and 7 (5.39%) patients had stage IV SCLC. The overall median survival time was 50 months (95% confidence interval, 10.8-89.2 months). The median survival time of stage I, II, III and IV SCLC patients was 148, 42, 32, and 10 months, respectively. In patients who underwent surgical treatment, postoperative adjuvant therapy and tumor stage were independent prognostic factors for survival (p < 0.05).Lobectomy and lymph nodes resection combined with adjuvant therapy were cautiously recommended for stage I-IIIa SCLC patients.

The mFI-5 and Postoperative Outcomes in Brain Tumor Patients: A Bayesian Approach to Quantifying Uncertainty

To the best of our knowledge, prior research has not investigated the uncertainty in the relationship between patient frailty and postoperative outcomes afterbrain tumor surgery. The present study used Bayesian methods to quantify the statistical uncertainty betweenthe5-factor modified frailty index (mFI-5) and postoperative outcomes for patients undergoing brain tumor resection. The present study used retrospective data collected from patients undergoing brain tumor resection during a 2-year period (2017-2019). Posterior probability distributions were used to estimate the means of model parameters that are most likely given the priors and the data. Additionally, 95% credible intervals (CrIs) were constructed for each parameter estimate. Our patient cohort included 2519 patients with a mean age of 55.27 years. Our multivariate analysis demonstrated that each 1-point increase in the mFI-5 score was associated with an 18.76% (95% CrI, 14.35%-23.36%) increase in hospital length of stay and a 9.37% (CrI, 6.82%-12.07%) increase in hospital charges. We also noted an association between an increasing mFI-5 score and greater odds of a postoperative complication (odds ratio [OR], 1.58; CrI, 1.34-1.87) and a nonroutine discharge (OR, 1.54; CrI, 1.34-1.80). However, no meaningful statistical association was found between the mFI-5 score and 90-day hospital readmission (OR, 1.16; CrI, 0.98-1.36) or between the mFI-5 score and 90-day mortality (OR, 1.12; CrI, 0.83-1.50). Although mFI-5 scores might be able to effectively predict short-term outcomes such as length of stay, our results demonstrate no meaningful association between mFI-5 scores and 90-day readmission or 90-day mortality. Our study highlights the need for rigorously quantifying statistical uncertainty to safely risk-stratify neurosurgical patients.

In Situ Attached Photothermal Immunomodulation-Enhanced Nanozyme for the Inhibition of Postoperative Malignant Glioma Recurrence.

Glioblastoma (GBM) is one of the most challenging malignant brain tumors to treat. Herein, we describe a nanoenzyme hemostatic matrix strategy with the tumor cavity in situ application that simultaneously serves as photothermal agent and induces immunogenic cell death after GBM surgical resection to enhance the antitumor immunity and delay tumor recurrence. The hemostatic matrix system (Surgiflo@PCN) contains Surgiflo, a multispace structure that can be used to penetrate different shapes of tumor cavities to prevent postoperative tumor cavity hemorrhage. As well, porous palladium-copper nanoclusters (PCNs) have adjustable enzyme-like activities (oxidase, peroxidase, and catalase) responsible for formation of reactive oxygen species (ROS) under near-infrared (808 nm) laser irradiation. When the Surgiflo@PCN entered the resected tumor cavity, the first action was the direct killing of glioma cells via ROS and photothermal therapy (PTT). The second action was the induction of immunogenic cell death by PCN-enhanced oxidative stress and PTT, which reversed the immunosuppressive tumor microenvironment and enhanced the antitumor immune response. This eradicated residual glioma cells and prevented recurrence. The collective findings demonstrate that Surgiflo@PCN kills glioma cells directly through ROS and PTT and enhances antiglioma immunity and kills glioma cells indirectly. The "one-stone, two-birds" strategy could become an effective photothermal immunotherapy in GBM patients.