The impact of previous abdominal surgery on colorectal cancer patients undergoing laparoscopic surgery.

The current study aimed to investigate whether previous abdominal surgery (PAS) could affect the outcomes of colorectal cancer (CRC) surgery. We conducted the search strategy in three databases (PubMed, Embase, and the Cochrane Library) from inception to May 26, 2022. The short-term and long-term outcomes were compared between the PAS group and the non-PAS group. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled up. Stata (V.16.0) software was used for data analysis. We included 34,827 patients from 14 studies in the current study. After pooling up all the data, we found that there were higher proportions of overall complications (OR = 1.12, I2 = 4.65%, 95% CI 1.03 to 1.23, P = 0.01), ileus (OR = 1.96, I2 = 59.74%, 95% CI 1.12 to 3.44, P = 0.02) and mortality (OR = 1.26, I2 = 0.00%, 95% CI 1.11 to 1.42, P = 0.00) in the PAS group than the non-PAS group. Patients with a history of PAS had higher risks of overall complications and death following CRC surgery. However, it did not appear to significantly affect the short-term outcomes apart from ileus. Surgeons should raise awareness of patients with a history of PAS, and take steps to reduce postoperative complications and mortality.

Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer.

Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The study demonstrated that EpCAM CAR-T cells can elicit lytic cytotoxicity to target cells in an EpCAM-dependent manner and secrete cytotoxic cytokines, including interferon gamma and tumor necrosis factor alpha. Furthermore, adoptive transfer of EpCAM CAR-T cells significantly delayed tumor growth and formation in xenograft models. In addition, the safety evaluation showed that CAR-T cells have no systemic toxicity in mice. The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors.

Establishing guidelines for CAR-T cells: challenges and considerations.

T cells, genetically modified by chimeric antigen receptors (CAR-T), are endowed with specificity to a desired antigen and are cytotoxic to cells expressing the targeted antigen. CAR-T-based cancer immunotherapy is a promising therapy for curing hematological malignancy, such as acute lymphoid leukemia, and is promising for extending their efficacy to defeat solid tumors. To date, dozens of different CAR-T cells have been evaluated in clinical trials to treat tumors; this necessitates the establishment of guidelines for the production and application of CAR-T cells. However, it is challenging to standardize CAR-T cancer therapy because it involves a combination of gene therapy and cell therapy. In this review, we compare the existing guidelines for CAR-T cells and discuss the challenges and considerations for establishing guidance for CAR-T-based cancer immunotherapy.

Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

Down-regulation of MFG-E8 by RNA interference combined with doxorubicin triggers melanoma destruction.

The pathogenic mechanism of malignant melanoma involves the dynamic interplay of transformed cell and normal host cell, but cancer treatments always target each partition separately. In the tumor microenvironment, milk fat globule epidermal growth factor-8 (MFG-E8) is a secreted glycoprotein highly expressed in the vertical growth phase of melanoma, leading to tumor progression through coordinated αvß3 and αvß5 integrin signaling in tumor cells and host cells. Doxorubicin (Dox) is one of the most widely used antitumor drugs against a lot of solid tumors, including melanoma. In this work, Dox was used to combine with down-regulation of MFG-E8 by RNA interference (RNAi) in order to determine the synergistic effect of the antitumor activity in vivo. And the possible mechanisms were investigated. Results showed that combination group (MFG-E8 RNAi plus Dox) could inhibit the growth of melanoma more effectively than monotherapy or control groups. We found that the combination treatment induced more tumor cell apoptosis and inhibited more neovascularization than other groups. Moreover, this combination treatment attenuated CD4(+) CD25(+) Foxp3(+) Treg cells in tumor-infiltrating lymphocytes compared with other groups. Our findings suggested that MFG-E8 down-regulation enhanced the antitumor function of chemotherapy through coordinated cell apoptosis and immune-mediated mechanisms, which might be a feasible way for cancer therapy.

3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma.

AIM: To compare transcatheter arterial chemoembolization (TACE) and 3D conformal radiotherapy (3D-CRT) with TACE monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched all the eligible studies from the Cochrane Library, PubMed, Medline, Embase, and CNKI. The meta-analysis was performed to assess the survival benefit, tumor response, and the decline in α-fetoprotein (AFP) level. According to the heterogeneity of the studies, pooled OR with 95%CI were calculated using the fixed-effects or random-effects model. An observed OR > 1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant. Statistical analyses were performed using Review Manager Software. RESULTS: Ten studies met the criteria to perform a meta-analysis including 908 HCC participants, with 400 patients in the TACE/3D-CRT combination group and 508 in the TACE alone group. TACE combined with 3D-CRT significantly improved 1-, 2- and 3-year overall survival compared with TACE monotherapy (OR = 1.87, 95%CI: 1.37-2.55, P < 0.0001), (OR = 2.38, 95%CI: 1.78-3.17, P < 0.00001) and (OR = 2.97, 95%CI: 2.10-4.21, P < 0.00001). In addition, TACE plus 3D-CRT was associated with a higher tumor response (complete remission and partial remission) (OR = 3.81; 95%CI: 2.70-5.37; P < 0.00001), and decline rates of AFP level (OR = 3.24, 95%CI: 2.09-5.02, P < 0.00001). CONCLUSION: This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC, which needs to be confirmed by large multicenter trials．

Diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer: a meta-analysis.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a new technique for identifying different malignant tumors using different uptake values between tumor cells and normal tissues. Here we assessed the diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer by pooling data of existing trials in a meta-analysis. METHODS: PubMed/MEDLINE, Embase and Cochrane Central Trials databases were searched and studies published in English relating to the diagnostic value of FDG-PET for testicular cancer were collected. The summary receiver operating characteristic (SROC) curve was used to examine the FDG-PET accuracy. RESULTS: A total of 16 studies which included 957 examinations in 807 patients (median age, 31.1 years) were analyzed. A meta-analysis was performed to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratio (NLR). SROC were derived to demonstrate the diagnostic accuracy of FDG-PET for testicular cancer. The pooled sensitivity and specificity were 0.75 (95% confidence interval (CI), 0.70-0.80) and 0.87 (95% CI, 0.84-0.89), respectively. The pooled DOR was 35.6 (95% CI, 12.9-98.3). The area under the curve (AUC) was 0.88. The pooled PLR and pooled NLR were 7.80 (95% CI, 3.73-16.3) and 0.31 (95% CI, 0.23-0.43), respectively. CONCLUSION: In patients with testicular cancer, 18F-FDG-PET demonstrated a high SROC area, and could be a potentially useful tool if combined with other imaging methods such as MRI and CT. Nevertheless, the literature focusing on the use of 18F-FDG-PET in this setting still remains limited.

Pretreatment thrombocytosis as a prognostic factor in women with gynecologic malignancies: a meta-analysis.

BACKGROUND: This study was performed to analyze the prognostic implications of pretreatment or preoperative thrombocytosis in women with gynecologic malignancies. MATERIAL AND METHODS: We surveyed 2 medical databases, PubMed and EMBASE, to identified all relevant studies. A total of 14 (n=3,490) that evaluated the link between thrombocytosis and 5-year survival were included. REVMAN version 5.1 was used for our analysis and publication bias was evaluated using the Begg's funnel plot and tested by STATA 11.0. Risk ratios (RRs) with 95% confidence intervals (CIs) generated by the random effect model were used to assess the strength of any association. RESULTS: 709(20.3%) of the 3,490 patients exhibited thrombocytosis (platelet counts >400?109/L) at primary diagnosis, and their mortality was 1.62-fold higher compared with the others (RR=1.62, 95%CI= [1.28- 2.05], p<0.0001). Thrombocytosis failed to have a stronger effect on the survival of advanced patients of stages III to IV in our study (n=478, RR=1.29, 95% CI= [1.13-1.48], p=0.0003), nor in women with cervical cancer in stage IB (n=1371, RR= 1.73, 95% CI= [1.71-2.58], p=0.007). In addition, when adjusted for different carcinoma, it was associated with worse prognosis for all except the ones with vulvar cancer (n=201, RR= 0.43, 95% CI= [0.14-1.29], p=0.13). CONCLUSIONS: This meta-analysis indicated that thrombocytosis might be associated with a worse prognosis for patients with gynecologic malignancies but without specificity or sensitivity for the ones in advanced stage. When adjusted for different gynecologic malignancies, it showed a significant effect on survival of all except vulvar cancers.