Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis.

BACKGROUND: Currently, there is a lack of affordable and accessible indicators that can accurately predict immune-related adverse events (irAEs) resulting from the use of immune checkpoint inhibitors (ICIs). In order to address this knowledge gap, our study explore the potential predictive value of two ratios, namely the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), for irAEs in cancer patients. METHODS: A systematic search was performed in PubMed, Embase, and the Cochrane library. Studies involving NLR or PLR with irAEs were included. Quality and risk of bias of the selected studies were assessed. Forest plots were created based on Cox model analysis. Random effects meta-analyses were conducted to estimate odds ratio (OR) and its 95% confidence interval (CI). RESULTS: After screening 594 studies, a total of 7 eligible studies with 1068 cancer patients were included. Analysis based on Cox regression showed that low neutrophil-lymphocyte ratio (L-NLR) (OR = 3.02, 95% CI 1.51 to 6.05, P = 0.002) and low platelet-lymphocyte ratio (L-PLR) (OR = 1.83, 95% CI 1.21 to 2.76, P = 0.004) were associated with irAEs. In the subgroup analysis of cut-off value, when the NLR cut-off value was 3, irAEs was significantly correlated with NLR (OR = 2.63, 95% CI 1.63 to 4.26, P < 0.001). CONCLUSIONS: Both L-NLR and L-PLR have been found to be significantly associated with irAEs. Consequently, patients identified as being at a higher risk for irAEs should be subjected to more diligent monitoring and close observation.

Third-line treatment options in metastatic pancreatic cancer patients: a real-world study.

Background: There are currently no standard therapy regimens for the third-line treatment of metastatic pancreatic cancer (mPC) patients. The aim of the present study was to compare the efficacy and safety of different third-line therapy regimens for mPC in the real-world. Methods: This study retrospectively analyzed mPC patients admitted to Zhejiang Provincial People's Hospital between June 2013 and January 2023. All patients' diagnoses were pathologically confirmed and their treatment was continued after the second-line therapy failed. The primary study endpoints included median overall survival (mOS), median progression-free survival (mPFS), and disease control rate (DCR). Results: A total of 72 patients were enrolled in the study. Of these, 36 patients received chemotherapy alone, 16 received chemotherapy combined with targeted therapy or immunotherapy, 14 received chemotherapy-free antitumor therapy, and six received palliative care. The mPFS value for these groups was 4.40 months, 5.20 months, 2.33 months, and 0.80 months, respectively. The mOS value was 6.90 months, 5.90 months, 3.33 months, and 0.80 months, respectively. The DCR was 33.4%, 31.3%, 21.4%, and 0.0%, respectively. Overall, there were significant differences in prognosis between the palliative care group and the other treatment groups (mOS, P < 0.001; mPFS P < 0.001; DCR, P < 0.001). The differences among the mPFS, mOS, and DCR for different antitumor therapy regimens were not statistically significant. Compared to the chemotherapy alone group, the chemotherapy combined with targeted therapy or immunotherapy group experienced more adverse events (100% vs. 75.0%; P = 0.002). Chemotherapy combined with targeted therapy or immunotherapy was associated with a higher risk of grade 3/4 hyperaminotransferemia compared to chemotherapy alone (31.3% vs. 0.0%; P = 0.020) and chemotherapy-free antitumor therapy (31.3% vs. 0.0%; P = 0.020). Conclusions: Third-line antitumor therapy can prolong the survival time of patients with mPC. Targeted therapy or immunotherapy failed to further improve survival benefits based on chemotherapy results. Patients who underwent the third-line treatment with good physical status and family history of cancer were independent prognostic factors for longer mOS. The sequencing of fluorouracil and gemcitabine in the front-line therapy did not affect third-line mOS.

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study.

BACKGROUND: Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy. METHODS: This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People's Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy. RESULTS: A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period. CONCLUSIONS: Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.

Comparison of the efficacy and safety of fruquintinib and regorafenib in the treatment of metastatic colorectal cancer: A real-world study.

Background: Fruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs. Materials and methods: The data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People's Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib. Results: A total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension. Conclusion: Fruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.

Targeted mechanical forces enhance the effects of tumor immunotherapy by regulating immune cells in the tumor microenvironment.

Mechanical forces in the tumor microenvironment (TME) are associated with tumor growth, proliferation, and drug resistance. Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells, thus promoting tumor progression and metastasis. Mechanical signals are transformed into biochemical signals, which activate tumorigenic signaling pathways through mechanical transduction. Cancer immunotherapy has recently made exciting progress, ushering in a new era of "chemo-free" treatments. However, immunotherapy has not achieved satisfactory results in a variety of tumors, because of the complex tumor microenvironment. Herein, we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.

A rare and highly malignant Stwart-Treves syndrome case after breast cancer surgery: a case report.

Background: Stewart-Treves syndrome (STS) is a lymphatic sarcoma secondary to chronic lymphedema of the extremities. Most STS patients have a history of breast cancer and have undergone radical mastectomy and postoperative radiation and chemotherapy. It usually occurs 11 to 12 years after surgery, and about 0.45% of patients are estimated to have the disease. The characteristics of STS include that it is clinically relatively rare, has a high degree of malignancy, can spread easily in the absence of timely treatment, and has low survival rate. Herein, we report a case of STS which developed 13 years after breast cancer-related lymphoedema (BCRL). It allows doctors to recognize and detect the disease earlier. Case Description: A 74-year-old woman had undergone modified radical mastectomy 13 years ago for invasive ductal breast cancer in her left breast. After multiple rounds of postoperative chemoradiotherapy, multiple purple lesions were found in the left upper limb during physical examination in April 2021. The lesions spread rapidly and were varied in size. An immediate skin biopsy reported the lesions as STS. The patient was diagnosed with lymphangiosarcoma with metastasis (STS). The surgical method was shoulder joint amputation, chest wall resection, and local flap transfer. After surgery, the patient underwent 6 rounds of paclitaxel 300 mg + carboplatin 300 mg chemotherapy. After chemotherapy, the patient's wound healed and the suspected metastasis disappeared. At the time of writing, she has survived for more than 13 months, and her quality of life has improved significantly, to the satisfaction of the patient and her family. The patient is able to eat normally and lead a normal life with some assistance, without significant weight loss. Conclusions: Although rare, STS is a serious invasive complication of breast cancer surgery. To increase their relative survival time, patients with BCRL need to identify and thoroughly investigate rapidly progressing skin lesions, and undergo timely surgery.

Tumor-like disorder of the brachial plexus region in a patient with hemophilia: A case report.

BACKGROUND: Various tumors and tumor-like disorders, originating from the neural sheath, as well as other types, may affect the brachial plexus region. Due to the infrequent presentation, brachial plexus palsy caused by spontaneous hematoma in patients with hemophilia might miss the treatment by early surgical decompression and progress to permanent nerve damage. CASE SUMMARY: The case reported here was a 30-year-old man with hemophilia, as well as both sensory and motor dysfunction of the left upper extremity. A presumptive diagnosis of brachial plexus tumor was initially made, which was subsequently confirmed to be an organized chronic hematoma rather than a neoplasm. The hemophilia-induced expanding hematoma compressing the brachial plexus was considered to be the main reason for the patient's complaints. The clinical symptoms were alleviated and the involved nerves partially recovered at a follow-up of 1 year. CONCLUSION: Early surgical intervention is crucial and it seems to be an essential precondition for recovery of nerve function in brachial plexus lesions.

Tissue-engineered bones with adipose-derived stem cells - composite polymer for repair of bone defects.

Background: Development of alternative bone tissue graft materials based on tissue engineering technology has gradually become a research focus. Engineered bone composed of biodegradable, biosafe and bioactive materials is attractive, but also challenging. Materials & methods: An adipose-derived stem cell/poly(L-glutamic acid)/chitosan composite scaffold was further developed for construction of biodegradable and bone-promoting tissue-engineered bone. A series of composite scaffold materials with different physical properties such as structure, pore size, porosity and pore diameter was developed. Results: The composite scaffold showed good biodegradability and water absorption, and exhibited an excellent ability to promote bone differentiation. Conclusion: This type of biodegradable scaffold is expected to be applied to the field of bone repair or bone tissue engineering.

In recent years, the application of bone graft materials in bone defect repair has become a research hotspot. Engineered bone composed of biodegradable, biosafe and bioactive materials is attractive but also challenging. A composite scaffold composed of adipose-derived stem cells and two polymers was developed for construction of biodegradable and bone-promoting tissue-engineered bone. A series of composite scaffold materials with different physical properties was prepared and studied. The composite scaffold showed good biodegradability and water absorption, and exhibited excellent ability to promote bone differentiation ­ that is, bone defect repair function. This kind of biodegradable scaffold is expected to be applied to the field of bone repair or bone tissue engineering.

Preparation of animal model of chicken for lymphatic anastomosis technique training.

Background: To discuss the preparation of a simple and practical animal model for lymphatic anastomosis technology training. At present, there is no widely used animal model for training lymphatic anastomosis. Methods: The neck of chicken is long enough, and there are abundant lymphatic lymph nodes. The caliber of lymphatic vessels in the neck of chicken is similar to the caliber of lymphatic vessels in human limbs, so multi-stage anastomosis practice can be carried out. The lymphatic vessels of chicken are easier to stain and fully exposed, which meets the requirements of lymphatic vein anastomosis model. This model allows for training of end-to-end anastomosis (LVA), end-to-side anastomosis, and lymph node vein anastomosis under microscope to be carried out. In this study, the trainees were divided into six groups, with five animals in each group. After 14-28 days of training, the average training was 21 days. Data were statistically analyzed by SPSS15. Results: Obvious and clear lymphatic staining could be obtained after animal modeling, and the success rate of dissecting and staining lymphatic vessels under microscope could reach 100%. After training, the trainees could perform the anastomosis of lymphatic vessel and vein and lymph node vein under ultra-microscopic conditions, and the immediate patency rate of the anastomosis of the trainees can reach 80% during the examination. Conclusions: This animal model can be used for effective lymphatic vein anastomosis training, which is a simple, practical, and effective microscopic lymphatic anastomosis technology training model.