BMC Cancer最新文献

Background: Breast cancer is a major health concern worldwide, and Ki-67 level index is a prognostic factor that indicates tumor proliferation and predicts survival outcomes. However, the standard Ki 67 cut-off level varies between local laboratories, and in Thailand, there is no established optimal cut-off level.

Objective: This study aimed to determine the optimal cut-off point for Ki-67 expression and investigate the association between Ki-67 levels and other prognostic factors with 8-year overall survival.

Method: A retrospective review of Ki-67 levels was conducted in non-metastatic breast cancer patients treated at Maharaj Nakorn Chiangmai hospital from January 2013-December 2015, including 507 breast cancer patients.

Results: The ROC curve analysis identified the optimal Ki-67 cut-point as ≥ 30%, with 75% sensitivity and 48.85% specificity. Age over 60 was associated with higher mortality regardless of cancer stage. Locally advanced staging, nodal involvement, Ki-67 ≥ 30%, and triple-negative subtype correlated with poorer survival. Even after adjustments, these factors remained significant in prognostic evaluation. Chemotherapy notably improved survival, especially in high Ki-67 (≥ 30) patients. However, this effect was not seen in low Ki-67 patients. High Ki-67 patients receiving chemotherapy showed improved survival in early-stage, node-negative cases compared to those who did not receive chemotherapy. HER2-positive patients with high Ki-67 benefited from chemotherapy, but statistical significance was not reached in hormone-positive patients.

Conclusion: This study identified the optimal cut point for Ki-67 in Northern Thailand as 30%. Patients with KI-67 above 30% show significantly lower 8-year survival rates. This is especially relevant for low-risk patients, like those with hormonal subtypes or early-stage nodal negativity. In these cases, KI-67 becomes crucial for treatment decisions. Our study not only aids Northern Thailand's understanding but also aligns with broader research, emphasizing KI-67's vital role in planning treatment for low-risk breast cancer patients.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin carcinoma. The pathogenesis involves Merkel cell polyomavirus (MCPyV) and ultraviolet radiation exposure. Studies on MCC in Turkey are scarce, with essential data on local etiopathogenic and prognostic factors still lacking. We aimed to analyze the clinical and histopathologic features, biomarkers, and to evaluate these findings alongside Turkish literature to infer the etiopathogenesis, prognosis, and possible treatment options for the disease.

Methods: We analyzed the clinicopathologic features of 7 MCC patients diagnosed at the Pathology Department of Pamukkale University between 2003 and 2024 in this retrospective study. Clinical data was retrieved from the hospital's electronic records. Formalin-fixed, paraffin-embedded tumor specimens stained with hematoxylin-eosin were examined microscopically. MCPyV, Retinoblastoma 1 (RB1), p53, PRAME, PD-L1, and MMR proteins were evaluated immunohistochemically. Research on MCC from Turkey was sourced from Turkish databases (ULAKBIM, Turkiye Atif Dizini, DergiPark, Turk Medline) and international databases (Pubmed, Google Scholar, Scopus, Embase). The literature review identified original research, case reports, theses, and conference presentations.

Results: The patients in our series, all aged over 50 (mean age 76.1 ± 14.8), with a slight predominance of one gender (F: M = 1.33:1). During a mean follow-up of 16.1 months, 42.9% (3/7) had lymph node metastases, and 57.1% (4/7) showed distant metastases. PRAME was positive in 42.9% of the cases (3/7). The total number of MCC cases reported from Turkey was estimated at 227 ± 46, with MCPyV status available in a subset, showing a positivity rate of 70.3%. PD-L1 expression was observed in the tumor microenvironment in 55% of virus-positive MCC cases from Turkey.

Conclusions: The 9% incidence of gluteal localization in Turkish MCC cases, considering its geographical significance, is noteworthy. Notably, all MCC cases from Turkey in which microsatellite instability status has been assessed were found to be microsatellite stable. PRAME should be investigated in larger series for its potential role in the shared oncogenic pathways of MCC.

Background: Chimeric antigen receptor (CAR) engineered natural killer (NK) cells have shown their efficacy and superiority against cancer and possess the potential to become off-the-shelf immunotherapy products. Nonetheless, some challenges associated with CAR-NK cells still exist including inhibitory receptor engagement, antigen escape, and inadequate activation.

Methods: Given this, based on the concept of synthetic biology, we rationally designed a novel dual-targeted CAR (dtCAR), primarily comprising PD-L1 nanoantibody (PD-L1^Nb) and NKG2D as the ectodomain, transmembrane and cytoplasmic domains (CP) of CD28, and the CP of 4-1BB and CD3ζ. NK92 cells were engineered to express this third-generation of dtCAR. We then elucidated the role of dtCAR-modified NK92 cells against cancer cells in vitro and in vivo.

Results: In vitro, the dtCAR-NK92 cells could still retain the characteristics of parental NK cells and exhibit improved NK cell cytotoxicity and produce more cytokines than NK92 cells when they were co-cultured with human lung cancer H1299 cells. Notably, the dtCAR-NK92 cell therapy might elicit clearance of H1299 cells by pyroptosis. Additionally, dtCAR-NK92 cells could considerably inhibit tumor growth in the human lung cancer H1299 cell tumor model.

Conclusions: We confirmed that expression of dtCAR enhanced NK92-cell activation and killing in vitro and in vivo, which provides a novel immunotherapeutic strategy for using NK-tailored CAR-engineered NK92 cells to treat human lung cancer.

Background: In Japan, the proportion of elderly gastric cancer patients is increasing. Although surgery in patients aged ≥ 80 years is relatively safe, postoperative pneumonia often occurs, reducing quality of life and being fatal. We retrospectively investigated the risk factors for pneumonia after gastrectomy in elderly patients at our hospital.

Methods: Between 2010 and 2019, 113 patients aged ≥ 80 years underwent gastrectomy for gastric cancer at our hospital. Of these, 88 patients were retrospectively investigated, excluding 25 patients who did not receive sufficient postoperative follow-up. The diagnosis of pneumonia was based on chest CT findings. Univariate and multivariate analyzes for risk factors of pneumonia were performed using the Cox proportional hazards model.

Results: The patients were aged 80-93 years (median 83 years) and consisted of 63 males and 25 females. The surgical procedures included distal gastrectomy in 54, total gastrectomy in 25, proximal gastrectomy in two, and local resection in seven. Postoperative pneumonia was observed in 38 patients. Seventeen of them died from pneumonia. The time to onset of pneumonia was 0.2-144.6 months (median 12.0 months), and the median observation period for patients without pneumonia was 38.8 months. Multivariate analysis revealed that age, Geriatric Nutritional Risk Index, respiratory history, and extent of gastrectomy (total vs. distal: hazard ratio 3.91, 95% confidence interval 1.69-9.02) were independent pneumonia factors.

Conclusions: In patients aged ≥ 80 years, age, low nutritional status, respiratory history, and total gastrectomy were risk factors for postoperative pneumonia.

Background: The relationship between vasectomy and the risk of prostate cancer (PCa) remains unclear, with observational studies reporting inconsistent results. To clarify this ambiguity, we embarked on a comprehensive investigation comprising both a meta-analysis and a Mendelian randomization (MR) study. This dual approach aimed to thoroughly examine not only the association but also the causality between undergoing a vasectomy and the subsequent risk of PCa.

Methods: Our systematic review meticulously examined cohort studies published until January 2024, employing a random effects model for the computation of relative risks (RR) and their 95% confidence intervals (CI). For MR Analysis, we leveraged aggregated data from the IEU Open GWAS database, investigating the correlation between genetic predisposition to vasectomy and PCa. We chose single nucleotide polymorphisms (SNPs) of European descent as instrumental variables (IVs) for this analysis. The primary method for calculating the odds ratios (ORs) and their 95% CIs was inverse variance weighting (IVW). Through sensitivity analysis, we confirmed the robustness of our findings.

Results: Our investigation synthesized data from 19 cohort studies, encompassing over four million participants. The combined analysis revealed a statistically significant link between vasectomy and an elevated risk of PCa across any grade (RR = 1.09; 95%CI: 1.05-1.14; P = 0.001; I² = 83.3%). This association was observed for both localized PCa (RR = 1.08; 95% CI: 1.04-1.13; P < 0.001; I² = 48.8%) and advanced PCa (RR = 1.07; 95% CI: 1.01-1.13; P = 0.016; I² = 0%). Nonetheless, the discovery cohort MR Analysis indicated no genetic causal link between vasectomy and PCa (OR = 0.067; 95%CI = 0.002-1.535; P = 0.09). A validation set in the Finnish population confirmed the robustness of the results. This conclusion remained consistent even after controlling for variables such as prostate-specific antigen (PSA) testing and body mass index (BMI), suggesting that while a statistical association exists, the genetic evidence does not support a causal relationship.

Conclusion: The cumulative analysis indicates a possible elevated risk of PCa in patients who have had a vasectomy. However, MR Analysis has not confirmed a direct causal link between vasectomy and PCa. This suggests that the association observed may not stem from direct causation, allowing for the continued consideration of vasectomy as a viable long-term contraceptive choice. Further research is imperative to uncover any factors that could potentially link vasectomy to an increased risk of prostate cancer, aiming to provide a more comprehensive understanding of the implications.

Background: Metastatic colorectal cancer (mCRC) poses a high rate of morbidity and mortality despite various treatment advances. Cetuximab, an anti-EGFR, has shown promising efficacy in improving outcomes when combined with chemotherapy. Understanding its efficacy is essential for optimizing treatment strategies in mCRC. This systematic review and meta-analysis aims to evaluate the effectiveness of combining cetuximab with chemotherapy in mCRC.

Methods: PubMed and Google Scholar were systematically searched following the benchmarks indicated by PRISMA. The primary outcomes of the study were progression-free survival (PFS) and overall survival (OS). Statistical analyses were executed using Stata version 16.

Results: The meta-analysis encompassed 25 studies involving 3788 mCRC patients. The median age spans from 18 to 77 years. The cetuximab plus chemotherapy exhibited a higher PFS and OS with a significant difference (PFS: HR = 0.79, 95% CI = 0.63-0.96, p < 0.01, I² = 38% and OS: HR = 0.78, 95% CI = 0.60-0.91, p < 0.01, I² = 47%) compared to the control group. Subgroup analysis based on randomized controlled trials demonstrated consistent treatment effects for PFS (HR = 0.77, 95% CI = 0.62-0.93) and OS (HR = 0.76, 95% CI = 0.61-0.88) in the cetuximab treatment group.

Conclusions: Combining cetuximab with chemotherapy offers a potential benefit in improving survival outcomes for metastatic colorectal cancer patients, as indicated by this study. These results suggest that cetuximab may be a valuable addition to mCRC treatment strategies, warranting further clinical investigation and integration into standard care.

Background: One-year of immune checkpoint inhibitor (ICI) treatment after concurrent chemoradiation (CCRT) in unresectable stage III non-small cell lung cancer (NSCLC) is a standard of care. The precise predictive biomarkers are under investigations either immunological markers or clinical characteristics. Here, we explored immune repertoire of T cell receptor β-chain (TCRβ) during ICI treatment.

Methods: During August 2019 and September 2021, stage III NSCLC, post CCRT patients from Ramathibodi Hospital was enrolled. All patients were treated by durvalumab after CCRT. Blood samples were collected together with clinical data and tumor assessment every 3-4 months until disease progression or discontinuation of treatment due to adverse events. CDR3 region and TCRΒ polymorphisms was explored by RNA sequencing using Next-Generation Sequencing (NGS) TCR beta short-read assay. Bioinformatic analysis was performed to analyze clonal diversity, TCR convergence frequency and the Shannon diversity from each timepoint. Immune repertoire and clinical correlation were explored using Spearman's correlation and Pearson's correlation. RStudio software version 2021 build 372 was used for analyses. A significance level was at P < 0.05.

Results: Forty-four blood samples from 12 patients were analyzed. Mean duration of durvalumab treatment was 284 days. After durvalumab treatment, increasing of TCR convergence frequency was found compared to baseline (R = 0.36). Interestingly, it was also significantly higher in non-progressive disease (non-PD) patients compared with progressive disease (PD) patients (P = 0.011). Furthermore, Shannon diversity was higher increasing in PD patients compared with non-PD patients. Taken together, our study found that increasing of TCR convergence with less T-cell diversity in non-PD patients probably demonstrated a T cell-specific clonal expansion response to durvalumab treatment in this population.

Conclusions: TCRβ repertoire is the potential biomarker for predicting durvalumab treatment response in post CCRT stage III NSCLC patients. However, a larger cohort with long-read assay should be explored.

Background: Female breast cancer, cervical cancer, uterine cancer, and ovarian cancer (FBCUO) pose a significant threat to global public health. Data from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 provide critical insights that can guide the understanding and management of these cancers. Our study aims to offer comprehensive global, regional, and national estimates of the FBCUO cancer burden and its attributable risk factors from 1990 to 2021, as well as project future incidence trends up to 2050. These projections are essential for developing targeted prevention and control strategies, thereby informing more effective public health interventions.

Methods: Incidence, age-standardised incidence rate (ASIR), deaths, age-standardised mortality rate (ASMR), disability-adjusted life years (DALYs), age-standardised rate of DALYs (ASDR), and the burden due to risk factors associated with FBCUO cancer were analysed from 1990 to 2021, and the Bayesian APC model was utilized for forecasting future epidemiological trajectories. All statistical analyses were performed using Join-point software (version 4.9.1.0).

Results: Between 1990 to 2021, the global incidence, death, and DALYs, of female breast, cervical, uterine and ovarian cancer both to varying degrees of elevation. However, the ASMR and ASDR both showed a decreasing trend for FBCUO cancer. In 2021, diet high in red meat was a major risk factor for female breast cancer DALYs, but the attributable ASDR for diet high in red meat decreased from 1990 to 2021. Unsafe sex was the leading risk factor for cervical cancer DALYs, high body-mass index were the leading risk factor for uterine cancer and ovarian cancer. Projections indicate a global increase in the total number of female breast cancer and ovarian cancer cases from 2021 to 2050. In contrast, both cervical cancer and uterine cancer are expected to show downward trends over the same period.

Conclusions: The burden attributable to FBCUO cancers has increased significantly in female populations from 1990 to 2021, underscoring the urgent need for targeted measures to mitigate this trend. Meanwhile, Annual Percentage Change (APC) analysis indicates that the age-standardized incidence rates (ASIR) for female breast and ovarian cancers may continue to rise from 2022 to 2050. This projection highlights the importance of timely interventions to address these growing challenges.

Background: The technical challenges and safety issues involving laparoscopic D2 lymphadenectomy plus complete mesogastric excision (D2 + CME) for high body mass index (BMI) patients are still unknown. This study was conducted to compare the short-term outcomes of laparoscopic D2 + CME and D2 lymphadenectomy in distal gastric cancer patients of different BMI status.

Methods: We retrospectively analyzed the data of patients with gastric cancer who underwent laparoscopic-assisted distal gastrectomy (LADG) at our center between 2019 June and 2023 September. Patients who underwent traditional laparoscopic D2 lymphadenectomy were divided into the D2 group, while patients undergoing laparoscopic D2 + CME were divided into the D2 + CME group. In each group, patients were further subdivided based on their BMI into the high BMI group (H-BMI, BMI ≥ 25) and normal BMI (N-BMI, BMI<25) group. A comparison was made between the characteristics of patients and their short-term outcomes in the two subgroups, respectively. Propensity score matching (PSM) at 1:1 ratio was performed to further assess the short-term outcomes of patients with high BMI in two groups.

Results: AII the qualified patients were divided into the D2 group (n = 329) and D2 + CME group (n = 261). In the subgroup analysis of early surgical outcomes of the D2 group, the high BMI subgroup had longer surgery time (p = 0.007), more blood loss (p = 0.006) and longer time to first flatus (p = 0.001), compared to the normal BMI subgroup. Conversely, in the D2 + CME group, significant differences were not observed in early surgical outcomes between the two subgroups(p > 0.05). PSM yielded 44 high BMI patients with comparable baseline characteristics into the A group and the B group. Compared to the A group, patients with high BMI in the B group who received laparoscopic D2 + CME had shorter surgery time(p<0.001), less blood loss(p = 0.004), more retrieved lymph nodes (LNs) (p = 0.016). No statistical differences were observed in terms of the first flatus time, pT stage, pN stage, pathological stage(pStage), vascular invasion, postoperative complications, or postoperative hospital stay(p > 0.05).

Conclusion: Our findings suggest the high BMI status had a significant impact on the early surgical results of laparoscopic conventional D2 lymphadenectomy. However, laparoscopic D2 + CME was unaffected by a high BMI. In addition, patients with high BMI benefit more from laparoscopic D2 + CME in terms of short-term outcomes. Laparoscopic D2 + CME is a recommended technique for distal gastric cancer patients with high BMI, which deserves further study and promotion.

Background: Though relatively rare, bone tumors significantly impact patient health and treatment outcomes.

Objective: This systematic review analyzes the incidence, types, survival rates, and risk factors associated with bone tumors, including both benign and malignant forms.

Methods: This systematic review was conducted using the keywords "bone tumors," "epidemiology," "benign bone tumors," "malignant bone tumors," "osteosarcoma," "Ewing sarcoma," "chondrosarcoma," "risk factors," and "survival" in electronic databases including PubMed, Scopus, Web of Science, and Google Scholar from 2000 to 2024. The search strategy was based on the PRISMA statement. Finally, 9 articles were selected for inclusion in the study.

Results: The systematic review highlights that primary bone tumors can be classified into benign and malignant types, with osteosarcoma being the most prevalent malignant form, particularly among adolescents and young adults. The epidemiology of bone tumors is influenced by factors such as age, gender, geographic location, and genetic predispositions. Recent advancements in imaging techniques have improved the detection of these tumors, contributing to an increasing recognition of their prevalence. Data shows that the limited-duration prevalence of malignant bone tumors has increased significantly. This increase is from 0.00069% in 2000 to 0.00749% in 2018, indicating an increasing recognition and diagnosis of these rare tumors over time. Survival rates vary significantly by tumor type, with approximately 50-60% for osteosarcoma and around 70% for Ewing's sarcoma, though these rates decrease with metastasis. Key risk factors identified include genetic predispositions such as Li-Fraumeni syndrome and TP53 mutations, environmental exposures like radiation, and growth patterns related to height.

Conclusion: The review highlights the importance of early diagnosis and treatment intervention, as survival rates are significantly better for patients with localized disease compared to those with metastatic conditions. The observed variations in survival rates across different tumor types underscore the need for tailored treatment strategies. Key risk factors include genetic predispositions and environmental exposures, highlighting the need for targeted screening and ongoing research to enhance diagnostic accuracy and treatment strategies.