Anticancer research最新文献

Background/aim: Surgery is the primary treatment for melanoma, but some patients refuse it, potentially affecting survival. This study examines demographic and clinical factors associated with surgery refusal to inform targeted interventions.

Patients and methods: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to analyze factors linked to surgery refusal in melanoma patients. Demographic, clinical, and treatment characteristics were compared using Pearson Chi-square and Wilcoxon Rank Sum tests.

Results: Among 1,048,575 melanoma patients considered for surgery, 605 (0.1%) refused. Those who refused were older (mean age 75.8 years), had more comorbidities, and were more likely to be racial minorities or socioeconomically disadvantaged (p<0.001). Survival analysis showed a lower overall survival rate in the refusal group, with 66.0% alive at follow-up compared to 78.3% in the non-refusal group.

Conclusion: Surgery refusal in melanoma patients is associated with advanced age, frailty, and socioeconomic disadvantages, including racial minority status and lower income. Addressing these barriers may improve treatment acceptance and survival outcomes.

Background/aim: Locally advanced rectal cancer (LARC) with adjacent organ invasion presents significant surgical challenges, particularly in achieving negative circumferential resection margins (CRM). Transanal total mesorectal excision (TaTME) offers improved visualization and dissection in the deep pelvis, potentially enhancing oncologic and functional outcomes. This study evaluates the feasibility, oncologic safety and the possibility of anal preservation of TaTME in cT4b rectal cancer requiring combined organ resection.

Patients and methods: This retrospective study analyzed 19 patients with cT4b rectal adenocarcinoma undergoing combined organ resection between January 2015 and December 2023. Surgical approaches included TaTME (n=4) and conventional transabdominal techniques (n=15). Patients requiring total cystectomy or combined uterine and posterior vaginal wall resection were included. Surgical parameters, postoperative complications, and oncologic outcomes were compared. Statistical analyses were conducted using Fisher's exact test and Student's t-test, with significance set at p<0.05.

Results: TaTME demonstrated superior anorectal preservation rates (100% vs. 33%; p=0.1772) and comparable surgical outcomes, including operative time (585 min vs. 550 min) and blood loss (397 ml vs. 380 ml). Negative distal margins were achieved in all cases, although tumor-positive resection surfaces were observed in 13% of conventional cases (p=0.0787). Local recurrence was absent, with minimal distant metastases reported.

Conclusion: TaTME is a safe and effective approach for cT4b rectal cancer, enabling enhanced pelvic dissection and anorectal preservation. While technical challenges remain, TaTME complements conventional methods, particularly for low rectal tumors, offering potential for improved functional outcomes and quality of life in select patients.

Background/aim: 5-Fluorouracil (5-FU) plays a major role in the treatment of gastric cancer (GC), and overcoming resistance to this drug remains a critical challenge. This study aimed to identify genes associated with resistance to 5-FU in GC.

Materials and methods: Gene expression levels were analyzed in 5-FU-resistant MKN-45/F2R cells compared to the parental MKN-45 strain before and after 5-FU treatment (24 and 72 h). Among the consistently over-expressed genes, those with high expression were further investigated for their roles in resistance and expression patterns in GC tissues.

Results: NPC1L1, a protein hypothesized to influence 5-FU resistance, did not exhibit resistance-related effects in tested cells. Its expression was subsequently studied in gastric cells. NPC1L1 was detected in the stomach, jejunum, duodenum, and liver, with increased mRNA levels in several GC samples. Immunostaining of samples from 95 GC patients revealed that 39 (41.0%) exhibited ≥10% higher NPC1L1 expression. Patients with NPC1L1-positive tumors had poorer prognoses than those with negative tumors.

Conclusion: NPC1L1 is expressed in both normal gastric tissues and GC tissues, with elevated levels at invasive sites associated with poor prognosis.

Background/aim: The aim was to analyze patterns of care, e.g., fractionation of radiotherapy and treatment completion, and prognostic factors for survival in patients irradiated for bone metastases who had excellent Eastern Cooperative Oncology Group (ECOG) performance status (PS), defined as ECOG PS 0.

Patients and methods: A retrospective analysis was performed (2010-2024, n=1,244 radiotherapy courses) that included patients with bone metastases treated with conventional palliative or stereotactic single- or multi-fraction regimens (SBRT).

Results: Patients with ECOG PS 0 (n=129, 10%) had 0% 30-day mortality, 99% 3-months survival, and 83% 12-months survival. Only three of 129 (2%) did not complete radiotherapy. Most patients had prostate or breast cancer with bone-only metastases. In restricted analysis without inclusion of blood test results, five significant predictors of unfavorable survival emerged: steroid medication, no continuation of systemic therapy, progressive disease outside of the irradiated target volume(s), adrenal gland metastasis, and prescription of fewer radiotherapy fractions. With blood tests included, the final multivariate model suggested that survival varied with lactate dehydrogenase (strata: normal/elevated), adrenal gland metastases (yes/no), progressive disease outside of the irradiated target volume(s) (yes/no), and fraction number (>10/≤10).

Conclusion: Many patients with ECOG PS 0 experience long-term survival, influenced by disease behavior and choice of fractionation, among others. The impact of fractionation was due to imbalances in baseline characteristics, e.g., proportion of patients with de novo hormone-sensitive prostate cancer with low-volume disease receiving fractionated radiotherapy to both prostate and bone metastases. No clear impact of equivalent radiation dose in 2-Gy fractions on survival emerged.

Background/aim: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and treatment outcomes for advanced disease remain suboptimal. Immunotherapy, particularly atezolizumab plus bevacizumab, has shown promise in improving survival. This study aimed to evaluate the prognostic value of ¹⁸F-fluorocholine positron emission tomography/computed tomography (FCH PET/CT) in patients with unresectable HCC undergoing this combination therapy.

Patients and methods: This prospective study included 29 patients with unresectable HCC treated with atezolizumab plus bevacizumab. All participants underwent FCH PET/CT prior to treatment. The tumor-to-liver ratio (TLR) of FCH uptake was calculated and analyzed as a potential prognostic biomarker. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis, and Cox proportional hazards models evaluated associations between TLR and clinical outcomes.

Results: Patients with higher TLR values of FCH uptake (cutoff: 1.36) demonstrated significantly shorter PFS compared to those with lower TLR values (hazard ratio=4.29, p=0.032). Other clinical variables, including age, sex, tumor size, and viral hepatitis status, were not significantly associated with PFS.

Conclusion: TLR of FCH uptake is a valuable non-invasive biomarker for predicting PFS in unresectable HCC patients treated with immunotherapy.

Background/aim: Drug-resistance in osteosarcoma results in a very poor clinical prognosis and has been a recalcitrant problem over many decades. We have previously reported the development of super methotrexate (MTX)-resistant osteosarcoma cells (143B-MTX^SR), selected from parental 143B osteosarcoma cells (143B-P) 143B-MTX^SR cells were previously selected by culturing the cells with increasing concentrations of MTX, resulting in osteosarcoma cells which are 5,500 times more MTX-resistant than the parental cells, due to extreme over-expression of dihydrofolate reductase (DHFR). In the present study, the potential therapeutic efficacy of methionine restriction, using recombinant methioninase (rMETase), was explored to overcome super MTX-resistant osteosarcoma cells.

Materials and methods: Previously-selected 143B-MTX^SR cells were used for the present study. Sensitivity to methionine restriction by rMETase was determined using the WST-8 assay and compared between 143B-MTX^SR and parental 143B-P cells.

Results: 143B-MTX^SR cells (rMETase IC₅₀: 0.38 U/ml) were very sensitive to methionine restriction by rMETase, very similar to 143B-P (rMETase IC₅₀: 0.36 U/ml).

Conclusion: rMETase overcame a 5,500-fold MTX-resistance of osteosarcoma cells. The present results suggest methionine restriction by rMETase can be a potential clinical strategy to overcome recalcitrant drug-resistance in osteosarcoma.

Background/aim: Mesonephric adenocarcinoma in males is an exceptionally rare malignancy arising from mesonephric remnants. Accurate diagnosis requires thorough histopathological and molecular analysis.

Case report: A 33-year-old male presented with right lower quadrant pain, and imaging revealed a pelvic mass compressing adjacent structures. Biopsy confirmed mesonephric adenocarcinoma. Genetic profiling revealed mutations in tuberous sclerosis complex 2 (TSC2) and phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha (PIK3CA), offering potential for targeted therapy.

Conclusion: This case highlights the diagnostic and therapeutic challenges of mesonephric adenocarcinoma in males. Molecular profiling provided insights into tumor biology and potential targeted treatments. Multidisciplinary collaboration and surveillance remain essential for managing rare malignancies effectively.

Background/aim: Cholinesterase (ChE) is important for estimating nutritional status and can be easily measured. This study aimed to investigate the effect of ChE on the short- and long-term prognoses of elderly patients with colorectal cancer.

Patients and methods: This study included 120 elderly patients who underwent scheduled surgery for colorectal cancer. ChE is a biomarker that can be easily measured using blood tests. The optimal cut-off level of ChE was determined using receiver operating characteristic analysis. We investigated the relationship of ChE with disease-free and overall survival using univariate and multivariate analyses.

Results: Seventy-two (60%) patients had low ChE levels (<255 U/l). In the multivariate analysis, low ChE (p=0.04) was an independent and significant predictor of postoperative complications. Low ChE (p=0.049), low prognostic nutritional index (p=0.04), and lymph node metastasis (p<0.01) were independent and significant prognostic predictors of poor disease-free survival. American Society of Anesthesiologists Physical Status 3 (p<0.01), low ChE (p<0.01), and lymph node metastasis (p<0.01) were independent and significant predictors of poor overall survival.

Conclusion: ChE level is a significant predictor of short- and long-term outcomes in elderly patients undergoing scheduled surgery for colorectal cancer.

Background/aim: To assess the effectiveness of circulating tumor cells (CTCs) in proposing second-line treatments for metastatic colorectal cancer (mCRC).

Patients and methods: We analyzed CTCs from 21 patients (first group) with mCRC, for whom first-line treatment regimens were ineffective. CTCs were isolated and used for chemo-sensitivity/viability assays on several chemotherapeutic drugs. Based on these assays, a second-line treatment was recommended for each patient. Using overall survival (OS) as primary endpoint, statistical analysis was performed, comparing the survival of a group of 21 mCRC patients (first group) with the survival of 12 mCRC patients treated only with best supportive care (BSC) (second group), as well as with the survival estimated by meta-analysis of the BSC summary statistics (medians) published in various papers and clinical trials. Furthermore, the statistical significance of the difference between the two groups was examined by applying statistical tests that can deal efficiently with small datasets, non-proportional hazard patterns, and crossing curves, such as K-sample omnibus, MaxCombo, multiple-direction, and weighted log-rank tests.

Results: The median OS (mOS) for the first group (9 months) was found longer than the mOS of the BSC group (about 5 months). This result was further verified since the weighted mOS, estimated by meta-analysis, was found at 5.15 months. This difference was found statistically significant for central and late hazards.

Conclusion: The preliminary results indicate that treatment based on CTCs' response in vitro prolongs mOS of mCRC patients compared with BSC patients, whereas a beneficial effect is gained for the prediction of treatment response in mCRC.

Background/aim: Cervical intraepithelial neoplasia (CIN) III/high-grade squamous lesions (HSIL) remains a significant challenge during pregnancy. Current data on the course of disease are contradictory, with cases of progression to cervical cancer (CC) during pregnancy being observed. Evidence suggests that the expression of L1 capsid protein is associated with a favorable prognosis in non-pregnant women. The aim of this study was to evaluate L1 expression in pregnant women with CIN III/HSIL.

Patients and methods: Between 2008 and 2021, the conventional PAP-smears from pregnant women were retrospectively analyzed for the expression of L1. Only women with histologically confirmed CIN III/HSIL during pregnancy were included.

Results: A total of 161 women were included in this study; among them, 32 women (19.9%) had regressive disease postpartum. The majority of women (n=123, 76.4%) had persistent disease. In six cases, invasive CC was histologically proven postpartum (3.7%). In 113 women (70.2%) the PAP-Smears were L1- and 29.2% (n=48) of women were L1+. The rates of regression for L1+ were higher than for L1-, 25% vs. 17.7%, respectively. Rates for persistence were similar, at 75% and 78%, respectively. All cases of progression to CC were L1 negative during pregnancy.

Conclusion: In pregnant women, the rates of regression were higher in L1+ CIN III/HSIL cases. All women who progressed to CC were L1-. Therefore, detecting L1 expression could serve as a valuable test to rule out progression to CC in pregnant women. This approach may provide reassurance to women, allowing them to continue their pregnancies with reduced fear and anxiety about CIN III/HSIL during pregnancy.