World Journal of Oncology最新文献

Since its discovery in 1992, mesothelin (MSLN) has generated significant interest as a therapeutic target. A number of characteristics make it ideal for this purpose. First, it is not expressed on the parenchyma of any vital organs. Second, it is differentially expressed on a number of cancer types that have relatively poor prognosis and lack effective systemic options. Third, it is expressed on the cell membrane making it accessible to large molecule targeted therapies. However, unlike other drug targets that have been exploited for therapeutic benefit, the precise function of MSLN, why it is expressed in certain cancers, and its biological role have not been clearly elucidated. Here the existing literature on the cellular function and expression patterns of MSLN across tumor types is reviewed in order to gain further understanding of this intriguing molecule. In doing so, we conclude that there remains significant ambiguity surrounding its function and role in cellular and tumor biology. Furthermore, the expression of MSLN and its relation of prognosis seems to depend on the type of tumor. Finally, the unified mechanism by which MSLN acts as a protein that conveys tumor aggressiveness remains elusive. What is clear is that there is much yet to be discovered in this realm and doing so may have large implications for treatment of otherwise lethal malignancies.

Background: Although genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption.

Methods: Using the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI).

Results: Offspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48).

Conclusion: Smokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.

Background: Metastatic colorectal cancer (mCRC) is often treated with a mFOLFOX6 regimen. The 5-fluorouracil (5-FU) bolus is often omitted from the regimen to reduce the risk of hematological adverse events (AEs) in patients with poor performance status. We aimed to investigate the incidence of hematological AEs in Asian patients with mCRC who were treated with the mFOLFOX6 with and without 5-FU bolus dosing.

Methods: This retrospective chart review was conducted at King Chulalongkorn Memorial Hospital, Thailand from June 2021 to June 2022. The primary endpoints were hematological AEs. Secondary endpoints were any AEs. The comparison of continuous data was conducted with an independent t-test. The Chi-squared test was used to compare categorical data.

Results: From 110 patients, we found that hematological and non-hematological AEs of any grade in the two groups were not significantly different. However, patients in the bolus arm had a significantly lower absolute neutrophil count (ANC) than those in the non-bolus arm (mean difference = 43.13 (95% confidence interval (CI): 20.74, 65.51), P-value = 0.0002). A subgroup analysis in patients who received first-line treatment with mFOLFOX6 showed that the bolus arm had a significantly lower ANC (mean difference = 46.01 (95% CI: 19.99, 72.03), P-value = 0.0007).

Conclusions: mCRC patients who were treated with bolus 5-FU had lower ANC. The 5-FU bolus omission from the mFOLFOX6 regimen may be required in patients with a high risk of neutropenia.

Spinal cord compression caused by cancer metastasis is a medical emergency that should be managed positively. Both multiple myeloma and lung cancer can lead to metastatic deposits in the spinal column to induce compression of the spinal cord. However, co-occurring multiple myeloma and lung cancer in a single patient causing spinal cord compression are rarely reported in the literature. We describe a case of a 61-year-old female with multiple myeloma and lung cancer whose radiologic characteristics of spinal cord compression mimicked those of metastatic lung cancer. Finally, the diagnosis was multiple myeloma. We showed the systematic imaging manifestations of metastatic multiple myeloma and discussed their therapeutic management.

Background: Robotic gastrectomy (RG) has been increasingly used for treatment of gastric cancer in the United States. However, it is unknown if there has been a nationwide improvement of short-term safety outcomes and oncological quality metrics over time.

Methods: We used the National Cancer Database to identify patients who underwent major gastrectomy from 2010 through 2018. The short-term safety outcomes and oncological metrics were compared between cases of open gastrectomy (OG), laparoscopic gastrectomy (LG), and RG. We also compared the indications and outcomes of RG between the three periods (2010 - 2012, 2013 - 2015, and 2016 - 2018).

Results: Of the 22,445 patients included, 1,867 (8%) underwent RG. Number of RG continued to increase from only 37 cases performed in 2010 to 412 cases performed in 2018. The number of lymph nodes (LNs) examined (OG, 16; LG, 17; and RG, 19) and the R0 rate (OG, 88%; LG, 92%; and RG 94%) were better for RG than for OG or LG (P < 0.001). In the RG group, the number of LNs examined (first period, 15; third period, 18; P < 0.001), R0 rate (first period, 88.6%; third period, 91.1%; P < 0.001), length of hospital stay (first period, 9 days; third period, 8 days; P < 0.001), 30-day readmission rate (first period, 10.1%; third period, 7.9%; P < 0.001), and 90-day mortality (first period, 7.3%; third period, 6.0%; P = 0.003) continued to improve cohort over time. The ratio of the robotic cases performed in academic institutions gradually increased (first period, 48.6%; third period, 54.3%; P < 0.001). In multivariable analyses, RG was associated with more than 15 LNs being examined (OR, 1.49; 95% CI, 1.34 - 1.65; P < 0.001). The indications for RG appeared expanding to include more advanced stage, high comorbidity, and patients who underwent preoperative therapy.

Conclusions: RG has been increasingly performed in the past decade. Although its indication was expanded to include more advanced tumors, we found that the oncological quality metrics and safety outcomes of RG have improved over time and were better than those of OG or LG.

Background: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). A lack of adherence to adjuvant endocrine therapy is common, 31.0-73.0% of women discontinue endocrine treatment before 5 years. The aim of the study was to assess adherence to HT in routine clinical practice in patients assisted at the Clinical Oncology Department of the Hospital de Clinicas - Universidad de la Republica, Uruguay.

Methods: Patients treated with HT for stage 0-III BC between 2017 and 2019 were included. The medication possession (MPR) rate was calculated using pharmacy records, and the Morisky-Green Scale was applied to assess adherence. Adherent patients were those with MPR ≥ 0.80 and who correctly answered the Morisky-Green treatment adherence questionnaire. The association of adherence with polypharmacy, treatment, and patient characteristics was assessed using simple logistic models. The associations between qualitative variables and adherence were assessed using simple logistic regression model or Fisher's exact test. The association between quantitative variables and adherence was assessed using the Student's t-test. The odds ratio (OR) for non-adherence to treatment and its 95% confidence interval were estimated.

Results: Totally, 118 patients were included; 65.2% were treated with aromatase inhibitors (AIs), 36.0% presenting polypharmacy. The adherence rate at the end of 2 years was 81.0 %; and it was associated with age (P = 0.03, OR = 0.96 for non-adherence), with adherent and non-adherent patients having a mean age of 65.0 and 60.3 years, respectively; however, adherence was not associated with polypharmacy, territory of origin, marital status, living alone, level of education, occupation, or stage. The adherence profile was similar for both drugs, but homemakers and retired women showed greater adherence to AI.

Conclusions: Adherence to HT was assessed in real life, with 19.0% of the patients not adhering to the treatment, despite the known benefit for OS, being a well-tolerated treatment, and being provided free of charge. Older patients were associated with being more adherent. The results show the need of the Pharmacy Service and Department of Clinical Oncology Medical Oncology combining efforts to develop coordinated strategies and interventions to increase adherence, given the impact that this may have on patients' OS.

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC.

Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes.

Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues.

Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy.

Background: Hemophilus influenzae (H. influenzae) is a common cause of widespread bacterial infections and has been associated with the stabilization of the microbiome. The microbiome, through modulating systemic inflammation with possible upregulation of the NLRP3 inflammasome, may potentiate the development of breast cancer (BC). The purpose of this study was to therefore evaluate the correlation between previous H. influenzae infection and the incidence of BC.

Methods: A large national database was used to collect International Classification of Disease Ninth and Tenth Codes to evaluate the incidence of BC between January 2010 and December 2019 in patients with and without H. influenzae history. A retrospective cohort study was performed where these groups of individuals were matched by age range, Charlson Comorbidity Index (CCI), and antibiotic treatment exposure. Significance and relative risk were obtained using standard statistical procedures.

Results: A total of 13,599 patients were matched by age range and CCI in both the experimental and control groups. BC incidence was 259 (1.905%) in the H. influenzae group compared to 686 (5.044%) in the control group (P < 2.2 × 10^-16; odds ratio (OR) = 0.604, 95% confidence interval (CI): 0.553 - 0.660). Matching by antibiotic treatment exposure resulted in two groups of 3,189 patients, in which BC incidence was 98 (3.073 %) in the H. influenzae group compared to 171 (5.362%) in the control group (P < 2.2 × 10^-16; OR = 0.584, 95% CI: 0.515 - 0.661).

Conclusion: The study shows a statistically significant correlation between H. influenzae and a reduced incidence of BC. These results warrant further research regarding H. influenzae's role in upregulating the NLRP3 inflammasome and its potential role in BC prevention and treatment.

Background: Early diagnosis and proper management of hepatocellular carcinoma (HCC) improve patient prognosis. Several studies attempted to discover new genes to understand the pathogenesis and identify the prognostic and predictive factors in HCC patients, to improve patient's overall survival (OS) and maintain their physical and social activity. The transcription factor FOS-like antigen 1 (FOSL1) acts as one of the important prognostic factors in different tumors, and its overexpression correlates with tumors' progression and worse patient survival. However, its expression and molecular mechanisms underlying its dysregulation in human HCC remain poorly understood. Our study was conducted to evaluate the expression of FOSL1 in HCC tissues and its relationship with various clinicopathological parameters besides OS.

Methods: This study is a retrospective cohort study conducted among 113 patients with a proven diagnosis of HCC, who underwent tumor resection and received treatment at South Egypt Cancer Institute. Immunohistochemistry for FOSL1 expression and survival curves were conducted followed by statistical analysis.

Results: HCC occurred at older age group and affected males more than females. There was a statistically significant correlation between combined cytoplasmic and nuclear expression of FOSL1 and worse prognosis in HCC patients. There was a statistically significant correlation of FOSL1 expression with histological grade, lymphovascular embolization, and tumor budding where high expression indicated potential deterioration of HCC patients. There was statistically significant correlation between tumor size, tumor grade and FOSL1 expression with the cumulative OS.

Conclusions: Combined cytoplasmic and nuclear FOSL1 expression has significant prognostic association with HCC and diagnostic importance, as it can identify cirrhosis and premalignant lesions that can progress to HCC. Furthermore, Kaplan-Meier survival analysis found that overexpressed FOSL1 was correlated with poor OS.