Journal of gastrointestinal oncology最新文献

Background: Hepatocellular carcinoma (HCC) patients with coronavirus disease 2019 (COVID-19) undergoing open surgery show increased adverse events (AEs) and mortality, while the safety of transarterial chemoembolization (TACE) in coinfected patients remains understudied, limiting available evidence. This study aims to investigate the safety of TACE in HCC patients coinfected with COVID-19, and to explore the potential risk factors affecting the occurrence of serious AEs (SAEs), thus providing evidence for clinical treatment strategies in such patients.

Methods: This retrospective study involved HCC patients who underwent TACE with or without COVID-19 infection at our institution from November 2022 to February 2023. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for the diagnosis of COVID-19. Patients were divided into an infected group (diagnosed with COVID-19 within 2 weeks before or after the procedure) and an uninfected group (tested negative for COVID-19). SAEs were ascertained according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Logistic regression analysis of multiple clinical factors in preoperative baseline characteristics was performed to identify risk factors that might predict the occurrence of SAEs.

Results: A total of 118 patients (73 in the infected group, 45 in the uninfected group) were included, of whom 83.9% were male (86.3% in the infected group vs. 80.0% in the uninfected group) and the median age was 55.9±12.4 years (56.8±12.3 vs. 54.5±12.7 years). The clinical spectrum of COVID-19 in the infected group were 80.8% mild, 13.7% moderate, 1.4% severe and 4.1% critical. Sixteen of the 118 patients experienced SAEs (19.2% vs. 4.4%, P=0.046). The predominant SAEs were respiratory system diseases (9.6% vs. 0.0%) and liver damage (2.7% vs. 2.2%). In the univariate analysis, infection status [odds ratio (OR): 5.102, P=0.04, 95% confidence interval (CI): 1.102-23.627], gender (OR: 2.857, P=0.09, 95% CI: 0.862-9.468), age (OR: 1.061, P=0.03, 95% CI: 1.007-1.118) and clinical spectrum of COVID-19 (OR: 4.259, P<0.001, 1.943-9.336) were considered as the potential risk factors of grade ≥3 AEs. In multivariate analysis, younger age (OR: 1.064, P=0.044, 95% CI: 1.002-1.131) and a milder clinical spectrum of COVID-19 (OR: 5.736, P=0.004, 95% CI: 1.772-18.568) were independent factors associated with a lower occurrence of SAEs.

Conclusions: TACE in HCC patients co-infected with COVID-19 was considered relatively safe. Age and clinical spectrum of COVID-19 were associated with SAEs in HCC patients treated with TACE.

Background: Following tumor resection, imaging recommendation for the follow-up of patients with intrahepatic cholangiocarcinoma (IHCCA) include frequent chest, abdomen and pelvis computed tomography (CT) imaging. The appropriateness of additional imaging studies is usually derived from their clinical utility. The purpose of this work is to determine the value of chest CT imaging in the follow-up of patients with IHCCA.

Methods: Data review of radiology reports of baseline post-operative chest, abdominal, and pelvic CT imaging reports following the resection of IHCCA, and of subsequent follow-up exams. The radiology findings were stratified as intrathoracic metastasis only, combined intra-thoracic and intraabdominal metastasis, intra-abdominal metastases without intrathoracic involvement. We assessed the prevalence of intra-thoracic disease progression in comparison to other groups. Descriptive statistical analysis was carried out using John's Macintosh Project (JMP) statistical software.

Results: Eighty-seven patients were included in the study, 6 patients were found to have disease progression in the chest without corresponding disease progression in the abdomen on follow-up CT, accounting for 6.9% of the total. Only four patients had disease progression in the chest with a normal CT chest at baseline (4.6%).

Conclusions: The use of short-interval chest CT for surveillance in IHCCA has limited utility, particularly in patients with disease-free abdominal studies.

Background: Orthotopic models offer a more accurate representation of colorectal cancer (CRC) compared to subcutaneous models. Despite promising results from the reported intra-rectal models, establishing a standardized method for CRC research remains challenging due to model variability, hindering comprehensive studies on CRC pathogenesis and treatment modalities, such as brachytherapy. This study aimed to establish a standardized workflow for an orthotopic intra-rectal animal model to induce the growth of colorectal adenocarcinoma in male and female mice.

Methods: HT-29 colorectal adenocarcinoma cells were injected into the rectal mucosa of female (n=21) and male (n=26) non-obese diabetic severe combined immunodeficiency (NOD SCID) gamma (NSG) mice. Mice were placed on a 45° wedge elevating their pelvis for better visualization of the anus. Tumor growth and localization were monitored using a 7-T magnetic resonance imaging (MRI) scanner with rapid acquisition with relaxation echo (RARE) sequence at weeks 1, 2, and 3 post-cell instillation. Once tumors reached 5-8 mm in diameter, the mice were euthanized. Histopathology and immunohistochemical analyses confirmed the tumors' morphology, including necrosis, vascularity (CD-31) and apoptosis (cleaved caspase-3).

Results: There was a 92% and 95% tumor growth success rate in male and female mice, respectively. Tumors grew to 5-8 mm in diameter within ~20 days. No significant difference in tumor size was observed between genders. Tumor morphology was consistent across cases. Most tumors exhibited a lack of central blood vessels, accompanied by varying degrees of necrosis and apoptosis, whereas external portions were highly vascularized.

Conclusions: An orthotopic intra-rectal model was successfully developed. This model will be used in future studies to evaluate the efficacy of CRC treatments.

Background: Regorafenib and trifluridine/tipiracil (TFD/TPI) are oral systemic therapies with survival benefit in chemorefractory metastatic colorectal cancer (mCRC) patients, but they are not widely available worldwide. We aimed to evaluate the treatment patterns and outcomes of patients with limited access to these drugs.

Methods: Retrospective study involving 510 patients with mCRC who were treated at five different centers in Brazil, from January 2011 to December 2019. We analyzed the characteristics and clinical outcomes of patients who were exposed to third-line and beyond systemic therapy (N=148).

Results: A total of 148 (29%) and 73 (14%) patients received third- and fourth-line therapies, respectively. Most patients had left-sided tumors (80%) and had undergone primary tumor resection (87%) and metastasectomy (62%). From the initiation of third-line therapy, median follow-up was 17.8 months and median overall survival (OS) was 13.1 months (95% confidence interval: 8.1-18.0) (58% of deaths). The most adopted therapies were reexposure to previous chemotherapy regimens (85% third-line and 71% fourth-line), followed by regorafenib (13% and 25%) and TFD/TPI (2% and 4%). In multivariable analysis, male patients and right-sided tumors were significant unfavorable prognostic factors for OS.

Conclusions: In a real-world setting with barriers to accessing the standard of care of chemorefractory mCRC, reexposure to chemotherapy was the main therapeutic strategy, with potential negative influence on OS. Our study highlights how barriers hamper the achievement of health equity in cancer care and increases the awareness of patients and stakeholders, contributing to engaging them in ensuring equitable access to high-quality cancer care.

Background: Colorectal cancer (CRC) screening via colonoscopy is now advised for most adults beginning at age 45 years, an update from the earlier recommendation of age 50 years. With the increase in CRC screening rates, it is crucial to examine how mortality rates have changed over time. The aim of this study is to identify trends and regional differences in CRC mortality over the last two decades, specifically in individuals within the CRC recommended screening age group.

Methods: This study used the Center for Disease Control's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) system to collect data on CRC mortality for people ages 45-84 years in the United States from 1999-2022.

Results: During the study period, the overall age-adjusted mortality rate (AAMR) for CRC decreased across all census regions. The Midwest consistently had the highest AAMR, while the West had the lowest. Among genders, males in the Northeast had the highest rates, whereas females in the West had the lowest. Black or African Americans in the Midwest experienced the highest AAMR among racial groups, while Asian or Pacific Islanders in the Midwest had the lowest AAMR.

Conclusions: The mortality rate of CRC has been decreasing since 1999, but differences between regional groups have persisted. Disparities in outcomes still exist, showing that vulnerable subgroups require targeted interventions such as improved screening and follow-up access to increase early-stage diagnoses and potential for curative treatments.

Background: Chemoresistance is a major cause of treatment failure in advanced colorectal cancer (CRC), severely impacting patient survival and quality of life. While conventional chemotherapy regimens can somewhat control tumor progression, their effectiveness is frequently compromised by the development of drug resistance in cancer cells. The aim of this study is to verify and elucidate the specific mechanisms by which leptin enhances chemosensitivity in CRC, providing valuable insights for the development of new combination chemotherapy options.

Methods: We examined the link between CRC chemoresistance and fatty-acid metabolism driven by the high expression of carnitine palmitoyltransferase-1b (CPT1B) through an integrated approach combining bioinformatics and clinical sample analysis. In vitro and in vivo experiments were conducted to evaluate the effect of leptin, an adipocyte-derived cytokine, on CRC cells' response to cisplatin.

Results: Leptin significantly enhanced CRC cells' chemosensitivity to cisplatin by downregulating CPT1B expression, thereby disrupting the fatty-acid oxidation pathways that support drug resistance. In mouse models, the coadministration of leptin and cisplatin resulted in notable reductions in tumor size and weight compared to cisplatin alone, underscoring leptin's potential to enhance chemotherapy efficacy.

Conclusions: These findings indicate that leptin, through modulation of CPT1B, may serve as a promising adjunct to chemotherapy for CRC, addressing the challenge of chemoresistance and improving therapeutic outcomes. The leptin-CPT1B axis may be potential therapeutic target, providing new avenues for CRC treatment strategies aimed at overcoming drug resistance.

Background: Gastrointestinal (GI) cancers, particularly pancreatic cancer, are characterized by a dense stromal tumor microenvironment where cancer-associated fibroblasts (CAFs) predominate. CAFs comprise highly heterogeneous subpopulations with different functions, which can be both tumor-promoting and tumor-restraining. This systematic review and meta-analysis aims to comprehensively assess the impact of the CAF marker fibroblast-activation protein (FAP) expression on clinical outcomes in GI cancers.

Methods: Adhering to PRISMA guidelines, we systematically searched PubMed/MEDLINE, Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles. Inclusion criteria involved studies comparing GI cancer patients with and without FAP overexpression. Meta-analysis evaluated overall survival (OS), histological differentiation, local tumor invasion, lymph node metastases, and distant metastases. For each observational study, the risk of bias was assessed using the risk of bias in non-randomized studies of exposure (ROBINS-E) tool.

Results: The meta-analysis included 31 cohort studies from six countries, comprising 3,976 patients. Patients without FAP overexpression exhibited a favorable OS [hazard ratio (HR) =1.74; 95% confidence interval (CI): 1.51-2.01]. Subgroup analyses revealed consistent results across esophageal, pancreatic, colorectal, and gastric cancers. While one-year survival rates showed no significant difference, subsequent years displayed lower rates for FAP-overexpressing groups. Lymph node metastases were more frequent in FAP-overexpressing patients, whereas distant metastases did not differ. None of 31 studies systematically controlled confounding and adjusted data so that all studies were categorized as "high risk of bias" for the domain "risk of bias due to confounding". For domains "risk of bias arising from measurement of exposure", "risk of bias due to post-exposure interventions", "risk of bias arising from measurement of outcomes", and "risk of bias in selection of the reported result", all studies were categorized as "low risk of bias".

Conclusions: This meta-analysis underscores the potential adverse prognostic significance of FAP expression in GI cancers. Limitations include heterogeneity in FAP expression cutoffs and definitions. Future research should focus on delineating the precise roles and clinical implications of FAP in GI cancers.