Journal of Gastrointestinal Cancer最新文献

Introduction and importance: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is increasingly used for glycemic control, weight loss, and cardiovascular risk reduction. While GLP-1 RAs are commonly associated with acute pancreatitis, emerging reports suggest a possible association with pancreatic cystic lesions, even in patients without typical risks factors such as alcohol, gallstones, or hereditary syndromes.

Case presentation: We present two cases of middle-age female patients without prior compline or pancreatic disease who developed large distal pancreatic mucinous cystic neoplasms following GLP-1 Ras use. Both underwent imaging and aspiration, which revealed elevated carcinoembryonic antigen (CEA) levels. Surgical management consisted of distal pancreatectomy and splenectomy. Pathology confirmed MCN with no malignancy. Both patients had uneventful recovery.

Discussion: These two cases suggest a possible association between GLP-1 receptor agonists, and the development of pancreatic mucinous cystic neoplasms (MCNs) in patients without prior pancreatic disease or conventional risk factors. While causality cannot be established, the temporal relationship, absence of alternative etiologies, and supportive literature suggest a possible drug-related effect. Preclinical studies have implicated GLP-1 RAs in pancreatic ductal hyperplasia and cyst formation, and recent clinical reports reinforce these findings. As semaglutide use expands, clinicians should be vigilant for structural pancreatic changes, and further studies are warranted to elucidate underlying mechanisms and clinical implications.

Conclusion: These cases raise concern regarding a potential association between semaglutide therapy and mucinous cystic neoplasms. Increased vigilance and further observational studies are warranted to evaluate this potential adverse effect.

Purpose: Bile acids (BAs) are important molecules in the carcinogenesis of pancreatic cancer (PC). The BA profile in pancreatic diseases and its role in PC remain unclear.

Methods: The concentrations of 63 BAs in serum were measured in a total of 421 participants from three medical centers using targeted metabolomics. The concentrations of seven common types of BAs in serum were determined and compared. The least absolute shrinkage and selection operator algorithm analysis was used to confirm the independent predictors and build a metabolite panel for prediction and discrimination.

Results: A panel of two BA metabolites DCA and ω-MCA showed high diagnostic performance for PC versus healthy controls with an AUC of 0.914 (95% CI 0.873-0.956) in the validation cohort and achieved a 94.20% positive rate in the validation cohort. This diagnostic panel correlated with advanced clinical stage (p = 0.006) and poorer overall survival (HR = 3.11, 95% CI 0.79-12.23, p = 0.006). Importantly, biliary obstruction altered total BA concentrations (2.4-fold increase, p < 0.001) but did not change BA compositional proportions (p > 0.05). Additionally, ω-MCA, GCA-3S, GCDCA-3S, UDCA, and secondary BAs may distinguish PC from pancreatic benign tumors. GLCA was able to differentiate PC from pancreatic premalignant lesions. TLCA, 3-oxoLCA, and NorCA can effectively separate PC from chronic pancreatitis.

Conclusion: BAs are potential diagnostic and prognostic biomarkers for PC, which may also be helpful in differentiating pancreatic diseases.

Background: Sphincter-preserving surgery for rectal cancer is associated with long-term bowel dysfunction, yet data on outcomes in patients managed with watch-and-wait is limited. This study compared bowel function in rectal cancer survivors managed with watch-and-wait versus sphincter-preserving surgery and evaluated the performance of two instruments: the Memorial Sloan Kettering Bowel Function Instrument (MSK-BFI) and the Low Anterior Resection Syndrome (LARS) score within each cohort.

Patients and methods: In this cross-sectional study, rectal cancer survivors treated with long-course chemoradiotherapy between 2011 and 2019 at Flinders Medical Centre were recruited. Participants without stomas completed the MSK-BFI, LARS, and comorbidity questionnaires. Demographics and clinical data were obtained from medical records. Outcomes were compared between the sustained watch-and-wait (WW) and surgical (SURG) cohorts. Associations were examined using regression models. Instrument comparisons were performed in each cohort using factor analysis.

Results: Of the 190 eligible survivors, 67 participants were included (WW, n=33; SURG, n=34). Surgery was associated with significantly worse bowel function across MSK-BFI domains and higher rates of Any LARS (91% vs. 67%) and Major LARS (70% vs. 36%). Female sex was independently associated with poorer bowel function. Factor analysis revealed that one factor accounted for bowel function in the SURG cohort, whereas two factors were required in the WW cohort, indicating greater complexity.

Conclusion: Surgery and female sex are associated with significantly worse bowel function in rectal cancer survivors. The WW cohort demonstrated more complex symptom patterns, supporting concurrent use of MSK-BFI and LARS until a WW-specific tool is developed. A larger, prospective study is underway to investigate the findings further.

Intrahepatic cholangiocarcinoma (iCCA) represents an aggressive primary hepatic malignancy with limited non-surgical therapeutic options. This review examines the evolution of transarterial radioembolization (TARE) with Yttrium-90 microspheres from palliative intervention to curative-intent therapy, driven by advances over the past few decades. Partition-model dosimetry demonstrates superior survival compared to empiric approaches (14.9 versus 5.5 months, P < 0.001), establishing the critical importance of individualized treatment planning. In first-line settings, multimodal strategies combining TARE with systemic therapy achieve median overall survival of 32.5 months, with intensive protocols demonstrating objective response rates of 39-85% and downstaging to curative resection in 22-54% of patients. Ablative radiation segmentectomy delivers tumor doses exceeding 190 Gy, achieving objective response rates of 94%, median survival of up to 72 months in early-stage disease. TARE-based bridging to liver transplantation yields 5-year survival of 57% from time of transplant listing. Optimal outcomes are observed for tumor burden below 25%, preserved hepatic function, favorable performance status, and personalized dosimetry delivering ≥205 Gy to tumor. Contemporary TARE represents a transformative paradigm in liver-directed therapy for appropriately selected iCCA patients.

Background: Pancreatic cancer (PC) remains one of the most lethal malignancies with limited treatment options, particularly in advanced stages. Emerging immunotherapeutic strategies, such as Gamma Delta (γδ) T cell therapy paired with microbiota management, have demonstrated promise.

Case presentation: We report a case of a 75-year-old male diagnosed with advanced-stage and poorly differentiated PC who demonstrated significant clinical improvement following a novel therapeutic approach combining fecal microbiota transplantation (FMT), γδ T cell therapy, and pembrolizumab. Initial chemotherapy and radiotherapy were discontinued due to adverse effects. Pre-treatment the CA19-9 (1206 U/mL), tumor markers were significantly elevated with CEA, CA15-3 and CA125 all within normal limits. No pathogenic mutations (e.g., BRCA1/2, PALB2) were identified. A comprehensive assessment revealed tumor progression, immunosuppression, and gut microbiota dysbiosis, resulting in FMT and γδ T cell therapy being introduced alongside pembrolizumab.

Outcomes: The combination therapy resulted in the clearance of circulating tumor cells (CTCs), normalization of CA19-9 to 72 U/mL, improved clinical symptoms, and a marked reduction in tumor size, as confirmed by CT. Tolerability was excellent with no serious adverse events occurred.

Conclusion: This case suggests that FMT combined with γδ T cell therapy may be a promising immunotherapeutic strategy for advanced PC. Further studies are needed to validate these findings.

Background: We analyzed China's colorectal cancer (CRC) burden from 1990 to 2023, focusing on incidence, mortality, disability-adjusted life years (DALYs), prevalence, and risk-attributable burden, to assess temporal trends and evaluate future prevention needs.

Methods: Using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates, we summarized all-age numbers and age-standardized rates (ASR) by sex. Joinpoint log-linear models calculated the average annual percent change (AAPC), and risk-attributable deaths and DALYs were profiled for 2023. And we conducted a brief sensitivity comparison of trends for 2010-2019 and 2019-2023 for both sexes combined. All results are model-based estimates and are reported with uncertainty intervals (UIs).

Results: In 2023, China was estimated to have 611,364 incident CRC cases (95% UI 493,490-771,955), 258,088 deaths (225,359-305,788), 3,375,669 prevalent cases (2,710,191-4,159,613), and 6,279,382 DALYs (5,563,225-7,428,441). Over 1990-2023, ASIR and ASPR increased, while ASMR and ASDR declined. Males consistently had higher rates than females, and burden rose steeply with age. AAPCs showed an increase in incidence across the 15-49, 50-74, and ≥ 75 years age groups, particularly in those aged 75 years and older. Mortality and DALY rates declined at younger ages and were stable at ≥ 75. In 2023, the risk-attributable CRC burden was concentrated in dietary risks and metabolic and behavioural risks, including high fasting plasma glucose, smoking, alcohol use, and low physical activity. The brief pre- and post-2019 comparison suggested broadly similar directions with wide uncertainty.

Conclusions: GBD 2023 estimates indicate that CRC remains a growing challenge in China, with rising ASIR and ASPR despite declining ASMR and ASDR. Prevention and screening planning should prioritise modifiable risks and strengthen service resilience, while interpreting model-based estimates in light of their uncertainty.

Background: Gastric cancer (GC) remains a significant global health burden, with Helicobacter pylori (H. pylori) infection being a major etiological factor. Despite extensive research, a comprehensive overview of the temporal evolution of research output, collaborative networks among countries and institutions, and shifting research foci in this field is lacking.

Methods: We conducted a bibliometric analysis utilizing the Citexs database and its analytics platform. Literature pertaining to GC and H. pylori published between January 2004 and December 2023 was retrieved and subjected to data mining and visualization to delineate research trends and hotspots.

Results: Analysis of 12,789 publications revealed a generally upward trend in annual output. The United States was the most productive country, while The American Journal of Gastroenterology was the leading journal. Baylor College of Medicine was the most prolific institution, and Yoshio Yamaoka was the most productive author. Keyword and thematic analysis identified core research areas, including H. pylori, gastritis, the cytotoxin-associated gene A (CagA), and GC itself. At the mechanistic level, current research focuses heavily on genes such as CXCL8, TNF, and NFKB1.

Conclusion: Future studies should prioritize deeper exploration of these core themes and pivotal signaling pathways to potentially facilitate advances in the prevention and treatment of H. pylori-associated GC.

Purpose: Earlier detection of colorectal cancer (CRC) can improve survival rates. A simple, effective blood test may help improve screening participation. The multi-target blood protein (MTBP; ColoSTAT^®) test and algorithm uses concentrations of five protein biomarkers of CRC and patient's sex and age to generate a CRC likelihood score. We compared the performance of the MTBP test in detecting CRC to colonoscopy, the 'gold standard'.

Methods: This cross-sectional, multicenter study enrolled participants into two cohorts: participants recently colonoscopically diagnosed with CRC and progressing to surgery or neoadjuvant treatment (Cohort 1), and participants with no CRC history who were scheduled for colonoscopy (Cohort 2). Due to COVID-19 pandemic-related recruitment delays, Cohort 1 was supplemented with bio-banked blood samples (BBS) from patients with clinically confirmed CRC. Performance goals for sensitivity and specificity of the MTBP test compared to colonoscopy were ≥ 73% (lower 95% confidence limit [LCL] > 60%) and ≥ 90% (LCL > 80%), respectively.

Results: Cohort 1 included 29 patients, Cohort 2 enrolled 768 patients and 192 BBS were included. Median age when providing samples was 64 years (range, 40-85 years); 53.4% were female. Definitive MTBP test results were obtained from 657 samples. 112 and 389 samples met the criteria for inclusion in the primary sensitivity and specificity analyses, respectively. The sensitivity of ColoSTAT^® for detection of all-stage CRC compared to colonoscopy was 81.3% (95%CL 73.0%-87.4%) and the specificity, 91.0% (95%CL 87.7%-93.5%).

Conclusions: The MTBP test met pre-specified primary performance endpoints and warrants further evaluation in clinical populations at elevated risk of CRC.