Journal of Gastrointestinal Cancer最新文献

Objectives: To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

Methods: All included trials were prospective studies with a median patient age of 63 years, of which 94.2% were MSS/pMMR mCRC patients, with a male to female ratio of 1.5:1. Based on durvalumab and tremelimumab treatment, one study performed surgical resection on resectable cases, while the other four studies performed radiotherapy or chemotherapy on unresectable cases. Analyses include objective response rate (ORR).etc. for drug activity, overall survival (OS) and progression-free survival (PFS) for therapeutic efficacy, and adverse events (AEs) for safety. The risk of bias was assessed by sensitivity analysis.

Results: 5 studies involving 228 patients were included in this meta-analysis. The pooled estimates showed a median OS of 9.26 months, median PFS of 2.53 months, partial response (PR) of 13.6%, stable disease (SD) of 32.8%, ORR of 12.5% and disease control rate (DCR) of 65.4%. AEs were generally low, with pruritus (27.5%), diarrhea (28.8%), and fatigue (53.9%) being the most common, while other AEs occurred at less frequencies.

Conclusions: Durvalumab and tremelimumab with concomitant treatment for MSS/pMMR mCRC patients is relatively effective and safe, which is helpful in addressing the problem of mCRC with MSS/pMMR that has minimal response to immunotherapy.

Background: High morbidity and mortality make pancreaticoduodenectomy (PD) one of the most complicated surgical procedures. This meta-analysis aimed to compare the outcomes of robotic pancreaticoduodenectomy (RPD) versus open pancreaticoduodenectomy (OPD).

Method: A comprehensive literature search of PubMed, Cochrane Central, and Google Scholar was conducted from inception to November 2024. Studies comparing RPD and OPD in adults aged ≥ 18 years were included. Data for the outcomes of interest were extracted.

Results: Forty-one studies with a total of 54,287 patients were pooled. RPD is significantly superior to OPD in terms of overall postoperative complications (RR = 0.91, 95% CI: [0.86-0.97]; p = 0.001), wound infections (RR = 0.63, 95% CI: [0.49-0.81], p = 0.0004), estimated blood loss (WMD = -171.99 ml, 95% CI: [ -217.76 to -126.22], p < 0.01) and hospitalization duration (WMD = -1.33 days, 95% CI: [ -1.84 to -0.82], p < 0.01) with a longer operating time (WMD = 73.22 min, 95% CI: [56.20 to 90.23], p < 0.01).

Conclusion: In conclusion, RPD shows a lower risk of wound infections and overall postoperative morbidity compared to OPD. It has lower estimated blood loss, shorter hospitalization duration, and a longer operating time. The two approaches were comparable in terms of resection quality. More high-quality RCTs are required to draw definite conclusions.

Purpose: Liquid biopsy technology has received widespread attention in the early diagnosis of cholangiocarcinoma (CCA).

Methods: We collected bile samples from 48 patients with CCA and 48 patients with gallstones at Shandong Provincial third Hospital. We quantified bile circulating free DNA (cfDNA) of syncytin-1 and SLC7A11, calculated the correlation between syncytin-1 and SLC7A11 expression and clinical parameters by Spearman rank correlation, plotted Receiver Operating Characteristic (ROC) curves, and compared the Area Under Curve (AUC) values to explored early diagnostic utility in patients.

Results: We first found the bile cfDNA of syncytin-1 and SLC7A11 levels in CCA were higher than in gallstones (3.06 vs. 1.32, p < 0.001; 2.39 vs. 1.30, p < 0.001). And there was significant correlation between syncytin-1 and SLC7A11 expression (p = 0.025). Additionally, bile cfDNA of syncytin-1 or SLC7A11 was differentially expressed in gallstones, cholangiocarcinoma stage I-II, and cholangiocarcinoma stage III-IV (p < 0.001; p < 0.001). The AUC of bile cfDNA of syncytin-1 was 0.805 (p < 0.001, specificity of 87.0%), the AUC of bile cfDNA of SLC7A11 was 0.755 (p < 0.001, specificity of 80.4%), and combination of bile cDNA of syncytin-1/SLC7A11/CA19-9 markers improved diagnostic efficiency in CCA patients (AUC: 0.927, p < 0.001).

Conclusion: The bile cfDNA of syncytin-1 and SLC7A11 was high expression in cholangiocarcinoma, which may be used as a novel biomarker for early diagnosis.

Purpose: Basophils play a crucial role in immunoglobulin E-mediated allergic reactions and parasitic infections. Recently, a low basophil count was reported to be a poor prognostic indicator in patients with malignant tumors. This study aimed to investigate the cut-off value to evaluate the clinicopathological and prognostic significance of the basophil count in patients with gastric cancer.

Methods: This study enrolled 1192 gastric cancer patient who underwent surgery without preoperative chemotherapy between 2001 and 2020. The cutoff value was 26/μl based on the receiver of characteristics curves for overall survival, and 606 patients were classified as the low basophil group. The clinicopathological and prognostic significance of the low basophil count was assessed by univariate and multivariate analyses.

Results: Elderly age (p < 0.001), high C-reactive protein level (p < 0.001), low lymphocyte count (p = 0.044), and low neutrophil count (p < 0.001) are independently associated with low basophil count. The low basophil group demonstrated a significantly worse overall survival than the high basophil group (p = 0.005). Although there was no significant difference in stage I, the low basophil group demonstrated poor overall survival in stage II/III/IV. In stage II, low basophil count was independently associated with poor OS. In stage III/IV, low basophil group tended to have poor overall survival rate. Including all stages, low basophil count was an independent risk factor for poor overall survival (hazard ratio (HR) = 1.29, 95% CI: 1.03-1.61, p = 0.027).

Conclusion: Low basophil count was significantly associated with elderly age, high C-reactive protein level, and low neutrophil count (<26/μl). In addition, low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer.

Purpose: Intrahepatic cholangiocarcinoma (ICC) arises from the epithelial cells of the bile ducts present inside the liver parenchyma and is associated with an overall poor prognosis due to advanced disease stage at the time of diagnosis. We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to determine ICC-related mortality patterns in the United States from 1999 till 2020.

Methods: Age-adjusted mortality rates (AAMR) and crude mortality rates (CMR) were extracted from the CDC WONDER database. Annual percentage change (APC) was calculated using Joinpoint regression.

Results: Our analysis of ICC-related deaths revealed a consistent upwards trend from 1999 to 2020 in the United States (APC: 3.59, 95% CI: 3.34 to 3.83, p < 0.05). AAMR remained higher in males (1.7, 95% CI: 1.6 to 1.7) than females in (1.3, 95% CI: 1.3 to 1.3). Upon stratification by geographical distribution, we observed the highest mortality rate in the Northeast region (AAMR: 1.6, 95% CI: 1 to 2) and urban areas (1.4, 95% CI: 1.3 to 1.5). The highest ICC-related AAMR was observed in Hawaii, Rhode Island, and Washington, with mortality rates being twice as high as states at the lower end of the spectrum, including Mississippi and Arkansas. Non-Hispanic Asian or Pacific Islanders exhibited the highest AAMR (1.9, 95% CI: 1.9 to 2) as compared to other racial groups, and adults aged ≥ 85 years exhibited the highest CMR (11.2, 95% CI: 10.3 to 12.1).

Conclusion: The rise in ICC-related deaths from 1999 to 2020 is concerning, with the AAMRs observed to be the highest in males, non-Hispanic Asian or Pacific Islanders, adults aged ≥ 85 years and residents of the Northeast region, urban areas, and Hawaii. Efforts must be directed towards vulnerable populations to decrease ICC-related mortality.

Background: Radioresistance is a major challenge in the treatment of patients with colorectal cancer (CRC) and impairs the efficacy of radiotherapy. The PI3K/AKT/mTOR signaling pathway plays a critical role in CRC and contributes to the development of radioresistance. Accordingly, targeting this signaling pathway may be a promising strategy to improve oncotherapy.

Methods: We performed a systematic search of Scopus, PubMed, Web of Science, Embase, and Medline databases. We included articles that investigated the effects of PI3K/AKT/mTOR pathway inhibitors on improving the efficacy of radiotherapy.

Result: Of the 32 articles included in our review, 27 were preclinical studies and 5 were clinical trials. We examined the effects of various signaling pathway inhibitors in combination with radiotherapy. While the efficacy of these therapies when used alone is limited, their combination is associated with reduced survival, induction of apoptosis, and cell cycle arrest, which may increase radiosensitivity. Despite the limited number of studies, this combination therapy has shown favorable treatment outcomes in patients with CRC.

Conclusion: PI3K/AKT/mTOR is a critical signaling pathway for cancer cell survival. By inhibiting this pathway, we can increase the efficacy of radiotherapy. These results provide valuable insights for the further development of research and clinical practice in the treatment of colorectal cancer.

Background: Colorectal cancer (CRC) stands as the third most prevalent malignancy globally and is recognized as the second leading cause of cancer-related mortality. Notably, nearly 50% of individuals diagnosed with CRC ultimately develop metastatic disease, with the peritoneum emerging as the second most frequent site for metastatic spread. Recent advancements in therapeutic frameworks have enhanced both survival rates and quality of life metrics for patients afflicted with colorectal cancer peritoneal metastases (CRCPM).

Objective: This study endeavors to facilitate an in-depth review of the current scientific landscape surrounding CRCPM, ultimately aiming to delineate future avenues for investigative research in this realm.

Methods: Employing R software through the Bibliometrix package, alongside analytical tools such as CiteSpace and VOSviewer, we performed a comprehensive bibliometric analysis. This enabled us to assess pivotal keywords, prominent authors, influential countries, notable institutions, relevant literature, and key journals pertinent to the field of CRCPM research.

Results: Our findings illustrate a significant uptick in the volume of publications addressing CRCPM, with the USA leading in overall contribution, complemented by substantial input from distinguished scholars in the Netherlands and France. The author Ignace H. J. T. de Hingh emerged as the most prolific contributor. Current research endeavors have predominantly focused on the characterization of primary malignancies with peritoneal metastases, therapeutic interventions for CRCPM, and the orchestration of clinical trials.

Conclusion: This analysis culminates in a systematic encapsulation of the prevailing research findings concerning CRCPM, underscoring current hotspots and predicting future trends within the global research spectrum. The exploration of treatment modalities for CRCPM remains vibrant, and ongoing multicenter clinical trials are anticipated to further enrich our understanding and management of this challenging clinical issue.

Pancreatic ductal adenocarcinoma is a devastating disease which is associated with an increase in cancer-related death in the USA. The minority of patients are cured by surgery alone and typically require adjuvant chemotherapy in order to improve clinical outcomes. Circulating tumor DNA (ctDNA) is an emerging technology whereby microscopic levels of minimal residual disease (MRD) can be detected in the bloodstream. Circulating KRAS mutations are frequently studied given that they are present in over 90% of pancreatic cancers. Other assays utilize whole exome sequencing and/or methylomics to detect MRD. We demonstrate that ctDNA has prognostic and predictive capabilities in patients with both resectable and unresectable pancreatic ductal adenocarcinoma. ctDNA opens the door to novel therapeutic options and is already being integrated into ongoing clinical trials.

Background: Metabolic reprogramming is increasingly recognized as a crucial factor influencing the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). Despite this, the potential association of specific metabolic characteristics and PDAC remains ambiguous due to the variability introduced by individual patient differences. In this study, we aimed to find out metabolic pathways that may be associated with the overall survival (OS) of PDAC patients.

Methods: We utilized Mendelian randomization (MR) to assess the associations between 1400 metabolites and metabolite ratios and PDAC. We performed functional annotation and pathway enrichment analysis on both significant metabolites and the shared proteins corresponding to the significant metabolite ratios. Additionally, we analyzed peripheral blood metabolites from 32 PDAC patients to correlate metabolites with clinicopathological features and OS. Functional enrichment analysis was also conducted on the significant metabolites.

Results: Our MR analysis revealed 55 metabolites/metabolite ratios associated with PDAC. Among the top 20 enriched metabolic pathways involving proteins related to significant metabolite ratios, seven were associated with amino acid metabolism, three with carbohydrate metabolism, and two with lipid metabolism. Serum metabolomics of PDAC patients highlighted significant upregulation in pathways related to primary bile acid biosynthesis, as well as taurine and hypotaurine metabolism, which correlated negatively with OS. Conversely, pathways involved in arginine biosynthesis, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis were notably downregulated and positively associated with OS. Both upregulated and downregulated differential metabolites were notably enriched in the pyrimidine metabolism pathway, which was linked to poorer OS. These associations were corroborated by MR analysis.

Conclusion: The study provides valuable insights into the metabolic characteristics associated with PDAC, offering a reference point for improving diagnosis and treatment for PDAC.

Background and objective: Gastric cancer (GC) remains a leading cause of morbidity and mortality worldwide. The current standard of care involves neoadjuvant chemotherapy (NACT) followed by radical gastrectomy. This study aims to evaluate the efficacy of neoadjuvant therapy with PD-1/PD-L1 inhibitors in comparison to chemotherapy alone for patients with locally advanced gastric cancer (LAGC).

Methods: We conducted a systematic search of PubMed, Web of Science, and Embase to identify studies examining the addition of PD-1/PD-L1 inhibitors to neoadjuvant therapy for LAGC. Odds ratios (OR) were calculated for binary outcomes, such as pathological complete response (pCR), with corresponding 95% confidence intervals (CI).

Results: Seven studies were included, encompassing a total of 1772 patients. Baseline median age ranged from 31 to 75 years. Most patients had an ECOG performance status score of 0 (942 patients), while 294 had an ECOG score of 1. The estimated pCR (OR 5.94, 95% CI 3.98-8.87; p < 0.000001) significantly favored the PD-1/PD-L1 inhibitors combined with chemotherapy over chemotherapy alone. Additionally, the incidence of certain adverse events increased significantly in the intervention group, including any-grade hypothyroidism (OR 4.55, 95% CI 2.27-9.10; p = 0.000019) and rash (OR 1.74, 95% CI 1.10-2.76; p = 0.017). Conversely, the control group showed a statistically significant lower incidence of grade ≥ 3 fatigue (OR 2.80, 95% CI 1.15-6.85; p = 0.024) compared to the intervention group.

Conclusion: This systematic review and meta-analysis indicate that the addition of PD-1/PD-L1 inhibitors to neoadjuvant chemotherapy is associated with a higher pathological complete response rate compared to chemotherapy alone in patients with locally advanced gastric cancer.