Journal of gastrointestinal oncology最新文献

Background: Numerous studies have documented a reduction in the number of lymph nodes (LNs) examined and the number of metastatic LNs in rectal cancer patients as a consequence of neoadjuvant chemoradiotherapy (NCRT). It is plausible that the current guidelines advocating a specific number of LNs to be examined in rectal cancer surgery may be inappropriate for patients undergoing neoadjuvant therapy. This study aimed to determine the optimal number of LNs to be examined in rectal cancer patients treated with NCRT.

Methods: We conducted a retrospective analysis of clinicopathologic data from rectal cancer patients who underwent NCRT and radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center (NCC) from January 2004 to December 2015, as well as patients diagnosed with rectal cancer who received neoadjuvant therapy followed by surgery in the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. The optimal cutoff value for the number of examined LNs (ELNs) was determined using the X-tile software. Prognosis was assessed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was employed to identify prognostic risk factors.

Results: A total of 6,634 patients were included, comprising 391 patients in the NCC cohort and 6,243 patients in the SEER cohort. In the NCC cohort, there was no significant survival difference between patients with <12 ELNs and those with ≥12 ELNs, with the 5-year disease-free survival (DFS) rates of 72.0% and 76.5%, respectively (P=0.10). Furthermore, the X-tile software identified 7 as the optimal cutoff value for ELNs. In this cohort, patients with <7 ELNs had a 5-year DFS rate of 65.1%, compared to 76.3% for those with ≥7 ELNs (P=0.03). Multivariate Cox analysis revealed that the number of ELNs (cutoff value at 7) was the independent prognostic factor for DFS [hazard ratio (HR) =3.255, 95% confidence interval (CI): 1.796-5.897, P<0.001]. In the SEER cohort, the 5-year cancer-specific survival (CSS) rate was 81.2% for patients with <12 ELNs compared with 83.1% for those with ≥12 ELNs (P=0.10). Among these patients, those with <7 ELNs had a 5-year CSS rate of 79.1%, compared to 83.0% for those with ≥7 ELNs (P=0.04). Multivariate Cox analysis demonstrated that the number of ELNs (cutoff at 7) was an independent prognostic factor associated with CSS (HR =1.606, 95% CI: 1.308-1.970, P<0.001).

Conclusions: The optimal minimum number of LNs to be examined in rectal cancer patients treated with NCRT appears to be 7. The current standard of examining ≥12 LNs may be inappropriate. This finding provides valuable insights for determining the appropriate number of ELNs during surgery for rectal cancer patients who have undergone neoadjuvant therapy.

[This corrects the article DOI: 10.21037/jgo-2025-167.].

Background: A 39-year-old woman, G2P0M0, 26 weeks and 4 days pregnant, presented at the hospital with nausea, abnormal increase in abdominal size, respiratory failure due to pleural effusion and ascites, pain and weight loss. She was diagnosed with metastatic gastric carcinoma [signet ring cell carcinoma, human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1 (PD-L1) combined positive score (CPS) 8, proficient mismatch repair (pMMR)]. Oxygen therapy through a high-flow nasal cannula was started at the intensive care unit and drainage of ascites and pleural effusion was performed. A multidisciplinary team (MDT) was convened to discuss if gastric cancer treatment could safely be started after clinical improvement and, if so, what the consequences could be for the mother and the unborn child.

Case description: An MDT consisting of intensivists, oncologists, clinical pharmacists, gynecologists and nurses was assembled to collaboratively decide, together with the patient and her partner, on the best treatment strategy. A health and safety risk matrix based on literature and experience in practice was used to weigh the risks associated with cancer treatment. Once the patient was stabilized, it was decided to initiate 5-fluorouracil (5-FU), folinic acid and oxaliplatin (FOLFOX) chemotherapy based on the health and safety matrix. Nivolumab was considered to pose too high risks for the unborn and was therefore excluded. The gynecologist closely monitored the unborn child. 5-FU levels were monitored to assess 5-FU kinetics during pregnancy. A normal therapeutic AUC of 25.3 mg·L/h (ref 20-30 mg·L/h) after 46 hours treatment with 4,000 mg 5-FU was found. The patient tolerated the chemotherapy well and showed a good clinical and radiological response. After the first course of chemotherapy, the ascites and pleural drains were removed. In week 33 of the pregnancy, a cesarean section was performed to achieve an optimal balance between risks of chemotherapy and premature birth. A healthy boy was delivered. Post-partum treatment was continued with FOLFOX-nivolumab.

Conclusions: This case report demonstrates that, with a multidisciplinary approach and careful monitoring, metastatic gastric cancer can be successfully managed during pregnancy. The good response to FOLFOX therapy and the safe delivery of the child underscore the significance of tailored treatment plans in such complex cases.

Background: Hyperbilirubinemia presents a significant challenge in the treatment of patients with hepatic dysfunction, particularly those with metastatic liver disease requiring chemotherapy. Many chemotherapeutic agents undergo hepatic metabolism and elimination, complicating treatment due to altered pharmacokinetics, increased toxicity risks, and the absence of standardized dose adjustments. Patients with severe hepatic impairment are frequently excluded from clinical trials, limiting available evidence on safe and effective treatment strategies for this group of patients. Emerging approaches, including corticosteroids, radiation therapy, and the use of non-hepatically metabolized agents, offer potential avenues for treatment, but clinical data remains limited.

Case description: We report a case of a 73-year-old woman diagnosed with a poorly differentiated neuroendocrine carcinoma of unknown primary, presenting with extensive liver metastases and severe hepatic dysfunction. Upon admission, she exhibited significant hyperbilirubinemia (total bilirubin 11.3 mg/dL), precluding the use of standard systemic chemotherapy. A staged therapeutic approach was adopted, beginning with palliative radiation therapy to the liver and corticosteroid administration to reduce hepatic inflammation and improve bile flow. This intervention successfully lowered bilirubin levels to 6.9 mg/dL, enabling the initiation of weekly cisplatin, a renally excreted chemotherapeutic agent. Over time, further reductions in bilirubin permitted the introduction of gemcitabine, albeit at a reduced dose. Despite initial stabilization and a progressive decline in bilirubin, follow-up imaging showed progressive disease with new metastases, ultimately necessitating a transition to palliative care.

Conclusions: This case highlights the potential role of a staged therapeutic strategy in managing severe hyperbilirubinemia in patients with advanced hepatic dysfunction. The use of corticosteroids and liver-directed radiation therapy facilitated chemotherapy initiation in a patient otherwise deemed ineligible for systemic therapy. While the patient ultimately experienced disease progression, this approach underscores the feasibility of individualized interventions to optimize treatment opportunities. This case demonstrates how staged interventions can create a therapeutic window in patients typically ineligible for chemotherapy. While initial bilirubin reduction allowed systemic therapy, disease progressed, highlighting the limits of current approaches and the need for further research into treatment sequencing and supportive strategies, including liver-directed therapies and emerging systemic agents.

Background: Metastasis is the primary cause of mortality in patients with hepatocellular carcinoma (HCC). Metabolic reprogramming is a well-known hallmark of cancer metastasis. The aim of this study was to elucidate the role of metabolism in HCC metastasis.

Methods: Bulk RNA data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases (GEO). A combination of in vitro and in vivo experiments was conducted to evaluate the effects of glutaryl-CoA dehydrogenase (GCDH) on HCC progression. RNA sequencing was performed to investigate the underlying molecular mechanisms.

Results: Our findings revealed that lysine degradation pathway activity declined during HCC progression and metastasis. GCDH, a key regulator of the lysine degradation pathway, was selected for further investigation into the role of the lysine degradation pathway in HCC metastasis. The downregulation of GCDH expression promoted HCC metastasis by activating the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, GCDH expression was inversely correlated with macrophage infiltration, suggesting that reduced lysine degradation is associated with modulation of the immunosuppressive microenvironment. This phenomenon was attributed to the upregulation of GDF15 expression, which was induced by decreased GCDH levels through NF-κB signaling.

Conclusions: Inhibition of the lysine degradation pathway facilitates HCC metastasis and was involved in immune microenvironment remodeling. Additionally, GCDH may serve as a biomarker for predicting HCC metastasis and prognosis.

Background: Gastric cancer is a major cause of cancer mortality globally, and surgery is the primary curative treatment. Postoperative malnutrition is common and can delay recovery. Providing effective nutritional support after surgery is therefore essential, but whether parenteral nutrition (PN) or enteral nutrition (EN) offers greater clinical benefit remains unclear. This study aimed to compare the effects of PN and EN on hospital stay and nutritional outcomes in gastric cancer patients after surgery.

Methods: A thorough search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted following the PICOS principles to identify randomized controlled trials (RCTs) published up to August 2025. Eligible studies enrolled gastric cancer patients who received either PN or EN after surgery, reporting on length of hospital stay, nutritional markers (albumin, prealbumin, CD4/CD8 ratio), and adverse events. Two authors independently extracted data and assessed risk of bias using the Cochrane RoB 2.0 tool.

Results: Nine RCTs were included, with 641 patients in the PN group and 637 in the EN group. The risk of bias among included studies was generally moderate. Length of hospital stay was longer with EN than with PN [weighted mean difference =3.45, 95% confidence interval (CI): 2.29-4.61, P<0.001]. Albumin levels were higher with EN on days 1 and 8. Prealbumin levels were higher with PN on days 1 and 8. No significant difference was detected between PN and EN regarding retinol-binding protein levels on day 8 and the CD4/CD8 ratio on day 1. Infectious complications were more frequent with EN than with PN [relative risk (RR) =1.55, 95% CI: 1.06-2.27, P=0.02]. No significant difference was observed between EN and PN concerning overall complications (RR =1.11, 95% CI: 0.89-1.40, P=0.35).

Conclusions: Compared with EN, PN could shorten the hospital stay, increase the prealbumin levels, and decrease the occurrence of infectious complications, while albumin levels were higher with EN than with PN. However, given the moderate risk of bias and heterogeneity among included studies, further high-quality RCTs are needed to determine the optimal nutritional support strategy in this population.

Background: The microbiota is pivotal in colorectal cancer (CRC), yet the prognostic value of the blood microbiome and its utility in clinical prediction models remain poorly explored. This study aims to develop a blood microbiome-associated prognostic score (MAPS) that integrates blood microbiome data with clinical factors to improve the accuracy of CRC prognosis prediction and enhance our understanding of the tumor microenvironment (TME).

Methods: We analyzed whole-genome and transcriptomic sequencing data of CRC patients from The Cancer Genome Atlas (TCGA). A MAPS was developed from blood microbiome data using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A nomogram integrating MAPS and key clinical factors was constructed to predict overall survival (OS). Its predictive accuracy was validated via time-dependent receiver operating characteristic (ROC) analysis, yielding area under the curve (AUC) values for 1-, 3-, and 5-year OS. Underlying mechanisms were investigated through gene set enrichment analysis (GSEA) and immune cell infiltration estimation from matched RNA sequencing (RNA-seq) data.

Results: The MAPS, comprising seven key blood microbes, was an independent prognostic factor. The integrative nomogram demonstrated robust predictive performance, with AUCs of 0.800, 0.805, and 0.755 for predicting 1-, 3-, and 5-year OS, respectively. Mechanistically, the high-MAPS subgroup exhibited enriched pro-tumorigenic pathways (e.g., inflammatory response, hypoxia) and an immunosuppressive TME characterized by increased Treg cell infiltration. We further identified S100A8 and PROK2 as potential therapeutic targets.

Conclusions: Our study delivers a validated prognostic nomogram based on the blood microbiome and elucidates its link to an immunosuppressive TME, highlighting its dual utility in patient stratification and target discovery.

Background: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality, emphasizing the need for effective later-line therapies. Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR)1-3 inhibitor, has emerged as a promising option for refractory mCRC. This systematic review and meta-analysis evaluates its efficacy and safety, both as monotherapy and in combination with programmed death-1 (PD-1) inhibitors.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across PubMed, Embase, Online Vendor of International Databases (OVID), Cochrane Library, and ClinicalTrials.gov (2010-2025). Included studies were randomized controlled trials (RCTs) or real-world data on fruquintinib in mCRC after at least two prior therapies. Real-world evidence was included to complement RCT findings, as it captures broader populations, treatment patterns, and outcomes not fully reflected in controlled trial settings. Primary outcomes were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Pooled hazard ratios (HRs) and event rates were calculated using a random-effects model.

Results: Fifteen studies were included; 12 qualified for meta-analysis (n=3,703). Fruquintinib improved PFS [HR =0.30; 95% confidence interval (CI): 0.26-0.35] and OS (HR =0.66; 95% CI: 0.57-0.76) vs. placebo. ORR was 4.9% (95% CI: 3.2-6.6%); DCR was 62.2% (95% CI: 57.1-67.3%). Combination therapy with PD-1 inhibitors was associated with a modestly higher ORR in observational data; however, this finding requires confirmation in randomized studies (7.8% vs. 4.0%, P=0.04). In cross-study comparisons, monotherapy appeared to yield numerically longer PFS, although this was not based on head-to-head trials. AEs occurred in 86.7%, with grade ≥3 in 30.9%, most often hypertension (8.1%) and hand-foot skin reaction (5.8%). High heterogeneity was observed for several outcomes including AEs and DCR.

Conclusions: Fruquintinib significantly improves PFS and disease control in refractory mCRC with manageable toxicity. Limitations include heterogeneity across studies, with most conducted in predominantly Chinese cohorts. Further studies should explore optimal combination strategies and biomarker-based selection.

Background: In advanced gastric adenocarcinoma (aGC), the TAGS study demonstrated a survival advantage of trifluridine/tipiracil (FTD/TPI) over placebo in ≥3^rd line setting. This led to approval in the United Kingdom (UK). Clinical trial and real-world patients often differ in age, fitness and comorbidity, which has implications for safety and survival. Real-world data can inform clinical practice. This study sought to define the UK patient population who have received FTD/TPI and compare outcomes to TAGS.

Methods: This was a retrospective study. Patients with aGC commenced on FTD/TPI prior to 1^st February 2024 were eligible. Patients were identified from electronic health records. Data on baseline demographics and cancer outcome, including survival and toxicity, were collected.

Results: Data was collected for 58 patients from 12 centres in England, Scotland and Northern Ireland. Median age was 68.5 (range, 40-85) years, 44 (75.9%) were male and 10 (17.2%), 35 (60.3%) and 13 (22.4%) were Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1, and ≥2, respectively. Most primary tumours were gastroesophageal junctional (70.7%) and 24.1% were human epidermal growth factor receptor 2 (HER2) positive. FTD/TPI was given in 3rd line for 44 (75.9%) patients, 48 (82.8%) were commenced on full dose and on progression 6 (10.3%) received subsequent therapy. Median number of cycles received was 3 (range, 1-11). Median overall survival (mOS) in the whole population was 4.0 months [95% confidence interval (CI): 3.5-5.4], with mOS 5.9 vs. 4.0 vs. 2.5 months for ECOG PS 0, 1, and ≥2 respectively. On cox-regression analysis, with age, sex, ECOG PS, HER2 status, primary site and albumin as variables, ECOG PS ≥2 [hazard ratio (HR) =3.00; 95% CI: 1.07-8.35; P=0.04] and albumin ≥35 g/L (HR =0.47; 95% CI: 0.25-0.89; P=0.02) were prognostic; 29 (50%) and 16 (27.6%) patients required dose delay and reduction respectively, most commonly due to neutropenia. Grade ≥3 toxicity, attributed to FTD/TPI, was observed in 17 (29.3%) patients; 14 (82.4%) due to neutropenia and 3 (17.6%) anaemia. One (1.7%) patient stopped due to toxicity.

Conclusions: We present UK real-world data regarding use of FTD/TPI for aGC. Compared to TAGS, the patient population differed and mOS was lower than the reported 5.7 months, but long-term survivors are observed. Pre-treatment ECOG PS and albumin appear prognostic. Toxicity is in line with that reported previously. Our data support the use of FTD/TPI in selected populations with aGC.