Journal of gastrointestinal oncology最新文献

Background: Small cell carcinoma of the esophagus (SCCE) is a rare malignant carcinoma, which is highly aggressive and prone to recurrence and metastasis. There is no standard therapeutic modality for SCCE. We aimed to describe the clinical characteristics and therapeutic outcomes of SCCE, analyse its prognostic factors, and provide a reference for establishing a standard treatment regimen.

Methods: We retrospectively evaluated 156 consecutive patients with SCCE, who received treatment at Fujian Cancer Hospital between 2007 and 2022. We finally included 140 patients in the analysis. The primary endpoint was overall survival (OS); the key secondary endpoint was progression-free survival (PFS). Multivariate Cox regression survival analysis was conducted to identify the independent prognostic factors. Subgroup analysis included treatment modalities used to patients with limited stage SCCE (LS-SCCE).

Results: The median OS was 24.0 [95% confidence interval (CI): 19.391-28.609] months and the 1-, 3-, and 5-year OS rates were 79.3%, 20.0%, and 9.3%, respectively. The multivariate Cox analysis suggested that chemotherapy was an independent prognostic factor [hazard ratio (HR) 0.519; 95% CI: 0.271-0.992; P=0.047]. In subgroup analysis for patients with LS-SCCE, the median OS was 26 months for patients receiving surgery-based multimodal therapy [surgery (S) ± chemotherapy (CT) ± radiotherapy (RT)] compared to 31 months for those receiving definitive chemoradiotherapy (CRT) (P=0.97). There was no significant difference between the two groups.

Conclusions: Our results suggest that CRT might be an effective first-line treatment for LS-SCCE and is not inferior to surgery. The conclusions are expected to provide a reference for the standardised treatment of SCCE.

Background: Nutritional indicators play an important role in predicting the prognosis of digestive system cancers. Measures of adipose tissue distribution derived from computed tomography (CT), such as subcutaneous fat volume, are promising for assessing systemic inflammation and nutritional status. However, their integration into standardized prognostic models is still limited. This study aimed to increase the performance of the Cox regression model (Coxm) by adding the third lumbar vertebra centroid level subcutaneous fat volume (L3 CLSFV) and to assess its influence on prognostic prediction model.

Methods: We constructed two Cox regression models, Coxm1 and Coxm2, using clinical features and nutritional indicators from the training cohort of patients with digestive system cancers. The Coxm1 model contained seven features, while Coxm2 incorporated an extra L3 CLSFV measured by CT. Performance was evaluated using multiple metrics in the validation cohort, including time-dependent receiver operating characteristic (timeROC), time-dependent concordance index (timeC-index), calibration curve, and Kaplan-Meier curve. The predictive accuracy of the model was further assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results: Both models had high area under the curve (AUC) (range, 0.78-0.89) and C-index values (range, 0.74-0.80). The timeROC curve showed that the inclusion of L3 CLSFV in Coxm2 did not improve the model's AUC, with similar values observed at 1-, 3-, and 5-year. Coxm2 did not improve time-dependent C-index in comparison with Coxm1. Calibration curves showed good agreement between predicted and actual survival probability in both models, with slight improvements seen in Coxm2 versus Coxm1 (Brier score, 0.166 vs. 0.168). NRI indicated that the inclusion of L3 CLSFV in Coxm2 improved the model's performance. The category NRI of Coxm2 versus Coxm1 was 0.0768 [95% confidence interval (CI): -0.0768 to 0.128], while the continuous NRI was 0.0639 (95% CI: -0.0363 to 0.293). The IDI of Coxm2 versus Coxm1 was 0.006 (95% CI: -0.003 to 0.028). In the Kaplan-Meier curves, both Coxm1 and Coxm2 were accurately differentiated between high- and low-risk groups.

Conclusions: The addition of the L3 CLSFV to the Cox model improved the predictive accuracy and reclassification ability. These findings suggest that incorporating extra nutritional indicators can enhance the performance of prognostic models in digestive system cancer.

Background: Anal cancer is a relatively less common gastrointestinal cancer, with common sites of distant metastasis being para-aortic nodes, liver, lungs, and skin. Intraocular metastasis from anal squamous cell carcinoma is an extremely rare occurrence with no reported cases so far.

Case description: We present a case of a 70-year-old male with a past medical history of metastatic anal squamous cell carcinoma who presented to the oncology clinic with complaints of sudden onset complete vision loss in his right eye. The patient was then referred to a retina specialist and was found to have a posterior choroidal tumor that raised concerns of a primary uveal melanoma vs. metastatic spread from his known metastatic anal squamous cell carcinoma. Given the severity of his symptoms and diagnostic uncertainty, he underwent right eye enucleation and prosthesis placement. Histopathologic evaluation of the enucleated specimen confirmed the diagnosis of metastatic carcinoma consistent with anal carcinoma.

Conclusions: This case presents the exceptionally rare phenomenon of intraocular metastasis from a primary anal squamous cell carcinoma. Per our literature review, this is the first reported case of such an occurrence, which adds to the clinical complexity of this case in terms of timely diagnosis, effective treatment modalities and prognosis. In these cases, early recognition and diagnosis is critical, as intraocular metastasis significantly affects quality of life as well as overall prognosis. Therefore, through this case report, we aim to highlight the rare intraocular presentation of metastatic anal cell carcinoma, so that clinicians maintain a broad differential diagnosis when evaluating new ophthalmic symptoms in patients with anal cancer.

Background: The optimal adjuvant therapy after liver resection in patients with hepatocellular carcinoma (HCC) is controversial. This study aimed to revisit the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in HCC patients after curative-intent hepatectomy.

Methods: A total of 387 patients were divided into PA-TACE group and no adjuvant treatment control group, and follow-up data were collected. The primary endpoints of recurrence-free survival (RFS) and overall survival (OS) were assessed before and after propensity score matching (PSM) analysis. Survival data were computed by means of the Kaplan-Meier method. Multivariable Cox proportional hazards model was used to determine the independent risk factors for patients' outcomes.

Results: The RFS rates were higher in patients treated with PA-TACE compared to those in the control group, with borderline statistical significance [P=0.050; hazard ratio (HR) =0.75, 95% confidence interval (CI): 0.56-1.0]. Patients in the PA-TACE group had significantly higher OS rates than those in the control group (P=0.04, HR =0.70, 95% CI: 0.50-0.99). After PSM, the impact of PA-TACE on RFS and OS remained significant (HR =0.70, P=0.04 for RFS; HR =0.65, P=0.04 for OS). On multivariate Cox regression analyses in the entire cohort, age >65 years, γ-glutamyl transferase (GGT) >40 U/L, microvascular invasion (MVI)-positive, and no PA-TACE were identified as independent predictors for HCC recurrence. In further subgroup analysis, PA-TACE significantly improved RFS and OS of HCC patients in MVI-positive group (HR =0.31, P<0.001 for RFS; HR =0.47, P=0.002 for OS). The benefit of PA-TACE on RFS and OS remained significant in MVI-positive group after PSM (HR =0.32, P<0.001 for RFS; HR =0.38, P=0.003 for OS). Furthermore, patients who received PA-TACE developed recurrent HCC with less aggressive tumor characteristics.

Conclusions: PA-TACE improves RFS and OS of HCC patients after liver resection, especially in MVI-positive patients. Furthermore, PA-TACE reduces the malignancy of recurrent tumors.

Background: Primary liver cancer (PLC) is one of the most common malignant tumors worldwide, with its incidence continuing to rise in recent years. As the main pathological subtype of PLC, hepatocellular carcinoma (HCC) has become a major disease burden threatening global public health. For HCC patients receiving treatment, accurate prognostic stratification is of crucial significance for improving patients' long-term survival. In view of this, this study was designed to explore the predictive value of the ratio of the preoperative prealbumin to the platelet distribution width (PDW), namely, the PPDWR, for the prognosis of HCC following radical resection. Additionally, a nomogram was constructed for survival prediction.

Methods: A retrospective analysis was carried out on the data of 205 patients who underwent radical resection for HCC at The Affiliated Hospital of Southwest Medical University between January 2016 and August 2021. These patients were randomly assigned to a training set or a validation set. The optimal cutoff value of the PPDWR was determined by the receiver operating characteristic (ROC) curve of overall survival (OS) in the training set of patients, after which patients were grouped accordingly. The associations between PPDWR and clinical characteristics, as well as its impact on survival, were analyzed. Prognosis-related variables were screened via least absolute shrinkage and selection operator (LASSO)-Cox regression and univariate and multivariate Cox regression. Nomograms for OS and recurrence-free survival (RFS) were subsequently constructed and validated. Finally, the time-dependent ROC curve, concordance index and decision curve analysis were used for survival prediction evaluation. P<0.05 indicated a statistically significant difference.

Results: The optimal cutoff value of the PPDWR was 14.514 which was correlated with multiple clinical indices. The sensitivity and specificity of this cutoff value were 88.5% and 45.1%, respectively. The OS and RFS of patients in the high-PPDWR subgroup were significantly superior to those in the low-PPDWR subgroup. A low PPDWR level, a high alpha-fetoprotein (AFP) level, were independent risk factors for OS. For RFS, the independent risk factors included a low PPDWR, China Liver Cancer Staging (CNLC) stage III. The constructed nomograms demonstrated good predictive accuracy in both the training set and the validation set.

Conclusions: A low preoperative PPDWR is an independent risk factor for poor postoperative prognosis in HCC patients. The nomogram constructed on the basis of the PPDWR can effectively predict the postoperative OS and RFS of patients, thus offering a reference for clinical treatment decision-making.

Background: Our preliminary experiments confirmed that follistatin-like 3 (FSTL3) expression is elevated in colorectal cancer (CRC) cells following CoCl₂ treatment. In this study, we investigated the regulatory role of FSTL3 in CRC progression and the molecular mechanisms underlying its high expression.

Methods: CoCl₂ (150 µM) was used to mimic hypoxia. Cell proliferation was measured by colony formation assay, wound healing assays were performed to assess cell migration, and Transwell assays were performed to evaluate invasion. The glucose metabolism pathways were assessed by detecting extracellular acidification rate, oxygen consumption rate, glucose uptake, and lactate production. The binding sites of zinc finger protein 454 (ZNF454) and FSTL3 gene promoter were analyzed by JASPAR databases, and were confirmed by chromatin immunoprecipitation (ChIP) and luciferase reporter assay. The expression levels of molecules at mRNA and protein levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively.

Results: We found that both FSTL3 and hypoxia-inducible factor 1α (HIF-1α) were upregulated in CRC tissues and in CRC cells under hypoxic conditions, with a positive correlation between their expression in clinical samples. Silencing FSTL3 reduced HIF-1α expression and suppressed the expression of glycolytic enzymes (glucose transporter 1, hexokinase 2, lactate dehydrogenase A, and pyruvate kinase muscle isozyme M2). Knockdown of FSTL3 increased oxygen consumption while decreasing extracellular acidification, glucose uptake, and lactate production. Moreover, FSTL3 downregulation markedly inhibited the proliferation, migration, and invasion of CoCl₂-treated CRC cells. We further identified ZNF454 as a potential transcription factor for FSTL3 and confirmed its binding to the FSTL3 promoter. Upregulation of ZNF454 significantly suppressed CRC cell proliferation, migration, invasion, and glycolysis, effects that were reversed by FSTL3 overexpression. In vivo, ZNF454 overexpression effectively inhibited tumor growth and reduced HIF-1α and glycolytic enzyme expression, whereas these effects were rescued by FSTL3 overexpression.

Conclusions: Collectively, our findings demonstrate that ZNF454 suppresses CRC development by inhibiting FSTL3/HIF-1α-mediated glycolysis through transcriptional repression of FSTL3. This study is the first to reveal the molecular mechanism responsible for FSTL3 overexpression in CRC, providing a novel perspective for CRC treatment.

Background: Primary liver cancer (PLC) is a leading cause of cancer-related mortality, with many patients ineligible for curative resection. Transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are two key interventional therapies recommended for unresectable cases. Recent studies suggest that combining them may enhance treatment efficacy compared to either approach alone. This prospective study aims to evaluate the safety and efficacy of TACE combined with HAIC in patients with unresectable PLC.

Methods: Patients with unresectable primary hepatocellular carcinoma (China Liver Cancer stage IIa-III, without distant metastasis) who received TACE combined with HAIC from February 2023 to September 2024, at the Department of Interventional Treatment, Beijing No. 6 Hospital, were included. The primary endpoint was overall survival (OS) and progression-free survival (PFS). Safety was evaluated in all patients who received at least one treatment cycle. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: Among the 29 eligible patients, the median follow-up month was 16 months. The mRECIST assessments were available for 22 patients. Among them, six (27.3%) achieved complete response, 11 (50.0%) showed partial response, two (9.1%) showed progressive disease, and three (13.64%) showed stable disease. The objective response rate was 77.3%, and the disease control rate was 90.9%. Three patients (10.3%) underwent successful surgical resection following treatment. Median OS and PFS were not reached. The estimated 6-, 12-, and 18-month OS rates were 90%, 85% and 85%, respectively. No grade 3-5 treatment-related adverse events were observed.

Conclusions: In patients with China Liver Cancer stage IIa-III, the combined treatment demonstrated a favorable safety profile and preliminary efficacy, also enabling transformative resection in some patients.

Background: Colorectal cancer (CRC) is a common malignancy worldwide, and its incidence and mortality are increasing annually. In recent years, researchers have gradually realized that the tumor microenvironment (TME) plays a crucial role in the development and progression of CRC. The in-depth study of CRC and its microenvironment provides not only a new perspective for understanding the occurrence and development of tumors, but also potential new strategies for clinical treatment. This study aims to explore the research hotspots and development trends between CRC and TME through bibliometric analysis.

Methods: The Web of Science Core Collection (WoSCC) was used to retrieve literature related to CRC and the TME published from 2009 to 2024. CiteSpace software and VOSviewer software were used to evaluate and visualize the authors, journals, institutions, countries, keywords and citations.

Results: A total of 8,410 relevant articles were analyzed, and the number of published articles tended to increase. The countries and institutions that had with the highest number of publications in this field were China and Sun Yat-sen University. Ogino, S was the most prolific author and the most cited literature was Sung, Hyuna's article "Global cancer statistics 2020" published in the CA-A Cancer Journal for Clinicians. The journals with the most published articles and citations were Cancers and Clinical Cancer Research, respectively. Keyword analysis revealed that the current popular research topics included the "immunotherapy", "tumor microenvironment", "prognosis" and "inflammation".

Conclusions: The study of CRC and the TME is still a hot topic. Future research will focus more on the interaction between various immune cells and molecules, study the expression of cancer-related genes and proteins, and explore new therapeutic targets and prognostic markers. These findings provide strong support for the precise and individualized treatment of cancer.

Background: To explore the value of semi-quantitative parameters of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) combined with tumor markers in predicting lymph node metastasis (LNM) in esophageal cancer (EC). This study aimed to explore the value of ¹⁸F-FDG PET/CT semi-quantitative parameters combined with tumor markers in predicting EC-related LNM.

Methods: A retrospective analysis was conducted on 200 pathologically confirmed EC patients (157 with LNM, 43 without LNM) who underwent preoperative ¹⁸F-FDG PET/CT. Inclusion criteria: no prior anticancer treatment, complete clinical/imaging/tumor marker data. LNM was confirmed by postoperative pathological examination. PET/CT parameters such as the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary lesions and common EC-related tumor markers were tested. Univariate/multivariate analyses identified independent predictors, and three prediction models with different parameter combinations were constructed. Predictive accuracy was assessed via receiver operating characteristic (ROC) curves.

Results: Patients were mostly male (75%) with median age 62 years and squamous cell carcinoma accounted for 90%. Univariate analysis showed significant differences in tumor diameter, tumor (T) stage, and all PET/CT parameters between LNM and non-LNM groups (all P<0.05). Multivariate analysis confirmed carcinoembryonic antigen (CEA) [odds ratio (OR) =1.326], SUVmax (OR =1.351), mean standardized uptake value (SUVmean) (OR =22.391), and MTV (OR =1.198) as independent predictors (all P<0.05). MTV had the best single-parameter predictive performance [area under the curve (AUC) =0.878, optimal cutoff 11.88]. The combined model [carbohydrate antigen 724 (CA724) + SUVmean + SUVmax + MTV + TLG] showed the highest efficacy (AUC =0.965, sensitivity 94.90%, specificity 86.05%).

Conclusions: ¹⁸F-FDG PET/CT metabolic parameters (especially MTV) combined with CA724 significantly improve the accuracy of preoperative LNM prediction in EC, helping clinicians optimize surgical scope and adjuvant therapy, thereby improving patient prognosis.