Journal of gastrointestinal oncology最新文献

Gastric cancer (GC) ranks among the top five most diagnosed cancers globally, with particularly high incidence and mortality rates observed in Asian regions. Despite certain advancements achieved through early screening and treatment strategies in many countries, GC continues to pose a significant public health challenge. Approximately 20% of patients infected with Helicobacter pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia (IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia (SPEM), has attracted much attention. SPEM represents a specific epithelial cell alteration within the gastric mucosa, characterized by the expressing trefoil factor 2 (TFF2) in basal glands, resembling the basal metaplasia of deep antral gland cells. It primarily arises from the transdifferentiation of mature chief cells, mucous neck cells (MNCs), or isthmus stem cells. SPEM is commonly regarded as a precursor lesion in the development of gastric inflammation and subsequent carcinogenesis. The formation of SPEM is intricately associated with chronic gastric inflammation, Helicobacter pylori infection, and various other environmental and genetic factors. Recently, with the profound exploration of the biological and molecular mechanisms underlying SPEM, a deeper understanding of its role in GC initiation and progression has emerged. This review summarizes the role, molecular mechanisms, and clinical significance of SPEM in the onset and progression of GC.

Background: The incidence and mortality rate of hepatocellular carcinoma (HCC) are increasing globally. HCC with inferior vena cava tumor thrombus (HCCIVCTT) represents an advanced stage of the disease. Research suggests that for patients with advanced HCCIVCTT, liver resection combined with thrombectomy is a safe and feasible option that can provide moderate survival benefit. The aim of this study was to evaluate the application value of multimodal transesophageal echocardiography (TEE) in the perioperative period for patients with HCCIVCTT.

Methods: TEE was used for routine intraoperative examination in 17 patients to determine the location and classification of tumor thrombi, guide the proper placement of the inferior vena cava occlusion band during surgery, and evaluate whether the tumor thrombus was completely removed postoperatively.

Results: Among the 17 patients with HCCIVCTT, tumor thrombi invaded the hepatic veins and extended into the inferior vena cava, with 3 cases of extension into the right atrium. The tumor thrombi varied in shape, size, and echogenicity, with high-velocity turbulent flow signals observed within the occluded vessels. There were 10 cases of type I, 4 cases of type II, and 3 cases of type III. Under the guidance of intraoperative TEE, preocclusion bands were successfully placed above the tumor thrombi in type I and II patients, with real-time dynamic monitoring showing no rupture or dislodgement of the thrombi, and postoperatively, the thrombi appeared to be completely removed.

Conclusions: TEE plays an important role in the perioperative management of HCCIVCTT. It can aid in deterring the type of tumor thrombus, selecting the suitable surgical method, and postoperatively assessing the completeness of tumor thrombus removal.

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, with a rising incidence observed in younger demographics. Despite surgical resection remaining the cornerstone of treatment, metastatic CRC poses significant therapeutic challenges. Immunotherapy, a mode of treatment that leverages the patient's immune system, presents a promising frontier in CRC management, particularly for late-stage cases with limited treatment options. The study was aimed to elucidate the relationships between genetic profiles and predictive biomarkers in CRC patients to inform immunotherapy decisions and improve outcomes.

Methods: We conducted a large-scale study involving 660 patients with CRC, analyzing genetic profiles and predictive biomarkers for immune checkpoint inhibitors (ICIs) using next-generation sequencing (NGS) and immunohistochemistry (IHC). The study focused on assessing the association between gene mutations and markers such as microsatellite instability (MSI) status, tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1) expression.

Results: Analysis revealed a diverse mutational landscape in CRC, with TP53 (73.64%), APC (67.58%), and KRAS (46.82%) being the most frequently mutated genes. We observed significant associations between KRAS mutations and co-occurrences with FBXW7, PIK3CA, and SMAD4 mutations, while KRAS mutations were mutually exclusive with TP53 mutations. KRAS mutations were enriched in the PD-L1 tumor proportion score (TPS) ≥1% population (P=0.03), whereas APC mutations were enriched in the PD-L1 TPS <1% population (P=0.10) as compared to their wild types. Additionally, specific mutations such as KRAS p.A146T, PIK3CA p.H1047R, and BRAF p.V600E were significantly associated with higher TMB and MSI-high status, indicating potential benefits from ICI therapy.

Conclusions: Our findings underscore the importance of genetic profiling in guiding treatment decisions for patients with CRC, particularly in the era of immunotherapy. Understanding the complex interplay between genetic alterations and immune markers is critical for optimizing therapeutic strategies and improving clinical outcomes. Further research is warranted to validate these findings and explore personalized treatment approaches in CRC.

Background: In recent years, the incidence of pancreatic cancer has shown an obvious increasing trend worldwide and even causes a greater disease burden to the mankind. Due to the lack of effective early surveillance methods, patients are often in the middle to advanced stages of their disease at the time of detection, thus losing the opportunity for surgery. The currently available chemotherapy regimens are yet to be further improved to prolong patient survival. The use of immune monotherapy in pancreatic cancer is even more frustrating, with poor therapeutic results.

Case description: Here, we present two cases of locally advanced pancreatic cancer in which neoadjuvant chemotherapy (gemcitabine with albumin-bound paclitaxel) was administered in combination with a programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), resulting in the opportunity for surgical intervention. Notably, one patient exhibited a pathological complete response, characterized by minimal residual highly intraepithelial neoplasia accompanied by extensive fibrosis and transparency. Genetic testing found that the patient had a KRAS mutation (c.35G>T, p.G12V).

Conclusions: The efficacy of this combination therapy has renewed our interest in the mechanism of action or drug resistance of tumor cells in chemotherapy and immunotherapy. An in-depth study of the possible synergistic mechanisms of action of these drugs will provide new research directions for the treatment of pancreatic cancer.

Background: Pancreatic acinar cell carcinoma (PACC) is a rare subtype of pancreatic cancer and the clinicopathological behavior of PACC is not yet fully understood. PACC rarely invades the main pancreatic duct (MPD), which causes intraductal growth. Thus, herein, we have reported a rare case of PACC that invaded the MPD and disseminated to the branches of the pancreatic duct (BDs) without exhibiting any continuity with the main tumor.

Case description: A 60-year-old man was found to have a hypo echoic pancreatic head mass on abdominal ultrasonography during a routine medical checkup. In computed tomography, a 30-mm hypo-dense mass was found in the pancreas head. An endoscopic retrograde pancreatography was performed to collect pancreatic juice for cytological examination. MPD was narrowing in pancreatic head and caudal MPD was slightly dilated. Although no malignant cells were detected, a pancreaticoduodenectomy was performed. Histological examination of the excised specimen confirmed the diagnosis of PACC with MPD invasion. Furthermore, tumor implantation was detected in multiple BDs that were downstream of the main tumor, without any continuity with the main tumor.

Conclusions: PACC can metastasize and get implanted in multiple BDs. Thus, post-surgical relapse can occur due to metastatic lesions implanted in the remnant pancreas.

Background: In China, transarterial chemoembolization (TACE) and systemic therapy are the primary treatment for patients with advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is more effective than TACE in treating large HCC (largest diameter ≥7 cm) without macrovascular invasion or extrahepatic spread. Additionally, HAIC in combination with camrelizumab and apatinib has shown promising efficacy and safety in the Barcelona Clinic Liver Cancer stage C (BCLC-C) HCC. The efficacy and safety of the modality of HAIC followed by TACE combined with camrelizumab and apatinib for the treatment of large HCC remains unknown. We present the first case of long-term survival after short-course HAIC followed by TACE combined with camrelizumab and apatinib in large HCC.

Case description: In April 2020, a 50-year-old Chinese woman was diagnosed with BCLC-C HCC. Magnetic resonance imaging (MRI) showed intrahepatic lesions involving the right and left lobes, with a total lesion size of 19 cm × 9 cm. After 3 cycles of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) plus camrelizumab and apatinib, followed by 2 cycles of TACE plus camrelizumab and apatinib, the efficacy was evaluated as a partial response (PR), with a total lesion size of 6.7 cm × 4.6 cm. The patient continued to take apatinib orally for 1.5 months after the last cycle of TACE but discontinued any antitumor therapy for financial reasons. Subsequent imaging consultation showed an efficacy evaluation of complete response (CR) per the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The patient did not experience any serious adverse events during treatment. As of September 2024, the patient's progression-free survival (PFS) has reached 53 months.

Conclusions: The treatment modality of short-course HAIC followed by TACE combined with camrelizumab and apatinib for large HCC is safe and effective, and long-term survival may be expected in patients who achieve a CR.

Background: PANoptosis is a cell death pathway involved in pyroptosis, apoptosis and necrosis, and plays a key role in the development of malignant tumors. However, the molecular signature of PANoptosis in colorectal cancer (CRC) prognosis has not been thoroughly explored. The present study aimed to develop a novel prognostic model based on PANoptosis-related genes in CRC.

Methods: We initially included transcriptome data of 404 CRC samples from The Cancer Genome Atlas (TCGA) cohort and identified differentially expressed genes related to PANoptosis. We then employed Cox, least absolute shrinkage and selection operator (LASSO) regression, and Random Forest methods to determine the prognostic value and constructed a PANoptosis prognostic model, followed by the validation on both internal (TCGA) and external datasets [Nanjing Colorectal Cancer (NJCRC) and Gene Expression Omnibus (GEO), n=635]. We performed immune infiltration analysis and gene set enrichment analysis to reveal biological processes and pathways against differential risk score. Ultimately, we carried out drug sensitivity analysis to predict the response of CRC patients to diverse treatment strategies.

Results: We constructed a predictive model based on four PANoptosis-related genes (TIMP1, CDKN2A, CAMK2B, and TLR3), with a high performance [area under the curve (AUC)_1-year =0.702, AUC_3-year =0.725, AUC_5-year =0.668] and being an independent prognostic factor in predicting the prognosis of CRC patients. Notably, colorectal tumor with high PANoptosis risk score performed higher levels of macrophage infiltration and immune scores, but a greater reduction of Tumor Microenvironment Score (TMEscore) and DNA replication. Particularly, patients in high-risk group exhibited higher sensitivity to fluorouracil, oxaliplatin and lapatinib compared to the low-risk group.

Conclusions: This study highlights the prognostic potential of PANoptosis-related features in CRC, demonstrating their role as key biomarkers significantly associated with patient survival and aiding in the identification of high-risk patients, thereby advancing immunotherapy approaches.

Background: Colonoscopy remains the predominant diagnostic modality for colorectal cancer (CRC), as the diagnostic performance of tumor markers in alone, particularly in the early stages of the disease, is limited. This study sought to develop a diagnostic model for CRC that integrated various laboratory parameters.

Methods: One hundred patients with CRC were assigned to an experimental group while 114 with benign colorectal diseases and 101 healthy individuals were assigned to a control group. The clinical and laboratory data, including the tumor markers such as carcinoembryonic antigen (CEA), glycan carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242), blood count parameters, blood biochemical parameters, and coagulation parameters, were collected for each participant. Three machine-learning models [multilayered perceptron (MLP), eXtreme Gradient Boosting (XGBoost), and random forest (RF)] were used to construct CRC diagnostic models. The performance of each model was evaluated based on its area under the curve (AUC), sensitivity, and specificity.

Results: There are 12 parameters: including CEA, CA19-9, CA242, absolute neutrophil value (NEUT), hemoglobin, the neutrophil/lymphocyte ratio, the platelet/lymphocyte ratio, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, albumin, and prothrombin time, were selected to build the diagnostic model. For the validation set, the RF machine-learning model achieved the highest performance in identifying CRC [AUC: 0.902 (95% confidence interval: 0.812-0.989), accuracy: 0.803, sensitivity: 0.908, specificity: 0.772, positive predictive value: 0.664, negative predictive value: 0.890, and F1 score: 0.763]. The AUC, sensitivity, specificity, and Youden's index for the combined diagnosis of tumor markers CEA, CA19-9, and CA242 were 0.761, 0.486, 0.983, and 0.469, respectively. The RF diagnostic model showed better diagnostic efficacy than the combined diagnosis model of tumor markers CEA, CA19-9 and CA242.

Conclusions: The use of machine learning combined with multiple laboratory parameters effectively improved the diagnostic efficiency of CRC and provided more accurate results for clinical diagnosis.