Surgical management of duodenal Crohn's disease.

BACKGROUND: The case of Crohn's disease involving the duodenum is rare, and its surgical management requires a thorough understanding. AIM: To investigate the surgical management of duodenal Crohn's disease. METHODS: We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1, 2004, to August 31, 2022. The general information, surgical procedures, prognosis, and other information of these patients were collected and summarized. RESULTS: A total of 16 patients were diagnosed with duodenal Crohn's disease, where 6 cases had primary duodenal Crohn's disease, and 10 had secondary duodenal Crohn's disease. Among patients with primary disease, 5 underwent duodenal bypass and gastrojejunostomy, and 1 received pancreaticoduodenectomy. Among those with a secondary disease, 6 underwent closure of duodenal defect and colectomy, 3 received duodenal lesion exclusion and right hemicolectomy, and 1 underwent duodenal lesion exclusion and double-lumen ileostomy. CONCLUSION: Crohn's disease involving the duodenum is a rare condition. Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

Expression of FXR and HRG and their clinicopathological significance in benign and malignant pancreatic lesions.

AIMS: The following study examines the FXR and HRG expression in benign and malignant lesions of the pancreas and evaluates the association between FXR and HRG expression with clinicopathological features and prognosis of pancreatic cancer. MATERIALS AND METHODS: Immunohistochemistry of FXR and HRG was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma (PDAC) specimens, 35 paracancer samples (2 cm away from the tumor, when possible or available), 55 benign lesions and 13 normal tissue samples. RESULTS: The percentage of cases with positive FXR and negative HRG expression was significantly higher in PDAC compared to pericancerous tissues, benign lesions and normal tissues (P<0.05 or P<0.01). In pancreatic tissues with benign lesions, tissues with positive FXR and/or negative HRG protein expression exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive FXR and negative HRG expressions was significantly higher in PDAC with lymph node metastasis, invasion, and TNM stage III+IV disease (P<0.05 or P<0.01). The expression of FXR was negatively correlated with HRG (P<0.05). In addition, the univariate Kaplan-Meier analysis showed that positive FXR and negative HRG expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, and invasion were closely associated with decreased overall survival in PDAC patients (P<0.05 or P<0.01). Moreover, multivariate Cox regression analysis identified that positive FXR and negative HRG expression were independent factors for poor prognosis in PDAC. The AUC for FXR was (AUC=0.709, 95% CI: 0.632-0.787), and for HRG was (AUC=0.719, 95% CI: 0.643-0.796) in PDAC compared to benign lesions. CONCLUSIONS: Positive FXR and negative HRG expression are closely associated with the carcinogenesis, clinical, pathological and biological behaviors, and poor prognosis in PDAC.

Inflammatory caspase-related pyroptosis: mechanism, regulation and therapeutic potential for inflammatory bowel disease.

As an essential part of programmed cell death, pyroptosis is an inflammatory response that is elicited upon infection by intracellular pathogens. Metabolic diseases, atherosclerosis and vital organ damage occur if pyroptosis is over-activated. Macrophages are the main cells that induce pyroptosis with the help of intracellular pattern-recognition receptors stimulated by danger signals and pathogenic microorganisms in the cytosol of host cells. Activated inflammatory caspases induce pyroptosis and produce pro-inflammatory cytokines, such as interleukin-1ß and interleukin-18. Inflammatory programmed cell death is classified as canonical or non-canonical based on inflammatory caspases, which includes caspase-1 (in human and mouse) and caspase-11 (in mouse) or caspase-4 and -5 (in humans). Activated inflammatory caspases cleave the pore-forming effector protein, gasdermin-D, inducing osmotic pressure deregulation of internal fluids and subsequently rupturing the cell membranes. Inflammatory caspases could be attractive therapeutic targets for inflammatory bowel disease (IBD) in which pyroptosis may play an important role. This article reviews the current understanding of the mechanism of pyroptosis, focusing on the regulation of inflammatory caspases and therapeutic strategies for IBD.

Glucose metabolism in gastric cancer: The cutting-edge.

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.

Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor prognosis of gallbladder adenocarcinoma.

BACKGROUND: Gallbladder cancer (GBC) is one of the most aggressive malignant neoplasms with an extremely poor prognosis. Early diagnosis significantly increases the survival rate. The present study was undertaken to evaluate the diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder lesions and to develop a possible alternative treatment for GBC. METHODS: A total of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15 gallbladder polyp, and 35 chronic cholecystitis tissues were included. S1P1 and ERp29 expressions were evaluated by immunohistochemistry. The correlation between S1P1 and ERp29 expression and tumor pathological features and prognosis was analyzed. RESULTS: S1P1 positive rate was significantly higher in gallbladder adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. On the contrary, ERp29 positive rate was significantly lower in adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative ERp29 expression showed moderate or severe atypical hyperplasia in the gallbladder epithelium. The overexpression of S1P1 or non-expression of ERp29 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis, and adenocarcinoma invasion. Univariate Kaplan-Meier analysis showed that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely associated with decreased survival rate. Multivariate Cox regression analysis showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an independent predictor of poor prognosis in gallbladder adenocarcinoma. CONCLUSION: S1P1 overexpression or ERp29 absence is related to the carcinogenesis and progression, and may be potential biomarkers for early detection of gallbladder adenocarcinoma.

Disruption of pRb-p16INK4 pathway: a common event in ampullary carcinogenesis.

BACKGROUND/AIMS: Aberrations of the pRb (Retinoblastoma gene protein)-p16INK4 pathway play a critical role in carcinogenesis. Our objective is to evaluate its role in tumorigenesis and the development of ampullary cancer. METHODOLOGY: We examined expression status of p16INK4 protein and pRb immunohistochemically and assessed their possible prognostic relevance in 36 ampullary cancers. RESULTS: Thirty-four specimens (94.4%) exhibited alteration of p16INK4 and/or pRb expression, with 63.9% (23/36) of cancers showing p16INK4 negative expression and 94.4% (34/36) pRb abnormal expression. p16INK4 protein negative expression correlated significantly with tumor progression features such as advanced tumor stages (p=0.0291), lymph node metastasis (p=0.005), pancreas invasion (p=0.0002) and duodenum invasion (p=0.0101). Cases with both p16RNK4 protein negative expression and pRb overexpression showed poorer differentiation, more invasive growth (p=0.0425), higher level tumor stages (p=0.0079) and more frequent pancreas invasion (p=0.0024), compared with the others. p16INK4 protein expression showed no relationship with pRb expression (p=0.2199). No association was found in pRb expression status compared with any clinicopathological parameters analyzed. CONCLUSIONS: The disruption of the pRb-p16NK4 pathway plays an important role in ampullary carcinogenesis, the absence of p16INK4 protein expression might be involved in ampullary tumor progression.

Measurement of des-gamma-carboxy prothrombin levels in cancer and non-cancer tissue in patients with hepatocellular carcinoma.

In a recent experiment, we discovered that liver tissue adjacent to HCC can also produce des-gamma-carboxy prothrombin (DCP). The goal of this study was to advance measurements of DCP levels in hepatocellular carcinoma (HCC) and non-cancer tissues using an electro-chemiluminescence immunoassay (ECLIA) and immunohistochemistry, and to assess their clinical significance. DCP levels in HCC tissues ranged from 0.7 to 209862.4 mAU/0.1 g tissue weight, with a median of 492.6 mAU/0.1 g. DCP levels in non-cancer tissues ranged from 0 to 2329.9 mAU/0.1 g tissue weight, with a median of 88.8 mAU/0.1 g. DCP levels in cell membranes were significantly higher than in the cytoplasm (p<0.001). DCP levels in HCC tissue were significantly higher than in non-cancer tissue (p<0.001). The logarithm of serum DCP levels correlated not only with that of DCP levels in HCC tissues (p=0.019), but also with that in non-cancer tissues (p=0.020), and the total DCP level of liver tissues (p=0.016). The logarithm of DCP levels in HCC tissues correlated with that of DCP levels in non-cancer tissues (p=0.011). DCP levels in HCC tissue with portal vein invasion were significantly greater than in HCC tissues without portal vein invasion (p=0.028). DCP levels in non-cancer tissues with intrahepatic metastatic lesions were significantly higher than in non-cancer tissues without intrahepatic metastatic lesions (p=0.023). Our results suggest that the origin of elevated serum DCP may lie not only in HCC tissue, but in non-cancer tissue. The existence of HCC may influence production of DCP in non-cancer tissue. Tissue DCP may be a prognostic factor, while increased DCP levels in non-cancer tissues may play an important role in hepatocarcinogenesis.

Des-gamma-carboxy prothrombin in cancer and non-cancer liver tissue of patients with hepatocellular carcinoma.

Des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K absence or antagonist II absence (PIVKA-II), has been considered as a useful serum tumor marker for hepatocellular carcinoma (HCC). However, the underlying mechanism causing the elevation of serum DCP levels in HCC patients remains unclear. This study was undertaken to identify the relationship between serum DCP levels and the expression of DCP in cancer and surrounding non-cancer liver tissues of HCC patients. Serum and tissue samples prepared from 92 patients with a single HCC nodule were subjected to clinicopathological study by measuring serum DCP levels and performing immunohistochemical staining for tissue DCP. Serum DCP levels correlated significantly with clinicopathological factors such as hepatitis markers, tumor differentiation, vascular invasion, intrahepatic metastasis, TNM stage, tumor size, tumor recurrence, and patient survival. DCP immunohistochemical staining was positive in cancer tissues for 68 (68/92, 73.9%) patients and in non-cancer tissues surrounding tumors for 24 (24/92, 26.1%) patients. There was no apparent correlation between serum DCP values and the expression of DCP in HCC tissues; however, there was a significant correlation between serum DCP levels and the expression of DCP in non-HCC tissues (p=0.0398). In conclusion, our results suggest that the origin of elevated serum DCP may lie not only in HCC tissue but also in non-cancer tissues. The HCC lesion itself appears to influence the production of DCP in surrounding non-cancer tissues.