A prospective, single-centre, randomized, double-blind controlled study protocol to study whether long-term oral metronidazole can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer.

INTRODUCTION: Fifteen to 25% of patients with colorectal cancer have combined liver metastases at the time of diagnosis, whereas an additional 15 to 25% will develop liver metastases after curative resection of primary colorectal cancer, with the vast majority (80-90%) of liver metastases unresponsive to curative resection at first. Colorectal cancer liver metastasis is also the leading cause of death in patients with colorectal cancer. In recent years, several studies have demonstrated that intestinal flora, especially Fusobacterium nucleatum, plays a crucial role in the development of colorectal cancer liver metastasis, so we hypothesized that long-term metronidazole use could effectively reduce the incidence of postoperative liver metastasis in colorectal cancer patients. METHODS/DESIGN: This study is a prospective, single-centre, randomized, double-blind controlled study in which 300 patients will be randomly assigned to the test group or the control group in a 1:1 allocation ratio. The aim of this trial is to demonstrate that long-term oral antibiotics can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210229). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046201. Registered on July 05, 2021.

Comparing intracorporeal mechanical anastomosis vs. hand-sewn esophagojejunostomy after total laparoscopic gastrectomy for esophagogastric junction cancer: a single-center study.

OBJECTIVE: This study aimed to compare the effects of continuous hand-sewn esophagojejunostomy with barbed suture and mechanical anastomosis in total laparoscopic gastrectomy for esophagogastric junction cancer. MATERIALS AND METHODS: The clinical data of 60 patients who underwent total laparoscopic total gastrectomy from January 2020 to October 2021 were collected retrospectively. Baseline data and short-term surgical results of patients in the hand-sewn anastomosis (n = 30) and mechanical anastomosis (n = 30) groups were analyzed. RESULTS: No significant differences were detected in the baseline data between groups. Meanwhile, the hand-sewn group had a shorter anastomosis time (21.2 ± 4.9 min vs. 27.9 ± 6.9 min, p < 0.001) and a decreased operation cost (CNY 70608.3 ± 8106.7 vs. CNY 76485.6 ± 3149.9, p = 0.001). The tumor margin distance in the hand-sewn group was longer than in the mechanical group (2.7 ± 0.4 cm vs. 2.2 ± 0.75 cm, p = 0.002). In esophagojejunostomy anastomosis, the distance between the jejunal opening and jejunal stump in the hand-sewn group was significantly shorter than that in the mechanical group (2.2 ± 0.54 cm vs. 5.7 ± 0.6 cm, p < 0.001). No significant difference was detected in the incidence of postoperative anastomotic complications. CONCLUSION: The continuous hand-sewn anastomosis with barbed suture in total laparoscopic gastrectomy for esophagogastric junction cancer is practical, safe, and cost-effective. It is also an effective supplementary technique for mechanical anastomosis.

Different 18F-FDG imaging: A rare case of liver multiple carcinomas.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

Study protocol for comparing the efficacy of left-open single-flap technique versus double-flap technique after proximal gastrectomy: A multicenter randomized controlled trial.

Background: Proximal gastrectomy has gradually gained more attention due to its superiority in retaining the function of part of the stomach. The inevitable loss of the antireflux barrier and postoperative complications resulting from proximal gastrectomy can severely affect the quality of life. Continuous improvements in digestive tract reconstruction after proximal gastrectomy have yielded the development of a variety of methods with antireflux functions. Recently, our center attempted the left-open single-flap technique and initiated a multicenter, prospective, randomized controlled trial for patients undergoing proximal gastrectomy to reduce the difficulty of surgical anastomosis and the incidence of perioperative complications compared with the double-flap technique. These findings will provide more evidence-based medical research for the development of clinical guidelines. Methods/design: This study is a prospective, multicenter, randomized controlled clinical trial. We plan to recruit 250 patients who are eligible for proximal gastrectomy. After informed consent is obtained, patients will be randomly assigned to the trial group (left-open single-flap technique) and the control group (double-flap technique) in a 1:1 allocation ratio. Discussion: Increasingly, clinical studies have focused on the improvement of reconstruction modalities after proximal gastrectomy. Among these methods, the double-flap technique is a clinically effective method. The purpose of this study is to establish a prospective randomized controlled trial to compare the efficacy of the left-open single-flap technique versus the double-flap technique after proximal gastrectomy, aiming to provide more evidence-based medical studies for digestive tract reconstruction in proximal gastrectomy. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT05418920].

Protocol for Comparing the Efficacy of Three Reconstruction Methods of the Digestive Tract (Kamikawa Versus Double-Tract Reconstruction Versus Tube-Like Stomach) After Proximal Gastrectomy.

Background: Appropriate gastrointestinal reconstruction after proximal gastrectomy can effectively reduce the incidence of postoperative complications in patients with proximal early gastric cancer. However, there is still great controversy about the choice of digestive tract reconstruction after proximal gastrectomy, and there is no clinical consensus on the choice of digestive tract reconstruction after proximal gastrectomy. Currently, there is a lack of large-sample, prospective, randomized controlled studies to compare the efficacy of Kamikawa, double-tract reconstruction, and tube-like stomach reconstruction after proximal gastrectomy. Methods/design: This study will investigate the efficacy of three reconstruction methods after proximal gastrectomy in a prospective, multicenter, randomized controlled trial, which will enroll 180 patients with proximal early gastric cancer. Patients will be randomly divided into three groups: Group A (Kamikawa, n = 60), Group B (double-tract reconstruction, n = 60), and Group C (tube-like stomach, n = 60). The general information, past medical history, laboratory findings, imaging findings, and surgical procedures of the patients will be recorded and analyzed. The incidence of reflux esophagitis will be recorded as the primary endpoint. The incidence of anastomotic leakage, anastomotic stenosis, operative time and intraoperative blood loss will be recorded as secondary endpoints. Discussion: This study will establish a large-sample, prospective, randomized controlled trial to compare the efficacy of Kamikawa, double-tract reconstruction, and tube-like stomach reconstruction after proximal gastrectomy. Trial registration: This study was approved by the Chinese Clinical Trial Registry and registered on April 30, 2021. The registration number is ChiCTR2100045975.

A retrospective study of the role of preoperative ultrasonography in the detection of deep vein thrombosis in 1750 patients with gastric and colorectal cancers.

BACKGROUND: There has been a lack of research in the past on the prevalence and risk factors associated with deep vein thrombosis (DVT) in patients with resectable gastric and colorectal cancers. The purpose of this study was to review the anatomical distribution, prevalence and risk factors associated with lower limb DVT in 1750 patients with preoperative gastric and colorectal cancers and to evaluate the role of preoperative ultrasonography in the detection of DVT in preventing postoperative pulmonary thromboembolism (PTE) in patients with gastric and colorectal cancers. METHODS: A total of 1750 patients with gastric and colorectal cancers who underwent preoperative venous ultrasonography of the lower limbs were retrospectively reviewed. The risk factors associated with preoperative DVT were identified using univariate and multivariate logistic regression analysis. RESULTS: Seventy-three of the 1750 patients with gastric and colorectal cancers had DVT detected by preoperative venous ultrasonography of the lower limb and the incidence of lower limb DVT was 4.17 % in 1750 patients with gastric and colorectal cancers. Univariate analysis showed a higher risk of DVT in patients who met the following criteria: aged ≥80 years, female sex, the performance status ≥1, stage IV, ASA class ≥ III/IV, and hypertension. Multivariate logistic regression analysis showed that female sex, stage IV and ASA class ≥ III/IV were significantly associated with DVT before gastric and colorectal cancer surgery. CONCLUSIONS: Our study showed that female sex, stage IV and ASA class ≥ III/IV were significantly associated with DVT before gastric and colorectal cancer surgery. Routine venous ultrasonography for the lower limb can identify the risk of PTE, which is of great significance in the prevention and occurrence of PTE.

Are preoperative oral antibiotics effective in reducing the incidence of anastomotic leakage after colorectal cancer surgery? Study protocol for a prospective, multicentre, randomized controlled study.

INTRODUCTION: The optimal preoperative preparation for elective colorectal cancer surgery has been debated in academic circles for decades. Previously, several expert teams have conducted studies on whether preoperative mechanical bowel preparation and oral antibiotics can effectively reduce the incidence of postoperative complications, such as surgical site infections and anastomotic leakage. Most of the results of these studies have suggested that preoperative mechanical bowel preparation for elective colon surgery has no significant effect on the occurrence of surgical site infections and anastomotic leakage. METHODS/DESIGN: This study will examine whether oral antibiotic bowel preparation (OABP) influences the incidence of anastomotic leakage after surgery in a prospective, multicentre, randomized controlled trial that will enrol 1500 patients who require colon surgery. The primary endpoint, incidence of anastomotic leakage, is based on 2.3% in the OABP ± mechanical bowel preparation (MBP) group in the study by Morris et al. Patients will be randomized (1:1) into two groups: the test group will be given antibiotics (both neomycin 1 g and metronidazole 0.9 g) the day before surgery, and the control group will not receive any special intestinal preparation before surgery, including oral antibiotics or mechanical intestinal preparation. All study-related clinical data, such as general patient information, past medical history, laboratory examination, imaging results, and surgery details, will be recorded before surgery and during the time of hospitalization. The occurrence of postoperative fistulas, including anastomotic leakage, will be recorded as the main severe postoperative adverse event and will represent the primary endpoint. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200173). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Protocol was revised on November 22, 2021, version 4.0. TRIAL REGISTRATION: ChiCTR2000035550 . Registered on 13 Aug 2020.

Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model.

Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30-100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used. Regulatory T cells (Tregs) can protect allografts from immune rejection, and our previous study showed that the effects of imDex were significantly associated with Tregs. Therefore, we incorporated Tregs into the treatment protocol to further reduce or avoid suppressant use. We defined the optimal exosome dose as approximately 20 µg (per treatment before, during and after transplantation) in rat liver transplantation and the antigen-specific role of Tregs in protecting liver allografts. In the co-treatment group, recipients achieved long-term survival, and tolerance was induced. Moreover, imDex amplified Tregs, which required recipient DCs and were enhanced by IL-2. Fortunately, the expanded Tregs retained their regulatory ability and donor-specificity. Thus, imDex and donor-specific Tregs can collaboratively induce graft tolerance.

Fbxw7 regulates hepatocellular carcinoma migration and invasion via Notch1 signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and also the leading cause of cancer-related death in the world. The mechanisms underlying the progression and metastasis of HCC remain unclear. The E3 ubiquitin ligase F-box and WD repeat domain-containing 7 (Fbxw7) is broadly considered as a tumor suppressor gene. However, the role of Fbxw7 in HCC is not clear. To investigate the expression and biological functions of Fbxw7 in HCC, we examined Fbxw7 expression level using HCC tissue microarray and immunohistochemistry. Our data showed that Fbxw7 expression is significantly reduced in HCC compared with non-cancerous tissues (P<0.05). Fbxw7 levels were significantly associated with tumor differentiation (P=0.013), the incidence of portal or hepatic venous invasion (P=0.031), metastasis (P=0.027) and AJCC cancer stage (P=0.047). Then, we observed a strong correlation between low Fbxw7 expression and a worse 5-year survival of HCC patients (P<0.001). Furthermore, multivariate Cox regression analyses demonstrated that the Fbxw7 expression (P<0.001) was an independent factor for the prediction of the overall survival of HCC patients. We also found that both Fbxw7 mRNA and protein levels were significantly reduced in HCC cell lines compared with human liver non-tumor cell line. Moreover, our in vitro experiments showed a remarkable increase of cell migration and invasion in Fbxw7-knockdown cells and a decrease in Fbxw7-overexpress cells. In addition, the present study demonstrated that Fbxw7 is involved in the migration and invasion of HCC cells via regulating Notch1 and the downstream molecules of Notch1. Taken together, our findings indicate that Fbxw7 can be used as a prognostic marker; it has an important role in HCC progression and inhibits HCC cell migration and invasion through the Notch1 signaling pathway.

Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): clinical analyses of patients and an HCC rat model.

MicroRNAs (miRNAs) are associated with human carcinogenesis and tumor development. Moreover, serum miRNAs can reflect the level of tissue miRNAs and be potential tumor markers. Serum microRNA-21 (miR-21) is overexpressed in many human cancers including hepatocellular carcinoma (HCC). However, how serum miR-21 changes during the HCC formation and whether miR-21 plays a regulatory role in this whole process are unknown. The current study evaluated the prognostic and diagnostic potential of serum miR-21 in HCC patients. Next, we established a HCC rat model and collected the blood and liver tissues at regular time points. AFP from the serum, RNA from the serum and liver tissues were collected and quantified separately. The results revealed that tissue and serum miR-21 was upregulated significantly in the groups of cirrhosis, early and advanced HCC compared with normal and fibrosis groups. The AFP levels were increased in early and advanced HCC compared with other groups. Then, the changes of miR-21 downstream proteins (i.e., programmed cell death 4 [PDCD4] and phosphatase and tensin homolog [PTEN]) in the liver tissues were measured. PDCD4 and PTEN expression was decreased gradually after tumor induction and negatively correlated with miR-21 expression. All these results suggested that serum miR-21 was associated with the prognosis of HCC; the changes in serum miR-21 were earlier and more accurately reflected the pathogenesis of HCC than AFP; therefore, it could be used as an early diagnostic marker for HCC. Our in vivo experiments further confirmed that miR-21 plays an important role in promoting the occurrence and development of HCC by regulating PDCD4 and PTEN.