The Adaptive Immune Response in Hepatitis B Virus-Associated Hepatocellular Carcinoma Is Characterized by Dysfunctional and Exhausted HBV-Specific T Cells.

This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.

Endoscopic calcium electroporation for colorectal cancer: a phase I study.

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Colonic Stent as Bridge to Surgery for Malignant Obstruction Induces Gene Expressional Changes Associated with a More Aggressive Tumor Phenotype.

BACKGROUND: Colonic stent is recommended as a bridge to elective surgery for malignant obstruction to improve short-term clinical outcomes for patients with colorectal cancer. However, since the oncological outcomes remain controversial, this study aimed to investigate the impact of self-expandable metallic stent (SEMS) on the tumor microenvironment. METHODS: Patients treated with colonic stent as a bridge to surgery from 2010 to 2015 were identified from hospital records. Tumor biopsies and resected tumor samples of the eligible patients were retrieved retrospectively. Gene expression analysis was performed using the NanoString nCounter PanCancer IO 360 gene expression panel. RESULTS: Of the 164 patients identified, this study included 21 who underwent colonic stent placement as a bridge to elective surgery. Gene expression analysis revealed 82 differentially expressed genes between pre- and post-intervention specimens, of which 72 were upregulated and 10 downregulated. Among the significantly upregulated genes, 46 are known to have protumor functions, of which 26 are specifically known to induce tumorigenic mechanisms such as proliferation, migration, invasion, angiogenesis, and inflammation. In addition, ten differentially expressed genes were identified that are known to promote antitumor functions. CONCLUSION: SEMS induces gene expressional changes in the tumor microenvironment that are associated with tumor progression in colorectal cancer and may potentiate a more aggressive phenotype. Future studies are warranted to establish optimal timing of surgery after SEMS insertion in patients with obstructive colorectal cancer.

Delay of surgery after stent placement for resectable malignant colorectal obstruction is associated with higher risk of recurrence.

BACKGROUND: Self-expanding metal stents can be used as bridge to elective surgery for acute malignant colonic obstruction. However, the impact on long-term oncological outcome and the optimal timing of surgery are still unknown. METHOD: This was a retrospective multicenter study performed at four colorectal centers. Patients undergoing stent placement as bridge to surgery, between January 2010 and December 2013, were included in the study. Primary outcomes were survival and recurrence rates along with location of the metastases. Additionally, we recorded time from stent placement to elective surgery. Secondary outcomes were postoperative complication rates. Complications were classified according to the Clavien-Dindo classification score. A logistic regression model was used to describe impact of delayed stent removal on risk of recurrence. RESULTS: This study included 112 patients, with a median follow-up of 43 months. Survival rate was 70%. We found a recurrence rate of 37%, primarily local recurrences (17%). Procedure-related complications at the stent placement were seen in 18%, and complications after subsequent elective surgery were seen in 39%. A significantly higher risk of recurrence with increased time from stent placement to elective surgery (OR 5.1 [1.6-15.8], p = 0.005) was found. CONCLUSION: Delay of elective surgery after stent placement may have a negative influence on long-term oncologic outcomes.

Evaluation of Sexual and Urinary Function After Implementation of Robot-assisted Surgery for Rectal Cancer: A Single-Center Study.

PURPOSE: Our objective was to report postoperative urogenital dysfunction after rectal cancer surgery, identifying possible predictors including conventional laparoscopic total mesorectal excision and robot-assisted total mesorectal excision laparoscopic surgery. MATERIALS AND METHODS: Questionnaires were mailed to 184 patients who underwent laparoscopic rectal cancer surgery between January 2009 and May 2013. Single questions were used to retrospectively assess preoperative urogenital dysfunction. Surgical data were collected from hospital records. Postoperative urinary and sexual function was measured with validated questionnaires and the results were statistically analyzed. RESULTS: A total of 97 questionnaires were included in the study. Of those sexually active before the operation, 81% reported some degree of erectile dysfunction (ED). In total, 73% reported some degree of orgasmic dysfunction (OD). On multivariate analyses, older age was the only predictor for ED (P=0.0012). Older age (P=0.007) and having a rectal extirpation procedure (P=0.013) were predictors of OD. CONCLUSIONS: ED and OD are common after rectal cancer surgery. Robotic surgery was seemingly not associated with ED or OD.

Limited Evidence for Robot-assisted Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To evaluate available evidence on robot-assisted surgery compared with open and laparoscopic surgery. METHOD: The databases Medline, Embase, and Cochrane Library were systematically searched for randomized controlled trials comparing robot-assisted surgery with open and laparoscopic surgery regardless of surgical procedure. Meta-analyses were performed on each outcome with appropriate data material available. Cochrane Collaboration's tool for assessing risk of bias was used to evaluate risk of bias on a study level. The GRADE approach was used to evaluate the quality of evidence of the meta-analyses. RESULTS: This review included 20 studies comprising 981 patients. The meta-analyses found no significant differences between robot-assisted and laparoscopic surgery regarding blood loss, complication rates, and hospital stay. A significantly longer operative time was found for robot-assisted surgery. Open versus robot-assisted surgery was investigated in 3 studies. A lower blood loss and a longer operative time were found after robot-assisted surgery. No other difference was detected. CONCLUSIONS: At this point there is not enough evidence to support the significantly higher costs with the implementation of robot-assisted surgery.

Surgical Residents are Excluded From Robot-assisted Surgery.

PURPOSE: Implementation of a robotic system may influence surgical training. The aim was to report the charge of the operating surgeon and the bedside assistant at robot-assisted procedures in urology, gynecology, and colorectal surgery. MATERIALS AND METHODS: A review of hospital charts from surgical procedures during a 1-year period from October 2013 to October 2014. All robot-assisted urologic, gynecologic, and colorectal procedures were identified. Charge of both operating surgeon in the console and bedside assistant were registered. RESULTS: A total of 774 robot-assisted procedures were performed. In 10 (1.3%) of these procedures, a resident attended as bedside assistant and never as operating surgeon in the console. CONCLUSIONS: Our results demonstrate a severe problem with surgical education. Robot-assisted surgery is increasingly used; however, robotic surgical training during residency is almost nonexisting.

[Poor evidence for the use of self-expanding metallic stents in the treatment of malignant colorectal obstruction].

Since the early 1990s self-expanding metallic stents (SEMS) have been used as an alternative to emergency surgery in the treatment of malignant colorectal obstruction. The sparse literature on the subject was reviewed. SEMS seems to be an acceptable palliative procedure in disseminated patients, but as a "bridge to surgery" before elective resection the results from expert single centers and small randomized multicenter trials are conflicting. The most worrying issue is a possible negative effect on long-term survival after SEMS because of a risk of disseminating tumour cells by the procedure.