Surgical strategies for challenging common bile duct stones in the endoscopic era: A comprehensive review of current evidence.

While endoscopic retrograde cholangiopancreatography (ERCP) remains the primary treatment modality for common bile duct stones (CBDS) or choledocholithiasis due to advancements in instruments, surgical intervention, known as common bile duct exploration (CBDE), is still necessary in cases of difficult CBDS, failed endoscopic treatment, or altered anatomy. Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes. This review elucidates relevant clinical anatomy, selection indications, and outcomes to enhance surgical understanding. The selection between trans-cystic (TC) vs trans-choledochal (TD) approaches is described, along with stone removal techniques and ductal closure. Detailed surgical techniques and strategies for both the TC and TD approaches, including instrument selection, is also provided. Additionally, this review comprehensively addresses operation-specific complications such as bile leakage, stricture, and entrapment, and focuses on preventive measures and treatment strategies. This review aims to optimize the management of CBDS through laparoscopic CBDE, with the goal of improving patient outcomes and minimizing risks.

Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.

BACKGROUND: Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as "master organizers" for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of TSPANs in patient-derived primary CRC tissues and their CMS classifications. METHODS: RNA samples were derived from primary CRC tissues (n = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and TSPAN-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed. RESULTS: Of the highly expressed TSPAN genes in CRC tissues (TSPAN8, TSPAN29, and TSPAN30), TSPAN8 was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC. CONCLUSIONS: The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.

Timed barium esophagography to predict recurrent achalasia after peroral endoscopic myotomy: a retrospective study in Thailand.

Background/Aims: Achalasia is a rare esophageal motility disease, for which peroral endoscopic myotomy (POEM) has emerged as a promising treatment option; however, recurrence remains a challenge. Timed barium esophagography (TBE) is a useful diagnostic tool and potential outcome predictor of achalasia. This study aimed to determine predictive tools for recurrence after POEM. Methods: This retrospective study enrolled achalasia patients who underwent POEM between January 2015 and December 2021. Patients were categorized into two groups using the 1-month post-POEM Eckardt scores and TBE: the discordant group (Eckardt score improved >50%, TBE decreased <50%) and the concordant group (both Eckardt score and TBE improved >50%). Recurrence was defined as a reincrease in the Eckardt score to more than three during follow-up. Results: Complete medical records were available in 30 patients who underwent POEM. Seventeen patients (56.7%) were classified into the discordant group, while 13 patients (43.3%) were in the concordant group. The overall recurrence rate was 11.9% at 1-year, increasing to 23.8% during the extended follow-up. The discordant group had a 6.87 fold higher recurrence rate than the concordant group (52.9% vs. 7.7%, p=0.017). Conclusions: These results strongly suggest that combining the Eckardt score with TBE can effectively predict recurrent achalasia after POEM. Patients in the discordant group had an elevated risk.

Spatial Transcriptomic Profiling of Tetraspanins in Stage 4 Colon Cancer from Primary Tumor and Liver Metastasis.

Stage 4 colon cancer (CC) presents a significant global health challenge due to its poor prognosis and limited treatment options. Tetraspanins, the transmembrane proteins involved in crucial cancer processes, have recently gained attention as diagnostic markers and therapeutic targets. However, their spatial expression and potential roles in stage 4 CC tissues remain unknown. Using the GeoMx digital spatial profiler, we profiled all 33 human tetraspanin genes in 48 areas within stage 4 CC tissues, segmented into immune, fibroblast, and tumor compartments. Our results unveiled diverse gene expression patterns across different primary tumor sub-regions. CD53 exhibited distinct overexpression in the immune compartment, hinting at a potential role in immune modulation. TSPAN9 was specifically overexpressed in the fibroblast compartment, suggesting involvement in tumor invasion and metastasis. CD9, CD151, TSPAN1, TSPAN3, TSPAN8, and TSPAN13 displayed specific overexpression in the tumor compartment, indicating potential roles in tumor growth. Furthermore, our differential analysis revealed significant spatial changes in tetraspanin expression between patient-matched stage 4 primary CC and metastatic liver tissues. These findings provide spatially resolved insights into the expression and potential roles of tetraspanins in stage 4 CC progression, proposing their utility as diagnostic markers and therapeutic targets. Understanding this landscape is beneficial for tailoring therapeutic strategies to specific sub-tumor regions in the context of stage 4 CC and liver metastasis.

Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma.

BACKGROUND: Surgical resection followed by indicated adjuvant therapy offers potential curative treatment in colonic adenocarcinoma. Beyond the well-established seed and soil theory of colon cancer progression, the 'normal-appearing' tissues near the tumor are not genuinely normal and remain as remnants in patients following surgery. Our objective was to elucidate the alteration of gene expression and pathways across various distances of resection margins in right-sided colonic adenocarcinoma. METHODS: Twenty-seven fresh samples of primary cancer and 56 matched non-tumor tissues adjacent to the tumor (NAT) were collected from patients with resectable right-sided colon cancer. NAT were systematically obtained at varying distances (1, 5, and 10 cm) on both proximal and distal sides. Comprehensive gene expression analysis was performed using 770-gene PanCancer Progression Panel, delineating distinctive pathways and functional predictions for each region. RESULTS: Distinctive gene signatures and pathways exhibited by normal-appearing tissues were discovered at varying distances from cancer. Notably, SFRP2, PTGDS, COL1A1, IL1B, THBS2, PTGIS, COL1A2, NPR1, and BGN were upregulated, while ENPEP, MMP1, and NRCAM were downregulated significantly in 1-cm tissue compared to farther distances. Substantial alterations in the extracellular matrix (ECM) and prostaglandin/thromboxane synthesis were significantly evident at the 1-cm distance. Functional analysis indicated enhanced cell viability and survival, alongside reduced cellular death and apoptosis. CONCLUSIONS: Different distances exerted a significant impact on gene alteration within the normal-looking mucosa surrounding primary cancer, influenced by various mechanisms. These findings may highlight potential therapeutic targets related to the ECM and prostaglandin/thromboxane pathways for treatment strategies.

Aerosol protection using modified N95 respirator during upper gastrointestinal endoscopy: a randomized controlled trial.

Background/Aims: The coronavirus disease 2019 pandemic has affected the worldwide practice of upper gastrointestinal endoscopy. Here we designed a modified N95 respirator with a channel for endoscope insertion and evaluated its efficacy in upper gastrointestinal endoscopy. Methods: Thirty patients scheduled for upper gastrointestinal endoscopy were randomized into the modified N95 (n=15) or control (n=15) group. The mask was placed on the patient after anesthesia administration and particles were counted every minute before (baseline) and during the procedure by a TSI AeroTrak particle counter (9306-04; TSI Inc.) and categorized by size (0.3, 0.5, 1, 3, 5, and 10 µm). Differences in particle counts between time points were recorded. Results: During the procedure, the modified N95 group displayed significantly smaller overall particle sizes than the control group (median [interquartile range], 231 [54-385] vs. 579 [213-1,379]×103/m3; p=0.056). However, the intervention group had a significant decrease in 0.3-µm particles (68 [-25-185] vs. 242 [72-588]×103/m3; p=0.045). No adverse events occurred in either group. The device did not cause any inconvenience to the endoscopists or patients. Conclusions: This modified N95 respirator reduced the number of particles, especially 0.3-µm particles, generated during upper gastrointestinal endoscopy.

The KRAS-Mutant Consensus Molecular Subtype 3 Reveals an Immunosuppressive Tumor Microenvironment in Colorectal Cancer.

Colorectal cancers (CRC) with KRAS mutations (KRASmut) are frequently included in consensus molecular subtype 3 (CMS3) with profound metabolic deregulation. We explored the transcriptomic impact of KRASmut, focusing on the tumor microenvironment (TME) and pathways beyond metabolic deregulation. The status of KRASmut in patients with CRC was investigated and overall survival (OS) was compared with wild-type KRAS (KRASwt). Next, we identified CMS, and further investigated differentially expressed genes (DEG) of KRASmut and distinctive pathways. Lastly, we used spatially resolved gene expression profiling to define the effect of KRASmut in the TME regions of CMS3-classified CRC tissues. CRC patients with KRASmut were mainly enriched in CMS3. Their specific enrichments of immune gene signatures in immunosuppressive TME were associated with worse OS. Activation of TGFß signaling by KRASmut was related to reduced pro-inflammatory and cytokine gene signatures, leading to suppression of immune infiltration. Digital spatial profiling in TME regions of KRASmut CMS3-classified tissues suggested up-regulated genes, CD40, CTLA4, ARG1, STAT3, IDO, and CD274, that could be characteristic of immune suppression in TME. This study may help to depict the complex transcriptomic profile of KRASmut in immunosuppressive TME. Future studies and clinical trials in CRC patients with KRASmut should consider these transcriptional landscapes.

Is fascial closure required for a 12-mm trocar? A comparative study on trocar site hernia with long-term follow up.

BACKGROUND: Despite the infrequency of trocar site hernias (TSHs), fascial closure continues to be recommended for their prevention when using a ≥ 10-mm trocar. AIM: To identify the necessity of fascial closure for a 12-mm nonbladed trocar incision in minimally invasive colorectal surgeries. METHODS: Between July 2010 and December 2018, all patients who underwent minimally invasive colorectal surgery at the Minimally Invasive Surgery Unit of Siriraj Hospital were retrospectively reviewed. All patients underwent cross-sectional imaging for TSH assessment. Clinicopathological characteristics were recorded. Incidence rates of TSH and postoperative results were analyzed. RESULTS: Of the 254 patients included, 70 (111 ports) were in the fascial closure (closed) group and 184 (279 ports) were in the nonfascial closure (open) group. The median follow up duration was 43 mo. During follow up, three patients in the open group developed TSHs, whereas none in the closed group developed the condition (1.1% vs 0%, P = 0.561). All TSHs occurred in the right lower abdomen. Patients whose drains were placed through the same incision had higher rates of TSHs compared with those without the drain. The open group had a significantly shorter operative time and lower blood loss than the closed group. CONCLUSION: Routine performance of fascial closure when using a 12-mm nonbladed trocar may not be needed. However, further prospective studies with cross-sectional imaging follow-up and larger sample size are needed to confirm this finding.

Management of aerosol generation during upper gastrointestinal endoscopy.

In the highly contagious coronavirus disease 2019 pandemic, aerosol-generating procedures (AGPs) are associated with high-risk of transmission. Upper gastrointestinal endoscopy is a procedure with the potential to cause dissemination of bodily fluids. At present, there is no consensus that endoscopy is defined as an AGP. This review discusses the current evidence on this topic with additional management. Prevailing publications on coronavirus related to upper gastrointestinal endoscopy and aerosolization from the PubMed and Scopus databases were searched and reviewed. Comparative quantitative analyses showed a significant elevation of particle numbers, implying that aerosols were generated by upper gastrointestinal endoscopy. The associated source events have also been reported. To reduce the dispersion, certain protective measures have been developed. Endoscopic unit protocols are recommended for the concerned personnel. Therefore, upper gastrointestinal endoscopy should be classified as an AGP. Proper practices should be adopted by healthcare workers and patients.

Laparoscopic surgery produced less surgical smoke and contamination comparing with open surgery: the pilot study in fresh cadaveric experiment in COVID-19 pandemic.

BACKGROUND: The SARS-CoV2 virus has been identified in abdominal cavity of the COVID-19 patients. Therefore, the potential viral transmission from any surgical created smoke in these patients is of concern especially in laparoscopic surgery. This study aimed to compare the amount of surgical smoke and surgical field contamination between laparoscopic and open surgery in fresh cadavers. METHODS: Cholecystectomy in 12 cadavers was performed and they were divided into 4 groups: laparoscopic approach with or without smoke evacuator, and open approach with or without smoke evacuator. The increased particle counts in surgical smoke of each group were analyzed. In the model of appendectomy, surgical field contamination under ultraviolet light and visual contamination scale between laparoscopic and open approach were compared. RESULTS: Open cholecystectomy significantly produced a greater amount of overall particle sizes, particle sizes < 5 µm and particle sizes ≥ 5 µm than laparoscopic cholecystectomy (10,307 × 103 vs 3738 × 103, 10,226 × 103 vs 3685 × 103 and 81 × 103 vs 53 × 103 count/m3, respectively at p < 0.05). The use of smoke evacuator led to decrease in the amount of overall particle sizes of 58% and 32.4% in the open and laparoscopic chelecystectomy respectively. Median (interquatile range) visual contamination scale of surgical field in open appendectomy [3.50 (2.33, 4.67)] was significantly greater than laparoscopic appendectomy [1.50 (0.67, 2.33)] at p < 0.001. CONCLUSIONS: Laparoscopic cholecystectomy yielded less smoke-related particles than open cholecystectomy. The use of smoke evacuator, abeit non-significantly, reduced the particles in both open and laparoscopic cholecystectomy. Laparoscopic appendectomy had a lower degree of surgical field contamination than the open approach.

Outcomes of Laparoscopic Common Bile Duct Exploration by Chopstick Technique in Choledocholithiasis.

BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy with common bile duct exploration (LC with LCBDE) remains the preferred technique for difficult common bile duct stone (CBDS) removal. The chopstick method uses commonly available instruments and may be cost-saving compared to other techniques. We studied the outcome of LCBDE using the chopstick technique to determine if it could be considered a first-choice method. METHODS: Data from all patients that underwent LCBDE from January 1, 2012 to April 30, 2019 were retrospectively analyzed. A standard 4-port incision and CBDS permitted extraction with two laparoscopic instruments by chopstick technique via vertical choledochotomy. Demographic data, stone clearance rate, surgical outcomes, complications, and other associated factors were evaluated. RESULTS: Thirty-two patients underwent LCBDE. The mean number of preoperative endoscopic retrograde cholangiopancreatography (ERCP) sessions was 2.4. In 65.5% of cases, the CBDS was completely removed by the chopstick technique, while 96.9% of stones were removed after using additional tools. The need for additional instruments was associated with increased age, increased numbers of stones, longer period from the latest ERCP session, and previous upper abdominal surgery. The conversion rate to open surgery was 28.1% and was significantly associated with a history of upper abdominal surgery. CONCLUSION: The chopstick technique is a good alternative and could be considered as a first-line technique in LCBDE to remove the CBDS in cases with 1 to 2 large suprapancreatic CBDS due to instrument availability, cost-effectiveness, and comparable surgical outcomes.