Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus.

This study aimed to identify BRCA1/2 mutational patterns in the tissue and blood of Egyptian colorectal cancer (CRC) patients and to study the possible correlation of this mutational pattern with Human papillomavirus (HPV) infection. Eighty-two colonoscopic biopsies and forty-six blood samples were collected from Egyptian CRC patients, as well as blood samples of age and sex-matched healthy controls (n = 43) were enrolled. The libraries were performed using Qiaseq Human BRCA1 and BRCA2 targeted DNA panel and sequenced via Ion proton sequencer. Also, the CRC tissues were subjected to conventional PCR targeting the HPV Late 1 (L1) region. Our analysis revealed that the BRCA-DNA damage pathway had been altered in more than 65% of the CRC patients. Comparing tissue and blood samples from CRC patients, 25 somatic mutations were found exclusively in tissue, while 41 germline mutations were found exclusively in blood. Additionally, we identified 23 shared BRCA1/2 pathogenic (PVs) mutations in both blood and tissue samples, with a significantly higher frequency in blood samples compared to tissue samples. The most affected exon in BRCA1 was exon 10, while the most affected exons in BRCA2 were 11, 14, 18, 24, and 27 exons. Notably, we revealed an ethnic-related cluster of polymorphism variants in our population closely related to South Asian and African ethnicities. Novel PVs were identified and submitted to the ClinVar database. HPV was found in 23.8% of the CRC tissues, and 54% of HPV-positive cases had somatic BRCA1/2 PVs. The results of this research point to a possible connection between infection with HPV and BRCA1/2 mutations in the occurrence of colorectal cancer in the Egyptian population, which has a mixed ethnic background. Our data also indicate that liquid biopsy (blood samples) may be more representative than tissue samples for detecting BRCA1/2 mutations. These findings may have implications for cancer screening and the development of personalized, targeted therapies, such as PARP inhibitors, which can effectively target BRCA1/2 mutations.

Impact of the vertical division of the rectum on the decrease in reloading of the endostapler for a complete division in colorectal cancer

Background: Despite several improvements in surgical techniques, the intracorporeal division of the distal end of the rectum is still challenging, particularly when it is too deep in a narrow pelvis. Even though it helps avoid spillage, the double-stapling technique (DST) raises concerns regarding safety and anastomotic leakage if multiple stapler firings are essential to complete the rectal division. Objective: To assess the feasibility of vertically dividing the rectum and its impact in reducing the number of reloads essential for that division in non-low rectal cancer patients undergoing total mesorectal excision (TME). Materials and Methods A retroprospective study. Results: From January 2017 to November 2021, a total of 123 patients with sigmoid and rectal cancers were enrolled in the present study; their data were collected and analyzed, and 21 patients were excluded. The remaining sample of 102 subjects was composed of 47 male (46%) and 55 female (54%) patients with a median age of 54 years (range: 30 to 78 years). Only 1 reload was enough to complete the rectal division in 82 (80.39%) cases, and 2 reloads were used in the remaining 20 (19.61%) patients. Anastomotic leakage was clinically evident in 4 cases (3.9%). No statically significant difference was observed when firing one or two staplers. No 30-day mortality was recorded in this series. Conclusion: Our early experience indicates that this type of division has a real advantage in terms of decreasing the number of reloads needed and, in turn, lowering the incidence of anastomotic leakage after partial mesorectal excision (PME) or TME when applied with proper patient selection. (AU)

Comparative Study Between Early versus Late Intraperitoneal Administration of Either Bupivacaine/Tramadol or Bupivacaine/Dexmedetomidine for Perioperative Analgesia in Abdominal Laparoscopic Cancer Surgeries: A Prospective Randomized Study.

Objective: Several modalities for analgesia after laparoscopic procedures have been used. This study aimed to investigate the efficacy of early versus late bupivacaine/tramadol combination and bupivacaine/dexmedetomidine combination in analgesia for laparoscopic cancer surgeries. Methods: A total of 100 patients of both genders scheduled for elective laparoscopic cancer surgeries were included. Patients were randomly assigned to one of four groups each comprises 25 patients. Group 1: early bupivacaine/tramadol, Group 2: late bupivacaine/tramadol, Group 3: early bupivacaine/dexmedetomidine, and Group 4: late bupivacaine/dexmedetomidine. Early groups received the intraperitoneal instillation before start of surgery and late groups received the instillation after completion of surgery. Perioperative heart rate (HR) and mean arterial blood pressure (MAP) were recorded. The degree of postoperative pain was measured at rest and with cough using Visual analogue scale (VAS) score at 2, 4, 6, 12, 18 and 24 h after surgery. In addition, the total intraoperative fentanyl and postoperative morphine doses were calculated. Results: Both late bupivacaine/tramadol, bupivacaine/dexmedetomidine groups had longer time to receive first analgesic requirement (13.4±3.9, 11.3±3.9 h) respectively as compared to early bupivacaine/tramadol, bupivacaine/dexmedetomidine groups (9.8± 3.6, 8.4± 2.8 h), respectively. Between each early and late group, intraoperative fentanyl consumption was higher for the late groups (75± 22.8, 73± 21.55µg) versus (32.7± 10.9, 37.5± 13.3 µg), respectively. As regards to rescue analgesic requirements, both early bupivacaine/tramadol and bupivacaine/dexmedetomidine groups consumed more analgesics (5.2± 2.0 and 6.1± 1.8 mg) as compared to the late groups (3.2± 0.8 and 4.3± 1.5 mg), respectively. The four groups were comparable for their perioperative HR and MAP values. Conclusion: Intraperitoneal instillation of bupivacaine/tramadol and bupivacaine/dexmedetomidine could be considered an effective route for analgesic administration during laparoscopic cancer surgeries. Early instillation reduced the intraoperative opioid consumption and late instillation resulted in reduced postoperative opioid consumption. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04813016.

Learning curve and volume outcome relationship of endoscopic trans-oral versus trans-axillary thyroidectomy; A systematic review and meta-analysis.

BACKGROUND: In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an exception, with the introduction of multiple endoscopic thyroidectomy techniques. Trans-oral endoscopic trans-vestibular thyroidectomy (TOT) is a novel technique with promising outcomes. We conducted this meta-analysis to compare surgical outcomes and learning curves for TOT and other endoscopic thyroidectomy techniques. METHODS: A systematic review in PubMed, MEDLINE, and EMBASE databases was conducted searching for publications on TOT versus trans-axillary thyroidectomy (TAT). The primary endpoint was operative (OR) time. Secondary endpoints were number of harvested lymph nodes (LNs), estimated blood loss (EBL), recurrent laryngeal nerve (RLN) injury, hoarseness, seroma, infection, chyle leak, hypocalcemia, hospital length of stay (LOS), and Cost. We also investigated the learning curve for each technique. Leave-out-out analysis, meta-regression, and subgroup analysis were used. Random effect inverse variance method was utilized. RESULTS: Among 3820 retrieved studies, 15 studies (10 unmatched and 5 matched), with 2173 (TOT: 1024(47.12%) and TAT:1149(52.87%)) patients, met the inclusion criteria. The operative time and harvested L. Ns number were higher in TOT versus TAT (standard mean difference (SMD) = 0.72 [95%CI 0.07; 1.37], P = 0.029 and SMD = 0.32 [95%CI 0.02; 0.62], P = 0.036 respectively) while less EBL in TOT versus TAT (SMD = -0.26 [-0.43; -0.09], P = 0.0018). All other outcomes showed no significant difference between both groups. Weighted mean values for TOT and TAT were 158.03 vs 144.97 min for OR time, 6.33 vs 5.16 for harvested LNs, and $5,919.05 vs $6,253.79 for the cost. Statistical significance in learning curve development was noticed ranging between 6 and 15 annual cases. CONCLUSION: Trans-oral thyroidectomy is a safe and reliable technique with outcomes comparable to other endoscopic techniques. It provides better access to the central compartment with a more feasible LN dissection. Improvement in surgical outcomes is expected with growing learning curve and technique mastery.

Randomized Controlled Trial of Laparoscopic versus Open Radical Cystectomy in a Laparoscopic Naïve Center.

BACKGROUND: Laparoscopic radical cystectomy is a challenging surgical procedure; however, it has been largely abandoned in favor of the more intuitive robotic-assisted cystectomy. Due to the prohibitive cost of robotic surgery, the adoption of laparoscopic cystectomy is of relevance in low-resource institutes. Methodology. This is a randomized controlled trial comparing laparoscopic radical cystectomy (LRC) to open radical cystectomy (ORC) at a single institute. Each group included thirty patients. The trial was designed to compare both approaches regarding operative time, blood loss, transfusion requirements, length of hospital stay, time to oral intake, requirement of opioid analgesia, and complications. RESULTS: LRC was associated with less hospital stay (9.8 vs. 13.8 days, P=0.001), less time to oral solid intake (6 vs. 8.6 days, P=0.031), and lower opioid requirements (23.3% vs. 53.3%, P=0.033). There was a trend towards lower blood loss and transfusion requirements, but this did not reach statistical significance. Overall complication rates were comparable. CONCLUSION: Laparoscopic radical cystectomy was associated with comparable postoperative outcomes when compared to ORC in the first laparoscopic cystectomy experience in our center. Benefitting from the assistance of an experienced laparoscopic surgeon is recommended to shorten the learning curve.