Arachidonic acid induces brain endothelial cell apoptosis via p38-MAPK and intracellular calcium signaling.

Arachidonic acid (AA), a bioactive fatty acid whose levels increase during neuroinflammation, contributes to cerebral vascular damage and dysfunction. However, the mode of injury and underlying signaling mechanisms remain unknown. Challenge of primary human brain endothelial cells (HBECs) with AA activated a stress response resulting in caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and disruption of monolayer integrity. AA also induced loss of mitochondrial membrane potential and cytochrome c release consistent with activation of intrinsic apoptosis. HBEC stimulation with AA resulted in sustained p38-MAPK activation and subsequent phosphorylation of mitogen-activated protein kinase activated protein-2 (MAPKAP-2) kinase and heat shock protein-27 (Hsp27). Conversely, other unsaturated and saturated fatty acids had no effect. Pharmacological and RNA interference-mediated p38α or p38ß suppression abrogated AA signaling to caspase-3 and Hsp27, suggesting involvement of both p38 isoforms in AA-induced HBEC apoptosis. Hsp27 silencing also blocked caspase-3 activation. AA stimulated intracellular calcium release, which was attenuated by inositol 1,4,5-trisphosphate (IP3) receptor antagonists. Blockade of intracellular calcium release decreased caspase-3 activation, but had no effect on AA-induced p38-MAPK activation. However, inhibition of p38-MAPK or blockade of intracellular calcium mobilization abrogated AA-induced cytochrome c release. AA-induced caspase-3 activation was abrogated by pharmacological inhibition of lipooxygenases. These findings support a previously unrecognized signaling cooperation between p38-MAPK/MAPKAP-2/Hsp27 and intracellular calcium release in AA-induced HBEC apoptosis and suggest its relevance to neurological disorders associated with vascular inflammation.

Complications of laparoscopic transgastric ERCP in patients with Roux-en-Y gastric bypass.

BACKGROUND: The altered anatomy of Roux-en-Y gastric bypass presents a challenge when duodenal access is required for ERCP. One technique, laparoscopic transgastric ERCP, was first described in 2002. Since that time, a total of 77 laparoscopic or percutaneous transgastric ERCPs have been reported. The largest case series includes 26 ERCPs, and no reports specifically address complications. We reviewed our experience with 85 transgastric ERCPs and report the limitations and complications associated with access and ERCP. METHODS: Retrospective review was conducted of gastric bypass patients who underwent transgastric ERCP in our practice from 2004-2014. RESULTS: Forty-one patients underwent 85 transgastric ERCPs during the study period. Conversion from laparoscopic to open procedure occurred in 4.8%, and selective cannulation rate was 93%. Forty-seven percent of cases were repeat ERCPs performed through a gastrostomy tube tract. During 15-month median follow-up, the overall complication rate was 19%, with 88% of complications related to access rather than ERCP. Most complications were minor; there were no deaths or cases of severe pancreatitis. Additional intervention, including repair of a posterior stomach laceration or transfusion for bleeding, occurred in 4.7% of cases. Operative intervention occurred in two cases: repair of a duodenal perforation, and debridement of an abdominal wall abscess. Post-ERCP hyperamylasemia was common but did not result in increased length of stay or significant clinical pancreatitis. CONCLUSIONS: Roux-en-Y gastric bypass eliminates the normal approach to the duodenum for ERCP. Transgastric access has a high rate of successful cannulation but is associated with complications. Conversion to open procedure occurred in 4.8%, and 16% developed a complication related to the access site, though the rate of operative intervention was low (2.4%). Our study is limited by its retrospective design, which may underestimate the complication rate, and by our homogenous patient population (94% female, 68% sphincter of Oddi dysfunction).

Spigelian Hernia: A Rare Ventral Hernia.

Ventral hernias occur when abdominal contents or the peritoneum displace through a defect in the abdominal wall. Among these, spigelian hernias are an exceptionally rare subtype, representing 0.12% to 2% of all ventral hernias. This case study focuses on an 86-year-old female presenting with a ventral hernia, notably a spigelian hernia, lacking common predisposing factors. The study emphasizes the use of laparoscopic techniques for repair, aiming to offer insights into managing this infrequent hernia type and aiding clinical decision-making. Due to its low incidence and challenging diagnosis and identification, reports such as ours detailing both the clinical course and the operative steps can assist others in their clinical decision-making.

Self-expanding metallic stents for palliation and as a bridge to minimally invasive surgery in colorectal obstruction.

BACKGROUND AND OBJECTIVES: Acute colorectal obstruction is a potentially life-threatening emergency that requires immediate surgical treatment. Emergency procedures had an associated mortality rate of 10% to 30%. This encouraged development of other options, most notably self-expanding metallic stents. The primary endpoint of this study to is to report our group's experience. METHODS: We performed a retrospective review of 37 patients who underwent self-expanding metallic stent placement for colorectal obstruction between July 2000 and May 2012. Data collected were age, comorbidities, diagnosis, intent of intervention (palliative vs bridge to surgery), complications, and follow-up. RESULTS: The study comprised 21 men (56.76%) and 16 women (43.24%), with a mean age of 67 years. The intent of the procedure was definitive treatment in 22 patients (59.46%) and bridge to surgery in 15 (40.54%). The highest technical success rate was at the rectosigmoid junction (100%). The causes of technical failure were inability of the guidewire to traverse the stricture and bowel perforation related to stenting. The mean follow-up period was 9.67 months. Pain and constipation were the most common postprocedure complications. DISCUSSION: The use of a self-expanding metallic stent has been shown to be effective for palliation of malignant obstruction. It is associated with a lower incidence of intensive care unit admission, shorter hospital stay, lower stoma rate, and earlier chemotherapy administration. Laparoscopic or robotic surgery can then be performed in an elective setting on a prepared bowel. Therefore the patient benefits from advantages of the combination of 2 minimally invasive procedures in a nonemergent situation. Further large-scale prospective studies are necessary.

Robotic-assisted ventral and incisional hernia repair with hernia defect closure and intraperitoneal onlay mesh (IPOM) experience.

BACKGROUND: The most common technique described for robotic ventral hernia repair (RVHR) is intraperitoneal onlay mesh (IPOM). With the evolution of robotics, advanced techniques including retro rectus mesh reinforcement, and component separation are being popularized. However, these procedures require more dissection, and longer operative times. In this study we reviewed our experience with robotic ventral/incisional hernia repair (RVHR) with hernia defect closure (HDC) and IPOM. METHODS: Retrospective chart review and follow-up of 31 consecutive cases of ventral/incisional hernia treated between August 2011 and December 2018. Demographics, operative times, blood loss, length of stay (LOS), hernia size, location, and type, mesh size and type, recurrence, conversion to open ventral hernia repair (OVHR) and complications including bleeding, seroma formation and infection were analyzed. RESULTS: Mean age was 63.9 years old, with median BMI of 31.24 kg/m2. Median hernia area was 17 cm2. Mean operating time was 142.61 min (SD 59.79). Mean LOS was 1.46 days (range 1-5), with 48% being outpatient, and overnight stay in 32% for pain control. Conversion was necessary in 12.9% cases. Complication rate was 3% for enterotomy. Recurrence was 14.81% after a mean follow-up of 26.96 months. There was significant association of recurrence with COPD history (P = 0.0215) and multiple hernia defects (P = 0.0376). CONCLUSION: Our recurrence rate (14.81%) compares favorably to those reported in literature (16.7%) for LVHR with HDC and IPOM. Our experience also indicates that IPOM is associated with satisfactory outcomes, low conversion and complications rates, and short LOS.

Robotic retro-rectus repair of parastomal hernias.

OBJECTIVE: To present our technique of robotic retrorectus parastomal hernia repair. BACKGROUND: Parastomal hernias represent a significant problem with high recurrence and long-term complications. An estimated of 120,000 new stomas are created per year with a prevalence of up to 800,000 patients in the U.S. 40-60% of these ostomies will never be reversed. Parastomal hernias cause skin breakdown and make adherence of ostomy appliances difficult, creating the need for frequent bag exchanges. They can also cause pain, bowel obstruction and bowel incarceration or strangulation. All of these factors affect quality of life and represent a significant burden to our health care system. There is no definitive gold-standard technique to repair parastomal hernias. The use of prosthesis decreases the recurrence rates, yet using prosthetic material can result in long-term complications. Surgeons have developed techniques of pre-peritoneal mesh placement to provide long-lasting repairs and at the same time prevent complications associated with the mesh. We believe that a robotic retro-rectus approach provides a secure repair and avoids leaving prosthetic material in the abdominal cavity at the same time. METHODS: A three-arm technique is used, inserting ports opposite to the target anatomy. Hernia contents are reduced protecting the ostomy loop and mesentery. The contralateral retro-rectus space is entered and this space is developed extensively across the midline and around the ostomy. The hernia defect is approximated. Concomitant ventral hernias are also repaired. A polypropylene mesh with a keyhole is used and wide coverage is ensured in all directions. The leaflets of the mesh are stitched together and the mesh is sutured to the abdominal wall. Finally, the retro-rectus space is closed. RESULTS: We have performed this technique in two patients safely and at 1-year follow-up there were no recurrences in either. On conclusion, this is a novel minimally invasive technique to repair parastomal hernias that provides wide coverage of the defect and avoids leaving mesh intraperitoneally.