Anesthetics Impact the Resolution of Inflammation

Local and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine) and a widely used inhaled anesthetic (isoflurane) impact the active process of resolution of inflammation.Using murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages. Addition of a lipoxin A(4) stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri) approximately 50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1). The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation, namely lidocaine delayed the onset of resolution (T(max)), while isoflurane shortened resolution interval (Ri).Taken together, both local and volatile anesthetics impact endogenous resolution program(s), altering specific resolution indices and selective cellular/molecular components in inflammation-resolution. Isoflurane enhances whereas lidocaine impairs timely resolution of acute inflammation

Laparoscopic Puestow: lateral pancreaticojejunostomy.

© 2016, Springer Science+Business Media New York. Introduction: Chronic pancreatitis is a painful inflammatory disease that leads to progressive and irreversible destruction of pancreatic parenchyma [1]. A lateral pancreaticojejunostomy, also known as the Puestow procedure, is performed for symptomatic chronic pancreatitis associated with a dilated pancreatic duct secondary to calcifications or strictures [4]. An open approach is used traditionally due to the complexity of the case, and there have only been a handful of laparoscopic case reports [2]. This video depicts a laparoscopic lateral pancreaticojejunostomy for chronic pancreatitis. Methods: A 45-year-old gentleman with a 20-year history of chronic alcohol abuse presented with diffuse abdominal pain. His pain was worse postprandially and associated with loose stools. A computed tomography scan revealed multiple calcified deposits within the body and tail of the pancreas, and a dilated pancreatic duct measuring 1.4 cm with a proximal obstructing calcified stone. A 5-port foregut technique was used, and a 15-cm pancreatic ductotomy was performed with an ultrasonic scalpel. Calcified stones were cleared from the duct, and a roux-en-y pancreaticojejunostomy was performed using a hand-sewn technique. Results: The patient had a relatively uncomplicated hospital course with return of bowel function on postoperative day 4. His patient-controlled analgesic device was discontinued on post operative day 3. He was ambulating, tolerating a regular diet and discharged home on postoperative day 5. At 12- and 26-month follow-up, he remains off narcotics, but still requires 1–2 tabs of pancreatic enzyme replacement per meal. Most importantly, he has not had any alcohol for over 2 years. Conclusion: The two primary goals in treating chronic pancreatitis include long-term pain relief and improvements in quality of life [3]. For patients with chronic pancreatitis and a dilated pancreatic duct, a laparoscopic lateral pancreaticojejunostomy may be an effective approach to decrease pain and improve quality of life

Laparoscopic bilateral cortical-sparing adrenalectomy for pheochromocytoma.

© 2016, Springer Science+Business Media New York. Introduction: Since laparoscopic adrenalectomy for pheochromocytoma was reported in 1992, the laparoscopic technique has largely replaced the open approach [4]. Numerous studies have demonstrated that the laparoscopic approach is associated with decreased blood loss, shorter hospitalization, faster recovery, and lower cost [1]. Conversion rates are reported at less than 5.5 %, yet concern still exists that intraoperative hypertensive crisis may be more severe with laparoscopy due to increased intraabdominal pressure [3]. Bilateral pheochromocytomas are common in patients with multiple endocrine neoplasia type 2 (MEN 2) or von Hippel-Lindau (VHL) disease. Total adrenalectomy commits the patient to lifelong steroid hormone replacement and the risk of Addisonian crisis after bilateral adrenalectomy [5]; [8]. The risk of malignant pheochromocytomas in patients with or without MEN 2 or VHL is low. The current literature supports cortical-sparing adrenalectomy in patients with bilateral pheochromocytomas [2, 7, 10]. This video presents a patient with bilateral pheochromocytomas who underwent bilateral laparoscopic cortical-sparing adrenalectomies. Methods: A 40-year-old female presented to her primary care physician with a history of a hypertensive crisis that required an emergent cesarean section. Her workup revealed elevated urinary metanephrines, and a CT scan showed a left adrenal lesion measuring 3.9 cm and a right adrenal lesion measuring 2.7 cm. After undergoing alpha blockade, she was consented for bilateral partial adrenalectomies. A left partial adrenalectomy was performed first using four ports. The ports were then closed and the patient was repositioned in a left lateral decubitus position for a subsequent right partial adrenalectomy. Results: The patient had an uncomplicated hospital course and was discharged home on postoperative day 4. She returned for follow-up at 2 weeks and 1 month and had returned to her normal activities. Testing for MEN and von Hippel-Lindau was both negative. Her electrolyte and cortisol levels normalized, and she was weaned off her postoperative steroids by week five. At 1-year follow-up, she remains off steroids and no longer requires anti-hypertensive medications. Conclusion: Laparoscopic adrenalectomy is the gold standard for removal of benign lesions of the adrenal gland. Bilateral pheochromocytomas are more common in the presence of hereditary conditions such as MEN and von Hippel-Lindau and should be ruled out [8, 10]. The risk of Addisonian crisis and lifelong steroid replacement should prompt cortical preservation with bilateral disease [9]. Laparoscopic bilateral partial adrenalectomies should be considered in patients with bilateral pheochromocytomas [6]. Finally, all patients undergoing pheochromocytoma excision require lifelong follow-up to monitor for recurrence

Laparoscopic Hiatal Hernia Repair with Falciform Ligament Buttress

© 2018, The Society for Surgery of the Alimentary Tract (This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply). Background: Using synthetic mesh to buttress the crural repair during laparoscopic hiatal hernia repair may be associated with dysphagia and esophageal erosions, while a biologic mesh is expensive and does not decrease long-term recurrence rates. This study documents outcomes of laparoscopic paraesophageal hernia repairs using the falciform ligament to reinforce the crural repair. Methods: This is a prospective study of laparoscopic paraesophageal hernia repairs with a falciform ligament buttress. Preoperatively and at 6 and 12 months postoperatively, medications, radiologic studies, and symptom severity and frequency scores were recorded. Patients with a hiatal defect greater than 5 cm were included, while patients with recurrent hiatal hernia repairs or prior gastric surgery were excluded. Symptom scores were compared pre- and postoperatively with a p \u3c 0.05 considered significant. Results: One hundred four patients were included with a mean age of 62.4 years, and 57 patients underwent an upper gastrointestinal series at least 12 months from the initial operation with a mean follow-up of 20.6 months. The mean symptom severity score decreased from 14.32 ± 0.93 to 4.75 ± 0.97 (p \u3c 0.001), mean symptom frequency score decreased from 14.99 ± 0.97 to 5.25 ± 0.99 (p \u3c 0.001), and mean total symptom score decreased from 29.31 ± 1.88 to 10.00 ± 1.95 (p \u3c 0.001). Five patients developed recurrent hiatal hernias on upper gastrointestinal series, but only three required operative intervention. Conclusions: Laparoscopic paraesophageal hernia repair with a falciform ligament buttress is a viable option for a durable closure. Ongoing follow-up will continue to illuminate the value of this approach to decrease morbidity and recurrence rates for hiatal hernia repair

Endogenous LXA4 Circuits Are Determinants of Pathological Angiogenesis in Response to Chronic Injury

Inflammation and angiogenesis are intimately linked, and their dysregulation leads to pathological angiogenesis in human diseases. 15-lipoxygenase (15-LOX) and lipoxin A4 receptors (ALX) constitute a LXA4 circuit that is a key feature of inflammatory resolution. LXA4 analogs have been shown to regulate vascular endothelial growth factor (VEGF)-A-induced angiogenic response in vitro. 15-LOX and ALX are highly expressed in the avascular and immune-privileged cornea. However, the role of this endogenous LXA4 circuit in pathological neovascularization has not been determined. We report that suture-induced chronic injury in the cornea triggered polymorphonuclear leukocytes (PMN) infiltration, pathological neovascularization, and up-regulation of mediators of inflammatory angiogenesis, namely VEGF-A and the VEGF-3 receptor (FLT4). Up-regulation of the VEGF circuit and neovascularization correlated with selective changes in both 15-LOX (Alox15) and ALX (Fpr-rs2) expression and a temporally defined increase in basal 15-LOX activity. More importantly, genetic deletion of 15-LOX or 5-LOX, key and obligatory enzymes in the formation of LXA4, respectively, led to exacerbated inflammatory neovascularization coincident with increased VEGF-A and FLT4 expression. Direct topical treatment with LXA4, but not its metabolic precursor 15-hydroxyeicosatetraenoic acid, reduced expression of VEGF-A and FLT4 and inflammatory angiogenesis and rescued 15-LOX knockout mice from exacerbated angiogenesis. In summary, our findings and the prominent expression of 15-LOX and ALX in epithelial cells and macrophages place the LXA4 circuit as an endogenous regulator of pathological angiogenesis