Sonia Ramamoorthy

Natural orifice surgery: initial clinical experience

BackgroundNatural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience.MethodsUnder an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance.ResultsNine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred.ConclusionThe limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access.

Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting

Abstract Objective: Assess comparative efficacy of liposome bupivacaine administered at doses ≤266 mg and bupivacaine HCl administered at doses ≤200 mg for postsurgical analgesia. Research design and methods: Analysis of pooled efficacy and safety data from nine double-blind, placebo or active (bupivacaine HCl) controlled multimodal analgesia studies using a single dose of liposome bupivacaine or comparator, given via administration into the surgical site before end of surgery (i.e., inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Data from study arms that received liposome bupivacaine doses ≤266 mg were included. Clinical trial registration: Pooled data analysis includes nine studies: Study 1 – NCT01203644; Study 2 – NCT00485433; Study 3 – NCT00485693; Study 4 – NCT00529126; Study 5 – NCT00745290; Study 6 – NCT00744848; Study 7 – NCT00813111; Study 8 – NCT00890721; Study 9 – NCT00890682. Main outcome measures: Outcome measures included area under the curve (AUC) of pain intensity scores assessed by numeric rating scale (NRS) through 72 h postsurgery, time to first use of rescue opioid medications, total amount (mg) of opioid medications used, and occurrence of opioid-related adverse events (ORAEs). Incidence of overall AEs was also assessed. Results: Mean cumulative pain score (AUC of NRS through 72 h) was significantly lower with liposome bupivacaine (283) compared with bupivacaine HCl (329, p = 0.039). Median time from administration of study drug to first use of opioid rescue medication was significantly longer for liposome bupivacaine (10 h vs 3 h, p < 0.0001). Liposome bupivacaine was associated with a significant reduction in opioid use (12 mg vs 19 mg; p < 0.0001) and incidence of ORAEs (20% vs 36%; p < 0.0001), compared with bupivacaine HCl. Conclusions: In this pooled analysis from nine studies representing five different surgical procedures, liposome bupivacaine administered at doses ≤266 mg in a multimodal setting was associated with statistically significant and clinically meaningful lower cumulative pain score at 72 h, delayed and less consumption of opioids, and fewer ORAEs than bupivacaine HCl.

Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia

Background Liposome bupivacaine is a novel formulation of the local anesthetic bupivacaine, designed to provide prolonged postsurgical analgesia. This analysis examined pooled efficacy data as reflected in cumulative pain scores from 10 randomized, double-blind liposome bupivacaine clinical studies in which the study drug was administered via local wound infiltration. Methods A total of 823 patients were exposed to liposome bupivacaine in 10 local wound infiltration studies at doses ranging from 66 mg to 532 mg in five surgical settings; 446 patients received bupivacaine HCl (dose: 75–200 mg) and 190 received placebo. Efficacy measures were assessed through 72 hours after surgery. Results Overall, 45% of patients were male and 19% were ≥65 years of age. In the analysis of cumulative pain intensity scores through 72 hours, liposome bupivacaine was associated with lower pain scores than the comparator in 16 of 19 treatment arms assessed, achieving statistically significant differences compared with bupivacaine HCl (P < 0.05) in five of 17 treatment arms. These results were supported by results of other efficacy measures, including time to first use of opioid rescue medication, proportion of patients avoiding opioid rescue medication, total postsurgical consumption of opioid rescue medication, and patient/care provider satisfaction with postoperative analgesia. Local infiltration of liposome bupivacaine resulted in significant systemic plasma levels of bupivacaine, which could persist for 96 hours; systemic plasma levels of bupivacaine following administration of liposome bupivacaine were not correlated with local efficacy. Liposome bupivacaine and bupivacaine HCl were generally well tolerated. Conclusion Based on this integrated analysis of multiple efficacy measures, liposome bupivacaine appears to be a potentially useful therapeutic option for prolonged reduction of postsurgical pain in soft tissue and orthopedic surgeries.

Hybrid natural orifice translumenal surgery (NOTES) sleeve gastrectomy: a feasibility study using an animal model

BackgroundThe indications for natural orifice translumenal surgery (NOTES) are yet to be determined. Morbidly obese patients may be one population that would benefit from this approach due to the elimination of wound complications and possibly a faster recovery. As a bariatric restrictive procedure, sleeve gastrectomy could be one indication for NOTES. To test the feasibility of this procedure with a NOTES approach, a pig model was used.MethodsAcute studies investigated five 40-kg farm pigs. The rectum was used as the port of entry to the peritoneal cavity, and the stomach was manipulated endoluminally using a gastroscope. Vision was acquired through a 5-mm laparoscope introduced transabdominally (i.e. via the hybrid technique). A 10-mm incision was made on the anterior wall of the rectum and dilated to accommodate a 12-mm trocar introduced through the rectal wall into the peritoneal cavity. The greater curvature of the stomach then was divided and detached, starting from the antrum and proceeding to the esophagogastric junction using a laparoscopic stapler. The sleeve gastrectomy was completed by dividing the short gastric vessels with an ultrasonic scalpel. The gastric pouch then was removed through the rectal incision.ResultsA NOTES gastric sleeve resection was successfully performed in all five pigs. The technique was developed, and feasibility was determined. After resection, the gastric remnant was inflated, with no evidence of leakage. At autopsy, intact suture lines were noted. Closure of the rectal incision was not attempted.ConclusionA NOTES sleeve gastrectomy is feasible in porcine animal models. The rectal port of entry allows rigid laparoscopic instruments to be introduced into the peritoneal cavity and enables performance of gastrointestinal procedures the same as in standard laparoscopic surgery. Extra-long instruments are necessary for dissection and division of the stomach at the esophagogastric junction and for accessing the short gastric vessels.

Impact of postsurgical opioid use and ileus on economic outcomes in gastrointestinal surgeries

Abstract Objectives: To assess the incidence and economic impact of postoperative ileus (POI) following laparotomy (open) and laparoscopic procedures for colectomies and cholecystectomies in patients receiving postoperative pain management with opioids. Methods: Using the Premier research database, we retrospectively identified adult inpatients discharged between 2008 and 2010 receiving postsurgical opioids following laparotomy and laparoscopic colectomy and cholecystectomy. POI was identified through ICD-9 diagnosis codes and postsurgical morphine equivalent dose (MED) determined. Results: A total of 138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more frequently in colectomy than cholecystectomy and more often when performed by laparotomy. Ileus patients receiving opioids had an increased length of stay (LOS) ranging from 4.8 to 5.7 days, total cost from

The safety of liposome bupivacaine, a novel local analgesic formulation.

9945 to

Decreased Jun-D and myogenin expression in muscle wasting of human cachexia.

13,055 and 30 day all-cause readmission rate of 2.3 to 5.3% higher compared to patients without ileus. Patients with ileus received significantly greater MED than those without (median: 285 vs. 95 mg, p < 0.0001) and were twice as likely to have POI. MED above the median in ileus patients was associated with an increase in LOS (3.8 to 7.1 days), total cost (

Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis

8458 to

Molecular mechanisms underlying Ca2+-mediated motility of human pancreatic duct cells

19,562), and readmission in laparoscopic surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients undergoing open procedures regardless of MED. Conclusions: Use of opioids in patients who develop ileus following abdominal surgeries is associated with prolonged hospitalization, greater costs, and increased readmissions. Furthermore, higher doses of opioids are associated with higher incidence of POI. Limitations are related to the retrospective design and the use of administrative data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore underestimated in our study. Assessment of pre-existing disease and preoperative pain management was not assessed. Despite these limitations, strategies to reduce opioid consumption may improve healthcare outcomes and reduce the associated economic impact.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis

Objective:Pooled safety data from 10 randomized, double-blind studies of liposome bupivacaine, a novel local analgesic formulation, were examined. Methods:Eight hundred twenty-three patients received liposome bupivacaine (dose, 66 to 532 mg) given locally at the surgical site in 5 different settings (hemorrhoidectomy, bunionectomy, breast augmentation, total knee arthroplasty, and hernia repair); 446 received bupivacaine HCl (dose, 75 to 200 mg) and 190 received placebo. Adverse events (AEs) were monitored for up to 36 days after administration. Results:Overall, 48% of patients were men and 21% were 65 years and older. Incidence of AEs was 62% for patients receiving liposome bupivacaine, versus 75% and 43% for patients receiving bupivacaine HCl and placebo, respectively. The most common AEs (incidence >10%) in the liposome bupivacaine arms were nausea, constipation, and vomiting. One death was reported in the liposome bupivacaine group and 1 in the bupivacaine HCl group; both deemed unrelated to study drug. Serious AEs were reported in 2.7% of patients receiving liposome bupivacaine, versus 5.4% and 1.1% of those receiving bupivacaine HCl and placebo, respectively. In both the liposome bupivacaine and bupivacaine HCl groups, 6% of patients experienced a cardiac AE; these were primarily tachycardia (4% vs. 5%, respectively) and bradycardia (2% vs. 1%, respectively). Overall incidence of treatment-related cardiac AEs was <1%; all were associated with liposome bupivacaine. All of these events were assessed by investigators as possibly related to study drug; all were mild or moderate in severity, and none required therapeutic intervention. Discussion:Liposome bupivacaine exhibited acceptable tolerability across 823 patient exposures.