HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial

BackgroundHTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free application during surgery. The active ingredients are released from the polymer by controlled diffusion over 72 hours.MethodsThis phase 2b, double-blind, placebo-controlled and active-controlled trial enrolled patients undergoing primary unilateral total knee arthroplasty under general anesthesia. Two hundred thirty-two patients were randomized into 4 groups: HTX-011 400 mg bupivacaine/12 mg meloxicam, applied without a needle into the surgical site, the same dose of HTX-011 with a separate 50 mg ropivacaine injection into the posterior capsule, bupivacaine hydrochloride (HCl) 125 mg injection, and saline placebo injection. Only opioids were permitted for postoperative pain rescue. Primary and key secondary endpoints were mean area under the curve of pain intensity scores over 48 hours and 72 hours, respectively, for HTX-011 groups vs placebo.ResultsBoth HTX-011 groups had significantly reduced mean pain intensity vs placebo through 48 and 72 hours (both P < .001). Ropivacaine added a small initial benefit in the first 12 hours. Both HTX-011 groups also had decreased mean pain intensity vs bupivacaine HCl alone through 48 and 72 hours (P < .05). The HTX-011 groups had significantly earlier discharge readiness along with lower opioid consumption through 72 hours. HTX-011 alone or with ropivacaine was well-tolerated with a safety profile similar to controls.ConclusionNeedle-free application of HTX-011 400 mg bupivacaine/12 mg meloxicam provided superior pain reduction through 72 hours after total knee arthroplasty compared with placebo and bupivacaine HCl alone.     

Braun Gastrointestinal Bypass Surgery Exerts Similar Hypoglycemic Effects, with Minimal Operation Time and Earlier Functional Recovery, than Roux-en-Y Bypass in Type 2 Diabetic Rats

Background

Despite the beneficial hypoglycemic and potentially curative effects in type 2 diabetes, large stomach volume deficits caused by Roux-en-Y gastrointestinal bypass (RYGB) surgery increase complications. Hypoglycemic effects of Braun surgery and RYGB surgery, both modified to maximally preserve stomach volume, were compared in rat type 2 diabetes models.

Methods

Three-month-old, male Goto-Kakizaki (GK) rats (n?=?40) were randomly divided into equal groups and not treated (control) or treated with sham surgery (sham group), modified stomach-preserving Braun gastrointestinal bypass (Braun group), or modified RYGB (RYGB group). Pre- and postoperative body weight and water intake were recorded, along with operative and defecation times. Fasting blood glucose at 12 h, and blood glucose 180 min after intragastric glucose administration, were measured at weeks 1, 2, 3, 4, 10, and 11 along with glycosylated hemoglobin (preoperatively, week 11).

Results

Statistically similar (P?>?0.05) increased body weight and decreased water intake, fasting blood glucose, blood glucose after intragastric glucose administration, and glycosylated hemoglobin were observed in Braun and RYGB groups compared with control and sham groups (P?<?0.05). By week 1, RYGB and Braun groups exhibited sustained reductions in fasting blood glucose from 13.0?±?4.1 to 6.9?±?1.4 mmol/L and 12.4?±?4.4 to 7.3?±?0.9 mmol/L, respectively (P?<?0.05); mean operative times were 139.1?±?4.9 and 81.6?±?6.4 min, respectively; and postoperative defecation times were 74.3?±?3.1 and 29.4?±?4.1 h, respectively (P?<?0.05).

Conclusions

Stomach volume-preserving Braun gastrointestinal bypass surgery was faster and produced hypoglycemic effects similar to RYGB bypass surgery, potentially minimizing metabolic disruption.     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Outcome of Negative-Pressure Wound Therapy for Open Abdomen Treatment After Nontraumatic Lower Gastrointestinal Surgery: Analysis of Factors Affecting Delayed Fascial Closure in 101 Patients

Background

Few studies have focused on the risk factors for failure to achieve fascial closure after use of negative-pressure wound therapy (NPWT) in an open abdomen (OA). We aimed at analyzing possible risk factors for failure of fascial closure and the risk of fistulas after nontrauma lower gastrointestinal (GI) tract surgery treated with OA.

Methods

This retrospective study included 101 nontrauma patients treated with OA from 2007 to 2011. Multivariate analyses of risk factors were performed.

Results

Indications for OA were diffuse peritonitis (n = 47), need for second look (n = 26), failure to achieve fascial closure (e.g., bowel edema) at primary laparotomy (n = 24), and fascial necrosis (n = 4). Of the 101 patients, 61 (60 %) were alive at discharge, with one death possibly related to OA (fistula from an iatrogenic perforation). Delayed fascial closure was obtained in 40 (66 %) of the surviving patients, with 80 % when the indications for OA was need for second look and 72 % in cases of diffuse peritonitis. Compared with need for second look [hazard ratio (HR = 1), 95 % CI], proportional HR for failure of delayed fascial closure were peritonitis 1.96 (1.10–3.49) and failure to achieve fascial closure at primary laparotomy 4.70 (2.17–10.2). In the presence of a stoma the HR was 2.02 (1.13–3.63).

Conclusions

OA using NPWT seems to be a safe procedure, with few procedure-related complications. Failure of fascial closure is related to the indication of OA and the presence of a stoma. Prospective multicenter studies are needed to establish which patients with lower GI surgery benefit from OA.     

Invited Editorial: “Enhanced Recovery Minimizes Opioid Use and Length of Stay in Patients Undergoing Mastectomy with Reconstruction”

Annals of Surgical Oncology -     

Cost Analysis of Enhanced Recovery Programs in Colorectal,Pancreatic, and Hepatic Surgery: A Systematic Review

Background

Enhanced recovery programs (ERPs) have been shown to improve postoperative outcomes after abdominal surgery. This study aimed to review the current literature to assess if ERPs in colorectal, pancreas, and liver surgery induce cost savings.

Methods

A systematic review was performed including prospective and retrospective studies comparing conventional management versus ERP in terms of costs. All kinds of ERP were considered (fast-track, ERAS^®, or home-made protocols). Studies with no mention of a clear protocol and no reporting of protocol compliance were excluded.

Results

Thirty-seven articles out of 144 identified records were scrutinized as full articles. Final analysis included 16 studies. In colorectal surgery, two studies were prospective (1 randomized controlled trial, RCT) and six retrospective, totaling 1277 non-ERP patients and 2078 ERP patients. Three of the eight studies showed no difference in cost savings between the two groups. The meta-analysis found a mean cost reduction of USD3010 (95% CI: 5370–650, p = 0.01) in favor of ERP. Among the five included studies in pancreas surgery (all retrospective, 552 non-ERP vs. 348 ERP patients), the mean cost reduction in favor of the ERP group was USD7020 (95% CI: 11,600–2430, p = 0.003). In liver surgery, only three studies (two retrospective and 1 RCT, 180 non-ERP vs. 197 ERP patients) were found, which precluded a sound cost analysis.

Conclusions

The present systematic review suggests that ERPs in colorectal and pancreas surgery are associated with cost savings compared to conventional perioperative management. Cost data in liver surgery are scarce.

     

Report: Asian Consensus Meeting on Metabolic Surgery. Recommendations for the use of Bariatric and Gastrointestinal Metabolic Surgery for Treatment of Obesity and Type II Diabetes Mellitus in the Asian Population

Background  

The report submitted is a detailed analysis of the happenings and outcomes of a two day deliberation that was organized in Trivandrum, India on the 9th and 10th August 2009.     

Incidence and Risk Factors for Severity of Postoperative Ileus After Colorectal Surgery: A Prospective Registry Data Analysis

World Journal of Surgery - Defining severe postoperative ileus in terms of consequences could help physicians standardize the management of this condition. The recently described classification...     

远端胃癌不同胃肠道重建方式对合并2型糖尿病患者血糖影响

目的探讨在远端胃癌根治术中,不同消化道重建方式对胃癌合并2型糖尿病患者的术后血糖影响。方法回顾性分析2008年1月至2012年6月期间,胃癌合并2型糖尿病患者102例行胃癌根治性手术的资料,根据手术方式分为BillrothⅠ组18例,BillrothⅡ组21例,RY1组(延长Roux袢胃空肠Roux-en-Y)28例及RY2组(延长胆胰分流袢胃空肠Roux-en-Y组)35例;对比观察术后12个月时患者糖化血红蛋白(Hb A1c)及缓解率。应用SPSS18.0统计软件进行统计分析,Hb A1c计量资料以均数±标准差表示,采用重复测量的方差分析(Bonferroni法);疗效分析多组间比较采用秩和检验(Kruskal-Wallis法),两组间比较采用秩和检验(Mann-Whitney法)。P0.05为有统计学意义,P0.01为有显著统计学意义。结果术后第12个月,只有BillrothⅠ组Hb A1c≥6.5%,与其他3组比较差异均有显著统计学意义(P0.01)。BillrothⅡ组、RY 1组、RY 2组之间术后第12个月Hb A1c水平差异无统计学意义。术后第12个月,在疗效方面,BillrothⅠ组、BillrothⅡ组、RY 1组、RY 2组缓解率分别为44.44%(8/18)、57.14%(12/21)、75%(21/28)、82.86%(29/35),差异有统计学意义(χ2=12.884,P=0.005);将疗效最好的RY2组与其他3组分别进行分析,RY 2组缓解率明显高于Billroth组Ⅰ(Z=-3.359,P=0.001)、BillrothⅡ组(Z=-2.066,P=0.039),差异有统计学意义。结论远端胃癌手术行BillrothⅠ、BillrothⅡ、延长Roux袢胃空肠Roux-en-Y吻合术及延长胆胰分流袢胃空肠Roux-en-Y吻合术均可改善2型糖尿病患者血糖水平。延长胆胰分流袢胃空肠Roux-en-Y吻合术对胃癌合并2型糖尿病患者血糖水平的治疗作用优于BillrothⅠ、BillothⅡ,且对2型糖尿病患者血糖水平改善方面较延长Roux袢胃空肠Roux-en-Y吻合术存在获益趋势。建议对远端胃癌合并2型糖尿病患者选择消化道重建方式时选择延长胆胰分流袢胃空肠Roux-en-Y吻合术。     

Desmoplastic Small Round Cell Tumor Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Results of a Phase 2 Trial

Background

Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma that primarily affects adolescents and young adults. Patients can present with many peritoneal implants. We conducted a phase 2 clinical trial utilizing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) with cisplatin for DSRCT and pediatric-type abdominal sarcomas.

Patients and Methods

A prospective cohort study was performed on 20 patients, who underwent CRS-HIPEC procedures, with cisplatin from 2012 to 2013. All patients were enrolled in the phase 2 clinical trial. Patients with extraabdominal disease and in whom complete cytoreduction (CCR0–1) could not be achieved were excluded. All outcomes were recorded.

Results

Fourteen patients had DSRCT, while five patients had other sarcomas. One patient had repeat HIPEC. Patients with DSRCT had significantly longer median overall survival after surgery than patients with other tumors (44.3 vs. 12.5 months, p = 0.0013). The 3-year overall survival from time of diagnosis for DSRCT patients was 79 %. Estimated median recurrence-free survival (RFS) was 14.0 months. However, RFS for patients with DSRCT was significantly longer than for non-DSRCT patients (14.9 vs. 4.5 months, p = 0.0012). Among DSRCT patients, those without hepatic or portal metastases had longer median RFS than those with tumors at these sites (37.9 vs. 14.3 months, p = 0.02). In 100 % of patients without hepatic or portal metastasis, there was no peritoneal disease recurrence after CRS-HIPEC.

Conclusions

Complete CRS-HIPEC with cisplatin is effective in select DSRCT patients. DSRCT patients with hepatic or portal metastasis have poorer outcomes.