Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial.

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Laparoscopic vs. robotic colectomy for left-sided diverticulitis.

Diverticulitis is a prevalent gastrointestinal disease that often warrants surgical intervention. However, the optimal approach between traditional laparoscopy (LC) and robotic-assisted laparoscopy (RAC) for diverticulitis remains unclear. Our research compares these techniques in patients diagnosed with left-sided diverticulitis treated at a single, tertiary referral center from 2019 to 2022. Among the 134 patients, 86 underwent laparoscopic and 48 robotic-assisted surgeries. The surgeries included in this analysis are left colectomy, sigmoid colectomy, low anterior resection, and Hartmann's procedure. Primary outcomes were major morbidity and 30-day mortality. Secondary outcomes were operative time, conversion to open, length of stay, unplanned return to the operating room, 30-day readmission rate, and overall morbidity. While demographics and comorbidities were similar for both groups, the robotic-assisted group displayed a statistically significant longer operative time (198.0 ± 84.4 LC vs. 264.8 ± 78.5 min RAC, p < 0.001). When investigated further, there was a significant difference in operative time for uncomplicated diverticulitis cases favoring the LC approach (169.17 ± 58.1 LC vs. 244.82 ± 58.79 min RAC, p < 0.001). This significant difference, however, was not present in complicated diverticulitis cases. Other factors, such as overall and major morbidity, rate of conversion to open approach, ostomy creation, estimated blood loss, time to return of bowel function, length of stay, and 30-day readmission rate, did not significantly differ between the groups. There was no 30-day mortality in either group. Favorable patient outcomes, lack of significant difference in operative time compared with traditional laparoscopy, and absence of differences in morbidities or efficacy, raises an interesting question in the world of minimally invasive surgery: is the robotic-assisted approach emerging as the advantageous approach for complicated diverticulitis cases? We encourage additional, multi-center analysis of specifically complicated diverticulitis managed with both surgical approaches to investigate if these findings are replicated outside of our institution.

Heteromerization between α1B -adrenoceptor and chemokine (C-C motif) receptor 2 biases α1B -adrenoceptor signaling: Implications for vascular function.

Previously, we reported that chemokine (C-C motif) receptor 2 (CCR2) heteromerizes with α1B -adrenoceptor (α1B -AR) in leukocytes, through which α1B -AR controls CCR2. Whether such heteromers are expressed in human vascular smooth muscle cells (hVSMCs) is unknown. Bioluminescence resonance energy transfer confirmed formation of recombinant CCR2:α1b -AR heteromers. Proximity ligation assays detected CCR2:α1B -AR heteromers in hVSMCs and human mesenteric arteries. CCR2:α1B -AR heteromerization per se enhanced α1B -AR-mediated Gαq -coupling. Chemokine (C-C motif) ligand 2 (CCL2) binding to CCR2 inhibited Gαq activation via α1B -AR, cross-recruited ß-arrestin to and induced internalization of α1B -AR in recombinant systems and in hVSMCs. Our findings suggest that CCR2 within CCR2:α1B -AR heteromers biases α1B -AR signaling and provide a mechanism for previous observations suggesting a role for CCL2/CCR2 in the regulation of cardiovascular function.

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy.

PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate post-operative period: a Phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis.

Aim: Evaluate safety/efficacy of intravenous meloxicam in a colorectal enhanced recovery after surgery protocol. Methods: Adults undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis received meloxicam IV 30 mg (n = 27) or placebo (n = 28) once daily beginning 30 min before surgery. Results: Adverse events: meloxicam IV, 85%; placebo, 93%. Adverse events commonly associated with opioids: 41 versus 61% - including nausea (33 vs 50%), vomiting (19 vs 18%) and ileus (4 vs 18%). Wound healing satisfaction scores (physician-rated), clinical laboratory findings and vital signs were similar in both groups. No anastomotic leaks were reported. Opioid consumption, postoperative pain intensity, length of stay and times to first bowel sound, first flatus and first bowel movement were significantly lower with meloxicam IV versus placebo. Most subjects (>92%) were satisfied with postoperative pain medication. Conclusion: Meloxicam IV was generally well tolerated and associated with decreased opioid consumption, lower resource utilization and functional benefits. Clinical Trial Registration: NCT03323385 (ClinicalTrials.gov).

Proving the Effectiveness of the Fundamentals of Robotic Surgery (FRS) Skills Curriculum: A Single-blinded, Multispecialty, Multi-institutional Randomized Control Trial.

OBJECTIVE: To demonstrate the noninferiority of the fundamentals of robotic surgery (FRS) skills curriculum over current training paradigms and identify an ideal training platform. SUMMARY BACKGROUND DATA: There is currently no validated, uniformly accepted curriculum for training in robotic surgery skills. METHODS: Single-blinded parallel-group randomized trial at 12 international American College of Surgeons (ACS) Accredited Education Institutes (AEI). Thirty-three robotic surgery experts and 123 inexperienced surgical trainees were enrolled between April 2015 and November 2016. Benchmarks (proficiency levels) on the 7 FRS Dome tasks were established based on expert performance. Participants were then randomly assigned to 4 training groups: Dome (n = 29), dV-Trainer (n = 30), and DVSS (n = 32) that trained to benchmarks and control (n = 32) that trained using locally available robotic skills curricula. The primary outcome was participant performance after training based on task errors and duration on 5 basic robotic tasks (knot tying, continuous suturing, cutting, dissection, and vessel coagulation) using an avian tissue model (transfer-test). Secondary outcomes included cognitive test scores, GEARS ratings, and robot familiarity checklist scores. RESULTS: All groups demonstrated significant performance improvement after skills training (P < 0.01). Participating residents and fellows performed tasks faster (DOME and DVSS groups) and with fewer errors than controls (DOME group; P < 0.01). Inter-rater reliability was high for the checklist scores (0.82-0.97) but moderate for GEARS ratings (0.40-0.67). CONCLUSIONS: We provide evidence of effectiveness for the FRS curriculum by demonstrating better performance of those trained following FRS compared with controls on a transfer test. We therefore argue for its implementation across training programs before surgeons apply these skills clinically.

A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consumption. The incidence of adverse events was similar between meloxicam IV- and placebo-treated subjects (63.0% versus 65.0%). Investigators assessed most adverse events as mild or moderate in intensity and unrelated to treatment. Adverse events of interest (injection-site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound-healing events) were similar between groups. Over the treatment period, meloxicam IV was associated with a 23.6% (P = .0531) reduction in total opioid use (9.2 mg morphine equivalent) compared to placebo-treated subjects. The results suggest that meloxicam IV had a safety profile similar to that of placebo with respect to numbers and frequencies of adverse events and reduced opioid consumption in subjects with moderate to severe postoperative pain following major elective surgery.

Reduction in Central Line-Associated Bloodstream Infections Correlated With the Introduction of a Novel Silver-Plated Dressing for Central Venous Catheters and Maintained for 6 Years.

OBJECTIVE: To assess a novel silver-plated dressing (SD) for central venous catheters in comparison to chlorhexidine gluconate-impregnated sponge (CHGIS) dressings in preventing central line-associated bloodstream infections (CLABSIs) in adult intensive care unit (ICU) patients. DESIGN: Retrospective cohort study. SETTING: Tampa General Hospital, an academic medical tertiary care center. PATIENTS: All adult ICU patients of an academic medical tertiary care center from January 2009 to December 2010. MEASUREMENTS AND MAIN RESULTS: A total of 3189 patient records were studied from 7 different ICUs during the 2-year period. Patients received either CHGIS dressings (January 2009-December 2009) or SDs (January 2010-December 2010). Primary outcomes measured were CLABSI rates per 1000 catheter days and ICU length of stay. There were 30 696 catheter days with CHGIS dressings and 31 319 catheter days with SDs. There was a statistically significant decrease in the rate of CLABSI per 1000 catheter days in the SD group, from 2.38 to 1.28 ( P = .001), with an absolute risk reduction of 1.1. There was a significantly lower incidence in the rate of CLABSI per 1000 catheter days in the SD group (incidence rate ratio [IRR] = 0.54, 95% confidence interval [CI]: 0.36-0.80). The relative risk of CLABSI in the SD group was 0.502 (95% CI: 0.340-0.730; P < .001). If SDs are used on all catheters, the decreased rate of CLABSIs observed would calculate to a cost savings of US$4070 to US$39 600 per 1000 catheter days. After successful implementation of the SD, we observed significant reductions in CLABSI rates and a sustained reduction in the subsequent 6 years. CONCLUSION: Use of SDs is associated with a significant decrease in CLABSI rates in adult ICU patients compared to CHGIS dressings, with an estimated cost savings of US$4070 to US$39 600 per 1000 catheter days.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

A randomized, double-blind, placebo controlled safety, tolerability, and pharmacokinetic dose escalation study of a gentamicin vancomycin gel in patients undergoing colorectal surgery.

BACKGROUND: Despite numerous interventions promulgated by the Surgical Care Improve Project (SCIP) and other organizations, surgical site infection (SSI) continues to be a significant medical problem. DFA-02 is a novel bioresorbable modified-release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL) to be applied during surgical incision closure for the prevention of SSIs. The following double-blind phase 2a trial was designed to test the safety and tolerability of DFA-02. METHODS: At six US sites, the study planned to randomize 40 subjects undergoing colorectal surgery (30 with DFA-02, and eight with placebo gel) in four ascending dose cohorts (10-, 20-, 30-, and 40-mL study drug per wound). Safety was ascertained and serum pharmacokinetics (PK) was determined. RESULTS: Study enrollment was discontinued after the first three dose cohorts (10, 20, and 30 mL) as even very large incisions could not accommodate more than 20 mL of gel, leaving no scientific justification for the 40-mL cohort. DFA-02 was well tolerated and showed no evidence of local tissue reaction or impairment of wound healing. No serious AEs were deemed related to study drug. Systemic exposure to gentamicin and vancomycin remained well below levels considered to be at higher risk for oto- or nephrotoxicity. The maximal gentamicin and vancomycin levels observed were 2.36 and 0.684 µg/mL at 6 h, which were well below the prespecified stopping criteria of 12 and 20 µg/mL, respectively. CONCLUSIONS: In this small phase 2a study, the study drug was well tolerated and appeared to be free of serious adverse effects. Consistent with these findings, the PK values were consistent with gradual release of the antibiotics from the gel in the surgical site. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01496352.

Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial.

BACKGROUND: Local excision is an organ-preserving treatment alternative to transabdominal resection for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared with transabdominal rectal resection. We investigated the oncological and functional outcomes of neoadjuvant chemoradiotherapy and local excision for patients with stage T2N0 rectal cancer. METHODS: We did a multi-institutional, single-arm, open-label, non-randomised, phase 2 trial of patients with clinically staged T2N0 distal rectal cancer treated with neoadjuvant chemoradiotherapy at 26 American College of Surgeons Oncology Group institutions. Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge, and with an Eastern Cooperative Oncology Group performance status of at least 2 were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m(2) twice daily on days 1-14 and 22-35), oxaliplatin (50 mg/m(2) on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m(2) twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The primary endpoint was 3-year disease-free survival for all eligible patients (intention-to-treat population) and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumours, and negative resection margins (per-protocol group). This study is registered with ClinicalTrials.gov, number NCT00114231. FINDINGS: Between May 25, 2006, and Oct 22, 2009, 79 eligible patients were recruited to the trial and started neoadjuvant chemoradiotherapy. Two patients had no surgery and one had a total mesorectal excision. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Thus, the per-protocol population consisted of 72 patients. Median follow-up was 56 months (IQR 46-63) for all patients. The estimated 3-year disease-free survival for the intention-to-treat group was 88·2% (95% CI 81·3-95·8), and for the per-protocol group was 86·9% (79·3-95·3). Of 79 eligible patients, 23 (29%) had grade 3 gastrointestinal adverse events, 12 (15%) had grade 3-4 pain, and 12 (15%) had grade 3-4 haematological adverse events during chemoradiation. Of the 77 patients who had surgery, six (8%) had grade 3 pain, three (4%) had grade 3-4 haemorrhage, and three (4%) had gastrointestinal adverse events. INTERPRETATION: Although the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection. FUNDING: National Cancer Institute and Sanofi-Aventis.

Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.

BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. FUNDING: National Institutes of Health National Cancer Institute.

Silver-based dressings for the reduction of surgical site infection: review of current experience and recommendation for future studies.

Surgical site infections (SSIs) are the most common hospital acquired infection in surgical patients, occurring in approximately 300,000-500,000 patients a year. SSIs occur across all surgical specialties, but have increased importance in abdominal, colorectal, obstetrical, gynecological, cardiac, vascular, neurological, transplant, and orthopedic procedures where either the inherent risk is elevated or the consequence of an infection would be severe. Current prevention guidelines reduce, but do not completely eliminate, the occurrence of SSIs. We have found the use of silver-nylon wound dressings to significantly reduce the risk SSI associated with colorectal surgery. In this review, we examine the incidence of SSI in high-risk groups, and identify procedures where silver dressings, and other silver products, have been evaluated for the prevention of SSI. Silver-nylon dressings are a useful adjunct in the prevention of SSI in colorectal surgery, neurological surgery, spinal surgery, and certain cardiovascular and orthopedic procedures. Gynecologic, obstetric, breast, transplant, neck, and bariatric procedures, and surgery in obese and diabetic patients, represent other areas where patients are at increased risk of SSI, but in which silver dressings have not been adequately evaluated yet. Recommendation is made for large prospective studies of silver dressings in these populations.

Do silver-based wound dressings reduce pain? A prospective study and review of the literature.

Silver-containing dressings are a mainstay in the management of burn injury and acute and chronic wounds. In addition to antimicrobial activity, there is anecdotal evidence that silver dressings may modulate or reduce wound pain. Pain is subjective and difficult to quantify, and most studies of silver-containing dressings evaluate pain as a secondary rather than a primary outcome. Nevertheless, a dressing with a proven ability to reduce pain independent of systemic analgesics would have great utility. In this study, we compared patient-reported pain levels in patients previously randomized to receiving silver-nylon dressings vs. conventional gauze dressings in a study of surgical site infection. Compared to gauze dressings, patients in the silver dressing group reported less pain between postoperative days 0 and 9 (p<0.02). Post hoc analysis of analgesic use did not reach statistical significance between the groups. The study was completed with a literature review of the effect of silver on pain. Silver-based dressings may reduce wound pain by providing an occlusive barrier or by other as-yet undefined mechanisms. The role of silver in pain relief, however, cannot be definitively stated until well-designed prospective randomized studies evaluating pain as a primary endpoint are carried out.

Bounceback branchpoints: using conditional inference trees to analyze readmissions.

BACKGROUND: We sought to identify risks for 30-day readmission in patients undergoing colorectal surgery. METHODS: We reviewed 2011 American College of Surgery National Surgical Quality Improvement Program data to identify patients readmitted after colorectal surgery. We found 3,228 readmissions from 30,412 records. Using statistically suggestive variables from logistic regression (P < .1), we built conditional inference trees (CTREES) with subsampled records to identify combined risks. RESULTS: Logistic regression identified 27 potentially significant variables. Using these in new logistic regression and CTREES, we found classification accuracies of 0.70 and 0.63, respectively. CTREES predicted that the majority of patients who required reoperation during their hospitalization were predicted to require readmission (n = 496), along with the majority of patients who developed organ space infection (n = 671). Patients with deep infections discharged ≤10 days from their index operation required readmission in 443 of 459 of records; this approach predicted a >99% risk of readmission in patients with these infections who were discharged ≤5 days (220/222). Additionally, >90% (253/271) of patients who returned to the operating room and were discharged ≤8 days from the first operation are predicted to return. CONCLUSION: Subgroups identified using the CTREES model demonstrate that patients with deep space infections or who return to the operating room have a greater readmission rate if they are discharged early. Modeled patients found to have organ space infections and who returned to the operating room had 30-day readmission risks of >50%, with those discharged a rate of >90%. We show herein that CTREES can be used with retrospective data on surgery populations to bring hidden patterns into relief.

Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis.

UNLABELLED: Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. STUDY REGISTRATION: This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

Liposome Bupivacaine for Postsurgical Analgesia in Adult Patients Undergoing Laparoscopic Colectomy: Results from Prospective Phase IV Sequential Cohort Studies Assessing Health Economic Outcomes.

BACKGROUND: Opioid-based postsurgical analgesia exposes patients undergoing laparoscopic colectomy to elevated risk for gastrointestinal motility problems and other opioid-related adverse events (ORAEs). The purpose of our research was to investigate postsurgical outcomes, including opioid consumption, hospital length of stay, and ORAE risk associated with a multimodal analgesia regimen, employing a single administration of liposome bupivacaine as well as other analgesics that act by different mechanisms. METHODS: We analyzed combined results from 6 Phase IV, prospective, single-center studies in which patients undergoing laparoscopic colectomy received opioid-based intravenous patient-controlled analgesia (PCA) or multimodal analgesia incorporating intraoperative administration of liposome bupivacaine. As-needed rescue therapy was available to all patients. Primary outcome measures were postsurgical opioid consumption, hospital length of stay, and hospitalization costs. Secondary measures included time to first rescue opioid use, patient satisfaction with analgesia (assessed using a 5-point Likert scale), and ORAEs. RESULTS: Eighty-two patients underwent laparoscopic colectomy and did not meet intraoperative exclusion criteria (PCA n = 56; multimodal analgesia n = 26). Compared with the PCA group, the multimodal analgesia group had significantly lower mean total postsurgical opioid consumption (96 vs 32 mg, respectively; P < 0.0001) and shorter median postsurgical hospital length of stay (3.0 vs 4.0 days; P = 0.0019). Geometric mean costs were $11,234 and $13,018 in the multimodal analgesia and PCA groups, respectively (P = 0.2612). Median time to first rescue opioid use was longer in the multimodal analgesia group versus PCA group (1.1 hours vs 0.6 hours, respectively; P=0.0003). ORAEs were experienced by 41% of patients receiving intravenous opioid PCA and 8% of patients receiving multimodal analgesia (P = 0.0019). Study limitations included use of an open-label, nonrandomized design; small population size; and the inability to isolate treatment-related effects specifically attributable to liposome bupivacaine. CONCLUSIONS: Compared with intravenous opioid PCA, a liposome bupivacaine-based multimodal analgesia regimen reduced postsurgical opioid use, hospital length of stay, and ORAEs, and may lead to improved postsurgical outcomes following laparoscopic colectomy.

Association between surgeon characteristics and their preferences for guideline-concordant staging and treatment for rectal cancer.

BACKGROUND: Rectal cancer guidelines recommend transrectal ultrasound or magnetic resonance imaging for locoregional staging and neoadjuvant chemoradiation therapy (CRT) for Stage II/III disease, but studies show these are underutilized. We examined how surgeon preferences align with guidelines or vary by training. METHODS: Questionnaires on training, years of practice, and staging/treatment preferences were sent to surgeons practicing in Florida. RESULTS: Of 759 surveys distributed, 321 (42%) responded; 158 were excluded because they were trainees, not treating rectal cancer, or not board certified/eligible. Among the remaining 163, 71% were general surgeons, 18% colorectal surgeons, and 11% surgical oncologists. Colorectal surgeons and surgical oncologists were more likely than general surgeons to prefer transrectal ultrasound/magnetic resonance imaging (79% vs 50%; P < .01), and neoadjuvant CRT (71% vs 45%; P < .01). Differences remained significant after adjusting for years in practice. CONCLUSION: Increased focus on appropriate use of staging procedures and neoadjuvant CRT within general surgery training/educational programs is warranted.