Prevalence and Predictors of Preoperative Venous Thromboembolism in Asymptomatic Patients Undergoing Major Oncologic Surgery.

BACKGROUND: Postoperative venous thromboembolism (VTE) is a leading cause of in-hospital mortality for cancer patients; however, the prevalence of preoperative VTE remains unclear. OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors associated with preoperative VTE in asymptomatic patients undergoing major oncologic surgery. METHODS: Retrospective analysis of 346 patients identified from our prospectively maintained database of patients undergoing abdominopelvic oncologic surgery from 2009 to 2016. RESULTS: The prevalence of preoperative VTE found on screening venous duplex scan was 10.1%. Patients with a history of prior VTE were more likely to have a preoperative deep vein thrombosis (DVT) versus those with no prior VTE (42.9% vs. 4.5%, p < 0.01). Relative risk for prior VTE was 8.2 [95% confidence interval (CI) 4.7-14.3]. Older age was also associated with preoperative VTE. Regression modeling determined that patients were 1.24-fold as likely to have a preoperative DVT for every 5-year increase in age (relative risk 1.24, 95% CI 1.09-1.42). Patients with preoperative DVT were more likely to have been diagnosed with sepsis 1 month prior to surgery (8.6% vs. 1.6%, p = 0.04). There were no postoperative pulmonary emboli. The overall postoperative complication rate was higher in those with a preoperative DVT (25.7% vs. 13.2%, p = 0.071). CONCLUSION: Asymptomatic patients undergoing major oncologic surgery have a 10.1% prevalence of preoperative DVT. Increasing age, recent diagnosis of sepsis, and a history of prior VTE are significantly associated with preoperative DVTs. This suggests high-risk oncologic patients may benefit from screening lower extremity venous duplex ultrasound prior to Surgery.

The neurokinin 1 receptor regulates peritoneal fibrinolytic activity and postoperative adhesion formation.

BACKGROUND: Intra-abdominal adhesions are a common source of postoperative morbidity. Previous studies in our laboratory have shown that a neurokinin 1 receptor antagonist (NK-1RA) reduces abdominal adhesion formation and increases peritoneal fibrinolytic activity. However, the cellular pathway by which the antagonist exerts its effects is unclear, as cultured peritoneal mesothelial cells exposed to the NK-1RA show increases in fibrinolytic activity despite having very low expression of neurokinin 1 receptor (NK-1R) messenger RNA and protein. Our aim was to determine whether the NK-1R plays an essential role in the adhesion-reducing effects of the NK-1RA, or if the NK-1RA is acting independently of the receptor. METHODS: Homozygous NK-1R knockout mice and age matched wild-type mice underwent laparotomy with cecal cautery to induce adhesions. At the time of surgery, mice received a single intraperitoneal dose of either NK-1RA (25 mg/kg) or saline alone. Adhesion severity at the site of cecal cautery was assessed on postoperative day 7. In a separate experiment, peritoneal fluid was collected from wild type and NK-1R knockout mice 24 h after laparotomy with cecal cautery and administration of either NK-1RA or saline. Tissue plasminogen activator levels, representative of total fibrinolytic activity, were then measured in peritoneal fluid. RESULTS: In wild-type mice, NK-1RA administration significantly decreased adhesion formation compared with saline controls. Among the NK-1R knockout mice, there was no significant reduction in adhesion formation by the NK-1RA. Fibrinolytic activity increased 244% in wild-type mice administered NK-1RA compared with saline controls; however, the NK-1RA did not raise fibrinolytic activity above saline controls in NK-1R knockout mice. CONCLUSIONS: These data indicate that the NK-1R mediates the adhesion-reducing effects of the NK-1RA, in part, by the upregulation of peritoneal fibrinolysis, and suggest that the NK-1R is a promising therapeutic target for adhesion prevention.

Histone deacetylase inhibitors decrease intra-abdominal adhesions with one intraoperative dose by reducing peritoneal fibrin deposition pathways.

BACKGROUND: We previously demonstrated that postoperative peritoneal injury and inflammation contribute to adhesiogenesis. Recent evidence suggests that in addition to their role of interfering with the acetylation status of nuclear histone proteins, histone deacetylase inhibitors (HDACIs) including valproic acid (VPA) can target nonhistone proteins to resolve inflammation and modulate immune cells. We hypothesized that HDACIs could reduce adhesions. METHODS: Seventy-two rats underwent laparotomy with creation of 6 peritoneal ischemic buttons to induce adhesions. A single intraperitoneal (IP) dose of 50 mg/kg VPA was administered intraoperatively, whereas controls received vehicle. To evaluate the timing, 25 rats underwent ischemic button creation with either an intraoperative or a delayed IP dose of VPA at 1, 3, or 6 hours postoperatively. On postoperative day 7, adhesions were quantified. To investigate mechanisms, ischemic buttons were created in 24 rats and either VPA or saline was administered in 1 intraoperative dose. At 3 or 24 hours later, peritoneal fluid was collected and fibrinolytic activity measured. Alternatively, button tissue was collected 30 minutes postoperatively to measure tissue factor, fibrinogen, and vascular endothelial growth factor (VEGF) by real-time polymerase chain reaction or Western blot. RESULTS: A single intraoperative dose of VPA reduced adhesions by 50% relative to controls (P < .001). Delayed dosing did not reduce adhesions. In operated animals, peritoneal fibrinolytic activity was not different between groups. Tissue factor mRNA was downregulated by 50% (P = .02) and protein by 34% (P < .01) in animals administered VPA versus saline. VPA decreased fibrinogen protein by 56% and VEGF protein by 25% compared with saline (P = .03). CONCLUSION: These findings suggest that VPA rapidly reduces the extravasation of key adhesiogenic substrates into the peritoneum. A single, intraoperative intervention provides an ideal dosing strategy and indicates an exciting new role for HDACIs in adhesion prevention.

Early versus late adhesiolysis for adhesive-related intestinal obstruction: a nationwide analysis of inpatient outcomes.

BACKGROUND: Classical teaching advocates watchful waiting for 2 days before operating on adhesive-related intestinal obstructions (AIOs). Our aim was to compare the clinical and cost outcomes of early versus late adhesiolysis for AIOs. DESIGN: Patients undergoing adhesiolysis for AIOs from the 2007 Nationwide Inpatient Sample were stratified to early (≤2 days from admission) vs. late (>2 days) adhesiolysis. The primary outcome was in-hospital mortality and secondary outcomes were post-operative complications (POCs), post-operative length of stay (PLOS), and in-hospital cost. RESULTS: From 5,443 patients who underwent adhesiolysis for AIOs, 53 and 47 % underwent early and late adhesiolysis, respectively. Late adhesiolysis patients were older (65.0 vs. 60.1 years) and more co-morbid compared to the early group (p < 0.05). After adjustment with propensity score methods, late adhesiolysis patients had no difference in mortality (odds ratio [OR] 0.95, 95%-confidence intervals [CI] 0.67-1.36, p = 0.79) or POCs (OR 1.01, 95%CI 0.89-1.14, p = 0.91) compared to the early group, but had 9.8 % increased PLOS and 41.9 % increased in-hospital cost (p < 0.001). CONCLUSIONS: The 2-day limit of watchful waiting is not associated with increased mortality or POCs for those patients undergoing adhesiolysis for an AIO. Late adhesiolysis, however, was associated with significantly increased PLOS and in-hospital cost compared to early adhesiolysis.

A sprayable hyaluronate/carboxymethylcellulose adhesion barrier exhibits regional adhesion reduction efficacy and does not impair intestinal healing.

BACKGROUND: While bioresorbable solid barriers such as Seprafilm® prevent adhesions, their efficacy is limited to sites of application. The aim of this study was to assess the effectiveness of the sprayable adhesion barrier Sepraspray® in preventing adhesions to sites of direct application and to remote sites. METHODS: Intraabdominal adhesions were induced in 30 rats by creating three ischemic buttons on each side of a midline incision. To assess efficacy, Sepraspray (5 mg/button) or Seprafilm (1 cm(2)/button) was applied over three buttons on one side of the peritoneum. Operated control animals received no treatment. On day 7, adhesions were scored as percent of buttons with adhesions. To assess safety, 81 rats underwent a colonic transection repaired with an end-to-end anastomosis. Both barriers were applied circumferentially to anastomoses. Controls received no product. The integrity of healing anastomosed colonic wounds was assessed by burst pressure and tensile strength at days 3, 5, and 7 postoperatively. RESULTS: The direct application of both Sepraspray and Seprafilm significantly (p < 0.001) reduced adhesion formation compared to controls. While Seprafilm had no remote effect on adhesion formation, Sepraspray significantly (p < 0.001) reduced adhesion formation to contralateral ischemic buttons. Neither barrier affected anastomotic integrity at any time point. CONCLUSIONS: Sepraspray has widespread efficacy throughout the peritoneum in reducing adhesions without compromising intestinal healing. Furthermore, this sprayable alternative offers the potential for easier intraabdominal application.

Preoperative infliximab is not associated with an increased risk of short-term postoperative complications after restorative proctocolectomy and ileal pouch-anal anastomosis.

INTRODUCTION: Considerable controversy exists over whether the preoperative use of infliximab (IFX) for refractory ulcerative colitis (UC) increases the risk for surgical complications after restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to assess the association between preoperative IFX use and short-term surgical complications in a single-surgeon cohort at a tertiary care academic center. METHODS: UC patients who underwent IPAA from September 2005 through May 2009 were retrospectively identified. Twenty-nine patients treated with IFX within 12 weeks of surgery and 52 non-IFX control subjects were identified. Short-term postoperative outcomes were compared between groups occurring within 30 days of loop ileostomy closure. RESULTS: Patients were similar with respect to demographics, co-morbidities, rate of emergency surgery, hand-sewn anastomosis, and preoperative use of cyclosporine, azathioprine, and high-dose steroids. IFX patients were more likely to have received a laparoscopic hand-assisted IPAA, low-, medium-, and any-dose steroids, 6-mercaptopurine (6-MP), methotrexate, and to have failed medical therapy. There was no short-term mortality. Overall postoperative and infectious complications were similar between IFX and non-IFX groups. Multivariate regression models revealed no independent predictors for postoperative complications when including IFX [odds ratio (OR) 0.78, p = 0.67], laparoscopic hand-assisted IPAA, 6-MP, methotrexate, steroids, failure of medical therapy, and body mass index. CONCLUSIONS: Preoperative IFX use was not associated with an increased risk of short-term postoperative complications after IPAA.

N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses.

BACKGROUND: Intraperitoneal adhesions occur in more than 94% of patients after abdominal surgery. Mechanisms that decrease oxidative stress and upregulate peritoneal fibrinolysis reduce adhesions. N-acetyl-l-cysteine (NAC) is a clinically relevant antioxidant whose effect on peritoneal fibrinolysis and ability to decrease adhesions has not been established. The aims of this study were to determine if NAC reduces adhesions and to characterize its potential mechanism(s) of action. METHODS: Male Wistar rats (n = 92) received 0.9% saline (OP Control), intraperitoneal NAC (150 mg/kg, OP + NAC), or oral NAC (1200 mg/kg) twice daily on preoperative day 1, day of operation, and postoperative day 1. Adhesions were induced on the day of operation using our previously described ischemic button model. Animals were killed on postoperative day 7 for adhesion scoring. Peritoneal tissue and fluid from the intraperitoneal NAC group were measured at 24 hours for fibrinolytic activity, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), total glutathione, and 8-isoprostane (8-IP). The effect of NAC on tPA and PAI-1 production was tested in vitro in human mesothelial cells. The effect of NAC on intestinal wound healing was measured using colonic anastomotic burst pressures. RESULTS: Intraperitoneal NAC reduced adhesions by 53% (P < .001) compared to OP Controls without affecting anastomotic wound healing. NAC increased the tPA/PAI-1 protein ratio and peritoneal fibrinolytic activity by 69% and 127%, respectively, compared to OP Controls (P < .05). NAC did not restore total glutathione levels in peritoneal adhesion tissue but decreased 8-IP by 46% and 65% (P < .05) in peritoneal tissue and fluid, respectively, compared to OP Controls. Human mesothelial cells incubated with NAC exhibited a concentration-dependent increase in the tPA/PAI-1 ratio, which supported in vivo observations (P < .05). Oral NAC did not decrease adhesions. CONCLUSION: NAC administered intraperitoneally decreased adhesion formation while upregulating peritoneal fibrinolytic activity and antioxidant defenses without affecting normal anastomotic wound healing. These data suggest a potential new therapeutic use for NAC in adhesion prevention.