Preoperative frailty assessment predicts loss of independence after vascular surgery.

OBJECTIVE: Frailty, a clinical syndrome associated with loss of metabolic reserves, is prevalent among patients who present to vascular surgery clinics for evaluation. The Clinical Frailty Scale (CFS) is a rapid assessment method shown to be highly specific for identifying frail patients. In this study, we sought to evaluate whether the preoperative CFS score could be used to predict loss of independence after major vascular procedures. METHODS: We identified all patients living independently at home who were prospectively assessed using the CFS before undergoing an elective major vascular surgery procedure (admitted for >24 hours) at an academic medical center between December 2015 and December 2017. Patient- and procedure-level clinical data were obtained from our institutional Vascular Quality Initiative registry database. The composite outcome of discharge to a nonhome location or 30-day mortality was evaluated using bivariate and multivariate regression models. RESULTS: A total of 134 independent patients were assessed using the CFS before they underwent elective open abdominal aortic aneurysm repair (8%), endovascular aneurysm repair (26%), thoracic endovascular aortic repair (6%), suprainguinal bypass (6%), infrainguinal bypass (16%), carotid endarterectomy (19%), or peripheral vascular intervention (20%). Among 39 (29%) individuals categorized as being frail using the CFS, there was no significant difference in age or American Society of Anesthesiologists physical status compared with nonfrail patients. However, frail patients were significantly more likely to need mobility assistance after surgery (62% frail vs 22% nonfrail; P < .01) and to be discharged to a nonhome location (22% frail vs 6% nonfrail; P = .01) or to die within 30 days after surgery (8% frail vs 0% nonfrail; P < .01). Preoperative frailty was associated with a >12-fold higher risk (odds ratio, 12.1; 95% confidence interval, 2.17-66.96; P < .01) of 30-day mortality or loss of independence, independent of the vascular procedure undertaken. CONCLUSIONS: The CFS is a practical tool for assessing preoperative frailty among patients undergoing elective major vascular surgery and can be used to predict likelihood of requiring discharge to a nursing facility or death after surgery. The identification of frail patients before major surgery can help manage postoperative expectations and optimize transitions of care.

Perineural bupivacaine injection reduces inguinodynia after inguinal hernia repair.

BACKGROUND: Inguinodynia, defined as pain lasting >3 months after inguinal hernia repair, remains the major complication of hernia operation. We sought to determine the effect of direct perineural infiltration on acute pain and inguinodynia after open inguinal hernia repair. METHODS: Patients who presented with an inguinal hernia at a university teaching hospital were evaluated prospectively and randomized to either (1) percutaneous ilioinguinal nerve block or (2) percutaneous ilioinguinal nerve block with additional perineural infiltration of the ilioinguinal, iliohypogastric, genitofemoral nerves. All patients in each group received a total of 12 mL of 0.5% bupivacaine. Self-reported faces of pain level (1-10), minutes to discharge from the recovery room, narcotic quantity consumed (oxycodone 5 mg/paracetamol 325 mg), days on narcotics, and incidence of inguinodynia at 3 months were all recorded. RESULTS: Ninety-two patients were randomized in the study. Patients who received perineural bupivacaine infiltration of nerves had less recovery room pain (1.3 vs 3.9, P < .001) and shorter recovery discharge times (89 vs 105 min, P = .047) and consumed fewer narcotics (9.7 vs 15.1 doses, P = .010). The incidence of inguinodynia at 3 months was less in the treatment group (8.2% vs 27.9%, P = .013). CONCLUSION: We have implemented a novel and inexpensive method of local nerve blockade that decreases pain immediately after operation and at 3 months postoperatively. Furthermore, our method leads to shorter recovery room stay and fewer narcotics after operation.

Trauma system overtriage: are we on track?

The American College of Surgeons (ACS) recommends trauma overtriage rate (OT) below 50 per cent to maximize efficiency while ensuring optimal care. This retrospective study was undertaken to evaluate OT rates in our Level I trauma center using the most recent criteria and guidelines. OT rates during a 12-month period were measured using six definitions based on combinations of Injury Severity Score (ISS), length of hospital stay (LOS, in days), procedures, and disposition after the emergency department. Reason for trauma activation was 55 per cent criteria, 16 per cent guidelines, 11 per cent paramedic judgment, five per cent no reason, and 13 per cent no documentation. OT rates ranged from 22.6 per cent (ISS less than 9, LOS 1 day or less, no consults) to 48.2 per cent (ISS less than 9, LOS 3 days or less, with procedures/consults) and were in compliance with ACS recommendations. Physiologic assessment criteria and anatomic injury had the lowest OT rates and contained all mortalities. Passenger space intrusion (PSI), pedestrian versus automobile (criterion and guideline), and extrication (guideline) all had consistently high rates of OT. We conclude that PSI should be reduced to a guideline, the pedestrian versus automobile criterion and guideline should be combined, and extrication could be removed from the triage scheme.

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

IMPORTANCE: Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. OBJECTIVE: To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. MAIN OUTCOMES AND MEASURES: Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. RESULTS: All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). CONCLUSIONS AND RELEVANCE: Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.

Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 µM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.

Impact of tumor grade on pancreatic cancer prognosis: validation of a novel TNMG staging system.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) patients demonstrate highly variable survival within each stage of the American Joint Committee on Cancer (AJCC) staging system. We hypothesize that tumor grade is partly responsible for this variation. Recently our group developed a novel tumor, node, metastasis, grade (TNMG) classification system utilizing Surveillance Epidemiology and End Results (SEER) data in which the presence of high tumor grade results in advancement to the next higher AJCC stage. This study's objective was to validate this TNMG staging system utilizing single-institution data. METHODS: All patients with PDAC who underwent resection at UCLA between 1990 and 2009 were identified. Clinicopathologic data reviewed included age, sex, node status, tumor size, grade, and stage. Grade was redefined as a dichotomous variable. The impact of grade on survival was assessed by Cox regression analysis. Disease was restaged into the TNMG system and compared to the AJCC staging system. RESULTS: We identified 256 patients who underwent resection for PDAC. Patients with low-grade tumors experienced a 13-month improvement in median survival compared to those with high-grade tumors. On multivariate analysis, tumor grade was the strongest predictor of survival with a hazard ratio of 2.02 (p = 0.0005). Restaging disease according to the novel TNMG staging system resulted in improved survival discrimination between stages compared to the current AJCC system. CONCLUSIONS: We were able to demonstrate that grade is one of the strongest independent prognostic factors in PDAC. Restaging with our novel TNMG system demonstrated improved prognostication. This system offers an effective and convenient way of adding grade to the current AJCC staging system.

Perioperative antibiotics for surgical site infection in pancreaticoduodenectomy: does the SCIP-approved regimen provide adequate coverage?

INTRODUCTION: The Joint Commission Surgical Care Improvement Project (SCIP) includes performance measures aimed at reducing surgical site infections (SSI). One measure defines approved perioperative antibiotics for general operative procedures. However, there may be a subset of procedures not adequately covered with the use of approved antibiotics. We hypothesized that piperacillin-tazobactam is a more appropriate perioperative antibiotic for pancreaticoduodenectomy (PD). METHODS: In collaboration with hospital epidemiology and the Division of Infectious Diseases, we retrospectively reviewed records of 34 patients undergoing PD between March and May 2008 who received SCIP-approved perioperative antibiotics and calculated the SSI rate. After changing our perioperative antibiotic to piperacillin-tazobactam, we prospectively reviewed PDs performed between June 2008 and March 2009 and compared the SSI rates before and after the change. RESULTS: For 34 patients from March through May 2008, the SSI rate for PD was 32.4 per 100 cases. Common organisms from wound cultures were Enterobacter and Enterococcus (50.0% and 41.7%, respectively), and these were cefoxitin resistant. From June 2008 through March 2009, 106 PDs were performed. During this period, the SSI rate was 6.6 per 100 surgeries, 80% lower than during March through May 2008 (relative risk, 0.204; 95% confidence interval [CI], 0.086-0.485; P = .0004). CONCLUSION: Use of piperacillin-tazobactam as a perioperative antibiotic in PD may reduce SSI compared with the use of SCIP-approved antibiotics. Continued evaluation of SCIP performance measures in relationship to patient outcomes is integral to sustained quality improvement.

CXCR2: a target for pancreatic cancer treatment?

INTRODUCTION: Pancreatic cancer, a leading cause of cancer deaths worldwide, is very aggressive and has minimally effective treatment options. For those who have no surgical options, medical treatments are limited. The chemokine receptor CXCR2 has become the subject of much interest recently because of multiple studies indicating its involvement in cancer and inflammatory conditions. Research now indicates that CXCR2 and its ligands are intimately involved in tumor regulation and growth and that inhibition of its function shows promising results in multiple cancer types, including pancreatic cancer. AREAS COVERED: In this study, the authors review basic molecular and structural details of CXCR2, as well as the known functions of CXCR2 and several of its ligands in inflammation and cancer biology with specific attention to pancreatic cancer. Then the future possibilities and questions remaining for pharmacological intervention against CXCR2 in pancreatic cancer are explored. EXPERT OPINION: Many current inhibitory strategies already exist for targeting CXCR2 in vitro as well as in vivo. Clinically speaking, CXCR2 is an exciting potential target for pancreatic cancer; however, CXCR2 is functionally important for multiple processes and therapeutic options would benefit from further work toward understanding of these roles as well as structural and target specificity.