Sustained Carbohydrate Antigen 19-9 Response to Neoadjuvant Chemotherapy in Borderline Resectable Pancreatic Cancer Predicts Progression and Survival.

BACKGROUND: As neoadjuvant therapy of borderline resectable pancreatic cancer (BRPC) is becoming more widely used, better indicators of progression are needed to help guide therapeutic decisions. MATERIALS AND METHODS: A retrospective review was performed on all patients with BRPC who received 24 weeks of neoadjuvant chemotherapy. Patients with chemotoxicity or medical comorbidities limiting treatment completion and nonexpressors of carbohydrate antigen 19-9 (CA19-9) were excluded. Serum CA19-9 response was analyzed as a predictor of disease progression, recurrence, and survival. RESULTS: One hundred four patients were included; 39 (37%) progressed on treatment (18 local and 21 distant) and 65 (63%) were resected (68% R0). Multivariate logistic regression analysis determined that the percent decrease in CA19-9 from baseline to minimum value (odds ratio [OR] 0.947, p ≤ .0001) and the percent increase from minimum value to final restaging CA19-9 (OR 1.030, p ≤ .0001) were predictive of progression. A receiver operating characteristics curve analysis determined cutoff values predictive of progression, which were used to create four prognostic groups. CA19-9 responses were categorized as follows: (1) always normal (n = 6); (2) poor response (n = 31); (3) unsustained response (n = 19); and (4) sustained response (n = 48). Median overall survival for Groups 1-4 was 58, 16, 20, and 38 months, respectively (p ≤ .0001). CONCLUSION: Patients with initially elevated CA19-9 levels who do not have a decline to a sustained low level are at risk for progression, recurrence, and poor survival. Alternative treatment strategies prior to an attempt at curative resection should be considered in this cohort. IMPLICATIONS FOR PRACTICE: This study identified percent changes in carbohydrate antigen 19-9 blood levels while on chemotherapy that predict tumor growth in patients with advanced pancreas cancer. These changes could be used to better select patients who would benefit from surgical removal of their tumors and improve survival.

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival?

BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Cerebral Hyperperfusion Syndrome Presenting As Status Epilepticus Following Carotid Endarterectomy.

Cerebral Hyperperfusion Syndrome (CHS) is a rare syndrome, commonly described as a prodrome of symptoms including a severe ipsilateral headache, focal neurological deficits, intracerebral hemorrhage, and occasionally includes seizures or encephalopathy. Our case involves a 76-year-old man who underwent a left carotid endarterectomy (CEA) for symptomatic high-grade stenosis of his left carotid artery. Post-operative day one, the patient was seen and examined in the early morning and found to be doing well, with blood pressures well-controlled and at his neurologic baseline. Three hours later, he was reported to have a sudden spike in his blood pressure and was experiencing focal motor seizures involving the right arm and face, both of which were unrelieved by anti-hypertensives and anti-seizure medications. The patient subsequently developed worsening respiratory function requiring intubation for status epilepticus. Repeat head and neck imaging with CT, CT angiography, and MRI demonstrated the known previous subacute infarct with new cerebral edema, patent carotid arteries bilaterally, and no acute infarct or intracerebral hemorrhage. While CHS is a rare syndrome with well-documented symptomatology, we present a unique case in which focal motor status epilepticus was the only presenting symptom in a patient who otherwise meets the criteria of CHS based on radiographic evidence of cerebral edema following an elective CEA.

Real-World Single-Center Experience with Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Patients.

BACKGROUND/AIMS: The approval of sofosbuvir (SOF), a direct-acting antiviral, has revolutionized the treatment of chronic hepatitis C virus (HCV). METHODS: We assessed the sustained virological response (SVR) of SOF-based regimens in a real-world single-center setting for the treatment of chronic HCV genotype 1 (G1) patients. This was a retrospective review of chronic HCV G1 adult patients treated with a SOF-based regimen at Virginia Mason Medical Center between December 2013 and August 2015. RESULTS: The cohort comprised 343 patients. Patients received SOF+ledipasvir (LDV) (n=155), SOF+simeprevir (SIM) (n=154), or SOF+peginterferon (PEG)+ribavirin (RBV) (n=34). Of the patients, 50.1% (n=172) had cirrhosis. The SVR rate was 92.2% for SOF/LDV, 87.0% for SOF/SIM, and 82.4% for SOF/PEG/RBV. Compared with the cirrhotic patients, the patients without cirrhosis had a higher SVR (96.8% vs 85.5%, p=0.01, SOF/LDV; 98.2% vs 80.6%, p=0.002, SOF/SIM; 86.4% vs 75.0%, p=0.41, SOF/PEG/RBV). In this study, prior treatment experience adversely affected the response rate in subjects treated with SOF/PEG/RBV. CONCLUSIONS: In this single-center, real-world setting, the treatment of chronic HCV G1 resulted in a high rate of SVR, especially in patients without cirrhosis.

A systematic multidisciplinary initiative for reducing the risk of complications in adult scoliosis surgery.

OBJECTIVE Systematic multidisciplinary approaches to improving quality and safety in complex surgical care have shown promise. Complication rates from complex spine surgery range from 10% to 90% for all surgeries, and the overall mortality rate is 1%-4%. These rates suggest the need for improved perioperative complex spine surgery processes designed to minimize risk and improve quality. METHODS The Group Health Research Institute and Virginia Mason Medical Center implemented a systematic multidisciplinary protocol, the Seattle Spine Team Protocol, in 2010. This protocol involves the following elements: 1) a comprehensive multidisciplinary conference including clinicians from neurosurgery, anesthesia, orthopedics, internal medicine, behavioral health, and nursing, collaboratively deciding on each patient's suitability for surgery; 2) a mandatory patient education course that reviews the risks of surgery, preparation for the surgery, and postoperative care; 3) a dual-attending-surgeon approach involving 1 neurosurgeon and 1 orthopedic spine surgeon; 4) a dedicated specialist complex spine anesthesia team; and 5) rigorous intraoperative monitoring of a patient's blood loss and coagulopathy. The authors identified 71 patients who underwent complex spine surgery involving fusion of 6 or more levels before implementation of the protocol (surgery between 2008 and 2010) and 69 patients who underwent complex spine surgery after the implementation of the protocol (2010 and 2012). All patient demographic variables, including age, sex, body mass index, smoking status, diagnosis of diabetes and/or osteoporosis, previous surgery, and the nature of the spinal deformity, were comprehensively assessed. Also comprehensively assessed were surgical variables, including operative time, number of levels fused, and length of stay. The authors assessed overall complication rates at 30 days and 1 year and detailed deaths, cardiovascular events, infections, instrumentation failures, and CSF leaks. Chi-square and Wilcoxon rank-sum tests were used to assess differences in patient characteristics for patients with a procedure in the preimplementation period from those in the postimplementation period under a Poisson distribution model. RESULTS Patients who underwent surgery after implementation of the Seattle Spine Team Protocol had a statistically significant reduction (relative risk 0.49 [95% CI 0.30-0.78]) in all measured complications, including cardiovascular events, wound infections, other perioperative infections, and implant failures within 30 days after surgery; the analysis was adjusted for age and Charlson comorbidity score. A trend toward fewer deaths in this group was also found. CONCLUSIONS This type of systematic quality improvement strategy can improve quality and patient safety and might be applicable to other complex surgical disciplines. Implementation of these strategies in the treatment of adult spinal deformity will likely lead to better patient outcomes.