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Background: Laparoscopic hysterectomies comprise a large proportion of all hysterectomies in the United States. Procedures completed under regional anesthesia pose a number of benefits to patients, but laparoscopic hysterectomies traditionally have been performed under general anesthesia. We describe a case of total laparoscopic hysterectomy under epidural anesthesia with the patient fully awake.Case: A 51-year-old woman with abnormal uterine bleeding underwent an uncomplicated total laparoscopic hysterectomy, bilateral salpingectomy, and excision of endometriosis. The procedure was completed under epidural anesthesia without intravenous sedation or systemic narcotics. Pneumoperitoneum with a pressure of 12 mm Hg and Trendelenburg to 15° allowed for adequate visualization. Anesthesia was achieved with midthoracic and low lumbar epidural catheters. Bilevel positive airway pressure was used for augmentation of respiratory function.Conclusion: With a committed patient, adequate planning, and knowledge of the potential intraoperative complications, regional anesthesia is an option for select women undergoing laparoscopic hysterectomy. [ABSTRACT FROM AUTHOR]

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab.

Background: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS., Methods: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used., Results: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period., Conclusions: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Pancreatic ductal adenocarcinoma (PDA) is rarely curable due to regional/metastatic spread at diagnosis. Identification of molecular markers may enhance diagnosis and early detection of PDA. The 2-electron reductase, NAD(P)H:quinone oxidoreductase (NQO1) has been found to be overexpressed in many solid tumors including PDA, and may be a useful clinically relevant diagnostic marker of malignancy. For this study, we used 37 surgical resection cases: 24 PDAs and 13 benign pancreatic tissue specimens. An additional 16 specimens from pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were included as a pilot series. NQO1 was detected by avidin-biotin based immunohistochemical and immunocytochemical methods. Both staining intensity and proportion of NQO1 positive tumor cells were scored. Moderate to strong (2 to 3+) staining for NQO1 was detected in 22/24 (92%) surgically resected PDAs, 9/9 (100%) EUS-FNAs with malignant diagnoses, one cytologically atypical but not diagnostic for malignancy EUS-FNA, and 1/6 (17%) EUS-FNAs initially diagnosed as negative for malignancy. Subsequent histologic assessment confirmed malignancy in all 9 cytologically positive EUS-FNAs and in the atypical case. The NQO1 positive case initially diagnosed as negative for malignancy showed no evidence of carcinoma on subsequent tissue biopsy. NQO1 staining was also observed in some benign ducts/cells; however, correlation of NQO1 expression with cellular morphology assessment minimizes the risk of false positive diagnosis. NQO1 is consistently overexpressed in PDA. Although NQO1 is observed in some benign tissue components, this marker may be a clinically useful diagnostic adjunct for detection of PDA, independent of tumor grade/stage.

Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a (pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-alpha2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.

Purpose: To determine the degree of correlation between radiographic size and true gross pathologic size for subjects with primary hepatocellular carcinoma (HCC)., Methods and Materials: This analysis included 18 patients with 27 tumors who underwent either partial hepatectomy or orthotopic liver transplantation for HCC at the University of Colorado Hospital between 1997 and 2002. Preoperative imaging was performed using computed tomography (CT) or magnetic resonance imaging (MRI). After surgical resection the size of each tumor on gross pathologic examination was recorded. The maximal measurement in one dimension on axial imaging and pathologic examination was extracted for statistical analysis. The clinical and pathologic sizes were compared using a percent size difference (%Deltasize) as an end point for each patient. A regression analysis was applied to study the association between pathologic and clinical size., Results: The median radiographic size was 2.90 cm (range 1.2-4.9). The median pathologic size was 2.50 cm (range 1-4.8). The radiographic size was larger than or equal to the pathologic size in 22/27 tumors (81%) and smaller in 5/27 (19%) tumors. The median %Deltasize was 17.5% (range -20-144%). Overall, the radiographic and pathologic sizes were positively correlated (r = 0.8). This correlation was not affected by choice of imaging modality (CT versus MRI, P = 0.71) or time of preoperative imaging (0-4 weeks versus 4-8 weeks before surgery, P = 0.61)., Conclusions: Our study shows that in most instances (81%), imaging by CT or MRI overestimates true gross pathologic size of HCC. Nineteen percent of tumors appeared smaller on preoperative imaging than on the final pathologic specimen. Radiation therapy utilizing a 0.5 or 1.0 cm margin around the radiographic tumor would have encompassed the gross pathologic tumor in 93% and 100% of cases, respectively.

Objectives: 1) To determine the degree and distribution and quantitate the severity of autonomic impairment in painful neuropathy (PN). 2) To assess the role of autonomic testing in evaluating PN., Methods: The authors studied 92 patients with PN (60 women and 32 men, age 56.9 +/- 12.4 years) using: 1) autonomic reflex testing (ART), Quantitative Sudomotor Axon Reflex Test (QSART), cardiac-vagal, head-up tilt, and surface skin temperature; 2) autonomic symptoms questionnaire; 3) nerve conduction (NCS) and laboratory studies; 4) quantitative sensory testing; 5) skin biopsy; and 6) Composite Autonomic Symptoms Score (CASS) scale to grade ART results from 0 (normal) to 10 (autonomic failure)., Results: Autonomic involvement in PN had characteristic features. Main symptoms were pain, secretory and skin vasomotor signs, hypertension, and impotence. ART results were abnormal in 86 (93.5%) (CASS < 4), QSART in 67 (72.8%), cardiac-vagal index in 58 (63%), skin temperature in 51 (55.4%), orthostatic hypertension in 39 (42.3%), and family history of PN in 26 (21%) of patients. Group 1 (abnormal NCS) (n = 45) had more severe ART and sensory abnormalities than the Group 2 (normal NCS) (n = 47): 1) CASS 2.0 +/- 0.96 vs 1.55 +/- 0.88 (p < 0.01), cardiac-vagal index (p < 0.02), skin temperature (p < 0.02), hypertension (p < 0.03), cooling (p < 0.002), and vibration (p < 0.0005) thresholds., Conclusions: Autonomic symptoms in painful neuropathy are predominantly cholinergic and form a unique constellation of features that are distinct from other autonomic neuropathies.

One hundred nineteen patients with coronary artery disease confirmed by coronary arteriograms were studied. Cine coronary arteriography confirmed progression of atherosclerosis in 106 (89%) patients (mean age 50.9 yr) and nonprogression in 13 (11%) patients (mean age 50.3 yr). Progression was defined as follows: any increase to 50% stenosis, 50% to 75% narrowing, 75% to 90%, 90% to 99%, 99% to total occlusion. Only one patient of the 106 who progressed (less than 1%) had ideal values for both cholesterol and triglyceride. Three of 13 patients (23%) who did not progress had ideal lipid values (P less than 0.005). Fifty four of 106 patients who progressed had cholesterol levels greater than or equal to 250 mg%; none of 13 patients who did not progress had such levels (P less than 0.005). Thirty-nine of 98 (40%) patients who progressed had hypertension; only one (8%) who did not progress had hypertension (P less than 0.025). Seventy-four of 96 patients who progressed were smokers (77%); two of 13 nonprogression patients smoked (15%) (P less than 0.005).