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Background: In patients in whom attempted endoscopic stenting of malignant biliary obstruction fails, combined percutaneous-endoscopic stenting and percutaneous stenting using expandable metallic endoprostheses offer alternative approaches to biliary drainage. Despite the popularity of the percutaneous route, there is no available evidence to support its superiority over combined stenting in this patient group. The objective of this study was to present the short- and long-term results of a large series of combined percutaneous-endoscopic stenting procedures and identify factors associated with adverse outcome.Methods: Data were retrospectively collected on patients undergoing combined percutaneous-endoscopic biliary stenting for malignant biliary obstruction between January 2002 and December 2006. Short- and long-term outcomes were recorded, and pre-procedure variables correlated with adverse outcome.Results: Combined biliary stenting was technically successful in 102 (96.2%) of 106 patients. Procedure-associated mortality rate was 0%. In-hospital morbidity and mortality rates were 24.5% and 16.7%, respectively, with the majority of deaths resulting from biliary sepsis. Median survival was 100 days, with a 13.7% stent occlusion rate. On multivariable analysis, baseline American Society of Anaesthesiologists (ASA) grade, decreasing serum albumin and increasing leucocyte count were independently associated with in-hospital mortality following combined stenting.Conclusion: Combined biliary stenting is associated with short- and long-term outcomes equal to those reported in recent series of percutaneous transhepatic stenting. Randomised control trials, including cost-effectiveness analyses, are required to further compare these techniques. Outcomes following combined stenting may be further improved by early recognition and treatment of sepsis and scrupulous management of co-morbid disease. [ABSTRACT FROM AUTHOR]

Objective: This study reports the infant to preschool outcomes of a laparotomy-assisted, two-port fetoscopic myelomeningocele (MMC) repair and compares the results with those of a contemporary, same-center cohort that underwent either fetal MMC surgery via hysterotomy or postnatal MMC repair., Methods: All MMC closures between December 2011 and July 2021 were screened. Singleton pregnancies with hindbrain herniation and MMC between T1 and S1 were included. Fetuses were excluded for genetic abnormalities, severe kyphosis, and other congenital anomalies. The pregnant woman determined the method of MMC repair (fetoscopic, hysterotomy, or postnatal repair)., Results: Two hundred MMC closures met the study criteria (100 fetoscopic, 41 hysterotomy, and 59 postnatal). The median length of follow-up was beyond 46 months for all groups. The median gestational age at delivery was 38.1 weeks (IQR 35.1, 39.1 weeks) for the fetoscopic group, 35.7 weeks (IQR 33.6, 37.0 weeks) for the hysterotomy group, and 38.6 weeks (IQR 37.7, 39.0 weeks) for the postnatal group. Vaginal delivery occurred in 51% of the fetoscopic cases, and there were no instances of uterine dehiscence or rupture. Treatment for hydrocephalus in the 1st year occurred in 35% (95% CI 27%-50%) of fetoscopic, 33% (95% CI 20%-50%) of hysterotomy, and 81% (95% CI 70%-90%) of postnatal repair cases. At 30 months, patients who underwent fetal intervention were twice as likely to be community ambulators (with or without devices) as those who underwent postnatal repair (52% [95% CI 42%-62%] of fetoscopic, 54% [95% CI 39%-68%] of hysterotomy, and 24% [95% CI 14%-36%] of postnatal cases). Surgery for symptomatic tethered cord occurred in 12% (95% CI 7%-19%) of fetoscopic, 17% (95% CI 8%-31%) of hysterotomy, and 2% (95% CI 1%-8%) of postnatal repair cases. Surgery for symptomatic spinal inclusion cysts was required in 4% (95% CI 1%-9%) of fetoscopic, 7% (95% CI 2%-18%) of hysterotomy, and none (95% CI 0%-8%) of the postnatal cases., Conclusions: Laparotomy-assisted, two-port fetoscopic repair provides significant benefits for maternal health. It negates the risk of uterine rupture for the index pregnancy and subsequent pregnancies and allows for vaginal delivery. The benefits to the fetus are the same as those of hysterotomy repairs, with a lower risk of prematurity. There was no difference in the rate of surgery for tethered cord or spinal inclusion cysts between fetoscopic and hysterotomy procedures. Overall, laparotomy-assisted, two-port fetoscopic repair is safer for the fetus and the mother than fetal MMC surgery via hysterotomy.

Background: Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been shown to persist in the dermis despite use of preoperative antibiotics and standard skin preparations. Studies have shown decreased rates of cultures positive for C acnes with use of preoperative benzoyl peroxide or hydrogen peroxide (H 2 O 2 ), but even with this positive deep cultures remain common. We sought to determine whether an additional application of H 2 O 2 directly to the dermis following skin incision would further decrease deep culture positivity rates., Methods: We performed a randomized controlled trial comparing tissue culture results in primary TSA in patients who received a standard skin preparation with H 2 O 2 , ethanol, and ChloraPrep (CareFusion, Leawood, KS, USA) vs. an additional application of H 2 O 2 to the dermis immediately after skin incision. Given the sexual dimorphism seen in the shoulder microbiome regarding C acnes colonization rates, only male patients were included. Bivariable and multivariable analyses were performed to compare rates of positive cultures based on demographic and surgical factors., Results: Dermal cultures were found to be positive for C acnes at similar rates between the experimental and control cohorts for the initial (22% vs. 28%, P = .600) and final (61% vs. 50%, P > .999) dermal swabs. On bivariable analysis, the rate of positive deep cultures for C acnes was lower in the experimental group, but this difference was not statistically significant (28% vs. 44%, P = .130). However, patients who underwent anatomic TSA were found to have a significantly greater rate of deep cultures positive for C acnes (57% vs. 28%, P = .048); when controlling for this on multivariable analysis, the experimental cohort was found to be associated with significantly lower odds of having positive deep cultures (odds ratio, 0.37 [95% confidence interval, 0.16-0.90], P = .023). There were no wound complications in either cohort., Conclusions: An additional H 2 O 2 application directly to the dermis following skin incision resulted in a small but statistically significant decrease in the odds of having deep cultures positive for C acnes without any obvious adverse effects on wound healing. Given its cost-effectiveness, use of a post-incisional dermal decontamination protocol may be considered as an adjuvant to preoperative use of benzoyl peroxide or H 2 O 2 to decrease C acnes contamination., (Published by Elsevier Inc.)

Objective: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions., Methods: This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality Care Collaborative), SIRS (Systemic Inflammatory Response Syndrome), the MEWC (the Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System), and the MEWT (Maternal Early Warning Trigger Tool). Sensitivity, false-positive rates, and C-statistics were reported for each screening tool. Analyses were stratified into cohort 1, which excluded patients with chorioamnionitis-endometritis, and cohort 2, which included those patients., Results: Delivery admissions at 59 hospitals were extracted for patients with sepsis. Cohort 1 comprised 647 patients with sepsis, including 228 with end-organ injury, matched with a control group of 2,588 patients without sepsis. Cohort 2 comprised 14,591 patients with chorioamnionitis-endometritis, of whom 1,049 had sepsis and 238 had end-organ injury. In cohort 1, the CMQCC and the UKOSS pregnancy-adjusted criteria had the lowest false-positive rates (6.9% and 9.6%, respectively) and the highest C-statistics (0.92 and 0.91, respectively). Although other screening criteria, such as SIRS and the MEWC, had similar sensitivities, it was at the cost of much higher false-positive rates (21.3% and 38.3%, respectively). In cohort 2, including all patients with chorioamnionitis-endometritis, the highest C-statistics were again for the CMQCC (0.67) and UKOSS (0.64). All screening tools had high false-positive rates, but the false-positive rates for the CMQCC and UKOSS were substantially lower than those for SIRS and the MEWC., Conclusion: During delivery admissions, the CMQCC and UKOSS pregnancy-adjusted screening criteria have the lowest false-positive results while maintaining greater than 90% sensitivity rates. Performance of all screening tools was degraded in the setting of chorioamnionitis-endometritis., Competing Interests: Financial Disclosure Melissa Bauer reports consulting fees from Institute for Healthcare Innovation. Vesela. Kovacheva reports consulting fees from Avania CRO unrelated to the current work. Paloma Toledo reports speaker fees from Pacira Biosciences, Inc. Kurt Wharton receives consulting fees from Molnlycke. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions., Methods: This was a case-control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non-pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), the MEWC (Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System) obstetric SIRS, and the MEWT (Maternal Early Warning Trigger Tool). Time periods were divided into early pregnancy (less than 20 weeks of gestation), more than 20 weeks of gestation, early postpartum (less than 3 days postpartum), and late postpartum through 42 days. False-positive screening rates, C-statistics, sensitivity, and specificity were reported for each overall screening tool and each individual criterion., Results: We identified 525 patients with sepsis during an antepartum hospitalization and 728 patients with sepsis during a postpartum readmission. For early pregnancy and more than 3 days postpartum, non-pregnancy-adjusted SIRS had the highest C-statistics (0.78 and 0.83, respectively). For more than 20 weeks of gestation and less than 3 days postpartum, the pregnancy-adjusted sepsis screening tools (CMQCC and UKOSS) had the highest C-statistics (0.87-0.94). The MEWC maintained the highest sensitivity rates during all time periods (81.9-94.4%) but also had the highest false-positive rates (30.4-63.9%). The pregnancy-adjusted sepsis screening tools (CMQCC, UKOSS) had the lowest false-positive rates in all time periods (3.9-10.1%). All tools had the lowest C-statistics in the periods of less than 20 weeks of gestation and more than 3 days postpartum., Conclusion: For admissions early in pregnancy and more than 3 days postpartum, non-pregnancy-adjusted sepsis screening tools performed better than pregnancy-adjusted tools. From 20 weeks of gestation through up to 3 days postpartum, using a pregnancy-adjusted sepsis screening tool increased sensitivity and minimized false-positive rates. The overall false-positive rate remained high., Competing Interests: Financial Disclosure Melissa Bauer disclosed receiving consulting fees from the Institute for Healthcare Innovation, and travel compensation from National AIM to present the ACOG/AIM Sepsis Bundle at the ACOG Annual Conference. Vesela Kovacheva disclosed receiving consulting fees from Avania CRO unrelated to the current study. Paloma Toledo disclosed receiving speaker fees from Pacira Biosciences, Inc. Kurt Wharton disclosed receiving consulting fees from Molnlycke. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.

Anesthesiologists are critical members of the multidisciplinary team managing patients with suspected placenta accreta spectrum (PAS). Preoperatively, anesthesiologists provide predelivery consultation for patients with suspected PAS where anesthetic modality and invasive monitor placement is discussed. Additionally, anesthesiologists carefully assess patient and surgical risk factors to choose an anesthetic plan and to prepare for massive intraoperative hemorrhage. Postoperatively, the obstetric anesthesiologist hold unique skills to assist with postoperative pain management for cesarean hysterectomy. We review the unique aspects of peripartum care for patients with PAS who undergo cesarean hysterectomy and explain why these responsibilities are critical for achieving successful outcomes for patients with PAS. KEY POINTS: · Anesthesiologists are critical members of the multidisciplinary team planning for patients with suspected placenta accreta spectrum.. · Intraoperative preparation for massive hemorrhage is a key component of anesthetic care for patients with PAS.. · Obstetric anesthesiologists have a unique skill set to manage postpartum pain and postoperative disposition for patients with PAS who undergo cesarean hysterectomy.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Accurate glenoid component placement in shoulder arthroplasty is often difficult even with the use of preoperative planning. Computer navigation and patient-specific guides increase component placement accuracy, but which patients benefit most is unknown. Our purpose was to assess surgeons' accuracy in placing a glenoid component in vivo using 3-dimensional preoperative planning and standard instruments among various glenoid wear patterns., Methods: We conducted a retrospective review of 170 primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) performed at a single institution. Commercially available preoperative planning software was used in all arthroplasties with multiplanar 2-dimensional computed tomography and a 3-dimensional implant overlay. After registration of intraoperative bony landmarks to the navigation system, participating surgeons with knowledge of the preoperative plan were blinded to the computer screen and attempted to implement their preoperative plan by simulating placement of a central-axis glenoid guide pin. Two hundred thirty-three screenshots of surgeon's simulated guide pin placement were included. Glenoid displacement, error in version and inclination, and overall malposition from the preoperatively planned target point were stratified by posterior wear status (with [Walch B2 or B3] or without [A1, A2, or B1]) and Walch classification (A1, A2, B1, B2, or B3). The glenoid component was considered malpositioned when version or inclination errors exceeded 10° or the starting point displacement exceeded 4 mm., Results: For rTSA, errors in version were greater for glenoids with posterior wear compared with those without (8.1° ± 5.6° vs. 4.7° ± 4.0°; P  < .001). On post hoc analysis, B2 glenoids had greater version error than A1, A2, and B1 glenoids. A greater proportion of glenoids undergoing rTSA that possessed posterior wear had an error in version >10° compared with those without (31% vs. 8%; P  < .001). Consequently, glenoids undergoing rTSA with posterior wear were malpositioned at a greater rate compared with those without (73% vs. 53%). In contrast, glenoids undergoing aTSA with and without posterior wear did not differ based on displacement error, version error, inclination error, or malposition occurrence., Conclusions: Posterior glenoid bone loss more commonly resulted in glenoid version errors exceeding 10 degrees and component malposition in rTSA, but not for aTSA. Malposition was still relatively high in patients without significant posterior wear for both aTSA (36%) and rTSA (53%). Surgeons should consider alternate techniques beyond preoperative planning and standard instrumentation when performing shoulder arthroplasty in patients with posteriorly worn glenoids.

Obstetric anesthesiologists can use the tenets of principlism to identify ethically supportable decisions. This approach begins with recognizing and upholding the fiduciary obligations that every physician has to their patient. For the pregnant patient, these obligations are both autonomy- and beneficence-based. Additional beneficence-based obligations arise in cases where the fetus is also considered a patient. Ethical dilemmas result from conflict between any of these obligations. A shared decision-making model that incorporates the foundational principles of ethics can be used to resolve these conflicts, leaving clinicians and patients confident that a sound decision-making process has taken place and an ethically supportable decision has been reached., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery., Methods: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well as instruction on the dangers of opioids in the home. Our primary outcome was to assess the absolute percent return rate through the use of a mail-back envelope., Results: Between November 2017 and October 2018, we identified 355 patients, of whom 331 were included in the analysis. In total, 64 (19.3%) returned opioids. In total, >2000 mL of liquid opioids and >250 tablets or nearly 3000 mg of oral morphine equivalents were removed from the homes of the 64 participants. Of those patients returning unused medications, the median rate of return was 58% (interquartile range = 34.7%-86.1%) of the written prescription., Conclusions: The findings suggest that providing a free mail-back return envelope is a suitable way to remove unused opioids from the home after pediatric surgery. Additional research is needed to identify barriers to return of unused medications., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

We describe the management of a pregnant patient with osteogenesis imperfecta with a history of numerous fractures, severe scoliosis, and anticipated difficult airway. Her pregnancy was complicated by progressive shortness of breath and a fetal diagnosis of osteogenesis imperfecta. Spine anatomy precluded neuraxial anesthesia. Cesarean delivery was performed under general anesthesia at 34 weeks. Immediately after awake fiberoptic intubation and induction of general anesthesia, capnography waveform was lost with rapid profound oxygen desaturation. A supraglottic airway device was placed, oxygenation maintained with supraglottic airway and positive pressure ventilation throughout case, and the baby was delivered with Apgars of 8 and 9.

Introduction: Follistatin (FST) is a protein with numerous biological roles and was recently identified as an exercise-inducible hepatokine; however, the signals that regulate this are not well understood. The purpose of this study was to delineate potential endocrine factors that may regulate hepatic FST at rest and during exercise., Methods: This study used four experiments. First, male and female C57BL/6J mice remained sedentary or were subjected to a single bout of exercise at moderate or exhaustive intensity with liver collected immediately post. Second, mice were injected with glucagon (1 mg·kg, 60 min), epinephrine (2 mg·kg, 30 min), glucagon then epinephrine, or saline. Third, mice were pretreated with propranolol (20-60 mg·kg, 30 min) before epinephrine injection. Fourth, glucagon receptor wild type (Gcgr) or knockout (Gcgr) mice were pretreated with saline or propranolol (20 mg·kg, 30 min) and were subjected to a single bout of exhaustive exercise with liver collected immediately post or after 2 h recovery. In all experiments liver FST mRNA expression was measured, and in experiment four FST protein content was measured., Results: A single bout of treadmill exercise performed at an exhaustive but not moderate-intensity increased FST expression, as did injection of glucagon or epinephrine alone and when combined. Pretreatment of mice with propranolol attenuated the epinephrine-induced increase in FST expression. The exercise-induced increase in FST expression was attenuated in Gcgr mice, with no effect of propranolol. Gcgr mice had higher protein content of FST, but there was no effect of exercise or propranolol., Conclusions: These data suggest that both glucagon and epinephrine regulate hepatic FST expression at rest; however, only glucagon is required for the exercise-induced increase.

Background: Choice of postcesarean delivery analgesic protocol may improve pain experience and reduce analgesic requirements., Methods: Cesarean delivery patients were randomly assigned either to choose their postcesarean delivery analgesia protocol or to have no choice and receive routine care. Choices were low (50 μg intrathecal morphine), medium (identical to routine care: 150 μg intrathecal morphine), or high (300 μg intrathecal morphine with 600 mg oral gabapentin). All groups received scheduled acetaminophen and ibuprofen. The primary outcome was oxycodone requirements 0-48 hours postdelivery in those offered versus not offered a choice., Results: Of 160 women enrolled, 120 were offered a choice and 40 were not offered a choice. There was no difference in oxycodone requirements or pain associated with choice, but those who had a choice expressed more satisfaction than those who did not have a choice (mean (95% CI) difference 5% (0% to 10 %), p=0.005). In the choice group, the high dose group required more oxycodone (5 (0 to 15) mg 0-24 hours after delivery and 15 (10 to 25) mg at 24-48 hours; p=0.05 and p=0.001) versus the low and medium groups. The low dose group had less pruritus (p=0.001), while the high dose group had more vomiting (p=0.01) requiring antiemetic treatment (p=0.04)., Conclusion: Having a choice compared with no choice routine care did not reduce oxycodone requirements or pain scores. However, women have insight into their analgesic needs; women offered a choice and who chose the higher dose analgesic protocol required more oxycodone, and women who chose the lower dose protocol required less oxycodone. Despite providing additional analgesic (six times more intrathecal morphine plus gabapentin in high dose vs low dose protocols), we still did not equalize postcesarean oxycodone requirement differences between groups., Trial Registration Number: NCT02605187., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objective: We examined the characteristics of women who choose nitrous oxide for labor analgesia and identified factors that predict conversion from nitrous oxide to labor neuraxial analgesia., Design: Retrospective descriptive study., Setting: Labor and Delivery Ward., Patients: 146 pregnant women who used nitrous oxide for analgesia during labor and delivery between September 2014 and September 2015., Interventions: Chart review only., Measurements: Demographic, obstetric, and intrapartum characteristics of women using nitrous oxide were examined. Multivariable logistic regression was performed to identify factors associated with conversion from nitrous oxide to neuraxial analgesia. Data are presented as n (%), median [IQR], adjusted relative risk (aRR), and 95% confidence intervals (CI) as appropriate., Results: During the study period, 146 women used nitrous oxide for labor analgesia (accounting for 3% of the total deliveries). The majority (71.9%) of women who used nitrous oxide were nulliparous, and over half (51.9%) had expressed an initial preference for "nonmedical birth." The conversion rate to neuraxial blockade was 63.2%, compared to a concurrent institutional rate of 85.1% in women who did not use nitrous oxide. Factors associated with conversion from nitrous oxide to neuraxial blockade were labor induction (aRR=2.0, CI 1.2-3.3) and labor augmentation (aRR=1.7, CI 1.0-2.9)., Conclusion: Only a small number of women opted to use nitrous oxide during labor, analgesia was minimal, and most converted to neuraxial analgesia. Women with induced and augmented labors should be counseled about the increased likelihood that they will convert to neuraxial analgesia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine., Materials and Methods: Whole body glucagon receptor deficient mice (Gcgr -/- ) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined., Results: Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr -/- mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr -/- mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr -/- mice., Conclusions: Gcgr -/- mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The study aim was to investigate internet use for obtaining information about epidurals for labor and delivery., Methods: Google Trends for US data was queried from 2004 to 2015 to find the most common searches and determine temporal trends. The Google Trends query used the term [epidural] and evaluated changes in search trends over time. Search comparisons were made for each year from 2004 to 2015, and three equal time epochs during the study period (2004-07, 2008-11, 2012-15) were compared. We also compared searches for epidurals with commonly searched birth-related terms., Results: Internet searches are increasing; there were 726000 searches for [epidural] in 2015. Search terms with the most significant growth in the past 4years (2012-15) were "birth with epidural," "pain after epidural," "labor without epidural," "epidural birth video," and "epidural vs natural". Searches for epidural side effects, risks, and pain on insertion were among the most common and were increasing most rapidly. Searches related to epidurals were more common than searches related to "natural births", "home births", and "labor pain", but were less common than searches for "midwives" or "doulas"., Conclusion: The findings provide an insight into internet use by those seeking information about labor analgesic options. Identifying the most common and rapidly increasing online search queries may guide physician-parturient interactions and online content creation, to address labor analgesic topics that most interest users., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The Golgi-Cox method of neuron staining has been employed for more than two hundred years to advance our understanding of neuron morphology within histological brain samples. While it is preferable from a practical perspective to prepare brain sections at the greatest thickness possible, in order to increase the probability of identifying stained neurons that are fully contained within single sections, this approach is limited from a technical perspective by the working distance of high-magnification microscope objectives. We report here a protocol to stain neurons using the Golgi-Cox method in mouse brain sections that are cut at 500 μm thickness, and to visualize neurons throughout the depth of these sections using an upright microscope fitted with a high-resolution 30X 1.05 N.A. silicone oil-immersion objective that has an 800 μm working distance. We also report two useful variants of this protocol that may be employed to counterstain the surface of mounted brain sections with the cresyl violet Nissl stain, or to freeze whole brains for long-term storage prior to sectioning and final processing. The main protocol and its two variants produce stained thick brain sections, throughout which full neuron dendritic trees and dendrite spines may be reliably visualized and quantified.

Cesarean delivery rates are increasing worldwide, and effective postoperative pain management is a key priority of women undergoing cesarean delivery. Inadequate pain management in the acute postoperative period is associated with persistent pain, greater opioid use, delayed functional recovery, and increased postpartum depression. In addition to pain relief, optimal management of patients after cesarean delivery should address the goals of unrestricted maternal mobility, minimal maternal and neonatal side effects, rapid recovery to baseline functionality, and early discharge home. Multimodal analgesia should include neuraxial morphine in conjunction with nonopioid adjuncts, with additional oral or intravenous opioids reserved for severe breakthrough pain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n = 80, ∼8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P < 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-α, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1β) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72.

Abstract: Sleeve gastrectomy has increased in popularity over the last five years and it is likely to supersede gastric banding. Nevertheless, it is unclear whether vitamin B12 supplementation is required after surgery. The aim of this short report is to identify any vitamin B12 deficiency and highlight the necessity of post laparoscopic sleeve gastrectomy vitamin B12 monitoring., Patients and Methods: A review of 66 patients underwent LSG in our institution. 25 patients were excluded as they had no postoperative vitamin B12 screening. 41 patients were included as screened for vitamin B12 and other micronutrients including selenium, serum folate, ferritin, iron, zinc, copper, magnesium and vitamin D., Result: There were 5 male (12%) and 36 females (88%), 8/41 patients (20%) had Vitamin B12 deficiency, none of them developed macrocytic anaemia. 17/21 (81%) patient were vitamin D deficient and 9/21 (43%) exhibited low selenium., Conclusion: In this small group, a 20% prevalence of vitamin B12 was identified. As a consequence vitamin B12 monitoring and supplementation will be a standard of care in the early postoperative period after LSG at this institution.

Introduction: The United Kingdom's Department of Health has identified reducing delays in patient discharge as a key aim for Health Service development. Laparoscopic cholecystectomy and laparoscopic inguinal hernia repair may be safely performed on a short stay basis, but day case rates remain low, with delays in discharge identified as a major contributing factor. Nurse-led discharge has been widely advocated to speed patient discharge across varied specialities, but objective evidence to support its use is lacking. This study aimed to assess the effectiveness of nurse-led discharge following laparoscopic surgery., Methods: A retrospective comparison of doctor-led and nurse-led discharge following laparoscopic surgery was performed by analysis of two consecutive 4-month periods, prior to and following the introduction of nurse-led discharge by a laparoscopic nurse specialist. Outcomes assessed included time to discharge, reasons for delayed discharge, hospital readmissions and primary care episodes following discharge., Results: A total of 128 patients were included in the study, with each discharge group containing 64 patients. Patients in the nurse-led discharge group were significantly more likely to be discharged on the day of surgery than patients in the doctor-led discharge group (17.2% vs. 4.7%; P = 0.023), with a highly significant difference in same day discharge rates noted among patients operated on during morning theatre lists (44.0% vs. 10.7%; P = 0.006). There was no significant difference between the discharge groups in readmission rates or in the number of patients seeking primary care attention following discharge., Conclusions: Nurse-led discharge may speed discharge following laparoscopic surgery with no apparent detriment to patient care., (© 2010 Blackwell Publishing Ltd.)

Introduction: The management of esophageal perforations and leaks remains a challenge. Although there are broad management principles, each situation may require a different surgical approach. The aim of this report was to describe the management of these esophageal crises by transluminal drainage via a transabdominal approach., Methods: Between 2005 and 2009, patients with anastomotic or gastric staple line leak (n = 4) or esophageal perforation (n = 2) underwent transabdominal surgery and transluminal drainage. This simple technique has, to the best of our knowledge, not been previously reported., Results: All six patients survived. The median intensive care unit and hospital stays were 12 days (range 0-32) and 63 days (range 32-99), respectively. At a median follow-up time of 25 months (range 15-60), five of the six patients remain alive and well. One patient with node positive esophageal carcinoma has died from relapsed disease., Conclusions: Transabdominal transluminal drainage should be added to the list of potential techniques that can be employed in management of esophageal leaks and perforations. It is a valuable adjunct to the armamentarium of the esophageal surgeon for dealing with these challenging situations.

Introduction: The Two Week Wait Referral Service (2WW) has been implemented as a means of fast-tracking patients with suspected upper gastrointestinal cancers for endoscopy. Whether or not it impacts on the outcome of these patients is unclear. The aim of this study was to compare the outcome of patients referred through 2WW with that of patients with oesophago-gastric cancer identified through alternate referral pathways (routine, emergency)., Methods: The study population was 340 patients with oesophago-gastric carcinoma (gastric 154) diagnosed during the time period 01/2006-12/2007 at University Hospitals of Leicester NHS Trust. Data were collected prospectively by the MDT co-ordinator and analysed retrospectively., Results: 135 of the 340 patients with oesophago-gastric cancer were diagnosed through the 2WW, 115 patients through routine referral pathways, and 90 patients were admitted on an emergency basis. Patients referred through 2WW had a median referral to 1st treatment time of 47 days (routine 79, emergency 28, p < 0.001 all group comparisons). The number of patients treated with potentially curative intent was 37 of 135 for the 2WW, 42 of 115 for the routine referrals and 10 of 90 for patients admitted as emergencies. The corresponding median survivals for the groups were 239 days (2WW), 405 days (routine) and 121 days (emergency), p < 0.001 (log rank)., Conclusions: Referral by 2WW resulted in more rapid treatment than routine referral but this did not translate into an improvement in survival. This suggests that the targeting of endoscopy to patients with alarm symptoms is flawed and a less selective approach should be promoted if curable cancers are to be detected., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. In Leicester, we developed a combined radiological and endoscopic technique (predating the use of endoscopic/ultrasound) to allow drainage of pancreatic pseudocysts into the stomach. The aim of the study was to evaluate the long-term results of this approach., Methods: This is a retrospective study of patients undergoing combined endoscopic/ultrasound-guided percutaneous stenting between 1994 and 2007. Data were extracted from case records and our computerised radiology database., Results: Thirty-seven combined endoscopic/ultrasound-guided procedures were undertaken. Median patient age was 52 years (range 26-84 years). Nineteen pseudocysts were secondary to acute pancreatitis and 18 were in patients with chronic pancreatitis. The diameter of pseudocysts on pre-procedure imaging ranged from 4 to 21 cm (median 11 cm). Median duration of hospital stay was 7 days (range 1-44 days) and 30-day mortality was 0%. Stents were inserted in 70.3% of patients (n= 26). Of those patients stented during the combined procedure, three developed infection of the pseudocyst, necessitating open cystgastrostomy within the first month. During a mean follow-up period of 41 months, two patients developed recurrent pseudocysts which were successfully drained with a further combined procedure (16 and 43 months). Repeat imaging in the remainder of patients failed to show any evidence of a persistent or recurrent pseudocyst beyond 2 months., Conclusion: Combined radiological and endoscopic drainage is safe, cost-effective and highly efficient in preventing recurrent pseudocyst formation., (© 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.)

Objective: To assess the impact of the laparoscopic inguinal release procedure with mesh reinforcement on athletes with groin pain., Design: Prospective cohort study., Setting: Private sector., Patients: Professional and amateur sportsmen/women undergoing the inguinal release for groin pain., Main Outcome Measurements: Change in patient's symptoms, functional limitation and time to resuming sporting activity following surgery., Results: 73 sportsmen/women underwent laparoscopic inguinal release in the study period, 37 (51%) of whom were professionals. 95% were male with a median age of 30 years. Following operation, patients returned to light training at a median of 1 week, full training at 3 weeks (professionals-2 weeks) and playing competitively at 4 weeks (professionals-3 weeks). 74% considered themselves match-fit by 4 weeks (84% of professionals). Following surgery, there was a highly significant improvement in frequency of pain, severity of pain and functional limitation in both the whole cohort and professional group. 88% reported a return to full fitness at follow-up, with 73% reporting complete absence of symptoms. 97% of the cohort thought the operation had improved their symptoms., Conclusions: This study shows that the laparoscopic inguinal release procedure may be effective in the treatment of a subgroup of athletes with groin pain.

Collagenous colitis is an uncommon inflammatory bowel disease, the aetiology of which is unknown. We report a case of toxic megacolon in a patient with collagenous colitis, a previously unreported complication.

Introduction: The routine use of positron emission tomography-computed tomography (PET-CT) in the staging of patients with esophageal carcinoma remains contentious, with conflicting reports of its benefit. In our unit, PET-CT has been used routinely in the staging of all patients considered for radical therapy (surgery or chemoradiotherapy). Our aim was to determine the frequency with which PET-CT influenced decision making in the management of patients with carcinoma of the esophagus or gastroesophageal junction., Methods: CT, PET-CT, and outcome information were collected on 38 patients considered for radical therapy. Patient proformas, with and without PET-CT findings, were constructed and each independently reviewed in a randomized and blinded fashion by five multidisciplinary team members (three surgeons, two oncologists) and a treatment strategy determined., Results: PET-CT changed the staging for ten patients (26%). This translated into a change in management decision for seven patients (18%). The concordance between individual management plans and treatment intent was 79% for CT (150 of 190 decisions) and it was 92% for PET-CT (175 of 190 decisions). Full concordance between multidisciplinary team members was 66% with CT staging and 74% with the addition of PET-CT., Conclusion: The use of PET-CT early in the staging algorithm for esophageal carcinoma altered the staging for a quarter of patients and the management for a fifth of patients, supporting its inclusion early in the staging algorithm.

Covered self-expanding metallic stents are commonly employed to relieve malignant oesophageal obstruction. We report a case of a patient with oesophageal cancer treated by stent insertion and curative chemoradiotherapy with subsequent stent migration to the stomach. The stent fractured with the distal fragment migrating as far as the terminal ileum where it caused perforation of the bowel.

Introduction: This study compared pathological characteristics and patterns of disease recurrence for patients with pT1 esophageal adenocarcinoma treated with either laparoscopic transhiatal esophagectomy or open esophagectomy., Methods: From January 2000-December 2006, 44 patients had pT1 esophageal adenocarcinoma after esophagectomy. No patients had neoadjuvant treatment. Twenty-four patients had an Ivor Lewis operation, 4 had an open transhiatal and 16 had a laparoscopic transhiatal operation., Results: There were 37 men. The median age was 64 years (range 35-80 years). Median lymph node yield was 19 (10-51) after an Ivor Lewis operation, 16 (3-28) after an open transhiatal operation and 15 (4-41) after a laparoscopic transhiatal operation. There were two in-hospital deaths (5%), both following open Ivor Lewis operation. All patients in the laparoscopic group had N0 disease; none received adjuvant treatment. Two patients (7%) in the open group had N1 disease, of whom one patient received adjuvant chemotherapy. Eleven patients had submucosal invasion. Alive patients had median follow-up of 36 months (range 5-87 months). One patient in the laparoscopic group had recurrence at 22 months. This patient had poorly differentiated N0 disease which was limited to the mucosa and died at 24 months. Two patients in the open group developed recurrence, at 6 months (N0 disease with submucosal invasion) and 8 months (N1 disease with submucosal invasion) and died at 7 and 14 months, respectively. Both patients had poorly differentiated tumours. The second patient with N1 disease is alive and well at 14 months. Estimated survival (Kaplan-Meier) at 3 years was 93%., Conclusions: As compared with open transthoracic esophagectomy, there is no oncological detriment in the treatment of pT1 esophageal adenocarcinoma by laparoscopic transhiatal esophagectomy. The incidence of recurrence is small (7%) but can occur even in patients with tumour limited to the mucosa or N0 disease.

Background: There is increasing evidence that the presence of a pre-operative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC). Socioeconomic deprivation was reported to correlate with the presence of the SIR and to independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of pre-operative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context., Patients and Methods: Clinicopathological data, including the Memorial Sloan-Kettering Cancer Centre Clinical Risk Score (CRS), were obtained from a prospectively maintained database for 174 patients who underwent hepatectomy for CLM between January 2000 and December 2005 at a single United Kingdom (UK) tertiary referral hepatobiliary centre. Inflammatory biomarkers (total and differential leucocyte counts, neutrophil-lymphocyte ratio, platelet count, haemoglobin, and serum albumin) were measured from routine pre-operative blood tests. Socioeconomic deprivation was measured using the Carstairs deprivation score., Results: On multivariable analysis, poor CRS (3-5), high neutrophil count (>6.0 x 10(9)/l) and low serum albumin (<40g/dl) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context., Conclusions: The presence of a pre-operative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.

Background: The goal was to develop an inexpensive and rapid method for health systems to classify people by their ability to access routine care. We sought to refine and revalidate a software algorithm, the Access Risk Classification System (ARCS), using automated claims data to classify people into one of four categories based on the probable need for care coordination or health system accommodations., Methods: Through simple linkages of longitudinal claims data, the algorithm assigned individuals into one of four categories. We evaluated the algorithm's sensitivity and specificity by comparing the predicted classification against self-report. The validation results were used to refine the algorithm., Results: When we classified people into two groups of any degree of functional limitation or no limitation, the sensitivity was 91% and the specificity was 26%. When classified into two groups of those needing proactive care coordination and all others, sensitivity was 83% and specificity was 30%. Thus, overall correct classification ranges from good to fair., Conclusions: The algorithm utilizes claims databases readily available to many health claims payers. Adding Healthcare Common Procedural Coding System claims and number of prescriptions improves correct classification rates. Even when the claims data are incomplete and imprecise, ARCSv2 (ARCS version 2) can be used as an initial screen to identify people who should be included in the calculation of quality measures and who should be surveyed for consumer reported quality measurement. When using four classification categories, 69% of the people with the greatest risk and need for care coordination are correctly identified. ARCS can increase the correct identification of people with disabilities by 400% over random digit dialing of a general population. However, the ARCS should be further refined and validated in a larger population that includes more men with disabilities, children, and people without disabilities before it is used to compute quality measures using administrative data. Correct classification might be improved by incorporating information on comorbidities and specific medication categories.

Context: Patients with resectable pancreatic cancer comprise a small subgroup of the overall population with the disease from around 15 to 20%, with nearly all patients dying from their disease within 7 years of surgery. In the light of such bleak statistics, data regarding what factors may influence outcome, following attempted curative resection is essential in order to optimise the treatment options for patients., Methods: This review analysed all English-language publications using PubMed and Web of Science databases for studies detailing outcomes following resection for pancreatic ductal adenocarcinoma from 1980 to the present day., Main Outcome Measures: The data examined from papers were post-operative mortality rates, median survival, yearly survival rates and other factors which may have influenced long-term survival; such as patient demographics, operative details and tumour characteristics (such as example tumour size, lymph node metastases and tumour differentiation)., Results: There has been significant improvement in post-operative mortality over the last decades with a modest improvement in long-term survival. With the exception of post-operative blood transfusion, tumour characteristics remain the only significant features influencing survival after pancreatic cancer surgery. Favourable prognostic factors include tumour size less than 2 cm, negative resection margin, lymph node negative tumours, well-differentiated tumours and absence of perineural or blood vessel invasion., Conclusion: In light of these data, it could be reasoned that tumour size, on cross-sectional imaging, might be employed as means of selecting the most appropriate candidates for surgery, in cases where the risks of resection are high.

Background and Objectives: Reactivation of the Notch signalling pathway occurs in a range of human malignancies. Previous research suggests that Notch3 is expressed in pancreatic adenocarcinomas, but neither cellular location nor association with clinical parameters has been described. The relationship between Notch3, clinical endpoints, and other proteins with potential to interact with Notch was therefore examined., Methods: An immunohistochemical study was performed on human pancreatic adenocarcinoma (n = 23) and normal pancreas (n = 12), to assess expression of Notch3, cyclin D1, pAkt, STAT3 and pSTAT3. Immunohistochemical data were then correlated with clinicopathological characteristics., Results: Notch3 was significantly overexpressed in the cytoplasm of 73.9% of tumours. Nuclear expression was not observed in normal pancreatic ductal tissue, but was noted in 43.5% of tumours. No tumour expressing nuclear Notch3 was resectable. There were significant correlations between expression and intracellular location of Notch3 and each of STAT3, pSTAT3 and pAkt, but not cyclin D1., Conclusion: The presence of Notch3 in tumour nuclei is likely to represent functional activation of the protein, and is clearly linked to a more aggressive tumour phenotype. The correlation with STAT3, pSTAT3 and pAkt expression has not previously been described and the concurrent intracellular localisation of these proteins suggests a functional relationship between them., ((c) 2007 Wiley-Liss, Inc.)

Objective: In 1997 with the start of CRO7 trial it was agreed that adequacy of surgical resection of rectal cancer would be determined by a pathologically determined grading of the mesorectum the so called total mesorectal excision score (TME score). Scores ranged from 1-3 with 3 being a perfect specimen. The aim of this study was to investigate factors which may influence TME scores and establish if local recurrence is related to them., Method: Data on all patients undergoing resectional surgery for rectal cancer in our unit are entered prospectively onto a database. Pathology reports of those patients who underwent total mesorectal excision were examined and the TME scores added to the database. Categorical variables were analysed using the chi2 test, continuous variables using ANOVA. Statistical significance was taken as P < 0.05., Results: Between January 2000 and June 2005, 518 patients underwent surgery for adenocarcinoma of the rectum, of these, 287 patients had a total mesorectal excision for mid or lower third tumours under the care of seven colorectal surgeons. All resected specimens were scored by a Consultant GI pathologist. Two hundred and fourteen patients underwent anterior resection and 73 underwent abdomino-perineal resection. The median age of the patients was 73 years (range 38-95 years). One hundred and ninety-four patients were male. Seventy-eight patients were treated with preoperative radiotherapy, 59 short course and 19 long course. TME scores were TME1 n = 30, TME2 n = 99, TME3 n = 158. Fifteen patients developed local pelvic recurrence at 2 years. Total mesorectal excision scores were not statistically influenced by Dukes' stage, width of tumour, preoperative radiotherapy or grade of surgeon. Male patients were statistically more likely to have a TME score of 2 or 3 compared with female P = 0.04. Patients undergoing an anterior resection were statistically more likely to have a TME score of 2 or 3 compared with abdomino-perineal resection P = 0.0001. Tumours with a circumferential resection margin (CRM) of more than 1 mm were more likely to have a TME score of 2 or 3 score (P = 0.0001). There was no relationship between TME and local recurrence (P = 0.966)., Conclusion: There is no relationship between the TME score in patients undergoing resectional surgery for adenocarcinoma of the rectum and the development of local recurrence at 2 years. Other factors such as CRM involvement are more likely to have an impact on local recurrence. The factors that influence the quality of TME are the operative procedure of anterior resection, male gender and CRM positivity. There appear to be no deleterious effects on the TME score by Specialist Registrars performing the operation under Consultant supervision. While TME scores may be an index of a technical performance, they appear to have little role in predicting future outcomes.

Background: Seroma are common early postoperative complications encountered in laparoscopic inguinal hernia repair. Previous anecdotal evidence from our surgical practice suggested a lower incidence of postoperative seroma formation with direct hernia repairs when the lax transversalis fascia (TF) is inverted by tacking to the pubic ramus. We undertook a study to investigate whether TF inversion in this way reduces the incidence of postoperative seroma., Method: A total of 216 patients undergoing transabdominal preperitoneal (TAPP) laparoscopic inguinal hernia repairs from August 2003 to December 2005 were included in this prospective non-randomised controlled study. Surgeon 1 would routinely invert the TF whereas surgeon 2 would not. At follow-up the presence of postoperative seroma and pain was recorded., Results: Mann-Whitney U test demonstrated no significant difference in terms of age, sex and time to follow-up between the surgeons' patient groups (P > 0.05), and Chi-square test demonstrated significantly that inversion of the TF is associated with a lower incidence of postoperative seroma (P < 0.05). There was no significant difference in terms of postoperative pain at follow-up., Conclusion: Inversion of the TF is associated with a statistically lower incidence of postoperative seroma, without increasing postoperative pain despite the use of one or two additional tacks.

Aims: We have maintained a highly conservative policy in selecting patients with carcinoma of the head of pancreas for resection. This has been based on tumour size, evidence of lymph node involvement or local invasion outside of the gland at laparotomy, laparoscopy or CT imaging. This study investigated our survival rates following pancreatic resection and examined clinicopathological predictors of survival., Methods: Sixty-two consecutive patients undergoing pancreatic resections for malignancy were identified from 1999 onwards. Thirty-three underwent resection for pancreatic ductal adenocarcinoma and were included in our analysis, the remainder included resections for ampullary adenocarcinoma (n=20) or other malignancies (n=9). Patient, tumour and operative characteristics were analysed to assess predictors of survival following resection (Kaplan-Meier survival curves)., Results: Median survival following resection for ductal pancreatic adenocarcinoma was 54 months (ampullary adenocarcinomas achieved a median survival of 62 months) and thirty-day mortality was 2.7% (n=1). Survival was not associated with any demographic or intraoperative factors, such as blood loss, operative duration or anaesthetic technique. Survival curves were significantly worse when perineural or vascular invasion was evident histologically (p=0.023 and 0.0023 respectively). Patients with positive lymph nodes had a significantly shorter survival (p=0.0030) especially when lymph node status was expressed as a percentage of total lymph node yield. If more than 20% of retrieved lymph nodes were positive for tumour, this was a clear predictor of survival (p<0.0001). A positive resection margin was also associated with shortened survival (p=0.0291)., Conclusion: Despite the advances made in the management of pancreatic cancer, tumour biology still dictates long-term survival. A highly selective surgical approach to the management of these patients results in good long-term survival.

Background: Staging laparoscopy for pancreatic malignancy is controversial. This study aimed to assess the efficacy of laparoscopy with intraoperative ultrasound in the management of patients with pancreatic carcinoma., Methods: The study involved patients undergoing laparoscopy and intraoperative ultrasound over a period of 42 months. The entry criteria specified radiologic (computed tomography) diagnosis of pancreatic carcinoma and no evidence of metastases., Results: The study enrolled 100 patients (52 men and 48 women) ages 21 to 83 years (mean, 63 years). On the basis of imaging, 75 patients had lesions judged to be operable, and 25 patients had a pancreatic head lesion larger than 4 cm radiologically, considered to be unresectable, but with no evidence of metastatic disease. At laparoscopy, three patients had a normal examination, with no evidence of a pancreatic mass, and an additional seven patients had other pathology including one lymphoma, one ampullary tumor, two cases of chronic pancreatitis, and three sarcomas. Of the patients with radiologically inoperable disease, 16% had previously undetected metastases, but 24% were judged to be suitable for curative resection. Half of these patients underwent successful resection. Of the patients with radiologically operable disease, undetected liver or peritoneal metastases were found in 20% of the body or tail lesions and in 26% of the pancreatic head lesions. Of the pancreatic head tumors, 12% were found to be larger than 4 cm and therefore unsuitable for curative resection. Consequently, only 53% were confirmed to be suitable for resection. Of the patients explored with a view to curative resection, 42% actually underwent resection, with clearance of resection margins achieved in 77.8%., Conclusion: Of the patients thought to have a resectable tumor on the basis of good quality preoperative imaging, 44% had their management approach altered after laparoscopy and avoided an open procedure. Laparoscopy should therefore be used in the preoperative staging of pancreatic tumors.

Glycogen synthase kinase (GSK) was initially described as a key enzyme involved in glycogen metabolism. However, since that time it has been found to regulate a diverse range of cell functions. In addition to having a major role in the regulation of the important onco-protein beta-catenin, GSK is also a critical regulator of NF-kappaB. NF-kappaB comprises a family of transcription factors which activate the expression of a wide array of genes involved in inflammation, tumourigenesis, metastasis, differentiation, embryonic development, apoptosis. Inflammation mediated by the NF-kappaB family has been implicated in the initiation of pancreatic cancer, resistance to chemotherapy and the development of the debilitating cancer cachexia seen with advanced disease. Hence, GSK has potential as an important new target both in the treatment of resectable pancreatic cancer as an adjuvant to surgery, and in the palliation of inoperable tumours.