Anesthesia and Oncology: Friend or Foe?

Cancer is a leading cause of death, and surgery is an important treatment modality. Laboratory research and retrospective studies have raised the suspicion that the choice of anesthetics for cancer surgery might affect the course of cancerous disease. The aim of this review is to provide a critical overview of the current state of knowledge. Inhalational anesthesia with volatiles or total intravenous anesthesia (TIVA) with propofol are the two most commonly used anesthetic techniques. Most data comparing volatile anesthetics with TIVA is from either in vitro or retrospective studies. Although conflicting, data shows a trend towards favoring propofol. Opioids are commonly used in anesthesia. Data on potential effects of opioids on growth and recurrence of cancer are scarce and conflicting. Preclinical studies have shown that opioids stimulate cancer growth through the µ-opioid receptor. Opioids also act as immunosuppressants and, therefore, have the potential to facilitate metastatic spread. However, the finding of an adverse effect of opioids on tumor growth and cancer recurrence by some retrospective studies has not been confirmed by prospective studies. Regional anesthesia has not been found to have a beneficial effect on the outcome of surgically treated cancer patients, but prospective studies are scarce. Local anesthetics might have a beneficial effect, as observed in animal and in vitro studies. However, prospective clinical studies strongly question such an effect. Blood products, which may be needed during extensive cancer surgery suppress the immune system, and data strongly suggest a negative impact on cancer recurrence. The potential effects of other commonly used anesthetic agents on the outcome of cancer patients have not been sufficiently studied for drawing valid conclusions. In conclusion, laboratory data and most retrospective studies suggest a potential advantage of TIVA over inhalational anesthesia on the outcome of surgical cancer patients, but prospective, randomized studies are missing. Given the state of weak scientific evidence, TIVA may be used as the preferred type of anesthesia unless there is an individual contraindication against it. Studies on the effects of other drugs frequently used in anesthesia are limited in number and quality, and have found conflicting results.

Gender differences in the provision of intensive care: a Bayesian approach.

PURPOSE: It is currently unclear whether management and outcomes of critically ill patients differ between men and women. We sought to assess the influence of age, sex and diagnoses on the probability of intensive care provision in critically ill cardio- and neurovascular patients in a large nationwide cohort in Switzerland. METHODS: Retrospective analysis of 450,948 adult patients with neuro- and cardiovascular disease admitted to all hospitals in Switzerland between 01/2012 and 12/2016 using Bayesian modeling. RESULTS: For all diagnoses and populations, median ages at admission were consistently higher for women than for men [75 (64;82) years in women vs. 68 (58;77) years in men, p < 0.001]. Overall, women had a lower likelihood to be admitted to an intensive care unit (ICU) than men, despite being more severely ill [odds ratio (OR) 0.78 (0.76-0.79)]. ICU admission probability was lowest in women aged > 65 years (OR women:men 0.94 (0.89-0.99), p < 0.001). Women < 45 years had a similar ICU admission probability as men in the same age category [OR women:men 1.03 (0.94-1.13)], in spite of more severe illness. The odds to die were significantly higher in women than in men per unit increase in Simplified Acute Physiology Score (SAPS) II (OR 1.008 [1.004-1.012]). CONCLUSION: In the care of the critically ill, our study suggests that women are less likely to receive ICU treatment regardless of disease severity. Underuse of ICU care was most prominent in younger women < 45 years. Although our study has several limitations that are imposed by the limited data available from the registries, our findings suggest that current ICU triage algorithms could benefit from careful reassessment. Further, and ideally prospective, studies are needed to confirm our findings.

Post-dural puncture headache.

Neuraxial analgesia and anesthesia are widely used in obstetric anesthesia. The most frequent complication after neuraxial blocks is post-dural puncture headache. It can occur after unintentional dural puncture during epidural procedures or after spinal anesthesia. Unintentional dural puncture occurs in 0.15-1.5% of labor epidural analgesia and 50-80% of these women develop post-dural puncture headache. The headache is typically orthostatic in nature and can be so incapacitating that the mother becomes bedbound and is no longer able to care for herself and her newborn child. A wide variety of prophylactic and therapeutic measures have been tried. So far, the therapeutic epidural blood patch is the only treatment for which there is enough evidence to recommend its routine use for severe cases of post-dural puncture headache. Larger multicenter trials are needed to back up alternative treatment strategies.

Cardiac Structure and Function in Morbidly Obese Parturients: An Echocardiographic Study.

BACKGROUND: The increasing prevalence of obesity worldwide is a major threat to global health. Cardiac structural and functional changes are well documented for obesity as well as for pregnancy, but there is limited literature on morbidly obese parturients. We hypothesized that there are both cardiac structural and functional differences between morbidly obese pregnant women and pregnant women of normal body mass index (BMI). METHODS: This prospective cross-sectional study was performed in 2 referral maternity units in Cape Town, South Africa, over a 3-month period. Forty morbidly obese pregnant women of BMI ≥40 kg·m (group O) were compared to 45 pregnant women of BMI ≤30 kg·m (group N). Cardiac structure and function were assessed by transthoracic echocardiography, according to the recommendations of the British Society of Echocardiography. The 2-sample t-test with unequal variances was used for the comparison of the mean values between the groups. RESULTS: Acceptable echocardiographic images were obtained in all obese women. Statistical significance was defined as P < .0225 after applying the Benjamini-Hochberg correction for multiple testing. Mean (standard deviation) mean arterial pressure was higher in group O (91 [8.42] vs 84 [9.49] mm Hg, P < .001). There were no between-group differences in heart rate, stroke volume, or cardiac index (84 [12] vs 79 [13] beats·minute, P = .103; 64.4 [9.7] vs 59.5 [13.5] mL, P = .069; 2551 [474] vs 2729 [623] mL·minute·m, P = .156, for groups O and N, respectively). Stroke volume index was lower, and left ventricular mass was higher in group O (30.14 [4.51] vs 34.25 [7.00] mL·m, P = .003; 152 [24] vs 115 [29] g, P < .001). S' septal was lower in group O (8.43 [1.20] vs 9.25 [1.64] cm·second, P = .012). Considering diastolic function, isovolumetric relaxation time was significantly prolonged in group O (73 [15] vs 61 [15] milliseconds, P < .001). The septal tissue Doppler index E' septal was lower in group O (9.08 [1.69] vs 11.28 [3.18], P < .001). There were no between-group differences in E' average (10.7 [2.3] vs 12.0 [2.7], P = .018, O versus N) or E/E' average (7.85 [1.77] vs 7.27 [1.68], P = .137, O versus N). Right ventricular E'/A' was lower in group O (1.07 [0.47] vs 1.29 [0.32], P = .016). CONCLUSIONS: Cardiac index did not differ between obese pregnant women and those with normal BMI. Their increased left ventricular mass and lower stroke volume index could indicate a limited adaptive reserve. Obese women had minor decreases in septal left ventricular tissue Doppler velocity, but the E/E' average values did not suggest clinically significant diastolic dysfunction.

Geburtshilfe: hypertensive Erkrankungen in der Schwangerschaft.

Hypertensive disorders of pregnancy are one of the most common complications in pregnancy. They are associated with a high maternal, fetal and neonatal morbidity and mortality. 99 % of all maternal deaths occur in developing countries, but we should not forget that even in highly developed countries mothers still die from the complications of hypertensive disorders of pregnancy. This term encompasses chronic hypertension as well as pregnancy specific disorders such as gestational hypertension and preeclampsia. The physiological changes of pregnancy can make the differentiation between benign symptoms of pregnancy and life threatening conditions challenging. In order to provide optimal care for these women, an interdisciplinary approach between all members of the obstetric care team is crucial. The current review article discusses new advances in the diagnosis and treatment of hypertensive disorders of pregnancy.

Puerperal sepsis in the 21st century: progress, new challenges and the situation worldwide.

Puerperal sepsis is one of the five leading causes of maternal mortality worldwide, and accounts for 15% of all maternal deaths. The WHO defined puerperal sepsis in 1992 as an infection of the genital tract occurring at any time between the rupture of membranes or labour and the 42nd day post partum; in which, two or more of the following are present: pelvic pain, fever, abnormal vaginal discharge and delay in the reduction of the size of the uterus. At the same time, the WHO introduced the term puerperal infections, which also include non-genital infections in the obstetric population. Recent epidemiological data shows that puerperal sepsis and non-genital tract infections are a major area of concern. In puerperal sepsis, group A streptococcus (GAS) is the most feared pathogen. Up to 30% of the population are asymptomatic carriers of GAS. GAS commonly causes throat infections. Women who died from GAS-positive sepsis all had signs of a throat infection themselves or one of their family members suffered from a throat infection. The pathway of infection is from the hands of the pregnant women or the mother to her perineum. In non-genital tract infections, influenza viruses and the HIV pandemic in the developing part of the world are responsible for many maternal deaths, and demand our attention. The physiological changes of pregnancy and the puerperium can obscure the signs and symptoms of sepsis in the obstetric population. A high level of suspicion is, therefore, needed in the care for the sick pregnant patient. If sepsis is suspected, timely administration of antibiotics, sepsis care bundles, multidisciplinary discussion and early involvement of senior staff members are important to improve outcome.

Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis.

In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a "detour" circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.

Behavioral testing strategies in a localized animal model of multiple sclerosis.

To assess neurological impairments quantitatively in an animal model of multiple sclerosis (MS), we have used a targeted model of experimental autoimmune encephalomyelitis (EAE), which leads to the formation of anatomically defined lesions in the spinal cord. Deficits in the hindlimb locomotion are therefore well defined and highly reproducible, in contrast to the situation in generalized EAE with disseminated lesions. Behavioral tests for hindlimb sensorimotor functions, originally established for traumatic spinal cord injury, revealed temporary or persistent deficits in open field locomotion, the grid walk, the narrow beam and the measurement of the foot exorotation angle. Such refined behavioral testing in EAE will be crucial for the analysis of new therapeutic approaches for MS that seek to improve or prevent neurological impairment.

Targeting experimental autoimmune encephalomyelitis lesions to a predetermined axonal tract system allows for refined behavioral testing in an animal model of multiple sclerosis.

In multiple sclerosis (MS) the structural damage to axons determines the persistent clinical deficit patients acquire during the course of the disease. It is therefore important to test therapeutic strategies that can prevent or reverse this structural damage. The conventional animal model of MS, experimental autoimmune encephalomyelitis (EAE), typically shows disseminated inflammation in the central nervous system, which leads to a clinical deficit that cannot be directly attributed to a defined tract system. For this reason we have developed a localized EAE model, in which large inflammatory lesions are targeted to the dorsal columns of the spinal cord, an area including the corticospinal tract. These lesions show the pathological hallmarks of MS plaques and lead to reproducible and pronounced deficits in hindlimb locomotion. Because of the anatomical specificity of this technique we can now use highly sensitive behavioral tests that assess the functional integrity of specific axonal tracts. We show that these tests are predictive of the site and extent of a given lesion and are more sensitive for assessing the clinical course than the scales commonly used for disseminated EAE models. We believe that this targeted EAE model will become a helpful new tool for the evaluation of therapeutic approaches for MS that attempt to protect axons or support their repair.

Rapid induction of autoantibodies against Nogo-A and MOG in the absence of an encephalitogenic T cell response: implication for immunotherapeutic approaches in neurological diseases.

Vaccinations against various antigens of the central nervous system (CNS) are gaining increasing interest as a therapeutic approach in a variety of neurological diseases such as spinal cord injury, ischemic stroke, Alzheimer disease, or spongiform encephalopathy. In the present work, the time window after spinal cord injury allowing potentially therapeutic antibody to penetrate the damaged blood-brain barrier (BBB) was measured by intravenous injection of a monoclonal anti-Nogo-A antibody. Although an influx of Nogo antibodies at the lesion site was detectable up to 2 wk after injury, a significant decrease in BBB permeability was noticed within the first week. Clearly, therefore, a vaccination protocol with a rapid antibody response is required for acute therapeutic interventions after CNS trauma. We designed a conjugate vaccine paradigm with particular focus on the safety and the kinetics of the antibody response. As antigen targets, we used Nogo-A and the strongly encephalitogenic myelin-oligodendrocyte glycoprotein (MOG). Intrasplenic autoimmunization of rats with a Nogo-A-specific region fused to the Tetanus toxin C-fragment (TTC) resulted in a fast IgM response against Nogo-A. A specific switch to IgG was observed as soon as 4-7 days after intrasplenic immunization in TTC-primed animals. In spite of the induction of a specific IgG response after intrasplenic immunization, no signs of experimental autoimmune disease (EAE) or inflammatory infiltrates on histological examinations were observable. In contrast to subcutaneous immunization with MOG, in vitro cytokine secretion assays (IL-2, IL-10, and IFN-gamma) did not reveal activation of MOG-specific T cells after intrasplenic immunization. Our findings have critical implications for future strategies in the development of safe and efficient therapeutic vaccines for neurological diseases.