Can There be a Place for Intraoperative Salvaged Blood in Spine Tumor Surgery?

Background

Intraoperative cell salvage (IOCS) has been used in musculoskeletal surgery extensively. However, it has never found its place in musculoskeletal oncologic surgery. We have conducted the first-ever study to evaluate the feasibility of IOCS in combination with a leucocyte-depletion filter (LDF) in metastatic spine tumor surgery. This was to pave the path for use of IOCS-LDF in musculoskeletal oncologic surgery.

Methods

Patients with a known primary epithelial tumor, who were offered surgery for metastatic spinal disease, were recruited. Blood samples were collected at three different stages during the surgery: from the operative field before IOCS processing, after IOCS processing, and after IOCS-LDF processing. Three separate samples (5 mL each) were taken at each stage. Samples were examined using immunohistochemical monoclonal antibodies to identify tumor cells of epithelial origin.

Results

Of 30 patients in the study, 6 were excluded for not fulfilling the inclusion criteria, leaving 24 patients. Malignant tumor cells were detected in the samples from the operative field before IOCS processing in eight patients and in the samples from the transfusion bag after IOCS processing in three patients. No viable malignant cell was detectable in any of the blood samples after passage through both IOCS and LDF.

Conclusions

The findings support the notion that the IOCS-LDF combination works effectively in eliminating tumor cells from salvaged blood, so this technique can be applied successfully in spine tumor surgery. This concept can then further be extended to whole musculoskeletal tumor surgery and other oncologic surgeries with further appropriate clinical studies.     

Introduction—Targeting the lesion,not the organ

The current diagnostic and therapeutic strategy for localized prostate cancer is not working. In fact, it is severely flawed and, as such, fraught with controversy. Our current strategy has arisen from the imprecision of our diagnostic pathway. We do not know where the cancer is, so we subject the prostate to randomly placed needles in the hope of hitting the tumor. This leads to overdiagnosis, underdiagnosis, missclassification of risk and overtreatment and undertreatment. If we do find cancer, we usually subject the entire prostate to radiotherapy or surgery, which damages the surrounding structures—neurovascular bundles, external urinary sphincter, rectum, and bladder neck. Multiparametric magnetic resonance imaging, coupled with an intensive sampling strategy (targeted biopsies), might be able to rule out clinically significant lesions with a negative predictive value in the order of 90% to 95%. Focal therapy certainly leads to less genitourinary and rectal side effects. Current data from more than 3,000 men treated internationally show that incontinence after focal therapy is 0% to 5% (radical therapy can lead to incontinence in 15%–20%) whereas erectile dysfunction occurs in 5% to 10% of men with good baseline function (radical therapy rates vary between 30% and 60%). Early to medium cancer control using biopsies after treatment shows between 80% and 90% of patients have a successful treatment, with 10% to 15% of men requiring redo-treatment with minimal additional morbidity.     

The development of pediatric fluid resuscitation: an interview with Dr. Frederic A. ‘Fritz’ Berry

Dr. Frederic A. ‘Fritz’ Berry (1935), Professor Emeritus of Anesthesiology and Pediatrics at the University of Virginia, has played a pioneering role in the development of pediatric anesthesiology through training generations of anesthesiologists. He identifies his early advocacy of balanced electrolyte solution for perioperative fluid resuscitation as his defining contribution. Based on his clinical experiences, he pushed to extend the advances in adult fluid resuscitation into pediatric practice. He imparted these and other insights to his colleagues although textbooks, book chapters, original journal publications, and decades of Refresher Course Lectures at the American Society of Anesthesiologists' annual meetings. A model educator, clinician, and researcher, he shaped the careers of hundreds of physicians‐in‐training while advancing the field of pediatric anesthesiology.     

Persistent phosphorylation of NKCC1 and WNK1 in the epicenter of the spinal cord following contusion injury

Background contextNKCC1 regulates neuronal homeostasis of chloride ions and mediates GABAergic activities in nociceptive processing. WNK1 is an upstream regulator of NKCC1 and acts via SPAK (STE20/SPS1-related proline/alanine-rich kinase) and oxidative stress-responsive kinase 1. NKCC1 activity has been shown to be important in edema formation and nociception following spinal cord injury (SCI).PurposeTo determine the role of NKCC1 and WNK1 in spinal cord tissues in the acute and chronic phases following contusional SCI.Study designAn experimental study investigating the phosphorylation profile of an important Cl-regulatory protein Na+-K+-Cl? cotransporter 1 (NKCC1) and its regulatory-kinase WNK1 (kinase with-no-lysine).MethodsSprague-Dawley rats underwent a contusive SCI at T9. The epicenter spinal cord tissues were harvested at Days 1, 3, and 7 for acute phase of injury or Days 35 and 42 in the chronic phase of injury. Western blot was used to compare phosphorylated levels of both NKCC1 and WNK1 in injured tissues compared with those of sham.ResultsA sustained increase in phosphorylation of NKCC1 and WNK1 was detected in the lesion epicenter in spinal cord during both acute and chronic phases following SCI.ConclusionsThese results suggest that persistent activation of NKCC1 and WNK1 may play an important role in SCI.     

Factors Predicting the Oculomotor Nerve Palsy following Surgical Clipping of Distal Vertebrobasilar Aneurysms: A Single-Institution Experience

Background The aim of our study was to identify various clinical and radiologic factors that correlate with the oculomotor nerve palsy following clipping of distal vertebrobasilar aneurysms. Methods A total of 48 patients with 51 aneurysms were included in this retrospective study . Patient''s age, gender, size, location, and projection of the aneurysm, preoperative Hunt and Hess (H&H) grade, presence of subarachnoid hemorrhage (SAH), temporary clipping, preoperative third nerve palsy, and Glasgow Outcome Scale were included in the model for analysis. Results A total of 15 patients (31.25%) developed oculomotor nerve palsy following clipping of basilar apex aneurysms. 38 patients (79.2%) presented with SAH and 35 patients (72.9%) had poor H&H grades at presentation. The size of the aneurysm (p = 0.03), preoperative H&H grade (p = 0.04), preoperative oculomotor nerve dysfunction (p = 0.007), and projection of an aneurysm (p = 0.004) had shown a significant correlation with the oculomotor nerve palsy. The size of the aneurysm (p = 0.030, odds ratio: 0.381; 95% confidence interval, 0.175–0.827] was an independent predictor of postoperative nerve dysfunction. Conclusion The size of the aneurysm, clinical grade at presentation, and projection of the aneurysm correlated with the oculomotor nerve dysfunction following clipping. These clinical and radiologic parameters can be used to predict the oculomotor nerve outcome.     

Clinical Correlates of the Anatomical Relationships of the Foramen Ovale: A Radioanatomical Study

Introduction Endonasal endoscopic transpterygoid approaches are commonly used techniques to access the infratemporal fossa and parapharyngeal space. Important endoscopic endonasal landmarks for the poststyloid parapharyngeal space, hence the internal carotid artery, include the mandibular nerve at the level of foramen ovale and the lateral pterygoid plate. This study aims to define the anatomical relationships of the foramen ovale, establishing its distance to other important anatomical landmarks such as the pterygoid process and columella. Methods Distances between the foramen ovale, foramen rotundum, and fixed anatomical landmarks like the columella and pterygoid process were measured using computed tomography (CT) scans and cadaveric dissections of the pterygopalatine and infratemporal fossae. Results The mean distances from the foramen ovale to columella and from the foramen rotundum to columella were found to be 9.15 cm and 7.09 cm, respectively. Analysis of radiologic measurements detected no statistically significant differences between sides or gender. Conclusions The pterygoid plates and V3 are prominent landmarks of the endonasal endoscopic approach to the infratemporal fossa and poststyloid parapharyngeal space. A better understanding of the endoscopic anatomy of the infratemporal fossa and awareness of the approximate distances and geometry among anatomical landmarks facilitates a safe and complete resection of lesions arising or extending to these regions.     

Analysis of changes in hepatic gene expression in a murine model of tolerance to acetaminophen hepatotoxicity (autoprotection)

Pretreatment of mice with a low hepatotoxic dose of acetaminophen (APAP) results in resistance to a subsequent, higher dose of APAP. This mouse model, termed APAP autoprotection was used here to identify differentially expressed genes and cellular pathways that could contribute to this development of resistance to hepatotoxicity. Male C57BL/6J mice were pretreated with APAP (400 mg/kg) and then challenged 48 h later with 600 mg APAP/kg. Livers were obtained 4 or 24 h later and total hepatic RNA was isolated and hybridized to Affymetrix Mouse Genome MU430_2 GeneChip. Statistically significant genes were determined and gene expression changes were also interrogated using the Causal Reasoning Engine (CRE). Extensive literature review narrowed our focus to methionine adenosyl transferase-1 alpha (MAT1A), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), flavin-containing monooxygenase 3 (Fmo3) and galectin-3 (Lgals3). Down-regulation of MAT1A could lead to decreases in S-adenosylmethionine (SAMe), which is known to protect against APAP toxicity. Nrf2 activation is expected to play a role in protective adaptation. Up-regulation of Lgals3, one of the genes supporting the Nrf2 hypothesis, can lead to suppression of apoptosis and reduced mitochondrial dysfunction. Fmo3 induction suggests the involvement of an enzyme not known to metabolize APAP in the development of tolerance to APAP toxicity. Subsequent quantitative RT-PCR and immunochemical analysis confirmed the differential expression of some of these genes in the APAP autoprotection model. In conclusion, our genomics strategy identified cellular pathways that might further explain the molecular basis for APAP autoprotection.     

Anti-Inflammatory Activity of Fruit Fractions in Vitro,Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease

Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases.