Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. Although the HIPEC procedure is adopted throughout the world, major differences exist between treatment protocols regarding the carrier solution, perfusate volume, use of an open or closed technique, duration of the perfusion and application of additional flushing. These differences can influence the pharmacokinetics and pharmacodynamics of oxaliplatin and might thereby have an impact on the efficacy and/or safety of the treatment. Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure.

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury.

PURPOSE: Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury. METHODS: We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool. RESULTS: Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007). CONCLUSIONS: Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model.

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass.

To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.

Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach?

Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue.

Some aspects of quality management in deep regional hyperthermia.

The hyperthermia effect is based on its thermal influence on tumours. Therefore a controlled heating of the tumours must be achieved. In order to guarantee this, two points must be fulfilled at least: First, the hyperthermia equipment must have the necessary power and steering capability. Second, the distribution of the 'hyperthermic drug', the heat, has to be measured and controlled over the whole treatment time. To reach this aim both a sophisticated technique and a staff trained in hyperthermia are required. In treating patients such as those with cervical cancer, the volume to be exposed and the dosage must be clarified. This means that very special technical and medical conditions must be fulfilled in hyperthermia. To reach and maintain a certain level of quality, hyperthermia is embedded in a framework of procedures. These procedures are defined in the modules of quality management. Therefore quality management must contain specific guidelines for each application, i.e. coordinated standards have to be defined. When adapting these standards in hyperthermia, comparable and comprehensible results of the treatment are guaranteed. Furthermore, an analysis of the treatments under a scientific point of view will be possible and finally result in improvements of this method.

Quality assurance for clinical studies in regional deep hyperthermia.

BACKGROUND: A guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients. According to this guideline, hyperthermia treatment is always applied in combination with chemotherapy and/or radiotherapy. METHODS: The guideline is based on practical experience from several hyperthermia centers. The procedure allows applying jointly coordinated standards and quality control in hyperthermia for studies. RESULTS: The guideline contains recommendations for hyperthermia treatments, including indication, preparation, treatment, and standardized analysis.

[Comparative experimental study of morphological and histochemical changes of chorioretinal complex after subthreshold laser exposure].

The influence of several subthreshold laser procedures on chorioretinal complex (CRC) tissues was experimentally studied in rabbits using histological and histochemical methods. Subthreshold micropulse laser radiation and transpupillar thermotherapy were found to have the most attenuated and advantageous effect on CRC structure. The feature of subthreshold laser exposure is partly reversible selective changes in CRC, that have temporary stimulating effect on cellular metabolism and local regenerative processes providing an opportunity for still viable tissues to function adequately.

Efficacy of thermotherapy for herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

BACKGROUND: Herpes zoster (HZ), is a painful skin rash disease with cutaneous symptoms and acute zoster-associated pain (ZAP). Postherpetic neuralgia (PHN), as the most frequent sequela of HZ, can persist a long time. Both HZ and PHN may significantly impact the quality of life and made great economical afford to affected patients. Its optimal treatment on HZ and PHN is still an urgent problem. In China, thermotherapy, including moxibustion and fire needle, is widely used because they can quickly promote the recovery of shingles and reduce the occurrence of PHN. Thermotherapy can also reduce pain intensity, relieve anxiety, and improve quality of life of PHN. Based on the current literatures, the effect and safety of thermotherapy will be systematically evaluated to provide appropriate complementary therapies for HZ and PHN. METHODS: Studies search for eligible randomized controlled trials (RCTs) that use thermotherapy including fire needle and moxibustion for HZ or PHN from the following databases: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), Technology Periodical database (VIP), and Wanfang database. Language restrictions for retrieving literature are English and Chinese. Their data extraction will be done by 2 researchers. Mean difference (MD) or relative risk (RR) with fixed or random effect model in terms of 95% confidence interval (CI) will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane's risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%). RESULTS: This meta-analysis will provide an authentic synthesis of the thermotherapy's effect on HZ and PHN, including incidence of postherpetic neuralgia and adverse events. DISCUSSION: The findings of the review offer updated evidence and identify whether thermotherapy can be an effective treatment for HZ and PHN for clinicians. REGISTRATION NUMBER: INPLASY2020110009.

Safe heat application for pediatric patients: a hot item.

Topical heat application has a number of therapeutic uses in nursing practice. However, factors such as surface temperature and duration of heat exposure to the modality used may result in accidental burning. The purpose of this clinical project was to find an effective and safe method of heat application for the pediatric population. Based on literature findings, the practice of heat therapy requires careful consideration of the benefits and risks involved and vigilant monitoring.

Immunomodulatory effects of ablation therapy on tumors: Potentials for combination with immunotherapy.

As a promising area of tumor treatment, immunotherapies, such as immune checkpoint inhibitors, have been applied to various types of cancer. However, many patients do not respond to such therapies. Increasing application of tumor ablation therapy, a minimally invasive treatment, has been observed in the clinic. Although it can boost the anti-tumor immune response of patients in many ways, ablation alone is not sufficient to remove the tumor completely or stop tumor recurrence in the long term. Currently, there is emerging research focusing on ablation in combination with immunotherapy, aiming to confirm the therapeutic value of this treatment for cancer patients. Hence, in this article, we review the classification, guideline recommendations, and immunomodulatory effects of ablation therapy, as well as the pre-clinical and clinical research of this combination therapy.

A literature survey on indicators for characterisation and optimisation of SAR distributions in deep hyperthermia, a plea for standardisation.

PURPOSE: To evaluate the predictive value of SAR indicators by assessing the correlation of a SAR indicator with the corresponding predicted temperature. Ultimately, this should lead to a number of verified SAR indicators for characterization and optimization of a predicted SAR distribution. METHODS: A literature survey is followed by an evaluation of the SAR indicators on their functionality, using a set of heuristic classification criteria. To obtain an objective assessment of the predictive value for SAR characterisation, all SAR indicators are evaluated by correlating the value of the SAR indicator to the predicted target temperature when heated with the BSD2000 Sigma 60 applicator. Two methods were followed. First, the specificity of the SAR indicator to target temperature was assessed for each of the 36 patient-specific models, using 30 randomly chosen phase and amplitude settings. Secondly, each SAR indicator was used as a goal function to assess its suitability for optimisation purposes. RESULTS: Only a selected number of SAR indicators correlate well with tumour/target-temperature. Hence, for target-related properties, an adequate set of SAR indicators is found in the literature. For hotspots, modifications are desirable. For optimisation purposes, improved objective functions have been defined. CONCLUSIONS: From the correlation of the SAR indicators with tumour temperature, a preferred set of SAR indicators is derived: For target heating, 'average SAR ratio', 'Hotspot-target SAR ratio', and 'homogeneity coefficient' provide suitable objective criteria, while for hotspot reduction, 'Hotspot-target SAR ratio' is considered the most useful indicator. For optimisation procedures, 'Hotspot-target SAR ratio' is currently the most suitable objective function.

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy, Part II: Implementation.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an extensive procedure used to treat peritoneal carcinomatosis, which is either primary or secondary to other cancers (eg, ovarian, colorectal, appendiceal) that have metastasized to the peritoneum. Morbidity, mortality, and quality of life have improved for patients selecting CRS with HIPEC as a cancer treatment. At Holy Name Medical Center in Teaneck, New Jersey, an interdisciplinary team was established to plan and coordinate performing this new procedure in the OR. The team created a written protocol for implementing CRS with HIPEC before patients were scheduled for surgery. This article explores the perioperative facets of implementing CRS with HIPEC and discusses care of the patient undergoing CRS with HIPEC, with a focus on perioperative nursing considerations.

Management of colorectal peritoneal metastases: Expert opinion.

When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication.

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Colorectal peritoneal metastases: Optimal management review.

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies.

Open Resection versus Laser Interstitial Thermal Therapy for the Treatment of Pediatric Insular Epilepsy.

BACKGROUND: Various studies suggest that the insular cortex may play an underappreciated role in pediatric frontotemporal/parietal epilepsy. Here, we report on the postsurgical outcomes in 26 pediatric patients with confirmed insular involvement by depth electrode monitoring. OBJECTIVE: To describe one of the largest series of pediatric patients with medically refractory epilepsy undergoing laser interstitial thermal therapy (LITT) or surgical resection of at least some portion of the insular cortex. METHODS: Pediatric patients in whom invasive insular sampling confirmed insular involvement and who subsequently underwent a second stage surgery (LITT or open resection) were included. Complications and Engel Class outcomes at least 1 yr postsurgery were compiled as well as pathology results in the open surgical cases. RESULTS: The average age in our cohort was 10.3 yr, 58% were male, and the average length of follow-up was 2.43 ± 0.20 (SEM) yr. A total of 14 patients underwent LITT, whereas 12 patients underwent open resection. Complications in patients undergoing either LITT or open resection were mostly minimal and generally transient. Forty-three percent of patients who underwent LITT were Engel Class I, compared to 50% of patients who underwent open insular resection. CONCLUSION: Both surgical resection and LITT are valid management options in the treatment of medically refractory insular/opercular epilepsy in children. Although LITT may be a less invasive alternative to craniotomy, further studies are needed to determine its noninferiority in terms of complication rates and seizure freedom, especially in cases of cortical dysplasia that may involve extensive regions of the brain.