Hilmy Ismail

Effect of neuraxial anaesthesia on tumour progression in cervical cancer patients treated with brachytherapy: a retrospective cohort study

BACKGROUND Recent evidence suggests that neuraxial and regional anaesthesia may influence the progression of the underlying malignant disease after surgery. METHODS This retrospective cohort study assessed whether neuraxial anaesthesia would affect the progression of cervical cancer in 132 consecutive patients who were treated with brachytherapy in a tertiary cancer centre in Australia. RESULTS Age, American Society of Anesthesiologists status, International Federation of Gynecologists and Obstetricians (FIGO) cancer staging, invasion into the uterus, tumour volume, and tumour cell types were not significantly different between patients who received neuraxial and general anaesthesia during their first brachytherapy treatment. The use of neuraxial anaesthesia during the first brachytherapy was not associated with a reduced risk of local or systemic recurrence [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.54-1.67; P=0.863], long-term mortality from tumour recurrence (HR 1.46, 95% CI 0.75-2.84; P=0.265), or all-cause mortality (HR 1.46, 95% CI 0.81-2.61; P=0.209), after adjusting for other prognostic factors. Tumour recurrence and long-term survival were only significantly associated with the tumour cell type, tumour volume, and FIGO tumour staging. Sensitivity analyses using proportions of all brachytherapy sessions performed under neuraxial anaesthesia also did not show any beneficial effects of neuraxial anaesthesia on tumour recurrence and long-term survival. CONCLUSIONS Using neuraxial anaesthesia during brachytherapy for patients with cervical cancer was not associated with a reduced risk of tumour recurrence and mortality when compared with general anaesthesia.

Improving Perioperative Outcomes: Fluid Optimization with the Esophageal Doppler Monitor, a Metaanalysis and Review

Study selection Randomised controlled trials (RCTs) of oesophageal Doppler monitoring used to guide intra-operative intravenous fluid therapy to optimise intravascular volume in the perioperative setting were eligible for inclusion. Length of stay in an acute care hospital setting was the primary outcome of interest. Other outcomes eligible for inclusion were: return to full oral diet; morbidity; mortality; and colloid and crystalloid volumes. Length of stay in a rehabilitation hospital was excluded.

Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination

Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.

Multimodal Prehabilitation Programs as a Bundle of Care in Gastrointestinal Cancer Surgery: A Systematic Review

BACKGROUND: Prehabilitation reflects a proactive process of preoperative optimization undertaken between cancer diagnosis and definitive surgical treatment, with the intent of improving physiological capacity to withstand the major insult of surgery. Prehabilitation before GI cancer surgery is currently not widely adopted, and most research has focused on unimodal interventions such as exercise therapy, nutritional supplementation, and hematinic optimization. A review of the existing literature was undertaken to investigate the impact of multimodal prehabilitation programs as a “bundle of care.” DATA SOURCE: A systematic literature search was performed utilizing Medline, PubMed, Embase, Cinahl, Cochrane, and Google Scholar databases. STUDY SELECTION: The quality of studies was assessed by using the Cochrane tool for assessing risk of bias (randomized trials) and the Newcastle-Ottawa Quality Assessment scale (cohort studies). INTERVENTION: Studies were chosen that involved pre-operative optimization of patients before GI cancer surgery. MAIN OUTCOMES: The primary outcome measured was the impact of prehabilitation programs on preoperative fitness and postoperative outcomes. RESULTS: Of the 544 studies identified, 20 were included in the qualitative analysis. Two trials investigated the impact of multimodal prehabilitation (exercise, nutritional supplementation, anxiety management). Trials exploring prehabilitation with unimodal interventions included impact of exercise therapy (7 trials), impact of preoperative iron replacement (5 trials), nutritional optimization (5 trials), and impact of preoperative smoking cessation (2 trials). Compliance within the identified studies was variable (range: 16%–100%). LIMITATIONS: There is a lack of adequately powered trials that utilize objective risk stratification and uniform end points. As such, a meta-analysis was not performed because of the heterogeneity in study design. CONCLUSION: Although small studies are supportive of multimodal interventions, there are insufficient data to make a conclusion about the integration of prehabilitation in GI cancer surgery as a bundle of care. Larger, prospective trials, utilizing uniform objective risk stratification and structured interventions, with predefined clinical and health economic end points, are required before definitive value can be assigned to prehabilitation programs.

Improved quality of anesthesia and cancer recurrence studies.

To the Editor While we applaud the conclusion of Durieux’s editorial1 suggesting that the best anesthesia practice in patients with cancer includes regional anesthesia, opioid reduction, and strategies supporting a decreased inflammatory response, we wish to express concern that data describing vital markers of cancer progression in the multitude of retrospective studies examining variations in anesthesia practice on cancer outcomes have been omitted. The American Joint Committee on Cancer (AJCC) group tumor-specific clinical outcome (survival) categories to provide prognostic categories that incorporate pathological variables beyond tumor-node-metastasis classification.2 For example, within the four broad disease stages of gastric cancer, a patient with “T1” disease but cancer infiltration of seven regional lymph nodes (Stage II, 4-year survival 50%) has a substantially more favorable prognosis than someone with invasive “T4b” disease without any nodal involvement (Stage III, 4-year survival 17%).3 The conclusions of studies examining associations between proposed interventions (such as a perioperative epidural) and clinical outcomes are hence significantly limited if AJCC staging is not used to determine specific tumor stage influence. The study by Myles et al.4 referenced by Dr. Durieux is an example of a study that examined for an association of effect of epidural and omitted AJCC stage classification. Six cancer groups were included in this study with consequent vast variation in recurrence patterns. Furthermore, the pathological variable of lymphovascular space invasion (LVSI) is not controlled for in many retrospective analyses. LVSI is a binary classification on the appearance (or not) of tumor invasion into adjacent lymphovascular structures—a prerequisite for metastatic spread. Considered a strong marker of “tumor aggression,” it predicts cancer recurrence following resection of gastric,5 prostate,6 esophageal,7 colon,8 ovarian,9 breast,10 endometrial,11 and cervical12 cancers. Scant data on LVSI status are presented in any of the studies referenced by Dr. Durieux; we feel that any analysis not including such indices overlooks important predictors of cancer recurrence and survival. In a recent study of perioperative epidural analgesia and cancer recurrence following gastroesophagectomy, we reported, on univariate analysis, the very strong association of LVSI with recurrence (hazard ratio 10.36, 3.70–29.02, P < 0.0001) compared with the influence of an epidural (hazard ratio 0.59, 0.32–1.09, P < 0.10).13 Only after controlling for LVSI using multivariate analysis was the association of benefit for an epidural on cancer outcomes revealed (hazard ratio 0.33, 0.17–0.63, P < 0.0001). Subgroups of patients with more aggressive disease (LVSI positive) may derive particular cancer benefit from epidural analgesia. While we await prospective studies of anesthetic technique on cancer recurrence, we would urge that future minor, appropriate acknowledgment may consist of cited references to the sections containing the work. We question the value of footnotes (used in the case of both our anonymous authors’ plagiarized chapters) that do not define what “a portion” means. Lam1 also is quite correct that “new authors copying from existing chapters without prior permission or shared authorship is never acceptable,” and as echoed by Moon and Camporesi,2 “portions of a previous chapter that are directly copied should be cited and referenced in the bibliography” and, we would add, surrounded with quotation marks. As stated in our Open Mind article,4 Harvard Medical School’s Guidelines for Editors and Authors of Medical Textbooks provide an example of how such issues may be resolved before publication. Wiwanitkit3 suggests several factors including inexperience, lack of concern, and differences in local culture as reasons that some so-called developing countries adhere to a different ethic when it comes to punishing or chastising those accused of plagiarism and/or other forms of scientific misconduct.5,6 Whether true or not, we adamantly believe that in the case of plagiarism, irrespective of economics, culture, or interest, only 1 standard must apply if science and truth and respect for academic institutions are to prevail. Wiwanitkit3 also commented that our article’s anonymous authorship was motivated by our concern for retaliation against the “whistleblowers.” While a reasonable assumption, identifying our 2 authors would have in turn identified the plagiarizers, as well as the book editors. This might have resulted in adverse academic decisions and distracted readers from our principal intent—to educate and prevent recurrences rather than retaliate. Finally, we have gratifying evidence of progress, as editors of 2 of the leading multiauthored anesthesia textbooks have informed us that as a result of our article, the next editions of each textbook will adopt our recommendations including scanning of each chapter for plagiarism and providing proper attribution to previous chapter authors if significant portions of the earlier chapters are included in the later versions.

Neuraxial Anesthesia Reduces Lymphatic Flow: Proof-of-Concept in First In-Human Study.

Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%–100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.

Perioperative Implications of Neoadjuvant Therapies and Optimization Strategies for Cancer Surgery

Patients with cancer having either cancer- or non-cancer-related surgery present to the perioperative clinician with a unique set of challenges. Adequate assessment, risk stratification, and optimization of these patients requires the perioperative physician to be familiar with the natural history of the cancer, the systemic effects of the malignant disease on the body, and also the effects of neoadjuvant treatments on the major organ systems. Deconditioning is a multisystem disorder that is related to cancer treatments, sedentary lifestyle, and the malignant disease itself. It is being increasingly recognized as condition that is amenable to reversal with appropriate “prehabilitation” strategies. This article will give the reader an overview of the perioperative issues and optimization strategies for patients awaiting cancer surgery.

Evaluation of Reliability of MYZONE MZ-3 Heart Rate Monitor: A Study for the Future of Telephysiotherapy for Preoperative Prehabilitation in Cancer Patients

BACKGROUND There are a number of commercially available heart rate (HR) monitors on the market. The reliability of these monitors has had varying results. To the best of our knowledge, there are no telemonitoring services utilizing these devices for perioperative prehabilitation services for patients undergoing major surgery. The goal of this study is to pilot the MYZONE® MZ-3 HR monitor to assess its level of reliability to provide a feasible telephysiotherapy prehabilitation service through prescription-based exercise programs to patients presenting for major cancer surgery within our leading oncological health service. MATERIALS AND METHODS Paired HR data from each participant were captured and analyzed using a Bland-Altman plot. RESULTS Seven healthy participants were included in the study with a total number of paired HR data points of 1,928. The bias (mean difference) between electrocardiogram and the MYZONE MZ-3 was 0.4 beats per minute (bpm) with an adjusted 95% limits of agreement of -4.5 to 5.3 bpm. CONCLUSION The commercially available MYZONE MZ-3 HR monitor is a reliable tool for delivering telephysiotherapy to patients undergoing major cancer surgery. Further studies are needed to validate its use in this setting.