scholarly journals Fibrin Scaffold Incorporating Platelet Lysate Enhance Follicle Survival and Angiogenesis in Cryopreserved Preantral Follicle Transplantation

2020 ◽  
Vol 9 ◽  
pp. 1558
Author(s):  
Alireza Rajabzadeh ◽  
Fatemeh Jahanpeyma ◽  
Ali Talebi ◽  
Faezeh Moradi ◽  
Hussein Eimani
Keyword(s):  
Survival Rate ◽  
Cancer Patients ◽  
Cancer Recurrence ◽  
Platelet Lysate ◽  
Preantral Follicle ◽  
Preantral Follicles ◽  
Promising Strategy ◽  
Significant Difference ◽  
Fibrin Scaffold ◽  
Risk Of Cancer

Background: Transplantation of cryopreserved follicles can be regarded as a promising strategy for preserving fertility in cancer patients under chemotherapy and radiotherapy by reducing the risk of cancer recurrence. The present study aimed to evaluate whether fibrin hydrogel supplemented with platelet lysate (PL) could be applied to enhance follicular survival, growth, and angiogenesis in cryopreserved preantral follicle grafts. Materials and Methods: Preantral follicles were extracted from 15 four-week-old NMRI mice, cryopreserved by cryotop method, and encapsulated in fibrin-platelet lysate for subsequent heterotopic (subcutaneous) auto-transplantation into the neck. Transplants were assessed in three groups including fresh follicles in fibrin-15%PL, cryopreserved follicles in fibrin-15%PL, and cryopreserved follicles in fibrin-0% PL. Two weeks after transplantation, histological, and immunohistochemistry (CD31) analysis were applied to evaluate follicle morphology, survival rate, and vascular formation, respectively. Results: Based on the results, fibrin-15% PL significantly increased neovascularization and survival rate (SR) both in cryopreserved (SR=66.96%) and fresh follicle (SR=90.8%) grafts, compared to PL-less fibrin cryopreserved transplants (SR=28.46%). The grafts supplemented with PL included a significantly higher percentage of preantral and antral follicles. Also, no significant difference was observed in the percentage of preantral follicles between cryopreserved and fresh grafts of fibrin-15% PL. However, a significantly lower (P=0.03) percentage of follicles (23.37%) increased to the antral stage in cryopreserved grafts of fibrin-15%PL, compared to fresh grafts (35.01%). Conclusion: The findings demonstrated that fibrin-PL matrix could be a promising strategy to improve cryopreserved follicle transplantation and preserve fertility in cancer patients at the risk of ovarian failure. [GMJ.2020;9:e1558]

Characteristics and Oncological Outcome of Clinical T3a Prostate Cancer Patients Undergoing Radical Prostatectomy in the Multi-Parametric MRI Era

2020 ◽  
Author(s):  
Kasumi Yoshitomi ◽  
Shinya Yamamoto ◽  
Tatsuya Yamamoto ◽  
Eri Fukagawa ◽  
Kosuke Hamada ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Digital Rectal Examination ◽  
Oncological Outcome ◽  
Risk Groups ◽  
Free Survival ◽  
Significant Difference ◽  
Preoperative Factors

Abstract We aimed to reveal the association between the method of diagnosis (multi-parametric magnetic resonance imaging [mpMRI] and digital rectal examination [DRE]) and oncological outcomes of patients with clinical T3a (cT3a) prostate cancer after radical prostatectomy (RP) and stratify them according to oncological risk. We included 132 cT3a prostate cancer patients who underwent RP between 2008 and 2018. The biochemical recurrence (BCR)-free survival rate was evaluated according to the method of diagnosis (mpMRI alone; mpMRI group vs. DRE [with or without mpMRI]; DRE group). Several preoperative factors were evaluated in the multivariate analysis. Patients were divided into risk groups by our prediction model. The mpMRI group had significantly longer BCR-free survival than the DRE group (p<0.0001). The method of diagnosis (hazard ratio [HR]=2.69; 95% confidence interval [CI] 1.45-5.06; p=0.0017) and % positive cores (HR=4.36; 95% CI 1.14-16.5; p=0.031) were independent prognostic factors. Patients were divided into three risk groups based on these factors. There was a significant difference in BCR-free survival rate among the groups (p=0.0002).The method of diagnosis of cT3a prostate cancer was associated with BCR-free survival, and we categorized patients into risk groups. These assessments were attributable to the appropriate therapeutic strategy for patients with cT3a prostate cancer.

scholarly journals Evaluation of chemotherapy response between Paclitaxel-Cisplatin, Paclitaxel -Gemcitabine and Gemcitabine - Cisplatin among non - resectable lung cancer patients, A retrospective study in tertiary care hospital.

2020 ◽  
Vol 38 (4) ◽  
pp. 172-175
Author(s):  
Md Harun Or Rashid ◽  
Quadrat E Elahi ◽  
Md Ashraful Alam ◽  
Fatima Sarker
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Survival Time ◽  
Cancer Patients ◽  
Median Survival ◽  
Median Survival Time ◽  
Chemotherapy Response ◽  
Care Hospital ◽  
Lung Cancer Patients ◽  
Significant Difference

Background: To compare the survival rate of paclitaxel plus cisplatin (PC arm), paclitaxel plus gemcitabine (PG arm) and gemcitabine plus cisplatin (GC arm) in chemotherapy patients with non resectable lung cancer. Methods: This was a retrospective observational study to evaluate chemotherapy response among non resectable lung cancer patients with their survival at cancer center CMH, Dhaka since 01 July 2013 to 31 March 2015. One hundred fifty-four (154) non resectable lung cancer patients were randomly divided into three groups, 50 patients in PC arm, 51 patients in PG arm and 53 patients in GC arm. In PC arm paclitaxel 175 mg/m2 (day 1) with cisplatin 75mg/m2 (day 1), in PG arm Paclitaxel 175 mg/m2 (day 1) with gemcitabine 1000 mg/m2 (days 1 and 8) and in GC arm gemcitabine 1000 mg/m2 (days 1 and 8) with cisplatin 100mg/m2 (day 1). Results: Patients characteristics were similar between the three groups. The overall response rate was 40% in the PC arm,43.1% in the PG arm, 43.4% in the GC arm. The median survival time in PC arm was 8.5 months, in PG arm was 8.8 months, in GC arm was 9.2 months. The major side effect was myelosuppression which accounts 71% patients. The average treatment costs were 57% and 30% lower in PC arm as compared with GC and PG arm respectively. Conclusion: The median survival time, disease free survival time and 1-year survival rate in PC, PG, GC arms without significant difference. Treatment were well tolerable; quality of life parameter was mostly similar but paclitaxel with cisplatin was most cost effective than others chemotherapy regimen. J Bangladesh Coll Phys Surg 2020; 38(4): 172-175

scholarly journals The Benefits of Exercise Effect on Cancer: A Review

2020 ◽  
Vol 29 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Namju Lee
Keyword(s):  
Quality Of Life ◽  
Aerobic Exercise ◽  
Cancer Patients ◽  
Physical Functioning ◽  
Exercise Intervention ◽  
Cancer Recurrence ◽  
Exercise Effect ◽  
Muscle Groups ◽  
Risk Of Cancer

PURPOSE: Exercise has been greatly shown to be effective on cancer patients and thus improves functional capacity in cancer patients and lowers a risk of cancer recurrence. The growing numbers of cancer population has been diagnosed and therefore, effect of exercise on cancer should be focused as a great intervention. Therefore, this study reviews the benefits of exercise on cancer and exercise guidelines for cancer population.METHODS: This study reviews 30 previous studies focusing on the benefits of exercise on various types of cancer such as breast, colon, colorectal, liver, lung, ovary, brain, prostate, and melanoma.RESULTS: Improvement in muscle strength, aerobic capacity, body balance throughout optimal exercise would be necessary for cancer patients and survivors for their life-long health by improving overall body function. To reach a healthy life, they need to conduct at least 150 minutes of moderate aerobic exercise or 75 minutes of vigorous aerobic exercise per week, and also at least 2 days per week of resistance exercise with moderate to high intensity for all major muscle groups. Exercise intervention needs to be safe during and after cancer treatments and results in improvements in physical functioning, cancer-related symptoms, and quality of life. Especially, patients and/or survivors with prostate cancer and melanoma are required to exercise with prescription because exercise may induce unexpected effects on health in those population.CONCLUSIONS: Implications for exercise affects related to cancer are still unknown; however, the benefits of exercise to physical functioning and quality of life are sufficient for cancer patients and survivors.

scholarly journals Development of a Mortality Prediction Model Combined With time to Positivity for Solid Tumor Patients with Escherichia Coli Bacteremia

2020 ◽  
Author(s):  
Qing Zhang ◽  
Haoyang Gao ◽  
Ding Li ◽  
Changsen Bai ◽  
Zheng Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Logistic Regression ◽  
Cancer Patients ◽  
Tumor Patients ◽  
Scoring Model ◽  
Time To Positivity ◽  
Significant Difference ◽  
Development And Validation ◽  
Risk Of Cancer

Abstract Background: To develop a scoring model incorporating time to positivity (TTP) into clinical variables for predicting the mortality of tumor patients with Escherichia coli caused bloodstream infection (ECBSI).Methods: A retrospective single center study enrolling hospitalized cancer patients with ECBSI was conducted from 2013 to 2018. The patients were randomly divided into development and validation groups. Univariable and multivariable logistic regression analysis were used to identify risk factors for mortality. The scoring model was developed and validated based on logistic regression coefficients.Results: 315 and 194 patients with ECBSI were included in development and validation groups, respectively. Six significant risk factors for mortality were identified and included in the scoring model: fever ≥ 39℃, inappropriate antibiotic therapy, metastasis, acute respiratory distress (ARDS), blood transfusion, and TTP ≤ 8h. Patients were classified into low-risk (<10% mortality), medium-risk (10%-20% mortality) and high-risk (≥20% mortality) categories based on the predicted mortality rates in each score. The predicted mortality for the three categories was 4.38%, 15.39%, and 51.77%, respectively, in the development group, and 3.72%, 13.88%, and 50.09%, respectively, in the validation group. The model showed excellent discrimination and calibration for both groups, with AUC curves being 0.858 versus 0.835, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P=0.48) and the Chi-square test (6.993, P=0.46). Sensitivity and negative predictive values (NPV) increased along with the decrease of cut-off values.Conclusion: The developed TTP-combined scoring model is feasible for clinicians to predict the mortality risk of cancer patients with ECBSI.

scholarly journals The influences of preoperative metformin on immunological factors in early breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14182-e14182
Author(s):  
Takahiro Takahiro ◽  
Tadahiko Shien ◽  
Naruto Taira ◽  
Mariko Kochi ◽  
Takayuki Iwamoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Control Group ◽  
Metformin Treatment ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Immunological Factors ◽  
Risk Of Cancer

e14182 Background: Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and some reports have suggested that metformin may reduce cancer risk. Diabetics treated with metformin have a 23% reduction in the risk of cancer, including breast cancer. In addition, it is reported that the breast cancer patients with metformin treatment for diabetes showed favorable prognosis compared with those without metformin treatment. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. Methods: We conducted a prospective study to evaluate the effect of preoperative metformin on early breast cancer patients. The patients took a daily dose of metformin orally for 7 to 21 days before surgery. We evaluated the effects on immunological factors (TILs, CD4+, CD8+, PD-L1 and ALDH1) by comparing core needle biopsies (CNB) obtained before surgery with surgical specimens. Results: Seventeen breast cancer patients were enrolled in this prospective study and administered metformin before surgery, during the period from January to December 2016. We analyzed 59 patients who received surgery during the same period as a control group. In the control group, there was no significant difference in TILs between CNB and surgical specimens (Rs = 0.63). In the metformin group, TILs were negative in CNB and surgical specimens of 15 (88%) and 8 (48%) cases, low in 2 (12%) and 8 (48%), and intermediate in 0 and 1 (6%), respectively. These TILs increases were confirmed in 5 (29%) patients (p = 0.09), while a decrease was confirmed in 2 (12%). The expressions of CD4+ and CD8+ by TILs were increased in 41% and 18% of surgical specimens, respectively. (p = 0.02, p = 0.09) However, there was no statistically significant difference in these immunological factors and PD-L1 or ALDH1 expression between before and after metformin. Conclusions: In our small cohort, preoperative metformin administration shows positive impact on CD4 positive lymphocytes significantly and has tendency of increasing both TILs and CD8 positive lymphocytes. However, we should keep in mind that our sample size is small. Further study is necessary to uncover the mechanisms of favorable effects of metformin on breast cancer patients.

Significance of stress myocardial perfusion scans in predicting cardiovascular events and mortality in cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17009-17009
Author(s):  
S. Chandra ◽  
A. T. Tong ◽  
A. Wei Wei ◽  
S. W. Yusuf ◽  
S. Javaid ◽  
...  
Keyword(s):  
Survival Rate ◽  
Myocardial Perfusion ◽  
Cancer Patients ◽  
Cardiac Death ◽  
Coronary Revascularization ◽  
Group Versus ◽  
Event Free Survival ◽  
Free Survival ◽  
Stress Myocardial Perfusion ◽  
Significant Difference

17009 Background: Cardiac risk assessment in cancer patients has not extensively been studied. We evaluated the role of stress myocardial perfusion scan (SMPS) in predicting cardiovascular outcomes in cancer patients. Methods: A retrospective chart review was performed on 787 patients who had a SMPS from 01/2002 - 03/2003. All patients were followed for at least 1.5 years. Cox proportional hazard model was used to determine the time-to-first event [cardiac death, myocardial infarction (MI) and coronary revascularization]. Cardiac death was defined as documented cardiac death or sudden unexplained death. Results: A total of 501/787 (64%) patients had normal SMPS, whereas 286/787 (36%) had abnormal SMPS. Adenosine [430/787 (55%)] and dobutamine [144/787 (14%)] were used for chemical stress while 213/787 (23%) patients underwent exercise testing. Mean age was 66±11 years and median follow-up duration was 1.8 years. The 3- year event-free survival rate was 0.71 (0.64–0.78) for abnormal SMPS and 0.87 (0.8–0.94) for normal SMPS (p<0.0001). Of all abnormal scans (n=286), 3-year event free-survival rate based on type of vascular defects varied from 0.79(0.67–0.93) for fixed defects, 0.68 (0.58-.08) for reversible defects and 0.63 (0.5–0.8) for co-existent fixed and reversible defects (p<0.0001). Other factors adversely affecting event-free survival were male gender (p=0.025), cardiomyopathy (p=0.001), coronary artery disease (p<0.0001), previous MI (p<0.0001), congestive heart failure (p=0.001) and hypercholesterolemia (p<0.0001). When we analyzed cardiac death as a separate event, SMPS results still made a significant difference with 3-year cardiac-survival rate of 0.79 (0.69–0.91) for abnormal scan group versus 0.88 (0.81–0.95) for normal scan group (p=0.05). Furthermore, the 3-year cardiac-survival rate in patients with both fixed and reversible defects was 0.4 (0.1–1), which was much worse than those with fixed [0.87 (0.76–0.99)] or reversible [0.85 (0.74–0.99)] defects alone (p=0.028). Conclusions: SMPS is a highly useful modality for predicting cardiac events and mortality in cancer patients. The characteristics of the perfusion defect further stratifies the patients at higher risk. No significant financial relationships to disclose.

scholarly journals Analysis of the selenium (Se) content in the toenail of colorectal cancer patients

2020 ◽  
Vol 5 (1) ◽  
pp. first
Author(s):  
Phuong Truc Huynh ◽  
Trần Tuấn Anh ◽  
Nguyễn Văn Hạnh ◽  
Nguyễn Thị Trúc Linh ◽  
Trương Thị Hồng Loan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Trace Element ◽  
Cancer Patients ◽  
Trace Element Content ◽  
Men And Women ◽  
Analysis Technique ◽  
Significant Difference ◽  
Colorectal Cancer Patients ◽  
Risk Of Cancer ◽  
Healthy Persons

Selenium (Se) is a trace element that plays an important role in the biological functions of the human body. Toenails are considered as suitable materials for finding the relationship between trace element content with human diseases. The goal of this study is to analyze and evaluate the Se content in the toenails of colorectal cancer patients in order to find out the risk of cancer in human. The Se content in the toenails of 60 colorectal cancer patients (63.3% for men) and 22 healthy persons (54.5% for men) was analyzed by the k0-standardization method of the instrumental neutron activation analysis technique. The results of the analysis showed that Se contents ib healthy persons were 1.13 mg/g and 1.32 mg/g for men and women, respectively; for colon cancer patients were 0.70 mg/g and 0.84 mg/g for men and women, respectively; for rectal cancer patients 0.86 mg/g and 0.82 mg/g for men and women, respectively. By the statistical analysis, it showed that the Se content was significantly different between the patients and the normal patients (p<0.05), but there was no significant difference between women and men. The conclusion of this study was that the Se content in the toenails of colorectal cancer patients is lower than that of normal patients.

scholarly journals The Feasibility of Hospital-based Exercise Program on the Level of Physical Activity and Body Composition in Cancer Survivor: An Exploratory Feasibility Study

2020 ◽  
Vol 29 (2) ◽  
pp. 195-200
Author(s):  
Mi Kyung Lee ◽  
Ji Yong Byeon ◽  
Jae Youn Chung ◽  
Justin Y. Jeon
Keyword(s):  
Physical Activity ◽  
Body Composition ◽  
Cancer Survivors ◽  
Cancer Patients ◽  
Controlled Trial ◽  
Exercise Program ◽  
Cancer Recurrence ◽  
Risk Of Cancer ◽  
Counselling Program

PURPOSE: Although physical activity may reduce the risk of cancer recurrence and risk of mortality in cancer patients, majority of cancer survivors are still remained physically inactive. Since most of cancer patients visit their oncologists on a regular basis, it would be ideal to provide exercise counselling program along with their hospital visit. However, the feasibility of hospital based exercise counselling program has not been tested. Therefore, the purpose of this exploratory study was to evaluate the feasibility of hospital-based exercise counselling program on the level of physical activity and body composition in cancer survivors.METHODS: Among 118 cancer survivors underwent exercise counselling program at the cancer prevention center of university affiliated hospital, 47 cancer survivors (mean age, 51.8 years) revisited after an 8-week. At baseline and after 8 weeks, the level of physical activity and body composition were measured.RESULTS: Compared to their baseline value, we observed significant increase in walking (baseline vs. 8 weeks: 170.7±197.8 vs. 362.2±343.4 minutes/week, <i>p</i><.05) and frequency of resistance exercise (baseline vs. 8 weeks: 0.21±1.2 vs. 2.5±2.5 day/week, <i>p</i><.05). Percent body fat was decreased (baseline vs. 8 weeks: 30.3±9.6 vs. 29.7±9.5%, <i>p</i>=.025) and skeletal muscle mass was increased at the 8th week follow up visit compared to their baseline value (baseline vs. 8 weeks: 22.9±3.7 vs. 23.2±3.8 kg, <i>p</i>=.019).CONCLUSIONS: The hospital-based exercise program was feasible intervention to increase the level of physical activity and improve body composition in cancer survivors. Considering that the current study is not a randomized controlled trial and also small portion of cancer survivors returned to the follow up test, the efficacy of this exercise counselling program should be tested with proper study design.

ACE inhibitors/ARB and the risk of breast cancer recurrence after surgery in Japanese population: A pilot study.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 52-52
Author(s):  
Takeo Fujii ◽  
Osamu Takahashi ◽  
Teruo Yamauchi
Keyword(s):  
Breast Cancer ◽  
Angiotensin Ii ◽  
Cancer Patients ◽  
Recurrence Rate ◽  
Cancer Recurrence ◽  
Asian Population ◽  
Breast Cancer Recurrence ◽  
Curative Surgery ◽  
Apoptosis Pathway ◽  
Significant Difference

52 Background: Angiotensin II can work as a growth promoter via angiotensin II type1 receptor (AT1R). In an in vivo study, Angiotensin Converting Enzyme Inhibitor (ACEI)/Angiotensin Receptor Blocker (ARB) down regulates vascular endothelial growth factor and activates apoptosis pathway through AT1R. In some clinical studies, the efficacy of ACEI/ARB to cancer patients has been investigated; however, the results are various. This has not been examined in Asian population. We investigated breast cancer patients in a single institution if the recurrence rate is related to ACEI/ARB use. Methods: This retrospective study will evaluate disease-free survival (DFS) for Japanese patients who were diagnosed with invasive breast cancer and had curative surgery between January 2004 and December 2006 at St Luke’s International Hospital. We will compare DFS of two groups with and without ACEI/ARB use. DFS is defined as the interval between curative surgery and the recurrence of breast cancer. Recurrence of disease was confirmed by radiographically or pathologically. Patients who took ACEI/ARB are defined as those who had taken them for at least 6 months after initial diagnosis. The following patient data will be extracted from their medical records; age, stage, body mass index, menopausal status, biomarker status (ER, PgR, and HER2), usage of bisphosphonate, usage of statin, diabetes, surgical procedure. Results: A total of 1,163 patients were analyzed. 76 were ACEI/ARB user and 1,087 were non-user. The recurrence rate of ACEI/ARB users was 17.1% (13/76). In comparison, that of non-users was 12.2% (133/1,087). The odds ratio (OR) was 1.480 (95 % CI: 0.793-2.762 p=0.218). Kaplan-Meier analysis did not show a significant difference between them (log-rank test p=0.194). Conclusions: Our study is the first one to evaluate the efficacy of ACEI/ARB in breast cancer recurrence among Asian population. Recurrence rate did not differ in the two groups although molecular biology suggested antitumor effect of ACEI/ARB. We will further explore if any confounding factors lie between the two groups, and plan to conduct a prospective study if ACEI/ARB exhibits antiproliferative effect in postoperative cancer patients.

scholarly journals Anaesthetic challenges in cancer patients: current therapies and pain management

2017 ◽  
Vol 24 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Jūratė Gudaitytė ◽  
Dominykas Dvylys ◽  
Indrė Šimeliūnaitė
Keyword(s):  
Pain Management ◽  
Cancer Patients ◽  
Cancer Recurrence ◽  
Anaesthetic Techniques ◽  
Organ Systems ◽  
Platinum Based Chemotherapy ◽  
Increased Risk ◽  
Pulmonary Damage ◽  
Chemotherapy Agents ◽  
Risk Of Cancer

The objective. The  aim is to present the  major effects of cancer treatment (chemotherapy, radiotherapy, surgery) that the  anaesthesiologist should consider preoperatively, and to review techniques of the analgesic management of the disease. Materials and Methods. To summarize the  major challenges that cancer patients present for the  anaesthesiologists, a  literature review was conducted. Articles presenting evidence or reviewing the  possible effects of anaesthetics on  cancer  cells were also included. Online databases of Science Direct, PubMed, and ELSEVIER, as well as reference lists of included studies were searched. Articles published from 2005 to 2016 were selected. Results. Anaesthesiologists should pay attention to patients receiving chemotherapy and its side effects on organ systems. Bleomycin causes pulmonary damage, anthracyclines are cardiotoxic, and platinum-based chemotherapy agents are nephrotoxic. A lot of chemotherapy agents lead to abnormal liver function, vomiting, diarrhoea, etc. Surgery itself is suspected to be associated with an increased risk of metastasis and recurrence of cancer. Regional anaesthesia and general anaesthesia with propofol should be used and volatile agents should be avoided to prevent cancer patients from perioperative immunosuppression that leads to increased risk of cancer recurrence. Pain management for palliative patients remains a major problem. Conclusions. To provide the best treatment for cancer patients, cooperation of anaesthesiologists with oncologists and surgeons becomes imperative. It has been established that anaesthetic techniques and drugs could minimize the perioperative inflammation. However, further research of the perioperative “onco-anaesthetic” is needed.

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