Regional Anesthesia and Breast Cancer Recurrence
Cathy X. Cao(曹锡清), MD
Medstar Washington Hospital Center
Washingon DC, USA May 10, 2014
Within the US alone, more than 3 million women are living with a history of breast cancer, about one in eight women will develop invasive breast cancer over the course of their lifetime. According to the National Center for Health Statistic, approximately 78,000 women get mastectomies each year. The number of new cases of invasive breast cancer in 2013 is estimated to be 232,000.
As anesthesiologists, we often confront challenges like what can we do perioperatively to affect our patients’ long term outcome? Can we make a difference by choosing a technique to improve their quality of life, alleviate postop pain and nausea/vomiting, minimize their cardiovascular and pulmonary complications, and even help reduce the risk of cancer recurrence or metastasis?
Recent research of regional anesthesia on breast cancer has shown consistent preliminary data that paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis approximately four-fold during 2.5 to 4 year follow-up period compared to opioid analgesia. The investigators will thus test the hypothesis that recurrence after breast cancer surgery is lower with regional anesthesia/analgesia than with general anesthesia and opioid analgesia. Currently, there is multi-center phase III clinical trial sponsored by NCI grant involving age 18-85 years old stage 1-3 women having mastectomies or isolated lumpectomies with axillary node dissection. Patients will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia with morphine analgesia. Participants will be followed for up to 10 years to determine the rate of cancer recurrence or metastasis.
Background Information
Surgery is the primary and most effective treatment of breast cancer, but residual disease in the form of scattered micrometastases and tumor cells are usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. At least three perioperative factors shift the balance toward progression of minimal residual disease:
1. Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGF, and releases growth factors that promote local and distant growth of malignant tissue.
2. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.
3. Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents.
However, regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia, and minimizing opioid requirement.
Techniques of Thoracic Paravertebral Block(TPVB)
A number of approaches and techniques have been described for performing ultrasound-guided thoracic paravertebral blocks. The ultrasound probe may be placed in a transverse position, a paramedian longitudinal position, or in an oblique plain. The needle may then be inserted in an in-plane or out-of-plane fashion. In addition, a catheter may be inserted using any of these approaches. A 5-12 MHz linear array probe is most commonly used, but a curved array ultrasound probe may be used as well. These blocks may be placed in the prone, lateral decubitus or seated position. Hence, the list of possible techniques available to place a thoracic paravertebral block is quite extensive. At the current time, no single technique has been shown to be more effective, easier to perform, or safer for the patient. A single injection will cover 4-5 dermatomes and is adequate for many procedures such as a mastectomy or pain management for rib fractures. Some practitioners prefer to perform a thoracic paravertebral block at two or three levels. The most commonly used agents are Bupivicaine 0.5% and Ropivicaine 0.5% with epinephrine 1:200,000-1:400,000.
The paramedian sagittal thoracic nerve block may be performed in plane and out of plane. An out of plane block may be placed in a parellel fashion with the probe in a longitudinal paramedian position or with the probe in a transverse position. An in plane paramedian sagittal block is placed with the probe in a vertical position approximately 2.5-3 cm lateral to the midline between two transverse processes. Both transverse processes should be visualized, with the superior costotransverse ligament and the pleura visible in between (figure 2). A 20 gauge blunt tipped block needle or a 22G Tuohy needle is introduced in a cephalad direction. The tip of the needle is advanced under direct visualization until it pierces the superior costotransverse ligament. If the superior coststransverse ligament is not easily seen, the needle is advanced until it is directly above the pleura. Due to the steep angle with which the block needle enters the tissue, the needle is often difficult to visualize. For this reason some practitioners choose to inject small aliquots of normal saline intermittently as they advance the needle to confirm the position of the tip. When the needle tip is located immediately above the pleura, the needle is aspirated to confirm the absence of blood or air. After this, 10-20 cc of local anesthetic is injected in 3-4 cc increments. Spread of local anesthetic with depression of the pleura will be clearly visualized. The extent of local anesthetic spread should be evaluated by moving the ultrasound probe superiorly and inferiorly.
When performing an out of plane paramedian sagital block the probe may be placed as described above. In this case the needle is placed at the side of the probe and is advanced with small aliquots of normal saline injected to evaluate the position of the tip by "tissue dissection". When the superior costotransverse ligament is pierced and after careful aspiration, the pleura will be depressed by the injection of normal saline. This is followed by injection of 10-20 cc local anesthetic injected in 3-4cc increments. When a catheter is placed using this technique it is generally threaded approximately 3 cm beyond the tip of the needle( Figure 3). The historical incidence of pneumothorax with TPVB is 0.3-0.5%, so patients receive a chest radiograph postoperatively to rule out pneumothorax before being discharged home.
Figure 2: Longitudinal, out-of-plane approach to thoracic paravertebral block. The transducer is first placed 5-6 cm lateral to the spinous processes to identify ribs, parietal pleura and intercostal spaces (A1-A3). The transducer is then moved progressively medially to identify transverse processes (B1-B3). Transverse processes (TP) appear square and deeper then ribs (round, superficial). The needle is inserted out-of-plane to contact the TP (C1-C2 and C3, line 1) and then walked off the TP (C3, line 2) inferior or superior to TP to enter the paravertebral space and injection local anesthetic (blue). Proper injection displaces the pleura (blue arrows). PVM - paravertebral muscles.
Figure 3. Continuous thoracic paravertebral block. The catheter is inserted 3 cm past the needle tip.
Mastectomy as an Outpatient Procedure Pathway
Mayo clinic has developed a program featuring multimodal pain control, including PVB, celebrex and gabapentin, which enable patients to be discharged home the same day of their operation. At the preop clinic, patients need to learn to change bandages, care for the incision, understand the surgical drain and be familiar with issues that may indicate the need for a doctor’s evaluation. Furthermore, before the implementation of the program, the multidisciplinary breast staff was educated as to the protocol and reassured the requirements of the patient could be met postoperatively prior to discharge home. Not only is TPVB associated with low pain scores, low PONV and high patient satisfaction, it has also proven to be cost-effective. Boughey et al. found that the use of TPVB decreased the overnight admission rate from 97% to 61% after major breast surgery. The benefits of TPVB continue beyond the length of local anesthetic. By blocking the nociceptic inputs, patients at their one-month, six-month and one-year follow up evaluations had significant less pain than their non-block counterparts, indicating a role in preventing chronic postmastectomy pain syndrome.
Reference:
1. www.cancer.gov/clinicaltrials/se ... =HealthProfessional
2. www.nysora.com
3.www2.kenes.com/asraspring2012/sci/Documents/Fleischmann_PS03_Thoracic%20Paravertebral%20Blocks.pdf
4. Exadaktylos AK et al. Can Anesthetic Technique for Primary Breast Cancer Surgery Affect Recurrence or Metastasis? Anesthesiology 2006; 105:660-664
5. Boughey JC et al. Improved postoperative pain control using thoracic paravertebral block for breast operations. The Breast Journal 2009; 15:483-488
6. Kairalumoa PH et al. Preincisional paravertebral block reduces the prevalence of chronic pain after breast surgery. Anesthesia and Analgesia 2006; 103:703-708b
This article demonstrated that anesthesia selection can affect long term outcome. It also proved that anesthesiologist and surgeon are equally important.
We always dream about a magic way to take care of all the problems such as cancers. It has not happened yet. As physicians, we are obligated to work as a team and do whatever takes to contribute ourselves with every little thing such as well controlling postoperative pain with less narcotics. Today is the Mother's Day. I wrote a story about my mom and I would like to post it over here since it was inspirited by this article written by Dr. Cathy Cao. Excuse me to write it in Chinese.
看到美国Cathy曹医生写的乳房癌术中术后镇痛的短文在中国新青年麻醉论坛刊登后，联想起母亲的两次癌症开刀经历。正好今天是母亲节，和大家共享。
Healthcare delivery system is changing. Anesthesiologists should can do their best for their patients (patient-centered). We should consider not only short term benefit (pain control and patient comfort), but also long term benefit (reduce recurrence). 方便和省事 as a goal is not acceptable.
Regional Anesthesia and Breast Cancer Recurrence 区域阻滞和乳腺癌的复发
Cathy X. Cao(曹锡清), MD
Medstar Washington Hospital Center
Washingon DC, USA
May 10, 2014
Within the US alone, more than 3 million women are living with a history of breast cancer, about one in eight women will develop invasive breast cancer over the course of their lifetime. According to the National Center for Health Statistic, approximately 78,000 women get mastectomies each year. The number of new cases of invasive breast cancer in 2013 is estimated to be 232,000.在美国，超过30万的女性有乳腺癌病史，大约1/8的女性会发展为乳腺浸润性癌。国家健康数据中心的数据显示每年大约7.8万的女性接受乳房切除手术。2013年，乳腺浸润性癌的新增病例大约是23.2万例。
As anesthesiologists, we often confront challenges like what can we do perioperatively to affect our patients’ long term outcome? Can we make a difference by choosing a technique to improve their quality of life, alleviate postop pain and nausea/vomiting, minimize their cardiovascular and pulmonary complications, and even help reduce the risk of cancer recurrence or metastasis?作为麻醉医生，我们经常需要面对一些挑战，类似于对于病人远期预后的影响我们到底能在围术期做些什么？ 我们是否能通过选择特定的技术来提高他们的生活质量，减轻术后疼痛和恶心呕吐的发生，尽量减少心血管和肺脏的并发症，甚至减少癌症复发或者转移的风险呢？
Recent research of regional anesthesia on breast cancer has shown consistent preliminary data that paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis approximately four-fold during 2.5 to 4 year follow-up period compared to opioid analgesia. The investigators will thus test the hypothesis that recurrence after breast cancer surgery is lower with regional anesthesia/analgesia than with general anesthesia and opioid analgesia. Currently, there is multi-center phase III clinical trial sponsored by NCI grant involving age 18-85 years old stage 1-3 women having mastectomies or isolated lumpectomies with axillary node dissection. Patients will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia with morphine analgesia. Participants will be followed for up to 10 years to determine the rate of cancer recurrence or metastasis.近期一项关于乳腺癌区域阻滞的研究，对比了乳腺癌手术术后应用椎旁阻滞和阿片类药物镇痛乳腺癌的复发或转移的风险，目前的初步数据显示， 在2.5-4年的随访中，应用椎旁阻滞的患者发生乳腺癌复发或转移的风险比阿片类药物镇痛低了将近四倍。调查员将会调查这一假说。当前，这项由NCI资助的多中心的III期临床试验正在开展，该项研究囊括18-85岁1-3期做过乳房切除术或者乳房肿瘤切除+腋窝淋巴结清扫术的女性。病人随机进行术后胸段硬膜外或椎旁神经阻滞镇痛，或者吗啡静脉镇痛。我们对参与的女性进行超过10年的随访来判断癌症复发或转移的发生率。
Background Information
背景资料
Surgery is the primary and most effective treatment of breast cancer, but residual disease in the form of scattered micrometastases and tumor cells are usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. At least three perioperative factors shift the balance toward progression of minimal residual disease:
手术是治疗乳腺癌最基本和最有效的治疗手段，但以微转移和肿瘤细胞的播散形式的残留疾病常难避免。微小转移瘤是否可以导致临床上肿瘤的转移，取决于宿主的防御功能和肿瘤的侵袭能力。
1. Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGF, and releases growth factors that promote local and distant growth of malignant tissue.手术本身抑制细胞免疫，降低肿瘤相关抗血管生成因子的浓度（如血管抑素和内皮抑素），增加促血管生成因子如血管内皮生长因子，释放生长因子促进恶性组织局部和远处的转移。
2. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.
麻醉损害大量免疫功能，包括中性粒细胞，巨噬细胞，树突状细胞，T细胞，自然杀伤细胞的这些免疫细胞的免疫功能。
3. Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents.阿片类镇痛药抑制了人体细胞免疫和体液免疫的功能，在龋齿类动物中增加血管生成，促进乳腺肿瘤的生长。
However, regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia, and minimizing opioid requirement.然而，区域阻滞衰减或防止这些不利的影响，区域阻滞在很大程度上能防止神经内分泌方面的手术应激反应，消除或者减少全身麻醉的需求，并且使阿片的需求最小化。
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