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 Table of Contents  
Year : 2013  |  Volume : 27  |  Issue : 3  |  Page : 121-131

Neurolytic celiac plexus block for pancreatic cancer pain: A review of literature

Department of Anesthesiology and Pain Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Date of Web Publication7-Jan-2014

Correspondence Address:
Sankalp Sehgal
320 E. 91st Street, Apt 2 FC, New York, NY-10128
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-5333.124584

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The effective management of pancreatic cancer pain continues to be a major challenge for patients and clinicians. Up to 80% of patients with advanced pancreatic cancer present with the symptoms of severe pain. One of the most important goals in their management is achieving the highest quality of life throughout the course of disease with effective palliation of pain. Majority of the current data supports the use Neurolytic celiac plexus block (NCPB) and has been shown to be more effective in reducing pain compared with standard pharmacotherapy. NCPBs have led to decreased opioid requirements and related side effects, thus preventing deterioration in quality of life. In this article, we discuss the treatment of pancreatic cancer pain and the advances in techniques of performing NCPB. We also analyzed the incidence of complications and the quality of pain relief with the use of NCPB. NCPB is effective, has a low incidence of complications, and should be used more often in patients with pancreatic cancer pain.

Keywords: Neurolytic celiac plexus block, pancreatic cancer, pain pathways in pancreatic cancer

How to cite this article:
Sehgal S, Ghaleb A. Neurolytic celiac plexus block for pancreatic cancer pain: A review of literature. Indian J Pain 2013;27:121-31

How to cite this URL:
Sehgal S, Ghaleb A. Neurolytic celiac plexus block for pancreatic cancer pain: A review of literature. Indian J Pain [serial online] 2013 [cited 2022 Dec 7];27:121-31. Available from: https://www.indianjpain.org/text.asp?2013/27/3/121/124584

  Introduction Top

Pancreatic cancer affects more than 30,000 people each year in the United States alone. According to the National Cancer Institute at the NIH, it is the fourth leading cause of deaths from cancer every year with overall 5-year relative survival rate of approximately 5%. [1] Despite advancements in diagnosis and treatment, unfortunately, this tumor has poor prognosis, being surgically resectable in only 10% of the patients. [2] The long-term benefits of chemotherapy and radiation therapy are limited [3] and surgical resection of the pancreas has a 5-year overall survival rate between 7% and 34% compared with a median survival of 3-11 months for unresected cancer. Hence the cornerstone of management of these patients is palliative care and pain control. The mainstay therapies used in the treatment of pancreatic cancer pain include pharmacologic therapy with systematic analgesic medication and neurolytic celiac plexus blocks (NCPBs). The effective management of pain associated with pancreatic cancer continues to be a major challenge for patients and clinicians.

The risk factors associated with the development of pancreatic cancer include advanced age, chronic pancreatitis, and tobacco use. Patients with pancreatic cancer often present with the symptoms of pain, nausea, lack of appetite, and weight loss and severe pain can be associated with up to 80% of patients with advanced cancer. [4]

The pain associated with pancreatic cancer is typically located in the upper abdomen, but often radiates to the mid-back. The pain may be constant or intermittent and the quality of the pain is frequently described as constant, gnawing, and visceral in character. At the time of diagnosis of pancreatic cancer, 26% of the patients have mild pain, 36% have moderate pain, 11% have severe pain, and 27% have no discomfort. [5] Importantly, cancer pain has been shown to be associated with a significant loss of quality of life. [6],[7] Inadequately controlled cancer pain can result in poor quality and significant loss of life. In order to optimize the quality of life of patients during their remaining existence, palliative care with adequate pain control is an essential priority. [8]

  Treatment of Pancreatic Cancer Pain Top

The two mainstay therapies used in the treatment of pancreatic cancer pain are: [9]

  1. Pharmacologic therapy with systemic analgesic medications
  2. NCPB

These two pain control therapies should not be considered mutually exclusive. Instead, the combination of both these therapies may provide the most effective pain relief in patients with pancreatic cancer.

Pain Pathways

The comprehensive pancreatic cancer pain necessitates the basic understanding of anatomy and pain pathways. The celiac plexus is a part of the sympathetic nervous system that transmits both visceral afferent and efferent information for the majority of upper abdominal viscera. The nerves of the pancreas can receive nocioceptive stimulation that is transmitted to the celiac plexus. [10],[11] The splanchnic nerves carry sympathetic nerve fibers that synapse at the celiac plexus and pass through the diaphragmatic crus to reach the spinal cord and the nocioceptive information is then transmitted to the thalamus and cortex of the brain, which is perceived as pain. The ascending pain information may also be modulated by descending mechanisms. [12]

There are a number of possible mechanisms that may be involved in pain associated with pancreatic cancer. [13] .

1. Pancreatic cancer may directly infiltrate or stretch the pancreatic nerves [10] causing neuritis or possibly a state of neuropathic pain. 2. It has also been shown that ductal cancer of the pancreas can express and secrete neurolytic enzymes, permitting tumor spread along nerve sheaths, [14] contributing to the neuritis. 3. Pancreatic cancer frequently metastasizes to the retroperitoneal lymph nodes including the nodes in close proximity to the celiac axis and surrounding neural ganglia. These enlarged and metastatic lymph nodes may infiltrate or stretch the surrounding nerves, also causing neural irritability. 4. Pancreatic cancer may also cause a form of localized 'pancreatitis' that can contribute to pain. [15] As a result, nerves within the pancreas may become sensitized to both chemical and mechanical stimuli associated with ongoing inflammatory processes. [11] 5. In chronic pancreatitis (without pancreatic cancer), there are increased numbers of eosinophils in the perineural infiltrate. [16] Due to localized inflammation, loss of perineural sheath can result in the nerves being hypersensitive to a variety of noxious chemical stimuli including prostaglandins, bradykinins, acidosis, and histamine. [17] To provide further support, there is an increased presence of neurotransmitters in afferent pancreatic nerves in patients with pancreatitis. [18] 6. The presence of increased ductal and interstitial pancreatic pressures may contribute to the pain associated with pancreatitis, which may occur with pancreatic cancer. [15],[18],[19] Intraductal pancreatic pressure has been found to be abnormally high in chronic pancreatitis. [20],[21],[22],[23] With this increased pancreatic pressure, the visceral afferent nerves that are already sensitized from noxious chemical stimuli due to both the pancreatitis and the pancreatic cancer can become hypersensitive to mechanical stimuli. [11] Also, the increased pressure of the parenchyma within a finite space, limited by a fibrotic pancreatic capsule, may result in a 'compartment syndrome' [18],[19] and the increased vascular resistance with reduced pancreatic blood flow can result in further neural irritability and pain from the ischemia. [19] It can be proven from the fact that surgical drainage to relieve increased pancreatic pressure improves pain in 70-80% of patients [24],[25] increased.

As a result, repeated visceral afferent stimulation from these described pain mechanisms associated with pancreatic cancer may result in a centrally sensitized pain state [Figure 1]. Tissue injury or visceral inflammation may increase afferent input to the spinal cord by activation of previously silent nocioceptors (pain receptors) in the viscera. [21] With repeated ongoing stimulation, these peripheral nerve endings may have increased sensitivity, decreased threshold to stimulation, and a prolonged and enhanced response to stimulation. A consequence of this increased activity at the spinal cord is the increased tonic release of neurotransmitters like glutamate and substance P that can then alter the excitability of spinal neurons. [26],[27] At this level of the central nervous system, these spinal neurons become more easily excitable resulting in an expanded peripheral receptive field, which is the perceived area of pain. [27] After tissue damage or irritation, this central sensitization may result in the amplification of pain from peripheral input that was previously interpreted as being normal or physiologic. As a result, patients may have decreased threshold to pain, enhanced responses to painful stimuli, and expanded areas of perceived pain.
Figure 1: Neurophysiological pain pathways involving transmission of the visceral nocioceptive information through peripheral nerves, sympathetic nerves, spinal cord, and ultimately to the brain

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In addition, these patients may also suffer pain from the resulting biliary obstruction and gastric outlet obstruction.

  Neurolytic Celiac Plexus Block Top

Celiac plexus blockade (CPB) refers to injection of steroids with or without local anesthetic to temporary relieve pain and inflammation of pancreatic origin. Celiac plexus neurolysis (CPN) is the chemical neurolysis of the efferent fibers that transmit pain from the intraabdominal viscera. It involves injection of neurolytic agent, such as ethanol or phenol, with a local anesthetic, to permanently destroy nerve fibers, and control pancreatic pain permanently. It was first described by Max Kappis in 1914 and in the past, the use of NCPB in the treatment of pain from pancreatic cancer was often reserved for patients who were not receiving adequate analgesia or not tolerating opioid medications. In fact, the Agency of Health Care Policy and Research (AHCPR) suggests reserving nerve blocks in the management of cancer pain until nearly all other pain modalities have failed. [28] However, in the past two decades, there has been evidence that NCPB may be a useful adjunct in the palliation of pancreatic cancer pain [9],[29] by improving pain intensity or decreasing systemic analgesic drug requirement. [30]

  Relevant Neural Anatomy for NCPB and Splanchnicectomy Top

The celiac plexus is located below the diaphragm, antero-lateral to the aorta immediately caudal to the celiac artery's origin, at the cephalad border of the L1 vertebral body [Figure 2]. It can vary in range in diameter from 0.5 to 4.5 cm, and vary in position from T12-L1 disc space to the middle of the L2 vertebral body. [31] It is formed by the splanchnic nerves that traverse the posterior mediastinum and enter the abdomen through the diaphragmatic crus to synapse at the right and left celiac ganglia. It is involved in nocioceptive transmission from the upper abdominal viscera including pancreas. Originating from higher levels, greater (T5-T10), lesser (T10-11), and least (T12) splanchnic nerves are comprised of preganglionic efferent and visceral afferent nerve fibers. From the celiac ganglia, the preganglionic efferent fibers then innervate their target visceral structures. There may also be some parasympathetic contributions, which originate from the cranio-sacral levels of the spinal cord, to the celiac plexus. The visceral afferent fibers that receive nocioceptive information about pain from the pancreas travel with the autonomic efferent fibers to the celiac plexus. The fibers, however, then pass without interruption to the dorsal root ganglia where their cell bodies are located. The fibers continue with the other afferent fibers in the dorsal root to terminate in the dorsal horn of the thoracic cord (T5-L2). At least one synapse occurs before the nocioceptive information is relayed to the higher brain centers.
Figure 2: Sketch depicting anatomy of the splanchnic nerves and celiac plexus and contributions of sympathetic and parasympathetic nervous systems in the formation of the celiac ganglia

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  Efficacy of NCPB Top

In an earlier study in 1987 by Brown et al., consisting of a large case series of 136 patients treated with NCPB for pancreatic cancer pain, 85% patients had good pain relief, with relief through their remaining life in 75% of patients. [4] Subsequently, several randomized controlled trials between 1993 and 1998 comparing percutaneous NCPB with pharmacologic therapy in the management of pancreatic cancer pain [32],[33],[34] revealed that patients randomized to NCPB had significantly decreased opioid consumption, which lasted from up to 50 days following the procedure until the time of death [32],[33],[34] and had less deterioration in quality of life estimates as a function of time compared with patients undergoing pharmacologic therapy. [33] They also suggested that NCPB provides more effective analgesia during first 4 weeks following the procedure. [33],[34] However, these studies had a limited number of subjects in each treatment arm (n = 10-12) and were not double-blinded.

In a notable study in 1993 by Lillemoe and colleagues, unresectable pancreatic cancer patients (n = 137) were randomized to intraoperative chemical splanchnicectomy (splanchnic neurolysis-similar to CPB) or saline placebo. [35] The chemical splanchnicectomy provided improved pain control along with decreased opioid requirements until their death. Interestingly in this study, a small subgroup of patients (n = 34) with pain at the time of exploratory laparotomy receiving the chemical splanchnicectomy had improvement of survival. The efficacy of NCPB for the treatment of upper abdominal cancer pain has also been evaluated by a meta-analysis by Eisenberg et al., which identified 24 papers: 2 randomized controlled trials, 1 prospective case series, and 21 uncontrolled retrospective case series. [36] The authors concluded that celiac plexus block has long-lasting benefit for 70-90% of patients with pancreatic and intraabdominal cancers. In another double-blind, randomized, placebo-controlled study by Staats et al., in 2001 involving 139 patients it was concluded that neurolytic block, as compared with medical management alone, improved pain, elevated mood, reduced pain interference with activity, and was associated with an increase in life expectancy. [37]

Contrary to others, in 2004 in a double-blind randomized clinical trial by Wong et al., conducted in 100 eligible patients in Mayo Clinic Rochester, MN with unresectable pancreatic cancer experiencing pain, although neurolytic CPB was found to improve pain relief versus optimized systemic analgesic therapy alone, it did not affect the quality of life or survival. [38] In a randomized study in 2008 in 56 patients with unresectable pancreatic cancer treated with neurolytic CPB versus pharmacotherapy, it was further supported that although in the CPB group the opioid consumption was significantly lower, the quality of life was not different in the two groups. [39] Lastly, in a multicenter randomized study in 2009 including 65 patients treated with three modalities: opioids, celiac plexus blocks and thoracic splanchnicectomy, no difference in pain relief or opioid consumption was noted between the three treatment groups. [40]

The potential duration of a NCPB, estimated at >3-6 months, [35],[41],[42] may match or outlast the median survival time of 6 months following the diagnosis of pancreatic cancer. [43] However, there may be some pancreatic cancer patients who receive analgesia from NCPB for a certain time interval, but then experience a return of worsening of pain, which may be due to incomplete destruction of nerve fibers and ganglia after using alcohol for neurolysis. [44] If needed, the celiac plexus block can be repeated in the future.

The analgesic effects of NCPB may be more efficacious in cases with tumor involving the head of the pancreas than in cases with advanced tumor proliferation. [7] Placement of a celiac catheter has been studied to improve the efficacy of NCPBs. [45] Also, the celiac plexus blocks should be considered earlier in the disease, [41],[46],[47] although another recent study compared early and late sympathetic neurolytic blocks with pharmacotherapeutic intervention in advanced cancer patients and found no major differences between the early and late block groups. [47]

The efficacy of diagnostic celiac plexus block has been evaluated with results showing that a positive response to diagnostic block correlates positively with NCPB for abdominal visceral pain due to malignancy but it is a poor predictor when the response is negative and hence clinical role is questionable and may not be warranted for patients with terminal malignancy. [48]

There have been studies to reveal that using the single-needle anterior approach, the spread of the neurolytic in the celiac area is hampered by the regional anatomic alterations [49] concluding that there is a close correlation between the block's efficacy and duration of analgesia with the spread of the injectate. A recent retrospective study [50] found that positive outcomes of NCPB were more likely in those patients who had a lower preblock opioid dose and in those patients who had pain of a shorter duration prior to block and limited sedative administration during the procedure.

  Techniques of NCPB Top

Celiac plexus blocks can be performed with a variety of techniques, namely, surgical, percutaneous ultrasonographic, fluoroscopic, computed tomography (CT)-guided, and endoscopic ultrasonographic (EUS).

Surgical Technique

NCPB can be performed during laparotomy or laparoscopy. [51] Laparoscopic celiac plexus block is performed at the time of operative staging, in which surgeons use a laparoscope to view the pancreas and surrounding organs to determine the extent of the disease. It allows surgeons to obtain an excellent view of the celiac plexus at the time of staging laparoscopy. Alternatively, chemical splanchnicectomy can be performed during surgery, which has been shown to provide pain relief in more than 80% of the patients, preventing development of pain for up to 6 months and with patients having a survival benefit. [35]

Other surgical methods of analgesia in patients with pancreatic pain may include percutaneous computerized-guided cryoablation of the celiac plexus, [52] percutaneous splanchnic radiofrequency ablation, [53] transdiscal percutaneous approach of splanchnic nerves, [54],[55] and thoracoscopic splanchnicectomy, which has been used for the management of upper abdominal pain for conditions such as chronic pancreatitis or supra-mesocolic malignant neoplasms, including unresectable pancreatic cancer. [56] In studies comparing NCPB and videothoracoscopic splanchnicectomy, the lower invasiveness of celiac plexus block, in combination with its more positive effect on quality of life, has been proven to be the preferred method for pain control. [57],[58]

Although newer techniques have largely replaced surgery for performing NCPB, its advantage is the ability to combine it with biliary bypass and gastrojejunostomy, thus performing palliation of pain, jaundice as well as gastric outlet obstruction.

Percutaneous Technique

Posterior approach

The most commonly used method for celiac plexus block involves the posterior approach with the percutaneous insertion of needles directed toward the celiac plexus and/or splanchnic nerves. [59] The patient is placed in a prone position and needles are inserted bilaterally slightly below the inferior ribs (T12) at points approximately 7 cm from the midline [Figure 3]. Radiographic guidance is typically used to direct the needles towards the celiac plexus, which is located at the antero-lateral aspect of the first lumbar vertebral body. The celiac plexus consists of a network of neural ganglia surrounding the aorta. On the left side (aortic side), once the needle advances past the vertebral body, it should be inserted an additional 1-2 cm, or until the dense wall of aorta is identified by pulsatile transmissions through the length of the needle. On the right side, the needle can be inserted another 1-2 cm beyond the anterior plane of the vertebral body. A variation of the technique uses a single needle placed on the left side with the patient in a lateral position. [60] Prior to the injection of any substance, the needle is carefully examined to rule out the presence of cerebrospinal fluid, blood, or urine. The needle position is then confirmed with the injection of several milliliters of a radio contrast agent, such as iothalamate or iopamidol. It is important to ensure that there is no spread of radio contrast to the epidural or intrathecal spaces, psoas muscle (which encases the lumbar plexus), nerve roots, and vascular structures, especially the aortic wall. Next, 10 ml of 0.5% bupivacaine is injected on each side. If there are no neurologic deficits after 10 min, 10 ml of neurolytic agent (absolute alcohol) is injected on each side to spread to the celiac plexus or splanchnic nerves to interrupt nerve transmission for 3-6 months duration. Previously, a diagnostic celiac plexus block with local anesthetic only was commonly performed prior to the NCPB on a separate day. [46] However, clinical observation and evidence suggest that nearly all patients receiving diagnostic celiac plexus block receive temporary benefit and then proceed to the actual neurolytic procedure. [46] As a result, many clinicians presently perform the NCPB without the need for a diagnostic celiac plexus block given the relative safety and analgesic efficacy of the former. [35],[41]
Figure 3: Patient positioning and surface landmarks for performing a percutaneous celiac plexus block via posterior approach. An isoceles triangle is formed by the lower borders of the twelfth ribs (7.5 cm from midline) to the T12-L1 vertebral body

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The final needle-tip position relative to the diaphragmatic crura [Figure 4] defines the NCPB as being anterocrural or retrocrural (anterior or posterior to the diaphragm, respectively) based on the attachment of the diaphragmatic crura to the vertebral bodies and discs and longitudinal ligament. [59],[61] The placement of the needle(s) at the L1 vertebral body will increase the probability of an anterocrural block or a 'true' celiac plexus block, which is the technique described earlier. [59],[61] The transaortic approach has also been advocated as another technique that is used to acco mplish anterocrural NCPB. [41],[62] From the left side, a single needle is inserted through the aorta so that the final needle-tip is anterior to the aorta at the lower portion of L1 vertebral body [Figure 5]. Using a similar posterior approach but with a more superior placement of needle(s) at T12 will likely result in a retrocrural block or a splanchnic nerve block. The accurate determination of a block as being anterocrural or retrocrural requires radiographic imaging. A study comparing anterocrural and retrocrural approaches with NCPB suggests that there is no significant difference in analgesia. [41]
Figure 4: Cross-sectional views demonstrating the anatomy of celiac plexus with surrounding structures and the needle path while performing percutaneous celiac plexus block from a posterior approach. Image on right shows the spread of injectate in relation to the diaphragm, anterior (anterocrural) and posterior (retrocrural) spread

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Figure 5: Antero-posterior and lateral radiographic images of needle placement anterolateral to the L1 vertebral body

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  Anterior Approach Top

There are a variety of techniques that have been described for the anterior approach to a NCPB. One technique involves percutaneous placement of a single needle through abdominal wall and possibly the stomach, intestine, and pancreas to the preaortic region of the celiac plexus. [63],[64],[65] This anterior percutaneous technique uses CT imaging or ultrasound guidance to guide and confirm needle placement. The endoscopic ultrasound-guided celiac plexus block is another anterior approach in which an endoscope is placed through the upper gastrointestinal tract into the stomach. A needle for injection is then advanced through the posterior wall of the stomach into the preaortic region of the celiac plexus using ultrasound imaging of the aorta and the surrounding structures. [13],[66] Another anterior technique is a chemical splanchnicectomy at the time of an open abdominal surgery. [35],[67],[68],[69] The stomach can be retracted to expose the celiac axis to inject neurolytic solution to either side of the aorta in the retroperitoneal compartment immediately posterior to the lesser omentum. [13]

Radiographic Technique

The use of radiographic guidance to perform the NCPB from a posterior approach continues to be an issue of discussion. [70] The procedure was originally described and performed using anatomical landmarks only. However, the increased availability of radiographic equipment over time has resulted in greater use of radiographic guidance to perform many nerve blocks. Fluoroscopy has been commonly used to assist in the correct placement of needles and for confirming appropriate spread of injected solution to the targeted area. [71] Others have advocated the use of CT imaging for greater accuracy, especially given the possibility of anatomic distortions with tumor spread. [71],[72] A previous meta-analysis evaluating NCPB was unable to conclude that the success of the block or frequency of adverse effects were significantly improved with radiographic guidance, including CT imaging, compared with nonradiographic methods. [36]

EUS-guided Celiac Plexus Neurolysis

EUS involves a high frequency linear array ultrasound probe with an oblique viewing endoscopic instrument, which is inserted through the mouth and into the stomach to obtain a detailed view of the celiac plexus. The route of the needle through the pancreatic lesion is visualized under EUS real time guidance. A biopsy of a pancreatic primary lesion for diagnostic and staging purposes is usually performed along-with. The patient is placed in a left lateral decubitus position under deep sedation and under direct endoscopic view, the linear EUS instrument is introduced into the stomach until it reaches the lesser curve in the sub-cardiac area [Figure 6]. The probe is then lightly pressed against the gastric wall to obtain a good view of surrounding structures. The ganglia are seen as discrete hypo echoic structures with hyper echoic focus or strands. The aorta is identified and confirmed using color Doppler. A 22 gauge cutting needle with a removable inner sheet occluding a single hole at the needle tip is used and two injections of alcohol at both sides of the celiac trunk are performed. Alternatively, a 20 gauge needle with a penetrating tip closed and with lateral holes may be used. The lateral holes help with a radial diffusion of alcohol to both sides of the celiac trunk.
Figure 6: Picture of an endoscopic ultrasound (EUS)-guided celiac plexus block showing the linear array probe inside the stomach, the needle, celiac plexus, and the aorta

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In a prospective randomized controlled trial by Gress and colleagues in 1999 in 22 patients comparing EUS and CT-guided celiac plexus block for managing chronic pancreatitis pain, EUS-guided celiac plexus block provided more persistent pain relief than CT-guided block. [73] In another randomized trial comparing fluoroscopy-guided percutaneous technique versus EUS-guided celiac plexus block for treatment of pain in chronic pancreatitis, EUS-guided celiac plexus block appeared to be better than percutaneous fluoroscopy-guided for controlling abdominal pain. [74] In 2006, Levy et al., reported endoscopic NCPB to be a safe alternative [75] and at least as effective as the percutaneous approach with fewer potential side effects. To further evaluate the efficacy of EUS CPB, 5 relevant studies with 119 patients with pancreatic cancer were identified between 1966 and 2007 and EUS-guided celiac plexus block was effective in alleviating abdominal pain in 72.54% of these patients, thus making it a reasonable option for patients with pancreatic cancer, especially with tolerance to narcotic analgesics. [76]

NCPB may be extended to regions containing the celiac, superior, and inferior mesenteric arteries, and such broad plexus neurolysis may provide more superior pain relief then celiac plexus block. [77],[78]

  Celiac Plexus Block Complications and Adverse Effects Top

NCPB is a relatively safe procedure. However, there are theoretical concerns and mild clinical effects that may be associated with this procedure. [79] Its potential risks and benefits should be considered in the context of a suffering cancer patient with a typically poor prognosis.

Most commonly reported adverse events include local pain (96%), hypotension (10%), and diarrhea (44%). [36] NCPB causes splanchnic sympathectomy and the resulting vasodilation of the splanchnic vasculature can result in orthostatic hypotension in some individuals. The diarrhea results from a relatively unopposed parasympathetic vagal efferent effect of bowel hyper mobility in the splanchnic regions as a result of neurolysis of the sympathetic celiac and splanchnic nerves. Also, enteric sympathetic nervous system denervation results in impairment of alpha adrenergic stimulation to the enterocytes and increased intestinal secretions. The diarrhea typically occurs within hours of the procedure, is transient and resolves spontaneously. Chronic diarrhea is rarely described. [80] Despite this, most patients compensate well with these fluid shifts. [4]

Neurolytic complications are the most worrisome concerns associated with NCPB. Although uncommon, these potential long-term neurological deficits may include sensory or motor deficits of the trunk and lower extremities, loss of bladder and/or bowel control, and impotence in males. In a case series of 2730 NCPBs, major complications were limited to 4 cases of neurological deficit (<0.2%) ranging from loss of anal or bladder control to paraplegia. [81] The mechanisms of these complications may include spread of injected solution into the intrathecal or epidural spaces, or involvement of the thoracic and lumbar nerve roots, and injury or spasm of the feeding arteries of the spinal cord. [82] The neurological complications may be less common with anterior approach, but is reported to cause retroperitoneal abscess formation. [83] Other nonneurological serious adverse effects may include pneumothorax, shoulder, chest and pleuritic pain, hematuria, and the reported incidence of all serious adverse events is approximately 2%. [36] Some rare complications may include silent gastric perforation, [84] superior mesenteric venous thrombosis, [85] anterior spinal artery syndrome, aortic dissection, and pseudoaneurysm.

The American Society of Gastrointestinal Endoscopy (ASGE) guidelines in 2005 revealed that the perforation rate associate with EUS approach was around 0.03%. [86] The risk of infection ranges from 0% to 8%, that of fever ranges from 0.4% to 1% and risk of pancreatitis from 0% to 2%, with severe hemorrhage infrequently reported.

  Systemic Analgesic Therapy Top

The AHCPR recommends the World Health Organization (WHO) analgesic ladder as an effective and validated approach in the pharmacologic treatment of cancer pain. [28] This simple method uses a stepwise approach, based on the severity of pain, beginning with nonopioid analgesics progressing to opioids for moderate pain, and then to opioids for severe pain, according to individual need. [28],[87],[88] These analgesics are prescribed on a time-scheduled basis with additional doses as needed.

Pain management with opioid medications may be acceptable for many patients, but may have certain disadvantages. In a study evaluating the use of the WHO analgesic ladder in cancer patients, the most frequent side effects were dry mouth (on 39% of the days of follow-up), drowsiness (38%), constipation (35%), and nausea and vomiting (22%). The lack of any significant opioid-related side effects was noted in only 24% of the days of follow-up. [3]

A more comprehensive pain management guideline was introduced by the National Comprehensive Cancer Network (NCCN) in 2007 that divided the systemic target therapy to those patients who are opioid naïve, opioid tolerant, and those requiring ongoing care. Other neoadjuvant medications such as corticosteroids, anticonvulsants, and bisphosphonates have also been emphasized upon, particularly in patients with borderline resectable disease.

  Conclusion Top

Achieving the highest quality of life throughout the course of disease is one of the most important goals in the management of patients with pancreatic cancer. However, optimal quality of life cannot be achieved without effective palliation of pain. The two mainstay pain control therapies-systemic analgesic therapy and NCPB-should not necessarily be considered mutually exclusive in the effort to provide effective pain control in pancreatic cancer. Instead, a combination of both these therapies may provide the most effective pain control in these patients. At present, the majority of current data supports the use of NCPB and in comparison to standard pharmacotherapy, it has been shown to be more effective in reducing pain and leads to decreased opioid requirements and thus their related side effects, and thus preventing deterioration in quality of life in such patients.

  References Top

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