Pancreatic Cancer Pain Research Articles

Tu1517 A Prospective Controlled Study on the EUS-CPN Bilateral Injection of 30 CC of Alcohol in Patients With Pancreatic Cancer Pain

A Prospective Controlled Study on the EUS-CPN Bilateral Injection of 30 CC of Alcohol in Patients With Pancreatic Cancer Pain Jose C. Ardengh*, Rafael Kemp, Eder R. Lima, Cristina G. Bertani, Gustavo A. Mota, Jose Sebastiao S. Dos Santos Anatomy and Surgery, Hosp. Clin. Fac. Med. Ribeirao Preto Universidade de Sao Paulo, Sao Paulo, Brazil; Endoscopy and Echoendoscopy, Hospital 9 de Julho, Sao Paulo, Brazil; Surgery, Hospital Federal dos Servidores do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Introduction: Celiac plexus neurolysis (CPN) is currently used as a treatment option for morphine (resistant patients). The technique of alcohol injection during EUS-CPN for pancreatic cancer pain has not yet been standardized. The one or two injections, bilateral, or central techniques and drug combinations has been discussed. The aim of this study is to demonstrate the safety and efficacy of bilateral injection of absolute alcohol (30 cc) in patients with uncontrollable pain related to pancreatic cancer. Patients and methods: Patients who had a confirmed diagnosis and staging of unresectable pancreatic cancer, after surgery, EUS-FNA, US-FNA or CT-FNA became eligible for this study. We selected those with uncontrollable pain (score 9) and morphine-resistant. All patients received 30 cc of absolute alcohol using a 19G needle (15 cc per side), and were assessed by a questionnaire for pain intensity (0-no pain, 2-mild, 4-tolerable, 6-moderate, 8-severe, 9-incapacitating) before and 30, 60 and 90 days after EUS CPN. Results: Between January 2006 and January 2011, 208 patients became eligible. Seventy-eight were studied and controlled (mean age 63.8y, range 37-84y). EUSFNA-CPN at the same time was performed in 44 and EUS-CPN in 34 patients. The average size of tumors identified by EUS was 3.8 cm (1.5 6.2 cm). Immediately after the procedure, 25/78 (32%) had pain relief, lowering the score from 9 to 4 (10) and 6 (15). After 30 days evaluation revealed that 61/78 (78%) had pain score improved to 2 (7), 4 (32) and 6 (22), while after 60 and 90 days, pain relief occurred in 33/78 (42.3%) and 37/65 (57%). In this interval 13/78 (16.6%) died. There were mild complications (20.5%) after the procedure, all managed by conventional measures (severe diarrhea (6), postural hypotension (5), reversible (3) and irreversible (2) lower limb edema). The mean follow-up after EUS-CPN was 8.6 months (1-18 months). There was no effect on quality of life or survival. Conclusion: EUS-CPN reduces pain and can moderate morphine consumption in patients with pain related to inoperable pancreatic cancer. EUSCPN can be performed in all patients with pancreatic mass, during EUS for diagnosis and staging.

Tu1545 A Prospective Feasibility Study on EUS Guided Broad Plexus in Combination of Celiac Ganglion Neurolysis in Pancreatic Cancer Pain

case. Staging based on clinical information and EGD alone was compared to the staging provided by EGD with EUS. A kappa statistic was used to assess interobserver agreement. Results: Two EUS-trained endoscopists who did not perform the original case correctly provided a T-stage in 11/16 and 12/16 cases with EGD alone compared that provided by EGD with EUS. The thoracic surgeon and gastroenterologist not trained in EUS correctly provided a T-stage grade in 9/16 and 8/16 cases, respectively. When we adjusted for the need for neoadjuvant therapy based on T stage only (T1 or T2 versus T3 or T4), gastroenterologists trained in EUS correctly staged the cancer in 13/16 (2 over-staged, 1 under-staged) and 12/16 (3 over-staged, 1 under-staged) cases, respectively. The thoracic surgeon and noninterventional gastroenterologist correctly staged the cancer in 9/16 (2 over-staged, 5 under-staged) and 12/16 (4 under-staged) respectively. The kappa statistic was 0.42 for T1-2 versus T3-4 for all observers and 0.76 for T1-2 versus T3-4 in EUS-trained endoscopists. Conclusions: In physicians with training in EUS, EGD alone allows accurate T-staging of esophageal malignancies in approximately 75% of cases when compared to EGD with EUS. Physicians trained in EUS tend to over-stage lesions on EGD; thus, possibly leading to recommendations of unnecessary neoadjuvant therapy. The kappa statistics demonstrated substantial interobserver agreement among endoscopists trained in EUS and moderate interobserver agreement for all evaluators. In summary, EGD alone cannot replace EGD with EUS for staging of esophageal cancer.

Overexpression of the B-type Eph and ephrin genes correlates with progression and pain in human pancreatic cancer.

B-type erythropoietin-producing hepatocellular (EphB) receptors and their ephrin ligands are associated with aggressive behavior and poor prognosis in a number of malignancies. The aim of this study was to determine the association between the aberrant expression of these genes and prognosis in human pancreatic cancer. The expression of EphB and the ephrin ligands was determined using real-time quantitative reverse transcription PCR in 46 human primary pancreatic cancers. Overexpression of EphB2 and a more modest overexpression of ephrin-B2 mRNA were observed in more than 44% (20/46) of the pancreatic cancer specimens examined. Overexpression (>upper quartile) of EphB2 and ephrin-B2 was markedly associated with abdominal and/or back pain. Multivariate analysis identified the overexpression of EphB2 as an independent prognostic factor for disease-free and overall survival (both P<0.05). The results of the present study suggest that an increased level of ephrin-B2, in the presence of a high expression of EphB2, leads to a more aggressive tumor phenotype and that EphB2 may be used as a prognostic factor in human pancreatic cancer.

The Efficacy and Safety of Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis for Treatment of Pain in Patients with Pancreatic Cancer

Introduction. Celiac plexus neurolysis is used in pain management of patients with advanced and unresectable pancreatic cancer. We retrospectively analyzed efficacy and safety of endoscopic ultrasound- (EUS-) guided celiac plexus neurolysis in patients treated in our unit. Methods. Twenty nine subjects with unresectable pancreatic cancer and severe pain despite pharmacological treatment underwent EUS-guided celiac plexus neurolysis with 98% ethanol. Patients scored their pain according to a 0–10 point scale and were interviewed 1-2 weeks and 2-3 months after the procedure. Results. Twenty five (86%) patients reported improvement in their pain at 1-2 weeks following the procedure. Of these, 7 (24%) reported substantial improvement (decrease in pain by more than 50%) and 4 (14%) complete disappearance of pain. Pain relief was still present in 76% of patients after 2-3 months. Treatment-related side effects included hypotonia in 1 patient, severe pain immediately postprocedure in 2 patients, and short episodes of diarrhea in 3 patients. Conclusion. Endoscopic ultrasound- (EUS-) guided celiac plexus neurolysis is a safe and effective treatment of severe pain from advanced pancreatic cancer.

Perineural invasion and associated pain in pancreatic cancer

Perineural invasion (PNI) is a prominent characteristic of pancreatic cancer. PNI is a process whereby cancer cells invade the surrounding nerves, thus providing an alternative route for metastatic spread and pain generation. PNI is thought to be an indicator of aggressive tumour behaviour and has been shown to correlate with poor prognosis of patients with pancreatic cancer. Recent studies demonstrated that some signalling molecules and pathways that are involved in PNI are also involved in pain generation. Targeting these signalling pathways has shown some promise in alleviating pain and reducing PNI, which could potentially improve treatment outcomes for patients with pancreatic cancer.

Randomized, Double-Blind, Controlled Trial of Early Endoscopic Ultrasound–Guided Celiac Plexus Neurolysis to Prevent Pain Progression in Patients With Newly Diagnosed, Painful, Inoperable Pancreatic Cancer

Celiac plexus neurolysis (CPN) is currently used as salvage therapy for morphine-resistant pancreatic cancer pain. Endoscopic ultrasound-guided CPN (EUS-CPN) can be performed early, at the time of EUS. We hypothesized that early EUS-CPN would reduce pain and morphine consumption, increase quality of life (QOL), and prolong survival. Patients were eligible if referred for EUS for suspected pancreatic cancer with related pain. If EUS and EUS-guided fine-needle aspiration cytology confirmed inoperable adenocarcinoma, patients were randomly assigned to early EUS-CPN or conventional pain management. Pain scores (7-point Likert scale), morphine equivalent consumption, and QOL scores (Digestive Disease Questionnaire-15) were assessed at 1 and 3 months. Five hundred eighty eligible patients were seen between April 2006 and December 2008. Ninety-six patients were randomly assigned (48 patients per study arm). Pain relief was greater in the EUS-CPN group at 1 month and significantly greater at 3 months (difference in mean percent change in pain score = -28.9 [95% CI, -67.0 to 2.8], P = .09, and -60.7 [95% CI, -86.6 to -25.5], P = .01, respectively). Morphine consumption was similar in both groups at 1 month (difference in mean change in morphine consumption = -1.0 [95% CI, -47.7 to 49.2], P = .99), but tended toward lower consumption at 3 months in the neurolysis group (difference in mean change in morphine consumption = -49.5 [95% CI, -127.5 to 7.0], P = .10). There was no effect on QOL or survival. Early EUS-CPN reduces pain and may moderate morphine consumption in patients with painful, inoperable pancreatic adenocarcinoma. EUS-CPN can be considered in all such patients at the time of diagnostic and staging EUS.

Celiac plexus block for pancreatic cancer pain in adults

Pancreatic cancer causes severe pain in 50 to 70% of patients and is often difficult to treat. Celiac plexus block (CPB) is thought to be a safe and effective technique for reducing the severity of pain. To determine the efficacy and safety of celiac plexus neurolysis in reducing pancreatic cancer pain, and to identify adverse effects and differences in efficacy between the different techniques. We searched Cochrane CENTRAL, MEDLINE, GATEWAY and EMBASE from 1990 to December 2010. Randomised controlled trials (RCTs) of CPB by the percutaneous approach or endoscopic ultrasonography (EUS)-guided neurolysis in adults with pancreatic cancer at any stage, with a minimum of four weeks follow-up. We recorded details of study design, participants, disease, setting, outcome assessors, pain intensity (visual analogue scale (VAS)) and methods of calculation. The search identified 102 potentially eligible studies. Judged from the information in the title and abstract six of these concerning the percutaneous block, involving 358 participants, fulfilled the inclusion criteria and were included in the review. All were RCTs in which the participants were followed for at least four weeks.We excluded studies published only as abstracts.We identified one RCT comparing EUS-guided or computed tomography (CT) -guided CPB but its aim was to assess efficacy in controlling chronic abdominal pain associated with chronic pancreatitis rather than pancreatic cancer, so it was excluded.For pain (VAS) at four weeks the mean difference was -0.42 in favour of CPB (95% confidence interval (CI) -0.70 to - 0.13, P = 0.004, fixed-effect model). At eight weeks the mean difference was -0.44 (95% CI -0.89 to - 0.01, random-effects model). At eight weeks there was significant heterogeneity (I(2) = 89%).Opioid consumption was significantly lower in the CPB group than the control group (P < 0.00001). Although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that CPB causes fewer adverse effects than opioids is important for patients. Further studies and RCTs are recommended to demonstrate the potential efficacy of a less invasive technique under EUS guidance.

Morphine Versus Oxycodone in Pancreatic Cancer Pain: A Randomized Controlled Study

Morphine Versus Oxycodone in Pancreatic Cancer Pain: A Randomized Controlled Study

Placebo response to interventional pain procedures and effect on patient outcome

Considerable debate exists over the effectiveness of numerous procedures performed in current interventional pain practice. Our goal was to review all current prospective, randomized, placebo-controlled trials pertaining to the most commonly performed interventional pain procedures and to present these results in the form of a comprehensive review article. A review of the literature was performed with extensive PubMed searches and no date restrictions. A review of various reference sections within articles was also done. All prospective, randomized, placebo-controlled trials acquired that pertained to the most commonly performed intervention pain medicine techniques were included in the review. Lumbar and transforaminal epidural steroid injections appear superior to placebo. Radiofrequency denervation and steroid injections for sacroiliac joint pain appear superior to placebo. Radiofrequency denervation for lumbar and cervical facetogenic pain appears superior to placebo. Intradiscal electrothermal therapy for discogenic low back pain may be more effective than placebo in a select group of patients. Alcohol neurolytic celiac plexus block appears superior to placebo in the treatment of pancreatic cancer pain. Current data do not support superiority over placebo for lumbar facet joint steroid injections, lumbar intradiscal steroid therapy, or vertebroplasty for treatment of osteoporotic fractures. A continued lack of prospective, randomized, placebo-controlled trials pertaining to interventional pain medicine still persists. The above results can only serve as a guide in current practice, as only tentative conclusions can be reached based on the current data.

Pain management in pancreatic cancer.

A majority of pancreatic cancer patients present with pain at the time of diagnosis. Pain management can be challenging in light of the aggressive nature of this cancer. Apart from conventional pharmacotherapy, timely treatment with neurolytic celiac plexus block (NCPB) has been shown to be of benefit. NCPB has demonstrated efficacious pain control in high quality studies with analgesic effects lasting one to two months. NCPB has also shown to decrease the requirements of narcotics, and thus decrease opioid related side effects. Another option for the control of moderate to severe pain is intrathecal therapy (IT). Delivery of analgesic medications intrathecally allows for lower dosages of medications and thus reduced toxicity. Both of the above mentioned interventional procedures have been shown to have low complication rates, and be safe and effective. Ultimately, comprehensive pancreatic cancer pain management necessitates understanding of pain mechanisms and delivery of sequential validated therapeutic interventions within a multidisciplinary patient care model.

Neurolysis for Pancreatic Cancer Pain: Same Song, Different Verse?

Since Kappis first performed percutaneous neurolysis in 1914, investigators have employed innumerable technical variations in an effort to enhance the efficacy. Similar efforts have been underway by endosonographers since Wiersema performed the first endoscopic ultrasound (EUS)-guided celiac plexus neurolysis in 1996. Although such efforts are important, the availability of multiple procedural options is indicative of the controversy and lack of meaningful progress. If one particular method was clearly superior, the other techniques would have become obsolete. Sakamoto et al. present a new method of EUS-guided neurolysis in an attempt to improve the outcomes. Although their data are promising, we eagerly await rigorously designed studies that may validate their findings.

Morphine Versus Oxycodone in Pancreatic Cancer Pain

According to experimental findings, oxycodone (OX) could have some advantages over morphine (MO) in clinical models of visceral pain. It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain. Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study. Patients were randomized to receive 30 mg/d of sustained release oral MO or sustained release oral OX (20 mg/d). Opioid doses were increased according to the clinical needs. Daily doses of opioids, pain and symptom intensity were recorded at admission (T0) and at weekly intervals for the subsequent 4 weeks (T1, T2, T3, and T4), with an extension at 8 weeks (T8). Opioid escalation index (OEI) as percentage (OEI %) and in mg (OEI mg) was calculated. Nineteen and 20 patients in groups OX and MO, respectively, were followed for the entire period of study (T4). No differences between groups were found in age (P=0.400), Karnofsky (P=0.667), or escalation indexes at T4 and T8 (OEImg, P=0.945 and OEI %, P=0.295). No statistical differences in pain and symptoms intensity between the groups were observed. OX and MO provided similar analgesia and adverse effects with similar escalating doses in patients with pancreatic cancer pain, resembling observations reported in the general cancer pain population. The experimental hypothesis that OX would be superior to MO in the clinical model of pancreatic cancer pain was not confirmed.

M1449: A Prospective Double Blind Randomized Controlled Trial of EUS Guided Celiac Neurolysis vs Sham for Pancreatic Cancer Pain

M1449: A Prospective Double Blind Randomized Controlled Trial of EUS Guided Celiac Neurolysis vs Sham for Pancreatic Cancer Pain

Endoscopic ultrasound-guided celiac plexus neurolysis

Endoscopic celiac plexus neurolysis (CPN) has become the procedure of choice for the management of patients with pancreatic cancer and abdominal pain unresponsive to medical treatment. It is necessary to differentiate between CPN and endoscopic celiac plexus block performed in patients with benign disease. In this review we describe the technique of this procedure with special emphasis on technical details.

Gene therapy for pancreatitis pain

Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replication defective Herpes (HSV-1, DPE) viral vector construct encoding the human preproenkephalin gene (HSV-Enk), used as a molecular therapy for alleviation of pancreatitis pain, is reviewed here. The characteristics of the gene therapy treatment for inflammation and pain-related behavior in two alcoholic pancreatitis animal models is described. Significant analgesia and protection of pancreatic tissue was provided for the duration of the transgene expression (approximately 4-6 weeks). These studies establish a basis for use of HSV-based gene therapy for chronic visceral pain. Targeted enkephalin gene therapy approaches are providing clear promise for pain control. As innovative means of significantly reducing pancreatic inflammation and preserving tissue architecture, they may extend their clinical usefulness for pancreatitis and pancreatic cancer pain patients.

EUS-Guided Celiac Plexus Neurolysis for Pain due to Chronic Pancreatitis or Pancreatic Cancer Pain: A Meta-Analysis and Systematic Review

The objective of this study was to evaluate the efficacy of EUS-guided CPN for pain relief in patients with chronic pancreatitis and pancreatic cancer. An initial search identified 1,439 reference articles, of which 130 relevant articles were selected and reviewed. Data was extracted from 8 studies (N = 283) for EUS-guided CPN for pain due to pancreatic cancer and nine studies for chronic pancreatitis (N = 376) which met the inclusion criteria. With EUS-guided CPN, the pooled proportion of patients with pancreatic cancer that showed pain relief was 80.12% (95% CI = 74.47-85.22). In patients with pain due to chronic pancreatitis, EUS-guided CPN provided pain relief in 59.45% (95% CI = 54.51-64.30). In conclusion, EUS-guided CPN offers a safe alternative technique for pain relief in patients with chronic pancreatitis or pancreatic cancer. In patients with pain due to chronic pancreatitis, better techniques or injected materials are needed to improve the response.

Repeated neurolytic celiac plexus block for pancreatic cancer pain: case report

Repeated neurolytic celiac plexus block for pancreatic cancer pain: case report

Pain Management

Both pancreatitis and pancreatic cancer patients suffer from severe pain. For the pancreatitis patient, pain is often the stimulus for going to the doctor to receive diagnosis. This pain originates from increased pressure in the pancreatic duct due to the inflammation and scarring associated with pancreatitis and/or inflammation of pancreatic nerves, since this organ is richly supplied with nerves and chronic inflammation in the area may also lead to the release of various substances that stimulate these nerves. In patients with unresectable pancreatic cancer, severe abdominal and back pain is a significant complication due to the spread of the disease to nerves in the surrounding area or pressure on nearby organs.

The significance of cancer pain in pancreatic cancer

15590 Background: Pancreatic cancer patients often have cancer pains. Although the therapeutic plans for pancreatic cancer are mainly based on imaging studies (CT, MRI, US, and ERCP) and performance status (PS), the presence of tumor cancer is usually not considered. In this study, we analyzed the significance of cancer pain in pancreatic cancer. Methods: The subjects were pancreatic cancer patients (UICC stage II - IV) who received medical treatments between Mar 2001 and Feb 2007 in our hospital. We divided these patients into two groups (no cancer pain, cancer pain (taking opioids or NSAIDs). We compared the presence of cancer pain with the overall survival by UICC stages and treatments using the log-rank test. Results: We examined 217 patients (stage II: 41, stage III: 47, stage IV: 129). The treatments were operation (44), chemotherapy (159), or supportive care (14). The status of cancer pain before treatment was as follows (nothing: 114, opioids: 75, NSAIDs: 24). Concerning UICC stages, the cancer pain group had significantly poor prognosis only at stage IV (p=0.001). Concerning treatments, the patients who received chemotherapy (p=0.002) or operation (p=0.04) in the cancer pain group had poor prognosis. Conclusions: The presence of cancer pain may correlate with the prognosis of pancreatic cancer. Especially on determining the indication of operation, we should consider the presence of cancer pain besides the imaging studies and PS. No significant financial relationships to disclose.

The Role of Neurolytic Celiac Plexus Block in the Treatment of Pancreatic Cancer Pain

Pancreatic carcinoma, an important leading cause of cancer death, has increased steadily in incidence and still has a poor prognosis. Pain is one of the most frequent symptoms, affecting more than 75% of patients. It is often present in the early stages of disease and may be severe and difficult to treat. Abdominal viscera, including pancreas, liver, gallbladder, adrenal, kidney, and the gastrointestinal tract from the level of the gastroesophageal junction to the splenic flexure of the colon are innervated, at least in part, via the celiac plexus. Thus, painful tumors in these viscera may have pain relieved through the use of a neurolytic celiac plexus block (NCPB). Although some investigators questioned the role and the efficacy of NCPB in the treatment of upper abdominal cancer pain, most of them have suggested that it may represent the optimal treatment, especially for pancreatic cancer pain. In this report we have reviewed the techniques, results, and complications of NCPB for the treatment of pancreatic cancer pain.