Management Of Pain In Pancreatic Cancer Research Articles

P-296 Pain management in pancreatic cancer

P-296 Pain management in pancreatic cancer

The combined analgesic effect of pregabalin and morphine in the treatment of pancreatic cancer pain, a retrospective study.

BackgroundPregabalin is commonly used to relieve neuropathic pain. However, data are lacking on its efficacy for the treatment of chronic cancer pain. The purpose of this study was to determine the analgesic efficacy of pregabalin combined with morphine in the management of pancreatic cancer pain.MethodsThis study reviewed patients who were prescribed morphine and 150 mg/d pregabalin between 1 January 2017 and 10 November 2018 in our institute. The primary outcomes of this study were the average pain score and dose of morphine. Secondary outcomes included characters of breakthrough cancer pain, functional interference related to pain, anxiety/depression status, and incidence of treatment‐related adverse events during the study.ResultsA total of 240 patients with pain related to pancreatic cancer were included in the study. The results showed that patients of both combination therapy group (pregabalin+morphine) and monotherapy group (morphine) achieved similar analgesic efficacy, demonstrated by NRS (2.4 ± 0.9 vs. 2.6 ± 0.9; combination vs. monotherapy) at the end of the study. Mean daily dose of morphine used in the combination group was significant lower compared to monotherapy group (39.5 ± 16.0 mg vs. 61.5 ± 19.3 mg, net difference 23.5, 95% CI: 18.4–28.6, p < 0.001). The change of functional interference score related to pain was significantly different between combination and monotherapy group (12.0 ± 0.4 vs. 9.8 ± 4.9; net difference, 2.3; 95% CI: 1.1–3.3; p < 0.001). Patients in combination therapy group had experienced shorter duration of breakthrough cancer pain than those in monotherapy group (X2 p < 0.001, Cramer's V:0.36). The incidence of somnolence, dizziness, and cognitive dysfunction were significantly higher in the combination group compared to monotherapy group. No serious treatment‐related side effects were observed.ConclusionsThe findings of this study supported the use of pregabalin with morphine to relieve pain in patients of pancreatic cancer.

The quality of pain management in pancreatic cancer: A prospective multi-center study

Background/objectivesPancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce. MethodsThis is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression. Results139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23–9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05–6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09–9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05–0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05–0.89, p = 0.034) was associated with less undertreatment. ConclusionsThe results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.

Invasive treatment of pain associated with pancreatic cancer on different levels of WHO analgesic ladder.

BackgroundPancreatic cancer is a malignant neoplasm with a high mortality rate, often associated with a delayed diagnosis, the early occurrence of metastasis and an overall, poor response to chemotherapy and radiotherapy. Pain management in pancreatic cancer consists mainly of pharmacological treatment according to the WHO analgesic ladder. Surgical treatment for pain relief, such as splanchnicectomy, is considered amongst the final step of pain management. It has been proven that splanchnicectomy is a safe procedure with a small percentage of complications, nevertheless, it is often used as a last resort, which can significantly decrease its effectiveness. Performance of thoracoscopic splanchnicectomy along the first step of the analgesic ladder may lead to long-lasting protection against the presence and severity of pain.Methods/DesignA prospective, open label, 1:1 randomized, controlled trial, conducted at a single institution to determine the effectiveness of invasive treatment of pain via splanchnicectomy, in patients with advanced pancreatic cancer. The size of tested group will consist of 26 participants in each arm of the trial, to evaluate the level of pain relief and its impact on quality of life. To evaluate the influence on patients’ rate of overall survival, a sample size of 105 patients is necessary, in each trial arm. Assessments will not only include the usage of analgesic pharmacotherapy throughout the course of disease, and overall patient survival, but also subjective pain perception at rest, in movement, and after meals (measured by NRS score questionnaire), the patient’s quality of life (measured using the QLQ-C30 and FACIT questionnaires), and any pain-related suffering (measured with the PRISM projection test). The primary endpoint will consist of pain intensity. Questionnaires will be obtained upon the initial visit, the day of surgery, the day after surgery, as well as during long-term follow-up visits, held every two weeks thereafter.DiscussionEarlier implementation of invasive treatment, such as thoracoscopic splanchnicectomy, can provide a higher efficacy of pain management, prevent deterioration in the patient’s quality of life, and lengthen their overall survival.Trial registrationClinicalTrials.gov identifier: NCT02424279. Date of registration January 2, 2015.

Road map for pain management in pancreatic cancer: A review.

Beside its poor prognosis and its late diagnosis, pancreatic cancer remains one of the most painful malignancies. Optimal management of pain in this cancer represents a real challenge for the oncologist whose objective is to ensure a better quality of life to his patients. We aimed in this paper to review all the treatment modalities incriminated in the management of pain in pancreatic cancer going from painkillers, chemotherapy, radiation therapy and interventional techniques to agents under investigation and alternative medicine. Although specific guidelines and recommendations for pain management in pancreatic cancer are still absent, we present all the possible pain treatments, with a progression from medical multimodal treatment to radiotherapy and chemotherapy then interventional techniques in case of resistance. In addition, alternative methods such as acupuncture and hypnosis can be added at any stage and seems to contribute to pain relief.

High-Intensity Focused Ultrasound: Current Status for Image-Guided Therapy

Image-guided high-intensity focused ultrasound (HIFU) is an innovative therapeutic technology, permitting extracorporeal or endocavitary delivery of targeted thermal ablation while minimizing injury to the surrounding structures. While ultrasound-guided HIFU was the original image-guided system, MR-guided HIFU has many inherent advantages, including superior depiction of anatomic detail and superb real-time thermometry during thermoablation sessions, and it has recently demonstrated promising results in the treatment of both benign and malignant tumors. HIFU has been employed in the management of prostate cancer, hepatocellular carcinoma, uterine leiomyomas, and breast tumors, and has been associated with success in limited studies for palliative pain management in pancreatic cancer and bone tumors. Nonthermal HIFU bioeffects, including immune system modulation and targeted drug/gene therapy, are currently being explored in the preclinical realm, with an emphasis on leveraging these therapeutic effects in the care of the oncology patient. Although still in its early stages, the wide spectrum of therapeutic capabilities of HIFU offers great potential in the field of image-guided oncologic therapy.

Endoscopic management of pain in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and one of the leading causes of cancer mortality in the United States. Due to its aggressive behavior and lack of effective therapies, palliation plays a critical role in the management of the disease. Most patients with pancreatic cancer suffer from severe pain, which adversely predicts prognosis and significantly impacts the quality of life. Therefore pain management plays a central role in palliation. Non-steroidal anti-inflammatory drugs and opioid agents are often first line medications in pain management, but they do not target the underlying pathophysiology of pain and their use is limited by adverse effects and dependence. The proposed mechanisms of pain development in pancreatic cancer include neurogenic inflammation and ductal hypertension which may be targeted by endoscopic therapies. Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and pancreatic duct stent placement are the two primary endoscopic modalities for palliative management in pancreatic cancer patients with refractory pain. Other endoscopic treatments such as biliary stent placement and enteral stent placement for biliary and duodenal obstruction may also help palliate pain in addition to their role in decompression. This article reviews the existing evidence for these endoscopic interventions for pain management in pancreatic cancer.

The role of Endoscopic Ultrasound (EUS) in the management of patients with pancreatic cancer: now bigger than ever.

In this issue of the Journal of Gastrointestinal Oncology De Angelis et al. provide a comprehensive review of the role of endoscopic ultrasound (EUS) in the management of pancreatic cancer. At present the two main established roles of EUS are imaging and tissue acquisition. In addition some EUS-guided therapieshave gained limited but expanding role in pancreatic cancer patients. As correctly pointed by the authors, the role of standard EUS imaging for diagnosis and staging has decreased with the advent of dynamic contrast enhanced multi-detector row computed tomography (MDCT). Nevertheless, contrary to the prevailing perceptions both EUS and MDCT are operator dependent and significant variability of image quality and interpretations exist with MDCT. Furthermore, EUS remains superior imaging modality to detect small pancreatic lesions, mural nodules within a cyst, small lymph nodes and coexisting biliary pathology. We concur with the authors that inmost patients EUS and MDCT should be considered complimentary rather than competing imaging modalities for the evaluation of patients with suspected pancreatic lesions with MDCT been the initial test in most patients. Anotable exception is the screening of populations at high risk for pancreatic cancer where the recent International Cancer of the Pancreas Screening (CAPS) Consortium summit endorsed EUS as the initial test of choice (1,2). EUS is also preferably used for serial surveillance of premalignant pancreatic lesions [e.g., Intraductal papillary mucinous neoplasm (IPMN)] without the radiation exposure associated with MDCT (3). The addition of contrast-enhanced EUS and elastography may expand the utility of EUS imaging for solid pancreatic masses but their role is yet to be determined (4,5). Furthermore, early data on EUS-guided needle based confocal laser endomicroscopy (nCLE) have shown promising results in the evaluation of pancreatic cysts (6,7). On the contrary, EUS with fine needle aspiration (EUS-FNA) has refused to share the scene with other sampling modalities and has become the preferred method for tissue acquisition in patients with pancreatic lesions. EUS may not be necessary in all pancreatic cancer cases but pretreatment pathological diagnosis is essential in most patients with both resectable and advanced disease. Recently the role of EUS sampling has expanded further with the introduction of a new needle with core trap that can provide histologic samples also refereed as fine needle biopsy (EUS-FNB) (8). This is an exciting development because EUS-FNB can facilitate accurate tissue diagnosis in situations where FNA cytology has been known to be inadequate (e.g., autoimmune pancreatitis, lymphoma) but also can provide assessment for tumor vascular and lymphatic invasion. Furthermore, in the forceable future treatment decisions and patient prognosis most likely will be based on molecular markers and EUS appears to be the ideal tool to gather adequate tissue for analysis (9). EUS has also has expanded its role in selected patients with pancreatic cancer as a valuable therapeutic tool. At present, EUS-guided fiducial placement is now routinely done to facilitate image guided radiation therapy (10), EUS-guided celiac plexus neurolysis can greatly facilitate the management of pancreatic cancer pain (11), and EUS-guided biliary drainage is a viable alternative to percutaneous drainage in patient that had failed endoscopic retrograde cholangiopancreatography (ERCP) or in patients with altered gastric anatomy (12). Importantly, in the future EUS most likely will play an important role in delivering novel local antitumor therapy. Ethanol ablation for selected small mucinous cyst has shown promising results and EUS fine needle injection (EUS-FNI) of various viral and biologic therapies has undergone preliminary evaluation (13). In conclusion, despitestiff competition from other imaging modalities standard EUS imaging remains a valuable tool. Contrast-enhanced EUS, EUS elastography and needle based confocal endomicroscopy may further expand the utility of EUS imaging but their exact role is yet to be determined. EUS-FNA is currently the preferred modality for tissue acquisition in patients with pancreatic lesions and the advent of FNB may further solidify this essential role. The therapeutic role of EUS has expanded and ranges from primary in the case of fiducial deployment to fall back strategy in the case of EUS-guided biliary drainage. In the forceable future, EUS-FNI most likely will play a central role for delivery of novel targeted antitumor medications but for now its role is limited to palliative celiac plexus neurolysis.

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

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.

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.

EUS-guided celiac plexus neurolysis vs. block: assessing interference with pancreatic surgery and adhesions in a pig survival model

Background/Purpose: Celiac plexus neurolysis (CPN) is used for pain management in pancreatic cancer. It involves the injection of alcohol to destroy the celiac neural structures, aimed at achieving longer-lasting analgesia than a steroid/anesthetic block alone (CPB). However, one concern in chronic pancreatitis is that subsequent surgery may prove difficult due to adhesions. The aim of the study was to determine the degree of interference and the adhesion burden from CPN vs. CPB in a blinded pig survival model.

Increasing the Efficacy of a Celiac Plexus Block in Patients with Severe Pancreatic Cancer Pain

The purpose of this study was to evaluate the technical possibilities of placing a catheter near the celiac plexus for performance of a celiac plexus block, and to study the efficacy of repeated neurolytic celiac plexus blocks with alcohol in patients with advanced pancreatic cancer pain resistant to opioid treatment. In 12 patients, a neurolytic celiac plexus block with alcohol, administered via an indwelling celiac catheter, was performed. To evaluate the efficacy, visual analog scale scores were recorded every day. Quality of life scores were registered before and 4 weeks following the procedure. Alterations in opioid consumption, and the time between the diagnosis of pancreatic cancer and the performance of the block, were registered. All patients were followed until they died. Two patients remained without pain after the first neurolytic celiac plexus block. In all other patients a second block was administered which provided only temporary relief. Additional intermittent administration of bupivacaine through the catheter was necessary to provide adequate pain relief in these patients. Quality of life increased significantly during the treatment. Opioid consumption decreased significantly in all patients. Our study indicates that a neurolytic celiac plexus blockade with alcohol results in a significant but short-lasting analgesic effect. The use of a celiac catheter improves the long-term management of pancreatic cancer pain.

Has the analgesic efficacy of neurolytic celiac plexus block been demonstrated in pancreatic cancer pain?

Cancer of the pancreas is rising in incidence and will strike 27,000 Americans this year. There is no curative therapy for most patients, so palliation of symptoms should be the prime concern. Severe pain is very common, and often difficult to treat. Neurolytic celiac plexus block (NCPB) is claimed by some to be the most effective way to treat pancreatic cancer pain (PCP), yet only a minority of patients undergo this procedure. We have reviewed the literature on NCPB to determine if it has been adequately evaluated in the management of PCP. There have been 15 published series since 1964 on NCPB for PCP. A total of 480 patients with cancer of the pancreas were reported; at least a satisfactory response to NCPB was reported in 418 (87%). We found major deficiencies in these reports. None described the pre-NCPB analgesic history. Post-NCPB data were also limited. No information was given concerning post-NCPB analgesic dosages, and only 4 series stated that most patients did not require opiates. Information on whether NCPB was effective until death was lacking or incomplete in 12 series. Many claimed additional benefits of NCPB such as decreased nausea, decreased constipation, and increased appetite, but none provided any data to support these claims. We conclude that the data available on NCPB for PCP are insufficient to judge for efficacy, long-term morbidity, or cost effectiveness, and rigorous evaluation of the technique is required.

Pain syndromes and pharmacologic management of pancreatic cancer pain

Patients with carcinoma of the pancreas present with a variety of pain symptoms that can be divided arbitrarily into a series of acute and chronic pain syndromes. Clarification of the specific pain syndrome is important to provide appropriate palliative care to such patients, the majority of whom present with advanced disease.’ At the time of diagnosis less than 10% of patients have tumors confined to the pancreas. Forty percent have locally advanced tumors involving lymph nodes and peripancreatic tissues, and more than 50% have visceral metastatic disease. The most frequent metastatic sites include regional lymph nodes, liver, peritoneum, and abdominal viscera.2 At the time of presentation, the type of pain and its pattern of symptoms are closely associated with the site of tumor within the pancreas. For example, tumor in the head of the pancreas produces biliary obstruction, “a painless jaundice,” with subsequent duodenal obstruction. Seventy-two percent of patients with tumor in the head of the pancreas will have pain, in contrast to 87% of patients with tumor occuring in the body or tail of the pancreas. s In the latter group, studies have suggested that pain occurs late in the course of the disease and results from gastric and retroperitoneal invasion. Metastases to the liver, to the peritoneum with resultant ascites, to the retroperitoneal nodes, to vascular structures and to the epidural space are the major sites of involvement for the development of intractable pain in this disorder. The dearth of literature that carefully details the variety of pain symptoms occurring in this patient population reflects what has been the general approach to such patients-one of lumping all pain symptoms as one “pain,” with