Amitabh Gulati

Pain in Cancer Survivors

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

Complementary Therapies and Integrative Medicine in Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND Physicians are often asked about complementary therapies by patients with cancer, and data show that the interest in and use of these therapies among patients with cancer is common. Therefore, it is important to assess the current evidence base on the benefits and risks of complementary therapies (modalities not historically used in modern Western medicine). METHODS A systematic literature review was carried out and recommendations were made according to the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines development methodology. RESULTS A large number of randomized controlled trials, systematic reviews, and meta-analyses, as well as a number of prospective cohort studies, met the predetermined inclusion criteria. These trials addressed many different issues pertaining to patients with lung cancer, such as symptoms of anxiety, mood disturbance, pain, quality of life, and treatment-related side effects. The available data cover a variety of interventions, including acupuncture, nutrition, mind-body therapies, exercise, and massage. The body of evidence supports a series of recommendations. An evidenced-based approach to modern cancer care should integrate complementary therapies with standard cancer therapies such as surgery, radiation, chemotherapy, and best supportive care measures. CONCLUSIONS Several complementary therapy modalities can be helpful in improving the overall care of patients with lung cancer.

Intrathecal pain pump infusions for intractable cancer pain: an algorithm for dosing without a neuraxial trial.

BACKGROUND:Patients with pain from advanced cancer often have limited life expectancy. Undergoing an epidural trial for placement of an intrathecal pump in these selected patients can exhaust limited days of life. We sought to analyze historical data at our cancer center to develop an algorithm to predict initial intrathecal pump dosing based on the starting preimplant systemic opioid regimen, thus averting an epidural trial and minimizing hospital stay. METHODS:We used data pre- and postpump from 46 cancer patients receiving systemic opioids undergoing intrathecal pump placement in the last 6 years, all of whom had undergone an epidural trial before pump placement. RESULTS:By analyzing intrathecal opioid dosage on discharge (in IV morphine equivalents) to age, type of pain, cancer type, preimplant opioid dose, and preimplant pain score using multiple regression, we created an algorithm that predicts, for cancer patients, an appropriate initial dose for an intrathecal pump based on the prepump systemic opioid dose, thus avoiding an epidural trial. The predicted value does have a broad 95% prediction interval (−122.7% to 147.6%) pointing to the value of a trial when feasible. CONCLUSIONS:When an epidural trial is not feasible and an intrathecal pump is required in a cancer patient, it is possible to predict an initial dose for the intrathecal pump based on the systemic opioid usage. This minimizes delays in achieving satisfactory analgesia and discharge to home.

A Retrospective Review and Treatment Paradigm of Interventional Therapies for Patients Suffering from Intractable Thoracic Chest Wall Pain in the Oncologic Population

INTRODUCTION Tumors invading the chest wall and pleura are often incurable, and treatment is targeted toward palliation of symptoms and control of pain. When patients develop tolerance or side effects to systemic opioid therapy, interventional techniques can better optimize a patients pain. We performed a retrospective review of 146 patients from April 2004 to January 2014 who underwent diagnostic and therapeutic procedures for pain relief. Using four patients as a paradigm for neurolytic approaches to pain relief, we present a therapeutic algorithm for treating patients with intractable thoracic chest wall pain in the oncologic population. MATERIAL AND METHODS For each patient, we describe the use of intercostal/paravertebral nerve blocks and neurolysis, pulsed radiofrequency ablation (PRFA) of the thoracic nerve roots, or intrathecal pump placement to successfully treat the patients chest wall pain. Analysis of 146 patient charts is also performed to assess effectiveness of therapy. RESULTS Seventy-nine percent of patients undergoing an intercostal nerve diagnostic blockade (with local anesthetic and steroid) stated that they had improved pain relief with 22% having prolonged pain relief (average of 21.5 days). Only 32% of successful diagnostic blockade patients elected to proceed to neurolysis, with a 62% success rate. Seven patients elected to proceed to intrathecal drug delivery. DISCUSSION Intercostal nerve diagnostic blockade with local anesthetic and steroid may lead to prolonged pain relief in this population. Furthermore, depending on tumor location, we have developed a paradigm for the treatment of thoracic chest wall pain in the oncologic population.

Novel use of noninvasive high-intensity focused ultrasonography for intercostal nerve neurolysis in a swine model.

Background High-intensity focused ultrasound (HIFU) is a noninvasive thermal ablation technique. High-intensity focused ultrasound has been used in small-animal models to lesion neural tissue selectively. This study aimed to evaluate the efficacy of HIFU in a large-animal model for ablation of nerves similar in size to human nerves. Methods Twelve acute magnetic resonance–guided HIFU ablation lesions were created in intercostal nerves in a swine model. In a second pig, as a control, 4 radiofrequency ablation and 4 alcohol lesions were performed on intercostal nerves under ultrasound guidance. Preprocedural and postprocedural magnetic resonance imaging was then performed to evaluate radiologically the lesion size created by HIFU. Animals were euthanized 1 hour postprocedure, and necropsy was performed to collect tissue samples for histopathologic analysis. Results On gross and histological examination of the intercostal nerve, acute HIFU nerve lesions showed evidence of well-demarcated, acute, focally extensive thermal necrosis. Four intercostal nerves ablated with HIFU were sent for histopathologic analysis, with 2 of 4 lesions showing pathologic damage to the intercostal nerve. Similar results were shown with radiofrequency ablation technique, whereas the intercostal nerves appeared histologically intact with alcohol ablation. Conclusions High-intensity focused ultrasound may be used as a noninvasive neurolytic technique in swine. High-intensity focused ultrasound may have potential as a neuroablation technique for patients with chronic and cancer pain.

Ultrasound-Guided Serratus Plane Block for Treatment of Postmastectomy Pain Syndromes in Breast Cancer Patients: A Case Series.

Postmastectomy pain syndrome is common after surgical treatment for breast cancer and may be challenging to manage. Currently, there are a wide variety of approaches to treat this type of pain, including medications, physical therapy, and interventional procedures. However, because of the complexity of innervation of the breast, the serratus plane block may better target the web of nerves innervating the anterior chest wall including the breast. We present a case series of 8 patients who were successfully treated with serratus plane block for pain after treatment for breast cancer. We feel that this particular application for the serratus plane block deserves further investigation, as it is relatively easy to perform and has good clinical utility for this type of pain.

The use of transcutaneous electrical nerve stimulation (TENS) in a major cancer center for the treatment of severe cancer-related pain and associated disability.

BACKGROUND Cancer pain is difficult to treat, often requiring a multimodal approach. While medication management remains the mainstay for the treatment of cancer pain, medications are often associated with undesired side effects. Transcutaneous electrical nerve stimulation (TENS) provides a potential adjunctive method for treating cancer pain with minimal side effects. OBJECTIVE Few studies have been performed evaluating the efficacy of TENS on cancer pain. We sought to examine the usefulness of TENS on all cancer patients and to specifically look at the use of TENS as a goal-directed therapy to improve functionality. DESIGN Retrospective cohort study. METHODS Since 2008, patients with chronic cancer pain and on multimodal pain regimens were trialed with TENS. Those patients who showed an improvement in pain symptoms or severity were educated about and provided with a TENS unit for use at home. Pain symptoms and scores were monitored with the visual analog scale (VAS), the numerical rating pain (NRP) scale, and Short-Form McGill Questionnaire at the start of TENS treatment and at 2 months follow-up. RESULTS TENS proved beneficial in 69.7% of patients over the course of 2 months. In TENS responsive patients, VAS scores decreased by 9.8 on a 0-100 mm scale (P < 0.001), and NRP scores decreased by 0.8 on a 1-10 scale (P < 0.001). LIMITATIONS Lack of placebo and lack of blinding of physician and patient. CONCLUSIONS TENS provides a beneficial adjunct for the treatment of cancer pain, especially when utilized as a goal-directed therapy.

Considerations for Evaluating the Use of Intrathecal Drug Delivery in the Oncologic Patient

While the majority of cancer pain patients are successfully managed with conservative medical management, some patients may suffer from intractable pain or intolerable side effects. The implantation of an intrathecal drug delivery system offers many advantages to improve both analgesia and side effect profile. Practitioners may decide to proceed toward implantation after appropriate patient selection, and, when applicable, a suitable trial for the device. Once implantation is completed, multiple medication combinations may be used to optimize the therapeutic benefit of the device. We describe a stepwise paradigm to implement an intrathecal drug delivery program in the cancer pain population.

A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice

Objective: To investigate the efficacy of N-methyl-D-aspartate receptor (NMDAR) antagonists for neuropathic pain (NeuP) and review literature to determine if specific pharmacologic agents provide adequate NeuP relief. Methods: Literature was reviewed on PubMed using a variety of key words for 8 NMDAR antagonists. These key words include: “Ketamine and Neuropathy,” “Ketamine and Neuropathic Pain,” “Methadone and Neuropathy,” “Methadone and Neuropathic Pain,” “Memantine and Neuropathic pain,” “Memantine and Neuropathy,” “Amantadine and Neuropathic Pain,” “Amantadine and Neuropathy,” “Dextromethorphan and Neuropathic Pain,” “Dextromethorphan and Neuropathy,” “Carbamazepine and Neuropathic Pain,” “Carbamazepine and Neuropathy,” “Valproic Acid and Neuropathy,” “Valproic Acid and Neuropathic Pain,” “Phenytoin and Neuropathy,” and “Phenytoin and Neuropathic Pain.” With the results, the papers were reviewed using the PRISMA (Preferred Reporting in Systematic and Meta-Analyses) guideline. Results: A total of 58 randomized controlled trials were reviewed among 8 pharmacologic agents, which are organized by date and alphabetical order. Of the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 positive trials, while amantadine and memantine each only had 2 trials showing NeuP analgesic properties. Dextromethorphan and valproic acid both had 4 randomized controlled trials that showed some NeuP treatment benefit while carbamazepine had over 8 trials showing efficacy. Finally, phenytoin only had 1 trial that showed clinical response in treatment. Conclusions: There are a variety of NMDAR antagonist agents that should be considered for treatment of NeuP. Nevertheless, continued and further investigation of the 8 pharmacologic agents is needed to continue to evaluate their efficacy for treatment of NeuP.

MRI-guided focused ultrasound ablation of lumbar medial branch nerve: Feasibility and safety study in a swine model

Abstract Purpose: About 10–40% of chronic low back pain cases involve facet joints, which are commonly treated with lumbar medial branch (MB) radiofrequency neurotomy. Magnetic resonance imaging-guided focused ultrasound (MRgFUS), a non-invasive, non-ionising ablation modality used to treat tumours, neuropathic pain and painful bone metastasis can also be used to disrupt nerve conduction. This work’s purpose was to study the feasibility and safety of direct MRgFUS ablation of the lumbar MB nerve in acute and subacute swine models. Materials and methods: In vivo MRgFUS ablation was performed in six swine (three acute and three subacute) using a clinical MRgFUS system and a 3-T MRI scanner combination. Behavioural assessment was performed, and imaging and histology were used to assess the treatment. Results and conclusions: Histological analysis of the in vivo studies confirmed thermal necrosis of the MB nerve could be achieved without damaging the spinal cord or adjacent nerve roots. MRgFUS did not cause changes in the animals’ behaviour or ambulation.