A nationwide neurosurgical inter-disciplinary service for cancer-related refractory pain.

PURPOSE: Neurosurgical ablative procedures, such as cordotomy and cingulotomy, are often considered irreversible and destructive but can provide an effective and individualized solution for cancer-related refractory pain, when all other approaches have been unsuccessful. This paper provides an in-depth exploration of a novel approach to managing refractory cancer pain. It involves an interdisciplinary team led by a neurosurgeon at a renowned national referral center. METHODS: a retrospective analysis of the medical records of all sequential patients who underwent their initial evaluation at our interdisciplinary refractory cancer pain clinic from February 2017 to January 2023. RESULTS: A total of 207 patients were examined in the clinic for a first visit during the study period. All patients were referred to the clinic due to severe pain that was deemed refractory by the referring physician. The mean age was 61 ± 12.3 years, with no significant sex difference (P = 0.58). The mean ECOG Performance Status score was 2.35. Conservative measures had not yet been exhausted in 28 patients (14%) and 9 patients were well controlled (4%). Neurosurgical ablative procedures were recommended for 151 (73%) of the patients. Sixty-six patients (32%) eventually underwent the procedure. 91 patients (44%) received a negative recommendation for surgery. Thirty-five patients (17%) were referred for further invasive procedures at the pain clinic. CONCLUSION: An Interdisciplinary cooperation between palliative care specialists, pain specialists, and neurosurgeons ensures optimal patient selection and provides safe and effective neurosurgery for the treatment of refractory cancer-related pain.

Attitudes of Patients with Advanced Chronic Illnesses Toward Palliative Extubation in a Country Where It Is Illegal.

Background: Palliative extubation (PE) is the cessation of mechanical ventilation (MV) during terminal illness. Although PE is widely practiced in many countries, it remains illegal in others. Attitudes toward PE of patients at the highest risk for MV were scarcely explored before. Objective: To assess the attitudes of patients with advanced chronic illnesses (ACI) toward PE and other end-of-life decisions in a country where PE is illegal. Design: A prospective observational study using questionnaire-based interviews. Setting/Subjects: Patients with ACI hospitalized between 2021 and 2022 in a large tertiary center. Attitudes toward PE and mechanical ventilation were evaluated. Predictors for favoring/opposing PE were analyzed using multivariate logistical regression models. Results: A total of 152 (40% female, 75 ± 11 years) patients were included. The most common ACIs were advanced heart failure (32%), metastatic malignancy (32%), and chronic obstructive pulmonary disease (22%). Around 132 patients (87%) supported the legalization of PE, and their main reason was to avoid pain and suffering (87%). Legalization of PE would change the decision to avoid mechanical intubation in 34% of the cases. Most patients thought that the decision to perform PE should be made by the patient's physician and primary caregiver collaboratively (64%). Religious observance was an independent predictor for opposing PE (adjusted odds ratio 0.18; 95% confidence interval 0.06-0.59; p < 0.01), whereas the type of ACI was not. Conclusion: Most admitted patients with ACIs support the legalization of PE. Such policy change could have major impact on patients' end-of-life preferences. At-risk patients should be the focus of future studies in this area.

Optimization of Radiofrequency Needle Placement in Percutaneous Cordotomy Using Electromyography in the Deeply Sedated Patient.

BACKGROUND AND OBJECTIVES: Cordotomy, the selective disconnection of the nociceptive fibers in the spinothalamic tract, is used to provide pain palliation to oncological patients suffering from intractable cancer-related pain. Cordotomies are commonly performed using a cervical (C1-2) percutaneous approach under imaging guidance and require patients' cooperation to functionally localize the spinothalamic tract. This can be challenging in patients suffering from extreme pain. It has recently been demonstrated that intraoperative neurophysiology monitoring by electromyography may aid in safe lesion positioning. The aim of this study was to evaluate the role of compound muscle action potential (CMAP) in deeply sedated patients undergoing percutaneous cervical cordotomy (PCC). METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy while deeply sedated between January 2019 and November 2022 in 2 academic centers. The operative report, neuromonitoring logs, and clinical medical records were evaluated. RESULTS: Eleven patients underwent PCC under deep sedation. In all patients, the final motor assessment prior to ablation was done using the electrophysiological criterion alone. The median threshold for evoking CMAP activity at the lesion site was 0.9 V ranging between 0.5 and 1.5 V (average 1 V ± 0.34 V SD). An immediate, substantial decrease in pain was observed in 9 patients. The median pain scores (Numeric Rating Scale) decreased from 10 preoperatively (range 8-10) to a median 0 (range 0-10) immediately after surgery. None of our patients developed motor deficits. CONCLUSION: CMAP-guided PCC may be feasible in deeply sedated patients without added risk to postoperative motor function. This technique should be considered in a group of patients who are not able to undergo awake PCC.

Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity.

Human pain is a salient stimulus composed of two main components: a sensory/somatic component, carrying peripheral nociceptive sensation via the spinothalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the CNS's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spinothalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intracranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway or indirectly influenced by interfering with the ascending spinothalamic tract.

[NOT ONLY FOR CANCER PATIENTS - PALLIATIVE CARE FOR NON-ONCOLOGIC PATIENTS AT THE END OF LIFE IN A GERIATRIC - INTERNAL MEDICINE DEPARTMENT].

AIMS: This article presents our ongoing experience in the care of palliative patients suffering from non-oncologic diseases. BACKGROUND: Palliative care is an approach intended to improve quality of life in patients facing life-threatening illness. This approach entails early identification, thorough assessment and treatment of pain and suffering as well as establishing a goals-directed care plan in order to improve these patients' quality of life. While in oncology patients there is a steady increase in the awareness of the need for palliative care, in non-oncology patients there is a marked deficit regarding identification of patients needing palliative care, determination of goals of care and delivery of palliative care throughout the disease and at the end of life. Furthermore, there is a lack of appropriate platforms to deliver such care. In Israel, the majority of deaths occur in-hospital. Therefore, it makes sense to implement good palliative care platforms in hospitals, in order to meet the need for palliative care. In January 2018, we opened an inpatient palliative care unit within the Geriatric-Internal Medicine Department in the Tel Aviv Sourasky Medical Center. METHODS: This is a retrospective study of all the patients who died in the Geriatric Internal Medicine Department, during the period 1.1.2018-31.7.2020. RESULTS: A total of 2,335 patients were admitted to the ward during the period 1.1.2018-31.7.2020. Within this group, 371 (16%) died during hospitalization, 257 died from oncologic diseases, 8 died unexpectedly and 106 died from non-oncologic diseases. Patients who suffered from non-oncologic diseases were older, with a shorter length of stay (9.6 vs. 10.5 days) and were more likely to be bed-ridden. The most common cause of death was infection (48%), pneumonia being the most prevalent. Most end-of-life decisions were made during hospitalization, with the guidance of the next of kin. CONCLUSIONS: Patients suffering from non-oncologic diseases represent a considerable number of palliative care patients. However, there is a marked deficit in the ability to recognize their palliative needs, prognostication and therefore, identifying the right platform to care for them. We have described such a platform in the Geriatric Internal ward.

Temporal Summation Predicts De Novo Contralateral Pain After Cordotomy in Patients With Refractory Cancer Pain.

BACKGROUND: Percutaneous cervical cordotomy (PCC), which selectively interrupts ascending nociceptive pathways in the spinal cord, can mitigate severe refractory cancer pain. It has an impressive success rate, with most patients emerging pain-free. Aside from the usual complications of neurosurgical procedures, the risks of PCC include development of contralateral pain, which is less understood. OBJECTIVE: To evaluate whether sensory and pain sensitivity, as measured by quantitative sensory testing (QST), are associated with PCC clinical outcomes. METHODS: Fourteen palliative care cancer patients with severe chronic refractory pain limited mainly to one side of the body underwent comprehensive quantitative sensory testing assessment pre-PPC and post-PCC. They were also queried about maximal pain during the 24 h precordotomy (0-10 numerical pain scale). RESULTS: All 14 patients reported reduced pain postcordotomy, with 7 reporting complete resolution. Four patients reported de novo contralateral pain. Reduced sensitivity in sensory and pain thresholds to heat and mechanical stimuli was recorded on the operated side (P = .028). Sensitivity to mechanical pressure increased on the unaffected side (P = .023), whereas other sensory thresholds were unchanged. The presurgical temporal summation values predicted postoperative contralateral pain (r = 0.582, P = .037). CONCLUSION: The development of contralateral pain in patients postcordotomy for cancer pain might be due to central sensitization. Temporal summation could serve as a potential screening tool to identify those who are most likely at risk to develop contralateral pain. Analysis of PCC affords a unique opportunity to investigate how a specific lesion to the nociceptive system affects pain processes.

Tailoring of neurosurgical ablative procedures in the management of refractory cancer pain.

INTRODUCTION: Neurosurgical ablative procedures can offer immediate and effective pain relief for patients suffering from refractory cancer pain. However, choosing the appropriate procedure for each patient may not be straightforward and warrants an interdisciplinary approach. The purpose of the current study was to evaluate the outcome of patients with cancer who were carefully selected for neurosurgical intervention by a dedicated interdisciplinary team composed of a palliative physician and nurse practitioner, a pain specialist and a neurosurgeon. METHODS: A retrospective review was carried out on all patients who underwent neurosurgical ablative procedures in our institute between March 2015 and September 2019. All patients had advanced metastatic cancer with unfavorable prognosis and suffered from intractable oncological pain. Each treatment plan was devised to address the patients' specific pain syndromes. RESULTS: A total of 204 patients were examined by our service during the study period. Sixty-four patients with localized pain and nineteen patients with diffuse pain syndromes were selected for neurosurgical interventions, either targeted disconnection of the spinothalamic tract or stereotactic cingulotomy. Substantial pain relief was reported by both groups immediately (cordotomy: Numerical Rating Scale (NRS) 9 ≥1, p=0.001, cingulotomy: NRS 9 ≥2, p=0.001) and maintained along the next 3-month follow-up visits. CONCLUSIONS: An interdisciplinary collaboration designated to provide neurosurgical ablative procedures among carefully selected patients could culminate in substantial relief of intractable cancer pain. TRIAL REGISTRATION NUMBER: IR0354-17.

"Death is inevitable - a bad death is not" report from an international workshop.

Palliative care is an approach meant to improve the quality of life of patients facing life-threatening illness and to support their families. An international workshop on palliative care took place in Caesarea, Israel under the auspices of the National Institute for Health Policy Research on July 4-5th, 2018, with the goal of discussing challenges to the development and integration of palliative care services in Israel. At the workshop, both national and international figures in the field of palliative care and health policy addressed several issues, including truth telling, religious approaches to end of life care, palliative care in the community, pediatric palliative care, Israel's Dying Patient Act, the Ministry of Health's National Plan for palliative care, and challenges in using advance directives. We summarize the topics addressed, challenges highlighted, and directions for further advancement of palliative care in the future, emphasizing the critical role of the Ministry of Health in providing a framework for development of palliative care.

Neurosurgical ablative procedures for intractable cancer pain.

OBJECTIVECancer patients suffering from severe refractory pain may benefit from targeted ablative neurosurgical procedures aimed to disconnect pain pathways in the spinal cord or the brain. These patients often present with a plethora of medical problems requiring careful consideration before surgical interventions. The authors present their experience at an interdisciplinary clinic aimed to facilitate appropriate patient selection for neurosurgical procedures, and the outcome of these interventions.METHODSThis study was a retrospective review of all patients who underwent neurosurgical interventions for cancer pain in the authors' hospital between March 2015 and April 2018. All patients had advanced metastatic cancer with limited life expectancy and suffered from intractable oncological pain.RESULTSSixty patients underwent surgery during the study period. Forty-three patients with localized pain underwent disconnection of the spinal pain pathways: 34 percutaneous-cervical and 5 open-thoracic cordotomies, 2 stereotactic mesencephalotomies, and 2 midline myelotomies. Thirty-nine of 42 patients (93%) who completed these procedures had excellent immediate postoperative pain relief. At 1 month the improvement was maintained in 30/36 patients (83%) available for follow-up. There was 1 case of hemiparesis.Twenty patients with diffuse pain underwent stereotactic cingulotomy. Nineteen of these patients reported substantial pain relief immediately after the operation. At 1 month good pain relief was maintained in 13/17 patients (76%) available for follow-up, and good pain relief was also found at 3 months in 7/11 patients (64%). There was no major morbidity or mortality.CONCLUSIONSWith careful patient selection and tailoring of the appropriate procedure to the patient's pain syndrome, the authors' experience indicates that neurosurgical procedures are safe and effective in alleviating suffering in patients with intractable cancer pain.

[NEUROSURGICAL INTERVENTIONS FOR INTRACTABLE ONCOLOGICAL PAIN].

INTRODUCTION: Pain is one of the most common symptoms among cancer patients, and particularly in those who suffer from metastatic or terminal disease. There is great importance in delivering good pain management to these patients in order to alleviate their suffering, improve their functional status and their overall quality of life. In most cases, pain management is based on pharmacotherapy with opioids and other medications. However, there are selected patients for whom pharmacotherapy does not achieve acceptable pain relief or is associated with marked side effects. These patients, who suffer from refractory cancer pain, may benefit from neurosurgical procedures selectively intervening in different locations along the pain signaling pathways. This article summarizes several of these neurosurgical procedures: percutaneous cordotomy for unilateral pain, punctuate midline myelotomy for visceral pain and stereotactic cingulotomy for diffuse pain syndromes. This article demonstrates the use of careful patient selection by an interdisciplinary team which is critical for the success of these procedures. The team consists of palliative care specialists, pain specialists and a neurosurgeon. These neurosurgical interventions are presented through representative clinical cases, followed by a discussion of the clinical considerations that guided the choice of the therapeutic approach for each case.

O-Arm-Guided Percutaneous Radiofrequency Cordotomy.

BACKGROUND: Pain is often one of the most debilitating symptoms in patients with advanced oncological disease. Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract. OBJECTIVES: Over the past year, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography imaging. We present our experience using this technique, focusing on technical nuances and complications. METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy between March 2016 and March 2017. RESULTS: Nineteen patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 16 out of 17 completed procedures, we achieved excellent immediate pain relief (94%). At 1 month after operation, 15 of the 17 (88%) patients were pain free, and at 3 months 5 out of 5 patients available for follow-up were still free of their original pain. Mirror pain developed in 6 of the 17 patients (35%), but was mild in 4 of these cases and controlled with medications. We experienced 1 serious complication (6%) of ipsilateral hemiparesis. CONCLUSION: Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.

Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain.

BACKGROUND: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool. METHODS: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain. RESULTS: Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks. CONCLUSIONS: Our initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain.

Improving Palliative Care Team Meetings: Structure, Inclusion, and "Team Care".

Increasing demands on palliative care teams point to the need for continuous improvement to ensure teams are working collaboratively and efficiently. This quality improvement initiative focused on improving interprofessional team meeting efficiency and subsequently patient care. Meeting start and end times improved from a mean of approximately 9 and 6 minutes late in the baseline period, respectively, to a mean of 4.4 minutes late (start time) and ending early in our sustainability phase. Mean team satisfaction improved from 2.4 to 4.5 on a 5-point Likert-type scale. The improvement initiative clarified communication about patients' plans of care, thus positively impacting team members' ability to articulate goals to other professionals, patients, and families. We propose several recommendations in the form of a team meeting "toolkit."

Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study.

OBJECTIVES: To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations. STUDY DESIGN: In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n=161), group 2 other antibiotics (n=213) and group 3 non-teratogens (n=740). RESULTS: A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR=1.41, 95% CI 0.47-4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups. CONCLUSION: Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.