Abdominal and back pain is the most frequent symptom in patients with pancreatic cancer, with pain management being extremely challenging. This study aimed to evaluate pain control, opioid consumption, pain-interfered quality of life, and survival after early and delayed computed tomography (CT)-guided celiac plexus neurolysis (CPN).n = 56) between June 2018 and June 2021 was done. The patients were grouped as early group (n = 22) and delayed group (n = 34) on the basis of the presence of persistent refractory pain according to expert consensus on refractory cancer pain.A retrospective analysis of pancreatic cancer patients receiving CPN for pain (p = 0.141). The pain scores were significantly reduced in both groups; early CPN resulted in significantly lower scores from 3 to 5 months. The opioid consumption gradually decreased to a minimum at 2 weeks but increased at 1 month ; significantly larger consumption from 2 to 4 months was seen in the delayed group. The total pain interference was lower than baseline in all patients, with significant improvement after early CPN in sleep, appetite, enjoyment of life, and mood. The average survival time of the two groups was comparable.Both groups were comparable in demographic characteristics and baseline pain conditions measured using the numeric rating scale (5.77 ± 1.23 vs. 6.27 ± 1.21; Early application of CT-guided CPN for patients with advanced pancreatic cancer may help reduce pain exacerbation and opioids consumption, without influencing the survival. Patients with pancreatic cancer frequently present with abdominal and back pain, with a reported incidence of 75% at the time of diagnosis and approximately 90% in patients with advanced staged cancer . AccordiCeliac plexus neurolysis (CPN) is a well-established verified technique for relieving pain, reducing opioid consumption, and improving cancer symptom burden for patients with abdominal malignancy . NeverthNevertheless, whether early CPN is more beneficial than a delayed procedure in patients with advanced pancreatic cancer remains unclear. Thus, we conducted this retrospective cohort study to evaluate pain control, opioid consumption, pain-related quality of life, and survival in patients with advanced pancreatic cancer undergoing early and delayed CPN.We conducted an observational retrospective cohort analysis of the medical records obtained from a single oncology specialized hospital of patients with advanced pancreatic cancer, who suffered from moderate to severe pain and underwent CPN at the pain management department, from June 2018 to June 2021. All patients signed an informed consent before receiving the interventional procedure. The data collection and publication protocols were regulated by the Institutional Review Board.Pain specialists in our department are responsible for providing comprehensive pain assessment, analgesic, and interventional treatment, as well as health follow-ups for cancer patients. Accordingly, patients experiencing pancreatic cancer pain were initially evaluated for their pain and previous analgesic strategies and then assigned to receive CPN after adequate preoperative optimization. Using a percutaneous antecrural approach under computed tomography (CT) guidance, a total of 6 mL of iohexol (Omnipaque) and lidocaine compounds was injected bilaterally into the target antecrural space. After confirming the spread of the contrast and successful test block, 20 mL of 100% ethanol was injected. The patients were then admitted for 24 h observation; after discharge, they continued to receive analgesic modulation and follow-up in our outpatient clinic.During the follow-up, the nurse specialist evaluated the following items at fixed time intervals —pain score using the numerical rating scale (NRS), frequency of breakthrough pain recorded when happening ≥3 times/day, analgesic consumption converted into morphine equivalent, and pain inferred quality of life measured by the brief pain inventory (BPI). The BPI is used to assess eight items of functioning interfered by pain: general activity, mood, walking ability, normal work, relationship with others, sleep, appetite, and enjoyment of life. Each item is rated from 0 (does not interfere) to 10 (complete interference). The pain scores and analgesics consumption were re-evaluated up to 6 months postoperatively, as the neurolytic effects reportedly remain stable for approximately 3–6 months , 21. HowData satisfying the following criteria was collected: (a) patients aged 18–80 years with advanced pancreatic cancer and received CPN at the pain management department; (b) having upper abdomen and/or middle back pain due to pancreatic cancer; (c) having NRS ≥4 points at baseline; (d) receiving analgesic medication and equivalent oral morphine ≥40 mg per day before procedure, and (e) having no invasion detected in the insertion path. Patients who were given further antitumor therapies or other interventions for pain control were excluded from the study.Patients were divided into the early CPN group—to receive the operation as soon as they fulfilled the criteria at the index visit, or the delayed group—those who underwent a wait-and-see analgesic titration and received CPN only when they developed persistent refractory pain or with intolerable adverse effects. This definition is based on the expert consensus from the Committee of Rehabilitation and Palliative Care of China, which identifies refractory cancer pain based on the following two criteria: (a) persistent pain score ≥4 and/or breakthrough pain ≥3 times/day and (b) unsatisfactory pain relief after at least 2 weeks of standardized medication and/or causes intolerable side effects .t-test. The outcome indicated the necessity of a sample size of 20 patients for each group.Demographic characteristics of all patients including age, gender, tumor classification, staging, course duration, comorbidities, and history of antitumor treatment were extracted from the hospital’s database. Data regarding pain score, adverse reactions, opioid consumption, and BPI pain inference were reviewed through previous follow-up records. Survival time data were obtained through the community health system before data analysis in December 2021.The sample size of the database study is primarily comprehensive, encompassing all the available data. However, a prior sample size calculation was conducted for scientific interpretation, focusing on the NRS scores at 3 months post-operation taking into account a potential dropout rate of 20%. This calculation aimed to provide 80% statistical power for detecting significant treatment differences, with a two-sided type 1 error set at 5% in a two-sample As the primary parameter of interest, we performed a multidimensional assessment of the pain conditions, with respect to location, intensity, and breakthrough times. Subsequently, analgesic changes were analyzed with morphine equivalent conversion. To compare the overall pain interference between early and delayed CPN, a total BPI score (0–80 points) and that for the eight items individually were calculated.t-test was used to compare the mean differences between continuous variables in the case of normally distributed data; otherwise, the Mann–Whitney U test was used for analysis. Breakthrough pain, tumor classification, staging, and complications were presented as frequency and percentages (%), and chi-square (χ2) or Wilcoxon rank-sum tests, as appropriate, were used for comparison between groups. Additionally, Kaplan–Meier survival curves were constructed for patient survival in months and compared using log-rank tests. A p-value of ≤0.05 was considered for statistical significance.We used SPSS version 26.0  to perform all analyses. NRS, BPI scores, and opioid consumption were presented as means with standard deviation. A two-sample n = 21, 37.5%), followed by head adenocarcinoma ; 39 patients were at stage IV (69.6%), and 39 were in a malnutrition condition (69.6%). All patients had received multicourse oncology treatment before CPN. The time gaps between the first visit to receiving CPN were 3.45 (1.65) vs. 35.06 (9.98) days in the early and delayed group. A total of 63 patients with pancreatic cancer underwent CPN between June 2018 and June 2021 at our hospital. Of these, two patients were excluded since they were administered implantable drug delivery systems (IDDS) as a combined pain control solution. Three patients who received hepatic perfusion chemotherapy for metastases after CPN, and two who received iodine-125 seed implantation were also not included in the analysis. The final analysis included data for 56 patients  . The majPatients in both groups reported experiencing moderate to severe pain, with a baseline NRS of 5.77 ± 1.23 and 6.27 ± 1.21, respectively. A significant reduction in NRS scores was observed in both groups after the procedure; however, a trend for a rebound was detected from 1 to 6 months. Nonetheless, those receiving early CPN presented with a lower pain score than the delayed group, and a significant difference was observed from 3 to 5 months . Addition = 12, 54.5% vs. n = 15, 44.1%), hypotension , and diarrhea  . Furthermore, patients in the delayed CPN group showed significantly greater opioid consumption from 2 to 4 months, and the increase in opioids started earlier compared with the early CPN group . Both gr, 29.4%) . Additioχ2 = 2.501, p = 0.114).The interference of pain with daily activities and emotional status was evaluated using BPI. The posttreatment total interference was significantly lower than baseline in all patients, suggesting that the overall health status was improved after CPN. Patients in the early group reported significantly low interference from 1 to 4 months posttreatment . SpecifiThe results of our study demonstrate that early CPN is beneficial in preventing pain progression and opioid consumption, besides improving the overall pain-interfered QoL. Pancreatic cancer is one of the most painful malignancies often associated with delayed diagnosis and the poorest prognosis rendering palliative pain management challenging for the patients . ChemicaAlthough the pain scores were comparable between the two groups from 1 day to 2 months postoperatively, the early group was associated with significantly reduced NRS and the number of breakthrough pain from 3 to 5 months, suggesting a better prognosis with the early procedure. CPN aims to block nociceptive transmission raised from the celiac plexus, which is located anterior to the abdominal aorta and the celiac trunk . AccordiWe observed that both early and delayed groups demonstrated decreased opioids consumption compared with baseline levels. To avert any withdrawal symptoms, the analgesic use was not reduced abruptly after the operation, with the lowest opioids consumption achieved by 2–4 weeks. Subsequently, the ongoing adjustment of opioids was increased in both groups, but the delayed group required an earlier rise and higher requirement. This outcome was not unexpected and was consistent with the pain progression, as well as the analgesic strategy we applied, i.e., sufficient opioids were administrated as required. Since CPN is not an isolated form of palliative pain management but a part of the broader analgesic strategy, opioids remain the mainstay for cancer pain control . NonetheExpectedly, the overall pain interference in QoL exhibited a greater improvement in patients who received early CPN, notably in terms of sleep, appetite, and mood-related interference items. However, early CPN did not produce a prominent improvement in work and walking. It is known that patients with advanced cancer experience improved mood and QoL, require less aggressive end-of-life care, and have longer survival by integrating early supportive care , 37, 38.There were certain limitations of this study. Since it was a retrospective study, our findings are based on limited data collected from baseline to 6 months from a single institution. Additionally, the BPI scores were only available for the first 4 months and patients in the delayed group had a poorer response to prior oncologic therapy and pain control, both of which may have affected the outcome. In terms of grouping, the definition of early and delayed intervention was based on whether CNP was performed from the first visit or after a wait-and-see policy after at least 2 weeks of analgesic titration. However, we believe that a refined grouping method or subgroup analysis which considering tumor staging or time from diagnosis may help determine the overall pain course, but was not available in our database. Nevertheless, our study is the first to show the potential benefits of early application of CPN for pain control in patients with advanced pancreatic cancer, whom have experienced a poor response on moderate dose of opioids.The results of this retrospective cohort study suggest that early application of CT-guided CPN for patients with advanced pancreatic cancer offers multiple potential advantages, including reduced exacerbation of pain, reduced opioids consumption, and improved pain-interfered QoL; nonetheless, it is not associated with improved survival. To investigate the optimal procedure timing in different subgroups, a further large-scale randomized-controlled trial is required.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving humans were approved by Ethics Committee of the Sichuan Cancer Hospital . The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.FL: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. XW: Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing – review & editing. JT: Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing – review & editing. XL: Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.


Incoercible or intractable pain is defined as pain that is refractory to pharmacological treatment to such an extent that opioid and analgesic adverse effects outweigh the therapeutic effects. The anterior cingulate cortex (ACC) is involved in the perception of pain, especially emotional pain, so it is logical that cingulotomy has an effective therapeutic effect. Therefore, we evaluated the effectiveness of cingulotomy for the treatment of incoercible pain. An observational, longitudinal, retrospective, and analytical study was carried out on a series of cases in which bilateral cingulotomy was performed for incoercible pain, and follow-up was performed 6 months after neurosurgery in the outpatient clinic at the Neurotraumatology Clinic. A positive correlation was observed between pain intensity and medication use, indicating that an increase in pain was associated with a greater requirement for analgesics. The result was a significant reduction in pain, as measured by the visual analog scale of pain, and decreased drug use after cingulotomy. We concluded that cingulotomy reduces incoercible pain and the need for medication. Pain is defined as an unpleasant sensory and emotional experience, associated with actual or potential tissue injury according to the International Association for the Study of Pain . Pain caIn a certain way, the usefulness of the above classification consists of pharmacological handling during a specific pain; for example, under severe intensity, major opioids are recommended, or under peripheral nerve damage, an anticonvulsant/antidepressant is preferred. However, it does not say what to do when it does not respond to pharmacological treatment, or which combinations are the most effective; for this, the WHO scale on pain handling is necessary , where iThe effectiveness of cingulotomy is attributed to the cutting of nociceptive fibers from the thalamic nuclei . This efAlthough this technique has been studied for its therapeutic action against pain, it has fallen into disuse since the introduction of deep brain stimulation (DBS), spinal cord neuromodulation, and intrathecal therapy.Modern practices generally reserve cingulotomy as a second- or third-line treatment after non-injury surgery failures; however, cingulotomy should be the treatment of choice in some scenarios: cachexic or malnourished patients who cannot tolerate the implantation of a foreign body, patients with terminal cancer with short life expectancy, and patients who do not want to have or cannot afford deep brain stimulation.It should be noted that ablative techniques offer the advantage of immediate pain relief; they do not require a routine medical examination or device maintenance in comparison to neuromodulative alternatives . For theAn observational, longitudinal, retrospective, and analytical study was carried out on a case series in which bilateral cingulotomy was performed due to incoercible pain. Follow-up was performed 6 months after hospitalization through outpatient clinic consultations at the Neurotraumatology Clinic between 2020 and 2022. All individuals were cared for by a multidisciplinary team comprising neurologists, neurosurgeons, psychiatrists, anesthesiologists, and neuropsychologists. Additionally, all patients were treated with Buprenorphine for pain management . We obseA 24-year-old male patient with a history of drug addiction every 2 days , accompanied with aggressive behavior, was repeatedly sent to rehabilitation centers, had inappropriate laughter attacks, generalized anxiety diagnosed by a psychiatrist after treatment with quetiapine, long-term epilepsy, which was controlled with clonazepam and magnesium valproate, and appendectomy without complications 3 years ago. He had a VAS score of 8/10 for headache, which is why he went in to receive service after being treated with Tramadol 1 tablet every 12 h, paracetamol 500 mg every 8 h, Ketorolac 30 mg every 12 h, and carbamazepine 1 tablet every 12 h. The pain of the headache was classified as chronic, psychogenic, somatic, and irruptive, ameliorated due to drug use, thus categorizing the pain with a poor prognosis, after which the decision was made to intervene by performing bilateral anterior cingulotomy , which wThe second case involved a 72-year-old female patient with no history of DM2 and HTN, with obesity, controlled hyperlipidemia, hypothyroidism treated with levothyroxine, was diagnosed with major depression and obsessive–compulsive disorder treated with psychiatry, and currently has asymptomatic structural epilepsy. She underwent surgical procedures at the C3, C4, and C5 levels (she has no reasoning recollection) and resection of the cavernoma (which left her with incoercible vertigo), has arteriovenous malformation (AVM) that left her with incoercible vertigo sequela, and has pacemakers placed via ventricular fibrillation, the surgical procedures of which had no apparent complications. She was admitted with cervial pain with a VAS score of 9/10, and her mood swings were being treated with vortioxetine, levetiracetam, trevinn, pregabalin, ketoprofen, ketorolac, and tramadol; therefore, it was decided to perform a cingulotomy to manage the pain. The uncomplicated cingulotomy  resultedA 71-year-old female patient had a history of Arnold–Chiari malformation, which was operated on 22 years ago without complications, hernioplasty 10 years ago, cesarean section 35 years ago, with sleep apnea for the last 2 years treated with oxygen at night with CPAP, and occasional marijuana use 1 year ago. She was admitted due to pain starting with VAS 2/10, which quickly increased to a VAS score of 10/10, treated with tramadol + paracetamol  1 tablet every 8 h, sublingual ketorolac 10 mg 1 tablet every 8 h, pregabalin 1 tablet every 24 h, gabapentin 300 mg 1 tablet at night, and magnesium valproate 200 mg 1 tablet every 12 h. However, due to no symptom improvement, it was decided to intervene by performing a cingulotomy , and theA 62-year-old female patient had a history of Systemic Arterial Hypertension (SAH), which was controlled with 1 tablet of losartan and spironolactone every 24 h. She was admitted due to failed back syndrome and cervicalgia from disc hernias (7 vertebroplasty surgeries in 2002) that caused generalized quadriparesis and spondyloarthrosis. She had fibromyalgia with chronic pain, which was sometimes psychogenic and at times nociceptive and persisted despite treatment with acetaminophen 500 mg 1 tablet every 8 h, tramadol 1 tablet every 12 h, celecoxib 200 mg 1 tablet every 8 h, gabapentin 300 mg 1 tablet every 12 h, sublingual buprenorphine , and 1 fentanyl patch every 72 h. As there was no improvement in the clinical profile, it was decided to opt for cingulotomy in order to treat the symptoms. The neurosurgery was carried out without complications , which rA 60-year-old female patient had a history of generalized chronic pain with a VAS score of 10/10 proclivity for the head, a history of tension headache, jaw stiffness, which was treated with rhizolysis, and drug blockade prior to bilateral cingulotomy, which was treated with xummer (etoricoxib) 90 mg 1 capsule every 12 h, ketorolac 10 mg 1 tablet every 12 h, duloxetine 60 mg 1 tablet every 12 h, gabapentine 300 mg 1 tablet every 12 h, zaldiar (tramadol and paracetamol) 1 tablet every 8 h, lamotigrine 100 mg 1 tablet every 12 h, and prednisone 5 mg 1 tablet every 24 h. After the bilateral cingulotomy , only xuA 63-year-old female patient had a history of a VAS score of 10/10 due to mixed polyneuropathy in the legs, smoking, cannabis use, SLE, osteoarthritis, COPD, catheterization due to AMI, and seizures during her intrathecal morphine pump infusion treatment for 6 years. Her surgical history was as follows: 2 “aesthetic” facial reconstruction surgeries at age 32, cross ligament reconstruction at age 28, BTO at age 35, cholecystectomy 15 years ago, cardiac catheterization 6 years ago due to AMI, morphine pump infusion placement in 2003, morphine pump removal in 2019 under cannabis treatment with 2 cigarettes daily (self-medicated), prednisone 5 mg every 12 h, pregabalin 150 mg every 12 h, acemetacin 60 mg 1 tablet every 24 h, losartan 100 mg every 12 h, metoprolol 100 mg every 12 h, carbamazepine 200 mg 2 tablets every 8 h, clonazepam 1 tablet every 12 h, celecoxib 100 mg 1 tablet every 8 h, ketoprofen 100 mg orally every 12 h, ibuprofen 800 mg orally every 8 h, tramadol 100 mg orally every 8 h, amlodipine 5 mg orally every 24 h, senosidos ab 2 tablets every 24 h, omeprazole 20 mg orally every 12 h, magnesium valproate 400 mg orally every 12 h, and indomethacin 25 mg orally every 24 h. After surgery, only morphine infusion  with subUnder the effects of anesthesia, the head frame was first placed and then helical computed tomography and magnetic resonance imaging were taken in order to plan the coordinates, after which trephination was performed, dura mater was coagulated, the cingulum was reached with “inomed” electrodes and radiofrequency lesion , which was performed at 90 s and 90° Celsius, obtaining an impedance of 390–620 ohms; this procedure was performed bilaterally. Three lesion sites were examined bilaterally on two levels (depending on the patient), which were performed in the anterior and posterior targets, as described below.p < 0.05. Statistical analysis was performed using R studio v.4.1.3, and data visualization was carried out using JASP 0.17, both for Mac.Poisson regression tests were used to assess the differences in medication and VAS scores before and after surgical intervention. The category “Pre-intervention surgery” was used as the reference level for each respective model. The results were reported as incidence rate ratios (IRR) with their respective 95% confidence intervals. Overdispersion was not observed in either model. In addition, Spearman’s correlation coefficient was calculated to measure the strength of the association between medication and VAS scores as follows: rho = 0.1–0.2 (poor), 0.3–0.5 (fair), 0.6–0.7 (moderate), and 0.8–0.9 (very strong) ,12. For Six patients took part in this study, and none of them experienced relapses after the cingulotomy surgery .After the intervention, patients scored lower on medication score (IRR = 0.39), indicating a 61% reduction in the probability of medication consumption due to the intervention  Figure .After the intervention, patients scored lower on the VAS score (IRR = 0.18), indicating an 82% reduction in pain perception due to the intervention  Figure .p < 0.05), reflecting a very strong association (rho = 0.83).Spearman’s correlation between medication and VAS score was significant . This is possibly attributed to the fact that the drugs had little or no effectiveness in pain management, and in this scenario, by following their best intentions, previous physicians wanted rapid improvement of the patients. It should be noted that by going to multiple doctors without adequate follow-ups, the patients ended up self-medicating a combination of multiple drugs; two of the patients even self-administered marijuana, and a third patient was immersed in drug addiction .The patients in this study had a 6-month follow-up after cingulotomy, in which they were evaluated to determine the effect of neurosurgery on pain, which coincided with two patients who were also involved in a study by Deng 2019 et al., where the effectiveness of cingulotomy continued to decrease the pain even after 12 months .The main limitation of the study is the sample size for data analysis, as well as the fact that patient follow-up was not continued over time due to the cost and time; however, this does not diminish the effectiveness of cingulotomy in managing incoercible pain.Bilateral cingulotomy decreases incoercible pain, which was measured after 6 months according to the visual analog scale, and likewise, it decreases the need for pain medication along with its adverse effects.


Few Australasian studies have evaluated persistent pain after breast cancer surgery.To evaluate the incidence, impact, and risk factors of moderate to severe persistent pain after breast cancer surgery in a New Zealand cohort.Prospective cohort study were assessed as risk factors using multiple logistic regression.Consented patients were reviewed at 3 timepoints . Pain incidence and interference, psychological distress and upper limb disability were assessed perioperatively. Clinical, demographic, psychological, cancer treatment-related variables, quantitative sensory testing, and patient genotype P < .004). Moderate to severe preoperative pain , COMT rs6269 GA genotype  and psychological distress at postoperative day 14  were identified as risk factors. Total intravenous anesthesia  was identified as protective.Of the 173 patients recruited, 140 completed the 6-month follow-up. Overall, 15.0%  of patients reported moderate to severe persistent pain after breast cancer surgery with 42.9%  reporting likely neuropathic pain. Pain interference, upper limb dysfunction and psychological distress were significantly higher in patients with moderate to severe pain (The incidence of moderate to severe persistent pain after breast cancer surgery is high with associated pain interference, physical disability, and psychological distress. Important modifiable risk factors were identified to reduce this important condition. Furthermore, key risk factors for the development of PPBCS may not only include clinical, demographic, and psychological variables, but may also include inherited factors and preoperative neurophysiology.COMT,GCH1KCNJ6OPRM1ESR1As such, this study had two aims: 1) to prospectively estimate the incidence and impact of moderate to severe PPBCS in a New Zealand cohort; 2) to identify key predictors for moderate to severe PPBCS development through assessment of clinical, demographic, and psychological variables as well as an exploratory, targeted assessment of inherited variation in genes previously associated with PPBCS  in Auckland, New Zealand, between October 15, 2016, and August 15, 2020. New Zealand Health and Disabilities Ethics Committee (16/NTA/55/AM06) granted ethical approval to conduct the study.Eligibility included 1) a diagnosis of breast cancer; 2) undergoing primary breast cancer surgery ; 3) >18 years old; and 4) being able to read and write English. Patients who had previous breast surgery, distant malignancy, or metastases were excluded from the study.Consented patients were assessed at a preoperative clinic (within 14 days before the operation), and at two postoperative clinic appointments (2 weeks and 6 months after surgery). At each time point, patients were assessed for pain  incidence, pain quality and pain interference with activities of daily living, neuropathic pain, upper limb disability and psychological distress. Risk factors for developing PPBCS  were also collected at each time point. QST and blood collection for genetic assessment were performed before surgery. Data collected at each review are shown in All patients received a simplified general anesthetic protocol which was utilized to limit variation in anesthetic practice and improve compliance. Details of this anesthetic protocol are provided in the ,Possible risk factors for developing PPBCS were based on findings from the existing literature2 , living with a partner or living alone, smoking status , highest educational level, and medical history  were collected from the patient and medical record. Patient ethnicity was categorized by self-identified ethnicity as recommended by the New Zealand census. Due to their small sample size, those who belonged to the Māori, Pacific Island, Asian and Other ethnicity categories were pooled into the non-European ethnicity category.Patient ethnicity, age in years , ethnicity, BMI in kg/mThe Short Form Brief Pain Inventory (BPI) and Douleur Neuropathique en 4-interview (DN4-interview) were completed to screen for preoperative pain intensity at any anatomical location, and likely neuropathic pain (DN4 interview ≥3/7), respectively. Pain intensity was categorized according to an 11-point numeric rating scale  of “average pain” from the BPI (question 5), where a score of 0–2/10 was considered no to mild pain, 3–10/10 moderate to severe pain and ≥1/10 any pain. The Depression, anxiety, and stress scale (DASS21) was used to screen for psychological distress.® MassARRAY iPlex platform . Details and protocols of the procedure are published elsewhere.Whole blood (8.5 mL) was collected into PAXgene blood DNA tubes  and stored according to the manufacturer's instructions until required for extraction of genomic DNA (gDNA). The gDNA extraction was performed according to the manufacturer's instructions using the PAXgene Blood DNA Kit . SNP genotyping was performed using the SequenomCOMT), ,OPRM1), (rs1799971 and rs563649),GCH1), ,ESR1), ,KCNJ6), Gene variants encoding catechol-o-methyl transferase enzyme , pressure pain 40 (PP40) and conditioned pain modulation (CPM) were performed , type of breast surgery , surgical management of intercostobrachial nerve (not handled vs handled and not transected versus transected), axillary surgery , primary reconstruction with prostheses, or autologous flap at time of primary breast cancer surgery versus none were recorded.Postoperative factors were collected at 2 time points (2 weeks and 6 months).Pain intensity  in the breast/chest wall, axilla, shoulder or arm on the operative side was collected using the BPI . The DN4-interview was used to screen for likely neuropathic pain at these sites. The DASS21 was used to screen for psychological distress.Data on adjuvant cancer therapies  and repeat surgery at the primary site of surgery  were collected at 6 months after surgery.The primary outcome was the presence of moderate to severe PPBCS, defined as average daily pain with a severity of NRS ≥ 3/10 (BPI question 5) in the ipsilateral breast, axilla, arm, shoulder or chest wall daily ≥6 months after surgery. A duration of ≥6 months was chosen to allow for the completion of adjuvant chemotherapy or radiotherapy and subsequent assessment of these variables as risk factors.Pain intensity was categorized according to an 11-point numeric rating scale of “average pain” from the BPI (question 5), where a score of 0–2/10 at ≥ 6 months after surgery was considered no to mild PPBCS, 3–10/10 moderate to severe PPBCS, and ≥1/10 any PPBCS. The primary outcome for the risk factor analysis was moderate to severe PPBCS in the ipsilateral breast/chest wall, shoulder, axilla, or arm Pain interference with activities of daily living at 6 months after surgery were collected using the BPI (question 9). Details of analgesic medications usage and their effectiveness to treat pain at the time of 6-month BPI completion were also collected (BPI question 7).Pain quality  and intensity ≥ 6 months after surgery were assessed using the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2).The Douleur Neuropathique en 4-interview (DN4-interview) was used to screen for likely neuropathic pain ≥ 6 months after surgery. Patients with a total DN4-interview score of ≥3/7 were considered having likely neuropathic pain.Upper limb disability was assessed using the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) at 6 months after surgery. A difference of 10 points on the total DASH score was considered clinically important.The short version Depression, Anxiety and Stress Scale (DASS21) questionnaire was completed at 6 months after surgery to measure of overall psychological distress.t-tests, one-way ANOVA, Kruskal-Wallis test, or Mann-Whitney U tests were used to examine between-group differences. The χ2 test or Fisher exact test was used to assess categorical variables. Confidence intervals were calculated using the modified Wald method.Depending on data distribution , independent 2 analysis was used for violation of the Hardy-Weinberg equilibrium (HWE). The association between PPBCS and SNP was investigated using four different genetic models . Associations between PPBCS and the COMT haplotypes and diplotypes comprising rs6269, s4633, rs4818 and rs4680, respectively  were also assessed by combining and classifying patients with the GCGG/GCGG and GCGG/ATCA diplotypes as “group 1”; the ATCA/ATCA and GCGG/ACCG diplotypes as “group 2”; and the ACCG/ACCG and ACCG/ATCA as “group 3.”All single-nucleotide polymorphisms (SNPs) were checked for agreement with minor allele frequency (MAF) reported in the literature, and χP values smaller than 0.05 were considered statistically significant. Variables were selected for entry into multiple regression (full) model based on either statistically significant univariate association or previously published associations with PPBCS.,,R2 tests.,Univariate logistic regression was performed to test the influence of variables for moderate to severe PPBCS. Subsequently, the two-stage linear setup procedure of Benjamini, Krieger, and Yekutieli to correct for multiple comparisons was performed.,A sample size of approximately 220 patients was required to estimate the incidence of PPBCS with a confidence limit of 5.5% on each side. Sample size calculation was based on a median prevalence of previous PPBCS estimates of 19.5%,P < .05) and confidence intervals of 95% were used. Statistical analyses were performed using GraphPad Prism 8 for Windows  or IBM SPSS Statistics for Windows, version 25.0 .A significance level of 5%  time from preoperative review to surgery was 7 days (IQR: 4 to 10 days); 88% of patients underwent surgery within 14 days of preoperative review. The median time from surgery to 2-week postoperative assessment was 15 days (IQR: 13 to 17 days), with PPBCS assessment at 6 month follow up a median of 6 months (IQR: 6–7 months). One patient did not present to the 2-week postoperative follow-up but attended the 6-month follow-up. No other data were missing from the 140 patients who completed the 6 month follow up.P = .05) and postoperative adjuvant endocrine therapy . There were no other significant differences between the two groups .Patient demographic and treatment variables were categorized according to PPBCS status (no to mild PPBCS vs moderate to severe PPBCS) and are displayed in Before surgery, 24 (17.1%) patients reported moderate to severe pain daily in any anatomical location. Of these, 15 (62.5%) patients reported pain in the breast, axilla, shoulder, or arm. Of the 24 patients, 12 (50%) developed any PPBCS (NRS ≥1) at these sites ≥ 6 months after surgery, while 9 (37.5%) developed moderate to severe PPBCS (NRS ≥ 3/10) at these sites ≥ 6 months after surgery. At 2 weeks after surgery, 30.7% (n = 43) patients reported moderate to severe pain at these sites. Of these 43 patients, 29 (67.4) developed any PPBCS (NRS ≥1) at these sites ≥ 6 months after surgery, while 11 (25.6%) developed moderate to severe PPBCS (NRS ≥ 3/10) at these sites ≥ 6 months after surgery.Of all patients reporting any pain (NRS ≥1) at these sites before surgery, 27.6% (n = 8/29) patients had likely neuropathic pain before surgery (DN4 ≥ 3/7), this increased to 42.1% (n = 43/102) at 2 weeks after surgery. Of the eight patients with likely neuropathic pain before surgery, seven developed any PPBCS (NRS ≥1) at these sites ≥ 6 months after surgery, with six reporting likely neuropathic pain (DN4 ≥ 3/7) ≥ 6 months after surgery.Overall, 38.5%  patients reported any PPBCS (NRS ≥1) at these sites ≥ 6 months after surgery. Moderate to severe PPBCS (NRS ≥3) at these sites was reported by 15.0% patients  ≥ 6 months after surgery, with a median average BPI pain of 4/10 (IQR: 3–5).Of the 21 patients who reported moderate to severe PPBCS, 13 (61.9%) reported any pain (NRS ≥1) at any anatomical location before surgery, while 9 (42.9%) reported moderate to severe pain (NRS ≥3) at any site. Of the 21 patients who reported moderate to severe PPBCS, approximately 19 (90.5%) reported any pain at these sites at 2 weeks after surgery, while 12 (57.1%) reported moderate to severe pain.P = .02).Overall, 40.7% (n = 22/54) of patients with any PPBCS (NRS ≥1) at these sites ≥ 6 months after surgery reported likely neuropathic pain (DN4 ≥ 3/7). Similarly, likely neuropathic pain was found at a significantly higher proportion in patients who reported moderate to severe PPBCS  compared to those with no to mild PPBCS  ≥ 6 months after surgery  and axilla (71.4%), followed by shoulder (48%). Many patients reported pain at multiple sites (71.4%) .Among patients with moderate to severe PPBCS (NRS ≥3) at these sites ≥ 6 months after surgery (n = 54), the pain was most frequently described as “aching” (85.7%), “tender” (71.4%), “shooting” (71.4%), “sharp” (66.7%), “stabbing” (61.9%), and “tiring-exhausting” (61.9%) on the SF-MPQ-2.P < .001) in patients who reported moderate to severe PPBCS at these sites ≥ 6 months after surgery, compared to those with no-mild PPBCS  at these sites ≥ 6 months after surgery, 38.1% reported using analgesic medications. Few patients in this group (14.3%) reported using multiple analgesics to treat pain with the majority using paracetamol (38.1%), followed by neuropathic pain agents (14.3%), opioids (9.5%), and NSAIDs (9.5%) .P > .37) between preoperative QST  and moderate to severe PPBCS development ≥ 6 months after surgery  from HWE , KCNJ6 (rs2835859) and OPRM1  could not be assessed using the additive model.Due to the low frequency of the homozygous variant genotype, SNP for COMT (rs6269 and rs4818) were found using both the additive  and overdominant genetic models , (P > .05).Statistically significant associations between PPBCS and  < .01), . There wP < .05) on univariate analysis , COMT rs6269 GA genotype  and psychological distress at postoperative day 14 . Propofol total intravenous anesthesia (TIVA) was protective for PPBCS . The overall model fit passed Hosmer and Lemeshow Goodness of Fit test = 9.25, P = .32 and the Nagelkerke R2 value was 0.308 (Identified risk factors for PPBCS include moderate to severe pain (NRS ≥3) at any anatomical site before surgery  greater pain interference, psychological distress  and upper limb disability. Sleep disruption was the most reported item on the pain interference scale of the BPI . In thisOnly 38.1% of patients with moderate to severe PPBCS reported receiving analgesic medications suggesting that patients either did not report their pain or did not seek medical treatment. Most patients received paracetamol as a single agent with only a few receiving multimodal analgesics. Moreover, first-line anti-neuropathic agents such as tricyclic antidepressants or gabapentinoids were rarely utilized, despite the high incidence of postoperative neuropathic pain.We identified moderate to severe preoperative pain (irrespective of the site of that pain), and psychological distress 2 weeks after surgery as two potentially modifiable risk factors for PPBCS. Propofol total intravenous anesthesia was identified as a protective factor for PPBCS.,,,Preoperative and early postoperative pain appear to be important for the development of PPBCS.,To further investigate differences in nociceptive system function that may predispose individuals to developing PPBCS, preoperative QST was undertaken. However, similar to previous studies, there were no associations identified between preoperative QST  and the development of PPBCS.COMT rs4680, previously associated with chronic pain, anxiety, and psychological distress.Negative affective constructs such as general psychological distress, anxiety, depression and pain catastrophizing have long been recognized as preoperative risk factors with a high predictive value for persistent postsurgical pain.COMT rs6269 (GA) and rs4818 (GC) as risk factors for PPBCS. However, only COMT rs6269 was included in the final model due to the complete LD between the two alleles. Interestingly, no patients carrying the rs6269 GG genotype reported PPBCS, supporting previous studies suggesting that the rs6269 G allele is protective for persistent postsurgical pain.COMT promoter region, the non-coding rs6269 SNP, most likely regulates COMT gene expression and subsequently affects both noradrenergic and dopaminergic transmission in the spinal cord and brain stem; both important pathways in the descending inhibition of pain, and implicated in the chronification of pain.,In this study, an exploratory assessment of targeted genetic factors was included in the risk factor analysis. The univariate analysis identified the heterozygous genotypes of Propofol intravenous anesthesia (TIVA) was identified as a potentially protective factor for PPBCS in this study. There is evidence that TIVA may reduce postoperative pain scores and opioid consumption,,This study has limitations. First, the sample size is small, and we did not achieve the target sample size of 220 patients as recruitment was limited by the coronavirus disease 2019 (COVID-19) pandemic. This may have affected the precision of estimated PPBCS incidence. Furthermore, it has caused us to limit our risk factor analysis to variables commonly reported in recent meta-analyses (ignoring others eg, number of preoperative breast biopsiesMoreover, there were statistically significant differences between the groups included and excluded from participating in our study. Patients in the inclusion group were approximately 5 years younger than the excluded group. Previous studies have identified younger age as a risk factor for PPBCS. However, these studies tend to categorize younger age in 10 year decrements,The study also has important strengths. To our knowledge, it is the first to comprehensively evaluate demographic, clinical, neurophysiological, and genetic risk factors for PPBCS with a 6-month follow-up in a New Zealand cohort, which includes Māori and Pacifica peoples.Persistent pain after breast cancer surgery appears to be an important consequence of breast cancer treatment. Strategies to improve outcomes will require accurate risk stratification and active, personalized management throughout the treatment course. The specific, potentially modifiable factors identified in this study may inform future intervention studies.pnad065_Supplementary_DataClick here for additional data file.


P = 0.020). Therefore, incorporating deviations from baseline patient vital signs improved the accuracy of pain visualization using machine learning techniques.Machine learning tools have demonstrated viability in visualizing pain accurately using vital sign data; however, it remains uncertain whether incorporating individual patient baselines could enhance accuracy. This study aimed to investigate improving the accuracy by incorporating deviations from baseline patient vital signs and the concurrence of the predicted artificial intelligence values with the probability of critical care pain observation tool (CPOT) ≥ 3 after fentanyl administration. The study included adult patients in intensive care who underwent multiple pain-related assessments. We employed a random forest model, utilizing arterial pressure, heart rate, respiratory rate, gender, age, and Richmond Agitation–Sedation Scale score as explanatory variables. Pain was measured as the probability of CPOT scores of ≥ 3, and subsequently adjusted based on each patient's baseline. The study included 10,299 patients with 117,190 CPOT assessments. Of these, 3.3% had CPOT scores of ≥ 3. The random forest model demonstrated strong accuracy with an area under the receiver operating characteristic curve of 0.903. Patients treated with fentanyl were grouped based on CPOT score improvement. Those with ≥ 1-h of improvement after fentanyl administration had a significantly lower pain index ( Pain has a wide variety of adverse effects on patients, including psychological stress, sleep disturbances, decreased respiratory function, increased heart rate and blood pressure, arrhythmia, and poor nutritional status that can lead to prolonged hospital stays, increased treatment costs, and poor life outcomes9.Many critically ill patients in the intensive care unit (ICU) experience intense pain regardless of whether they have undergone surgery10 and Critical Care Pain Observation Tool 17. The comprehensive analysis of time-series data conducted by Kobayashi et al.17 allowed three types of machine learning methods to predict pain with high accuracy, with the best random forest method achieving an area under the receiver operating characteristics curve (AUROC) of 0.85 for predicting whether the patient had a CPOT score of ≥ 3. However, individual differences in vital signs  may affect the accuracy of pain prediction in conventional models, thereby reducing the prediction accuracy.Machine learning analysis of vital sign data can overcome the shortcomings of conventional pain assessment methods and predict pain at a given time with extremely high accuracyTherefore, the purpose of this study was to investigate (1) the possibility of improving the prediction accuracy by incorporating deviations from baseline patient vital signs into the prediction model and (2) the concurrence of the predicted artificial intelligence (AI) values with the scores obtained using the CPOT, a conventional objective pain assessment, during analgesic administration.Among the 10,299 eligible patients  before and after bolus administration of fentanyl was visualized  the possibility of improving the prediction accuracy by incorporating deviations from baseline patient vital signs into the prediction model and (2) the concurrence of the predicted AI values with the scores obtained using the CPOT, a conventional objective pain assessment, during analgesic administration. The results showed that (1) pain visualization accuracy corresponded to AUROC 0.902; (2) pain index decreased in tandem only when the CPOT score decreased after a bolus dose of fentanyl.18. The BPS and CPOT have shown the best validity and reliability to date. CPOT, in particular, has been optimized for use in patients with atypical behaviors, such as those with brain injury19. In contrast, neuromuscular blocking agents (NMBAs) are sometimes used in patients with severe breathing problems, such as patients with acute respiratory distress syndrome; however, they chemically paralyze the patient and hinder behavioral assessment20. Therefore, periodic discontinuation of NMBA is recommended21, and alternative pain assessment methods must be used for the duration of its administration. Although vital signs can be used as a guide for the administration of analgesics and sedatives, they are not recommended as an appropriate indicator of pain due to the large variability that occurs when they are used for pain assessment25. However, the AI in this study can predict pain with high accuracy despite the use of vital signs and may be applicable even to patients for whom behavioral indicators are not available. Since vital signs are data that are automatically obtained in many patients in ICUs, it may be possible to assess pain automatically and continuously if this AI can be put to practical use.Pain measurement tools can be divided into self-report tools and behavioral assessment tools. Patients who cannot self-report pain but have observable behaviors must be assessed using behavioral assessment tools26. A method of assessing the pupillary response by applying gentle electrical stimulation to the skin has also been developed; however, it can only be used in patients who are under moderate-to-deep sedation for pain27. The validity of adding new pain to patients for pain assessment is also questionable. The Analgesia Nociception Index (ANI), which indicates pain on a scale of 0 to 100, has been reported to be particularly useful during dressing changes, with a negative predictive value of 90% using a cut-off of 42.5 points. However, the sensitivity and specificity were 61.4% and 77.4%, respectively, and the number of participants was only a few dozen29. The Nociception Level (NOL) is a new multiparameter pain assessment system that, similar to the ANI, can display pain on a scale from 0 to 10030. In addition to HRV, the device combines photoplethysmography pulse wave amplitude, skin conductance, and body temperature. Pilot studies have shown that NOL is associated with NRS and CPOT during endotracheal suctioning and cuff inflation as well as chest tube removal32. However, the number of applicable patients in both studies was limited and further validation must be performed in the future. The pain index validated in this study is a new tool to determine pain using vital signs without HRV. It was modeled on data from approximately 10,000 patients and can be varied in parallel with CPOT with an accuracy better than an AUROC of 0.9.Recent topics in new objective pain assessment methods, such as the present study, include several electrophysiological tools. Pupil monitoring, a method of assessing pain by recording fluctuations in the pupils in relation to the sympathetic-parasympathetic responses, has been reported to give inconsistent results in critically ill patientsThe limitations of this study include its retrospective, single-center design and the possible heterogeneity in general patient background data. In addition, CPOT score was also assessed in patients who were able to communicate to provide continuous pain visualization throughout their ICU stay, and this was used as training data to calculate the scores. The pain index indicates the probability of achieving a CPOT score of ≥ 3. In this situation, there is an immediate risk of accidental tube removal and falls, and the ability to predict these and pain may be useful for patients in ICU. Another problem is that the pain index could not be displayed immediately after ICU admission because the system needs time to establish the baseline as the point at which the patient's condition stabilizes after ICU admission; the pain index is displayed after that point. Furthermore, the fentanyl dose per body weight was not constant in the validation step using the fentanyl bolus dosing data. Lastly, although the pain management protocol was followed, the final dosing decision was made by the charge nurse, and there may have been differences in decision criteria.In conclusion, this study confirmed that incorporating individual patient baseline data into a previously developed pain visualization model improved the accuracy and treatment follow-up. The next step in the practical application of this model is an open-label, prospective, randomized, controlled trial in a multicenter setting.https://www.umin.ac.jp/ctr/index.htm).This retrospective observational study was conducted in a single intensive care unit (ICU) at a single institution in Japan. Ethical approval was obtained from Ethics Committee Tohoku University Graduate School of Medicine (Study No. 2022-1-334). Owing to the retrospective design of the study, the requirement for obtaining written informed consent was waived from Ethics Committee Tohoku University Graduate School of Medicine. All methods used in this study were conducted in accordance with the tenets and regulations of the Declaration of Helsinki. The study design was entered into a database  aged ≥ 20 years with (2) at least five CPOT, RASS, and CAM-ICU assessments and (3) electrocardiography (ECG) and arterial pressure monitoring for at least 30 min were included in the study. Data from the following patients whose vital signs differed significantly from those of the general adult population were excluded: (1) patients who had undergone cardiopulmonary bypass; (2) pregnant patients; (3) patients who had undergone organ transplantation, artificial heart transplantation, extracorporeal membrane oxygenation, and intra-aortic balloon pump surgery; and (4) patients with a do-not-resuscitate order. Data were obtained from the electronic medical records system of the institution . Patient identification information was not collected. In addition, patients admitted to the ICU between April 2019 and April 2022 who had received a bolus dose of fentanyl (25–100 µg) with vital sign data available for each minute were selected to test the treatment response of a dataset not involved in the creation and validation of these machine learning models.The CPOT score was used as the training target of the model to assess the pain level of all eligible patients. The CPOT assessments were performed by ICU nurses every 8 h and when obvious pain was observed. The RASS was used to assess the sedation level. Delirium was assessed using the CAM-ICU scale. The RASS, CAM-ICU, and CPOT assessments were used simultaneously by several nurses to ensure agreement among the data recorded by them. In cases of disagreement, the final decision was made by the intensivist. The patients were treated according to our pain management protocol . In this study, the predicted probability was defined as the pain index. A grid search was performed on the training data, and the hyperparameters that yielded the highest accuracy for each model were selected. In addition, the harmonic means of the sensitivity, specificity, and AUROC were calculated.17, was used in this study. Two other machine learning methods (logistic regression and LightGBM) were also used for supplementary analysis. The characteristics of each machine learning method are shown in Supplementary Table We used a machine learning algorithm to predict pain when the CPOT score was assessed by a healthcare professional. Random forest, which was reported to be the most accurate algorithmThe noise in the vital sign data was removed according to the requirements listed in Supplementary Table Hourly records of patients admitted to the ICU were extracted.Approximately 90% of the hourly data were evaluated for availability and two-tailed linear completion was performed.The hourly data were divided into three chronological orders. Friedman tests were performed to evaluate statistically significant differences among the three age groups. The condition was considered unstable if a significant statistical difference was observed, and the condition was returned to condition (ii) after 20 min.Variability (standard deviation/mean) was calculated to ensure that the condition did not deviate from the threshold values established for each type of vital sign in previous studies. The condition was considered unstable if the threshold was exceeded, and the patient was moved to (ii) after 20 min.The 5-min moving average during this period was used as the baseline.Baselines were obtained for each patient and adjusted as shown below  had only temporary and limited use and were analyzed for periods when these drugs were not administered.Data analysis was performed using JMP v15 . Normally distributed data were reported as mean ± standard deviation, and non-normally distributed data were reported as median and interquartile range. The AUROC was used to compare the accuracy and was classified as low (0.5–0.7), moderate (0.7–0.8), and high (≥ 0.8).Supplementary Information.


There is a lack of consensus in selecting patients who do or do not benefit from surgery when patients present with abdominal pain and gallbladder stones are present. This review aimed to give an overview of results from recent trials and available literature to improve treatment decisions in patients with uncomplicated cholecystolithiasis.First, an overview of different symptom criteria for laparoscopic cholecystectomy in patients with uncomplicated cholecystolithiasis is given, based on national and international guidelines. Second, treatment outcomes  are summarized, with data from three clinical trials. Finally, personal advice for treatment decisions in patients with uncomplicated cholecystolithiasis is provided, based on recent trials, the available literature, and expert opinion.This review describes different guidelines and criteria sets for uncomplicated cholecystolithiasis, provides an overview of outcomes after cholecystectomy, and advises on treatment decisions in patients with abdominal pain and gallbladder stones. After cholecystectomy, biliary colic is resolved in 95 per cent of patients. However, non-specific abdominal pain persists in 40 per cent. Irritable bowel syndrome and functional dyspepsia significantly increase the risk of persistent pain. Age, previous abdominal surgery, baseline pain score on a visual analogue scale, pain characteristics, nausea, and heartburn are part of the SUCCESS criteria, and are associated with clinically relevant pain reduction after gallbladder removal.The surgical community can now give more personalized advice on surgery to improve care for patients with abdominal pain and uncomplicated cholecystolithiasis. The diagnostic evaluation and treatment of patients with abdominal pain and gallstones are subject to change. The present review has shown that the surgical community can improve patient selection for cholecystectomy, and recent research has increased awareness of the negative impact of concomitant abdominal disorders on pain reduction after cholecystectomy. A recent study3 of National Health Service data showed that the total number of cholecystectomies annually increased by 72.2 per cent between 2000 and 2019 (from 39 022 to 67 204). Although the number of laparoscopic cholecystectomies has increased over recent decades5, international guidelines6–8 have provided no reason to broaden the indication for surgery. The 5 per cent increase in the prevalence of gallbladder stones, from 15 to 20 per cent, does not explain the exponential increase in cholecystectomy numbers.Worldwide, laparoscopic cholecystectomy is the most common abdominal surgical procedure, accounting for over 750 000 operations in the USA and approximately 70 000 operations in the UK each year9. The majority of gallbladder stones consist primarily of cholesterol (over 90 per cent), whereas a minority are black (bilirubin) and brown  pigmented stones. Predisposing factors include obesity, female sex, diabetes mellitus, and hypertension, but only one in five develops symptoms1. Symptomatic patients mostly suffer from typical symptoms of biliary colic10–12. Frequent episodes of biliary colic or complicated gallstone disease  are accepted indications for cholecystectomy6–8. However, in most patients, gallstones remain without symptoms and are not the primary cause of abdominal pain. Patients with abdominal pain and uncomplicated symptomatic cholecystolithiasis are confronted with two options: wait and see or laparoscopic cholecystectomy. However, there is lack of consensus regarding selection of those who do or do not benefit from surgery, as 10–40 per cent of patients have persistent abdominal pain after operation6–8. This provides the clinical equipoise to suggest an alternative strategy for better selection of patients for cholecystectomy13–16.In Europe, approximately one-fifth of the population has gallbladder stonesThe present review aimed to provide an overview of different guidelines and criteria sets for uncomplicated cholecystolithiasis; to summarize outcomes after cholecystectomy; and to give personalized advice on treatment decisions in patients with symptomatic cholecystolithiasis.17. Identifying the true aetiology of abdominal pain is the main challenge for several reasons. Most patients with cholecystolithiasis do not develop symptoms1. Only 60 per cent of patients in primary care with abdominal pain and a suspected diagnosis of gallbladder stones appear to have stones confirmed on radiological imaging18. Even with the diagnosis of gallstones, there is no definite correlation with abdominal pain19.In the UK, approximately 2.3 per cent of the primary care population presents with abdominal pain each year20 recently undertook a primary care analysis to explore general practitioner (GP) management of patients with gallstones in order to assess concomitant gastrointestinal diagnoses for pain. This study showed that 360 of 633 included patients with gallstones (57 per cent) were also diagnosed with another gastrointestinal disorder in the years before and after the diagnosis of symptomatic gallstone disease. Recorded International Classification of Primary Care codes were abdominal pain (31 per cent), stomach ache (14 per cent), constipation (11 per cent), and acid-related disease (10 per cent). Medication was prescribed to treat abdominal pain in 95 per cent of patients with gallstones. Most commonly prescribed medications included non-steroidal anti-inflammatory drugs (84 per cent), antacids (80 per cent), and analgesics (61 per cent). The patient characteristics of this cohort consulting a GP were similar to those of patients with gallstones consulting surgeons and gastroenterologists14, with a male : female ratio of 1 : 1.6, and a mean BMI of 30 kg/m2. Figure 1 illustrates the characteristics, diagnostics, and treatment in primary care of patients with cholecystolithiasis.The authors20. After cholecystectomy, more than half of the patients (52 per cent) returned to the GP with persistent abdominal pain. Specifically, if a patient was diagnosed with a concomitant abdominal disorder, their chance of returning to the GP with persistent abdominal pain was significantly increased compared with that of patients without such a diagnosis . This observation is consistent with a study18 in a general practice of 107 patients with gallstones in whom neither biliary colic nor another abdominal complaint was consistently related to gallstones. In the authors’ experience, it is pivotal that a GP manages the expectations of patients with regard to treatment outcomes early in the healthcare trajectory. Once a patient has been referred to a surgeon, implying a relationship between the presence of gallstones and pain, it is hard to convince a patient that a wait-and-see policy is more appropriate.Some 79 per cent of patients with gallstones in primary care are referred to secondary care. Patients were most often referred to the emergency department, surgeon or gastroenterologist . Ultimately, 79 per cent of all referred patients underwent cholecystectomy21. For example, the definition of symptomatic gallstone disease and the indication for cholecystectomy are poorly described. Most guidelines advocate cholecystectomy in patients with symptomatic cholecystolithiasis or biliary colic7. The issue is, however, that both conditions are ill defined.Quality assessment of 14 international guidelines on cholecystolithiasis showed that only five guidelines were suitable for clinical practice, as most recommendations were based on a low level of evidence summarizes guidelines and criteria sets for symptomatic cholecystolithiasis. Most guidelines refer to the Rome criteria to define symptomatic gallstone disease: pain in severe attacks, in the epigastrium or upper right quadrant, and lasting 15–30 min or longer10–12. The Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland commission guide22 from 2016 slightly modified these criteria to epigastric or upper right abdominal pain, frequently with radiation to the back, lasting from several minutes to hours, and often occurring during the night. The Society for Surgery of the Alimentary Tract23 has similar criteria , whereas the European Association for the Study of the Liver6 has reported more than 10 criteria. The various symptoms and criteria reported in these guidelines illustrate the lack of consensus among healthcare professionals.14. The study randomized patients with gallstones and abdominal pain between usual care  and a restrictive strategy. In the restrictive arm of the study, cholecystectomy was advised only for patients who had all five prespecified symptoms based on the Rome III criteria and on predictors identified during a previous clinical study: severe pain in attacks, pain in the upper right quadrant or epigastrium, pain lasting 15–30 min or longer, pain radiating to the back, and positive response to simple analgesics25. The primary aim of the SECURE trial was to assess the percentage of patients who were pain-free after 1 year of follow-up. The trial demonstrated a 7 per cent higher cholecystectomy rate in the usual-care arm (75 per cent of 537 patients) compared with the restrictive arm (68 per cent of 530 patients) (P = 0.005). Despite more cholecystectomies, the usual-care strategy resulted in more patients who were pain-free after 12 months of follow-up . Rates of gallstone-related complications were similar in the two groups: 8 per cent in the usual-care and 7 per cent in the restrictive arm (P = 0.155). The SECURE trial14 also illustrated the limited validity of Rome III criteria regarding the indication for cholecystectomy in patients with cholecystolithiasis; 35 per cent of patients with typical biliary colic (by Rome definition) reported persistent gastrointestinal symptoms after surgery.This variation in criteria for surgery was one of the reasons for initiating the SECURE trial, which tested one set of symptom criteria summarizes patient characteristics and preoperative symptoms in patients with uncomplicated cholecystolithiasis. The data are based on three clinical trials , which included patients between 2014 and 2019 in 30 Dutch hospitals.26 and SUCCESS24 trials showed that laparoscopic cholecystectomy effectively resolved biliary colic. However, both trials confirmed that persistent abdominal pain after cholecystectomy is present in 40 per cent of patients13–15. Several causes of persistent abdominal pain after surgery have been identified. The literature suggests that several gastrointestinal symptoms originating from disease aetiologies other than gallstones are responsible for the development of postcholecystectomy pain28. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) have a prevalence of 20–30 and 20 per cent respectively in the primary care population. Both are causes of pain with similar pain characteristics30. These conditions generally involve similar population groups: mainly middle-aged women who are overweight. These similarities complicate diagnosis of the condition responsible for a patient’s complaints and, as a result, potentially lead to abdominal pain being wrongfully attributed to gallstones and therefore influencing the choice of treatment (cholecystectomy)31. Figure 2 is an infographic illustrating the characteristics and preoperative symptoms of patients with uncomplicated cholecystolithiasis included in the SECURE, PERFECT, and SUCCESS trials. The figure illustrates the percentage of patients with persistence of pain, and the impact of the concurrent presence of FD and IBS on postoperative pain relief. Finally, it shows that biliary complications occurred in 5 per cent of patients: 2 per cent minor (emergency department visit with biliary colic) and 3 per cent major  biliary complications. Surgical complications occurred in 11 per cent and 2 per cent of patients underwent treatment for a major complication.The PERFECT26 was initiated to evaluate the prevalence of FD and IBS in patients with gallbladder stones, and to explore the relationship between the concomitant presence of FD or IBS and patient-reported outcomes in terms of pain relief after laparoscopic cholecystectomy. This trial analysed 401 patients with symptomatic gallbladder stones (eligible for surgery). Of these patients, 34.9 per cent met the criteria for FD and/or IBS. A similar proportion of patients in the FD and/or IBS group and in the group without FD and/or IBS underwent surgery . After cholecystectomy, 57 per cent of patients were pain-free; the difference between patients with and without FD and/or IBS was significant . There was no significant difference between groups in the presence of biliary colic after surgery .The PERFECT trial19 in the USA, focusing on identification of symptoms associated with upper abdominal pain relief after surgery, documented similar findings. Among 1008 patients who underwent cholecystectomy, only 59 per cent reported absence of upper abdominal pain 12 months after surgery. Preoperative pain characteristics  and presence of concomitant gastrointestinal symptoms or disorders  predicted the odds of pain relief after cholecystectomy.A previous prospective cohort study32 was performed that compared observation versus surgical intervention in patients with uncomplicated cholecystolithiasis. Sixty-eight patients were randomized to cholecystectomy and 69 to observation. During the 67 months of follow-up, 60 patients (88 per cent) and 35 patients (51 per cent) respectively eventually underwent cholecystectomy. No difference in admissions for pain attacks or gallstone-related complications, such as acute cholecystitis, choledocholithiasis or acute pancreatitis, was observed. Eight of 95 patients who underwent cholecystectomy developed a major complication. There were no differences between the groups in either quality-of-life or pain scores. In 2011, Schmidt and colleagues33 reported 14-year follow-up data, which showed that almost no operations were performed beyond 5 years in either group. Biliary complications occurred in 3 of 69 patients (4 per cent) randomized to observation; 1 of 68 patients (1 per cent) randomized to surgery had biliary pancreatitis before operation (P = 0.298). The authors concluded that, when the symptoms are intolerable, cholecystectomy is advised in patients with uncomplicated, symptomatic, gallbladder stones. However, conservative treatment is also an option, with a minimal risk of development of cholecystitis, cholangitis or pancreatitis.In 2002, the first randomized study34 is randomizing patients with symptomatic gallstones between surgical or conservative treatment. The investigators have hypothesized that there will be no difference in quality of life between conservative management and surgery after follow-up of 18 months. The study protocol includes all patients with radiologically confirmed gallbladder stones regardless of the severity and frequency of symptoms. This trial will investigate the effectiveness of surgical versus conservative treatment.The C-GALL trial14, 171 patients did not undergo cholecystectomy. This group had characteristics  similar to those of the group that underwent cholecystectomy. However, these patients less frequently reported biliary colic, and had lower pain scores. As noted previously, biliary complications were similar between usual-care and restrictive strategies. The surgeon’s dogma of gallbladder removal to prevent biliary complications does not stand for all patients as the risk of developing biliary pancreatitis is below 2 per cent. Factors associated with biliary complications in patients with gastrointestinal pain and gallbladder stones should be investigated further. The 5-year follow-up of the Dutch trials will elucidate the rate of biliary complications in patients being treated according to a wait-and-see strategy.In the restrictive arm of the SECURE trialA shared decision regarding cholecystectomy between physician and patient is crucial, and most important for patients with concomitant FD and/or IBS. The patient should be aware of the high chance of persistent symptoms (divided into biliary colic and other non-biliary symptoms) after cholecystectomy, especially in patients with gallstones and FD and/or IBS.Based on the available literature, the authors advise that the doctor should focus on patient characteristics, pain characteristics, and symptom severity during the first outpatient clinic visit. According to these pain characteristics and symptom severity, physicians should make the distinction between biliary colic and functional gastrointestinal symptoms. Cholecystectomy is the preferred treatment. However, when the most important symptoms match those of a functional abdominal disease, an evaluation after approximately 3 weeks is advised. In the meantime, the patient should register their symptoms. If, at the time of the evaluation, functional abdominal symptoms appear to be the main problem, these should be treated first. Expectant management is considered safe as the complication rate  is very low.24, a criteria set was developed and validated to allow selection of patients with uncomplicated gallstone disease for surgery based on prediction of becoming pain-free or achieving a relevant reduction in pain. The SUCCESS cohort provided the data for development of the criteria set: 494 patients with radiologically confirmed gallbladder stones, gastrointestinal pain symptoms, and a referral to the surgery department of the hospital. The criteria set comprised: older patients, with a high baseline pain score, no history of abdominal surgery, radiation of pain to the back, nausea, effective result after simple painkillers, and no symptoms of heartburn. Patients with these characteristics/symptoms more frequently had a relevant reduction in pain after gallbladder removal. External validation of the SUCCESS criteria in the SECURE data indicated good distinction between patients with and without a relevant reduction in pain. For daily clinical use, an online tool was developed, which can be accessed easily via the QR code in Fig. 2 and at https://gallbladderresearch.shinyapps.io/SUCCESS/. To tailor treatment for individual patients, Fig. 3 illustrates a decision tree. When patients with proven gallbladder stones complain of repeated biliary colic, this is considered to represent symptomatic gallstone disease, and cholecystectomy is advised in shared decision-making with the patient. An option talk is advocated for patients who report abdominal pain reminiscent of, but not completely typical of, biliary colic (33 per cent of patients) (Table 2). Use of the online decision tool is advised to predict the probability of a relevant pain reduction after surgery during this option talk with such patients. For example, for a 57-year-old patient, with a pain score of 7 and no history of abdominal surgery, absence of pain radiating to the back, a positive effect of simple painkillers, reporting nausea and heartburn, the predicted probability of a relevant pain reduction is 0.45 (95 per cent c.i. 0.23–0.70). Finally, an expectant policy is justified for patients with non-specific biliary pain or noted to have functional gastrointestinal disease. Other diagnoses must be considered in patients with atypical abdominal pain and, if symptoms remain, referral to the gastroenterology department or GP could be considered.In addition to this approach, a criteria set with patient characteristics and preoperative symptoms is of high value in improving treatment decision-making. In the SUCCESS trialThe diagnostic evaluation and treatment of patients with gallbladder stones and abdominal pain are subject to change. The symptom criteria for symptomatic cholecystolithiasis differ across international guidelines. Although biliary colic is frequently resolved after cholecystectomy, non-biliary symptoms persist in up to 40 per cent of patients. This review guides surgeons on how to tailor diagnosis and treatment in patients with symptomatic cholecystolithiasis.Disclosure. The authors declare no conflict of interest.znac154_Supplementary_DataClick here for additional data file.


Background and Objectives: Degenerative disk disease is a widespread chronic condition that causes diskogenic pain. Diskogenic pain can be treated with various therapy methods. Disc-FX is a revolutionary, minimally invasive, percutaneous nucleo-annuloplasty method that combines manual diskectomy with nuclear and annular remodeling using radiofrequency ablation to relieve diskogenic pain. In this study, the technical features, clinical outcomes, and complications of Disc-FX are summarized. Materials and Methods: A comprehensive literature review was performed. By exploring several databases, we collected studies on Disc-FX for treating diskogenic pain. The outcomes included perioperative data, clinical results, and complications. Results: In the 15 studies included, data from 570 patients were collected. L4–L5 was the most frequently operated level, and most cases underwent single-level procedures. The follow-up period for these patients ranged from 2 months to 24 months. One study reported a procedure time between 35 and 60 min, whereas the remaining studies reported a procedure time of less than 30 min. The mean visual analog scale score decreased from 7.22 preoperatively to 1.81 at the final follow-up. The mean numerical rating scale score decreased from 6.98 preoperatively to 3.9 at the final follow-up. The mean Japanese Orthopaedic Association score improved from 16.26 preoperatively to 25.88 in the final follow-up. The mean Oswestry Disability Index score decreased from 35.37 preoperatively to 14.66 at the final follow-up. The mean satisfaction rate (based on the Macnab criteria) was 87.6% . The total incidence of postoperative transient pain was 8.77% (50/570) after nucleo-annuloplasty using Disc-FX, and recurrence was 1.58% (9/570). Conclusions: According to our comprehensive evaluation, using percutaneous nucleo-annuloplasty for treating lumbar diskogenic diseases provided considerable pain alleviation and improved functional outcomes with fewer complications. Disc-FX is a safe and effective procedure that is a good treatment option for patients with diskogenic pain. In the past, individuals with degenerative disk disease or lumbar disk herniation resulting in diskogenic pain were treated conservatively with rest, medications, injections, and/or physical therapy ,2,3. UnfMinimally invasive approaches for treating degenerative disk diseases have several advantages, including greater preservation of the spine architecture, less tissue loss, and decreased risk ,6. In reThe results of several studies suggest that nucleo-annuloplasty using the Disc-FX system may be a reasonable treatment option for those with degenerative disk diseases ,15. HoweThis systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. From database inception to 15 May 2022, papers published in English or Chinese were searched for from the Cochrane Library, PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data. The following keyword combinations were used to obtain the highest search sensitivity: “Disc-FX”, “nucleo-annuloplasty”, or “intradiscal radiofrequency”. Furthermore, we discovered pertinent papers from references to help with our search. Two researchers separately evaluated the titles and abstracts of all search results. The relevance of those whose material looked to be relevant was then evaluated further. Discussions with a third party were used to settle any disagreements. To prevent any possible data duplication, when analyzing studies from the same institution or authors, we only evaluated the most recent study or the study with a longer follow-up.All relevant clinical research and original papers were searched for, including prospective, retrospective, and randomized controlled trials. The collected data included the authors, year of publication, type of study, number of patients, level of surgery, follow-up duration, perioperative data, clinical outcomes, and complications. The primary outcomes were visual analog scale (VAS) scores for back and/or leg pain, numerical rating scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores, which were measured preoperatively and in the final follow-up. Additionally, Macnab’s outcome evaluation of patient satisfaction was performed. All data were summaries of qualitative research. No statistical analysis or meta-analysis was performed.The Newcastle–Ottawa Scale (NOS) was utilized to evaluate the quality of non-randomized trials. Each study was assessed on the basis of selection, comparability, and exposure/outcome. Employing these criteria, we regarded papers that received five or more stars in our review.All procedures were performed under local anesthesia in the operating room. On the Jackson table, each patient was placed in the prone position. Magnetic resonance imaging (MRI) was used to plan skin entrance locations before surgery. A standard posterolateral approach was used. Under fluoroscopic assistance, the skin entrance location was indicated. The pathological side was the chosen approach side. In the lateral view, the puncture needle was inserted through the Kambin’s triangle at an angle of 30–45° to the dorsal plane, with the needle tip positioned in the posterior third of the intervertebral disk. The needle core was withdrawn, and diskography was performed by injecting a mixture of iontophoresis and melanin in a 9:1 ratio. A guidewire was placed through the puncture needle, and a 0.7 cm incision was made in the skin. Under fluoroscopic guidance, a cannula was introduced through the guidewire over the annular . A pair of gripping forceps was used for manual diskectomy, and diseased disks were removed separately. The Surgi-Max system  can control the radiofrequency-generating device using a unique design of bipolar radiofrequency electrodes that can be flexed (Trigger-Flex), extended, and steered to enter the nucleus pulposus through the working channel. First, a radiofrequency of 1.7 MHz was used to ablate the nucleus pulposus with the Bipolar Turbo mode, once for 3–4 s, repeated 4–6 times; then, the Trigger-Flex tip was bent to the dorsal side; we fluoroscopically determined that the Trigger-Flex tip is located in the contralateral fibrous ring, and we slowly pulled out the fibrous ring to the ipsilateral side with 1.7 MHz (Bipolar Hemo mode), once for 4–6 s, which was repeated 4–6 times. The intervertebral space was repeatedly irrigated with saline through the working channel until the irrigation solution was clear. The working channel was removed, without the need for suturing the incision; then, the band-aid patch was applied. The patients were usually dismissed the same or the next day.Through the database search, 96 studies were discovered. Following a title and abstract screening, which eliminated 5 irrelevant articles, the remaining 17 possibly relevant articles were obtained. Following a thorough examination of the complete text, 15 articles were finally included in this review ,27,28,29All 15 studies used a retrospective comparative cohort design with moderate to high quality as assessed by the NOS .Eight papers  providedTen studies  providedFive studies provided JOA scores. The mean JOA scores improved from 16.26 preoperatively to 25.88 at the final follow-up . Seven sRegarding postoperative complications, three papers reported postoperative transient pain. The total incidence of postoperative transient pain was 8.77% (50/570) after the Disc-FX procedure. The total recurrence rate was 1.58% (9/570) after the Disc-FX procedure reported in four articles. Furthermore, some niche complications have been reported, such as nerve injury (2), hematoma (1), infection (1), lumbar venous plexus injury (1), and reoperation (1).In this systematic review, we found that postoperative VAS and NRS scores for diskogenic pain using the Disc-FX system were significantly lower than preoperative scores, postoperative ODI scores were lower than preoperative ones, postoperative JOA scores were significantly higher than preoperative scores, and fewer surgical adverse events occurred; additionally, the patient satisfaction rate was 87.6% .Diskogenic pain is discomfort caused by damaged intervertebral disks, and its primary cause is the degeneration and deterioration of the intervertebral disks and the formation of fissures or ruptures in their fibrous rings that separate from each other, stimulating pain receptors distributed on the surface of the fibrous rings of the disks and causing pain ,31. AddiDiskogenic pain is difficult to diagnose because it often has only subjective symptoms and lacks objective auxiliary examination indicators. Since patients with diskogenic pain lack obvious manifestations of lumbar disk herniation, locating the painful intervertebral space is often impossible based on symptoms and physical examination, and locating the source of pain using MRI is difficult, whereas diskography can screen normal physiologically degenerated disks from pathologically degenerated disks, thus effectively clarifying the responsible segment and avoiding overtreatment and mistreatment ,34. HoweSeveral conservative treatments have been used for diskogenic pain, including opioids, non-steroidal anti-inflammatory drugs, and physical therapies, such as acupuncture, massage, and physical therapy . AlthougThe Disc-FX system is an innovative, minimally invasive technique based on the Yeung endoscopy spine system technology developed by Yeung, which is versatile and fills the gap between interventional and open surgery with multiple functions, such as tissue extraction, nucleus pulposus removal, radiofrequency ablation, annuloplasty, irrigation/aspiration, and observation. The Disc-FX system for treating diskogenic pain is closely related to its possible mechanism of occurrence, which can achieve intra-disk decompression, the inactivation of sinus nerve terminals growing into the ruptured annulus fibrosus fissure, and the destruction of inflammatory factors . IntraopThe Disc-FX system employs a radiofrequency of 1.7 MHz from the Elliquence Surgi-Max generator to achieve nucleus ablation (Bipolar Turbo mode) and annular remodeling (Bipolar Hemo mode), respectively . While cThe Disc-FX system’s 3 mm outer working channel clearly offers less trauma than conventional endoscopic spine surgery and does not require the steep learning curve and lengthy training required for microscopic surgery. However, the careful monitoring of surgical indications remains necessary to achieve optimal results. The indications for surgery using the Disc-FX system should be strictly limited to diskogenic low back pain because of the mild inclusion of disk herniation and fibular ring tears, particularly in young and middle-aged patients with normal or mildly reduced disk height, while severe disk herniation, free nucleus pulposus, and significant nerve root symptoms should be avoided.Nevertheless, the Disc-FX system also has its limitations. (1) Because of the restriction of the high iliac crest, the working channel cannot be placed in the optimal position at the L5–S1 level in some patients, and for the L2–L3 level and above, the puncture path is closer to the midline to avoid the kidney. (2) Because all surgeries are performed under X-ray guidance, some are blindfolded, and controlling the quantity of nucleus pulposus tissue excised is difficult, particularly for patients of varying ages and degrees of degeneration, and the amount of nucleus pulposus tissue excised frequently varies substantially. (3) The Disc-FX system is indicated in cases with an intact fibrous ring and posterior longitudinal ligament, although it has also applied in cases with fibrous ring tears. (4) Unlike full endoscopic spine surgery, which has multiple surgical approaches, Disc-FX has only one posterolateral approach, limiting its extensive use. (5) Finally, it is not a fully visualized surgical approach.The following are possible complications associated with the Disc-FX system: (1) Postoperative transient pain is caused by recurrent episodes of transient pain caused by the space formed after the disk is removed and then filled with blood or other tissues causing compression or intraoperative manipulation that irritates the nerve roots and causes edema ; this coThis is the first systematic review of the efficacy of nucleo-annuloplasty using Disc-FX for treating lumbar diskogenic lesions. However, this review also has some limitations. This review is of a low evidence-based grade because it consists mainly of retrospective studies; there are no randomized controlled trials or prospective comparative studies to refer to. Additionally, there was variation in the duration of follow-up in this study, which may have provided the incomplete reporting of complication rates. Finally, some studies failed to disclose accurate data on issues such as age, gender, and follow-up duration.According to our comprehensive evaluation, percutaneous nucleo-annuloplasty for lumbar diskogenic diseases provided considerable pain alleviation and improved functional outcomes with fewer complications. Disc-FX is a safe and effective procedure that is a good treatment option for patients with diskogenic pain. Existing research, including several that are still underway, are primarily confined to small cohorts and short-term follow-ups. Further prospective studies and randomized trials with large sample sizes and long-term follow-ups should be conducted.