This study assessed the efficacy and tolerability of intravenous ibuprofen in the improvement of post-operative pain control and the reduction of opioid usage. Patients were randomly divided into placebo, ibuprofen 400 mg and ibuprofen 800 mg groups. All patients received patient-controlled intravenous morphine analgesia after surgery. The first dose of study drugs was administered intravenously 30 min before the end of surgery and then every 6 hours, for a total of 8 doses after surgery. The primary endpoint of this study was the mean amount of morphine used during the first 24 hours after surgery. Morphine use was reduced significantly in the ibuprofen 800 mg group compared with the placebo group (P = 0.04). Tramadol use was reduced significantly in the ibuprofen 400 mg and ibuprofen 800 mg groups compared with the placebo group (P < 0.01). The area under the curve of visual analog scale pain ratings was not different between groups. Safety assessments and side effects were not different between the three groups. Intravenous ibuprofen 800 mg was associated with a significant reduction in morphine requirements, and it was generally well tolerated for postoperative pain management in patients undergoing radical cervical cancer surgery. Undertreated postoperative moderate-to-severe pain is associated with an increased risk for progression to a chronic painful state. Undertreated postoperative pain increases the risk of myocardial ischemia, impairs rehabilitation and wound healing, delays gastrointestinal motility, alters immune responses, and increases pulmonary complications due to the poor respiratory effort and thromboembolism due to immobilization6.Postoperative pain in the recovery process remains a challenge for anesthesiologists. Approximately 80% of patients experience postoperative pain, and over 30% of patients experience severe pain8. However, the failure of acute postoperative pain treatment may be the result of the use of opioid monotherapy9. Opioids cause respiratory depression, sedation, drowsiness, pruritus, skin rash, urinary retention, delayed gastrointestinal motility, and postoperative vomiting and nausea10. The concept of “multimodal analgesia” was proposed in the early 1990s to overcome these opioid-induced adverse effects and achieve sufficient analgesia12. The efficacy and safety of intravenous (IV) ibuprofen as a multimodal approach to pain management was investigated in different clinical trials, and it is accepted as an adjunct to opioids for acute postoperative pain management16. The purpose of this study was to assess the efficacy and tolerability of different doses of IV ibuprofen in the improvement of pain control and the reduction of opioid use in patients undergoing radical cervical cancer surgery.Opioids are widely used in the treatment of acute postoperative pain. Over 60% of patients who experience moderate or severe postoperative pain received morphine as a postoperative pain therapyThis study was a prospective, randomized, double-blind, placebo-controlled trial. This study was performed at the Third Affiliated Hospital, Harbin Medical University and the ethics committee of the Third Affiliated Hospital, Harbin Medical University approved this study. This study was registered in the Chinese Clinical Trial Registry . All methods were performed in accordance with the relevant guidelines and regulations. Informed consent forms and all amendments were reviewed and approved by the ethics committee of the Third Affiliated Hospital, Harbin Medical University, before any study-specific screening procedures were performed and any preoperative medications were administered.The study population consisted of 60 female patients who were scheduled for radical cervical cancer surgery and were expected to require postoperative hospitalization and patient-controlled IV analgesia (PCIA) of morphine for at least 24 hours. Included patients were 18 to 70 years old with American Society of Anesthesiologists (ASA) physical status I-III and the ability to reliably provide self-reports of pain. Patients were excluded from the study if they had a history of allergy or hypersensitivity to ibuprofen, aspirin, COX-2 inhibitors or other non-steroidal anti-inflammatory drugs (NSAIDs), or a history of tolerance or dependence to narcotics or opioids. Patients with Hb <90 g/L, weight <40 kg, a history of asthma or heart failure, or pregnant or nursing were also excluded. Patients were not eligible if they had a platelet count less than 80,000/mm3, gastrointestinal bleeding history within the previous 6 weeks, a history of bleeding diathesis, or a recent history or increased risk of intracerebral hemorrhage. Patients with alanine aminotransferase or aspartate aminotransferase levels over 1.5 times the normal upper limit or creatinine over the normal upper limit were not eligible. Patients were excluded if they were taking warfarin, lithium, or a combination of angiotensin-converting enzyme inhibitors and furosemide. Patients were excluded if they received any analgesic, muscle relaxant, or sedative medications within 24 hours of study medication administration, excluding the sedatives or muscle relaxants that were used during the surgical procedure. Local anesthesia, nerve blocks, epidural anesthesia and analgesia were not allowed during the pre/intra-operative periods.All patients were assigned in a 1:1:1 ratio using a double-blind, simple randomization scheme to receive IV placebo, ibuprofen 400 mg, or ibuprofen 800 mg every 6 hours for a total of 8 doses in the first 48 hours of the study. Investigators, patients, and care providers were blinded to intervention assignment. Only the study pharmacist was unblinded.2 at 35–45 mmHg.Anesthesia methods were standardized in all three groups. Anesthesia was induced using 2 μg/kg remifentanil, 0.05 mg/kg midazolam, 1–2 mg/kg propofol, and 0.6 mg/kg rocuronium. A tracheal catheter was inserted after 2 min of rocuronium administration. The entire course of anesthesia was maintained using 4–8 mg/kg/h propofol and 5–12 µg/kg/h remifentanil, which sustained changes in blood pressure within 20% of the initial levels and bispectral index (BIS) between 40 and 60 during surgery. Ventilation rate was 12/min. Tidal volume was adjusted to 6–10 ml/kg to maintain end-tidal COMorphine (100 mg) was diluted in 200 ml of 0.9% saline and added to the PCIA pump. The PCIA pump was set at a loading dose of 1.5 mg, a background infusion of 0.5 mg/h, a 1 mg bolus, and a lockout interval of 5 min. All patients received PCIA pump infusions 30 min before the end of surgery.The first dose of IV ibuprofen or placebo was administered 30 min before the end of surgery Fig. . Subsequ17. VAS was recorded at 1, 3, 6, 12, 24, 36 and 48 hours after administration of the first dose of study medication. The area under curve (AUC) of VAS up to 24 hours after administration of the first dose of study medication was analyzed between groups. BCS and OPPS were evaluated at 1, 3, 6, 12, 24, 36 and 48 hours after administration of the first dose of study medication.The primary endpoint of this study was the mean amount of morphine used during the first 24 hours after surgery. Secondary endpoints included tramadol requirement  and the mean change in pain intensity. Pain intensity at rest and with movement were assessed using patient self-reporting with a 100-mm visual analog scale , the Bruggemann comfort scale  and revised overall pain performance scale Tolerability and safety were evaluated as adverse events, vital signs, and laboratory assessments of patients in all three groups. Adverse events, including pyrexia, headache, dizziness, cough, postoperative inflammation, epigastric pain, pruritus, nausea, vomiting, time of exhaust, gastrointestinal bleeding, urinary tract infection, and concomitant medications were recorded and compared until day 4 of the study. Vital signs, including blood pressure, heart rate, respiratory rate, and body temperature were recorded at 1, 3, 6, 12, 24, 36 and 48 hours after administration of the first dose of study medication. Laboratory assessments included biochemistry, blood routine, blood coagulation function , urinalysis, and electrocardiogram 24–48 hours after administration of the last dose of study medication.Sample size calculation was according to morphine use of the pilot study. Initial power calculations indicated that 14 patients of each group would provide 80% power to show a reduction in morphine use between the placebo group and the ibuprofen 800 mg group at an α level of 0.05. Assuming a dropout rate of approximately 10%, 16 patients in each group should be enrolled.Quantitative variables are presented as the means ± standard deviation (SD). Level variable are presented as interquartile range. Categorical variables are presented as percentages. The general characteristics of the patients, VAS scores, the AUC of VAS, the morphine dose, and tramadol dose were analyzed using ANOVA followed by the LSD test. BCS and OPPS scores were analyzed using a Kruskal-Wallis H test and Mann-Whitney U test. Chi-square and Fisher’s exact test were used to compare differences in side effects and the number of patients with abnormal laboratory assessments between groups. P < 0.05 was considered statistically significant. All statistics were assessed using SPSS 22.0.Within 60 patients, one patient was excluded due to surgical procedure change and 3 patients withdrew consent Fig. . A totalMorphine use was significantly reduced during the first 24 hours in the ibuprofen 800 mg group (17.6 ± 3.2 mg) compared with the placebo group  and ibuprofen 800 mg (42.1 ± 50.7 mg) groups compared to the placebo group (97.5 ± 25.5 mg) during the first 24 hours after the surgery (P < 0.01, Fig. Based on VAS evaluation, the patients of the ibuprofen 800 mg group was associated with significant reductions in pain intensity at rest compared with the patients of the placebo group at 1 hour after administration of the first dose of study medication (P = 0.049, Fig. BCS scores in the ibuprofen 400 mg and 800 mg groups were significantly higher than the placebo group at 36 hours after administration of the first dose of study medication (P = 0.03, Fig. The safety assessment of the three groups over the course of the study were shown in Table 18. The use of single morphine analgesia greatly increased the incidence of side effects, such as intractable nausea, vomiting, respiratory issues and emesis, which hinders perfectly effective postoperative pain management. The use of additional medications to reduce the need for opioids is widely endorsed21. Various analgesics act at different sites in the nervous system, which results in synergistic analgesia and a reduction in the side effects of the sole agent11.Postoperative pain continues to be a considerable problem despite advances in our understanding of the mechanisms involved. A patient’s unwillingness to use opioids may be one reason for inadequate pain relief. Concern about side effects is a main contributor to this reluctance23. Oral ibuprofen effectively blocks pain and inflammation, in part via the prevention of prostaglandin production24. An IV formulation of ibuprofen may arrest the inflammatory cascade triggered by invasive procedures, reduce or prevent the development of postoperative pain, and avert the sensitization of pain receptors. However, there are some safety concerns to NSAIDs use. The gastrointestinal and renal toxicity and general bleeding risks are increased with NSAIDs use25. However, many of these effects are associated with longer-term use26. An IV ibuprofen preparation would most likely be used on a short-term basis in hospitalized patients and in out-patient surgical procedures, which would decrease the incidence of these safety concerns. Some studies examined investigational formulations of IV ibuprofen, and none of these studies demonstrated any safety concerns29. These studies used a range of ibuprofen doses up to 800 mg and found no renal issues, gastrointestinal toxicity or bleeding, and no effect on transfusion requirements or hemoglobin levels.Opioids block only the perception of pain, and the anti-inflammatory activity of ibuprofen helps prevent and alleviate the tissue inflammation that causes pain. Oral ibuprofen has been widely used as a safe and effective treatment for pain, fever, and inflammation for more than 30 years30. The strategy presented in this study involving IV ibuprofen as an adjunct to morphine may prove beneficial for these patients. The results of this study suggest that the use of IV ibuprofen at a dose of 800 mg, but not 400 mg, every 6 hours alleviated postoperative pain and was significantly morphine-sparing with a reduction in morphine use in patients undergoing radical cervical cancer surgery. This use of ibuprofen may reduce some of the well-established adverse events associated with opioid analgesia. IV ibuprofen 800 mg significantly reduced pain at rest and with movement in postoperative pain management16. A meta-analysis of 17 randomized controlled trials, comprised of 400 patients who received opioid analgesia plus an NSAID for the management of postoperative pain and 389 patients who received monotherapy with opioid analgesia, demonstrated that patients who received both medications consumed fewer opioids and had lower pain scores than patients who received opioid monotherapy20. No difference in the incidence of adverse effects was observed between opioids and opioids plus NSAIDs groups20. Our results are consistent with these reports. There was no significant difference in the incidence of gastrointestinal bleeding, toxicity, renal toxicity, or generalized bleeding between the ibuprofen 400 mg, ibuprofen 800 mg, and placebo groups. The findings of this study on IV ibuprofen at different doses further add to the body of evidence supporting the effectiveness of multimodal analgesic regimens for the management of acute postoperative pain33.The current study evaluated the safety and efficacy of IV ibuprofen-assisted postoperative analgesia in patients undergoing radical cervical cancer surgery. Evidence from epidemiological studies suggests that women undergoing hysterectomy may be particularly at risk for adverse pain experiences16. The current study was the first trial to focus on patients undergoing radical cervical cancer surgery, which provides evidence to physicians in evaluating the safety and efficacy of IV ibuprofen-assisted postoperative analgesia in these patients.One limitation of the study was the small number of patients, which may reduce the statistical power of the results. However, the main results of this study are consistent with previous studiesIn conclusion, the findings of this study suggest that postoperative IV injections of ibuprofen 800 mg, but not 400 mg, was associated with significant reductions in morphine requirements for postoperative pain management, which may reduce some of the well-established adverse events associated with opioid analgesia in patients after surgery. There was no significant difference in the incidence of gastrointestinal bleeding, toxicity, renal toxicity, generalized bleeding or other side effects between the ibuprofen 400 mg, ibuprofen 800 mg, and placebo groups. IV ibuprofen was generally well tolerated for postoperative pain management.


Results show significant decrease in pain  and disability . In-clinic gait and TUG were also significantly improved ; however, DPA, including the percentage of physical activities  and the number of steps, showed no significant change after PSI . We hypothesize that DPA may continue to be truncated to an extent by conditioned fear-avoidance, a psychological state that may prevent increase in daily physical activity to avoid pain.This study evaluates the effect of paravertebral spinal injection (PSI), utilizing both subjective and objective assessments in chronic low back pain (LBP) associated with facet joint arthrosis over a one-month duration. Subjective questionnaires included the visual analogue scale (VAS) for pain, the Oswestry Disability Index, the Health Survey SF-12, and the short Falls Efficacy Scale International (FES-I). Objective assessments included in-clinic gait and Timed Up and Go (TUG) tests using wearable sensors, as well as 48 h daily physical activity (DPA) monitored using a chest-worn triaxial accelerometer. Subjective and objective measures were performed prior to treatment, immediately after the treatment, and one month after the treatment. Eight LBP patients were recruited for this study (mean age = 54 ± 13 years, body mass index = 31.41 ± 6.52 kg/m Low back pain (LBP) is the second most common source of disability in the United States, affecting more than 80% of the population during their lifetime ,2. This Among its many causes, lumbar facet joint pain accounts for up to 75% of the patients who present with LBP . One speAlthough PSI has been commonly implemented for LBP treatment, there are few clinical trials pertaining to the use of lumbar PSI, and among those available, no consensus regarding effectiveness has been reached . One stuThe primary aim of this study was to investigate the efficacy of paravertebral facet injection for degenerative facet osteoarthropathy, both subjectively and objectively over a period of one month, using wearable sensor technology to track DPA. Notable differences separating this study from previous investigations were the inclusion of previously unreported measures, the comparison of pain-related subjective and objective measures (both in-clinic and in-home measures), as well as the inclusion of patients with more diverse etiologies of LBP, which most accurately reflects the typical patient population. Specifically, we investigated: (1) how objectively measured DPA would change over the one-month period following spinal injection treatment; and (2) if and how much DPA measurement would be associated with post-treatment alterations in pain, disability, and objective in-clinic measures of gait and Timed Up and Go (TUG).Participants with degenerative facet osteoarthropathy were recruited from the Southwestern tertiary integrated academic health care system based on clinical and radiologic diagnosis with plain film radiography, CT, and MRI images. The inclusion criteria were as follows: (1) LBP symptoms of at least three months prior to assessment; (2) 18 years of age or older; and (3) ability to walk 20 m without any assistive device. The exclusion criteria included the following: (1) prior spine, hip, or lower-extremity surgeries within one month of the spinal injection; (2) opioid use for pain; and/or (3) severe comorbidities that altered gait or balance performance, such as Parkinson’s disease, stroke, diabetic neuropathy, or peripheral vascular disease. We selected participants over a large age range, and also those with general facet joint pain, to represent a normal LBP patient population. The study was approved by the University of Arizona Institutional Review Board. Written informed consent according to the principles expressed in the Declaration of Helsinki  was obtaParavertebral facet injections were performed at the same facility by a single orthopaedic surgeon (MD) according to the North American Spine Society’s recommendations . Under fParticipants were asked to report pain, health survey, and disability information in, at most, three sessions: pre-injection within three days prior to the procedure (baseline), immediately post-injection, and one month post-injection. The 10-point visual analog scale (VAS)  was usedTo measure DPA, a previously validated method involving a wearable triaxial accelerometer  ,23,24,25In-clinic motor performance, including normal gait and the TUG test, was performed within 20–30 min following the spinal injection using a validated system . Briefly, three-dimensional acceleration and angular velocity of shanks, thighs, and the trunk were measured using five wearable sensors, each including a triaxial accelerometer and a triaxial gyroscope to derive gait and TUG outcome measures following procedures identical to those explained in earlier studies see . Sensorsp ≤ 0.05. For continuous data over the one-month period , the repeated measure analysis of variance (ANOVA) tests, adjusted for age, gender, and body mass index (BMI), was utilized. The Student’s t-test was used to compare pre-injection versus immediate post-injection parameters (pain and DPA parameters from PAMSys), as well as pre-injection versus one month post-injection parameters . Means with standard deviation and 95% confidence intervals for data, as well as the Cohen’s effect size for Student’s t-test and the Eta-squared for ANOVA, were calculated.Data were analyzed in JMP , which is a commercialized computer program for statistical analysis. Statistical significance was concluded when 2, 168.87 (10.06) cm, and 90.32 (22.50) kg, respectively.Eight LBP patients  were recruited for this study, with two lost for the one-month follow-up. Mean (SD: standard deviation) age, BMI, height, and weight of the participants were 54 (13) years, 31.41 (6.52) kg/mp < 0.05, p > 0.07).Pain at the moment and Oswestry scores were significantly improved from baseline to the one-month follow-up; pain and Oswestry scores decreased (improved) by 46% and 21%, respectively  post-injection, similar trends of improvements were not observed in DPA measures.Pain in general decreases patients’ quality of life depending on its extent, duration, and intensity . With reConsidering subjective evaluations of PROMs, pain and disability, as measured by the visual analog scale and the Oswestry Disability Index, were significantly improved in patients after PSI see . This reAlthough several studies have reported subjective pain reduction after spinal injection, few investigated both subjective and objective measures. One study assessed pain, disability, and physical impairment one week post-injection for lumbar spinal stenosis. Although a different type of spinal disorder was targeted in that study, interestingly, and similar to our findings, they found that improvements in pain and function compared to baseline measurement did not positively correlate with the objective assessment of total DPA over a period of seven days ; no signAccording to current results, while immediate in-clinic assessments of gait and TUG revealed significant differences regarding gait speed, gait cycle time, and total TUG duration, no significant change in DPA for a duration of two days was observed at baseline, at the immediate follow-up, or at the one-month follow-up after the treatment see . This diThe study is limited by its sample size as well as the duration of follow-up. In future studies, more patients of disparate ages with diverse origins of LBP should be included to increase generalizability of the current findings. Specifically, follow-up should extend to a minimum duration of one year post-injection to better understand the time lag between pain relief and improvements in DPA. Several factors may positively or negatively skew the amount of DPA, such as weather conditions, special daily events, or daily personal mood. Therefore, in addition to quantitative measures of DPA, future studies with more reliable parameters related to quality of daily activities should be investigated, such as walking symmetry, variability, and regularity. Furthermore, a control group with patients who have no LBP could be used to determine if the severity of the chronic LBP correlates with the amount of time it takes to improve DPA. Additionally, in future studies, changes in DPA due to other types of neuromuscular disorders should be investigated.Subjective measures of pain and disability or even in-clinic measures of motor function (gait and TUG) after PSI for chronic LBP may not correlate with short-term (one-month) improvements in DPA. Clinically, chronic LBP patients may not expect an immediate increase in DPA immediately post-injection. Hypothetically, differences between in-home activity and in-clinic measures of motor function may be related to fear of pain  and could affect patients’ ability to perform activities of daily living. Future studies should include measures of fear-avoidance to better understand the underlying mechanism of DPA improvements. In addition, consideration of adjunctive cognitive behavioral therapy with therapists or coaches could help address thoughts, emotions, and behaviors related to LBP by examining unhelpful thinking patterns and devising new ways of reaching optimal DPA goals for patients undergoing PSI for LBP.


To compare the effect of metamizole versus etoricoxib as baseline analgesic for treating postoperative pain after tonsillectomy.Single centre prospective cohort study.Two consecutive cohorts of tonsillectomy patients.124 patients ; median age 30.5 years; 50% women.Patients rated their pain on first postoperative day using the questionnaires of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including numeric rating scales  for pain determination. The influence of preoperative and postoperative parameters on patients' pain was estimated by univariate and multivariate statistical analysis.The demographic parameters showed no differences between the patients in the metamizole group and the etoricoxib group  with one exception: Patients in the metamizole group had significantly more preoperative pain than patients in the etoricoxib group (p = 0.001). The metamizole group had a mean postoperative pain in activity of 4.4 ± 2.1 and the etoricoxib group of 4.5 ± 2.2. Maximal pain for the metamizole group and the etoricoxib group were 5.6 ± 2.2 and 6.1 ± 1.9, respectively. Pain in activity, maximal pain and minimal pain were not different between both groups . Patients of the etoricoxib group received more frequently piritramide in recovery room as demand medication (p = 0.046). In the whole cohort, patients with peritonsillar abscess had more preoperative pain in comparison to chronic tonsillitis (p<0.001). Patients under 30.5 years reported higher maximal pain than older patients (p = 0.049). On the other hand, a significant influence of patients’ age on the pain in activity and minimal pain could not be demonstrated . Men reported lower minimal pain than women (p = 0.041). Also, patients with ASA status I had lower minimal pain than patients with higher ASA status (p = 0.019). The multivariate analysis did not show an association between postoperative pain in activity and preoperative counseling on postoperative pain management . Special preoperative counseling on postoperative pain management resulted in lower levels of maximal pain (p = 0.024). Linear regression demonstrated an independent association of higher pain in activity with higher mobility impairment (p = 0.034) and respiratory impairment (p = 0.002). The linear regression of minimal pain identified female gender (p = 0.005) as an independent influencing factor with higher pain levels. In terms of satisfaction, no preoperative pain therapy (p = 0.016) could be found as an independently significant influencing factor with higher satisfaction.Etoricoxib does not have an advantage as baseline analgesic for post tonsillectomy pain in comparison to metamizole. Tonsillectomy, the surgical removal of the palatine tonsils, is still one of the most common surgical procedures in adults. For instance, 54.441 tonsillectomies were performed in Germany in 2014 . QUIPS wFor pain therapy after tonsillectomy typically a combination of a non-opioid as basic analgesic with an opioid is used in adults, e.g. a non-steroid anti-inflammatory drug (NSAID) like metamizole and more recently, also cyclooxygenase (COX)-2-inhibitors are combined with an opioid like piritramide or tramadol.The present prospective clinical study used QUIPS data to analyse 1) if the COX-2-inhibitor etoricoxib 90mg per os once a day in the morning as basic analgesic after tonsillectomy reduces postoperative pain better than metamizole 1g intravenous four times a day every six hours, 2) the quality of pain management after tonsillectomy, and 3) other factors that influence postoperative pain.The present prospective cohort study was part of the German-QUIPS registry. Institutional review board approval was obtained prior to study initiation by the Ethics Committee of the Jena University Hospital, Thuringia, Germany. The patients gave written consent.Patients treated in the hospital as in-patients between November 2008 and May 2009 (metamizole cohort) and February 2013 and December 2013 (etoricoxib cohort) were included. By German law, the German procedure classification (OPS-301) has to be used by all German hospitals for coding of surgical procedures (OPS codes). To select all patients with tonsillectomy, first all patients with the OPS codes 5–281.0 (tonsillectomy without adenoidectomy) and 5–281.1 (tonsillectomy for peritonsillar abscess) were selected. 124 of 189 adult patients were included. 55 patients were excluded because they refused to participate, and 5 patients because of a lack of knowledge of the German language. One patient was in bad physical conditions and not able for performing the questionnaires. In two cases the histopathological examinations revealed a malignant tumor. In two patients the medication for pain management was not following the protocol and therefore they were excluded.The QUIPS questionnaires are presented in detail elsewhere . The QUIThe statistical analysis was performed with IBM SPSS statistics software (Version 23.0.0.0). Data are presented as mean ± standard deviation (SD) if not otherwise indicated. Clinical and outcome parameters of all patients were summarized descriptively. To compare the metric data of two independent groups the nonparametric Mann-Whitney-U-test was used. If there were variables with more than 2 possible answers, the nonparametric Kruskal-Wallis-ANOVA-test was used. To check for significance in nominal variables, Pearson`s chi-square test was applied. The significance level was set at p<0.05. For the comparison of dependent variables, the nonparametric Wilcoxon-test was used. For correction of multiple testing, the Bonferroni method was applied. Multivariable binary logistic regression models with stepwise entry were used for the dichotomized categorized outcome parameters to analyse the association to pain-related interferes and pain therapy side effects. Patients’ characteristics and clinical parameters for regression analysis were derived from those suggestive for significant associations from the univariate analyses (p<0.05). In general, nominal p values of two-tailed tests are reported.Patients`characteristics are documented in In S2 and .There was a significant correlation between the age of the patients and the maximal pain. Patients younger than 30.5 years reported significantly higher maximal pain than older patients (p = 0.049). A significant influence of patients’ age on the stress pain and minimal pain could not be demonstrated . Men reported lower minimal pain than women (p = 0.041). Patients with ASA status I had significantly lower minimal pain than patients who belonged to ASA groups II and III (p = 0.019). For pain in activity, maximal pain and minimal pain there were no significant differences between metamizole and etoricoxib group. The results of the univariate analyses on factors associated to postoperative pain are summarized in Younger patients felt more affected by pain in their mood than older patients in the group . The diagnosis of chronic tonsillitis was associated with lower satisfaction scores; Patients with a diagnosis of peritonsillar abscess, on the other hand, were significantly more satisfied with pain management (p = 0.002). Detailed values can be found in S7 and  The counseling was performed by the same physician who explained the surgery. The general counseling included the fact that tonsillectomy will lead to pain. This pain will be treated by pain medication. The detailed counseling included information about the difference of baseline and PRN medication. The patients were asked not to hesitate to ask for PRN medication. It was explained how important it is that the patient does not reach pain peaks as late as before asking for pain medication. The short-term use of opioids was explained in detail.Patients who received opioids in the recovery room reported significantly higher maximal pain than those in the recovery room without opioids (p = 0.011). The same was observed with the administration of opioids on ward (p < 0.001). This was also evident with regard to pain in activity (p = 0.001). When a patient received metamizole in the recovery room, he also reported higher minimal pain (p = 0.049). In contrast to tramadol and tilidine, patients receiving piritramide had significantly more pain in activity and maximum pain than patients who did not receive piritramide . The choice of baseline pain medication on ward had no significant effect on postoperative pain intensity: pain in activation, maximal pain and minimal pain were not significantly lower in the etoricoxib group than in the group receiving metamizole . Also, there was no significantly lower pain in the etoricoxib group in those patients who had already received etoricoxib preoperatively as premedication . Already preoperative pain therapy was associated with higher pain in activity (p = 0.003) and maximal pain (p = 0.020). In addition, significant correlations between pain counseling and the pain intensity were found: Patients informed about special pain therapy procedures reported lower pain in activity and maximal pain . Detailed values can be found in No significance association could be found between the pain in activity and preoperative counseling on postoperative pain management . Special preoperative counseling on postoperative pain management resulted in lower maximal pain (p = 0.024).Linear regression demonstrated higher mobility impairment (p = 0.034) and higher respiratory impairment (p = 0.002) as independent factors for more pain in activity; that means, patients with more pain received more opioids, so that the increased administration of opioids could be related to respiratory impairment and mobility impairment because of respiratory impairment.Table 4.Female Gender (p = 0.005) was an independent influencing factor for more minimal pain. In terms of satisfaction with pain therapy, only the preoperative pain therapy (p = 0.016) could be found as an independently influencing factor with lower satisfaction in case of preoperative pain therapy. Details on the multivariate analyses can be found in Although tonsillectomy is known to be one of the most painful surgeries, there iStrengths of this study are the large sample size and the standardized assessment of process and outcome parameters with QUIPS . The weaOne should also be aware that COX-2-inhibitors have a specific safety profile. Due to a higher risk of cardiovascular risks compared to NSAIDs , the appYounger patients under 30.5 years reported higher maximal pain than older patients. Patients younger than 50 years were significantly more affected in their mood than patients who were older. The literature often reports a lower level of pain experienced by older patients compared to the younger ones , 13, howFor pain therapy in the recovery room 41% of patients received a non-opioid (mainly metamizole), while 48% of patients received the opioid piritramide. There was a significant difference between the etoricoxib group and the metamizole group in 39%. The PRN administration of significantly more piritramide in the group of etoricoxib could be part of the conclusion that metamizole showed better analgetic results.The positive correlation between maximal pain and administration of opioids in the recovery room and between minimal pain and administration of metamizole in the recovery room found in the univariate analysis could not be confirmed as independent factors in the multivariate analysis. In contrast, Inhestern et al., also using the QUIPS tool, showed a correlation between the administration of opioids and non-opioids and the pain or pain-related impairments on the first postoperative day . InhesteDespite important pain levels, the satisfaction with the pain therapy was quite high in both groups. Such a paradox effect has been described in numerous studies , 18, 19.Mood impairment and the desire for more painkillers were factors influencing satisfaction with pain therapy. A negative influence of pain in activity or maximum pain on satisfaction found in the analysis could not be confirmed as independent in the multivariate analysis.It has been already shown that preoperative counseling of patients can lead to a significant reduction of postoperative pain. Two recent studies were able to demonstrate a positive influence of the preoperative special education about the pain therapy on pain parameters, postoperative impairments and the satisfaction of the patients by means of QUIPS, 26. A tIt will be necessary to continue to search for suitable painkillers or pain therapy concepts and to test their effectiveness with the help of QUIPS. Maybe a combination of diclofenac, etoricoxib or metamizole with oxycodone or a combination of tilidine and naloxone is conceivable. In the future pain should be asked standardized daily from the first postoperative day to the last day in hospital. After each pain therapy the pain intensity should be collected and compared with the success of therapy. The preoperative counseling of patients about pain therapy should be an integral part of conservation between doctor and patient because it could have a positive effect on postoperative pain.The present study on 124 adult tonsillectomy patients showed average pain values above the intervention limit of 4 on the NRS despite standardized pain therapy. Optimal post-tonsillectomy analgesia remains unclear. The administration of etoricoxib as a basic analgesic did not improve the level of pain when compared directly to metamizole. It will be necessary to continue to search for suitable painkillers or pain therapy concepts and to test their effectiveness with the help of QUIPS. Maybe a combination of diclofenac, etoricoxib or metamizole with oxycodone or a combination of tilidine and naloxone is conceivable. In the future pain should be asked standardized daily from the first postoperative day to the last day in hospital. After each pain therapy the pain intensity should be collected and compared with the success of therapy. The preoperative counseling of patients about pain therapy should be an integral part of conservation between doctor and patient because it could have a positive effect on postoperative pain.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.S7 Table(DOCX)Click here for additional data file.S8 Table(DOCX)Click here for additional data file.


There is an increased enthusiasm in treating osteolytic metastatic acetabulum via injecting polymethyl-methacrylate (PMMA) as a bone filler to provide pain relief and potential structural support. The aim of this respective study is to determine the function and quality of life improvement after cement acetabuloplasty.Thirty two patients underwent acetabular cement augmentation between May 2014 and March 2018 were respectively reviewed. Isolated percutaneous acetabuloplasty (PA) was performed in 15 patients (group A) while radiofrequency ablation with PA (RFA-PA) in 12 patients (group B). Together with PA, open reconstructive surgery on ipsilateral femur was performed in another 5 cases (group C). Pre- and posttreatment functional evaluation and quality of life (QoL) assessment were carried out.P = .00). Significant improvement (P = .00) was observed in scales of global QoL and pain-related restrictions in daily activities. Both isolated PA and RFA-PA procedures were equally effective towards the improvement of function and quality of life (P > .05). Regarding 5 patients in group C, pain intensity decreased when loading the affected limb and they could walk with crutches or cane.The average followup duration was 11.5  months. None of major complications occurred. 81.2% (26/32) of patients achieved complete pain relief. Reduction of pain intensity and improvement of functional status achieved significantly differences after treatment (Bone cement acetabuloplasty is an adequate and effective mini-invasive procedure to relieve pain, restore function, and enhance the quality of life of patients for as long as possible in metastatic patients with short life expectancy. Ipsilateral surgery appears to be safe and well tolerated. Therefore, function and QoL are profoundly important considerations when treating metastatic disease of the acetabulum due to the patient's limited life expectancy.The number of patients suffering from metastatic carcinoma to the pelvis has been increasing, and, osteolytic lesion at weight-bearing dome will cause hip pain and decreased mobility, with a significant degradation of quality of life (QoL).,5 When nonoperative treatment options unable to provide pain relief or function restoration, operative intervention should be indicated. However, currently, no specific guidelines exist that provide indications for surgical intervention of acetabular metastases. The Harrington periacetabular reconstructive surgery is technically challenging, and carries a substantial risk of complications, the undesirable effects of this large operation may outweigh the clinical benefits for those patients.,7External beam radiation therapy helps reducing hip pain, however, 20% to 30% of patients reported no pain relief, and also radiation does not improve the mechanical properties of the affected acetabular region. in 1995, and a few reports thereafter have shown this technique is reliable for the management of acetabular osteolysis in patients who cannot be candidates to major surgery and in patients whom radiotherapy was not effective. Recently, radiofrequency ablation (RFA) has been reported to be used for metastatic bone disease or combined with PA (RFA-PA) in the same procedure.–11 We conducted this retrospective study and hypothesized that the combination of RFA and PA has additional merits for local tumor control and produces better clinical outcome compared with PA alone. Moreover, few papers addressed the quality of life improvement after the procedure.Percutaneous acetabuloplasty (PA), analogous to vertebroplasty, was first adopted by Cotten et al2This study was approved by Review Board/Ethics Committee of the Peking University People's Hospital. Informed consents from all subjects were waived due to the retrospective nature of this study. The medical files of 32 patients with acetabular metastases (Harrington III) treated with PA at our institution between May 2014 and April 2018 were retrospectively reviewed  and magnetic resonance imaging. Tumor size was calculated on measurement of the largest cross sectional area of a given lesion in coronal, axial, and sagittal planes on 2-mm-slice CT scans. The decision make process was carried out from patient's general condition and life expectancy, starting from a minimally invasive palliative treatment to periacetabular reconstructive surgery. Tables  and Musculoskeletal Tumor Society score (MSTS), respectively. QoL was assessed using the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire (QLQ-C30), which consists of 5 functional scales , 3 symptom scales , and a global health and quality-of-life scale. Each health profile is scored on a 100-point scale: a higher score in the functional scales indicates better function while a higher score in the symptom scales reflects a heavier symptomatic burden; a higher score on the global health and quality-of-life scale indicates better health and better QoL.All patients were evaluated before and 1, 3, 6, 12 months after treatment regarding pain, general condition, and function related to surgery, by using the Visual Analog Scale (VAS), the Eastern Cooperative Oncology Group performance status (ECOG),P = .03). All patients were incapacitated by hip pain. Twenty-three (71.9%) had severe pain requiring continuous use of narcotics, 9 (28.1%) had moderate pain requiring periodic use of narcotics. Ten (31.3%) of them could not walk, 14 (43.7%) needed crutches or a single cane to walk, and the remaining 8 walked without assistive devices.Fifteen men and 17 women with an average age of 57.6  years were included. Eighteen patients had history of cancer and the other 14 patients presented with acetabular metastasis at diagnosis and received biopsy during the same procedure. Twenty-five patients (78.1%) had multiple bone lesions, while 7 with solitary bone lesion. All metastatic acetabular bone lesions with non-small cell lung cancer (12 cases) and breast cancer (5 cases) occurring most frequently. The mean time interval between the diagnosis of lung cancer and the manifestation of the acetabular metastasis was 0.5  month, while for breast cancer was 110.4  months , while the RAF-PA in 12 patients (group B). In the other 5 patients (group C), together with PA, the proximal femoral locking plate or intramedullary nail was implanted to prevent impending fracture of ipsilateral femoral diaphysis in 3 patients; a femoral head prosthesis . The procedure was conducted according to the protocol supplied by the equipment manufacturer. Once the target intra-tumoral temperature of 100 °C was obtained, this temperature was maintained 5 to 10 minutes, which was considered as an indicator of adequate thermocoagulation. A single ablation was performed in 5 patients with lesions ≤3 cm in the longest diameter. For large lesions >3 cm in the other 7 patients, the cluster RFA electrode technique (4 needles spaced 5 mm apart) was used.Polymethyl methacrylate (PMMA) was mixed and injected through the trocar into the lesion using a screw injector  with intermittent fluoroscopy to monitor cement distribution. During the procedure, we mobilized the hip joint just in case of unwanted cement extravasation into the joint space. Although there was no explicit criterion for adequate cement filling within the lesion, in general, we sought to fill the weight bearing surface and at least 50% of the lesion under positive injection pressure. After the procedure, AP and lateral radiographs and CT scans showed a more precise determination of the filling Fig. .While, in group C, the 5 cases required ipsilateral femur fixation or alloplasty, and the cement was injected using an open surgery method.2.2The patients of groups A and B were permitted to walk with partial weight-bearing the next day. Multiplex bisphosphonates were administrated to all patients after the procedure. Adjuvant treatment was administrated in 27 patients (84.3%) according to the primary tumor's histology: systemic chemotherapy or targeted medicine in 5 cases, radiotherapy in 14, and combination therapy in 8 patients. Routine followup evaluation was performed 1, 3, 6, 12 months postoperatively. Each followup evaluation included clinical and imaging studies.2.3t tests and Fisher exact test. Paired-samples t tests were applied to compare the pre- and posttreatment scores of VAS, ECOG, MSTS, and each domain of QLQ-C30. Significance was set at P < .05.Statistical analysis was carried out using SPSS software package version 16.0 . The comparison of demographic and clinical variables among groups was analyzed by using the independent samples 3Mechanical stabilization of the acetabular lesion was achieved in all patients. Five patients (2 in PA and 3 in RFA-PA) experienced transitory worsening in pain following injection, and resolved spontaneously within 48 hours. The average volume of PMMA injection was 9  mL. Small cement leaks into soft tissue due to cortical osteolysis or puncture holes were detected in 6 patients (18.7%) without clinical symptoms. Other potential complications including pulmonary embolism, vascular or nervous injury, hip joint cement leakage, and infection were not observed. Complete pain regression was achieved in 26 patients (81.2%) after treatment, and pain reduction in 6 patients (19%) who required periodic use of narcotics, and the pain did not increase when loading the affected limb.P = .13). Posttreatment radiographs did not reveal osteolysis in the area of cementation, bone cement dislocation, or loosening within the acetabular bone  months. During the followup, 9 patients  received further operation at tibia, humerus, clavicle, thoracic, or lumber spine, respectively. All patients were alive at 3 months; at 6 months 4 patients died of disease; at 12 months, another 7 patients died of disease; after 12 months, another 3 patients were dead. Eight of 12 patients with lung cancer metastases died at the mean of 9.5  months after treatment despite of systematic chemotherapy or targeted medicine, while only 1 of 5 patients with breast cancer died of brain metastasis at 11 months after PA . With regard to physical function, although more restrictions were complained in scales of long distance walk and heavy luggage carry, there was slightly improvement after treatment compared with pretreatment score . Restrictions in the ability to perform hobbies or other daily activities (role function) were reported to be a mean score of 31.05, a slightly difference to 27.27 pretreatment (P = .06). With respect to other functional scales , no significant difference was found after treatment. A minor improvement (P = .08) was observed in the scale of sleeping component due to pain relief after treatment. Significant improvement  was seen in the symptom domains of pain and pain-related restrictions in daily activities. Also, the scores of financial difficulties were 62.12 pretreatment and 68.18 posttreatment, and the difference was more pronounced (P = .04).The QoL improvement of the patients after treatment was also evident. Most patients restored the ability of carrying out standard daily activities. The mean functional and symptom scores of QLQ-C30 before and after treatment were shown in Table 3.2P = 1.000, Fisher exact test). At baseline, the median scores of VAS, ECOG, MSTS, and QoL were 7.40, 2.66, 38.15%, and 33.98 in group A, while in group B they were 7.50, 2.83, 36.00%, and 39.80, respectively. In terms of pain, limb function, and QoL improvement, the superiority of RFA-PA procedure did not reach significant differences over PA alone, as shown in Table To detect whether the application of RFA has added benefits, we compared VAS, ECOG, MSTS, and global QoL between groups A and B. Groups A and B were similar regarding the age, the median size of bone lesion, the cement injection volume, and the average followup period Table . Also, 13.3For 5 patients in group C, the mean VAS, ECOG, and MSTS score were 8.0, 3.2, and 30% respectively before the surgery, and 4.2, 3.0, and 34% at 1 month, 3.8, 2.8, and 38% at 3 months, 4.3, 3.0, and 41% at 6 months, and 5.5, 3.0, and 30% at 12 months after treatment, respectively. Three patients could walk with 1 crutch or cane and 2 patients with 2 crutches. Regarding the improvement of health-related QoL, the following mean scores were recorded at last followup was 35.01 compared with 29.98 preoperatively.4 There was a statistically significant improvement of QoL after surgery (P = .00), and pain reduction was also significantly changed (P = .00). In addition, 14 of 46 patients underwent curative en-bloc resection did not have survival benefit compared with curettage (P = .61). Another study conducted by Ruggieri et al also did not demonstrate any statistically significant difference in oncological outcome between the patients after wide resection and those after intralesional resection. In line with this, we have explored alternative methods of providing structural reinforcement which are less invasive and less prone to the major morbidities of open reconstruction in recent years.Our center previously presented the data of 46 patients who underwent Harrington reconstructive surgery for peri-acetabular metastases in 2011.Some limitations in our study included its retrospective nature, small population size, the heterogeneity of the histotype, multiple bone lesions, and lack of adjustments for other potential confounders such as pre-procedure analgesic use and concurrent radiotherapy/chemotherapy. However, we included only lesions located at acetabular dome (Harrington III) without soft tissue mass/neurovascular bundle compression in this study to make the evaluation parameters comparable. Lesions in the ilium, sacrum, medial wall (Harrington II), or involving the entire hemipelvis were excluded. The mean duration of followup was only 11.5 months, which is within the range reported by other series, possibly it is due to 37.5% (12/32) of the patients were metastatic lung carcinoma.–19 Maccauro et al have performed PA in 25 patients, complete pain regression was recorded in the majority of patients. In Gupta's study, 11 patients with lytic metastases to acetabulum underwent percutaneous acetabuloplasty, 81.8% of them achieved complete pain regression. Moser et al observed a therapeutic response in 78.1% of 44 pelvic metastatic lesions (30 located at acetabulum). Two main factors, we believe, may account for pain relief. One is the exothermic reaction developed during the polymerization of the cement mediates tumor eradication or neurolysis of pain fibers. The another is that PMMA provides structural buttressing of the weight-bearing portion of the joint even with subtotal lesional filling, resulting in improved biomechanics.As we expected, cement injection succeeded in achieving satisfactory pain relief in this cohort of patients (81%), which was similar to previous reports.,20 It is understandable, because 25 patients (78.1%) in this study had multiple bone lesions , obviously, the general condition of our patients was poorer and 9 patients received further operations for other bone metastases. Therefore, the general condition improvement evaluated by ECOG index was not significant. However, the functional performance status assessed by MSTS score was significantly improved after the treatment  was seen in the scales of symptom domains of pain and pain-related restrictions in daily activities. Interestingly, we observed that the change of financial difficulties was more pronounced (P = .04) in this series, we think it was related to the increasing economic burden of chemotherapy, radiotherapy, or targeted medicine or more operations needed to solve metastasis at other sites.In terms of improvement of QoL, few studies have addressed this issue. Scaramuzzo et al,16–19,21 some studies suggest that the combination of RFA and cement injection may have a synergistic effect on pain management.–11 The majority of these studies are single-arm observational studies and there is lack of level 1 evidence supporting increased efficacy in pain management following combined RFA and cement injection. Toyota et al described RFA combined with cementoplasty in 17 patients. Pain relief was achieved in 100% of patients, the mean duration of pain relief was 7.3 months. Wallace et al reported the outcomes of 12 patients who underwent RFA combined with cementoplasty. The median posttreatment pain score was 3, a significant difference compared with pretreatment of 8 (P = .00). 73% of patients experienced partial pain relief and no immediate symptomatic complications occurred after treatment. In a retrospective single-center observational study, 55 spinal metastases received combined RFA and vertebroplasty over a median follow-up period of 34 weeks, Wallace et al reported 89% (41/46) and 70% (21/30) radiographic local control rate at 3 months and 1 year post procedure, respectively, despite systemic metastatic disease progression. These preliminary results from combined RFA and cement augmentation were promising. In contrast, Orgera et al performed a randomized controlled trial of 36 consecutive patients with spinal osteolytic lesions secondary to multiple myeloma, reported similar pain scores post procedure in both vertebroplasty alone and combined RFA and vertebroplasty groups . Both groups also had similar analgesic use and functional levels at all time points without any major complications following procedure. They concluded that additional RFA may not provide added benefit in pain management of patients with multiple myeloma and vertebral deposits in the medium term. However, to date, there has been no published trial on the topic of acetabuloplasty in a population of patients with metastatic acetabular osteolytic lesions.While RFA and cement acetabuloplasty are independently effective in pain palliation,–18,21,25 also indicated that the exothermic reaction arising from the cement's polymerization is basically the same as that obtained by radiofrequency, therefore, no increase of cytotoxic effect on tumor should be obtained. Finally, the majority of patients had postoperative radiation in this study, radiation after cement injection which may act synergistically to achieve better pain palliation and local tumor control.In this study, the information of the 2 procedures was documented, with regard to the sex, the average age, the median volume of bone lesion, the cement injection volume, and the average followup period. There were no significant differences between these 2 groups Table , which mIt is difficult to decide which parameters must be considered to perform isolated PA or RFA-PA. The combination selection could be the inclination of the surgeon and the blood supply of the tumor, particularly in patients who do not respond to medical therapy for the systemic disease. Therefore, we have to state explicitly here that this study does not currently constitute sufficient evidence to recommend a change in practice, for example, the cessation of radiofrequency ablation treatment. Hence, a randomized prospective comparative assessment of the 2 techniques is urgently requiring.,22 The clinical and functional results of resection alloplasty on the proximal femur combined with periacetabular cement injection were good. This enables the patients to avoid the risk of hemorrhage, and the problems linked to open acetabular reconstruction (patient 29 and 30). The same considerations were made for combined lesions of the femoral shaft and the acetabulum in another 2 patients (patient 28 and 32) and 1 patient with bilateral femur disease (patient 31).The contemporary presence of an impending proximal femoral fracture was an indication for acetabular cementoplasty during the same anesthesia, which was also reported in previous reports.5The growing number of cases in literature together with our consecutive series support that PA is an effective therapeutic mini-invasive procedure to improve patient's functional performance and health-related QoL in a specific group of patients with minimal complications. PA can also be used for combined lesions of the acetabulum and the ipsilateral femur.The authors thank Ms Yanchun for assistance with data collection.Conceptualization: Taiqiang Yan.Data curation: Taiqiang Yan, Zhiqing Zhao, Xiaodong Tang, Rongli Yang, Shun Tang.Formal analysis: Zhiqing Zhao, Sen Dong.Supervision: Wei Guo.Writing – original draft: Taiqiang Yan, Zhiqing Zhao, Xiaodong Tang, Wei Guo, Rongli Yang, Shun Tang, Sen Dong.Writing – review & editing: Taiqiang Yan.


BackgroundPain and discomfort at the tourniquet and wound site are recognised complications of carpal tunnel surgery. Studies have shown that longer tourniquet times lead to increased pain, local and systematic complications. We hypothesise that minimising the intraoperative tourniquet time will reduce post-operative pain and complications.ObjectiveOur aim is to present the results of our novel operative technique for carpal tunnel decompression which minimises tourniquet time.MethodThe study represented a prospective case series in which 55 consecutive and unselected patients with positive nerve conduction study results were operated on by a single surgeon at a single hospital site over a period of 12 months. The patients filled in a questionnaire based on a visual analogue score (VAS) (1-10) for pain at (1) first presentation at the clinic, (2) recovery in theatre post-operatively and (3) on discharge from care at 12 weeks post-operatively. Questions included the perception of pain at the tourniquet site and at the wound site.Results A total of 55  patients participated in the study. The average tourniquet time was 5 minutes 50 seconds. 98% of patients had a VAS of 1 at both the wound and tourniquet site post-operatively. One patent had a score of 3 at the tourniquet site. Eleven patients had undergone contralateral carpal tunnel decompression surgery. Of the remaining 43 patients, all said they would have the other side operated on in the same way.Conclusion We have demonstrated a safe and efficient technique to reduce post-operative pain by minimising tourniquet inflation time. Our patient cohort experienced no significant complications and minimal pain post-operatively. Carpal tunnel decompression under local anaesthetic is an accepted method of treatment for carpal tunnel syndrome . Pain anOur aim is to present a safe and reproducible operative technique for carpal tunnel decompression under local anaesthetic which aims to minimise post-operative pain caused by the tourniquet. Our technique focuses on reducing the length of tourniquet time by the surgeon to help reduce the post-operative pain for patients.Fifty-five consecutive and unselected patients with positive nerve conduction study results were operated on by a single surgeon at a single site over a period of 12 months. The patients filled in a questionnaire based on a visual analogue score (VAS) (1-10) for pain at (1) first presentation at the clinic, (2) at recovery in theatre post-operatively and (3) on discharge from care at 12 weeks post-operatively. Questions included the perception of pain at the tourniquet site and at the wound site.Patient pathwayThe procedure is explained to all patients during the consent process in the clinic. All patients are admitted as a day case procedure.Once in the operating theatre complex, the tourniquet is applied to the upper arm but not inflated in the anaesthetic room Figure . Local aFifty-five patients were included in this study and their demographics are displayed in the table below Table . The aveCarpal tunnel release has been shown to be an excellent procedure in relieving pre-operative pain and has a high patient satisfaction . The maiThe main limitation of our study is that we have described a single surgeon technique, therefore, our results may not be replicable accounting for variation in surgeon experience and skill. Secondly, patient-related outcome measures were not assessed, as our main outcome measure was post-operative pain scoring.We have demonstrated a safe and efficient technique for carpal tunnel release under local anaesthesia and tourniquet. By focusing on carefully timing the inflation and deflation of tourniquet, we were able to minimise overall tourniquet time and reduce pain for the patient. Our patient cohort experienced no significant complications and 98% of our cohort had no pain post-operatively and at follow-up.


Calciphylaxis is a rare and life-threatening disease that classically manifests with painful skin lesions. It occurs mainly in patients with end-stage renal disease (ESRD) treated with dialysis, has poor outcomes, and has no FDA-approved treatment. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. Data from 70 calciphylaxis patients who were evaluated at the Massachusetts General Hospital between January 2014 and April 2018 were collected from the institutional electronic database. The median age was 58 years (interquartile range [IQR]: 49–69 years), 60% were women, and 73% were of white race. Most (74%) patients reported severe pain at the time of calciphylaxis diagnosis with a median pain intensity score of 8/10 (IQR: 6–10) on a 0–10 pain scale. The median time from symptom onset to clinical diagnosis was 9 weeks (IQR: 6–16 weeks). The majority (87%) of patients presented with open necrotic wounds (advanced stage lesion) at the time of diagnosis. Common cutaneous clinical features included ulceration (79%), induration (57%), and erythema (41%), while common pathological features included cutaneous microvascular calcification (86%) and necrosis (73%). The presence of fibrin thrombi in skin biopsies was associated with pain severity (p = 0.04). The stage of a skin lesion positively correlated with the presence of necrosis on histological analyses (p = 0.02). These findings have implications for improving understanding of calciphylaxis origins and for developing novel treatments. Calciphylaxis, or calcific uremic arteriolopathy, is a rare and devastating disease characterized by calcification of microvessels in the subcutaneous adipose tissue, causing painful, ischemic skin lesions ,2. PatiePublished literature on calciphylaxis has largely focused on risk factors and outcomes; however, data regarding cutaneous clinical features of calciphylaxis and corresponding histological features are scant. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. We hypothesized that certain clinical features and previously described risk associations may predict histological features of calciphylaxis, and our study will improve the understanding of this enigmatic disease and its pathobiology, and enhance the development of novel future therapies.Data from 70 adult patients (age ≥ 18 years) with calciphylaxis who were hospitalized at the Massachusetts General Hospital between January 2014 and April 2018 and had a diagnosis of calciphylaxis via review of histopathology or clinical lesion characteristics were reviewed. Six patients did not have histopathology data available from skin biopsy, surgical debridement, or amputation and were not included in this study for detecting correlations between clinical and pathological characteristics. Data for the study patients were abstracted from the insititutional electronic database. The study protocol was approved by the Partners Institutional Review Board, and all data was anonymized before accession. These data included demographic  and clinical characteristics (body mass index (BMI), vital signs, pain score on a scale of 0–10, and cutaneous lesion characteristics), pathological findings, medications, laboratory results, and comorbid conditions. Patients having a pain score of 6 or more were classified as having “severe” pain, while patients having a pain score of 5 or less were considered as having “non-severe” pain. Cutaneous lesion characteristics included induration, ulcer, retiform purpura, livedo racemosa, black eschar, plaques, nodules, erythema, edema, lesion length, and lesion location. Histopathological characteristics included microvascular calcification , necrosis, adipose tissue necrosis, perieccrine calcification, fibrin thrombi, intimal fibrosis, fibrointimal hyperplasia, ischemia, panniculitis, and location of extravascular calcium deposition in the skin . Data for previously published risk associations for calciphylaxis , were abstracted .Each patient’s medical record contained information for at least one lesion. We applied a previously described schema to classify calciphylaxis lesions into four stages . A lesioEach patient’s most severe skin lesion was classified using the scoring system adapted from the Mayo Clinic . This waFrequency , median and interquartile range (IQR) were reported , and mean and standard deviations (SD) were reported . Categorical variables were compared using a Chi-squared test. Continuous variables were compared using a Wilcoxon rank sum test. To examine the associations between clinical and histological features of calciphylaxis, univariate logistic regression models were applied to compute odds ratio (OR) and 95% confidence intervals (CI). Univariate logistic regression models were also applied to examine the association between lesion stage and histological features.All analyses were performed using the SAS statistical software (version 9.4) . Statistical significance was set as P<0.05. To account for multiple comparisons while examining the associations between clinical and histological characteristics we applied Bonferroni correction by setting the significance cut off at <α/n (i.e. <0.001). To account for multiple comparisons while examining the associations between lesion stage and histological characteristics we applied Bonferroni correction by setting the significance cut off at <α/n (i.e. <0.01).Based on a lesion staging system described in the methods section , 20% of The most common site of skin biopsy was the upper thigh (50%). The most common histological features were microvascular calcification (86%) and necrosis (73%). Almost half (47%) of patients had fibrin thrombi present on histological analyses. Out of the 14% of patients who did not have microvascular calcification, diagnosis was confirmed by presence of perieccrine calcification and/or fibrin thrombi, with cutaneous ulceration.In terms of the location of calcification in the skin, the majority of microcalcification was found to be in the subcutaneous tissue (76%). Perieccrine calcification was noted in 23% of patients. Subcutaneous adipose tissue necrosis was reported in 39% of patients. Intimal fibrosis was noted in 25% of patients while fibrointimal hyperplasia was reported in 14% of patients. Among the five histological characteristics examined for the association, the stage of a skin lesion was associated with necrosis . This association, however, did not reach the statistical significance by Bonferroni correction. Additionally, the median length of a lesion was 2.5 cm (IQR: 2.0–5.0 cm) for patients reporting non-severe pain, and 5.0 cm (IQR:1.6–9.5 cm) for patients reporting severe pain.There was no significant association found between previously described risk factors for calciphylaxis  and clinical or histological features of calciphylaxis. There was no association between pain severity or fibrin thrombi and mortality.Our study identifies associations between cutaneous clinical features and histopathological findings in calciphylaxis patients. The presence of fibrin thrombi in skin biopsies was associated with pain severity and the stage of a skin lesion positively correlated with the presence of necrosis on histological analyses. Furthermore, microvascular calcification was found to be eight times more common in patients with ulcerated lesions than in those without.Our analyses suggest that there is frequently a significant delay in the diagnosis of calciphylaxis. Most patients have advanced stage lesions and severe pain at the time of diagnosis. The median number of weeks between the onset of symptoms and calciphylaxis diagnosis was 9 weeks (IQR: 6–16 weeks). In a nationwide German Registry study, it was found that the median time between onset and diagnosis was 24 days 11–50 days) [–50 days We noted that the presence of a fibrin thrombus on histology is significantly associated with pain severity. In fact, the presence of diffuse thromboses as well as thrombosis within calcified vessels has been shown to be more common in calciphylaxis patients than in other non-calciphylaxis diagnoses , includiThe association between fibrin thrombi and pain severity prompts us to speculate regarding an important role of fibrin in the etiopathogenesis of calciphylaxis. It is possible that cutaneous microvessels in patients with predisposition to calciphylaxis are chronically narrowed from calcification and then thrombosis triggers and dictates the onset and severity of acute pain by causing cutaneous infarction. The possible origins of fibrin and thrombus may include endothelial injury, vascular stasis, and/or local or systemic thrombophilias. Whether and how these factors disrupt the laminar blood flow in cutaneous microvessels in patients with calciphylaxis requires further mechanistic investigation.The lack of association between the previously described risk factors for calciphylaxis and histological characteristics may suggest that there is a final common pathway leading to calciphylaxis that leads to histological characteristics independent of risk factor exposure. Furthermore, this finding may suggest that the development and progression of calciphylaxis may be distinct phases with risk factors such as warfarin triggering the disease and yet unknown factors are responsible for the disease progression and clinical and histological features.Given that calciphylaxis patients face severe pain due to open skin lesions, finding novel therapies for pain relief is an integral part of a multi-disciplinary approach to treatment . A potenThe Mayo Clinic scoring system implemented in this study identified 32% of our patient cohort as having “Definite” calciphylaxis. However, all 70 patients had a confirmed diagnosis of calciphylaxis by histopathology or clinical suspicion suggesting that additional evaluation of its sensitivity and specificity and validation in prospective studies is required.There was no significant association between warfarin use and the pathological variables studied. Warfarin is a risk factor for developing calciphylaxis ,16,18,19Our study has limitations. A larger sample size may strengthen the significance of some of the notable findings between clinical characteristics and histopathological findings. In that regard, it is important to note that none of the associations were statistically significant after applying the correction for multiple comparisons. Correlation between these variables does not necessarily imply causation. Our study was a retrospective study, and we restricted our study to patients hospitalized at our institute, and thus future studies that include outpatients with calciphylaxis are needed. Investigation of clinical and histological correlation will not only improve our understanding of this rare yet life-threatening disease, but also help design experimental studies to uncover pathobiology, and our ability to develop effective therapeutic treatments. Future larger studies should examine whether and how calciphylaxis risk factors influence the clinical presentation and histological features.In conclusion, the majority of our patient cohort were middle-aged, had ESRD, and presented to the hospital with open, ulcerated lesions with severe pain, indicating a potential delay in diagnosis. Clinical characteristics may correlate with histopathological findings in calciphylaxis patients. The presence of fibrin thrombi is associated with pain severity, which opens a potential avenue for a future therapeutic target. These preliminary findings need confirmation in a larger prospective study.S1 Table(DOCX)Click here for additional data file.


After excision of a primary malignant melanoma (MM), treatment of stage IB or higher MM consists of sentinel lymph node biopsy (SLNB). If malignant cells are identified, a complete lymph node dissection (CLND) can be performed.To determine the natural history of pain and sensory changes after MM surgery.We prospectively followed 39 patients  from before inguinal or axillary surgery through 6 months after surgery on measures of pain intensity, sensory symptoms, allodynia, and questionnaires of anxiety, depression, and catastrophizing.P < 0.003); clinically meaningful pain  was reported by 3% of patients after SLNB-only compared with 40% after CLND (P < 0.001). At 6 months, all SLNB-only patients were pain-free. By contrast, 4 of 7 in the SLNB + CLND group still had pain (P < 0.002). At 6 months, symptoms of altered sensation or numbness were reported by 32% and 42% of SLNB-only patients, and by 67% and 67% of patients undergoing CLND surgery (both P > 0.05).No patient had pain preoperatively. Ten days after surgery, 35% had surgical site pain after SLNB-only compared with 90% after CLND (Acute pain is more common after CLND surgery. Undergoing SLNB followed by more invasive CLND surgery may increase the likelihood of pain at 6 months. Persistent sensory symptoms typical of those associated with nerve injury are more common after CLND. Surgery for MM is a good model for studying the natural history of postsurgical pain and sensory changes. If melanoma cells are found in the sentinel node, all regional lymph nodes may be removed at a later date through complete lymph node dissection (CLND). The most common complications after SLNB and CLND include pain, sensory changes, seroma, lymphedema, and wound infection.18Malignant melanoma (MM) is the fifth most common cancer in the United States with a projected estimate of 91,270 new cases and 9320 deaths in 2018.17 For melanoma, 2 retrospective studies reported sensory changes after MM surgery.9 Høimyr et al.9 reported 32% of 124 patients undergoing SLNB reported sensory changes and 14% reported pain at 2 years after surgery; of the 51 patients undergoing CLND, 84% reported sensory changes and 34% reported pain. Three prospective studies of pain after SLNB or CLND reported pain after surgery for MM (0.9%–8.9% of the patients). The study populations had similar demographics but were very heterogeneous in terms of length of follow-up, and their description of the definition of pain was lacking or minimal.18 A more extensive prospective literature exists within the field of breast cancer. However, breast cancer treatment often includes procedures that independently may contribute to postoperative pain, such as local radiotherapy and chemotherapy after lumpectomy or mastectomy, or neoadjuvant therapy consisting of a biopsy followed by chemotherapy and radiation before lumpectomy.In all body regions, the SLNB procedure typically requires a 3-cm incision to remove an average of 3 sentinel lymph nodes. For comparison, an axillary CLND incision is usually 7 to 10 cm long and an average of 15 to 20 lymph nodes is removed. The surgical field may expose the intercostobrachial, thoracodorsal, and long thoracic nerves. For an inguinal CLND, the incision is typically 15 to 20 cm long and an average of 10 to 15 lymph nodes is removed. The surgical field may expose the femoral, ilioinguinal, genitofemoral, and iliohypogastric nerves. Damage to these large nerves or smaller nerves in the surgical field can lead to sensory abnormalities and chronic neuropathic pain. Given the extent of tissue resection, reported complication rates of 50% from CLND have been reported.The purpose of this study was to prospectively describe the natural history of pain and sensory changes in MM patients undergoing only SLNB, only CLND, or SLNB followed by CLND.6 To be eligible, patients had to have: an expected survival of more than 6 months, be able to speak English, and be willing to provide written informed consent. Exclusion criteria were neurological disorders, preexisting neuropathic pain, medication use that could interfere with pain ratings or sensory assessments, or previous surgery in the affected area. Eligibility was confirmed by medical history, review of medical records, and neurological examination. The study was approved by the CPMC Institutional Review Board and conducted in accordance with good clinical practice and the Helsinki declaration. All patients gave written consent before study inclusion.At the Center for Melanoma Research and Treatment at California Pacific Medical Center (CPMC), all patients with newly diagnosed cutaneous MM scheduled to undergo axillary or inguinal SLNB or CLND at the CPMC between March and December of 2012 were invited to participate. Patients were diagnosed by a pathologist on the basis of a local resection of the skin lesion. Staging was performed according to AJCC criteria.11 recommendations for studies of postoperative pain. Patients were examined preoperatively  and postsurgically . If any of the lymph nodes removed during SLNB contained malignant cells, the patient would return for CLND approximately 30 days later. These patients would then complete 2 additional postsurgical visits analogous to V2 and V3 after SLNB: (V2b) at 4 hours after CLND and (V3b) at 10 days after CLND. The 3-month and 6-month follow-up visits would then follow the date of the CLND surgery. Patients not able to attend in person for the V4 and V5 visits were contacted by phone to complete the interview and questionnaires, but physical examination and sensory evaluation could not be completed.The study was designed as a 5- to 7-session prospective observational study Fig. . This de6 Anesthesia was maintained with inhaled desflurane or sevoflurane. Analgesia was provided using i.v. fentanyl or i.v. hydromorphone during the surgery. In all patients, a local anesthetic (lidocaine 1% or Marcaine 0.25%) was injected around the site of excision and wound closure. Melanomas stage T1b or above more severe stages were all reexcised with 1- or 2-cm margins, with or without a skin graft, in combination with an SLNB.Surgical procedures were performed by S.P. Leong. Adhering to AJCC-staging and guidelines, general anesthesia with intravenous (i.v.) propofol combined with the nondepolarizing neuromuscular blocker rocuronium was used.13 Intraoperatively, a gamma-probe was used to identify possible sentinel lymph nodes , which were then excised. The same technique was used in both inguinal and axillary regions. For patients with a positive SLNB, the CLND was performed within approximately thirty days. Complete lymph node dissection of the axilla was performed as en bloc resection of the lymphatic and fatty tissue of levels I, II, and III. The CLND of the groin was performed through an incision crossing the inguinal crease and en bloc resection of the contents of trigonum femorale.The lymphatic drainage system was imaged preoperatively by lymphoscintigraphy using a Lymphoseek.The schedule of events is shown in Table Pain was defined as the presence of any pain using a 100-mm Visual Analogue Scale (VAS) anchored by 0 = “no pain” and 100 = “worst pain imaginable.” Clinically meaningful pain was defined as pain of intensity ≥30/100. The primary outcome measure, overall pain during the past 48 hours, was rated before any testing was performed. For visits V2 and V2b-only, because they occurred 4 hours after surgery, overall pain during the past 48 hours was not relevant and patients were only asked about current pain severity at the SLNB or CLND site. At all visits, patients were asked about use of either opioid or nonsteroidal anti-inflammatory drug analgesics for symptoms related to SLNB or CLND.Patients reported “yes/no” to the presence of 6 sensory symptoms  and 3 pain descriptors  at the surgical site (SLNB or CLND).Allodynia severity was rated at all visits in the surgical sites (reexcision and SLNB or CLND) by gently stroking the skin with the 2.5-cm wide foam paintbrush 3 times at 1-second intervals. Patients and the investigator rated allodynia as present or absent. Allodynia ratings were not performed at V2 and V2b visits due to bandages and possible lingering effects of surgical local anesthesia.Sensitivity to mechanical stimulation was determined around the surgical sites (SLNB and/or CLND) using a 26.0-g von Frey hair. Each site was stimulated 3 times with 1 second between stimulations. After the 3 stimulations, patients were first asked whether they felt the stimulations (yes/no). If the stimulations were felt, the patients were asked whether stimulations were painful (yes/no) in comparison with a similar stimulus in an unaffected area.19 Each question is scored on a 0- to 3-point Likert scale allowing for a maximum of 21 points on each scale. For each scale, a score <8 is considered normal, a score of 8 to 11 is considered borderline abnormal, and a score >11 is considered abnormal.The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with measures of anxiety and depression.16 Each item is scored on a 0- to 4-point Likert scale for a maximum of 52 points. The PCS is designed to tap into 3 dimensions of catastrophizing: rumination (exemplified by “I can't stop thinking about how much it hurts”), magnification (exemplified by “I worry that something serious may happen”), and helplessness (exemplified by “It's awful and I feel that it overwhelms me”). Higher scores indicate a higher level of catastrophizing. A total score above 30 is considered clinically relevant.The Pain Catastrophizing Scale (PCS) is a patient-completed, 13-item questionnaire.Surgical reports as well as medical records after surgery were reviewed for the presence of complications such as seroma, wound infection, hematoma, and lymphedema.The goal of the study was to describe the natural history of pain and sensory symptoms in patients with newly diagnosed cutaneous MM undergoing SLNB, with or without secondary CLND, or CLND-only, for 6 months after surgery. The primary outcome was overall pain within past 48 hours. Given the number of outcomes in the anticipated sample size, types of procedures, and variety of body locations, the analyses were planned to be primarily descriptive.P values <0.05 were considered statistically significant.Where appropriate, a 2-sample test of 2 proportions was performed using STATA version 13.1 . Patient flow is shown in Figure Twenty-nine underwent only SLNB, 2 underwent CLND without preceding SLNB, and 8 underwent SLNB followed by CLND .At baseline (V1), no patients reported pain in the area where surgery was going to be performed. Figure P < 0.003; clinically meaningful pain P < 0.001).At 10 days after the SLNB procedure , 12 of 34 SLNB patients reported pain  with a mean VAS of 7.4 mm (0–89). Sixteen of the 34 patients were still taking opioid analgesics. At 10 days after CLND, 9 of 10 patients reported pain  with a mean VAS of 26.6 mm (0–68). Seven of the 10 patients were still taking opioid analgesics. The difference in proportions with pain and clinically meaningful pain was significantly greater after CLND (pain P = 0.15) and vs CLND-only (P < 0.002)]. No patient reported use of any type of analgesic for SLNB/CLND symptoms at 6 months.At the 6-month visit, 0 of 19 SLNB patients, 4 of 7 SLNB + CLND patients , and 0 of 2 CLND-only patients reported pain [proportion with pain SLNB + CLND vs SLNB-only ; the same was true for the proportion reporting numbness (P = 0.2). At 6 months, no patient reported burning or painful cold. However, as shown in Figure The 10 patients undergoing CLND also reported altered skin sensation and numbness as the most common sensory disturbances at 10 days after surgery; 60% reported altered skin sensation and 70% reported numbness. At 6 months after the CLND, 67% and 67% of the 9 patients with data reported altered skin sensation or numbness. Compared to the SLNB-only group, the proportion reporting altered skin sensation was not significantly different , and abnormal anxiety or abnormal depression on the HADS  and associated lesioning of the nerves as part of the procedure.The incidence of chronic postoperative pain varies across studies. This study is the first prospectively gathered quantitative data on pain severity in MM patients. These prospectively observed incidences of pain at 6 months are lower for SLNB but higher for CLND than in the retrospectively collected data of Høimyr et al., who reported “any chronic pain” in 14% of those undergoing SLNB-only  and in 34% of those undergoing CLND .Douleur Neuropathique en 4 Questions (DN4) has shown a high specificity (90%) and sensitivity (83%); it has been validated in painful diabetic neuropathy, spinal cord injury, breast cancer surgery, cancer, and lower back pain.5 Neuropathic pain often includes spontaneous and evoked pain. Evoked pain manifests as allodynia and/or hyperalgesia on examination, and described as a burning sensation, painful cold, or electric shocks. Spontaneous pain, may be described as an unpleasant or abnormal sensation, called dysaesthesia . Therefore, in our study, we interviewed patients for the presence of descriptors from the DN4 for allodynia, hyperalgesia, and sensibility changes. The most common sensory disturbances reported were altered skin and numbness in the area of surgery. These symptoms were still present at 6 months in over 30% for those undergoing only SLNB and in 67% at 6 months in those undergoing CLND (with or without prior SLNB). The incidence of tingling, pins and needles, and itching was actually higher at 6 months in the CLND group than at ten days. These observed incidences are similar to the retrospective study of Høimyr et al.,9 where 32% of those undergoing SLNB-only and 82% of those undergoing CLND reported sensory disturbances. Similar findings have been observed in breast cancer patients undergoing the same nodal procedures.1Several questionnaires have been developed to identify neuropathic pain. The Recruiting a substantial number of patients was not difficult, with 39 successfully enrolled over 7 months from a single melanoma surgical center-of-excellence. The major weakness of this study is the low number of patients and large amount of missing data due to the small number of participants returning for physical examination at the later follow-up time points. For example, sensory testing data at 6 months after surgery were available in only 10 patients. Many patients were lost to follow-up or provided 6-month data only by phone. The CPMC, part of the Sutter Health system, is an urban teaching hospital with a large melanoma program. It draws Sutter Health patients from all of Northern California and has many outside referrals. A substantial proportion of patients travel long distances to San Francisco. At 6 months, SLNB-only patients are considered “cured” and may not be engaged with ongoing treatment. Complete lymph node dissection patients receiving chemotherapy from their local oncologist, or those engaged in a clinical trial, may have no further contact with the surgeon and would have little motivation to make the long trek back to the study site. Telephone follow-up is suboptimal compared with an in-person interview for obtaining a pain VAS and completing questionnaires, and precludes sensory testing.Combined with the other advantages of the melanoma population  makes the postoperative pain after surgery for MM a viable model for studying neuropathic pain in a clinical setting. The strengths of this study are the prospective follow-up, standardized surgery performed by only one surgeon, and the interview-based symptom assessment.14 At 3.9 years, none of the 29 subjects who had been pain-free at 6 months had a recurrence of pain. Only 2 of the 14 subjects with postherpetic neuralgia (PHN) at 6 months still had pain at 3.9 years. One subject with PHN at 6 months was free of symptoms at 3.9 years but had very mild pain at 7.7 years. Sensory function continued on a path toward normalization, but was still abnormal in many subjects, especially those who met criteria for PHN at 6 months. Even at 7.7 years, reinnervation of HZ-affected skin was not apparent. That study demonstrated that resolution of pain and resolution of sensory disturbances are separate processes; pain may fully resolve, although sensory disturbances and loss of cutaneous innervation are permanent.An instructive prospective natural history study has been conducted in herpes zoster (HZ) patients systematically followed from rash onset with pain and sensory assessments, the capsaicin response test, and serial skin biopsy.11 future studies would benefit from strategies that would make it easier for patients to be evaluated directly at later time points for better phenotyping, and from preoperative collection of blood samples for genetic testing. Established normal values as reference for training of investigators, intensive standardized sensory testing, regular in-person follow-up visits, and tracking more closely the analgesic use of patients are all elements that if included in standardized protocols would increase generalizability of the results and help identify small differences, and that otherwise could have been hidden in confounding from variability in patient management.As proposed by Kehlet and Rathmell,We conclude that chronic pain after melanoma surgery may depend on the type of surgery. The less invasive procedure of SLNB is rarely followed by long-term pain. Persistent pain and sensory symptoms appear to be more common in patients undergoing CLND , which should be taken into account when discussing treatment with the patients.Prospectively studying neuropathic pain after melanoma surgery in a clinical setting may give valuable information on pain mechanisms and the process of acute pain becoming chronic, particularly because of the ease of patient recruitment, absence of preexisting pain, and the lack of complicating treatment comorbidities.The authors have no conflict of interest to declare.