Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

OBJECTIVE: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. METHODS: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. RESULTS: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. CONCLUSION: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Quantitative somatosensory assessments in patients with persistent pain following groin hernia repair: A systematic review with a meta-analytical approach.

OBJECTIVES: Quantitative sensory testing (QST) provides an assessment of cutaneous and deep tissue sensitivity and pain perception under normal and pathological settings. Approximately 2-4% of individuals undergoing groin hernia repair (GHR) develop severe persistent postsurgical pain (PPSP). The aims of this systematic review of PPSP-patients were (1) to retrieve and methodologically characterize the available QST literature and (2) to explore the role of QST in understanding mechanisms underlying PPSP following GHR. METHODS: A systematic literature search was conducted from JAN-1992 to SEP-2022 in PubMed, EMBASE, and Google Scholar. For inclusion, studies had to report at least one QST-modality in patients with PPSP. Risk of bias assessment of the studies was conducted utilizing the Newcastle Ottawa Scale and Cochrane's Risk of Bias assessment tool 2.0. The review provided both a qualitative and quantitative analysis of the results. A random effects model was used for meta-analysis. RESULTS: Twenty-five studies were included (5 randomized controlled trials, 20 non-randomized controlled trials). Overall, risk of bias was low. Compared with the contralateral side or controls, there were significant alterations in somatosensory function of the surgical site in PPSP-patients. Following thresholds were significantly increased: mechanical detection thresholds for punctate stimuli (mean difference (95% CI) 3.3 (1.6, 6.9) mN (P = 0.002)), warmth detection thresholds (3.2 (1.6, 4.7) °C (P = 0.0001)), cool detection thresholds (-3.2 (-4.9, -1.6) °C (P = 0.0001)), and heat pain thresholds (1.9 (1.1, 2.7) °C (P = 0.00001)). However, the pressure pain thresholds were significantly decreased (-76 (-123, -30) kPa (P = 0.001)). CONCLUSION: Our review demonstrates a plethora of methods used regarding outcome assessments, data processing, and data interpretation. From a pathophysiological perspective, the most consistent findings were postsurgical cutaneous deafferentation and development of a pain generator in deeper connective tissues. TRIAL REGISTRATION: CRD42022331750.

Effect of a Nurse Navigation Intervention on Mental Symptoms in Patients With Psychological Vulnerability and Breast Cancer: The REBECCA Randomized Clinical Trial.

Importance: The unmet needs regarding symptom management of psychological distress among patients with breast cancer must be addressed. However, little evidence exists on effective interventions, such as nurse navigation. Objective: To compare the long-term effects of the REBECCA (Rehabilitation After Breast Cancer) nurse navigation intervention vs usual care in patients with breast cancer who were psychologically vulnerable. Design, Setting, and Participants: This parallel randomized clinical trial recruited and evaluated for eligibility adult female patients with newly diagnosed breast cancer and symptoms of psychological distress (distress score of ≥7 points on Distress Thermometer) at Rigshospitalet in Copenhagen, Denmark, from August 2017 to October 2019. This study continued the work of a pilot study, extending the follow-up to 18 months. Patients who met the inclusion criteria were randomized to either standard care or the REBECCA intervention. Intention-to-treat analyses were performed from June 2021 to October 2022. Interventions: Patients who were randomized to the REBECCA intervention received nurse navigation and symptom screening as well as standard care. Standard care included regular treatment, nurse support at chemotherapy and radiotherapy appointments, and municipality-based rehabilitation. Main Outcomes and Measures: The primary outcome was distress, as measured using the Distress Thermometer. The secondary outcomes included symptoms of anxiety, symptoms of depression, breast cancer-specific health-related quality of life, fear of recurrence, sleep, cognitive function, patient activation, pain, health behavior, body mass index, and need for support. Long-term effects at 6, 12, and 18 months were examined using mixed-effect models, adjusting for randomization strata of age and treatment modality. Results: A total of 309 female patients were included in the analysis, with 153 patients randomized to the standard care group and 156 patients randomized to the REBECCA intervention group. Mean (SD) age was 56 (11) years with only small between-group differences. Patients receiving the REBECCA intervention compared with standard care had reduced (although not significant) symptoms of distress, especially at the 12-month follow-up (estimated effect = -0.51 [95% CI, -1.05 to 0.04]; effect size [ES] = -0.49). Significant effects were seen for symptoms of depression at 6 months (estimated effect = -1.39 [95% CI, -2.33 to -0.44]; ES = -0.27), and breast cancer-specific health-related quality of life at 12 months (estimated effect = 4.03 [95% CI, 1.28- 6.77]; ES = 0.31). Nonsignificant reductions were seen for symptoms of anxiety at 6 months (estimated effect = -1.00 [95% CI, -1.95 to -0.06]; ES = -0.21) and 12 months (estimated effect = -1.01 [95% CI, -1.97 to -0.04]; ES = -0.21), and a nonsignificant increase was seen for patient activation at 18 months (estimated effect = 3.52 [95% CI, -0.09 to 7.12]; ES = 0.25). Stronger intervention effects were observed for younger age, low patient activation, less education, and low social support. Conclusions and Relevance: Results of this study indicate that patients with breast cancer who were psychologically vulnerable (ie, having moderate to high psychological distress) did not experience significant reduction in distress with nurse navigation. Further research is needed to develop the intervention's framework and investigate its potential use in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03254875.

Use of Medical Supplies at the Roskilde Festival 2016: A Prospective Observational Study.

INTRODUCTION: Music festivals are popular events often including camping at the festival site. A mix of music, alcohol, drugs, and limited hygiene increases health risks. This study aimed to assess the use of medical supplies at a major music festival, thereby aiding planning at similar events in the future. METHOD: The Medical Health Care Organization (MHCO) at Roskilde Festival 2016 (Denmark) collected prospective data on disposable medical supply use and injuries and illnesses presenting to the MHCO. RESULTS: A total of 12,830 patient presentations were registered by the MHCO and a total of 104 different types of disposable medical supplies were used by the MHCO from June 25, 2016 through July 3, 2016. Out of 12,830 cases, 594 individuals (4.6%) had a potential or manifest medical emergency, 6,670 (52.0%) presented with minor injuries, and 5,566 (43.4%) presented with minor illnesses. The overall patient presentation rate (PPR) was 99.0/1,000 attendees and the transport-to-hospital rate (TTHR) was 2.1/1,000 attendees. For medical emergencies, the most frequently used supplies were aluminum rescue blankets (n = 627), non-rebreather masks (n = 121), and suction catheters for an automatic suction unit (ASU) for airway management (n = 83). Most used diagnostic equipment were blood glucose test strips (n = 1,155), electrocardiogram electrodes (n = 960), and urinary test strips (n = 400). The most frequently used personal protection equipment were non-sterile gloves (n = 1,185 pairs) and sterile gloves (n = 189). CONCLUSION: This study demonstrates a substantial use of disposable medical supplies at a major music festival. The results provide aid for planning similar mass-gathering (MG) events.

Effect of progressive resistance training on persistent pain after axillary dissection in breast cancer: a randomized controlled trial.

PURPOSE: Persistent pain is a known challenge among breast cancer survivors. In secondary analyses of a randomized controlled trial, we examined the effect of progressive resistance training on persistent pain in the post-operative year in women treated for breast cancer with axillary lymph node dissection. METHODS: We randomized 158 women after BC surgery with Axillary Lymph Node Dissection (ALND) (1:1) to usual care or a 1-year, supervised and self-administered, progressive resistance training intervention initiated 3 weeks after surgery. A questionnaire at baseline, 20 weeks and 12 months assessed the intensity and frequency of pain, neuropathic pain and influence of pain on aspects of daily life. We analysed the effect using linear mixed models and multinomial logistic regression models for repeated measures. RESULTS: A high percentage of participants experienced baseline pain (85% and 83% in the control and intervention groups respectively) and by the 12 month assessment these numbers were more than halved. A high proportion of participants also experienced neuropathic pain (88% and 89% in control and intervention group respectively), a finding that was stable throughout the study period. The effect on intensity of pain indicators favoured the exercise group, although most estimates did not reach statistical significance, with differences being small. CONCLUSION: For women who had BC surgery with ALND, our progressive resistance training intervention conferred no benefit over usual care in reducing pain. Importantly, it did not increase the risk of pain both in the short and long term rehabilitative phase.

Use of Medication at the Roskilde (Denmark) Music Festival 2015 - A Prospective Observational Study of 15,133 Treated Attendees.

BACKGROUND: Outdoor music festivals (OMFs) attract large numbers of guests and benefit from the help of large numbers of volunteers. Studies have previously described the injury patterns at OMFs, but no studies have described the use of medication and sales from on-site pharmacies at a large OMF. METHOD: The usage of medication and prescriptions in the Medical Health Care Organization (MHCO), including sales from the on-site pharmacy, at the Roskilde (Denmark) Festival 2015 were prospectively recorded. RESULTS: In excess of 130,000 attendees (guests and volunteers) participated in the Roskilde Festival 2015. The number of attendees contacting the MHCO was 15,133, of which 3,723 (25%) had a consultation with a doctor. Of all attendees evaluated by a doctor, 669 attendees received some form of medication in relation to the consultation. The MHCO administered and/or handed out a total of 6,494 units of prescription and over-the-counter medication, of which analgesics represented nearly 51%. Asthma was the condition with the highest proportion of attendees requiring pharmaceutical treatment, as 28 out of 48 (58%) received medication during the consultation. Sixty-five attendees received both medicine and a prescription. The MHCO handed out 562 prescriptions. In total, 609 prescriptions were redeemed at the on-site pharmacy. Antibiotics represented more than 78% of all redeemed prescriptions at the on-site pharmacy. CONCLUSION: The most utilized medications were analgesics and antibiotics. The data indicate a need for on-site prophylaxis using tetanus toxoid in combination with diphtheria toxoid vaccine and an on-site pharmacy. The content of the formulary at a mass-gathering event should be based on: evacuation time by ambulance/helicopter to hospitals with the level of competence needed; types of conditions to be treated on-site; level of competencies of festival medical staff; expected incidence and type of illness and injuries; and treatment of acute, life-threatening illnesses and or injuries.

Development and Validation of a Screening Tool for Surgery-Specific Neuropathic Pain: Neuropathic Pain Scale for Postsurgical Patients.

BACKGROUND: Despite the existence of several screening tools for neuropathic pain, none of these are specific to surgery. We have developed a simple questionnaire tool, the Neuropathic Pain scale for Postsurgical patients (NeuPPS), to measure neuropathic pain in postsurgical patients. OBJECTIVES: The aim was to validate this tool in a breast cancer population using an item response theory model, resulting in an easy-to-use scale. STUDY DESIGN: Development was based on literature reviews and interviews with patients and experts and consisted of 6 items. It was tested among 2,217 long-term breast cancer survivors, and cross-validated in another data set of breast cancer survivors with 18 months follow-up. SETTING: We tested the questionnaire tool among breast cancer survivors in 2 cohorts, one nationwide and one of consecutively treated patients at Rigshospitalet, Copenhagen, Denmark. METHODS: Items were assessed for criterion-related construct validity using the Rasch model, and for convergent validity by comparison to another neuropathic pain screening tool, the self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale. RESULTS: The selected 5-item model showed good fit, unidimensionality, monotonicity, and homogeneity. This result was reproducible in the cross-validation population. In a combined dataset with data from both studies, the model displayed a slightly lower fit, suggesting that items to some degree may vary over time. The Spearman rank correlation between the NeuPPS and S-LANSS was P = 0.57. LIMITATIONS: We observed differential item functioning between the primary study population and the cross-validation population, meaning that some items behave differently at different follow-up times or study populations. CONCLUSIONS: With the NeuPPS, we have validated a simple and easy-to-fill-out questionnaire tool for the measurement of neuropathic pain among postsurgical patients. The items are additive, giving a total score that measures neuropathic pain symptoms. KEY WORDS: Scale validation, Rasch analysis, item response model, persistent postoperative pain, intercostobrachial nerve, neuropathy, neuropathic pain, quantitative sensory testing, breast cancer.

The effects of individually tailored nurse navigation for patients with newly diagnosed breast cancer: a randomized pilot study.

AIM: Our aim was to determine the feasibility and effectiveness of an individual, nurse-navigator intervention for relieving distress, anxiety, depression and health-related quality of life in women who have been treated for breast cancer (BC) and are experiencing moderate-to-severe psychological and physical symptoms. METHODS: Fifty women with newly diagnosed BC who reported distress (score ≥7 on distress thermometer) before surgery were included consecutively in a pilot study and randomized 1:1 to the intervention or the control group. The intervention comprised repeated screening with patient reported outcome measures and nurse navigation. A total of 66 women who were not distressed (score <7) were followed longitudinally as an observational group. Participants filled in four questionnaires, at baseline, after 6 months and 12 months. The primary outcome was psychological distress and the secondary outcomes were anxiety, depression, health-related quality of life and feasibility of the intervention. RESULTS: Women in the intervention group reported significantly greater satisfaction with treatment and rehabilitation and lower levels of distress (mean 2.7 vs. 5.1, p<.01), anxiety (mean 5.1 vs. 7.8, p = .02) and depression (mean 2.2 vs. 4.4, p = .04) after 12 months compared to the control group. No significant effects were seen on health-related quality of life. CONCLUSIONS: The study shows promising feasibility of the individually tailored nurse-navigation intervention and while no significant effects were observed after 6 months, we did find statistically significant effects on distress, anxiety and depression 12 months after diagnosis. Our results will assist in developing rehabilitation to the most vulnerable patients.

The Relationship Between Sensory Loss and Persistent Pain 1 Year After Breast Cancer Surgery.

Moderate to severe persistent pain after breast cancer surgery (PPBCS) affects 10 to 20% of the patients. Sensory dysfunction is often concomitantly present suggesting a neuropathic pain state. The relationship between various postoperative pain states and sensory dysfunction has been examined using quantitative sensory testing (QST), but only 2 smaller studies have examined PPBCS and sensory dysfunction in the surgical area. The purpose of this prospective study was to assess the relative importance of sensory function and PPBCS. QST consisted of sensory mapping, tactile detection threshold, mechanical pain threshold, and thermal thresholds. Two hundred ninety patients were enrolled and results showed that 38 (13%) had moderate to severe pain and 246 (85%) had hypoesthesia in the surgical area 1 year after surgery. Increased hypoesthesia areas were associated with pain at rest as well as during movement (P = .0001). Pain during movement was associated with a side-to-side difference of 140% (P = .001) for tactile detection threshold and 40% (P = .01) for mechanical pain threshold as well as increased thermal thresholds in the axilla (P > .001). Logistic regression models controlling for confounders showed larger areas of hypoesthesia as a significant risk factor, odds ratio 1.85 per 100 cm2 for pain at rest and odds ratio 1.36 per 100 cm2 for pain during movement. PERSPECTIVE: PPBCS is associated with increasing areas of hypoesthesia as well as intraoperative nerve preservation. Thus, we hypothesize that PPBCS is associated with an interaction between a peripheral nociceptive drive in macroscopically preserved nerves and the central nervous system causing PPBCS as well as hypoesthesia. QST may identify patients suitable for intervention.

Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery.

Purpose Persistent pain after breast cancer surgery is a well-recognized problem, with moderate to severe pain affecting 15% to 20% of women at 1 year from surgery. Several risk factors for persistent pain have been recognized, but tools to identify high-risk patients and preventive interventions are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity at 1 year postoperatively were developed by logistic regression analyses in the Finnish patient cohort. The models were tested in two independent cohorts from Denmark and Scotland by assessing the areas under the receiver operating characteristics curves (ROC-AUCs). The outcome variable was moderate to severe persistent pain at 1 year from surgery in the Finnish and Danish cohorts and at 9 months in the Scottish cohort. Results Moderate to severe persistent pain occurred in 13.5%, 13.9%, and 20.3% of the patients in the three studies, respectively. Preoperative pain in the operative area ( P < .001), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen for patients at high risk of developing persistent pain after breast cancer surgery.

Pain, sensory disturbances and psychological distress are common sequelae after treatment of ductal carcinoma in situ: a cross-sectional study.

Sequelae such as pain, sensory disturbances and psychological distress are well known after treatment for invasive breast cancer (IBC). Patients treated for ductal carcinoma in situ (DCIS) receive a similar treatment as low-risk IBC. The aim of this cross-sectional study was to describe prevalence of postoperative pain, sensory disturbances, psychological distress and rehabilitation needs among Danish women with DCIS. METHODS: A total of 574 women treated for DCIS in Denmark in 2013 and 2014 were enrolled and 473 (82%) completed a detailed questionnaire on demographic factors, pain, sensory disturbances, psychological aspects and rehabilitation needs 1-3 years after surgery. RESULTS: Median age was 60 years. A total of 33% of patients reported any pain and 12% reported moderate to severe pain in the area of surgery. Younger age (<50 years OR 4.7 (95% CI: 1.6-14.0, p = 0.006)), aged 50 to 65 years OR 2.8 (95% CI: 1.1-7.0, p = 0.02) and anxiety and depression (measured by HADStotal >15 OR of 3.1 (95% CI: 1.5-6.3, p = 0.003)) were significantly associated with moderate to severe pain. Approximately one-third of the patients reported sensory disturbances such as pins and needles (32%), numbness (37%) and painful itch (30%) and 94 women (20%) reported anxiety ≥8, 26 (6%) depression and 51 (11%) reported distress. CONCLUSIONS: This cross-sectional study showed that women treated for DCIS suffered from pain, sensory disturbances and psychological impairment and had unmet rehabilitation needs. Further research is warranted, specifically addressing rehabilitation after diagnosis and treatment of DCIS.

Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) affects 25 - 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. OBJECTIVES: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. STUDY DESIGN: This prospective pilot study was performed in 2 parts: Part 1 determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. SETTING: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. METHODS: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic ultrasonography to establish the sonoanatomy of the ICBN. Part 2: Six patients with PPBCS who had pain in the axilla and upper arm were recruited for the study. Summed pain intensity (SPI) scores and sensory function were measured before and 30 minutes after the block was administered. SPI is a combined pain score of numerical rating scale (NRS) at rest, movement, and 100kPa pressure applied to the maximum point of pain using pressure algometry (max = 30). Sensory function was measured using quantitative sensory testing, which consisted of sensory mapping, thermal thresholds, suprathreshold heat pain perception as well as heat and pressure pain thresholds. The ICBN block was performed under ultrasound guidance and 10 mL 0.5% bupivacaine was injected. OUTCOME ASSESSMENT: The ability to perform the ICBN block and its analgesic and sensory effects. RESULTS: Only the second intercostal space could be seen on ultrasound which was adequate to perform the ICBN block. The mean difference in SPI was -9 NRS points (95%CI: -14.1 to -3.9), P = 0.006. All patients had pre-existing areas of hypoesthesia which decreased in size in 4/6 patients after the block. LIMITATIONS: The main limitation of this pilot study is its small sample size, but despite this, a statistically significant effect was observed. CONCLUSION: We have successfully managed to block the ICBN using ultrasound guidance and demonstrated an analgesic effect in patients in PPBCS calling for placebo-controlled studies.

Preoperative Distress Predicts Persistent Pain After Breast Cancer Treatment: A Prospective Cohort Study.

PURPOSE: Persistent pain after breast cancer treatment (PPBCT) affects 25% to 60% of breast cancer survivors and is recognized as a clinical problem, with 10% to 15% reporting moderate to severe pain several years after treatment. Psychological comorbidity is known to influence pain perception, and evidence links signs of depression and anxiety with development of PPBCT. The purpose of this study was to assess preoperative distress as a predictive factor for development of PPBCT. METHODS: Between October 2008 and October 2009, 426 women diagnosed with primary breast cancer, undergoing surgery at the Department of Breast Surgery, Rigshospitalet, Denmark, were invited to participate in the study. Patients filled out a questionnaire preoperatively, and 4 and 8 months after surgery. Preoperative distress was measured with the Distress Thermometer (DT; 11-point scale, 0-10). We examined the association between severe preoperative distress (using DT ≥7) and moderate to severe PPBCT 8 months after diagnosis using a logistic regression model. RESULTS: A total of 357 patients participated in this study and 291 (82%) returned all follow-up questionnaires. Preoperative distress was significantly associated with moderate to severe PPBCT at 8 months, with an adjusted odds ratio (OR) of 2.05 (95% CI, 1.18-3.59; P=.01), and at 4 months, with an OR of 2.23 (95% CI, 1.23-4.05; P=.01). CONCLUSIONS: Preoperative distress was associated with PPCBT, suggesting distress as an independent risk factor for PPBCT. Preoperative identification of patients at risk for PPBCT allows for further research in psychological and pharmacological treatment of this condition.

Predictive factors for the development of persistent pain after breast cancer surgery.

Previous studies have reported that 15% to 25% of patients treated for breast cancer experience long-term moderate-to-severe pain in the area of surgery, potentially lasting for several years. Few prospective studies have included all potential risk factors for the development of persistent pain after breast cancer surgery (PPBCS). The aim of this prospective cohort study was to comprehensively identify factors predicting PPBCS. Patients scheduled for primary breast cancer surgery were recruited. Assessments were conducted preoperatively, the first 3 days postoperatively, and 1 week, 6 months, and 1 year after surgery. A comprehensive validated questionnaire was used. Handling of the intercostobrachial nerve was registered by the surgeon. Factors known by the first 3 weeks after surgery were modeled in ordinal logistic regression analyses. Five hundred thirty-seven patients with baseline data were included, and 475 (88%) were available for analysis at 1 year. At 1-year follow-up, the prevalence of moderate-to-severe pain at rest was 14% and during movement was 7%. Factors associated with pain at rest were age <65 years (odds ratio [OR]: 1.8, P = 0.02), breast conserving surgery (OR: 2.0, P = 0.006), axillary lymph node dissection with preservation of the intercostobrachial nerve (OR: 3.1, P = 0.0005), moderate-to-severe preoperative pain (OR: 5.7, P = 0.0002), acute postoperative pain (OR: 2.8, P = 0.0018), and signs of neuropathic pain at 1 week (OR: 2.1, P = 0.01). Higher preoperative diastolic blood pressure was associated with reduced risk of PPBCS (OR: 0.98 per mm Hg, P = 0.01). Both patient- and treatment-related risk factors predicted PPBCS. Identifying patients at risk may facilitate targeted intervention.

Test-retest agreement and reliability of quantitative sensory testing 1 year after breast cancer surgery.

OBJECTIVES: Quantitative sensory testing (QST) is used to assess sensory dysfunction and nerve damage by examining psychophysical responses to controlled, graded stimuli such as mechanical and thermal detection and pain thresholds. In the breast cancer population, 4 studies have used QST to examine persistent pain after breast cancer treatment, suggesting neuropathic pain being a prominent pain mechanism. However, the agreement and reliability of QST has not been described in the postsurgical breast cancer population, hindering exact interpretation of QST studies in this population. The aim of the present study was to assess test-retest properties of QST after breast cancer surgery. METHODS: A total of 32 patients recruited from a larger ongoing prospective trial were examined with QST 12 months after breast cancer surgery and reexamined a week later. A standardized QST protocol was used, including sensory mapping for mechanical, warmth and cold areas of sensory dysfunction, mechanical thresholds using monofilaments and pin-prick, thermal thresholds including warmth and cold detection thresholds and heat pain threshold, with bilateral examination. Agreement and reliability were assessed by Bland-Altman plots, descriptive statistics, coefficients of variance, and intraclass correlation. RESULTS: Bland-Altman plots showed high variation on the surgical side. Intraclass coefficients ranged from 0.356 to 0.847 (moderate to substantial reliability). Between-patient variation was generally higher (0.9 to 14.5 SD) than within-patient variation (0.23 to 3.55 SD). There were no significant differences between pain and pain-free patients. The individual test-retest variability was higher on the operated side compared with the nonoperated side. DISCUSSION: The QST protocol reliability allows for group-to-group comparison of sensory function, but less so for individual follow-up after breast cancer surgery.

Development in self-reported arm-lymphedema in Danish women treated for early-stage breast cancer in 2005 and 2006--a nationwide follow-up study.

The main purpose of this nationwide follow-up study was to examine the development of self-reported lymphedema in the population of women with early-stage breast cancer in Denmark. In 2008 and 2012 two identical questionnaires were sent to the women aged 18-70 years treated for unilateral primary breast cancer in 2005 and 2006. 2293 women (87%) reported on lymphedema in 2008 and 2012. Overall 37% reported lymphedema in 2008 while 31% reported lymphedema in 2012 and severity of symptoms decreased. 50% of women treated with SLNB and reporting lymphedema in 2008 did not report symptoms by 2012 in contrast to 30% treated with ALND. However, 19% of women treated with ALND and not reporting lymphedema in 2008 had developed lymphedema by 2012. In conclusion lymphedema remains a frequent problem, years after treatment for breast cancer, though, number of women reporting lymphedema and overall severity of symptoms decreased.

Breast reconstruction with an expander prosthesis following mastectomy does not cause additional persistent pain: a nationwide cross-sectional study.

INTRODUCTION: Few studies have examined the prevalence of persistent pain after breast reconstruction with an implant after tissue expansion in comparison to mastectomy without breast reconstruction. Our primary objective was to evaluate the prevalence of persistent pain after breast reconstruction with a subpectoral implant after tissue expansion in a population-based study. Secondary objectives were to evaluate sensory disturbances, lymphoedema and functional impairment. METHOD: This was a nationwide cross-sectional questionnaire study of breast cancer patients aged 18-69 years who were treated with or without reconstruction after mastectomy for primary breast cancer in Denmark between 1 January 2005 and 31 December 2006. The response rate was 84% for mastectomy without reconstruction and 83% for patients treated with breast reconstruction. RESULTS: A total of 129 patients treated with mastectomy and breast reconstruction with a subpectoral implant were compared with 1131 patients treated with mastectomy without reconstruction. Prevalence of persistent pain for patients treated with mastectomy followed by reconstruction with an implant was 40% compared to 48% of patients treated only with mastectomy. We found no increased risk of persistent pain in patients having a reconstruction with an implant compared with mastectomy without reconstruction (odds ratio (OR) 0.82, 95% confidence interval (CI) 0.55-1.22, P=0.33) when adjusting for age, axillary procedure, radiotherapy and chemotherapy. We observed no difference in the prevalence of pain between patients treated with immediate or delayed breast reconstruction (P=0.116). CONCLUSION: Breast reconstruction with a subpectoral implant after tissue expansion does not confer increased prevalence of persistent pain.

Persistent pain and sensory disturbances after treatment for breast cancer: six year nationwide follow-up study.

OBJECTIVE: To examine the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain. DESIGN: Repeated cross sectional study in a previously examined nationwide cohort. All eligible women who underwent surgery for primary breast cancer in Denmark in 2005 and 2006 and were examined in 2008 were surveyed again with the same questionnaire. SETTING: Surgical centres in Denmark. MAIN OUTCOME MEASURES: Prevalence, location, and severity of persistent pain after treatment for breast cancer in well defined treatment groups and changes in pain reporting and sensory disturbances from 2008 to 2012. PARTICIPANTS: In 2012, 2828 women were eligible in our database, and 108 were excluded. Exclusion criteria were death; new, recurrent, or other cancer; reconstructive breast surgery; and emigration. RESULTS: 2411 (89%) women returned the questionnaire. Prevalence of persistent pain after treatment for breast cancer ranged from 22% to 53% depending on treatment. In 2012, 903 (37%) women reported such pain, a fall from 45% in 2008. Of these, 378 (16%) reported pain of ≥ 4 on a numerical rating scale (scale 0-10), a fall from 19%. Among women reporting pain in 2008, 36% no longer reported it in 2012. In contrast, 15% of the women who did not report pain in 2008 reported it in 2012. Risk factors for having pain were axillary lymph node dissection rather than sentinel lymph node biopsy (odds ratio 2.04, 95% confidence interval 1.60 to 2.61; P<0.001) and age ≤ 49 (1.78, 1.25 to 2.54; P<0.001). No particular method of treatment or age was associated with an increase in pain from 2008 to 2012. CONCLUSIONS: Persistent pain after treatment for breast cancer remains an important problem five to seven years later. The problem is not static as it can either progress or regress with time. TRIAL REGISTRATION: Clinicaltrials.gov NCT No 01543711.

Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer: cyclophosphamide, epirubicin and fluorouracil compared with docetaxel + epirubicin and cyclophosphamide.

BACKGROUND: Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for persistent pain after breast cancer treatment (PPBCT) and sensory disturbances. The purpose was to compare patients treated with cyclophosphamide, epirubicin and fluorouracil (CEF) and cyclophosphamide and epirubicin + docetaxel (CE + T) in relation to PPBCT, sensory disturbances, peripheral sensory disturbances and functional impairment. MATERIAL AND METHODS: A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. INCLUSION CRITERIA: women treated with chemotherapy as adjuvant treatment for primary breast cancer, age 18-69 years, without recurrence. RESULTS: One thousand two hundred and forty-one patients allocated to CEF in 2005-2006 and 1652 patients allocated to CE + T in 2007-2008 were included. Six hundred and sixty-four (53%) with CEF and 861 (53%) patients with CE + T reported pain. In the multivariate analysis including available risk factors, CE + T did not confer an increased risk of PPBCT, OR 0.95 (95% CI 0.81-1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, OR 0.75 (95% CI 0.62-0.90), p = 0.002. More CE + T patients reported peripheral sensory disturbances in the hands, OR 1.56 (95%CI 1.27-1.92), p < 0.0001, and in the feet, OR 2.0 (95% CI 1.66-2.42) p < 0.0001, compared to CEF. There was no difference in functional impairment (p = 0.62). CONCLUSION: Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase risk for peripheral sensory disturbances.

Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: a randomized trial.

Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60% of patients depending on surgical and adjuvant treatment. External breast radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the question whether intraoperative radiation therapy (IORT), with its smaller radiation field may reduce the development of PPBCT. Using data from the TARGIT-A trial, the aim of this study was to compare these two treatments with regard to development of PPBCT. A total of 281 patients enrolled in the TARGIT-A trial from the Copenhagen University Hospitals was screened for participation, and a total of 244 patients were included and received a detailed questionnaire. The response rate was 98%, leaving 238 patients for the final analysis. Pain prevalence were 33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with IORT may not alter the risk of PPBCT.