Pulsed radiofrequency or surgery for anterior cutaneous nerve entrapment syndrome: Long-term results of a randomized controlled trial.

PURPOSE: Patients with anterior cutaneous nerve entrapment syndrome (ACNES) often require a step-up treatment strategy including abdominal wall injections, pulsed radiofrequency (PRF) or a neurectomy. Long-term success rates of PRF and surgery are largely unknown. The aim of the current study was to report on the long-term efficacy of PRF and neurectomy in ACNES patients who earlier participated in the randomized controlled PULSE trial. METHODS: Patients who completed the PULSE trial were contacted about pain status and additional treatments in the following years. Treatment success was based on numerical rating scale (NRS) following IMMPACT recommendations and Patient Global Impression of Change (PGIC) scores. RESULTS: A total of 44 of the original 60 patients were eligible for analysis (73.3%). Median follow-up was 71.5 months. One patient (4.3%) was still free of pain after a single PRF session, and five additional patients (21.7%) were free of pain by repetitive PRF treatments. By contrast, 13 patients (61.9%) in the neurectomy group were still free of pain without additional treatments. All pain recurrences and therefore primary re-interventions occurred in the first 2 years after the initial treatment. CONCLUSION: Approximately one in five ACNES patients undergoing PRF treatment reports long-term success obviating the need of surgical intervention. Surgery for ACNES is long-term effective in approximately two of three operated patients. Recurrent ACNES beyond 2 years after either intervention is rare.

HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study.

Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromosome 17). CEP17 gain can lead to difficulty in interpretation of HER2 status, since this might represent true polysomy. With this study we investigated whether isolated polysomy is present and how this effects HER2 status in six breast cancer cell lines and 97 breast cancer cases, using HER2 FISH and immunohistochemistry, DNA ploidy assessment and multiplex ligation dependent probe amplification. We observed no isolated polysomy of chromosome 17 in any cell line. However, FISH analysis did show CEP17 gain in five of six cell lines, which reflected gains of the whole chromosome in metaphase spreads and aneuploidy with gain of multiple chromosomes in all these cases. In patients' samples, gain of CEP17 indeed correlated with aneuploidy of the tumour (91.1%; p < 0.001). Our results indicate that CEP17 gain is not due to isolated polysomy, but rather due to widespread aneuploidy with gain of multiple chromosomes. As aneuploidy is associated with poor clinical outcome, irrespective of tumour grade, this could improve future therapeutic decision making.

A Randomized Controlled Trial to Evaluate the Effect of Pulsed Radiofrequency as a Treatment for Anterior Cutaneous Nerve Entrapment Syndrome in Comparison to Anterior Neurectomy.

BACKGROUND: Chronic abdominal pain can be due to entrapped intercostal nerves (anterior cutaneous nerve entrapment syndrome [ACNES]). If abdominal wall infiltration using an anesthetic agent is unsuccessful, a neurectomy may be considered. Pulsed radiofrequency (PRF) applies an electric field around the tip of the cannula near the affected nerve to induce pain relief. Only limited retrospective evidence suggests that PRF is effective in ACNES. METHODS: A multicenter, randomized, nonblinded, controlled proof-of-concept trial was performed in 66 patients. All patients were scheduled for a neurectomy procedure. Thirty-three patients were randomized to first receive a 6-minute cycle of PRF treatment, while the other 33 were allocated to an immediate neurectomy procedure. Pain was recorded using a numeric rating scale (NRS, 0 [no pain] to 10 [worst pain possible]). Successful treatment was defined as >50% pain reduction. Patients in the PRF group were allowed to cross over to a neurectomy after 8 weeks. RESULTS: The neurectomy group showed greater pain reduction at 8-week follow-up (mean change from baseline -2.8 (95% confidence interval [CI] -3.9 to -1.7) vs. -1.5 (95% CI -2.3 to -0.6); P = 0.045) than the PRF group. Treatment success was reached in 12 of 32 (38%, 95% CI 23 to 55) of the PRF group and 17 of 28 (61%, 95% CI 42 to 72) of the neurectomy group (P = 0.073). Thirteen patients were withdrawn from their scheduled surgery. Adverse events were comparable between treatments. CONCLUSIONS: PRF appears to be an effective and minimally invasive treatment option and may therefore be considered in patients who failed conservative treatment options before proceeding to a neurectomy procedure. Anterior neurectomy may possibly lead to a greater pain relief compared with PRF in patients with ACNES, but potential complications associated with surgery should be discussed.

Chronic localized back pain due to entrapment of cutaneous branches of posterior rami of the thoracic nerves (POCNES): a case series on diagnosis and management.

INTRODUCTION AND AIM: Chronic back pain (CBP) may be caused by a variety of conditions including dysfunctional muscles, ligaments or intervertebral discs, improper movement of vertebral column joints, or nerve root compression. Recently, CBP was treated successfully in a patient having an entrapment of cutaneous branches of the posterior rami of the thoracic nerves, termed posterior cutaneous nerve entrapment syndrome (POCNES). Our aim is to describe clinical presentation, differential diagnosis, and management of patients with such a neuropathic pain syndrome. METHODS: This study analyzed prospectively obtained data from consecutive patients suspected of having POCNES, presenting to two Dutch hospitals between January 2013 and September 2016. Patients received a diagnostic 2-5 mL 1% lidocaine injection just below the thoracolumbar fascia. Pain was scored using a numerical rating scale (0 = no pain to 10 = worst possible pain). A >50% pain reduction was defined as success. A neurectomy was proposed if pain reduction was temporary or insufficient after one to three injections. Long-term treatment effect was determined using a verbal rating scale (VRS; 1 = very satisfied, no pain, to 5 = pain worse). RESULTS: Fourteen patients (12 women, median age 26, age range 18-73) were diagnosed with POCNES. Eighty-one percent (n=11) reported a >50% pain drop after injection (NRS pain scores of median 8.0 [IQR 7.0-8.0] to median 3.0 [IQR 1.5-3.5], P<0.001). In one patient, repeated injections were successful long-term (VRS score of 2). Two patients declined surgery, whereas the remaining eleven underwent a neurectomy that was successful in seven (64%). A 57% long-term efficacy (median 29 months follow-up, range 5-48, VRS score 1-2) was attained in the entire study population. CONCLUSION: POCNES should be considered in the differential diagnosis of chronic localized back pain. A treatment regimen including injections and neurectomy of the specific cutaneous branch results in long-term pain relief in more than half of these patients.

Adding steroids to lidocaine in a therapeutic injection regimen for patients with abdominal pain due to anterior cutaneous nerve entrapment syndrome (ACNES): a single blinded randomized clinical trial.

Background and aims Anterior cutaneous nerve entrapment syndrome (ACNES) may result in chronic abdominal pain. Therapeutic options include local injection therapy. Data on the efficacy of adding corticosteroids to these injections is lacking. Methods Patients ≥18 years with ACNES were randomized to receive an injection of lidocaine with (LC-group) or without (LA-group) the addition of methylprednisolone into the point of maximal abdominal wall pain. Pain was recorded using a numeric rating scale (NRS: 0-10) and a verbal rating scale (VRS: 0=no pain, 5=unbearable pain) at baseline and 6 weeks after the start of a bi-weekly injection regimen consisting of a total of three injections. A minimal 50% reduction on NRS and/or two points on VRS were considered successful responses. Results Between February 2014 and August 2016, 136 patients (median age 46 year, range 18-79, 75% females) were randomized (68 vs. 68). The proportion of patients demonstrating a successful response after 6 weeks did not significantly differ between groups (LA 38%, LC 31%, p=0.61). At 12 weeks, the number of patients still experiencing a minimal 50% pain relief had decreased but no group difference was observed (LA 20%, LC 18%, p=0.80). Minor side effects included temporary increase of pain, tenderness at injection sites or transient malaise (LA23/68, LC 29/68, p=0.46). Conclusions Adding corticosteroids to a lidocaine does not increase the proportion of ACNES patients with a successful response to injection therapy. Lidocaine alone can provide long term pain relief after one or multiple injections, in approximately 1 of 5 patients.

Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial.

BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is thought to be caused by the entrapment of end branches of the intercostal nerves residing in the abdominal wall. If ACNES is suspected, a local injection of an anesthetic agent may offer relief. If pain is recurrent following multiple-injection therapy, an anterior neurectomy entailing removal of the entrapped nerve endings may be considered. After 1 year, a 70% success rate has been reported. Research on minimally invasive alternative treatments is scarce. Pulsed radiofrequency (PRF) treatment is a relatively new treatment for chronic pain syndromes. An electromagnetic field is applied around the nerve in the hope of leading to pain relief. This randomized controlled trial compares the effect of PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES patients having short-lived success following injections are randomized to PRF or neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed to cross over to a neurectomy. Primary outcome is pain relief after either therapy. Secondary outcomes include patient satisfaction, quality of life, use of analgesics and unanticipated adverse events. The study is terminated 6 months after receiving the final procedure. DISCUSSION: Since academic literature on minimally invasive techniques is lacking, well-designed trials are needed to optimize results of treatment for ACNES. This is the first large, randomized controlled, proof-of-concept trial comparing two therapy techniques in ACNES patients. The first patient was included in October 2015. The expected trial deadline is December 2017. If effective, PRF may be incorporated into the ACNES treatment algorithm, thus minimizing the number of patients requiring surgery. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on 15 April 2015.

Treatment response and central pain processing in Anterior Cutaneous Nerve Entrapment Syndrome: An explorative study.

BACKGROUND: 10-30% of chronic abdominal pain originates in the abdominal wall. A common cause for chronic abdominal wall pain is the Anterior Cutaneous Nerve Entrapment Syndrome (ACNES), in which an intercostal nerve branch is entrapped in the abdominal rectus sheath. Treatment consists of local anaesthetics and neurectomy, and is ineffective in 25% of cases for yet unknown reasons. In some conditions, chronic pain is the result of altered pain processing. This so-called sensitization can manifest as segmental or even generalized hyperalgesia, and is generally difficult to treat. OBJECTIVE: The aim of this study was to assess pain processing in ACNES patients responsive and refractory to treatment by using Quantitative Sensory Testing, in order to explore whether signs of altered central pain processing are present in ACNES and are a possible explanation for poor treatment outcomes. METHODS: 50 patients treated for ACNES with locally orientated treatment were included. They were allocated to a responsive or refractory group based on their response to treatment. Patients showing an improvement of the Visual Analogue Scale (VAS) pain score combined with a current absolute VAS of <40mm were scored as responsive. Sensation and pain thresholds to pressure and electric skin stimulation were determined in the paravertebral bilateral ACNES dermatomes and at four control areas on the non-dominant side of the body, i.e. the musculus trapezius pars medialis, musculus rectus femoris, musculus abductor hallucis and the thenar. The ACNES dermatomes were chosen to signal segmental hyperalgesia and the sum of the control areas together as a reflection of generalized hyperalgesia. Lower thresholds were interpreted as signs of sensitized pain processing. To test for alterations in endogenous pain inhibition, a conditioned pain modulation (CPM) response to a cold pressor task was determined. Also, patients filled in three pain-related questionnaires, to evaluate possible influence of psychological characteristics on the experienced pain. RESULTS: Patients refractory to treatment showed significantly lower pressure pain thresholds in the ACNES dermatomes and for the sum of as well as in two individual control areas. No differences were found between groups for electric thresholds or CPM response. Duration of complaints before diagnosis and treatment was significantly longer in the refractory compared to the responsive group, and refractory patients scored higher on the pain-related psychological surveys. CONCLUSION AND IMPLICATIONS: In this hypothesis-generating exploratory study, ACNES patients refractory to treatment showed more signs of sensitized segmental and central pain processing. A longer duration of complaints before diagnosis and treatment may be related to these alterations in pain processing, and both findings could be associated with less effective locally orientated treatment. In order to validate these hypotheses further research is needed. REGISTRATION NUMBER: NCT01920880 (Clinical Trials Register; http://www.clinicaltrials.gov).

Chronic Localized Back Pain Due to Posterior Cutaneous Nerve Entrapment Syndrome (POCNES): A New Diagnosis.

Most patients with chronic back pain suffer from degenerative thoracolumbovertebral disease. However, the following case illustrates that a localized peripheral nerve entrapment must be considered in the differential diagnosis of chronic back pain. We report the case of a 26-year-old woman with continuous excruciating pain in the lower back area. Previous treatment for nephroptosis was to no avail. On physical examination the pain was present in a 2 x 2 cm area overlying the twelfth rib some 4 cm lateral to the spinal process. Somatosensory testing using swab and alcohol gauze demonstrated the presence of skin hypo- and dysesthesia over the painful area. Local pressure on this painful spot elicited an extreme pain response that did not irradiate towards the periphery. These findings were highly suggestive of a posterior version of the anterior cutaneous nerve entrapment syndrome (ACNES), a condition leading to a severe localized neuropathic pain in anterior portions of the abdominal wall. She demonstrated a beneficial albeit temporary response after lidocaine infiltration as dictated by an established diagnostic and treatment protocol for ACNES. She subsequently underwent a local neurectomy of the involved superficial branch of the intercostal nerve. This limited operation had a favorable outcome resulting in a pain-free return to normal activities up to this very day (follow-up of 24 months).We propose to name this novel syndrome "posterior cutaneous nerve entrapment syndrome" (POCNES). Each patient with chronic localized back pain should undergo simple somatosensory testing to detect the presence of overlying skin hypo- and dysesthesia possibly reflecting an entrapped posterior cutaneous nerve.Key words: Chronic pain, back pain, posterior cutaneous nerve entrapment, peripheral nerve entrapment, surgical treatment for pain, anterior cutaneous nerve entrapment.

Brief fixation enables same-day breast cancer diagnosis with reliable assessment of hormone receptors, E-cadherin and HER2/Neu.

AIMS: Preoperative core needle biopsy (CNB) is commonly used to confirm the diagnosis of breast cancer. For treatment purposes and for determining histological type, especially in case of neoadjuvant therapy, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and E-cadherin assessments are crucial. Considering the increasing demand for same-day diagnosis of breast lesions, an accelerated method of CNB processing was developed, in which the tissue fixation time is radically reduced. METHODS: To determine whether short fixation time frustrates assessment of ER, PR and E-cadherin immunohistochemistry (IHC) and HER2 fluorescence in situ hybridisation (FISH), 69 consecutive patients with 70 invasive breast carcinomas were included through the same-day diagnostics programme of breast lesions of the Radboud university medical center and the hospital Pantein. IHC for ER, PR and E-cadherin and HER2 FISH were compared between CNBs fixed for approximately 60-90 min and traditionally fixed resection specimens. RESULTS: Overall agreement between CNBs and resection specimens was 98.6% for ER (p<0.001; κ=0.93), 90.0% for PR (p<0.001; κ=0.75), 100% for E-cadherin (p<0001; κ=1.00) and 98.6% (p<0.001; κ=0.94) for HER2 FISH. Positive and negative predictive values were respectively 98.4% and 100% for ER, 95.9% and 76.2% for PR, 100% and 100% for E-cadherin and 90% and 100% for HER2 FISH. CONCLUSIONS: Hormone receptors and E-cadherin IHC and HER2 FISH are highly comparable between briefly fixed CNBs and the corresponding traditionally fixed resection specimens, and can therefore reliably be used in the daily clinical practice of same-day diagnostics of breast cancer.

Long-term success rates after an anterior neurectomy in patients with an abdominal cutaneous nerve entrapment syndrome.

BACKGROUND: Surgery occasionally is proposed in patients with chronic abdominal wall pain caused by an anterior cutaneous nerve entrapment syndrome (ACNES) who are refractory to injection therapy. An anterior neurectomy may seem successful, but follow-up is usually short and populations are small. The primary aim of this study was to determine the long-term success rate of surgery in a large ACNES population. METHODS: In this retrospective observational study, patients with ACNES ≥18 years who underwent a primary anterior neurectomy between January 2004 and February 2012 in one single center were studied. Pain scores were obtained before surgery, after surgery, and at the moment of questioning using a pain intensity numeric rating scale (PI-NRS 0-10) and a 6-point verbal category rating scale. Success was defined as a ≥50% PI-NRS reduction or ≥2 point verbal rating scale reduction. RESULTS: Data of 181 neurectomies in 154 individuals were available for analysis (female, n = 127, 82.5%; age 47 ± 17 years, range, 20-83). Pain before operation was severe (mean PI-NRS 8.08, SD 1.43). Short-term (1-3 months postoperative) success was 70% (127/181 procedures). Three subjects showed spontaneous remission of complaints after ≥3 months. After a mean 32 months (range, 3-93) follow-up, a success rate of 61% (109/180) on the long-term was found. CONCLUSION: A 70% short-term success rate and a 61% long-term success rate after a primary anterior neurectomy in patients with chronic abdominal pain due to ACNES were attained. Surgery is the method of choice in ACNES patients who are refractory to a conservative regimen.

A double-blind, randomized, controlled trial on surgery for chronic abdominal pain due to anterior cutaneous nerve entrapment syndrome.

OBJECTIVE: To clarify the role of a surgical neurectomy on pain in refractory patients after conservatively treated anterior cutaneous nerve entrapment syndrome (ACNES). BACKGROUND: ACNES is hardly ever considered in the differential diagnosis of chronic abdominal pain. Treatment is usually conservative. However, symptoms are often recalcitrant. METHODS: Patients older than 18 years with a diagnosis of ACNES were randomized to undergo a neurectomy or a sham procedure via an open surgical procedure in day care. Both the patient and the principal investigator were blinded to the nature of surgery. Pain was recorded using a visual analog scale (1-100 mm) and a verbal rating scale (score 0-5; 0 = no pain, 5 = severe pain) before surgery and 6 weeks postoperatively. A reduction of at least 50% in the visual analog scale score and/or 2 points on the verbal rating scale was considered a "successful response." RESULTS: Forty-four patients were randomized between August 2008 and December 2010 (39 women, median age = 42 years; both groups, n = 22). In the neurectomy group, 16 patients reported a successful pain response. In contrast, significant pain reduction was obtained in 4 patients in the sham group (P = 0.001). Complications associated with surgery were hematoma (n = 5, conservative treatment), infection (antibiotic and drainage, n = 1), and worsened pain (n = 1). CONCLUSIONS: Neurectomy of the intercostal nerve endings at the level of the abdominal wall is an effective surgical procedure for pain reduction in ACNES patients who failed to respond to a conservative regimen.

Construction and validation of a questionnaire distinguishing a chronic abdominal wall pain syndrome from irritable bowel syndrome.

OBJECTIVE: The irritable bowel syndrome (IBS) population is heterogeneous, harbouring a variety of abdominal symptoms. Therefore, IBS is often termed a 'diagnosis of exclusion'. Chronic abdominal wall pain (CAWP) is a poorly recognized entity, frequently caused by the anterior cutaneous nerve entrapment syndrome (ACNES). Some patients may be misdiagnosed because IBS and CAWP share symptoms. Aim of this study was to construct and validate a questionnaire to distinguish patients with CAWP (including ACNES) patients with IBS. DESIGN: A questionnaire was designed of 17 ACNES characteristic items obtained from ACNES patients (n=33) and expert opinion of two specialized surgeons. Eleven IBS-related items ('Rome III' criteria) were added leading to a questionnaire containing 28 items. This was validated in a 'gold standard' ACNES group (successfully operated ACNES patients, n=68) and a 'prospective' IBS group (n=64) as well as in a 'prospective' ACNES group (n=47). Distinctive power of individual items was analyzed by χ2. Reliability was tested with Crohnbach's α. ROC curve was used to determine cut-off values. RESULTS: Eighteen of 28 items were significantly distinctive (p<0.01) between ACNES and IBS patients leading to an 18-point ACNES score with good internal consistency (α=0.85). Cut-off value of 10 points resulted in 94% sensitivity, 92% specificity and areas under the curve (AUC) of 0.98. Evaluation of the prospective ACNES group led to 85% sensitivity, 92% specificity and AUC 0.95 indicating high discriminative properties of the questionnaire. CONCLUSIONS: This novel questionnaire may be useful and valid as a simple tool distinguishing patients harbouring a CAWP syndrome from those having IBS.

Surgery for refractory anterior cutaneous nerve entrapment syndrome (ACNES) in children.

BACKGROUND: Chronic abdominal pain (CAP) in children may be caused by entrapment of cutaneous branches of intercostal nerves (anterior cutaneous nerve entrapment syndrome, or ACNES). Local injection of anesthetics may offer relief, but pain is persistent in some children. This study is the first to describe the results of a 'cutaneous neurectomy' in children with refractory ACNES. METHODS: Chronic abdominal pain children with suspected ACNES refractory to conservative treatment received a cutaneous neurectomy in a day care setting. They were interviewed postoperatively using an adapted quality of life questionnaire (testing quality of life in children). RESULTS: All subjects (n = 6; median age, 15 years; range, 9-16 years) were previously healthy school-aged children without prior illness or earlier surgery. Each presented with intense abdominal pain and a positive Carnett sign. Blood, urine tests, and abdominal ultrasound investigations were normal. Delay in seeing a physician was 16 weeks, and school absence was 25 days. Before surgery, quality of life (pain, daily activities, and sports) was greatly diminished. After the neurectomy, all children were free of pain and had resumed their normal daily routine (follow-up at 6 months). CONCLUSIONS: The role of the abdominal wall as the source of childhood CAP is underestimated. Some children with CAP have ACNES. Children with refractory ACNES should be offered a cutaneous neurectomy, as this simple technique is effective in the short and long term.

Pain after anterior mesh hernia repair.

BACKGROUND: The results of a randomized clinical trial comparing the Lichtenstein procedure, mesh plug repair, and the Prolene Hernia System provided a database for analyzing chronic pain after anterior mesh hernia repair to determine the characteristics and identify risk factors. STUDY DESIGN: A total of 334 patients with primary inguinal hernia were randomly allocated to receive one of the three meshes. Data on patient characteristics, hernia, and procedure were collected. Longterm followup was completed for 319 of 333 (95.8 %) patients with a postal questionnaire that included a Visual Analog Scale pain score, pain descriptions, and questions about numbness and prosthesis awareness. Chronic pain was analyzed irrespective of the technique used. RESULTS: With increasing age, significantly less intense chronic pain was reported (R = -0.267, p < 0.001) and pain descriptors were used less frequently (p < 0.001). This indirectly reflected the significance of employment (p = 0.019) and body mass index (R = -0.166, p = 0.005) in a univariate analysis because the elderly were, for the most part, unemployed and had a higher body mass index. Longterm Visual Analog Scale pain score correlated significantly with pain directly after an operation (R = 0.253, p = < 0.001). Reported pain increased with the presence of numbness (p < 0.001) and the number of descriptions used (R = 0.389, p < 0.001). Patients using only neuropathic descriptions (n = 56) suffered significantly more intense pain (Visual Analog Scale 26.5 versus 16.6, p = 0.014) than those using only words indicating nociceptive pain (n = 47). CONCLUSIONS: Chronic pain after anterior mesh hernia repair is determined by younger age and stronger pain directly after the operation. Especially in patients with chronic neuropathic pain, its intensity is aggravated when numbness is present and the number of words to describe pain increases.