The objective of treatment is to minimize the symptoms produced by the identified pain generators using targeted therapy. In addition, management of psychiatric comorbidity is essential to improving outcomes. A comprehensive history and careful physical exam is used to identify the individual pain diagnoses present. Following this, each diagnosis is approached separately.
Gynecologic pain
A fundamental principle of medicine is the assignment of a tissue-specific etiology as a diagnosis. Chronic pelvic pain in women that is related to the time of menses or that is reproduced by uterine manipulation can generally be termed gynecologic pain. Within this category, there are a wide variety of diagnoses, including adenomyosis, endometriosis, and uterine fibroids.[12]Won HR, Abbott J. Optimal management of chronic cyclical pelvic pain: an evidence-based and pragmatic approach. Int J Womens Health. 2010 Aug 20;2:263-77.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990894
http://www.ncbi.nlm.nih.gov/pubmed/21151732?tool=bestpractice.com
For most gynecologic pain, management begins with nonsteroidal anti-inflammatory drugs (NSAIDs), typically combined with some form of ovulation suppression.[25]American College of Obstetricians and Gynecologists. Practice bulletin no. 114: management of endometriosis. Jul 2010 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2010/07/management-of-endometriosis
First-line treatment options include medical ovarian suppression with a cyclic combined oral contraceptive. Intermittent dosing results in a monthly withdrawal bleed. A thorough history should be obtained, and Medical Eligibility Criteria for contraceptive use applied, to determine safe use of contraception for menstrual suppression.[44]American College of Obstetricians and Gynecologists. Clinical consensus no. 3: general approaches to medical management of menstrual suppression. Sep 2022 [internet publication].
https://www.acog.org/clinical/clinical-guidance/clinical-consensus/articles/2022/09/general-approaches-to-medical-management-of-menstrual-suppression
[45]Nguyen AT, Curtis KM, Tepper NK, et al. U.S. medical eligibility criteria for contraceptive use, 2024. MMWR Recomm Rep. 2024 Aug 8;73(4):1-126.
https://www.cdc.gov/mmwr/volumes/73/rr/rr7304a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/39106314?tool=bestpractice.com
[46]Faculty of Sexual and Reproductive Healthcare. UK medical eligibility criteria for contraceptive use. Sep 2019 [internet publication].
https://www.fsrh.org/Common/Uploaded%20files/documents/fsrh-ukmec-full-book-2019.pdf
If cyclic contraceptive management fails or the patient has severe symptoms, a trial of continuous ovarian suppression using a continuous combined oral contraceptive, with the objective of eliminating menses altogether, can be done.
Other second-line options include the use of long-acting hormonal contraception (e.g., medroxyprogesterone), or the levonorgestrel-releasing IUD.[25]American College of Obstetricians and Gynecologists. Practice bulletin no. 114: management of endometriosis. Jul 2010 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2010/07/management-of-endometriosis
Medroxyprogesterone provides an injectable management option with the objective of inducing amenorrhea. However, an increased risk of meningioma has been reported in patients taking high doses of medroxyprogesterone for several years (including injectable formulations) in epidemiologic studies and case reports, although the absolute risk appears to be small.[47]Roland N, Neumann A, Hoisnard L, et al. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024 Mar 27;384:e078078.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10966896
http://www.ncbi.nlm.nih.gov/pubmed/38537944?tool=bestpractice.com
High doses of medroxyprogesterone may therefore be contraindicated in patients with a meningioma or a history of meningioma, and treatment should be stopped in patients who are diagnosed with meningioma during treatment.[48]European Medicines Agency. Medroxyprogesterone acetate - direct healthcare professional communication (DHPC). Oct 2024 [internet publication].
https://www.ema.europa.eu/en/medicines/dhpc/medroxyprogesterone-acetate
The levonorgestrel-releasing IUD has been more extensively studied and has a proven efficacy in chronic pelvic pain.[49]Bayoglu Tekin Y, Dilbaz B, Altinbas SK, et al. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril. 2011 Feb;95(2):492-6.
http://www.ncbi.nlm.nih.gov/pubmed/20883991?tool=bestpractice.com
For patients unresponsive to initial medical management, laparoscopy can be both diagnostic and therapeutic, although there are significant limitations to its long-term benefit.[25]American College of Obstetricians and Gynecologists. Practice bulletin no. 114: management of endometriosis. Jul 2010 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2010/07/management-of-endometriosis
[50]Coccia ME, Rizzello F, Palagiano A, et al. Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain. Eur J Obstet Gynecol Reprod Biol. 2011;157:78-83.
http://www.ncbi.nlm.nih.gov/pubmed/21481523?tool=bestpractice.com
As a diagnostic procedure, endometriosis, adhesions, and other anatomic problems related to chronic pelvic pain can be found. Often these entities can be dealt with at the same time, through fulguration or excision of endometriosis and lysis of adhesions. When endometriosis is found and treated, follow-up treatment with menstrual suppression improves the effect of the surgery. There remains significant questions regarding the relationship of endometriosis and pain.[51]Hsu AL, Sinaii N, Segars J, et al. Relating pelvic pain location to surgical findings of endometriosis. Obstet Gynecol. 2011 Aug;118(2 Pt 1):223-30.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155822
http://www.ncbi.nlm.nih.gov/pubmed/21775836?tool=bestpractice.com
Nerve sprouting into endometriosis implants and central sensitization may be important factors in the development and maintenance of pain in some patients.[52]Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011 May-Jun;17(3):327-46.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072022
http://www.ncbi.nlm.nih.gov/pubmed/21106492?tool=bestpractice.com
Induction of menopause with gonadotropin-releasing hormone (GnRH) agonists (which may include add-back estrogen-replacement therapy) provides the final medical management option for patients who have failed to respond to cyclic and continuous ovarian suppression treatment and laparoscopy. Several drugs and routes are available. For convenience, and to improve compliance, some can be dosed once every 3 months. See Endometriosis.
Patients with inoperable endometriosis may be candidates for medically-induced menopause. Without inducing menopause (either medically or surgically) endometriosis can be expected to recur, resulting in repeated laparoscopy. Due to the increase in complications with every subsequent surgery, this approach should be avoided if possible. The benefits of surgical compared to medical management have not been conclusively demonstrated; an individualized approach based on careful patient counseling and management of expectations can provide the best results.[53]Yunker A, Sathe NA, Reynolds WS, et al. Systematic review of therapies for noncyclic chronic pelvic pain in women. Obstet Gynecol Surv. 2012 Jul;67(7):417-25.
http://www.ncbi.nlm.nih.gov/pubmed/22926248?tool=bestpractice.com
If childbearing is complete, hysterectomy can be very effective for gynecologic-based pain, but as many as 20% of patients may return for an oophorectomy later.[54]Lamvu G. Role of hysterectomy in the treatment of chronic pelvic pain. Obstet Gynecol. 2011 May;117(5):1175-8.
http://www.ncbi.nlm.nih.gov/pubmed/21508759?tool=bestpractice.com
[
]
In women with benign gynecological conditions, what are the benefits and harms of subtotal compared with total hysterectomy?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.322/fullShow me the answer To completely eradicate endometriosis a concomitant oophorectomy may also be required. Careful evaluation for other causes of chronic pelvic pain is required to provide optimal surgical outcomes.
Interstitial cystitis
Diagnosis and management of interstitial cystitis (bladder pain syndrome) has evolved to incorporate a multimodal approach that categorizes treatments into behavioral, medical, instillations, procedures, and surgery.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
Many patients with interstitial cystitis can identify dietary triggers for their pain, which may include caffeine, acidic foods, spicy foods, and a wide range of other dietary items. Some patients will get significant relief from careful dietary modification. Maintaining a food diary can help in identifying possible dietary triggers.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
[55]Sesti F, Capozzolo T, Pietropolli A, et al. Dietary therapy: a new strategy for management of chronic pelvic pain. Nutr Res Rev. 2011 Jun;24(1):31-8.
http://www.ncbi.nlm.nih.gov/pubmed/20969811?tool=bestpractice.com
Initial therapies include antihistamines, pentosan polysulfate sodium, and mild analgesics. Combinations of these drugs may be used. Pentosan is only effective in about 50% of patients following 6 months of therapy.[56]Nickel JC, Barkin J, Forrest J, et al. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology. 2005 Apr;65(4):654-8.
http://www.ncbi.nlm.nih.gov/pubmed/15833501?tool=bestpractice.com
Pentosan is related to heparin, and so should be avoided in patients taking concurrent anticoagulation or those at risk for serious consequences from bleeding. Pentosan exposure has also been linked to maculopathy, therefore periodic retinal examination is required during treatment.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
Bladder instillation therapy (also known as intravesical instillations) can be used with various different mixtures of drugs placed 2 or 3 times per week for 6 weeks.[57]Poletajew S, Brzózka MM, Krajewski W, et al. Glycosaminoglycan replacement therapy with intravesical instillations of combined hyaluronic acid and chondroitin sulfate in patients with recurrent cystitis, post-radiation cystitis and bladder pain syndrome: a narrative review. Pain Ther. 2024 Feb;13(1):1-22.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10796878
http://www.ncbi.nlm.nih.gov/pubmed/37917298?tool=bestpractice.com
Instillation is then repeated as needed. Many individual components have been tried, including alkalinized lidocaine, heparin, dimethyl sulfoxide, and others, used in various combinations.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
The urethra and vulva are cleaned using a sterile antiseptic solution and a urologic syringe of lidocaine jelly is applied to the urethra, passing the lidocaine jelly into the bladder. A thin, straight bladder catheter is then passed through the urethra into the bladder and the instillation mixture is poured into the bladder. Patients are asked to hold the solution as long as possible and indicate the extent, if any, of relief they experience with the solution in their bladder. Some patients may experience prolonged relief, even after voiding, and the change in symptoms helps gauge the probability of interstitial cystitis. The overall risks are very low, but include urinary tract infection, which must be ruled out before therapy begins.
Relief of bladder pain symptoms at the time of alkalinized lidocaine instillation is diagnostic for pain of bladder origin, i.e. interstitial cystitis, provided infections have been excluded. Patients who report relief of bladder pain with instillation (for any amount of time), can usually expect longer-term relief from hydrodistension.
For patients with interstitial cystitis, hydrodistension is a second line treatment that may be diagnostic and therapeutic. Many different protocols have been summarized and reviewed.[58]Turner KJ, Stewart LH. How do you stretch a bladder? A survey of UK practice, a literature review, and a recommendation of a standard approach. Neurourol Urodyn. 2005;24(1):74-6.
http://www.ncbi.nlm.nih.gov/pubmed/15486948?tool=bestpractice.com
However, not all patients will respond to distension. Interstitial cystitis is often a relapsing condition, so patients should expect multiple treatments, possibly as frequently as every 3 months. Optimization of medical management decreases the need for repeat hydrodistension. The major complication specific to distension is rupture of the bladder, which may occur as frequently as 10% in some series.[59]Higson RH, Smith JC, Whelan P. Bladder rupture: an acceptable complication of distension therapy? Br J Urol. 1978 Dec;50(7):529-34.
http://www.ncbi.nlm.nih.gov/pubmed/753506?tool=bestpractice.com
Neurostimulator implantation is used when all other efforts to control pain have failed.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
[60]Fariello JY, Whitmore K. Sacral neuromodulation stimulation for IC/PBS, chronic pelvic pain, and sexual dysfunction. Int Urogynecol J. 2010 Dec;21(12):1553-8.
http://www.ncbi.nlm.nih.gov/pubmed/20972541?tool=bestpractice.com
Several different devices are available, all of which rely on placement of an electrode onto the pudendal nerve or other nerve root under anesthesia guidance. An electrical pulse is then tonically produced to suppress nerve action. The response rate varies between 40% and 70%; however the data supporting neurostimulator use are limited.[61]Marcelissen T, Jacobs R, van Kerrebroeck P, et al. Sacral neuromodulation as a treatment for chronic pelvic pain. J Urol. 2011 Aug;186(2):387-93.
http://www.ncbi.nlm.nih.gov/pubmed/21683381?tool=bestpractice.com
Chemical neuromodulation with botulinum toxin has become a standard treatment for patients with drug-resistant urinary urgency and frequency. There is some evidence intradetrusor injection of onabotulinumtoxinA also reduces pain and improves quality of life, however the effects are short term.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
OnabotulinumtoxinA injected in the ambulatory setting allows for symptom relief and minimizes risk for acute urinary retention requiring self-catheterization. Small studies have shown efficacy for this treatment combined with hydrodistention.[62]Yu WR, Jiang YH, Jhang JF, et al. Treatment outcomes of intravesical botulinum toxin A injections on patients with interstitial cystitis/bladder pain syndrome. Toxins (Basel). 2022 Dec 11;14(12):871.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9783021
http://www.ncbi.nlm.nih.gov/pubmed/36548768?tool=bestpractice.com
Patients with Hunner ulcers require initial procedural management. The American Urological Association recommends fulguration (with electrocautery) and/or injection of triamcinolone. Oral cyclosporine is an option for patients with persistent or refractory symptoms.[3]Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022 Jul;208(1):34-42.
https://www.auajournals.org/doi/10.1097/JU.0000000000002756
http://www.ncbi.nlm.nih.gov/pubmed/35536143?tool=bestpractice.com
See Interstitial cystitis (bladder pain syndrome).
Fibromyalgia
Fibromyalgia should be individualized and multimodal. It may include patient education, self-management, physical activity, pharmacotherapy, and psychologic therapies. Pharmacologic therapy may include tricyclic antidepressants, gabapentinoids, or selective-norepinephrine reuptake inhibitors (SNRIs).[63]Horne AW, Vincent K, Cregg R, et al. Is gabapentin effective for women with unexplained chronic pelvic pain? BMJ. 2017 Sep 21;358:j3520.
http://www.ncbi.nlm.nih.gov/pubmed/28935652?tool=bestpractice.com
[64]Lian YN, Wang Y, Zhang Y, et al. Duloxetine for pain in fibromyalgia in adults: a systematic review and a meta-analysis. Int J Neurosci. 2020 Jan;130(1):71-82.
http://www.ncbi.nlm.nih.gov/pubmed/31487217?tool=bestpractice.com
[65]Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics. 2000 Mar-Apr;41(2):104-13.
https://www.sciencedirect.com/science/article/pii/S0033318200706396
http://www.ncbi.nlm.nih.gov/pubmed/10749947?tool=bestpractice.com
[66]Arnold LM, Choy E, Clauw DJ, et al. An evidence-based review of pregabalin for the treatment of fibromyalgia. Curr Med Res Opin. 2018 Aug;34(8):1397-409.
http://www.ncbi.nlm.nih.gov/pubmed/29519159?tool=bestpractice.com
Pharmacologic therapy is, at best, modestly effective in a minority of patients.[67]Nüesch E, Häuser W, Bernardy K, et al. Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis. Ann Rheum Dis. 2013 Jun;72(6):955-62.
https://ard.eular.org/article/S0003-4967(24)21484-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/22739992?tool=bestpractice.com
See Fibromyalgia.
Trigger-point injection is a second-line therapy and can be done using a variety of agents.[26]European Association of Urology. Guidelines on chronic pelvic pain. Mar 2024 [internet publication].
https://uroweb.org/guidelines/chronic-pelvic-pain
Initially, precise infiltration of the tender area with local anesthetics (such as 1% lidocaine) can produce immediate relief and be both diagnostic and therapeutic. Patient response to trigger-point injection may include prolonged relief, minimal relief, or a short-term flare of symptoms once the anesthetic has worn off. Patients who cannot identify a discrete trigger point (or points) are unlikely to benefit. A reproducible tender area should be discerned before injection. Patients should be queried during injection to assure that the actual trigger point is treated. Failure to relieve symptoms indicates either that the trigger point was missed, or that the patient does not have a trigger point amenable to injection therapy. Patients with trigger points who have the correct point injected will report immediate relief of symptoms, which should be reproducible by the examiner. Due to the action of local anesthetics, a burning sensation will always precede pain relief.
Repeat injections may be necessary and can also be done using onabotulinumtoxinA, or dry needling (acupuncture). Some patients will respond to trigger-point release massage or physical therapy.[36]Rawicki B, Sheean G, Fung VS, et al; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement. Eur J Neurol. 2010 Aug;17(suppl 2):122-34.
http://www.ncbi.nlm.nih.gov/pubmed/20633183?tool=bestpractice.com
Levator ani syndrome (pelvic floor tension myalgia)
Initial management includes NSAIDs and physical therapy, often called Thiele massage. Most patients can tolerate some level of physical therapy, particularly massage. The addition of physical therapy can frequently improve symptoms in compliant patients.[26]European Association of Urology. Guidelines on chronic pelvic pain. Mar 2024 [internet publication].
https://uroweb.org/guidelines/chronic-pelvic-pain
[68]Montenegro ML, Vasconcelos EC, Candido Dos Reis FJ, et al. Physical therapy in the management of women with chronic pelvic pain. Int J Clin Pract. 2008 Feb;62(2):263-9.
http://www.ncbi.nlm.nih.gov/pubmed/18067562?tool=bestpractice.com
Stretching exercises of the affected muscle groups may also be beneficial. Exercise may exacerbate muscle-based symptoms.
Trigger-point injection has demonstrated benefit.[36]Rawicki B, Sheean G, Fung VS, et al; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement. Eur J Neurol. 2010 Aug;17(suppl 2):122-34.
http://www.ncbi.nlm.nih.gov/pubmed/20633183?tool=bestpractice.com
Vulvodynia
A topical anesthetic applied to the affected area prior to coitus may control vulvodynia and permit comfortable intercourse.[69]Andrews JC. Vulvodynia interventions: systematic review and evidence grading. Obstet Gynecol Surv. 2011 May;66(5):299-315.
http://www.ncbi.nlm.nih.gov/pubmed/21794194?tool=bestpractice.com
[70]American College of Obstetricians and Gynecologists. Committee opinion no. 673: persistent vulvar pain. Sep 2016 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2016/09/persistent-vulvar-pain
Using lidocaine on a long-term basis failed to provide significant response beyond placebo.[71]Foster DC, Kotok MB, Huang LS, et al. Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):583-93.
http://www.ncbi.nlm.nih.gov/pubmed/20733439?tool=bestpractice.com
Amitriptyline or gabapentin can be used as an adjunct in a manner similar to fibromyalgia.[72]Haefner HK, Collins ME, Davis GD, et al. The vulvodynia guideline. J Low Genit Tract Dis. 2005 Jan;9(1):40-51.
https://journals.lww.com/jlgtd/Fulltext/2005/01000/The_Vulvodynia_Guideline.9.aspx
http://www.ncbi.nlm.nih.gov/pubmed/15870521?tool=bestpractice.com
Although, given the increasing reports of abuse and the potential risks associated with gabapentin, clinicians should consider alternative treatment options to gabapentin for managing chronic pelvic pain, particularly in patients with no identifiable pelvic pathology.[73]Horne AW, Vincent K, Hewitt CA, et al. Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2020 Sep 26;396(10255):909-17.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7527829
http://www.ncbi.nlm.nih.gov/pubmed/32979978?tool=bestpractice.com
[74]Allaire C, Yong PJ, Bajzak K, et al. Guideline no. 445: management of chronic pelvic pain. J Obstet Gynaecol Can. 2024 Jan;46(1):102283.
https://www.jogc.com/article/S1701-2163(23)00646-1/abstract
http://www.ncbi.nlm.nih.gov/pubmed/38341225?tool=bestpractice.com
If first-line approaches fail, careful excision of the painful area can be considered.[75]Wu C, Goldstein A, Klebanoff JS, et al. Surgical management of neuroproliferative-associated vestibulodynia: a tutorial on vestibulectomy with vaginal advancement flap. Am J Obstet Gynecol. 2019 Nov;221(5):525.e1-2.
http://www.ncbi.nlm.nih.gov/pubmed/31408632?tool=bestpractice.com
Partial removal of the vestibule can be considered in carefully selected patients.[70]American College of Obstetricians and Gynecologists. Committee opinion no. 673: persistent vulvar pain. Sep 2016 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2016/09/persistent-vulvar-pain
Such patients should have clear evidence of provoked pain localized to small areas of the vestibule and have failed conservative management. Caution must be taken to avoid vaginal stenosis following excision.