Antenatal sildenafil administration to prevent pulmonary hypertension in congenital diaphragmatic hernia (SToP-PH): study protocol for a phase I/IIb placenta transfer and safety study.

Trials. 2018 Sep 27;19(1):524

Authors: Russo FM, Benachi A, Van Mieghem T, De Hoon J, Van Calsteren K, Annaert P, Tréluyer JM, Allegaert K, Deprest J

Abstract
BACKGROUND: Congenital diaphragmatic hernia is an orphan disease with high neonatal mortality and significant morbidity. An important cause for this is pulmonary hypertension, for which no effective postnatal therapy is available to date. An innovative strategy aiming at treating or preventing pulmonary hypertension more effectively is urgently needed. Prenatal sildenafil administration to expectant mothers prevented fetal and neonatal vascular changes leading to pulmonary hypertension in several animal models, and is, therefore, a promising approach. Before transferring this antenatal medical approach to the clinic, more information is needed on transplacental transfer and safety of sildenafil in humans.
METHODS: This is a randomized, investigator-blinded, double-armed, parallel-group, phase I/IIb study with as a primary objective to measure the in-vivo transplacental transfer of sildenafil in women in the second and early third trimester of pregnancy (sub-study 1; weeks: 20.0-32.6) and at term (sub-study 2; weeks: 36.6-40). Participants will be randomized to two different sildenafil doses: 25 or 75 mg. In sub-study 1, a single dose of the investigational product will be administered to women undergoing termination of pregnancy, and maternal and fetal blood samples will be collected for determination of sildenafil concentrations. In sub-study 2, sildenafil will be administered three times daily from 3 days before planned delivery until actual delivery, following which maternal and umbilical cord samples will be collected. Proxies of maternal and fetal tolerance as well as markers of fetal pulmonary vasodilation will also be measured.
DISCUSSION: This is the first study evaluating in-vivo transplacental passage of sildenafil in humans.
TRIAL REGISTRATION: EU Clinical Trials Register 2016-002619-17, validated on 12 August 2016. Trial sponsor: UZ Leuven, Herestraat 49, 3000 Leuven.

PMID: 30261903 [PubMed - in process]

[Why are new drugs so expensive?]

Med Sci (Paris). 2018 Apr;34(4):354-361

Authors: Le Galès C

Abstract
Putting an end to an innovation crisis, the reality of which is the subject of debate, recent pharmaceutical innovations, the result of a combination of scientific, industrial, financial, political and economic reasons, lead to a diversification of products and to a strong interest of pharmaceutical companies for the so-called "niche" products (targeted therapies, rare diseases, etc.). These new molecules are put on the market at much higher prices than in the past. In the absence of reliable information on the costs borne by manufacturers, and knowing that high levels of margins have been observed, these prices raise legitimate questions. These are also motivated by the lack of relationship between the price and the therapeutic benefit of these new molecules. In France, faced with levels of expenditure likely to weaken the financial sustainability of the social protection system, the public authorities have so far always favored interventions on prices or the conditions and volume of reimbursement, in accordance with the existing regulation. Other regulations (use of the statutory license, group purchase, etc.) could in the future be used in a growing concern for the efficiency of public expenditure. The difficulties encountered in regulating a deeply transformed industrial sector call for a reform of national evaluation and regulation systems.

PMID: 29658480 [PubMed - indexed for MEDLINE]

Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial.

Lancet. 2017 Oct 14;390(10104):1758-1768

Authors: Ory DS, Ottinger EA, Farhat NY, King KA, Jiang X, Weissfeld L, Berry-Kravis E, Davidson CD, Bianconi S, Keener LA, Rao R, Soldatos A, Sidhu R, Walters KA, Xu X, Thurm A, Solomon B, Pavan WJ, Machielse BN, Kao M, Silber SA, McKew JC, Brewer CC, Vite CH, Walkley SU, Austin CP, Porter FD

Abstract
BACKGROUND: Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD.
METHODS: In this open-label, dose-escalation phase 1-2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA. To explore the potential effect of 2-week dosing, three additional participants were enrolled in a parallel study at Rush University Medical Center (RUMC), Chicago, IL, USA. Participants from the NIH were non-randomly, sequentially assigned in cohorts of three to receive monthly initial intrathecal HPβCD at doses of 50, 200, 300, or 400 mg per month. A fifth cohort of two participants received initial doses of 900 mg. Participants from RUMC initially received 200 or 400 mg every 2 weeks. The dose was escalated based on tolerance or safety data from higher dose cohorts. Serum and CSF 24(S)-hydroxycholesterol (24[S]-HC), which serves as a biomarker of target engagement, and CSF protein biomarkers were evaluated. NPC Neurological Severity Scores (NNSS) were used to compare disease progression in HPβCD-treated participants relative to a historical comparison cohort of 21 NPC1 participants of similar age range.
FINDINGS: Between Sept 21, 2013, and Jan 19, 2015, 32 participants with NPC1 were assessed for eligibility at the National Institutes of Health. 18 patients were excluded due to inclusion criteria not met (six patients), declined to participate (three patients), pursued independent expanded access and obtained the drug outside of the study (three patients), enrolled in the RUMC cohort (one patient), or too late for the trial enrolment (five patients). 14 patients were enrolled and sequentially assigned to receive intrathecal HPβCD at a starting dose of 50 mg per month (three patients), 200 mg per month (three patients), 300 mg per month (three patients), 400 mg per month (three patients), or 900 mg per month (two patients). During the first year, two patients had treatment interrupted for one dose, based on grade 1 ototoxicity. All 14 patients were assessed at 12 months. Between 12 and 18 months, one participant had treatment interrupted at 17 months due to hepatocellular carcinoma, one patient had dose interruption for 2 doses based on caregiver hardship and one patient had treatment interrupted for 1 dose for mastoiditis. 11 patients were assessed at 18 months. Between Dec 11, 2013, and June 25, 2014, three participants were assessed for eligibility and enrolled at RUMC, and were assigned to receive intrathecal HPβCD at a starting dose of 200 mg every 2 weeks (two patients), or 400 mg every two weeks (one patient). There were no dropouts in this group and all 3 patients were assessed at 18 months. Biomarker studies were consistent with improved neuronal cholesterol homoeostasis and decreased neuronal pathology. Post-drug plasma 24(S)-HC area under the curve (AUC8-72) values, an indicator of neuronal cholesterol homoeostasis, were significantly higher than post-saline plasma 24(S)-HC AUC8-72 after doses of 900 mg (p=0·0063) and 1200 mg (p=0·0037). CSF 24(S)-HC concentrations in three participants given either 600 or 900 mg of HPβCD were increased about two fold (p=0·0032) after drug administration. No drug-related serious adverse events were observed. Mid-frequency to high-frequency hearing loss, an expected adverse event, was documented in all participants. When managed with hearing aids, this did not have an appreciable effect on daily communication. The NNSS for the 14 participants treated monthly increased at a rate of 1·22, SEM 0·34 points per year compared with 2·92, SEM 0·27 points per year (p=0·0002) for the 21 patient comparison group. Decreased progression was observed for NNSS domains of ambulation (p=0·0622), cognition (p=0·0040) and speech (p=0·0423).
INTERPRETATION: Patients with NPC1 treated with intrathecal HPβCD had slowed disease progression with an acceptable safety profile. These data support the initiation of a multinational, randomised, controlled trial of intrathecal HPβCD.
FUNDING: National Institutes of Health, Dana's Angels Research Trust, Ara Parseghian Medical Research Foundation, Hope for Haley, Samantha's Search for the Cure Foundation, National Niemann-Pick Disease Foundation, Support of Accelerated Research for NPC Disease, Vtesse, Janssen Research and Development, a Johnson & Johnson company, and Johnson & Johnson.

PMID: 28803710 [PubMed - indexed for MEDLINE]

[Castleman's Disease - A Case Series of a Rare Lymphoproliferative Disease].

Laryngorhinootologie. 2017 Aug;96(8):522-527

Authors: Riepl R, Hoffmann TK, Greve J

Abstract
Castleman's disease is a very rare and potentially severe lymphoproliferative disorder. First sign may be cervical lymphadenitis, requiring sufficient support in diagnosis and therapy by an ENT specialist. Based on a case series the current manuscript gives an overview of the symptoms, the course of disease and the therapy options. Patients with the first diagnosis of a Castleman's disease at the ENT clinic of Ulm University during the years 2011-2015 were included. The duration of symptoms, the applied diagnostic and therapeutic algorithms were evaluated. The duration of the rather weak symptoms was inhomogenous and lasted from 14 days to 14 years. After diagnostic exstirpation a hyaline-vascular type of Castelman's disease was confirmed in all cases. One of the 5 cases proved a multicentric type with an additional axillary manifestation, the others were monocentric. In all patients the diagnostic exstirpation was sufficient for therapy without need for adjuvant medication. At the time of publication all patients are in remission for at least 18 resp. 61 months. The ENT specialist encounters Castleman's disease mostly as a long-lasting swelling of cervical lymph nodes refractory to therapy and without severe concomittant symptoms. Due to potentially unfavorable outcomes a timely diagnostic lymph node exstirpation under general anesthesia is indicated. In most cases this surgical intervention represents the sufficient therapy.

PMID: 28486739 [PubMed - indexed for MEDLINE]

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Somatic Mutation in Pediatric Neurological Diseases.

Pediatr Neurol. 2018 Aug 11;:

Authors: Rodin RE, Walsh CA

PMID: 30249355 [PubMed - as supplied by publisher]

Authors' reply to Rare diseases in Romania - a response to 'Transposition and implementation of EU rare diseases policy in Eastern Europe'.

Expert Rev Pharmacoecon Outcomes Res. 2018 08;18(4):349-350

Authors: Pejcic AV, Iskrov G, Stefanov R

PMID: 29923755 [PubMed - indexed for MEDLINE]

Rare diseases in Romania - a response to 'transposition and implementation of EU rare diseases policy in Eastern Europe'.

Expert Rev Pharmacoecon Outcomes Res. 2018 06;18(3):233-234

Authors: Severin E

PMID: 29683365 [PubMed - indexed for MEDLINE]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

[Anesthesia in patients with NBIA : Neurodegeneration with brain iron accumulation].

Anaesthesist. 2018 Sep 20;:

Authors: Warnecke T, Schmitz J, Kerkhoff S, Hinkelbein J

Abstract
BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) forms a group of rare hereditary diseases with rapid neurodegenerative progression due to an abnormal accumulation of iron in the basal ganglia. This causes extrapyramidal symptoms as well as dystonia and mental retardation. The most common form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome). There are multiple anesthesiological challenges with great implications for the clinical routine, particularly regarding the preparation for general anesthesia and the premedication visits. As with other orphan diseases, the available recommendations are mainly based on case reports.
OBJECTIVE AND METHODS: This article gives a short overview of complications associated with NBIA pertaining to general anesthesia. This includes anesthesia-relevant clinical symptoms and perioperative management. The published literature and case reports (available on PubMed) were reviewed to extract a set of recommendations.
RESULTS: So far only a few reports have included the anesthesia management of NBIA patients. Most of them refer to PKAN as the predominant type (50% of cases). Recommendations were found on www.orphananesthesia.eu and consensus guidelines on PKAN in general. In particular, dystonia-related restrictions in the maxillofacial area can complicate airway management and cause difficulties with respect to intubation. Furthermore, local or regional anesthesia as the sole anesthesia technique is not eligible/viable due to the reduced compliance of the patient. Special attention should be paid to a timely premedication visit and evaluation to ensure sufficient time to safely plan and prepare the anesthetic procedure.
CONCLUSION: The handling of NBIA patients requires good preparation, including an interdisciplinary team and customized time management. In principle, both general anesthesia as a balanced method and total intravenous anesthesia (TIVA) seem to be possible/viable options. The main focus is on airway management. Even after brief sedation in the context of diagnostic measures, the patient should be monitored for longer than usual.

PMID: 30238129 [PubMed - as supplied by publisher]

A limb-girdle muscular dystrophy 2I model of muscular dystrophy identifies corrective drug compounds for dystroglycanopathies.

JCI Insight. 2018 Sep 20;3(18):

Authors: Serafini PR, Feyder MJ, Hightower RM, Garcia-Perez D, Vieira NM, Lek A, Gibbs DE, Moukha-Chafiq O, Augelli-Szafran CE, Kawahara G, Widrick JJ, Kunkel LM, Alexander MS

Abstract
Zebrafish are a powerful tool for studying muscle function owing to their high numbers of offspring, low maintenance costs, evolutionarily conserved muscle functions, and the ability to rapidly take up small molecular compounds during early larval stages. Fukutin-related protein (FKRP) is a putative protein glycosyltransferase that functions in the Golgi apparatus to modify sugar chain molecules of newly translated proteins. Patients with mutations in the FKRP gene can have a wide spectrum of clinical symptoms with varying muscle, eye, and brain pathologies depending on the location of the mutation in the FKRP protein. Patients with a common L276I FKRP mutation have mild adult-onset muscle degeneration known as limb-girdle muscular dystrophy 2I (LGMD2I), whereas patients with more C-terminal pathogenic mutations develop the severe Walker-Warburg syndrome (WWS)/muscle-eye-brain (MEB) disease. We generated fkrp-mutant zebrafish that phenocopy WWS/MEB pathologies including severe muscle breakdowns, head malformations, and early lethality. We have also generated a milder LGMD2I-model zebrafish via overexpression of a heat shock-inducible human FKRP (L276I) transgene that shows milder muscle pathology. Screening of an FDA-approved drug compound library in the LGMD2I zebrafish revealed a strong propensity towards steroids, antibacterials, and calcium regulators in ameliorating FKRP-dependent pathologies. Together, these studies demonstrate the utility of the zebrafish to both study human-specific FKRP mutations and perform compound library screenings for corrective drug compounds to treat muscular dystrophies.

PMID: 30232282 [PubMed - as supplied by publisher]

Case report: two cases of extremely rare primary pure squamous cell carcinoma of the breast.

Medicine (Baltimore). 2018 Sep;97(37):e12340

Authors: Yoneto T, Hasumi K, Yoshimoto T, Takahashi N, Takeda Y

Abstract
RATIONALE: Since primary pure squamous cell carcinoma of the breast is a rare disease, few reports describe the characteristic findings on performing preoperative imaging that can be used to distinguish it from normal breast cancer. The rapid evolution and lack of an established method of treatment has resulted in several reports of advanced cases of primary pure squamous cell carcinoma of the breast.
PATIENT CONCERNS: Case 1 was a 44-year-old woman with an elastic, hard tumor in the left C region. Ultrasonographic analysis revealed a maximal 11-mm hypoechoic area. Histologically, the tumor was a well-differentiated squamous cell carcinoma with prominent keratinization, and there was prominent inflammatory cell infiltration, necrosis, and fibrosis. Case 2 was a 58-year-old woman with an elastic, hard tumor in the left C/D region. Ultrasonographic analysis revealed a maximal 31-mm hypoechoic area with partially calcified areas and a hyperechoic margin. Histologically, the tumor was a squamous cell carcinoma with prominent keratinization exhibiting an infiltrative growth pattern. The tumor had no connection to the epidermis and partially transitioned into the atypical ductal epithelium in the area surrounding the focus.
DIAGNOSES: The patient in Case 1 was preoperatively diagnosed with T1cN0M0 Stage I cancer of the left breast, but both patients were finally diagnosed with T2N0M0 Stage IIA cancer.
INTERVENTIONS: Case 1: left partial mastectomy and axillary lymph node dissection were performed. The patient was administered 4 courses of FEC100 and 4 courses of DTX as postoperative adjuvant therapy. Case 2: left modified radical mastectomy and axillary lymph node dissection were performed without any postoperative adjuvant therapy.
OUTCOMES: Case 1: no sign of relapse was observed, but the patient moved away from the area to another hospital in March 2014 and eventually died due to relapse in January 2016. Case 2: four years after surgery, no relapse has been observed.
LESSONS: We should always keep the presence of primary pure squamous cell carcinoma among breast cancers in mind although the crisis rate is very low. Due to its high malignancy, needle biopsy and aspiration biopsy cytology should be performed to make a definitive diagnosis.

PMID: 30212985 [PubMed - indexed for MEDLINE]

Desmoplastic small round cell tumor: A nationwide study of a rare sarcoma.

J Surg Oncol. 2018 Jun;117(8):1759-1767

Authors: Stiles ZE, Dickson PV, Glazer ES, Murphy AJ, Davidoff AM, Behrman SW, Bishop MW, Martin MG, Deneve JL

Abstract
BACKGROUND AND OBJECTIVES: Desmoplastic small round cell tumor (DSRCT) is a rare peritoneal surface malignancy. Current research is limited by the scarcity of this disease.
METHODS: Patients with DSRCT were identified in the 2004-2014 NCDB. Factors affecting overall survival (OS) were assessed. Additionally, trends were examined based on the volume of cases treated at individual facilities.
RESULTS: A total of 125 patients were identified with a median age of 21 (IQR 15-27). Six had extra-abdominal disease and 15 (12%) had liver involvement. Median OS was 28 months. Systemic chemotherapy (HR 0.4, P = 0.015) and surgery (HR 0.6, P = 0.047) were associated with reduced mortality. For the 74 patients undergoing surgery, absence of liver involvement and receipt of postoperative chemotherapy were associated with improved OS on univariate analysis. On multivariable analysis, two factors approached significance: adjuvant chemotherapy was associated with a reduced risk of mortality (HR 0.3, P = 0.073) and residual macroscopic disease after resection correlated with increased risk of mortality (HR 5.3, P = 0.071). High-volume facilities (≥5 cases) experienced improved OS (median 59.1 vs 28.8 months), albeit not significantly (P = 0.135), compared to low-volume centers.
CONCLUSION: Despite multimodal treatment, DSRCT is associated with dismal outcomes. Facilities familiar with treating this uncommon disease may experience superior outcomes.

PMID: 29878371 [PubMed - indexed for MEDLINE]

Isolated severe microblepharon in a neonate: a rare case.

Int Ophthalmol. 2018 Oct;38(5):2175-2178

Authors: Meel R, Devi S, Ganger A, S M, Pushker N

Abstract
PURPOSE: To report a rare case of isolated severe microblepharon in a neonate.
METHODS: A 27 days old male child was brought by parents with redness, photophobia and discharge for two weeks. Thorough ophthalmological and systemic examination was performed.
RESULTS: The diagnosis of isolated severe microblepharon with infectious keratitis was made. After the appropriate management of infectious keratitis and achieving complete resolution, the child was subjected to bilateral lid reconstruction was done in the form of upper lid skin grafting and tarsorrhaphy and the patient is being followed up.
CONCLUSION: A rare case of bilateral isolated severe microblepharon affecting all four eyelids is being reported. Urgent surgical intervention is recommended in such cases in order to achieve good corneal coverage which results in faster healing of infective keratitis and a good visual outcome.

PMID: 28803395 [PubMed - indexed for MEDLINE]

Inflammatory myofibroblastic tumor of the lung.

Adv Respir Med. 2018;86(1):27-35

Authors: Khatri A, Agrawal A, Sikachi RR, Mehta D, Sahni S, Meena N

Abstract
Inflammatory myofibroblastic tumors (IMT) of the lung, first reported in 1939, are considered a subset of inflammatory pseudo -tumors. They are a distinctive lesions composed of myofibroblastic spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. IMTs may be benign, invade surrounding structures, undergo malignant transformation, recur or may even metastasize. They can occur due to a genetic mutation or can occur secondary to infectious or autoimmune diseases. Patients may be asymptomatic, or present with cough, hemoptysis, dyspnea, pleuritic pain, constitutional symptoms or pneumonia. In this article we review the pathophysiology, genetics, clinical presentation, imaging findings of IMT of the lung. We also discuss the various surgical and non-surgical treatment options and the prognosis associated with this disease.

PMID: 29490419 [PubMed - indexed for MEDLINE]

A Rare Case of Misdiagnosis: Recurrence of Dermatofibrosarcoma Protuberans That Was Treated Surgicallyas a Keloid.

Med Arch. 2018 Feb;72(1):74-75

Authors: Ucak M

Abstract
Aim: In this report, we presented the patient with Dermatofibrosarcoma Protuberans (DFSP), removed by considering as the keloid scar in the general surgery clinic with misdiagnosis.
Case report: The patient was a 19-year-old female student with no scar or previous trauma history in the lesion area. Pathology report of excisional biopsy revealed as a DFSP, reachedsubcutis and dermis. In staging by CT, there had been no distant metastases. There was a lesion with the size of 2x1.5x1.5cm. A large resection was made to include the entire mass and the lower fascia. The defect area was repaired with a Limberg flap. There was no tumor recurrence in the first 6 months following the operation with high-level aesthetics for patient satisfaction.
Conclusion: DFSP should be remembered in cases of operative or spontaneous keloid scarring lesions. The surgical treatment is possible after extensive resection with flap or graft repair.

PMID: 29416224 [PubMed - indexed for MEDLINE]

Salivary duct carcinoma.

Curr Opin Otolaryngol Head Neck Surg. 2018 Apr;26(2):142-151

Authors: D'heygere E, Meulemans J, Vander Poorten V

Abstract
PURPOSE OF REVIEW: The review puts new information on geno- and phenotype of salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO classification.
RECENT FINDINGS: The proportion of SDC is increasing. This may be because of a true rise in incidence, but certainly to better diagnostic tests and changed WHO definitions. In this light, a substantial proportion of carcinoma expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC' and 'SDC in-situ' of the former WHO classification, are now named low-grade and high-grade intraductal carcinoma (IDC), respectively. Recent series quantify biologic aggressiveness: perineural growth, vascular invasion, and extracapsular extension in lymph node metastasis are each observed in two out of three patients with SDC. Most patients die within 3 years, but once 5-year disease-free survival is reached, further disease activity is exceptional. The typical molecular biological profile with high human epidermal growth factor receptor 2 and androgen receptor expression is increasingly successfully exploited in clinical trials for advanced SDC.
SUMMARY: The aggressive SDC is increasingly diagnosed. Despite intensive combined surgery and radiation therapy, many patients recur, for whom new bullets, targeting the molecular biological mechanisms, are the subject of ongoing clinical trials.

PMID: 29373327 [PubMed - indexed for MEDLINE]

The recurrent pleomorphic adenoma conundrum.

Curr Opin Otolaryngol Head Neck Surg. 2018 Apr;26(2):134-141

Authors: Bradley PJ

Abstract
PURPOSE OF REVIEW: Recurrent pleomorphic adenoma (RPA) is uncommon. Treatment selection is based on the likely possibility of minimizing the risk of tumour recurrence, avoiding local functional and cosmetic sequelae, and eradicates the possibility of metastatic or malignant transformation. Much has changed since the topic was reviewed in 2001, and this manuscript comments on clinical progress and discusses patient treatment options.
RECENT FINDINGS: Surgery is the preferred treatment for head and neck pleomorphic adenoma. Over the recent decade the surgical radicality is favoured for parotid and submandibular gland pleomorphic adenoma, from total gland and tumour removal to endoscopic or minimal open extracapsular tumour excision. Currently molecular pathology and biomarker research has not identified any evidence that separates pleomorphic adenoma from RPA, thus supporting that tumour recurrence is likely associated with surgery. Revision surgery has been reported to be frequently noncurative depending on the extent of the primary surgery, with the added risk of local cosmetic and functional sequelae. Radiotherapy as a nonsurgical modality has advanced and has been shown to be effective in controlling, if not curing, high-risk patients who have identifiable prognostic factors of developing a recurrence and patients with RPA.
SUMMARY: Current surgical management of pleomorphic adenoma is associated with improved quality of life and minimal disturbance to cosmetic and functional. The reported incidence of RPA has been reduced by 'expert surgeons' but with limited short-term follow-up following more recent surgical modifications. Patients with RPA should be offered treatment that includes surgery and/or radiotherapy and should be encouraged to partake of this decision making process.

PMID: 29278551 [PubMed - indexed for MEDLINE]