Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.

J Clin Oncol. 2018 01 01;36(1):7-13

Authors: Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B

Abstract
Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

PMID: 29072975 [PubMed - indexed for MEDLINE]

Rare Diseases with Periodontal Manifestations.

Int J Environ Res Public Health. 2019 03 09;16(5):

Authors: Hanisch M, Hoffmann T, Bohner L, Hanisch L, Benz K, Kleinheinz J, Jackowski J

Abstract
Background: The object of this paper was to provide an overview of rare diseases (RDs) with periodontal manifestations and allocate them to relevant categories. Methods: In ROMSE, a database for "Rare Diseases with Orofacial Involvement", all 541 entities were analyzed with respect to manifestations of periodontal relevance. Inclusion criteria were periodontally relevant changes to the oral cavity, in accordance with the 2018 version of the Classification of Periodontal and Peri-Implant Diseases and Conditions. Rare diseases were recorded, using the methodology described, and subsequently compared with the Orphanet Classification of Rare Diseases. Results: A total of 76 RDs with periodontal involvement were recorded and allocated in accordance with the Classification of Periodontal and Peri-Implant Diseases and Conditions. Of the 541 RDs analyzed as having known orofacial manifestations, almost 14 percent indicated a periodontally compromised dentition. Conclusions: Around 14 percent of RDs with an orofacial involvement showed periodontally relevant manifestations, which present not only as a result of gingivitis and periodontitis, but also gingival hyperplasia in connection with an underlying disease. Thus, dentists play an important role in therapy and early diagnoses of underlying diseases based on periodontally relevant manifestations.

PMID: 30857312 [PubMed - indexed for MEDLINE]

Bronchiectasis update.

Curr Opin Infect Dis. 2018 04;31(2):194-198

Authors: O'Donnell AE

Abstract
PURPOSE OF REVIEW: Bronchiectasis, once thought to be an orphan disease, is being diagnosed with increased frequency in the United States and around the world. The present review aims to provide an update on recent publications on the diagnosis and management of bronchiectasis.
RECENT FINDINGS: Two large bronchiectasis patient registries have published initial reports regarding demographics and other patient data in 2017. Updates on the microbiology, microbiome, and inflammation in patients with bronchiectasis are clarifying the complexities of airway infection in this disease. A consensus definition of 'exacerbation' in bronchiectasis has been agreed upon this year. Reports on novel treatments, including the repurposing of older therapies, have also been published in 2016-2017. A new European guideline for the management of adult bronchiectasis is also now available.
SUMMARY: Bronchiectasis, a resurgent disease, is now being better defined with a rapidly expanding portfolio of demographic, clinical, and therapeutic research and publications.

PMID: 29489526 [PubMed - indexed for MEDLINE]

The rapidly evolving state of gene therapy.

FASEB J. 2018 04;32(4):1733-1740

Authors: Gruntman AM, Flotte TR

Abstract
Gene therapy is emerging as a viable option for clinical therapy of monogenic disorders and other genetically defined diseases, with approved gene therapies available in Europe and newly approved gene therapies in the United States. In the past 10 years, gene therapy has moved from a distant possibility, even in the minds of much of the scientific community, to being widely realized as a valuable therapeutic tool with wide-ranging potential. The U.S. Food and Drug Administration has recently approved Luxturna (Spark Therapeutics Inc, Philadelphia, PA, USA), a recombinant adeno-associated virus (rAAV) 2 gene therapy for one type of Leber congenital amaurosis 2 ( 1 , 2 ). The European Medicines Agency (EMA) has approved 3 recombinant viral vector products: Glybera (UniQure, Amsterdam, The Netherlands), an rAAV vector for lipoprotein lipase deficiency; Strimvelis (Glaxo Smith-Kline, Brentford, United Kingdom), an ex vivo gammaretrovirus-based therapy for patients with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID); and Kymriah (Novartis, Basel, Switzerland), an ex vivo lentivirus-based therapy to engineer autologous chimeric antigen-receptor T (CAR-T) cells targeting CD19-positive cells in acute lymphoblastic leukemia. These examples will be followed by the clinical approval of other gene therapy products as this field matures. In this review we provide an overview of the state of gene therapy by discussing where the field stands with respect to the different gene therapy vector platforms and the types of therapies that are available.-Gruntman, A. M., Flotte, T. R. The rapidly evolving state of gene therapy.

PMID: 31282760 [PubMed - indexed for MEDLINE]

Mucocutaneous lesions and nail pigmentation in a patient with essential thrombocytosis.

Aust Fam Physician. 2017;46(4):222-224

Authors: Calleja Algarra A, Miguel RA, Tous Romero F, Maroñas Jiménez L

PMID: 28376576 [PubMed - indexed for MEDLINE]

A clinical and surgical challenge: Retrorectal tumors.

J Cancer Res Ther. 2019 Jan-Mar;15(1):132-137

Authors: Kilic A, Basak F, Su Dur MS, Sisik A, Kivanc AE

Abstract
Aims: Retrorectal tumors are rare, mostly benign tumors and named due to their localization. Diagnoses of these tumors are usually delayed because of nonspecific complaints and symptoms. Magnetic resonance imaging has beneficial uses both for diagnosis and treatment. In this study, we reviewed a case series of retrorectal tumors.
Subjects and Methods: The patients who were diagnosed with retrorectal tumors between 2008 and 2015 were analyzed. This investigation was conducted at a Tertiary Education and Research Hospital. Sixteen patients were included in this study. Patients' demographic data, imaging workups, surgical operation reports, pathologic examination results, postoperative complications, and follow-up results were examined. Descriptive statistics, median, and standard deviation for continuous variables were used. The primary outcomes measured were diagnostic conflict, knowledge, and preference for surgery.
Statistical Analysis Used: Definitive statistical methods (mean, standard deviation, median, frequency, and percentage) were used to evaluate the study data.
Results: One patient refused operation and one was in preoperative preparation period. Fourteen of sixteen patients were operated. Two (14.3%) of operated patients have malignant histopathological result (one gastrointestinal stromal tumor, one ganglioneuroblastoma). Rest of the operated patients' histopathological reports was as follows: Four schwannomas, three epidermoid cysts, two tailgut cyst, one dermoid cyst, one teratoma, and one angiomyolipoma. Eight patients were operated by posterior incision, five patients with transabdominal approach, and one patient with combined approach.
Conclusions: Retrorectal tumors are rare cases, and treatment of retrorectal tumors is surgery and should be operated in referenced hospitals to avoid diagnostic and therapeutic problems.

PMID: 30880768 [PubMed - indexed for MEDLINE]

Rapid on-site evaluation facilitated the diagnosis of a rare case of Talaromyces marneffei infection.

Cytopathology. 2018 10;29(5):497-499

Authors: Ma W, Thiryayi SA, Holbrook M, Shelton D, Narine N, Sweeney LC, Augustine T, Bailey S, Al-Najjar H, Rana DN

PMID: 29722932 [PubMed - indexed for MEDLINE]

Proximal-type epithelioid sarcoma of the vulva: Cytopathological diagnosis of a rare neoplasm.

Cytopathology. 2018 10;29(5):471-473

Authors: Sundaram A, Elangovan A, Rajwanshi A, Srinivasan R, Kapoor R

PMID: 29683530 [PubMed - indexed for MEDLINE]

Paediatric genomics: diagnosing rare disease in children.

Nat Rev Genet. 2018 05;19(5):253-268

Authors: Wright CF, FitzPatrick DR, Firth HV

Abstract
The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition. However, making a molecular diagnosis with current technologies and knowledge is often still a challenge. Paediatric genomics is an immature but rapidly evolving field that tackles this issue by incorporating next-generation sequencing technologies, especially whole-exome sequencing and whole-genome sequencing, into research and clinical workflows. This complex multidisciplinary approach, coupled with the increasing availability of population genetic variation data, has already resulted in an increased discovery rate of causative genes and in improved diagnosis of rare paediatric disease. Importantly, for affected families, a better understanding of the genetic basis of rare disease translates to more accurate prognosis, management, surveillance and genetic advice; stimulates research into new therapies; and enables provision of better support.

PMID: 29398702 [PubMed - indexed for MEDLINE]

9 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 2019/07/16

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.

9 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 2019/07/16

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.

First-line genomic diagnosis of mitochondrial disorders.

Nat Rev Genet. 2018 07;19(7):399-400

Authors: Raymond FL, Horvath R, Chinnery PF

PMID: 29789687 [PubMed - indexed for MEDLINE]

8 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 2019/07/12

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.

Sarcomatoid Squamous Cell Carcinoma of the Penis - a Report of Two Cases.

Folia Med (Plovdiv). 2017 Jun 01;59(2):232-237

Authors: Bachurska SY, Antonov PA, Staykov DG, Dechev IY

Abstract
BACKGROUND: Sarcomatoid (spindle cell) squamous cell carcinoma is a rare, highgrade, aggressive tumor consisting of the squamous cell carcinoma admixed with the malignant spindle cell (sarcomatoid) elements. These tumors are relatively uncommon in the genitourinary system and particularly in the penis.
MATERIALS AND METHODS: Two sarcomatoid squamous cell carcinomas of the penis were diagnosed in our hospital between 2012 and 2015. Clinical histories, pathology reports, hematoxylin and eosin-stained and immunohistochemical slides were reviewed.
RESULTS: In both cases, the tumors presented as single, pedunculated, extensive masses with surface ulceration; histology study showed a mixture of high-grade squamous cell carcinoma component and spindle cell neoplastic component in different proportions. Immunohistochemical stains of CK AE1/AE3, p63 and CK903 showed positive immunoreactivity in both components in both cases. Vimentin was positive in spindle cell component and negative in squamous cell carcinoma areas.
CONCLUSION: Sarcomatoid squamous cell carcinoma of the penis is an uncommon tumor of this site with aggressive behavior and bad prognosis which might be related to the delay in medical examination and diagnosis. A correct and thorough morphological study is of great importance for the staging of the disease, treatment and follow up of patients.

PMID: 28704194 [PubMed - indexed for MEDLINE]

7 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 2019/07/10

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.

[Susac syndrome-interdisciplinary tracking of the chameleon: two different case reports].

Ophthalmologe. 2019 Jul 05;:

Authors: Schelenz D, Kleffner I, Tsiampalis N, Dick HB, Rehrmann J

Abstract
BACKGROUND: The diagnosis of Susac syndrome, a presumed autoimmune retinocochleocerebral microvasculopathy, is extremely complex. At the onset of this orphan disease patients can present with an incomplete clinical triad consisting of sensorineural hearing loss, visual loss because of retinal ischemia and diverse neurological symptoms. In terms of the pathophysiology, it is assumed that the vascular endothelial cells swell, occlude the lumina of the vessels and consequently cause ischemia in the surrounding tissue. Due to the wide range of symptoms it is extremely challenging to establish a correct diagnosis. Susac syndrome should be considered as an important differential diagnosis from other neurological, ophthalmological, psychological and otorhinolaryngological diseases.
CASE REPORT: This report presents two different courses of the disease in patients with Susac's syndrome. The first case of a 46-year-old woman, with previously confirmed Susac's syndrome, describes the treatment adjustment and monitoring. The second case of a 30-year-old woman shows the establishment of the initial diagnosis.
DISCUSSION: The two reported cases of Susac's syndrome show the multifaceted range of clinical findings and courses of the disease. Furthermore, the diagnostic and therapeutic options are discussed with respect to the current literature. Diagnostic criteria already published by the European Susac Consortium and a good interdisciplinary collaboration enable a diagnosis as early as possible, which is essential for avoiding delayed treatment and reducing morbidity.

PMID: 31278469 [PubMed - as supplied by publisher]

21 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 2019/07/06

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.

21 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 2019/07/06

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.

Gastric neuroendocrine neoplasias: manifestations and comparative outcomes.

Endocr Relat Cancer. 2019 Jul 01;:

Authors: Felder S, Jann H, Arsenic R, Denecke T, Prasad V, Knappe-Drzikova B, Maasberg S, Wiedenmann B, Pavel ME, Pascher A, Pape UF

Abstract
Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analyzed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification were: gNEN-1 (n=86/60.6%), gNEN-2 (n=7/4.9%) gNEN-3 (n= 24/16.9%) and gNEN-4 (n=25/17.6%); while hypergastrinemia-associated gNEN-1 and -2 were all low grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification OS differed for early and advanced stages, while WHO-grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs. -4).

PMID: 31272081 [PubMed - as supplied by publisher]

Targeting angiosarcomas of the soft tissues: A challenging effort in a heterogeneous and rare disease.

Crit Rev Oncol Hematol. 2019 Jun;138:120-131

Authors: Weidema ME, Versleijen-Jonkers YMH, Flucke UE, Desar IME, van der Graaf WTA

Abstract
Angiosarcomas are rare malignant tumors with a heterogeneous clinical presentation and generally poor prognosis. It has been difficult to establish consistent molecular characteristics and driver events in angiosarcoma development. Oncogenic and angiogenesis-related pathways have been investigated pre-clinically and clinically with varying results. A few promising responses to checkpoint inhibitors have been described, but immunological features require further elucidation. With this review we present an overview of the critical biological pathways and processes affected in angiosarcoma, and their potential role in novel, non-cytotoxic, systemic treatments.

PMID: 31092367 [PubMed - indexed for MEDLINE]