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Klin Monbl Augenheilkd 2019 Apr 18. Epub 2019 Apr 18.

Benign orbital neoplasms comprise a wide spectrum of different entities. The origin of the tumours can be epithelial or mesenchymal. Epithelial neoplasms of the orbit originate from the lacrimal gland. Read More

Ophthalmic Plast Reconstr Surg 2019 Mar 26. Epub 2019 Mar 26.

Oculoplastic Department, Bristol Eye Hospital, Bristol, United Kingdom.

Sebaceous carcinoma is an aggressive malignancy with a high mortality rate that commonly arises in the periorbital area. Rarely, the lacrimal apparatus may be involved by either contiguous or noncontiguous spread. The authors describe 2 unusual cases of sebaceous carcinoma in the lacrimal sac, presenting as a medial canthal mass simulating chronic dacryocystitis. Read More

Ophthalmic Plast Reconstr Surg 2019 Mar/Apr;35(2):e41-e43

Wills Eye Hospital, Philadelphia, Pennsylvania, U.S.A.

Integrase interactor 1 (INI1) is a tumor suppressor gene that is ubiquitously expressed in all nucleated cells. The loss of INI1 protein activity was first demonstrated in aggressive pediatric tumors, including atypical teratoid/rhabdoid (AT/RT) tumor of the central nervous system and malignant rhabdoid tumor of the kidney. Subsequently, INI1 deficiency was discovered in other pediatric and some adult neoplasms. Read More

Digit J Ophthalmol 2018 18;24(1):1-5. Epub 2018 Feb 18.

Department of Ophthalmology, Rhode Island Hospital, Providence, Rhode Island.

Adenoid cystic carcinoma (ACC) is a rare neoplasm of secretory epithelium that most commonly occurs in the fifth and sixth decades of life. It is characterized by high recurrence rates and poor response to chemotherapy, In the orbit, ACC usually presents as a lacrimal gland mass. We describe the rare case of a 70-year-old woman who presented with pain during mastication and bilateral facial numbness in the cranial nerve V2 distribution. Read More

BMJ 2019 Feb 21;364:l93. Epub 2019 Feb 21.

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK.

Cancer Manag Res 2019 1;11:1155-1166. Epub 2019 Feb 1.

Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany,

Introduction: We evaluated treatment outcomes of CIRT in an active raster-scanning technique alone or in combination with IMRT for lacrimal gland tumors.

Methods: A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan-Meier estimates. Toxicity was assessed according to the CTCAE version 5. Read More

Sci Rep 2019 Feb 14;9(1):2068. Epub 2019 Feb 14.

Université Paris Descartes Sorbonne Paris Cité, INSERM UMR-S970, Cardiovascular Research Center - PARCC, Paris, France.

To evaluate the relative contribution of different Magnetic Resonance Imaging (MRI) sequences for the extraction of radiomics features in a cohort of patients with lacrimal gland tumors. This prospective study was approved by the Institutional Review Board and signed informed consent was obtained from all participants. From December 2015 to April 2017, 37 patients with lacrimal gland lesions underwent MRI before surgery, including axial T1-WI, axial Diffusion-WI, coronal DIXON-T2-WI and coronal post-contrast DIXON-T1-WI. Read More

J Pediatr Ophthalmol Strabismus 2019 Feb 8;56:e8-e11. Epub 2019 Feb 8.

A case of a 6-year-old boy presenting with epiphora, medial canthal swelling, and lymphadenopathy is reported. Biopsy revealed a poorly differentiated squamous cell carcinoma. The child underwent neoadjuvant chemotherapy and showed tumor progression after a remarkable initial response. Read More

Korean J Ophthalmol 2019 02;33(1):95-96

Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Oncotarget 2019 Jan 11;10(4):480-493. Epub 2019 Jan 11.

Dr. Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Identification of molecular targets is the first step in developing efficacious therapeutic strategies for tumors. A tumors' biological response to perturbagens yields important information on the molecular determinants for tumor growth. The aim of this study was to characterize the response of adenoid cystic carcinoma of the lacrimal gland (LGACC) to intra-arterial cytoreductive chemotherapy (IACC) in order to identify novel targets to enhance therapy. Read More

Haematologica 2019 Mar 31;104(3):444-455. Epub 2019 Jan 31.

Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

IgG4-related disease is a fibro-inflammatory condition that can affect nearly any organ system. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. This review focuses on the hematologic manifestations of IgG4-related disease, including lymphadenopathy, eosinophilia, and polyclonal hypergammaglobulinemia. Read More

Case Rep Oncol 2018 Sep-Dec;11(3):835-841. Epub 2018 Dec 11.

Department of Medical Oncology, Sapporo Medical University, Sapporo, Japan.

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. Read More

Biomed Rep 2019 Feb 7;10(2):92-96. Epub 2018 Dec 7.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.

The aim of the present study was to investigate the clinicopathological features of cystic lesions in the eyelid. Clinicopathological profiles were retrospectively searched based on medical records of 35 patients with cystic lesions of the eyelids, which were surgically resected from January 2003 to June 2016. The cohort consisted of 16 men and 19 women. Read More

J Pediatr Ophthalmol Strabismus 2019 Jan;56(1)

Graefes Arch Clin Exp Ophthalmol 2019 Apr 21;257(4):785-790. Epub 2019 Jan 21.

Save Sight Institute, University of Sydney, Sydney Eye Hospital Campus, 8 Macquarie Street, Sydney, NSW, 2000, Australia.

Purpose: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol production, has been found to contribute to lipid secretion from skin sebaceous glands and hair follicles. We assessed for HMGCR expression in human eyelid tissue and in immortalized human meibomian gland epithelial cells (HMGECs) using immunohistochemistry.

Methods: Full thickness human eyelid specimens in archival paraffin blocks were obtained. Read More

Oncol Lett 2019 Jan 15;17(1):462-467. Epub 2018 Oct 15.

Department of Diagnostics and Public Health-Section of Pathology, University and Hospital Trust of Verona, I-37134 Verona, Italy.

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. Read More

Anal Cell Pathol (Amst) 2018 17;2018:8120579. Epub 2018 Dec 17.

Research Institute, National Cancer Center Research Institute, Goyang 10408, Republic of Korea.

Environmental and genetic factors exert important influences on lifespan and neoplastic transformation. We have previously shown that spontaneous tumors form frequently in mice homozygous for a full-length deletion. In general, mutations of BRCA1 are closely associated with induction of breast and ovarian cancers but are also known to contribute to the incidence of other cancers at a low frequency. Read More

Zhonghua Yi Xue Za Zhi 2019 Jan;99(1):53-56

Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

To investigate the diagnostic value of apparent diffusion coefficient in diffusion weighted imaging at 3.0 T MR for the differentiation in the larcrimal gland tumors. A total of 73 cases, 36 males and 37 female; mean age 14-81(44±15)years, with lacrimal gland tumors confirmed by pathology in Beijing Tongren Hospital were retrospectively analyzed between January 2011 and April 2016. Read More

Acta Otolaryngol 2019 Jan 10;139(1):100-104. Epub 2019 Jan 10.

a Department of Otolaryngology - Orbital Surgery , Clinica Clarós , Barcelona , Spain.

Background: Lacrimal gland (LG) tumours are rare neoplasms. Pleomorphic adenoma (PA) is the most common histologic variant, representing ∼20% of all LG tumours. PA tends to recur leading to great morbidity. Read More

Dermatol Surg 2019 01;45(1):17-25

All authors are affiliated with the University of Rochester Medical Center, Rochester, New York.

Background: Basal cell cancer is the most common cutaneous malignancy. It rarely presents with locally advanced or metastatic disease. Rare presentations such as intraorbital invasion remain a difficult clinical problem with significant potential morbidity. Read More

Graefes Arch Clin Exp Ophthalmol 2019 Feb 28;257(2):405-411. Epub 2018 Nov 28.

Department of Oculoplastic, Orbital, and Lacrimal Surgery, Aichi Medical University Hospital, 1-1 Yazako-Karimata, Nagakute, Aichi, 480-1195, Japan.

Purpose: To examine the clinicopathological characteristics of patients with thyroid eye disease (TED) who showed asymmetric lacrimal gland enlargement.

Methods: Sixteen patients were included in this retrospective, observational case series. The following data were collected: sex, age, laterality, past medical history, laboratory results for thyroid function and other autoimmune disorders, pathological results, other systemic lesions related to lacrimal gland pathology, and the clinical course after treatment. Read More

N Engl J Med 2018 Nov;379(18):1766

University Hospital Messina, Messina, Italy

Int J Pediatr Otorhinolaryngol 2018 Dec 19;115:54-57. Epub 2018 Sep 19.

Department of Oculoplastic, Orbital, and Lacrimal Surgery, Aichi Medical University Hospital, Aichi, Japan.

Objective: To examine the surgical outcome of dacryoendoscopy-assisted nasal endoscopic marsupialization for congenital dacryocystocele.

Methods: This is a retrospective, observational study that included 7 sides of 6 patients with congenital dacryocystocele. The surgical indication in 5 of the patients was acute dacryocystitis while one of the patients had no spontaneous resolution after long-term observation. Read More

J Craniofac Surg 2019 Jan;30(1):158-160

Department of Oculoplastic, Orbital, and Lacrimal Surgery, Aichi Medical University Hospital, Aichi, Japan.

The authors present 2 female patients of mantle cell lymphoma (MCL) involving the lacrimal gland. The patients include a 75-year-old female and a 59-year-old female. Both patients presented with palpable upper eyelid masses. Read More

BMJ Case Rep 2018 Oct 17;2018. Epub 2018 Oct 17.

Otolaryngology, Concord Repatriation General Hospital, Concord, New South Wales, Australia.

Paranasal mucoceles are cystic masses lined with epithelium thought to result from chronic obstruction of an impaired sinus ostia. If sufficiency large, they can cause ophthalmological sequelae including diplopia, visual acuity, globe displacement as well as the rhinological symptoms of facial pain and headache. We present the case of a 57-year-old man who presented with a 1-year history of epiphora and right globe prominence with associated diplopia. Read More

Ocul Oncol Pathol 2018 Sep 12;4(2):67-72. Epub 2017 Aug 12.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, New York, NY, USA.

Neoplasms arising in accessory lacrimal glands are rare. We describe a 33-year-old man with adenocarcinoma arising in the left lower eyelid accessory lacrimal gland. Microscopic evaluation demonstrated an infiltrative neoplasm composed of mildly to moderately pleomorphic cells with abundant eosinophilic cytoplasm and focal intracytoplasmic vacuoles, arranged predominantly in ductules. Read More

Korean J Ophthalmol 2018 Oct;32(5):426-427

Department of Ophthalmology, Catholic University of Daegu College of Medicine, Daegu, Korea.

Histopathology 2019 Feb 2;74(3):514-525. Epub 2018 Dec 2.

Department of Human Pathology, School of Medicine, Juntendo University, Tokyo, Japan.

Aims: Pleomorphic adenoma gene 1 (PLAG1) rearrangement is well known in pleomorphic adenoma (PA), which is histologically characterised by admixed epithelial and mesenchymal components. Multiple fusion variants of PLAG1 and HMGA2 have been reported; currently, however, little is known regarding the clinicopathological impacts of these fusion types METHODS AND RESULTS: We examined the PLAG1- and HMGA2-related fusion status in 105 PAs and 11 cases of carcinoma ex PAs (CXPA) arising from salivary glands and lacrimal glands to elucidate their correlation to the clinicopathological factors. Forty cases harboured PLAG1 fusion genes: CTNNB1-PLAG1 in 22 cases, CHCHD7-PLAG1 in 14 cases and LIFR-PLAG1 in four cases. Read More

Am J Rhinol Allergy 2018 Nov 25;32(6):518-525. Epub 2018 Sep 25.

1 Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China.

Background: The intranasal endoscopic prelacrimal recess approach (PLRA) access to all aspects of the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct and its use have been reported in the treatment of many maxillary sinus and lateral skull base diseases.

Objective: To retrospectively assess the effectiveness of a 10-year multicenter follow-up for the resection of inverted papilloma of the maxillary sinus (IPMS) via a PLRA.

Methods: A total of 71 patients were admitted and underwent IPMS excision via an intranasal endoscopic PLRA from 2003 to 2013. Read More

Orbit 2018 Sep 20:1-5. Epub 2018 Sep 20.

a South Australian Institute of Ophthalmology , Royal Adelaide Hospital , Adelaide , Australia.

Purpose: To report a case of a lacrimal sac tumour and describe a prelacrimal approach to the maxillary sinus to excise the nasolacrimal duct in its management. To our knowledge, this approach has not been adapted to remove the nasolacrimal duct for the management of pathological processes involving the nasolacrimal system.

Methods: A 58-year-old female patient presented with a 6-month history of epiphora. Read More

Medicine (Baltimore) 2018 Sep;97(37):e12198

Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy.

Rationale: Primary poorly differentiated lacrimal gland adenocarcinoma in the orbital region is an extremely rare type of neoplasm with only 1 related case in the literature. Its high grade of malignancy makes the timely data reported necessary. Hence, we present an extremely rare disease with biopsy results and recommendations on clinical treatment in an elderly male with Chinese descent. Read More

Oxf Med Case Reports 2018 Sep 25;2018(9):omy066. Epub 2018 Aug 25.

Division of Internal Medicine, Department of Hematology/Oncology, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA.

Although the histologically diverse classification of salivary gland tumors can be successfully applied to the epithelial lacrimal gland neoplasms, it is not clear whether the molecular makeup differs between these two different tumor types. Adenocarcinomas have known to have driver mutations in non-small cell lung cancer, however, besides HER2 expression not much is known regarding molecular drivers in lacrimal tumors. Androgen receptor (AR) expression and deprivation combined with checkpoint inhibition (CPI) have not been described before in lacrimal gland adenocarcinoma. Read More

Ultrasound 2018 Aug 29;26(3):145-152. Epub 2018 Mar 29.

Department of Clinical Radiology, St George's University Hospitals NHS Foundation Trust, UK.

Background: Multiple disease processes may arise within the orbit and imaging plays a vital role in the evaluation of such lesions. The anterior orbital contents are readily amenable to evaluation by ultrasonography. Furthermore, the modality can be used to guide tissue sampling (fine needle aspiration or core biopsy) and may obviate the requirement for invasive surgical biopsy. Read More

Int J Ophthalmol 2018 18;11(8):1296-1302. Epub 2018 Aug 18.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Aim: To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors.

Methods: Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated. Read More

BMC Clin Pathol 2018 2;18. Epub 2018 Aug 2.

1Department of Pathology, Specialties Hospital, Ibn Sina University Hospital, Rabat, Morocco.

Background: In lacrimal gland, lymphomas and inflammatory lesions predominate. Primary epithelial tumours represent less than 30% of lacrimal gland lesions. Myoepithelial carcinoma of lacrimal gland is rare. Read More

Can J Ophthalmol 2018 08 11;53(4):e132-e134. Epub 2017 Dec 11.

Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Electronic address:

Ophthalmic Plast Reconstr Surg 2018 Sep/Oct;34(5):e157-e160

Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut, U.S.A.

A 41-year-old woman presented with several days of right eye pain and blurred vision. Examination and radiologic workup were consistent with a veno-lymphatic malformation, including demonstration of cystic fluid-fluid levels on imaging. Histopathology supported the presence of cystic spaces but revealed the final diagnosis of lacrimal epithelial-myoepithelial carcinoma, a rare neoplasm typically associated with the salivary gland. Read More

Bone Joint J 2018 08;100-B(8):1100-1105

Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.

Aims: The aim of this study was to validate the Mirels score in predicting pathological fractures in metastatic disease of the lower limb.

Patients And Methods: A total of 62 patients with confirmed metastatic disease met the inclusion criteria. Of the 62 patients, 32 were female and 30 were male. Read More

Pan Afr Med J 2018 5;29:198. Epub 2018 Apr 5.

Service d'Oncologie Médicale, Institut Salah Azaiz, Tunis, Tunisie.

Primary lung lymphomas are rare tumors representing less than 1% of malignant tumors of the lung. The most frequent form is the mucosa-associated lymphoid tissue (MALT). Ocular involvement is also rare and it is mostly located in the lachrymal glands. Read More

Ophthalmic Plast Reconstr Surg 2018 Sep/Oct;34(5):e154-e157

Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Secretory carcinoma is a salivary gland malignancy that recapitulates secretory carcinoma of the breast, along with its shared ETV6-NTRK3 gene fusion. Characterization of histopathologic, immunohistochemical, and molecular genetic features of this neoplasm has led to reclassification of a heterogeneous group of salivary gland carcinomas as secretory carcinoma and to identification of this neoplasm in other gland-containing tissues. The authors describe a 52-year-old man who presented with a 2-week history of diplopia and a well-circumscribed right orbital mass. Read More

Ned Tijdschr Geneeskd 2018 Jul 13;162. Epub 2018 Jul 13.

Franciscus Gasthuis en Vlietland, afd. Kindergeneeskunde, Rotterdam.

Newborn twins both had a blue, smooth tumour in the inner angle of the orbit; one of them had two such tumours. They were diagnosed with congenital dacryocystoceles. If decompression into the nose is not effective, patients should undergo probing early in life to reduce the incidence of dacryocystitis and orbital cellulitis. Read More

Curr Opin Ophthalmol 2018 Sep;29(5):458-468

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Purpose Of Review: The goal of this article is to review the key clinical and radiological features, treatment strategies, and prognosis of lacrimal gland tumors.

Recent Findings: Debulking of the orbital lobe of the lacrimal gland may offer improved control rates in dacryoadenitis without compromise of tear film function. Contrary to previous belief, careful biopsy of the lacrimal gland prior to excision does not appear to increase the risk of recurrence in cases with suspected pleomorphic adenoma. Read More

Oncol Lett 2018 Aug 1;16(2):2215-2220. Epub 2018 Jun 1.

Department of Ultrasound Diagnosis, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.

Color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in the diagnosis of lacrimal apparatus tumors were investigated. In total, 48 patients undergoing preoperative two-dimensional and color Doppler ultrasound and CEUS examinations were included in this study. Conventional ultrasound and CEUS characteristics of 48 patients pathologically and clinically diagnosed with lacrimal apparatus tumors were retrospectively analyzed. Read More

Chin Med J (Engl) 2018 07;131(14):1746-1747

Department of Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, Shandong 266042, China.

Am J Ophthalmol 2018 Sep 28;193:178-183. Epub 2018 Jun 28.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: Secretory carcinoma has been described in the breast, salivary glands, skin, and other organs, but has not been reported in the lacrimal gland to date. Since lacrimal and salivary glands show similar tumors, we hypothesized that lacrimal secretory carcinoma may exist but has been misclassified in the past.

Design: We undertook a retrospective review of all lacrimal gland tumors at 2 tertiary institutions with centralized ocular pathology practices. Read More

J Craniofac Surg 2018 Oct;29(7):1855-1858

Department of Orbital & Oculoplastic Surgery, Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Purpose: The aim of this study is to describe a minimally invasive technique of en bloc resection of malignant tumors from lacrimal drainage system (LDS).

Methods: This was a noncomparative, retrospective chart review of the clinical and pathologic findings of patients presenting with a LDS malignant tumor who underwent endoscopic prelacrimal recess approach with a small external incision for en bloc excision of the LDS.

Results: A total of 12 patients from April 2010 to July 2017 were reviewed in this study. Read More

Ophthalmic Plast Reconstr Surg 2018 Jul/Aug;34(4):e133-e136

Harvard Medical School, Boston, Massachusetts, U.S.A.

A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Read More

Ophthalmic Plast Reconstr Surg 2018 Sep/Oct;34(5):e147-e148

Allure Laser Center & Medispa, Kirkland, Washington, U.S.A.

Primary extracranial meningioma is a rare tumor, unlike its common intracranial counterpart. Infrequently found in the head and neck region, it can cause local or neurologic symptoms depending on its location and interaction with cranial nerves. While uncommon, it is an important diagnosis to have on the differential of periorbital lesions as surgical removal and prognosis are generally good. Read More

Arch Soc Esp Oftalmol 2018 Oct 1;93(10):494-496. Epub 2018 Jun 1.

Servicio de Reumatología, Hospital Privado Universitario de Córdoba, Córdoba, Argentina.

Case Report: The case is presented of a 64-year-old woman with bilateral palpebral swelling and dacryoadenitis, exophthalmos, and a history of chronic rhinitis and asthma. An increase in serum IgG4 was observed, and an incisional biopsy of lacrimal glands was performed, which showed fibrosis and a lymphoplasmacytic infiltrate with IgG4 producing cells.

Discussion: Orbital involvement in IgG4-related disease is frequent. Read More