Office-based 532-nm KTP laser as a therapeutic modality for recurrent laryngeal papillomatosis: efficacy and relative factors.

This study aims to investigate the efficacy of office-based potassium-titanyl-phosphate (KTP) 532-nm laser in the management of recurrent laryngeal papillomatosis (RLP) following other treatments. A retrospective assessment was performed on 55 patients in 259 cases of RLP between 2012 and 2019. Derkay scores were obtained for all patients who underwent 532-nm KTP laser procedure (6 W of power with a continuous output mode) prior to treatment and after treatment. Analysis of parameters is based on the distribution characteristics of data. An ordinal logistic regression was also performed. Patients received a median of 3 (range 1-24) office-based KTP laser treatments. Among them, 96.36% (53 patients) were previously on cold steel equipment, CO2 laser, or microdebrider treatment under general anesthesia, and all previous treatments on them had failed. One patient progressed to invasive cancer, so he was excluded from the following analyses. After final KTP treatment, 36 patients (66.67%) received complete resolution with follow-up time ranging from 12.9 to 80.53 months (median 55.54 months). Results of subjective voice-quality indicators such as VHI-30 and GRBAS all improved greatly at the last follow-up. The initial Derkay scores and treatment intervals were found to be predictive of complete lesion remission. Arytenoid involvement may also correlate with lesion resolution. Serial office-based KTP treatment is an effective option for RLP patients, with ideal disease control and voice quality preservation. KTP laser therapy should be repeated with an interval of 1 month from the beginning of treatment until the lesion has been evaluated and subsided. Non-bulk or scattered laryngeal papilloma is an appropriate indication for KTP laser treatment.

Squamous papilloma of the proximal oesophagus associated with an inlet patch: a potential aetiological relationship.

Squamous papillomas are rare benign lesions that can be found in the oesophagus. It has been theorised that irritation of the esophageal mucosa leads to squamous papilloma formation. There is evidence to suggest that squamous papillomas of the distal oesophagus are related to irritation due to reflux of gastric acid. In this case report, we describe for the first time a squamous papilloma of the upper oesophagus located just distal to an inlet patch. Inlet patches consist of gastric mucosa located in the proximal oesophagus. They are capable of producing acid. This case raises the possibility that just as squamous papillomas of the distal oesophagus may be related to acid exposure from the reflux of gastric acid, squamous papillomas of the proximal oesophagus may be related to acid exposure from the locally-produced acid of inlet patches.

Immune delineation of laryngeal papilloma reveals enhanced neutrophil associated gene profile.

Laryngeal papilloma (LP) is a rare benign disease, caused by recurrent multisite papillomas that are referred to as recurrent respiratory papillomatosis (RRP). RRP is caused primarily by two types of human papillomavirus (HPV): HPV6 and HPV11. The immune dysregulation within the microenvironment of the lesions has been shown to likely play a role in the development of RRP. The present study aimed at analyzing the transcriptional profile of immune response genes and cancer-related genes in the LP microenvironment. We used the NanoString® nCounter® analysis system to study expression of 730 genes among seven paired samples of LP and healthy laryngeal (HL) tissue. qRT-PCR and flow cytometric analysis was performed to confirm identified transcripts and follow-up scores of infiltrating immune cells, respectively. In total, 113 differentially expressed transcripts were detected of which 37 showed increased expression levels and 76 decreased expression levels in the LP samples compared to the HL samples (fold change ≥ 2). Transcripts with increased expression levels included S100As (A7, A8, and A12), CEACAM1, neutrophil activation associated cytokines (IL8), chemokines (CXCL6), and IL receptors, e.g., IL4R. Transcripts with decreased expression in LP were associated with innate and adaptive immunity. Overall, HPV6 and 11 were present in 67% and 33% of the patients, respectively. There was a significant increase in neutrophils and a significant decrease in CD8+ T cells in LP. LP samples display an immune profile characterized by enhanced expression of neutrophilic markers and significantly reduced T cell-associated markers.

Systemic bevacizumab as adjuvant therapy for recurrent respiratory papillomatosis in children: A series of three pediatric cases and literature review.

Recurrent respiratory papillomatosis (RRP), a viral disease caused by human papillomavirus (HPV), is the most common benign neoplasm of the larynx among children and the second most frequent cause of infantile hoarseness. The course of the disease is variable; some patients experience spontaneous remission, while others may develop an aggressive respiratory compromise. Especially juvenile-onset RRP cases experience shorter intervals between surgical interventions and thus more surgeries overall, causing high rates of depression and voice-related quality of life. Various local adjuvant therapies have been studied with mixed efficacy and some early potential but have failed to show consistent effect across large cohorts of patients. Bevacizumab, a recombinant monoclonal antibody that inhibits VEGF, has shown efficacy in patients with rapid regrowth of papillomas with severe airway compromise, and/or distal multisite spread of disease. We present three juvenile-onset RRP cases successfully managed with systemically administered bevacizumab.

Environmental DNA monitoring of oncogenic viral shedding and genomic profiling of sea turtle fibropapillomatosis reveals unusual viral dynamics.

Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally co-induced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. We applied environmental (e)DNA-based viral monitoring to assess viral shedding as a direct means of transmission, and the relationship between tumor burden, surgical resection and ChHV5 shedding. To elucidate the abundance and transcriptional status of ChHV5 across early, established, regrowth and internal tumors we conducted genomics and transcriptomics. We determined that ChHV5 is shed into the water column, representing a likely transmission route, and revealed novel temporal shedding dynamics and tumor burden correlations. ChHV5 was more abundant in the water column than in marine leeches. We also revealed that ChHV5 is latent in fibropapillomatosis, including early stage, regrowth and internal tumors; higher viral transcription is not indicative of poor patient outcome, and high ChHV5 loads predominantly arise from latent virus. These results expand our knowledge of the cellular and shedding dynamics of ChHV5 and can provide insights into temporal transmission dynamics and viral oncogenesis not readily investigable in tumors of terrestrial species.

Involvement of Laryngopharyngeal Reflux in Select Nonfunctional Laryngeal Diseases: A Systematic Review.

OBJECTIVES: To investigate the existing published evidence supporting the role of laryngopharyngeal reflux (LPR) in the development of the select nonfunctional laryngeal diseases of laryngotracheal stenosis, granuloma, leukoplakia, and laryngeal infections. DATA SOURCES: PubMed, Cochrane Library, and Scopus. REVIEW METHODS: A systematic review was performed by 3 independent investigators for studies providing information about the prevalence and role of LPR in the development of laryngotracheal stenosis, granuloma, leukoplakia, and laryngeal infections. Diagnostic criteria and clinical outcome evaluation of included studies were analyzed with PRISMA criteria. RESULTS: Of the 64 relevant publications, 27 clinical and 4 basic science studies were included. Ten studies used objective reliable examinations for LPR diagnosis (eg, dual- or triple-probe or oropharyngeal pH monitoring, multichannel intraluminal impedance-pH monitoring, or pepsin detection). According to the bias analysis and the results of studies, the association between LPR and laryngotracheal stenosis, leukoplakia, laryngeal papillomatosis, or vocal fold granuloma remains poorly demonstrated. There is a notable heterogeneity among included studies regarding their inclusion criteria, diagnostic methods, and clinical outcome evaluation. Although some experimental findings support the involvement of bile salts and other gastroduodenal proteins active in alkaline pH, no included clinical studies assessed the role of nonacid and mixed reflux through multichannel intraluminal impedance-pH monitoring. CONCLUSION: The involvement of LPR in the development of leukoplakia, laryngotracheal stenosis, vocal fold granuloma, and laryngeal papillomatosis is currently not demonstrated. The potential relationship between LPR and these select nonfunctional laryngeal diseases must be confirmed through future clinical and experimental studies considering acid, nonacid, and mixed LPR.

Method to Study Skin Cancer: Two-Stage Chemically Induced Carcinogenesis in Mouse Skin.

Two-stage chemical carcinogenesis method is widely used to elucidate genetic and molecular changes that lead to skin cancer development, as well as to test chemotherapeutic properties of novel drugs. This protocol allows researchers to reliably induce benign papilloma development and their conversion to squamous cell carcinoma in the skin of susceptible mouse strains in response to a single dose of carcinogen 2,4-dimethoxybenzaldehyde (DMBA) and repetitive applications of tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA).

Resección quirúrgica de papilomatosis glandular endobronquial / Surgical Resection of Endobronchial Glandular Papilloma

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Gingival Papillomatosis as the Oral Sign of Cowden Syndrome: A Case Report.

Cowden syndrome (CS) is a rare autosomal dominant, hereditary, multiorgan disease with higher risk for malignancies (breast, thyroid, endometrium). Mucocutaneous lesions occur in 90% of cases and are characterized by facial trichilemmomas, oral mucosal papillomas, and benign acral keratoses. We present the case of a 39-year-old female patient with the chief complaint of "white spots" on the upper and lower attached gingiva accompanied with skin changes on the face, hands, and soles. The patient's family medical history revealed that her mother had an endometrial polyp and the sister had thyroid cancer. In the patient's medical personal history she reported follicular thyroid adenoma, thyroid abnormalities (i.e. lymphocytic thyroiditis), fibrocystic changes and juvenile breast papillomatosis, lipoma, multiple fibromas, and genitourinary tumors. Based on extensive family and personal medical history, physical examination and histopathological findings, diagnostic criteria were fulfilled for the diagnosis of Cowden syndrome.

Prevalence, clinical presentations, associated risk factors and recurrence of laryngeal papillomatosis among inpatients attended at a Tertiary Hospital in Northern zone Tanzania.

INTRODUCTION: Although Laryngeal papillomatosis is a rare disease and can be conventionally managed through surgical excision as well as adjuvant therapy yet Laryngeal papillomatosis has high tendency to recur raising its prevalence in the community, airway involvement warrants dangerous complications requiring emergency tracheostomy, especially if clinical course is poorly understood and misdiagnosis is common. The study aims to determine the prevalence, clinical features, risk factors and recurrence of Laryngeal Papillomatosis among patients attending ENT department at KCMC from 2005 to 2015. METHODS: This was a 10 year experience/ Descriptive hospital based cross-sectional study conducted based on patients' medical record at KCMC. Information was recorded into data collection sheets, entered and analyzed through SPSS version 20, summarized and presented in tables and charts, proportions and percentage used to compare groups. RESULTS: 51 patients were identified over the 10 years study period corresponding to a prevalence of 0.09%. 26 were males and 25 females, ages ranging from 1 to 67 years. The median age of onset was 6 years. Children less than 5 years accounted for 19 (37.3%) and 58.8% had repeated surgeries. Clinical presentation ranged from hoarseness in 43 (84.3%) patients to weight loss 3 (5.9%) and 96.1% showed complete or partial presence of the clinical triad of risk factors. CONCLUSION: Laryngeal papillomatosis is a rare disease that carries severe morbidity due to its highly recurring nature. It is primarily a paediatric disease, generally affecting more males; its clinical features highly resemble other airway obstructive diseases and therefore a careful thorough clinical evaluation is required in order to correctly diagnose Laryngeal papillomatosis.

Papilomatosis confluente y reticulada con pseudoestrías lineales: descripción de 20 casos / Confluent and Reticulated Papillomatosis With Linear Pseudo-striae: A Description of 20 Cases

La papilomatosis confluente y reticulada, o síndrome de Gougerot y Carteaud, es una enfermedad infrecuente, crónica, de etiología desconocida, que se presenta habitualmente en adultos jóvenes y se caracteriza por placas pardo-eritematosas ovales, que confluyen en un patrón reticulado y afectan el tronco, particularmente la región intermamaria e interescapular, y el cuello. Su diagnóstico es fundamentalmente clínico, se basa en la localización y el aspecto de las lesiones, así como en la respuesta al tratamiento con minociclina. Presentamos 20 casos de papilomatosis confluente y reticulada, confirmados por histopatología, en quienes se identificó la presencia de pseudoestrías lineales, un hallazgo semiológico poco reconocido

Confluent and reticulated papillomatosis, also known as Gougerot-Carteaud Syndrome, is a rare chronic disease typically affecting young adults. Of unknown etiology, the condition is characterised by oval grayish-brown or erythematous papules that coalesce to form a reticular pattern, usually on the trunk, especially in the intermammary or interscapular region and on the neck. Diagnosis is primarily clinical, based on the appearance of the lesions, the areas affected, and the response to treatment with minocycline. We report 20 cases of patients with histologically confirmed confluent and reticulated papillomatosis who presented linear pseudo-striae, a little known diagnostic sign

Elevated HuR in Pancreas Promotes a Pancreatitis-Like Inflammatory Microenvironment That Facilitates Tumor Development.

Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR-overexpressing pancreas displays a fibroinflammatory response and other pathological features characteristic of chronic pancreatitis. This pathology is reflected in changes in the pancreatic gene expression profile due, in part, to genes whose expression changes as a consequence of direct binding of their respective mRNAs to HuR. Older mice develop pancreatic steatosis and severe glucose intolerance. Elevated HuR cooperated with mutant K-rasG12D to result in a 3.4-fold increase in pancreatic ductal adenocarcinoma (PDAC) incidence compared to PDAC presence in K-rasG12D alone. These findings implicate HuR as a facilitator of pancreatic tumorigenesis, especially in the setting of inflammation, and a novel therapeutic target for pancreatitis treatment.

Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8).

BACKGROUND: Currently, seven equine papillomaviruses (PV) are known and are associated with one of three different and distinct clinical presentations. HYPOTHESIS/OBJECTIVES: To report the clinical, histopathological and immunohistochemical findings in horses with generalized papillomatosis associated with a novel equine PV, Equus caballus papillomavirus 8 (EcPV8). ANIMALS: Three client-owned quarter horses. METHODS: Case report, retrospective. RESULTS: Dozens to thousands of papillomas involved the axilla, inguinal area and proximal limbs as well as the ventral and lateral neck, thorax and abdomen. Lesions were sometimes confluent in ventral areas. Fewer lesions were on the face, ears, distal limbs and genitalia. Plaque-type papillomas were small, 0.5 to 1.5 cm in diameter and hyperkeratotic. Histologically, plaque-type papillomas prominently involved follicular infundibula. Immunohistochemical findings demonstrated PV antigen in superficial keratinocyte nuclei. PCR using degenerate primers for the PV L1 gene and sequencing of amplicons revealed PV DNA sequences that were 98% identical for all three cases, but shared <70% identity to other PVs. Horses were otherwise healthy; serum immunoglobulin levels and peripheral blood lymphocyte phenotyping did not identify a known immunodeficiency syndrome. Lesions nearly completely resolved after 1.5 years in one horse and persisted for two years in another, despite intralesional human IFN-alpha treatment. The oldest horse was lost to follow-up. CONCLUSION AND CLINICAL IMPORTANCE: A novel equine papillomavirus (EcPV8) is associated with a distinct, plaque-type, generalized papillomatosis. Papillomas persisted for months to years, with or without treatment.

Florid cutaneous papillomatosis as a marker of neoplastic recurrence.

Florid cutaneous papillomatosis is a rare paraneoplastic dermatosis, most commonly associated with gastric adenocarcinoma. It is characterized by a sudden onset of hyperkeratotic papules, clinically indistinguishable from viral warts. We report an 80-year-old man who presented to our department with a two-month history of multiple verrucous lesions affecting the face, perioral region, and hands. Two years before, he was treated for a gastric adenocarcinoma with a subtotal gastrectomy, but showed no evidence of residual disease or recurrence. Given the clinical background, a diagnosis of florid cutaneous papillomatosis was considered. Skin biopsy excluded a viral origin, and tumour recurrence was later identified through an abdominal ultrasound. The onset of this entity is typically prior or concurrent with the diagnosis of the internal malignancy, but it may also represent the first sign of recurrence of a previously treated neoplasm. Its early recognition is essential to ensure a thorough investigation and prompt treatment.

[Lymphedema complicated with verrucous papillomatosis]. / Lymphœdème compliqué de papillomatose verruqueuse.

Limb lymphedemas are due to a malfunction of the lymphatic system responsible for lymph stasis in the interstitial tissue and secondarily to an increase in the volume of the affected limb. They are divided into primary lymphedema (PL) and secondary lymphedema (SL). SLs develop most frequently in lower limbs after breast cancer treatment while lymphedemas are either secondary (iatrogenic or infectious) or primitive, most often sporadic, sometimes familial or they can be part of syndromes resulting in malformations and/or more complex genetics in upper limbs. The diagnosis of lymphedema is essentially based on clinical examination. Erysipelas are the main complication of lymphedema. Other abnormalities are often visible: yellowish skin and nails, lymphangiectasias, keratotic papules with papillomatosis, lichenified plaques. The main differential diagnosis in patients with limb lymphedema is lipoedema, defined as body fat distribution from the hips up to the ankles and affecting almost exclusively obese women. We report the case of a 30 year old man with left lower limb lymphedema occurred at puberty complicated by verrucous papillomatosis. It is a late-revelation congenital lymphedema.

Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP. METHODS: We performed a phenotypic characterization of peripheral blood mononuclear cells (PBMC) collected from 16 RRP patients and 12 age-matched healthy controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR cytokine analysis, differentiating between Th1-, Th2-, Th3/regulatory-, and inflammatory immune responses. RESULTS: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B expressing lymphocytes. There was an overall suppression of cytokine mRNA production and an aberrant cytokine mRNA profile in the activated NK cells. CONCLUSION: These findings demonstrate an immune dysregulation with inverted CD4+ /CD8+ ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls.

The papillomas of the sinonasal tract. A comprehensive review.

Papillomas are uncommon tumors of the sinonasal tract histologically derived from the Schneiderian membrane. Three distinctive variants are described, the exophytic, the inverting and the oncocytic types. On physical examination, their appearance varies from exophytic-fungiform seen in the exophytic variant, to polypoid-papillary in both the inverting and oncocytic variant. The presence of an asymptomatic mass or epistaxis and unilateral nasal obstruction are the typical presenting symptoms. Clinically they tend to recur and, although benign, they may erode the bone laminas by pressure, especially the inverting type, causing proptosis and other co-morbidities. Malignant transformation is seen both synchronously, on a pre-existing papilloma, and metachronously after several recurrences of papilloma. Schneiderian papillomas are at a date a topic of controversy regarding their etiology, pathogenesis and biological behavior. Furthermore, histologic criteria to assess dysplasia and malignant transformation are ill-defined. The present study aims to comparatively review the histologic types of papillomas, their etiology, the currently available criteria for malignant transformation, their treatment and prognosis.

[Establishment of a SD rat model of vulvar lichen simplex chronicus and detection of the expression of protease activated receptor 2].

OBJECTIVE: To establish a SD rat model of vulvar lichen simplex chronicus (LSC) and investigate the expression of protease activated receptor 2 (PAR2) in the genital skin. METHODS: Seventy female SD rats were randomly divided into group A (blank control group, n=10), group B (with application of acetone solution 3 times per week for 10 weeks, n=10), group C (with chronic mechanical irritation 3 times per week for 10 weeks, n=10), and group D (with topical treatment with 0.5= 7,12-Dimethylbenzanthracene [DMBA] in acetone solution and chronic mechanical irritation 3 times per week for 10 weeks, n=40). The changes of the genital skin changes were observed regularly and the expression of PAR2 in groups A and D was detected with immunohistochemistry, Western blotting and qRT-PCR. RESULTS: In group D, LSC occurred in 23 rats (57.5=) at 8 weeks and in 38 rats (95=) at 10 weeks; 8 rats (20=) showed papilloma at 12 weeks. Acetone treatment or chronic mechanical irritation did not cause LSC in the rats. Immunohistochemistry, Western blotting and qRT-PCR showed significantly increased expressions of PAR2 in group D at both the protein and mRNA levels as compared with those in group A (P<0.05). CONCLUSION: 0.5= DMBA in acetone solution along with chronic mechanical irritation can induce LSC in female SD rats, and PAR2 is closely related with the occurrence and progression of LSC.