Recurrent Laryngeal Papillomas Research Articles

Airway loss in a child with recurrent laryngeal papilloma: A rare complication

Airway loss in a child with recurrent laryngeal papilloma: A rare complication

Effect of Bevacizumab on Recurrent Laryngeal Papilloma

Laryngeal papilloma is an intractable disease that can easily to recur. Therefore, it`s treatment is often difficult. We herein report a case of recurrent laryngeal papilloma successfully treated with bevacizumab. The patient was a woman in her 70 s. He was referred to our hospital with a chief complaint of hoarseness for the past six months. Laryngoscopy revealed a tumor behind the left vocal cord. A biopsy was performed under general anesthesia, and a diagnosis of laryngeal papilloma was made. Since the patient was undergoing systemic chemotherapy due to lung cancer, Yokuinin and Hochuekkito were administered, and the patient was followed up for laryngeal papilloma on an outpatient basis. After the laryngeal papilloma shrank, the respiratory physician administered bevacizumab. However, the laryngeal papilloma rapidly increased in size again after the administration of bevacizumab had been completed. Because of dyspnea, the tumor was debulked twice under general anesthesia. However, since recurrence of laryngeal papilloma was observed again, the administration of bevacizumab for lung cancer was started again. The laryngeal papilloma disappeared and her voice quality improved. He has been treated with bevacizumab once a month for more than two years without recurrence of laryngeal papilloma and maintains a good voice.

Spontaneous Regression of Recurrent Respiratory Papillomatosis with HPV Vaccination: A Case Study

Recurrent respiratory papillomatosis (RRP) is characterized by recurrent laryngeal papillomas and treated with repeated surgical excision. The human papillomavirus (HPV) vaccine prevents infection with strains of HPV unrelated to RRP, and has recently been shown to increase the interval between surgeries when used as an adjuvant. The objective of this study was to report one case from our institution in which HPV vaccination was found to induce spontaneous regression of disease, absent of surgical intervention or use of other adjuvants. Retrospective case study. Records of one patient with RRP receiving partial HPV vaccination was reviewed with attention to videolaryngostroboscopic findings, Derkay score, need for surgical intervention, and voice quality. Spontaneous regression of disease after vaccination was seen in this patient, as evidenced by reduced tumor burden and decreased voice handicap index. The patient was a 30-year old female, who had improved disease burden and voice quality after one dose and total resolution of disease following the second dose. Vaccine administration was the sole therapeutic mechanism. These findings suggest that HPV vaccination can treat RRP without surgical intervention. Further studies are needed to investigate the underlying mechanism of disease regression and which patients may benefit most. We believe that HPV vaccination for all patients with RRP, even over the age of 45 years, may decrease treatment costs for individuals and the healthcare system overall.

Coblation and silicon stent implantation for recurrent laryngeal papilloma with extensive lesions

Objective:To evaluate the feasibility and long-term outcome of radiofrequency coblation combined with silicon stent implantation in the treatment of recurrent laryngeal papilloma with extensive lesions. Method:From March 2009 to April 2016, a total of 13 patients (8 males, 5 females; aged 28-67 years) who suffered recurrent laryngeal papilloma were enrolled in this retrospective study. All the cases had undergone at least one operation at other hospitals before this hospitalization. The recurrence interval (RI) of these cases ranged from 2 to 6 months. Video-laryngoscopy or stroboscopy were preformed preoperatively and postoperatively, as well as vocal function assessment. These cases underwent radiofrequency coblationin combination of different stent implantation (member, 7 cases; tube, 4 cases; T-shaped tube, 2 cases) under general anesthesia. The follow-up was 12 to 76 months. Result:Laryngoscopy revealed that the lesions mainly located in the vocal folds, anterior commissure, ventricular band, posterior commissure, epiglottis and even in subglottic area. Varying extent of mucosal adhesion of anterior or/and posterior commissure were observed in all cases, and two cases suffered mild subglottic tracheal stenosis. Two to six weeks after surgery, the silicon stent were removed and no mucosal adhesion were found except for 2 cases who suffered mucosal adhesion of anterior commissure again. Compared to preoperative scores, VHI-10 and G scores showed the significant improvement of voice quality postoperatively in all cases. The recurrence of papilloma was observed in 3 cases during 1-year follow-up, and 4 cases during 2-year follow-up, no recurrence in 6 cases. These recurrence lesions mainly located in ventricular band, subglottic area and trachea. However, no recurrence occurred in these cases who received ablation again. No serious complications were observed in these cases. Conclusion:Radiofrequency ablation may be an effective approach in the treatment of recurrent laryngeal papilloma with extensive lesions. One-stage application of suitable silicon stents can effectively prevent the adhesion of the wound and the onset oflaryngo-tracheal stenosis, and improve the quality of voice.

Mnogie nowotwory i transformacja Richtera u pacjenta z rozpoznaniem chłoniaka z małych limfocytów B – dylematy diagnostyczno-terapeutyczne

A clonal lymphocyte proliferation in patients with NHL interferes with the immune system, disturbing both humoral and cellular immunity. An antileukemic therapy additionally affects the immune system functioning. A higher than expected in general population incidence of infections and other malignancies is the consequence of impaired immunological surveillance. The fate of patients is also influenced by the possibility of low grade NHL transformation in more aggressive large B cell lymphoma, called the Richter's transformation.We present the case of patient with multiple malignancies small lymphocytic B-cell lymphoma (SLL), renal cell carcinoma (RCC), pulmonary adeno-carcinoma and recurrent laryngeal papillomas, that occurred in different stages of lymphoma diagnosis and treatment. He also developed SLL transformation in large B-cell lymphoma 7 years after the initial diagnosis.A clinical course, together with diagnostic and therapeutic difficulties we faced, are discussed in relation to the literature data.

In Situ Hybridization Signal Patterns in Recurrent Laryngeal Squamous Papillomas Indicate that HPV Integration Occurs at an Early Stage

Laryngeal papillomas are benign tumors that frequently recur and can compromise airways. We investigated HPV genotype, physical status, and protein expression in juveniles versus adults. Thirty-five laryngeal papilloma specimens were obtained from ten juveniles (1-16years) and eleven adults (24-67years). In cases of recurrent papillomatosis (7 juveniles, 7 adults), the first and last papillomas were assayed. HPV type was determined by GP5+/6+ PCR and dot blot hybridization. In situ hybridization (ISH) was performed on 34 specimens; the data were recorded in terms of diffuse (episomal HPV) and punctate (integrated HPV) signal patterns. Immunohistochemistry for the HPV L1 capsid protein, a marker of HPV productive status, was performed on 32 samples. All samples tested HPV positive: HPV 11 in 2/10 (20.0%) juveniles and 5/11 (45.5%) adults; HPV 6 in 7/10 (70%) juveniles and 5/11 (45.5%) adults; and HPV 6/11 double infection was noted in one juvenile and one adult. ISH signals (punctate±diffuse) were detected among 7/10 (70.0%) juveniles and 7/11 (63.6%) adults. L1 staining was detected in 1/9 (11.1%) juveniles and 6/10 (60.0%) adults (P=0.06). These data support the idea that integration of low-risk HPV types into the cell genome is an early and common event in the etiology of juvenile and adult recurrent laryngeal papillomas. Productive HPV infections may be more common in adults; accordingly, constant laryngeal re-infection by HPV shed from a productive lesion may contribute to adult recurrent lesions, whereas the mechanism of papilloma recurrence in juveniles may be more attributable to HPV integration.

The Treatment for Recurrent Laryngeal Papillomas in Children

Objective: To discuss the therapeutic methods for laryngeal papillomas in children. Methods: 52 children with laryngeal papillomas were randomly divided into three groups; all of them received surgery first. Group one (18cases) was given α- interferon treatment after operation; Group two (17cases) was given throat pharynx local injections of mealses vaccine and intramuscular α- interferon; Group Three (17cases) was taken pidotimod (Cell immunity regulator) and measles vaccine injection (same to group two). Postoperative periodic review of them was done regularly. Result: The recurrence rate reach to 77.8% after three month of surgery. 17 patients with recurrent problem received several times of operations during three years of follow-up. The recurrence rate of Group two and Group three postoperative three months are 17.6% and 25.5%, postoperative one year are 41.8% and 41.7%. There was significant difference in the recurrence rate between Group two and three with Group one after three months of surgery. But no significant difference found in the same term of reoccurrence between Group two and Group three after three month or half year of surgery. Conclusion: α- interferon, measles vaccine and pidotimod can regulate the immunity. The Systemic application immunity regulator combines with throat pharynx local injections of mealses vaccine,which can reduce the recurrent rate of laryngeal papillomas, prolong the recurrent time, reduce operation, and improve the children's life quality.

Effect of human papilloma virus expression on clinical course of laryngeal papilloma

Conclusion. Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. Objectives. HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. Subjects and methods. Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. Results. We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.

Observation and nursing of 33 infant patients with recurrent laryngeal papilloma

目的 探讨婴幼儿复发性喉乳头状瘤的观察与护理.方法 对33例婴幼儿复发性喉乳头状瘤患儿密切观察病情,以赢取抢救机会;进行有效的术前术后护理,包括完善术前准备和进行术前护理评估及术后并发症的预防、气管切开术后呼吸道管理等.结果 33例中31例均好转出院 , 2例病情变化抢救无效死亡.结论 婴幼儿复发性喉乳头状瘤患儿的术前、术后观察与护理对及时发现患儿病情变化,进行有效的抢救措施至关重要。

Submyeloablative Cord Blood Transplant Corrects Clinical Defects Seen in IPEX Syndrome.

IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) is a disorder of regulatory T cell function caused by mutations in the FOXP3 gene. This disorder is generally associated with a fatal outcome early in life from complications related to bleeding, infection, or enteritis. Allogeneic stem cell transplant (SCT) can be curative for this disorder, but pre-transplant disease-related complications may preclude a full myeloablative conditioning regimen. We report a seven year old boy with IPEX whose pre-transplant course was complicated by recurrent laryngeal papillomas and severe airway obstruction, frequent pulmonary infections, and recurrent gastrointestinal hemorrhage. Due to these problems he underwent a submyeloablative conditioning regimen consisting of fludarabine 30 mg/m2/day for 6 days, Busulfan 0.8 mg/kg/dose every 6 hours for 2 days, then anti-thymocyte globulin 2.5 mg/kg/dose for 4 days. Mycophenylate and cyclosporine were used for graft versus host disease (GVHD) prophylaxis. This patient received an HLA 5/6 matched (A,B,DR) unrelated donor cord blood transplant with 1.1 ×108 total nucleated cells/kg and 3 × 105 CD34+ cells/kg. His diarrhea and airway issues resolved following the conditioning regimen. The patient achieved myeloid engraftment on day 14, and was platelet and red cell transfusion independent by day 29 and 56, respectively. He had 81% and 98% donor chimerism at 2 and 9 months post-transplant, respectively. While tapering cylcosporine he developed graft versus host disease of the lower GI tract, which was sucessfully treated with a course of corticosteroids. He also experienced reactivation of EBV and was treated with 4 weekly doses (375 mg/m2) of anti-CD20 monoclonal antibody. This patient has had full resolution of his clinical symptoms and is currently 17 months post-transplant, with no signs of GVHD. For those children who do not respond or have only partial improvement following immunosuppressive therapy, allogeneic SCT using a submyeloablative approach can be well tolerated and result in sustained donor chimerism.

Intralesional Cidofovir application in recurrent laryngeal papillomatosis

Recurrent laryngeal papillomatosis is a benign disease of the larynx often leading to organic and functional restrictions. The therapeutic treatment of choice in larynx-obstructing papillomatosis is at present surgical laser ablation. The effectiveness of adjuvant intralesional injection of the virustaticum Cidofovir has been investigated recently in a variety of therapeutic models. The present case study deals with the treatment of recurrent laryngeal papillomatosis by means of surgical laser ablation of the laryngeal papillomas with adjuvant local injection of the virustaticum Cidofovir (dose of 5 mg/1 ml). Within the period from October 2001 to August 2004, ten patients aged between 5- and 70 years were treated with intralesional injections of Cidofovir. Papillomatosis was confirmed histologically in all cases, and the virus types were defined in part. Each of the patients underwent clinical-phoniatric examinations and was photographed for documentation. After 2-7 treatments with surgical laser papilloma ablation and intralesional Cidofovir injections, all patients showed a definite papilloma reduction, while in six cases complete remission was achieved. During the follow-up period of 8-30 months, not a single recurrence of the laryngeal papillomatosis occurred. In the majority of patients, a clear improvement in the voice was achieved. There were no local or systemic side effects caused by the virustaticum. Intralesional injection of Cidofovir is an adjuvant, but not a curative therapeutic option in recurrent laryngeal papillomatosis. Remission of previously frequently recurrent laryngeal papillomas can be achieved, but recurrence after longer treatment-free intervals is also possible.

S077 An Epigenetically Derived Monoclonal Origin for Recurrent Laryngeal Papillomas

Background: Promoter methylation of tumor suppressor genes has been investigated by a variety of means, recently including pyrosequencing. Methods: Fresh tumor tissue and normal tissue from resection margin were obtained from 79 patients undergoing resection for squamous cell carcinoma. DNA was extracted and bisulphite treated. Polymerase chain reaction primers were designed to amplify 75– to 200– base pair regions of the CpG-rich gene promoters of p16, RAR-beta, E-Cad, CYGB, cyclin A1, MGMT, ATM, hMLH1, STAT1, and TIMP3. Methylation status of 5 to 22 individual CpG sites per gene was determined by pyrosequencing. Reverse transcriptase–PCR was used to correlate these data with mRNA expression. Results: Significant CpG methylation of gene promoters within tumor specimens was found in most genes studied; however, despite previous reports, there was no evidence in the mismatch repair genes ATM, STAT1, or hMLH1. Promoter methylation was in evidence in highly tumor-specific pattern for most genes; however, the quantitative nature of these data revealed that for RAR-beta and E-cadherin, the pattern was not tumor specific. Concordant methylation was demonstrated in this tumor series (P=.03), but it was difficult to identify a true methylator phenotype (CIMP). Cyclin A1 promoter methylation showed an inverse trend with histological grade. Promoter methylation of CYGB is common in head and neck SCC. Conclusions: Promoter methylation analysis using pyrosequencing reveals valuable quantitative data from several CpG sites. In contrast to qualitative data generated from methylation-specific PCR, our data clarify which genes are methylated in a tumor-specific pattern. Cytoglobin is a novel candidate tumor suppressor gene highly methylated in upper aerodigestive tract squamous cancer.

Stability of cidofovir in extemporaneously prepared syringes

Cidofovir is a nucleotide analogue with potent antiviral activity, especially against papillomaviruses.[1][1] Many investigators have reported that cidofovir is effective in the treatment of recurrent laryngeal papillomas in adults and young children.[2–][2],[8][3] The most frequently used dosage

Endotracheal Tube Obstruction: A Rare Complication in Laser Ablation of Recurrent Laryngeal Papillomas

During the past 25 years, use of the carbon dioxide (CO2) laser has been accepted as the most appropriate surgical method for the treatment of recurrent laryngeal papillomatosis. Although CO2 laser technology and surgical techniques continue to improve, laser-related complications still occur. We describe a case of a very rare complication--to our knowledge, only the second such case reported in the literature--in which an endotracheal tube was almost completely obstructed by a piece of papillomatous tissue during CO2 laser microlaryngoscopy for the treatment of recurrent laryngeal papillomatosis.

α‐ＩＮＦが有効であった喉頭乳頭腫例

Although laryngeal papilloma is a benign tumor, it is difficult to control this disease because of the rapid recurrence after surgery. We reported a patient with recurrent laryngeal papilloma who responded well to a-interferon after laser surgery.The patient was a 16-year-old man with a history of dyspnea and hoarseness. He underwent laser surgery three times, but the papilloma repeatedly relapsed. We treated him with intramuscular injection of α-interferon at a dosage of 3×106 IU twice a week for 1 year. Symptoms were rapidly relieved by this therapy. We conclude that α-interferon may be effective for recurrent laryngeal papilloma after laser surgery.

Powered laryngeal shavers and laryngeal papillomatosis: a preliminary report.

Carbon dioxide (CO2) laser ablation is widely accepted as the most effective first line surgical treatment of recurrent laryngeal papilloma. However, vaporization of papilloma with the CO2 laser exposes the patient and staff to a potentially infective plume. Furthermore, unsuitable pathological tissue specimens and scarring of the surrounding laryngeal architecture are inevitable consequences of the thermal energy generated by this instrument. Following their innovative use in endonasal surgery, powered laryngeal microresecting instruments (Xomed Shavers) have been developed for laryngeal surgery. We assessed the value of these new instruments in five patients who had previously undergone laser ablation. All of the patients reported that their postoperative recovery was the 'same as' or 'better than' that following laser surgery. The surgeon reported that though there was more bleeding, shaver excision of papilloma provided good clearance of disease; easy collection of pathological samples; and a potentially safer and faster alternative to laser excision.

Intralesional Cidofovir for Recurrent Laryngeal Papillomas: Preliminary Report

This is a preliminary report of an ongoing study to test the efficacy of intralesional injections of the antiviral drug cidofovir in adults with recurrent laryngeal papillomas in whom multiple other treatments have previously failed. This study has been designed to include 10 to 20 patients, a number sufficient to either prove or disprove the safety and efficacy of this agent. This report conveys information on the first three patients enrolled in the trial. Each patient received an overall dose of 5 to 10 ml of cidofovir, at a concentration of 4.17 mg/ml, intralesionally at 2- to 4-week intervals. The approximate volume injected into each wart was 0.2 to 0.5 ml. Biopsies of the lesion sites were obtained at the initiation and completion of therapy. No other treatment was given. Resolution of lesions was monitored by videolaryngoscopy and still photography 1 to 2 weeks after each treatment. In time, the lesions resolved in all three patients, although all three later experienced a minor recurrence. We conclude that intralesional cidofovir appears to be a promising new treatment for controlling--and perhaps at higher dosages curing--refractory laryngeal papillomas, while causing little or no injury to laryngeal structures.

Unusual adverse reaction in a patient sensitized with Photosan 3

Serious side effects of photodynamic therapy (PDT) are rare (A.L. Abramson, M.J. Shikowitz, M.J. Shikowitz, V.M. Mullooly, Clinical effects of photodynamic therapy on recurrent laryngeal papillomas, Arch. Otolaryngology Head Neck Surg., 118 (1992) 25–29; A.L. Abramson, M.J. Shikowitz, Clinical exacerbation of systemic lupus erythematosus after photodynamic therapy of laryngotracheal papillomatosis, Laser Surg. Med., 13 (1993) 677–679). The most frequent side effects of PDT are hypersensitive skin reactions, local edema, nausea, a metallic taste and liver-toxicity (J. Feyh, E. Kastenbauer, Treatment of laryngeal papillomatosis with photodynamic laser therapy, Laryngorhinootologie, 71 (1992) 190–192; J. Feyh, R. Gutmann, A. Leunig, Die Photodynamische Therapie im Bereich der Hals-, Nasen-, Ohrenheilkunde Laryngorhinootologie, 72(6) (1993) 273–278; M.S. Kavuru, A.C. Mekta, Treatment of recurrent respiratory papillomatosis, N. Engl. J. Med., 326 (1992) 204–205; B.L. Wenigg, D.M. Kurtzmann, Photodynamic therapy in the treatment of squamous cell carcinomas of the head and neck, Arch. Otolaryngol Head Neck Surg., 116 (1990) 1267–1270). In this case a patient (aged 57 years) suffering from a recurrent larynx papillomatosis was treated with PDT. He was sensitized with Photosan 3 (DHE) 2.5 mg kg −1 body weight, 24 h to photoradiation. As a light source, an argon dye lase, operating at a wavelength of 630 nm was used, coupled with a cylindrical light applicator. After treatment the patient was admitted to an intensive care unit for 24 h. 3 h after photoradiation, general urticarial wheals arose, as well as techycardia and a decrease in blood pressure followed by all the signs of serious anaphylaxis. 1.5 h after treatment with adrenaline and cortisone and stabilization of the cardiac and circulatory situation no more skin lesions were visible.

Are laryngeal papilloma virus-infected cells viable in the plume derived from a continuous mode carbon dioxide laser, and are they infectious? A preliminary report on one laser mode

The purpose of this study was to determine the potential risk of transmitting viable viral infected cells as well as viral infectivity of laryngeal papilloma in the plume derived from a continuous mode carbon dioxide laser. Each of 10 juvenile recurrent laryngeal papilloma specimens was divided into two equal parts, and one part was irradiated with a carbon dioxide laser employing a continuous mode at the power setting of 10 watts with 0.5 mm spot size and a power density of 1667 W/cm2. The resultant laser plume was trapped and was cultured simultaneously with the other part of the specimen which served as the control. All irradiated specimens tested yielded negative culture results while all the control counterparts revealed viable cell growth. To detect the viral infectivity, laser plume was cultured with two separate cell systems, one was the porcine PS clone D cell line and the other normal mucosal cells obtained from the same patient, and to control these systems both cell lines were also designed to be infected with polio virus. Both cell lines in the viral infectivity testing systems revealed no sign of viral infection. The results suggest that papilloma virus-infected cells cannot survive the continuous mode of carbon dioxide laser irradiation. We primarily conclude that, to avoid airborne transmission of plume containing laryngeal papilloma viral-infected cells and infectious viral particles, the carbon dioxide laser parameters should be in a continuous mode with the power density equal to, or more than, 1667 W/cm2.

Deletion in the L1 open reading frame of human papillomavirus type 6a genomes associated with recurrent laryngeal papilloma

Human papillomavirus (HPV) type 6a genomes with a large deletion in their L1 open reading frames (ORF) were found in two of five recurrent cases of laryngeal papilloma. One of these mutant HPVs had a 186 base pair (bp) deletion near the N-terminus end of the L1 ORF, which encodes a major capsid protein. The other had a 454 bp deletion at the C-terminus end of L1 at which is located a nuclear localising signal (NLS). No other large deletion or insertion was found in the remaining regions of all five HPV6a genomes. The laryngeal papillomas which harboured the mutant viruses showed typical hyperplasia and pathological changes as observed in tumours induced by the wild-type virus. The biological significance of the two large deletions in the late region of HPV6a associated with laryngeal papilloma is discussed.