Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan.

BACKGROUND: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers. METHODS: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients. RESULTS: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372). CONCLUSION: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.

One hundred supracricoid laryngectomies with cricohyoidoepiglottopexy: do we achieve better local control?

OBJECTIVE: Supracricoid laryngectomy with cricohyoidoepiglottopexy has been known to be able to cope with tumor excisions with minimal margins. Extended resection may result in a limited margin and may impair the prognosis. We conducted a clinicopathologic analysis of local recurrence in supracricoid laryngectomy with cricohyoidoepiglottopexy patients. METHODS: Between 1997 and 2013, 100 patients with glottic cancers underwent supracricoid laryngectomy with cricohyoidoepiglottopexy. The clinicopathologic findings were evaluated. We also analyzed: (i) cancer-specific and overall survival rates, (ii) the correlation between locoregional recurrence and overall survival, (iii) T staging and larynx preservation rates and (iv) previous radiation history and larynx preservation rates. RESULTS: Local recurrence was recognized in eight of the 100 patients (8%); all were initially staged as T3 or T4. Recurrence was identified in the submucosal regions of the ipsilateral arytenoid and/or infraglottis. Six patients were salvaged by completion total laryngectomy except two. Cancer-specific survival at 5 years was 93%; overall survival at 5 years was 89%. There was no significant difference between overall survival and locoregional recurrence. There was a significant difference between larynx preservation in T1-2 and T3-4 patients. There was no significant difference between larynx preservation and the previous radiation therapy status. CONCLUSIONS: Our experience convinced us of the clinical potential of supracricoid laryngectomy with cricohyoidoepiglottopexy as one of the effective options for functional larynx preservation. Supracricoid laryngectomy with cricohyoidoepiglottopexy is the most suitable for unfavorable T2 and T3a cases and is applicable for appropriately selected radiation-failed patients. Thorough pre-operative evaluation, proper surgical techniques and careful follow-up are prerequisites for the success of supracricoid laryngectomy with cricohyoidoepiglottopexy.

[A Pediatric Case of Retropharyngeal Abscess Causing Multiple Instances of Cranial Nerve Palsy].

Deep neck abscesses are relatively rare in children compared with adults. Diagnosis can be difficult in pediatric patients because of the various clinical symptoms, therefore, it is important to correctly understand the pathology. We report herein on a rare pediatric case of a deep neck abscess that caused multiple instances of cranial nerve palsy. The patient was a 7-year-old boy who, despite treatment by a local physician for fever, swelling of the left neck and neck pain, developed torticollis, dysarthria, dysphagia and hoarseness and consequently consulted our department. We observed palsy associated with the IX, X, and XII left cranial nerves and a retropharyngeal abscess was diagnosed based on the computed tomography findings. The patient was hospitalized and underwent conservative treatment, and on day 21 of hospitalization, the patient was discharged after his symptoms had eased and the size of the abscess had reduced. We believe that palsy of the cranial nerves in the present case occurred as a result of pressure being applied to the cranial nerves in the carotid space due to an abscess in the retropharyngeal space.

Effect of a poly(ADP-ribose) polymerase-1 inhibitor against esophageal squamous cell carcinoma cell lines.

Effective molecular target drugs that improve therapeutic efficacy with fewer adverse effects for esophageal cancer are highly anticipated. Poly(ADP-ribose) polymerase (PARP) inhibitors have been proposed as low-toxicity agents to treat double strand break (DSB)-repair defective tumors. Several findings imply the potential relevance of DSB repair defects in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). We evaluated the effect of a PARP Inhibitor (AZD2281) on the TE-series ESCC cell lines. Of these eight cell lines, the clonogenic survival of one (TE-6) was reduced by AZD2281 to the level of DSB repair-defective Capan-1 and HCC1937 cells. AZD2281-induced DNA damage was implied by increases in γ-H2AX and cell cycle arrest at G2/M phase. The impairment of DSB repair in TE-6 cells was suggested by a sustained increase in γ-H2AX levels and the tail moment calculated from a neutral comet assay after X-ray irradiation. Because the formation of nuclear DSB repair protein foci was impaired in TE-6 cells, whole-exome sequencing of these cells was performed to explore the gene mutations that might be responsible. A novel mutation in RNF8, an E3 ligase targeting γ-H2AX was identified. Consistent with this, polyubiquitination of γ-H2AX after irradiation was impaired in TE-6 cells. Thus, AZD2281 induced growth retardation of the DSB repair-impaired TE-6 cells. Interestingly, a strong correlation between basal expression levels of γ-H2AX and sensitivity to AZD2281was observed in the TE-series cells (R(2)  = 0.5345). Because the assessment of basal DSB status could serve as a biomarker for selecting PARP inhibitor-tractable tumors, further investigation is warranted.

Clinical outcomes of 849 laryngeal cancers treated in the past 40 years: are we succeeding?

OBJECTIVE: We analyzed the clinical outcomes of 849 laryngeal cancers treated in the past 40 years, which overlapped with the era of the global treatment shift. METHODS: To compare the chronological outcomes, patients were divided into four groups according to their registration year as 1972-82, 1983-92, 1993-2002 and 2003-12; treatment trends, larynx preservation rate and overall survival rate were compared. RESULTS: There were 104, 173, 253 and 319 patients registered in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. Five-year overall survival rates were 74, 76.5, 75.6 and 82.2% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. The five-year larynx preservation rates were 65.5, 75.7, 75.4 and 80.9% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. CONCLUSIONS: The number of patients treated at our institute increased, and the overall survival and larynx preservation rates exhibited favorable improvements over the past four decades. In the analysis of nonsurgical options, S1 combined radiotherapy showed superiority over concurrent chemoradiotherapy and radiotherapy in larynx preservation, and S1 combined radiotherapy, concurrent chemoradiotherapy and Tegafur Uracil combined radiotherapy showed superiority over radiotherapy in overall survival. In nonsurgical approaches, proper case selection is the key to success and may be much more important than pursuing radiotherapy dose escalation. In the analysis of surgical options, laser and supracricoid laryngectomy with cricohyoidoepiglottopexy contributed to larynx preservation in early- and intermediate-stage cancers, respectively. Supracricoid laryngectomy with cricohyoidoepiglottopexy demonstrated overall survival not worse than total laryngectomy, which is the prerequisite treatment basis for larynx preservation options. We must make extra efforts in pursuing an ideal balance between nonsurgical and surgical larynx preservation options.

A clinical study of transoral pharyngectomies to treat superficial hypopharyngeal cancers.

BACKGROUND: For years, it has been a major interest for surgeons and oncologists to develop a novel technique to detect hypopharyngeal cancers at an early stage and to treat the lesions in a less invasive manner. The advent of the narrow band imaging system combined endoscopy and various endoscopic approaches shed light on the new era of the minimum invasive management of superficial cancers in hypopharyngeal regions. METHODS: Three endoscopic approaches, endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery, were chronologically introduced at our institute. In this study, we focused on the clinical outcomes, advantages and limitations of each procedure. RESULTS: A total of 30 patients (42 procedures) received transoral pharyngectomies between June 2006 and May 2012. Tracheotomy was performed in 9 of 42 (21%) patients. Three patients developed local recurrence and were subsequently controlled by additional transoral pharyngectomies. The 2- and 5-year local control rates were 92.8 and 83.5%. The 2- and 5-year overall survival rates were 82.1%. CONCLUSIONS: Endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery-transoral pharyngectomies are useful procedures for treating superficial hypopharyngeal cancers. Endoscopic mucosal resection manifested the least invasiveness and may be beneficial for resecting small superficial lesions, endoscopic submucosal dissection may be advantageous for patients with difficult laryngopharyngeal exposure and endoscopic laryngopharyngeal surgery has shown the optimal effectiveness and minimal complications and can be applied to most of the hypopharyngeal sub-sites. All three procedures require a high level of technical skill and close collaboration between otolaryngologists and gastroenterologists.

Fascia implantation with fibroblast growth factor on vocal fold paralysis.

PURPOSE: The purpose of this prospective study was to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on unilateral vocal fold paralysis (UVFP) in a rat model. MATERIALS AND METHODS: Unilateral recurrent laryngeal nerve (RLN) section was performed on 15 rats. Ten rats received an autologous fascia implant and gelatin hydrogel with or without bFGF (1 µg) to their larynxes (fascia only, "fascia group"; bFGF + fascia, "fascia + bFGF group"), while the rest underwent RLN transection ("RLN section group"). Four months later, evaluation of the laryngeal glottal gap and histological analysis were performed. RESULTS: The glottal gap was significantly reduced in the fascia + bFGF group, and fat volume increased significantly relative to the RLN section. The volume of the remaining fascia in the bFGF + fascia group was significantly greater than that of the fascia group. CONCLUSIONS: ATFV with controlled release of bFGF may compensate for diminished laryngeal volume in UVFP by reducing resorption of the implanted fascia and increasing fat volume. Our findings suggest that this modality may represent an attractive option for treating UVFP.

Surveillance after endoscopic mucosal resection or endoscopic submucosal dissection for esophageal squamous cell carcinoma.

The objectives of surveillance after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma are: (i) early detection and treatment of recurrence; and (ii) early detection and treatment of metachronous esophageal squamous cell carcinoma and second primary cancers. Protocols for follow up after EMR or ESD for esophageal squamous cell carcinoma should be based on the risks of lymph node metastasis and distant metastasis as assessed on the basis of tumor staging at initial treatment. Early detection of recurrence or metachronous carcinomas often allows curative or less invasive treatment. Particular attention should be paid to the development of metachronous esophageal squamous cell carcinomas and second primary cancers (in particular, head and neck cancer and gastric cancer because of their high incidence).

Functional organ preservation for laryngeal cancer: past, present and future.

OBJECTIVE: Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done. METHODS: Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer. RESULTS: There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience. CONCLUSIONS: Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.

Clinical significance of positive Delphian node in supracricoid laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVE: A positive Delphian node is known to predict a poor prognosis in laryngeal cancer. To elucidate the clinical significance of positive Delphian node metastasis in supracricoid laryngectomized patients, we conducted a thorough clinical review. METHODS: We reviewed clinical data from 65 patients who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy; in these patients, the Delphian node was examined by frozen section as a routine process. Incidence, positivity rates and clinical impact of the positive Delphian node were analyzed. RESULTS: The presence of the Delphian node was detected in 27 of 65 (41.5%) patients; among these 27 patients, 3 (3/65 = 4.6%) were positive for metastasis. Case 1 (pT3N2b) died of lung metastases 32 months after supracricoid laryngectomy with cricohyoidoepiglottopexy. Case 2 (pT4N2c) underwent conversion to total laryngectomy during supracricoid laryngectomy with cricohyoidoepiglottopexy because of unexpected submucosal lymphatic infiltration; this patient is currently alive with disease 23 months after surgery. Case 3 (T3N1) is currently alive without disease 48 months after surgery. CONCLUSIONS: The positive Delphian node is exclusively encountered in advanced laryngeal cancers and suggests an ominous outcome. Sufficient dissection of the paratracheal and lateral neck nodes is recommended. Delphian node evaluation is advised for all supracricoid laryngectomy surgeries.

Delayed wound infection after supracricoid partial laryngectomy following failure of high dose radiation.

Past radiation therapy is known as a major risk factor promoting post-supracricoid partial laryngectomy (SCPL) complications. Risk of post-SCPL complications may further increase following failure of high dose radiation; in these patients, wound infection may become evident more than 1 month after an uneventful post-surgical course. By defining this complication as "Delayed Wound Infection" and reviewing the clinical features, we intended to elucidate the mechanism, risk factors, and management of this post-SCPL complication. Between 1997 and 2009, 60 patients received SCPL. The incidence of post-SCPL wound infection was analyzed in reflect to radiation status, radiation dose, and medical histories. Of 60 patients, delayed wound infection was identified in 4 (7%); radiation doses were 65, 68, 70, and 76.8 Gy (avg. 70 Gy). Blood data including white blood cell and C-reactive protein showed slight elevation before the delayed infection became evident. Patients with high dose radiation (≥ 65 Gy) accompanied by histories of diabetes and renal insufficiency are considered a high risk group. Delayed re-epithelialization of the inner surface of the cricohyoido gap was presumed to be the main pathogenesis. Early initiation of antibiotics and hyperbaric oxygen therapy are effective for rapid recovery. "Delayed Wound Infection" was treatable and patients undergoing surgery after failure of high dose radiation should be managed with extra precaution, but should not be excluded from the indications for SCPL.

Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer.

OBJECTIVE: A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. METHODS: In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. RESULTS: Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). CONCLUSIONS: The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.

Two-year results for scoliosis secondary to Duchenne muscular dystrophy fused to lumbar 5 with segmental pedicle screw instrumentation.

BACKGROUND: Instrumentation and fusion to the sacrum/pelvis has been a mainstay in the surgical treatment of scoliosis in patients with Duchenne muscular dystrophy since the development of the intrailiac post. It is recommended for correcting pelvic obliquity. However, caudal extent of instrumentation and fusion has remained a matter of considerable debate. This study was performed to determine the efficacy and safety of stopping segmental pedicle screw constructs at L5 during surgical treatment of scoliosis associated with Duchenne muscular dystrophy (DMD). METHODS: From May 2005 to June 2007, a total of 20 consecutive patients underwent posterior spinal fusion and segmental pedicle screw instrumentation only to L5 for scoliosis secondary to DMD. All patients had progressive scoliosis, difficulty sitting, and back pain before surgery. A minimum 2-year follow-up was required for inclusion in this study. Assessment was performed clinically and with radiological measurements. The Cobb angles of the curves and spinal pelvic obliquity were measured on the coronal plane. Thoracic kyphosis and lumbar lordosis were measured on the sagittal plane. These radiographic assessments were performed before surgery, immediately after surgery, and at a 3-month interval thereafter. The operating time, blood loss, and complications were evaluated. Patients were questioned about whether they had difficulty sitting and felt back pain before surgery and at 6 weeks, 1 year, and 2 years after surgery. RESULTS: A total of 20 patients, aged 11-17 years, were enrolled. The average follow-up period was 37 months. Preoperative coronal curves averaged 70 degrees (range 51 degrees -85 degrees ), with a postoperative mean of 15 degrees (range 8 degrees -25 degrees ) and a mean of 17 degrees (range 9 degrees -27 degrees ) at the last follow-up. Pelvic obliquity improved from 13 degrees (range 7 degrees -15 degrees ) preoperatively to 5 degrees degrees (range 3 degrees -8 degrees ) postoperatively and 6 degrees (range 3 degrees -9 degrees ) at the last follow-up. Good sagittal plane alignment was recreated and maintained. Only a small loss of correction of scoliosis and pelvic obliquity was noted. The mean operating time was 271 min (range 232-308 min). The mean intraoperative blood loss was 890 ml (range 660-1260 ml). The mean total blood loss was 2100 ml (range 1250-2880 ml). There was no major complication. All patients reported that difficulty sitting and back pain were alleviated after surgery. CONCLUSION: Segmental pedicle screw instrumentation and fusion only to L5 is safe and effective in patients with DMD scoliosis of <85 degrees and pelvic obliquity of <15 degrees . Good sagittal plane alignment was achieved and maintained. All patients benefited from surgery in terms of improved quality of life. There was no major complication.

Clinicopathological analyses of fifty supracricoid laryngectomized specimens: evidence base supporting minimal margins.

OBJECTIVES: Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins. METHODS: The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses. RESULTS: The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin. CONCLUSIONS: The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

Inner-ear function test in cases of posterior canal-type benign paroxysmal positional vertigo.

Otolaryngologists typically perform diagnoses and offer medical treatment for vestibular dysfunction. This vestibular dysfunction manifests as benign paroxysmal positional vertigo (BPPV), Ménière's disease, vestibular neuronitis, and so on. The etiology of BPPV is still not clear, so in this article we discuss inner-ear function, etiology, and factors related to BPPV. We examined by pure-tone audiometry and hot and cold caloric tests patients whom we identified as having diagnosed posterior canal-type BPPV. We observed canal paresis at a high rate on the affected side (p < .01). The term of recovery at the first treatment was longer in patients with canal paresis as compared to those without. Deterioration of hearing level was observed more frequently on the affected side (p < .01). The horizontal semicircular canal and cochlea are important potential sites of lesions affecting posterior canal-type BPPV, and the posterior circular canal and otolith are already considered to be sites of affecting lesions.

Correlation between arteriosclerotic changes and prognosis in patients with peripheral vestibular disorders.

Symptoms such as vertigo and unsteady gait occur in various diseases and are among the relatively common chief complaints. Even at present, the mechanisms underlying these disorders are unclear. We report a significant correlation between a prolonged period of resolution of benign paroxysmal positional vertigo (BPPV) and histories of lifestyle-related illnesses. We consider the possibility of correlating between BPPV prognosis and arteriosclerotic changes. Using carotid ultrasonography, we examined maximum intima-media thickness (IMT), maximum common carotid artery IMT, and biochemical examinations in 105 patients with peripheral vertigo. We divided patients with BPPV into groups with and without abnormal thickness of the IMT. The maximum IMT was 1.35 mm in patients with peripheral vestibular disorders. The proportion of peripheral vestibular disorder patients with a maximum IMT of > or = 1.1 mm (i.e., thickening) was 58%. The rate at which the feeling of positional vertigo remained at the halfway point in the observation period was significantly higher in the group of patients with an IMT of > or =1.1 mm (p = .0007). Our results indicate that cervical ultrasonography is useful for noninvasive examination of arteriosclerotic changes in patients with peripheral vestibular disorders. We saw indications that such patients show progression of arteriosclerotic changes. This study suggested that the arteriosclerotic change was related to prognosis.

[Clinical review of supracricoid laryngectomy with CHEP and CHP: 50 patients treated in 11 years].

An analysis of clinical data on 50 patients undergoing supracricoid laryngectomy (SCL) between 1997 and 2008 i.e., cricohyoidoepiglottopexy (CHEP) in 47 and cricohyoidopexy (CHP) in 3 cases showed that the number of SCL cases operated on within a year surpassed that of Total Laryngectomy after 2003. Selection criteria included performance status 0-1 and blood gas PO2>80 torr, especially in those patients over 70-years-old. Postoperative wound infection occurred in 16 patients (32%), with four requiring additional surgical intervention (two ruptured pexis and two chondritis induced by C3-C4 osteophytes). A history of radiotherapy and systemic complications, i.e., diabetes and renal failure, added to the risk of wound infection. Introducing a clinical pathway shortened hospitalization. Vocal function was achieved in 96% and swallowing function in 89% of patients. Five-year crude survival in CHEP was 69% and in TL 51%. Laryngeal preservation was 70%, increasing to 89% after the introduction of SCL. SCL-CHEP is thus indicated for unfavorable T2 (ASCO 2006), well-selected T3, T4, and rT1-4 (radiation failures). Effort should emphasize a good balance in prognosis and function in organ preservation for laryngeal cancer.

Investigation of Stress Levels before the Onset of Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVES: We hypothesized that patients with idiopathic sudden sensorineural hearing loss (ISSHL) would have experienced more stress prior to the onset than they typically did. This study investigated stress levels in patients before the onset of ISSHL. MATERIALS AND METHODS: Forty-two patients with ISSHL were investigated. We used an original questionnaire to evaluate subjective stress levels in 1 week before onset. Serum hemoglobin A1c (HbA1c) and total cholesterol were examined to evaluate biochemical stress markers reflecting the preceding 1 to 2 months. The results on admission were compared with those at the follow-up visit. RESULTS: Significantly more patients reported greater physical exhaustion, greater mental exhaustion, or a worse physical condition on admission than at follow-up (p<0.01, for each variable). On admission, 81% of patients reported greater than normal stress with regard to at least 1 of 3 items. The mean serum HbA1c was slightly but nonsignificantly lower at the follow-up visit (p=0.10), while the mean serum total cholesterol was significantly lower at follow-up than on admission (p<0.01). CONCLUSION: The results indicate that patients were under a greater degree of stress before the onset of ISSHL, suggesting that stress plays a role in inducing ISSHL.

Similarities between N-glycan glycoform of tonsillar IgA1 and that of aberrant IgA1 abundant in IgA nephropathy patient serum.

BACKGROUND: There are many reports on the presence of an incompletely glycosylated O-linked oligosaccharide(s) in the IgA1 hinge region of some IgA nephropathy patients. As the candidates of such IgA1, tonsillar IgA1 and aberrant IgA1, which are abundant in an IgA nephropathy patient, were proposed. On the other hand, in mice, the abnormality of the N-linked oligosaccharide chain of IgA induced the IgA nephropathy. Therefore, analyses of the N-glycan glycoform on serum IgA1, aberrant IgA1 and tonsillar IgA1 were carried out using the 3-dimensional mapping method. RESULTS: The sugar chain composition was almost the same in these 3 IgA1 preparations. However, the structural characteristics for the aberrant IgA1 showed a drastic increase in the neutral N-glycans; in particular, 25% of the sugar chains in the aberrant IgA1 were the high mannose-type as compared with approximately 5%-6% in the serum IgA1 and tonsillar IgA1. The neutral complex-type N-glycan chain with fucose was higher in both the aberrant IgA1 and tonsillar IgA1 than in the serum IgA1. A typical component in the aberrant IgA1 was the fully galactosylated biantenna with the fucose residue. CONCLUSIONS: We found an abnormality in the N-linked oligosaccharides of the aberrant IgA1. In addition to our previous report about the abundance of asialo-O-linked oligosaccharide in both the tonsillar IgA and aberrant IgA, our results concerning the N-glycan glycoform of the aberrant IgA showed the possible promotion of its self-aggregation and its glomerular deposition by the synergistic difference in the O- and N-linked carbohydrate chains, and also the derivation of the aberrant IgA1 in the sera from the tonsillar tissue.