Porfimer sodium-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma.

BACKGROUND: Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma. METHODS: Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6-180 months). RESULTS: The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %-72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01). CONCLUSIONS: Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease.

Clinical analysis of false-negative fine needle aspiration cytology of head and neck cancers.

BACKGROUND: Fine-needle aspiration (FNA) cytology is frequently used for initial and/or preoperative diagnosis of tumors in the head and neck region. However, false-negative results can lead to misdiagnosis. The aim of this study was to investigate the diagnostic results of FNA in the head and neck region and the reasons for false-negative cases. METHODS: The study population comprised 1,341 patients with pathologically confirmed head and neck tumors in whom FNA was performed before surgery or biopsy in the Otolaryngology Department at Numazu City Hospital between 2002 and 2016. We evaluated the false-negative FNA cytology rate as well as the site of the primary nodule, patient age and sex, sensitivity, accuracy, specificity, positive predictive value, negative predictive value, and the pathologic diagnosis after resection. RESULTS: The rate of false-negative FNA results was 5.9% (78/1,315 cases). The main sites of false-negative cases were the thyroid gland (n = 50), the lymph nodes (n = 16), and the salivary glands (n = 9). The sensitivity of FNA for head and neck tumors was 82.0%, with specificity and accuracy rates of 94% and 92.0%, respectively. CONCLUSIONS: We have assessed the quality of preoperative FNA cytology in head and neck tumors. To avoid misdiagnosis by FNA, it is important that the target tumor is punctured accurately. If the specimen obtained is too small, FNA should be repeated.

Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different Steroid Treatments.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.

Trough-Shaped Audiograms Are Common in Patients with Acoustic Neuroma and Sudden Sensorineural Hearing Loss.

Acoustic neuroma sometimes presents with sudden-onset sensorineural hearing loss as a primary symptom. We investigated 848 untreated cases that included 20 cases with acoustic neuroma with sudden-onset sensorineural hearing loss and 828 cases without acoustic neuroma. Fourteen of the 20 acoustic neuroma and 90 of the 828 cases of sudden-onset sensorineural hearing loss showed a trough-shaped audiogram with the greatest amount of hearing loss in the mid-frequency range. The incidence of a trough-shaped audiogram was significantly higher in patients with acoustic neuroma than in those without (p < 0.01). This study suggests that a trough audiogram is a significant finding in patients with sudden-onset sensorineural hearing loss and indicates the presence of acoustic neuroma.

The Efficacy of Touch Smear Cytology in the Diagnosis of Salivary Gland Cancers.

PURPOSE: Methods for cytologic diagnosis, such as fine-needle aspiration (FNA) and touch smear (TS) cytology, have been frequently used for malignant tumor screening; however, false-negative cases often result in misdiagnosis. The purpose of this study was to investigate the causes of false-negative cases and methods to decrease the false-negative rate in salivary gland tumor TS cytology. MATERIALS AND METHODS: In this cross-sectional study, the authors examined pathologically confirmed salivary gland tumors in 127 cases in which FNA and TS cytology were performed before the operation or open biopsy at Numazu City Hospital (Numazu, Japan) from 2002 to 2016. The authors evaluated the false-negative rates of TS and FNA cytology separately and when used in combination and other variables, such as age, gender, sensitivity, accuracy, specificity, and overall pathologic diagnosis by resection. RESULTS: The overall false-negative rate of postoperative pathologic diagnosis was lower when TS and FNA were combined (1 of 127 cases; 0.8%) compared with FNA cytology alone (10 of 127 cases; 7.9%; P = .034). Suggested causes of a false-negative FNA (or TS) result include cytologic difficulties present in certain malignancies, such as mucoepidermoid carcinoma, adenoid cystic carcinoma, and others. CONCLUSION: False-negative cases were decreased when a combination of preoperative FNA and intraoperative TS cytology was performed. TS cytology appears to be a useful method to avoid misdiagnosis in salivary gland diseases.

Photodynamic therapy in patients with head and neck squamous cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-three patients with HNSCC were treated with porfimer sodium-mediated PDT followed by intraoperative light activation at 630 nm via fiber optic microlens delivered after 48 hours of injection. RESULTS: The complete response (CR) rate was 72.7%, while the efficacy (CR + partial response) rate was 97.0%. The rate of good local control (i.e., CR without recurrence after PDT) achieved after the initial PDT (82.6%) was significantly higher than that achieved after the second or third PDT (10%); this rate remained at 62.1% without functional disturbance and disfigurement even after excluding four previously untreated patients. The final local control rate following PDT plus additional therapies was 73.8%. CONCLUSIONS: PDT is an effective therapy to treat HNSCC, and leads to an improved quality of life in patients with residual or recurrent disease. Lasers Surg. Med. 50:420-426, 2018. © 2018 Wiley Periodicals, Inc.

The impact of iatrogenic glottic atresia due to photodynamic therapy for laryngeal cancer: A report of two cases.

Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment of premalignant and malignant diseases, including head and neck carcinomas. It can be applied before or after chemotherapy, irradiation, or surgery. Unlike irradiation and surgery, it can be repeated many times at the same site, and it is also associated with better cosmetic and functional outcomes [1]. We have treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we describe two such patients who developed vocal cord adhesion due to PDT. To our knowledge, there are no previous reports of patients with glottis atresia due to PDT, thus the cases reported herein are rare, and educationally valuable.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids.

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.

Galanin has tumor suppressor activity and is frequently inactivated by aberrant promoter methylation in head and neck cancer.

PURPOSE: There is accumulating evidence that galanin receptors (GALRs) may be tumor suppressors in head and neck squamous cell carcinoma (HNSCC). Promoter methylation status and gene expression were assessed in a large panel of primary tumors, based on the hypothesis that CpG hypermethylation might silence the galanin gene. EXPERIMENTAL DESIGN: Galanin expression was examined using reverse transcription-polymerase chain reaction (PCR). The methylation status of the galanin promoter was studied using bisulfate sequencing and methylation-specific PCR. UM-SCC-54 was stably transfected to express galanin. RESULTS: Galanin expression was absent in 3/12 (25.0%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expression. Galanin methylation was found in 24/100 (24.0%) cases. HNSCC tumor specimens was significantly correlated with the GALR1 methylation status (P = 1.88E-06). The presence of galanin promoter hypermethylation was statistically correlated with a decrease in disease-free survival (log-rank test, P = 6.02E-05). A multivariate logistic regression analysis showed that methylation of galanin and methylation of the gene pair galanin and GALR1 had an odds ratio for recurrence of 8.95 [95% confidence interval (CI), 2.29-35.03] and 23.84 (95% CI, 2.74-207.17), respectively. UM-SCC-54 cells that are GALR1-proficient but have hypermethylated galanin exhibited suppressed cell proliferation following exogenous expression of galanin. CONCLUSIONS: Association of frequent promoter hypermethylation and gene silencing with poor survival, combined with growth suppression of HNSCC cells after forced gene expression, supports the hypothesis that galanin acts as a tumor suppressor. These data suggest that galanin and GALR1 are potential therapeutic targets and prognostic factors.

Undifferentiated sarcoma of the maxillary sinus: report of a rare case in an adult.

A 51-year-old man complained of left facial swelling and recurrent nasal bleeding. A giant solid tumor in the left maxillary sinus was detected on head CT and MRI, and this tumor was destroying the maxilla and extending into the orbit, pterygoid muscle and posterior paranasal sinuses. The resected specimen consisted of spindle cells containing necrotic material. Histological examination revealed immature tumor cells, and immunohistological study of the tumor showed staining was only positive for vimentin. We accordingly diagnosed undifferentiated sarcoma in the maxillary sinus. Combination chemotherapy with vincristine, doxorubicin, cyclophosphamide/ifosfamide with mesna and etoposide was administered; however, the tumor was unresponsive and the patient died after around 3 months.

Epigenetic inactivation of galanin receptor 1 in head and neck cancer.

PURPOSE: One copy of the galanin receptor 1 (GALR1) locus on 18q is often deleted and expression is absent in some head and neck squamous cell carcinoma (HNSCC) cell lines. To determine if loss of heterozygosity and hypermethylation might silence the GALR1 gene, promoter methylation status and gene expression were assessed in a large panel of HNSCC cell lines and tumors. EXPERIMENTAL DESIGN: Promoter methylation of GALR1 in 72 cell lines and 100 primary tumor samples was analyzed using methylation-specific PCR. GALR1 expression and methylation status were analyzed further by real-time PCR and bisulfite sequencing analysis. RESULTS: The GALR1 promoter was fully or partially methylated in 38 of 72 (52.7%) HNSCC cell lines but not in the majority 18 of 20 (90.0%) of nonmalignant lines. GALR1 methylation was also found in 38 of 100 (38%) primary tumor specimens. Methylation correlated with decreased GALR1 expression. In tumors, methylation was significantly correlated with increased tumor size (P = 0.0036), lymph node status (P = 0.0414), tumor stage (P = 0.0037), cyclin D1 expression (P = 0.0420), and p16 methylation (P = 0.0494) and survival (P = 0.045). Bisulfite sequencing of 36 CpG sites upstream of the transcription start site revealed that CpG methylation within transcription factor binding sites correlated with complete suppression of GALR1 mRNA. Treatment with trichostatin A and 5-azacytidine restored GALR1 expression. In UM-SCC-23 cells that have total silencing of GALR1, exogenous GALR1 expression and stimulation with galanin suppressed cell proliferation. CONCLUSIONS: Frequent promoter hypermethylation, gene silencing, association with prognosis, and growth suppression after reexpression support the hypothesis that GALR1 is a tumor suppressor gene in HNSCC.

Tick bites in the external auditory canal.

We report a case of Ixodes ovatus tick in the external auditory canal. Chief complaints of earfullness and pruritus appeared after the contact with dog. Using a removal method consisting of excising the abdomen of the tick and suctioning its body fluids, followed by removal of the tick body 3 days later, the patient was successfully treated without the development of complications.

Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats.

BACKGROUND: Establishment of non-invasive urinary biomarkers for the prediction of acute renal failure (ARF) is important. We evaluated whether urinary oxidative stress markers reflect intrarenal oxidative stress in cisplatin (CDDP)-induced ARF, and whether these markers can be used for the prediction of future ARF. METHODS: Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured up to day 14 post-CDDP (6 mg/kg) injection in rats. MDA and 8-OHdG expressions were examined in kidneys. RESULTS: CDDP induced an increase in serum creatinine (Scr), blood urea nitrogen (BUN), and tubular damage at day 5, increased urinary MDA excretion and MDA expression in kidneys at day 1 (but returned to basal values by day 3), increased urinary excretion of 8-OHdG at day 5 till day 14 (though the number of 8-OHdG-positive tubular cells increased at day 5 and then gradually decreased). Urinary MDA levels at day 1 correlated significantly with Scr (rho = 0.721, P < 0.01) and tubular damage score (rho = 0.840, P < 0.01) at day 5. CONCLUSION: Our findings demonstrated divergent changes of urinary oxidative stress markers in CDDP-induced ARF, and suggested that urinary MDA may be a useful marker for the prediction of the development of CDDP-induced ARF.

[Comparison of audiological performance bewteen bone-anchored and conventional hearing aids].

The bone-anchored hearing aid (BAHA) is an implantable bone-conduction device that vibrates the skull directly via a surgically implanted titanium screw behind the ear. The BAHA has advantages for patients with aural atresia or chronic ear drainage, who cannot wear air-conduction hearing aids. We compared the function of BAHA to conventional bone and air-conduction hearing aids based on functional gain and speech discrimination tests in quiet and noisy environments in 2 patients with chronic ear problems. All expressed a clear preference for the BAHA over conventional bone-conduction hearing aids. The BAHA and air-conduction hearing aid provided similar audiological performance when the functional gain of each hearing aid coincided. As the air-bone gap widens, however, audiological performance with the BAHA showed an evident preference, indicating that the width of the air-bone gap is of some help in BAHA preference compared to air-conduction hearing aids.

A case of relapsing polychondritis preceded by inner ear involvement.

Relapsing polychondritis is a rare disease of unknown etiology causing systematic inflammation of the whole cartilaginous tissues. We report a patient with relapsing polychondritis preceded by inner ear involvement. A 68-year-old female visited our hospital for a chief complaint of sudden bilateral hearing loss. On pure-tone audiometry, sensorineural hearing loss, 47dB on the right and 51dB on the left, was observed. Later, bilateral auricular chondritis and uveitis developed. On biopsy of the auricular cartilage, perichondritis was observed. The patient was diagnosed with relapsing polychondritis in the early stage, 2 weeks after the onset. Oral predonine administration was initiated, and the auricular inflammation was improved within 10 days. The hearing loss disorder was gradually improved. The steroid dose was reduced, and no decrease in hearing has been observed so far.

Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer.

Loss of 18q was analyzed in 21 sets of head and neck squamous cell carcinoma (HNSCC) cell lines derived from primary and secondary tumors in the same patients. Only 3 of the 21 cell line pairs had no loss of 18q. In the remaining 18 sets, loss of heterozygosity (LOH) affecting 18q was found in either the primary or the secondary lines or both. In every case but one, the same chromosome was affected in both the primary and secondary cell lines. In 8 sets, the 18q loss occurred in the primary tumor and remained stable through the subsequent tumor progression. The primary and secondary lines differed in 18q loss in 10 of 18 (56%) cases with 18q LOH. In 3 of the 10 pairs that differed, 18q LOH was found in only the primary line, indicating that the loss developed after the metastatic or recurrent tumor population had diverged from the primary tumor population. In the other 7 pairs, 18q LOH developed or progressed with tumor recurrence or metastasis. Of these, 3 of 7 had 18q LOH in only the secondary lines, and 4 of 7 had 18q LOH in both the primary and secondary lines, but the extent of LOH was greater in the secondary lines than in the primary lines, indicating that additional rearrangements of the same chromosome occurred with progression. These cases showed that interstitial loss often progresses to consolidated loss in vivo. However, in vitro, the cell lines from the primary tumors with interstitial loss maintain those chromosomes over long-term culture. LOH on 18q in cell lines from previously untreated primary tumors was significantly associated with advanced tumor stage (P=0.0242) and decreased survival (P=0.0453). The findings are consistent with the concept that 18q LOH is an event associated with tumor progression and suggest that inactivation and loss of one or more genes on 18q contributes to aggressive tumor behavior.

Vascular endothelial growth factor (VEGF) expression correlates with p53 and ki-67 expressions in tongue squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, which is associated with tumor progression or metastasis. PATIENTS AND METHODS: Immunohistochemical analysis was performed in 109 patients with tongue squamous cell carcinoma. Cox's proportional hazards regression analysis was used to identify the multivariate predictive value of the prognostic factors. RESULTS: High VEGF expression was found in 69 patients (63%) and low VEGF expression in 40 patients (37%). VEGF overexpression correlated with Ki-67 and p53 overexpressions (p=0.0034 and 0.0065, respectively). High VEGF expression was significantly associated with advanced stage (stage III and IV)(p=0.048). The 5-year relapse-free survival (RFS) rate of patients with high VEGF expression (20%) was significantly lower than that of patients with low VEGF expression (76%) (p<0.0001). Multivariate analysis revealed that VEGF expression and stage grouping were independent predictors for RFS (p<0.0001 and 0.04, respectively). CONCLUSION: VEGF expression plays an important role in tumorprogression.

Prognostic value of glucose transporter 1 expression in patients with hypopharyngeal carcinoma.

BACKGROUND: The increase of glucose transport is a distinguishing marker of tumor cells. We hypothesized that a hypopharyngeal carcinoma, characterized by high frequency of lymph node spread or distant metastasis, was associated with glucose transporter 1 (Glut 1) overexpression. MATERIALS AND METHODS: We investigated the incidence of Glut1 expression by immunostaining in 99 patients with hypopharyngeal carcinoma, and revealed the correlation with the clinical characteristics. RESULTS: The analysis showed 46 patients (46%) of Glut1 overexpression (> 70% tumor cell stained). Glut1 expression did not correlate with gender, subsite, histological grade, tumor size, lymph node status or stage grouping. The 5-year relapse-free survival (RFS) rate of patients with Glut1 overexpression (> 70%) (35%) was significantly lower than that of patients with low Glut1 expression (< or = 70%) (57%) (p = 0.047). Multivariate analysis showed that advanced tumor stage (stages III and IV) and Glut1 overexpression were predictors of reduced RFS (p = 0.031 and 0.021, respectively). CONCLUSION: Glut1 expression is an indicator for predicting the prognosis of hypopharyngeal carcinoma.