Incidence and spread pattern of lymph node metastasis from submandibular gland cancer.

OBJECTIVES: To clarify the indication of neck dissection (ND) for patient with submandibular gland (SMG) cancer. METHODS: A total of 43 patients with SMG cancer were retrospectively analyzed. Forty-one patients underwent ND: Levels I-V in 19 patients, Levels I-III in 18 patients, and Level Ib in 4 patients. The other two patients did not undergo ND, since preoperative diagnoses were benign. Postoperative radiotherapy was performed in 19 patients with positive surgical margin, high grade cancer or stage IV disease. RESULTS: LN metastases were pathologically confirmed in all patients with cN + and 6 out of 31 patients with cN-. No patients developed regional recurrence during follow-up periods. Ultimately, LN metastases were pathologically confirmed in 17 of 27 high grade, one out of 9 intermediate grade, but not in 7 low grade. CONCLUSIONS: Prophylactic neck dissection should be considered in T3/4 and high grade SMG cancers.

A novel parotid carcinoma with a prominent ghost cell population: a masquerading tumor or "salivary ghost cell carcinoma"?

Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and discuss diagnostic problems. The patient was a 90-year-old Japanese male, who complained of swelling of the left parotid area for four months. Positron emission tomography indicated no cervical lymph node metastasis or distant metastasis. The tumor was successfully resected with no signs of recurrence or metastasis for six months after surgery. Histologically, the tumor was mainly composed of squamous cells forming irregularly shaped nests with a mixture of pleomorphic giant or multinucleated cells and bland basaloid cell. Keratinized areas were occupied by a prominent ghost cell population. Immunohistochemically, CK5/6 and CK19 were widely positive as well as AE1/AE3, p40 and p63. Nuclear expression of ß-catenin was also observed. The present case can be regarded as a particular form of squamous cell carcinoma and is believed to contain a large number of ghost cells resulting from an unclear mechanism. However, it seems difficult to consider such tumors as a clinicopathologically independent entity at present. Applying a term such as "salivary ghost cell carcinoma" would be premature.

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study.

Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

Extent of neck dissection for patients with clinical N1 oral cancer.

BACKGROUND: No clear consensus has been reached on the indication of supraomohyoid neck dissection (SOHND) for clinically positive lymph-node metastasis. PATIENTS: Consecutive 100 patients with previously untreated oral cancer treated at Kobe University Hospital were included in this study. All patients were clinically staged as anyTN1M0 and underwent radical dissection of the primary site and level I-V neck dissection as the initial treatment. RESULTS: None of the 100 patients had pathological lymph-node metastasis (pLN) to level V. pLN to level IV was observed in two patients with tongue cancer in whom clinical lymph-node metastasis was preoperatively observed at level II. CONCLUSIONS: Level V may be excluded in the neck dissection for patients with N1 oral cancers. Level IV dissection should be considered in the patient with tongue cancer and clinical lymph-node metastasis at level II.

Salvage surgery for structural local recurrence of papillary thyroid cancer: recurrence patterns and surgical outcome.

To clarify the patterns of the recurrence and to assess the oncological and functional outcomes after salvage surgery for the patients with structural local recurrence of papillary thyroid cancer (PTC), twenty-five patients who underwent salvage surgery for structural local recurrence of PTC were retrospectively reviewed. Structural recurrences were observed in the tracheal lumen in 5 patients, intraluminal or intramuscular esophagus in 5 patients, trachea, and cricoid cartilage in 9 patients, cricoid and thyroid cartilage in 2 patients, intra-lumen of the larynx in 1 patient and soft tissue around thyroid in 3 patients, respectively. Although all local disease was resected with macroscopically negative margin, 10 patients diagnosed as microscopically positive margin. Major surgical complications occurred in 6 patients, including common carotid artery injury (n = 1), unintentional pharyngeal or esophageal injury (n = 2), recurrent laryngeal nerve paralysis (n = 2), and pharyngeal fistula resulting in common carotid artery rupture (n = 1), and were successfully managed. During the follow-up periods, 6 patients were alive without disease, 15 patients survived with distant metastases and/or locoregional recurrence, and 4 patients died of the disease. While tracheocutaneous fistula remained in 7 patients, the vocal function was preserved in all patients but one who underwent total laryngectomy. Normal oral intake was retained in all patients. In conclusion, although salvage surgery for structural recurrence of PTC has a high risk of complications, it may be worthwhile when macroscopic curative resection is available. The decision should be made considering various factors including curability, risk of surgical procedure, functional outcome, and life expectancy.

Clinical impact of a cytological screening system using cyclin D1 immunostaining and genomic analysis for the diagnosis of thyroid nodules.

BACKGROUND: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; however, some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Similar to BRAF, cyclin D1 may be a strong marker of cell proliferation. METHODS: One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. The identification of the optimal cut off points for the diagnosis of malignancy were evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) of markers were evaluated from crosstabs based on cut off points and significance were calculated. We also analyzed genetic variants by target NGS for thyroid nodule samples. RESULTS: The positive predictive value (PPV) and median stain ratio (MSR) of cyclin D1 nuclear staining was determined in papillary thyroid carcinoma (PPV = 91.5%, MSR = 48.5%), follicular adenoma (PPV = 66.7%, MSR = 13.1%), and adenomatous goiter and inflammation controls (MSR = 3.4%). In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P < 0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. In surgical specimens, ROC curve analysis showed a 5.8% cyclin D1 immunostaining score predicted thyroid neoplasms at 94.4% sensitivity and 92.3% specificity (P = 0.003), while a 15.7% score predicted malignancy at 86.4% sensitivity and 80.5% specificity (P < 0.0001). Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P < 0.001). CONCLUSION: Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.

Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1.

Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.

Functional and oncological outcomes after retropharyngeal node dissection for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma frequently metastasizes to central and lateral neck lymph nodes, but metastasis to retropharyngeal lymph nodes (RPLN) is rare. PATIENTS AND METHODS: We retrospectively reviewed 16 patients with RPLN metastasis of PTC who underwent therapeutic dissection of RPLN metastases. RESULTS: Among 16 patients, 7 patients underwent RPLN dissection with initial surgery and remaining 9 patients as salvage surgery. RPLN metastasis arose unilaterally in 15 patients and bilaterally in 1 patient. Eleven patients showed temporal dysphagia and four patients showed temporal vocal cord paralysis, but both symptoms eventually recovered in all cases. Two patients with salvage RPLN dissection died of distant metastasis and six patients survived with distant metastasis and/or persistent loco-regional disease. Other eight patients have been alive without disease. CONCLUSIONS: Although transcervical approach for RPLN metastases of PTC provided acceptable functional and oncological outcomes, half of the patients with RPLN metastasis have had distant metastasis and/or persistent locoregional disease. Indications of surgery for patients with RPLN metastasis need to be performed carefully in consideration of patients' prognosis and quality of life.

Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers.

AIMS: We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The aim of the present study was to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal squamous cell carcinomas (HPSCCs) or oropharyngeal squamous cell carcinomas (OPSCCs). METHODS AND RESULTS: The study cohort consisted of consecutive patients with HPSCC (n = 130) and OPSCC (n = 65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10 of 130 HPSCCs (8%) and seven of 65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survival than those with SOX2-positive HPSCC, whereas such a prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. As SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific polymerase chain reaction for the SOX2 promoter was performed. Methylated alleles were found in nine of 10 SOX2-negative HPSCCs but in none of SOX2-positive HPSCCs. CONCLUSIONS: Similarly to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost completely lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.

Role of intensive nutrition support and prophylactic percutaneous endoscopic gastrostomy during concomitant chemoradiotherapy for oropharyngeal cancer.

BACKGROUND: Concomitant chemoradiotherapy (CCRT) produces severe mucositis and swallowing dysfunction, often resulting in malnutrition. Intensive nutrition support (INS) in addition to percutaneous endoscopic gastrostomy (PEG) is reported to decrease adverse effects during CCRT. PATIENTS AND METHODS: Fifty-eight patients with oropharyngeal cancer treated by CDDP-based CCRT were retrospectively analyzed. Twenty-nine patients treated with INS in addition to PEG were classified as INS group, and other 29 patients treated with PEG but without INS were classified as control group. RESULTS: INS in addition to PEG significantly increased calorie intake in the second half of CCRT and reduced adverse events including mucositis (p = 0.0019), leukopenia (p = 0.04), and renal function (p = 0.006). Moreover, 21 out of 29 patients had successfully administration of 200 mg/m2 or more of CDDP, while only 10 out of 29 patients had enough amount of CDDP in control group. CONCLUSIONS: These results suggest that INS in addition to prophylactic PEG not only decreases adverse effects but also may potentially improve oncological outcome of the patients with oropharyngeal cancer treated by CCRT.

Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy.

BACKGROUND: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. METHODS: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. RESULTS: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. CONCLUSIONS: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

[18F]Fluorodeoxyglucose uptake by positron emission tomography predicts outcomes for oropharyngeal and hypopharyngeal cancer treated with definitive radiotherapy.

This study evaluated the prognostic significance of the maximum standardized uptake value of the primary site (pSUVmax) in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of patients with oropharyngeal or hypopharyngeal cancer who were treated using definitive radiotherapy. The study included 86 patients who were primarily treated with radiotherapy for oropharyngeal or hypopharyngeal cancer. Sixty-nine patients underwent concurrent chemotherapy. The associations between pre-treatment pSUVmax and treatment outcomes were evaluated. The most appropriate pSUVmax cut-off value for predicting disease-free survival (DFS) and local control (LC) was selected using receiver operating characteristic (ROC) curves. The median follow-up time for surviving patients was 60 months, while the median survival time in the entire patient cohort was 55 months. A pSUVmax cut-off value of 9.0 showed the best discriminative performance. Five-year OS and DFS rates were 65.9% and 60.0%, respectively. In univariate analyses, pSUVmax (p = 0.009), T-stage (p = 0.001), N-stage (p = 0.039), and clinical stage (p = 0.017) were identified as significant prognostic predictors for DFS. The multivariate analysis did not identify any statistically significant factors, but the association between pSUVmax and DFS was borderline significant (p = 0.055). Interestingly, pSUVmax was predictive of local controllability in T1-T2 disease (p = 0.024), but there was no significant association for T3-T4 disease (p = 0.735). In this study, pSUVmax was predictive of DFS and LC in patients with oropharyngeal or hypopharyngeal cancer that was treated with definitive radiotherapy. pSUVmax was strongly associated with LC in T1-T2 disease.

FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT.

OBJECTIVE: To evaluate the accuracy of PET/CT using (18)F-fluorodeoxyglucose (FDG) with IV contrast for suspected recurrent head and neck squamous cell carcinoma (HNSCC). METHODS: One hundred and seventy patients previously treated for HNSCC underwent PET/CT, consisting of non-contrast-enhanced and contrast-enhanced CT, to investigate suspected recurrence. Diagnostic performance of PET/contrast-enhanced CT (PET/ceCT), PET/non-contrast-enhanced CT (PET/ncCT) and contrast-enhanced CT (ceCT) for local or regional recurrence, distant metastasis, overall recurrence and second primary cancer was evaluated. The reference standard included histopathology, treatment change and imaging follow-up. RESULTS: The patient-based areas under the receiver operating characteristic curves (AUC) for ceCT, PET/ncCT and PET/ceCT were 0.82, 0.96 and 0.98 for local recurrence, 0.73, 0.86 and 0.86 for regional recurrence, 0.86, 0.91 and 0.92 for distant metastasis, 0.72, 0.86 and 0.87 for overall recurrence, and 0.86, 0.89 and 0.91 for a second primary cancer. Both PET/ceCT and PET/ncCT statistically showed larger AUC than ceCT for recurrence, and the difference between PET/ceCT and PET/ncCT for local recurrence reached a significant level (p = 0.039). The accuracy of PET/ceCT for diagnosing overall recurrence was high, irrespective of the time interval after the last treatment (83.3-94.1 %). CONCLUSION: FDG-PET/CT was a more accurate HNSCC restaging tool than ceCT. The added value of ceCT at FDG-PET/CT is minimal. KEY POINTS: • FDG-PET/CT is a more accurate post-treatment surveillance tool than ceCT for HNSCC. • FDG-PET/ceCT was useful, irrespective of the time interval after the last treatment. • FDG-PET/ceCT showed high negative predictive value and limited positive predictive value. • The added value of ceCT at FDG-PET/CT is minimal and likely not clinically relevant.

Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss.

The sigma-1 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma-1 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise-induced or aging-associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging-associated hearing loss. These results suggest that cutamesine reduces noise-induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise.

Treatment outcomes of the patients with early glottic cancer treated with initial radiotherapy and salvaged by conservative surgery.

OBJECTIVE: This retrospective study analyzed the oncological and treatment outcomes of the patients with T1-T2N0 glottic cancer, who were treated with radiotherapy as initial treatment and salvaged by conservative surgery for radiation failure. METHODS: Between May 1999 and December 2010, 115 patients with glottic laryngeal cancer were treated at Kobe University Hospital. At presentation, 54 patients had stage T1a disease, 26 had stage T1b disease and 35 had stage T2 disease. Seventy-nine patients were treated with conventional radiotherapy and 36 patients were treated with hyperfractionated radiotherapy as initial treatment. RESULTS: Median duration of follow-up was 61 months. Five-year local control rates of radiotherapy were 92% in T1a, 83% in T1b and 86% in T2. Of 12 patients who developed local recurrence, larynx was successfully preserved in 3 patients by laryngomicrosurgery, 7 patients by vertical partial laryngectomy and one patient by subtotal laryngectomy. Ultimate 5-year laryngeal preservation rate and local control rate of all cases were 99 and 100%, respectively. CONCLUSIONS: Present results suggest that initial treatment with radiotherapy salvaged by organ preservation surgery is an effective strategy for laryngeal preservation in the treatment of T1-T2N0 glottic laryngeal cancer.

Prevalence of human papillomavirus in oropharyngeal cancer: a multicenter study in Japan.

BACKGROUND: The incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) have risen steadily in the USA and in northern Europe. These increases are thought to be a consequence of persistent infection with high-risk human papillomavirus (HPV) in OPSCC patients. HPV is an emerging etiologic factor in OPSCC. In Japan, the incidence of OPSCC has significantly increased over the last three decades. However, the population of HPV-positive OPSCC patients is currently unknown. We examined the nationwide trends with regard to HPV incidence in OPSCC patients at 21 specific sites, and examined the relationship between the presence of HPV and survival in OPSCC patients in Japan. METHODS: Tumor samples were obtained from patients with OPSCC prior to treatment, and HPV infection was investigated by polymerase chain reaction (PCR). Hybrid Capture 2 (HC2) was also adopted for swab examination on the surface of fresh tumors. RESULTS: HPV was detected by PCR in 79 (50.3%) out of 157 OPSCC patients. The clinical features of HPV-positive OPSCC were low differentiation, a tendency to involve the lateral wall, and high nodal staging. The sensitivity and specificity of HC2 were 93.7 and 96.2%, respectively, indicating its utility as a screening test. HPV-positive patients had significantly better overall survival and disease-free survival than HPV-negative patients.

Particle radiotherapy using protons or carbon ions for unresectable locally advanced head and neck cancers with skull base invasion.

OBJECTIVE: To study the oncological outcome of the patients with unresectable locally advanced primary head and neck cancers invading the skull base, treated with particle radiotherapy. METHODS: Fifty-seven patients with unresectable primary head and neck cancers invading the skull base received proton or carbon ion radiotherapy as definitive treatment at Hyogo Ion Beam Medical Center between 2003 and 2009. Forty-seven patients were treated with proton radiotherapy and 10 patients were treated with carbon ion radiotherapy. A retrospective review was performed with clinical charts and recorded imagings. RESULTS: With a median follow-up of 32 months, the 3-year actual survival and local progression-free rates of all the patients were 61 and 56%, respectively. The 3-year actual survival rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 83, 44, 75, 0 and 38%, respectively. The 3-year actual local control rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 63, 31, 83, 50 and 0%, respectively. Distant metastasis was observed in 13 of 25 patients in adenoid cystic carcinoma, two of 14 patients in squamous cell carcinoma, one of six patients with olfactory neuroblastoma, two of four patients with adenocarcinoma, three of four patients with malignant melanoma and two of three patients with undifferentiated carcinoma. Mucositis and dermatitis were seen as acute toxicities. The most common late toxicity was visual disorder. Grades 2, 3 and 4 visual disorders were observed in seven, five and two patients, respectively. CONCLUSIONS: Proton and carbon ion radiotherapy resulted in satisfactory local control in patients with locally advanced unresectable primary head and neck cancers invading the skull base.

Prediction of glomerular filtration rate in cancer patients by an equation for Japanese estimated glomerular filtration rate.

BACKGROUND: Assessment of renal function is important for safe cancer chemotherapy, and eligibility criteria for clinical trials often include creatinine clearance. However, creatinine clearance overestimates glomerular filtration rate, and various new formulae have been proposed to estimate glomerular filtration rate. Because these were developed mostly in patients with chronic kidney disease, we evaluated their validity in cancer patients without kidney disease. METHODS: Glomerular filtration rate was measured by inulin clearance in 45 Japanese cancer patients, and compared with creatinine clearance measured by 24-h urine collection as well as that estimated by the Cockcroft-Gault formula, Japanese estimated glomerular filtration rate developed in chronic kidney disease patients, the Modification of Diet in Renal Disease study equation and the Chronic Kidney Disease Epidemiology Collaboration equation. The Modification of Diet in Renal Disease study and Chronic Kidney Disease Epidemiology Collaboration equations were adjusted for the Japanese population by multiplying by 0.808 and 0.813, respectively. RESULTS: The mean inulin clearance was 79.2 ± 18.7 ml/min/1.73 m(2). Bias values to estimate glomerular filtration rate for Japanese estimated glomerular filtration rate, the Cockcroft-Gault formula, creatinine clearance measured by 24-h urine collection, the 0.808 × Modification of Diet in Renal Disease study equation and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation were 0.94, 9.75, 29.67, 5.26 and -0.92 ml/min/1.73 m(2), respectively. Precision (root-mean square error) was 14.7, 22.4, 39.8, 16.0 and 14.1 ml/min, respectively. Of the scatter plots of inulin clearance versus each estimation formula, the Japanese estimated glomerular filtration rate correlated most accurately with actual measured inulin clearance. CONCLUSION: The Japanese estimated glomerular filtration rate and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation estimated glomerular filtration rate with lower bias and higher precision than the other formulae. We therefore propose Japanese estimated glomerular filtration rate for the estimation of glomerular filtration rate in Japanese cancer patients.

COVID-19 presenting as acute epiglottitis: A case report and literature review.

Coronavirus disease 2019 (COVID-19) occasionally causes acute laryngitis, requiring emergency treatment. Understanding the characteristic laryngeal findings can help diagnose COVID-19 earlier, prevent worsening infection, and properly manage airway obstruction. Herein, we report the case of a 44-year-old male with acute epiglottitis likely caused by COVID-19. On presentation, chest computed tomography (CT) showed no signs of pneumonia. However, the larynx had extensive necrotic-like erosive lesions resembling those of tuberculous laryngitis. COVID-19 was diagnosed by reverse-transcription polymerase chain reaction, and secondary bacterial superinfections were suspected after blood testing. The symptoms improved after administration of antibiotics (sulbactam sodium/ampicillin sodium), steroids (dexamethasone), and favipiravir. The patient developed a high fever on the sixth day of hospitalization, and pneumonia was identified on CT. Various culture tests, including tuberculosis, were negative. Thus, remdesivir was administered for COVID-19-induced pneumonia. The patient gradually recovered, was transferred to another hospital, and was discharged on the 35th day of hospitalization. Six previous case reports of COVID-19-induced acute epiglottitis suggested that acute epiglottitis preceded the onset of pneumonia. The laryngeal findings from this report may be useful for diagnosing COVID-19 that does not cause pneumonia and for bringing attention to pneumonia after a COVID-19 diagnosis.