Intraoperative molecular assessment for lymph node metastasis in head and neck squamous cell carcinoma using one-step nucleic acid amplification (OSNA) assay.

BACKGROUND: Conventional intraoperative pathological examination for Sentinel node navigation surgery (SNNS) has been controversial. We evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of cervical lymph node (CLN) metastasis compared with histopathological examination in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 175 CLNs dissected from 56 patients with HNSCC who underwent surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima Medical University, between April 2008 and December 2011 were enrolled. CLN samples were sectioned into four equal pieces, with two of each used for OSNA assay and other histopathological examinations. The diagnostic value of OSNA assay in HNSCC patients in predicting the results of histopathological diagnosis was evaluated using the area under the receiver operating characteristic (AUROC) curve. RESULTS: OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95 % confidence interval [CI] 0.852-0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131 copies/µl (sensitivity: 82.4, 95 % CI 65.5-93.2; specificity: 99.3, 95 % CI 96.1-100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2]. CONCLUSIONS: We demonstrated that OSNA assay is useful in intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay could be applied for SNNS in HNSCC patients.

Feasibility of ICG fluorescence-guided sentinel node biopsy in animal models using the HyperEye Medical System.

BACKGROUND: The sentinel lymph node (SLN) concept is accepted for several types of cancers. Current methods for sentinel node detection involve radioisotopes and blue dye. They have shown good results, but some drawbacks remain. Indocyanine green (ICG) fluorescence using the HyperEye Medical System (HEMS) was evaluated as a new method. METHODS: This was a prospective, nonrandomized, experimental study in four Japanese white rabbits and six Yorkshire pigs. ICG and indigo carmine were injected into the tongue, larynx, or hypopharynx, and ICG fluorescence detection was evaluated using both transcutaneous visualization of lymphatic vessels and intraoperative identification of SLNs. RESULTS: The SLNs appeared as shining fluorescent spots with HEMS transcutaneously in rabbits, but no SLNs were detected transcutaneously in pigs. Eleven procedures identified SLNs, but one did not due to a technical problem. CONCLUSIONS: HEMS could become useful for predicting lymph node metastasis during surgery for head and neck cancer.

Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies.

A few mutations in the gene encoding the gamma 2 subunit of the gamma-aminobutyric acid receptor type A (GABRG2) have been reported in various types of epilepsy. The aim of this study is to investigate the role of GABRG2 in the pathogenesis of childhood epilepsy in a large Japanese cohort. Genetic analysis of GABRG2 was performed on 140 Japanese patients with various childhood epilepsies largely including Dravet syndrome and genetic epilepsy with febrile seizures plus. The mutational analysis identified one novel missense mutation of GABRG2 (c.236A>G: p.N40S) in a patient with generalized tonic-clonic seizures (GTCS). The mutation was heterozygous and replacing a highly conserved Asn residue with a Ser. The affected amino acid was located at residue 40 of the mature GABRG2 protein, which was near the first one of two high-affinity benzodiazepine-binding domains of the gamma2 subunit (Lys-41-Trp-82). This mutation in such an important position may hamper the function of the channel and contribute to the case's pathogenesis of GTCS.

Phase I study of S-1 plus nedaplatin in patients with advanced/recurrent head and neck cancer.

BACKGROUND: Cisplatin plus fluorouracil is widely used for the treatment of head and neck cancer. However, the cisplatin plus fluorouracil regimen necessitates hospitalization. Therefore, we planned to develop a new regimen that can be administered on an outpatient basis and performed a phase I study of S-1 + nedaplatin. METHODS: S-1 was given orally at a fixed dose for 14 days, and nedaplatin was administered intravenously on day 8 of S-1 administration. The dose of nedaplatin was increased in 10-mg/m(2) steps to find the maximum tolerated dose, depending on the appearance of dose-limiting toxicities. RESULTS: A total of 14 patients were registered. The maximum tolerated dose of nedaplatin was determined to be 90 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. The response rate was 57.1%. CONCLUSION: The recommended dose of nedaplatin for a phase II study was determined to be 80 mg/m(2). We concluded that our regimen was well tolerated and that the response rate was acceptable.

Concurrent chemoradiotherapy for organ function preservation in advanced patients with hypopharyngeal and laryngeal cancer.

Preservation of the larynx is the most critical factor influencing quality of life in the treatment of head and neck cancer. This clinical study focuses on laryngeal function-preserving chemoradiotherapy for locally advanced hypopharyngeal and laryngeal cancer. Thirty-two resectable cases with histologically proven squamous cell carcinoma undergoing function-preserving therapy were examined. Induction chemotherapy comprised cisplatin and 5-fluorouracil, and another cycle of chemotherapy was performed for responders. Chemoradiotherapy comprised conventional irradiation and weekly chemotherapy (nedaplatin plus docetaxel). Non-responder patients were excluded from further chemotherapy and were changed to other surgical treatment. Three patients were non-responders for induction chemotherapy, and 29 patients were treated with chemoradiotherapy. Thus, 21 out of 29 patients obtained preserved laryngeal function. Initial larynx preservation rate with these treatment strategies was 93.8%. This study provides a new concept for laryngeal function-preserving treatment that should be considered for locally advanced laryngeal and hypopharyngeal cancer.

Paraneoplastic limbic encephalitis associated with mixed olfactory neuroblastoma and craniopharyngioma: A case report and literature review.

RATIONALE: Paraneoplastic limbic encephalitis (PLE) is a rare disorder of the nervous system associated with malignant disease. It has a subacute onset with the following symptoms: cognitive dysfunction, seizures, irritability, hallucinations, and short-term memory loss. Herein, we report the case of a 35-year-old man with PLE, an olfactory neuroblastoma (ONB) admixed with craniopharyngioma, and serum anti-Hu antibodies. PATIENT CONCERNS: The patient presented with generalized seizures, short-term memory loss, and a polypoid mass located high in the nasal cavity. INTERVENTIONS: He underwent surgical resection of the tumor and postoperative chemoradiotherapy with concurrent intra-arterial cisplatin administration. DIAGNOSIS: Pathological examination indicated an ONB admixed with craniopharyngioma. OUTCOMES: The patient's neurological symptoms gradually diminished after surgery. No evidence of recurrence was observed during a 4-year follow-up. LESSONS: We reported a histologically unusual heterogeneous tumor that comprised ONB and craniopharyngioma. This is the first reported case of PLE with anti-Hu antibodies possibly associated with ONB admixed with craniopharyngioma.

Primary diffuse large B-cell lymphoma of the frontal sinus: A case report and literature review.

Diffuse large B-cell lymphoma arising as a primary tumor in the frontal sinus is very rare. Moreover, it is often difficult to diagnose frontal sinus lesions. A 67-year-old Japanese man initially presented with diplopia and a swollen left upper eyelid. Diffusion-weighted magnetic resonance imaging suggested a malignant lymphoma of the frontal sinus, and subsequent extensive examination revealed diffuse large B-cell lymphoma of the frontal sinus with left orbital invasion. Six courses of combined immunodirected chemotherapy were administered. The patient is tumor-free owing to the accurate diagnosis of lymphoma at an early stage.

Mutation screening of AP3M2 in Japanese epilepsy patients.

Evidence that some types of epilepsies show strong genetic predisposition has been well documented. AP3M2 is considered to be an epileptogenic gene because AP3M2 knockout mice exhibit symptoms of spontaneous epileptic seizures. In order to investigate whether the AP3M2 gene causes susceptibility to epilepsy, we performed mutation screening of the genomic DNA of 190 patients with six epilepsy types; this screening involved all the 9 exons and the relevant exon-intron boundaries of AP3M2. Although neither missense nor nonsense mutations were detected, we identified 21 sequence variations, of which 16 variations were novel. Of the 21 variations, 11 were detected in 5' and 3' UTRs, while the remaining variations were detected in introns. Although the present study failed to identify the possible AP3M2 mutations that may cause epilepsy, our results suggest that some AP3M2 mutations still remain candidates for unmapped disorders including epilepsy, febrile seizure, and other neuronal developmental disorders associated with functional abnormalities of GABAergic transmission.

Validity of sentinel lymph node biopsy by ICG fluorescence for early head and neck cancer.

AIM: This study was designed to assess the validity of sentinel lymph node (SLN) biopsy using either the combination of indocyanine green (ICG) fluorescence and radioisotope (RI) or ICG-alone in SLN mapping for early head and neck cancer patients. PATIENTS AND METHODS: Nineteen patients received SLN biopsy with the following method. Thirteen patients received SLN biopsy with only RI, 2 patients with only ICG and 4 patients with the combination of ICG and RI. Detection time for each method of SLN biopsy was measured to evaluate the validity of SLN with the combination of ICG and RI. RESULTS: A total of 41 SLNs were identified by RI or ICG. All SLNs identified by ICG could be localized intraoperatively. The number of SLNs identified by the combination of ICG and RI was greater than that of SLNs identified by RI-alone. One of the patients who underwent SLN biopsy by RI-alone was diagnosed with a metastatic lymph node one year later, then underwent neck dissection. Mean detection time for SLN biopsy with ICG or with the combination of ICG and RI tended to be shorter than that of RI-alone. CONCLUSION: SLN biopsy with the combination of ICG and RI enabled us to identify SLNs more easily and rapidly than by using RI alone.

Diagnostic evaluation of sentinel lymph node biopsy in early head and neck squamous cell carcinoma: a meta-analysis.

BACKGROUND: The purpose of this study was to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in early head and neck squamous cell carcinoma (HNSCC). METHODS: The PubMed database was searched for studies published before October 31, 2012. Pooled values for the sentinel lymph node identification rate, sensitivity, false-negative rate, negative predictive value, and accuracy were calculated. RESULTS: A total of 16 studies (987 patients) was included. The pooled identification rate, sensitivity, false-negative rate, negative predictive value, and accuracy were 95.2%, 86.3%, 13.7%, 94.2%, and 95.0%, respectively. The subgroup with high methodological quality showed a mean identification rate of 95.4% for SLNB validation trials and 94.2% for SLNB alone trials, and mean sensitivity of 91.0% for SLNB validation trials and 84.2% for SLNB alone trials. CONCLUSION: The SLNB procedure has shown a high sensitivity rate, but the pooled sensitivity and false-negative rate were worse in SLNB alone trials than in SLNB validation trials.

[Appropriate use of rapid diagnostic testing for influenza].

To determine a more timely acquisition of accurate results for influenza patients, a rapid diagnostic testing for influenza were studied on 877 pediatric patients performed during the 2002-2003 flu season in our hospital. Of these, 337 patients were finally diagnosed as influenza based on the test results and treated with antiviral agents, amantadine or oseltamivir. Ten (29%) of the 34 patients whose tests were negative within 12 hours after onset became positive over 12 hours after onset. On the other hand, diagnoses based on antigen tests over 12 hours after onset were reliable because all 13 patients first confirmed negative were unchanged when tested afterward. These 10 patients missed the opportunity to take antivirals early, which possibly caused them to have significantly longer (p = 0.0003) febrile duration and higher frequency of admission (p < 0.0001) than the 106 patients first confirmed positive within 12 hours after onset. Days from onset until starting antivirals (mean 1.4 days), the febrile duration (mean 2.7 days) and frequency of hospitalization (20.5%) of the 219 patients who tested positive over 12 hours after onset were significantly worse (p < 0.0001, p < 0.0001 and p = 0.0406, respectively) than those of patients testing positive within 12 hours after onset (mean 0.2 days, mean 1.7 days and 11.3%, respectively). The febrile duration (mean 2.3 days) of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was tolerable but significantly longer (p < 0.0001) than that of patients confirmed positive within 12 hours after onset. The frequency (19.6%) of hospitalization of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was not significantly different from that of patients confirmed positive within 12 hours after onset. These results suggested that over 12 hours but within 48 hours after onset of illness is the best period for the rapid diagnosis to correctly determine whether a patient should be treated with antiviral agents based on the result.

Feasibility of concurrent chemoradiotherapy with S-1 administered on alternate days for elderly patients with head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) improves survival and organ preservation in patients with head and neck squamous cell carcinoma (HNSCC), compared with radiotherapy. However, such regimens are not always feasible because of substantial toxicities. Therefore, we evaluated the feasibility of S-1, administered on alternate days, and concurrent radiotherapy among elderly patients with HNSCC. PATIENTS AND METHODS: Nineteen eligible patients were treated with CCRT. S-1 was administered at a dose of 80 mg/day on alternate days with the intention to reduce the toxicity. RESULTS: With a median follow-up period of 19.2 months, the two-year overall survival rates were 62.5% for patients with stage III disease and 50.0% for those with stage IV. The Complete Response (CR) rates were 100% for stage II and 66.7% for stage III/IV disease. Grade 3 mucositis occurred in three patients. Grade 3 or 4 hematological toxicities were not observed. CONCLUSION: CCRT with S-1 administered on alternate days was effective and well-tolerated among elderly patients with HNSCC.

Head and neck cancer with dermatomyositis: a report of two clinical cases.

Dermatomyositis is well known to be associated with several types of malignancy and patients with dermatomyositis have higher rates of mortality from cancer. Although rare in Japan, head and neck cancer, especially nasopharyngeal cancer, is the predominant type of cancer associated with dermatomyositis in several areas in Asia, including Hong Kong and Singapore. Here we report two cases of head and neck cancer with dermatomyositis as well as a literature review. Both cases were treated with chemotherapy and radiotherapy. Although the patients were immunosuppressed due to dermatomyositis treatment, no grade 3 or 4 adverse events occurred.

A first Japanese case of Bartonella henselae-induced endocarditis diagnosed by prolonged culture of a specimen from the excised valve.

Bartonella henselae, the causative agent of cat scratch disease, is increasingly recognized as a cause of culture-negative endocarditis. This report describes the first Japanese case, which was diagnosed after a prolonged culture of the excised aortic valve. High IgG and IgM titers to B. henselae pointed to a subacute course of the disease.