Middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland.

Background. Middle-ear carcinoid tumour is a rare malignant tumour with an indolent course occasionally causing regional or distant metastasis. This paper presents a case of middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland 20 years after the first surgery.Case report. A 35-year-old woman who underwent multiple tympanomastoidectomies for middle-ear carcinoid presented with tumours of both the parapharyngeal space and parotid gland, detected by regular imaging. Based on the clinical course, metastatic relapse of middle-ear carcinoid was suspected. This was treated with subtotal parotidectomy with elective neck dissection (levels II and III), leading to the pathological diagnosis of carcinoid tumour. A cervico-parotid approach was selected to avoid complications associated with parapharyngeal space tumour removal. Transient facial palsy (House-Brackmann grade III) occurred, which completely recovered two months after surgery.Conclusion. Awareness of parapharyngeal space tumours possibly caused by metastasis from a middle-ear tumour is necessary.

New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear.

BACKGROUND: The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. METHODS: Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. RESULTS: Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). CONCLUSION: It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.

Effect of tumor burden and growth rate on treatment outcomes of nivolumab in head and neck cancer.

BACKGROUND: Nivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan-Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3-6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC. METHODS: We retrospectively reviewed the clinical records of 27 consecutive R/M HNSCC patients treated with nivolumab from 2014 to 2018. Tumor size was evaluated by RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3log(D0/Dpre)/t, where D0 and Dpre are the sum of the diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1t defined as 4 weeks. RESULTS: Twenty-five patients were enrolled. Survival was significantly worse in patients with disease progression within 3 months. Outcomes appeared poorer in patients with higher pre-treatment Gr and bigger SumTLs at baseline. We therefore explored the association between prognosis, Gr and SumTLs. Recursive partitioning analysis showed that the characteristics of patients with disease progression after 3 months were Gr < 0.76 and SumTLs < 31.0 mm. Further, Gr < 0.76 and SumTLs < 31.0 mm was associated with significantly longer PFS (p = 0.01) and OS (p < 0.01). CONCLUSIONS: These results suggest that Gr and SumTLs at baseline are significantly associated with OS and PFS in R/M HNSCC patients treated with nivolumab.

Sequential changes in oral dryness evaluated by a moisture-checking device in patients with oropharyngeal cancer during chemoradiotherapy: a pilot study.

PURPOSE: Although oral dryness is a predictor for oral mucositis caused by Chemoradiotherapy (CRT) for head and neck cancer, there have been few reports evaluating the sequential changes in oral dryness during therapy. Studies have determined the reliability and usefulness of a moisture-checking device for the evaluation of dry mouth. This study aimed to evaluate the oral moisture level in patients with Oropharyngeal Cancer (OPC) during CRT using a moisture-checking device. METHODS: Oral moisture level was measured with an oral moisture-checking device (Moisture Checker Mucus®) at the lingual and buccal mucosa before, at the midpoint, and at the end of CRT in patients with OPC. Sequential changes in oral dryness were evaluated. RESULTS: A significant decrease in oral moisture level at the lingual mucosa was found when comparing values before and at the end of CRT (P=0.017). Decreases in oral moisture level at the buccal mucosa were not significant. CONCLUSIONS: A moisture-checking device is considered a useful tool for determining the sequential changes in oral dryness during CRT for head and neck cancer. Our findings provide a basis for future larger long-term studies of oral moisture levels in OPC patients receiving CRT.

E10A, an adenovirus-carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma.

Most cancer chemotherapeutic agents are administered at the maximum-tolerated dose (MTD) in short cycles with treatment breaks. However, MTD-based chemotherapies are often associated with significant toxicity and treatment breaks allow the opportunity for tumor regrowth and acquisition of chemoresistance. To minimize these drawbacks, a metronomic strategy, in which chemotherapeutics are administered at doses significantly below the MTD without treatment breaks, has been suggested by many investigators. The antitumor effect of metronomic chemotherapy may be partially due to inhibition of tumor angiogenesis, and it could be enhanced by a combination therapy, including antiangiogenic agents. In this study, we evaluated the synergistic effect of E10A, an adenovirus carrying the endostatin gene, the most potent inhibitors of tumor angiogenesis, in combination with weekly low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma. The E10A induced mRNA and protein expressions of endostatin in H891 cells in vitro. E10A significantly enhanced the in vivo tumor growth inhibitory effect of cisplatin. Immunohistochemical analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay and anti-CD31 antibodies revealed that the combination of E10A and cisplatin induced high levels of cell apoptosis and inhibited tumor angiogenesis. Importantly, E10A increased the platinum concentrations in tumors to fivefold higher than that induced by cisplatin alone.

Expression and regulation of human CD275 on endothelial cells in healthy and inflamed mucosal tissues.

The CD275-CD278 costimulatory pathway is a new pathway for CD28-B7 family molecules involved in the effector phase of T-cell-mediated immune responses. Expression of CD275 in oral mucosa at healthy and disease states has not been examined. We generated monoclonal antibodies against human CD275 and investigated its expression and regulation in cultured tissue cell lines and oral mucosal tissues. CD275 on monocytes was efficiently upregulated by interleukin-4, while interferon-gamma abrogated this effect. CD275 on cultured endothelial cells (EC) was rapidly enhanced by tumour necrosis factor-alpha. In healthy oral mucosa, CD275 was not detected on keratinocytes, Langerhans cells or intraepithelial lymphocytes within the epithelium or on interstitial dendritic cells or lymphocytes in the sub-epithelium. Constitutive expression of CD275 on EC in the connective tissues was observed in healthy mucosa, but CD275 expression on EC in oral lichen planus was either upregulated or down regulated. Approximately 20% of the T cells found within infiltrating mononuclear cells in the sub-epithelium expressed high levels of the CD278 receptor. CD275 on lymphoid and nonlymphoid cells is positively or negatively regulated by various cytokines. Our results suggest that CD275 on EC is involved in the recruitment or extravasation of receptor-positive effector T cells into inflamed tissues.

Infective endocarditis-induced crescentic glomerulonephritis dramatically improved by plasmapheresis.

A 50-year-old woman was referred to our hospital because of skin purpura, anemia, high fever, and acute renal insufficiency. Five years ago, she had been diagnosed as having ventricular septal defect without any complications. A blood culture drawn during the hospitalization grew Streptococcus viridans. She was diagnosed as having infective endocarditis-induced crescentic glomerulonephritis (GN) according to echocardiography and renal biopsy results. Although antibiotic treatment alone showed no apparent efficacy, after the initiation of plasmapheresis, the high fever and acute renal insufficiency were dramatically improved. After clinical stability was achieved, closure of the ventricular septal defect was performed. This result suggests that plasmapheresis may be beneficial in the treatment of infective endocarditis-induced crescentic GN. The possible mechanisms of this therapy are discussed.

A case of myasthenia gravis in childhood associated with chronic inflammatory demyelinating polyradiculoneuropathy.

We report a 14-year-old girl who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia gravis, which was clinically of ocular type, but with waning phenomenon of the extremities, occurred at 2 years and 4 months of age. Muscle weakness of the lower extremities gradually developed over the next 6 years. The electrophysiological and pathological findings fulfilled the criteria of "possible CIDP" with severe axonal involvement. The signs of myasthenia gravis and CIDP fluctuated synchronously. A common immunological abnormality was suggested to underlie this rare association of myasthenia gravis and CIDP in childhood.

[CT and MR imaging of desmoid tumors--comparison of two modalities].

As desmoid tumors invade locally and postoperative recurrence is common, accurate diagnosis of the extent of the tumor is needed prior to surgery. CT and/or MRI evaluation of tumor extension was retrospectively studied in eight patients with desmoid tumors, and the results were correlated with the histopathological findings. All tumors were completely resected even in patients who were evaluated by CT alone. However, the delineation of tumor and local invasion were not clearly demonstrated by CT. On the other hand, the delineation of tumor and local invasion were well visualized on MRI. The MRI picture of desmoid tumors was mainly composed of two different areas of signal intensity. The area of hypointensity in both T 1- and T 2-weighted images was found to have abundant collagen fibers, while the area of isointensity or slight hyperintensity in T 1-weighted images and hyperintensity in T 2-weighted images was found to have fibroblasts. In conclusion, MRI is better suited to the evaluation of patients with desmoid tumors than CT.

[CT features of chronic maxillary osteomyelitis in adults].

CT findings were reviewed in four adult patients with chronic maxillary osteomyelitis (CMO) that was histologically proved. The CT features of CMO included bone destruction and soft tissue mass, predominantly in the inferior portion of the maxillary antrum (all 4 cases), thickening of the antral wall (3 cases) and abnormal soft tissue around the antrum associated with or without bony wall destruction (3 cases). CMO could not be distinguished from cancer of the maxillary antrum on CT because of the similar findings. However, abnormal soft tissue around the antrum together with an undestructed bony antral wall may be useful for differentiating the two diseases.

Two cases of Fabry's disease: a hemizygote with a point mutation in the alpha-galactosidase A gene and his relative.

A 34-year-old Japanese male had leg pain, edema of the legs, hypohidrosis, whorl-like opacities of the bilateral cornea, bilateral subcapsular cataracts, and chest discomfort on exercise. He had no characteristic angiokeratomas but did have telangiectases. The electrocardiogram revealed high voltage. The echocardiogram revealed mild mitral regurgitation. The alpha-galactosidase A activity in cultured lymphoblasts was deficient (0.5 nmol/h/mg protein). Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts. He had a G--> A transition at nucleotide 982 in the coding sequence of the alpha-galactosidase A gene which resulted in a glycine to arginine amino acid substitution at residue 328. His uncle also had leg pain, edema of the legs, hypohidrosis, and chest pain on exercise. He had no characteristic angiokeratomas but did have telangiectases. Cardiovascular examination revealed hypertrophic cardiomyopathy and stenoses of coronary arteries. Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts.

[CT-guided percutaneous lung biopsy using a cutting needle and an automated biopsy gun. Comparison with lung biopsy using a manual aspiration needle].

Twenty-five percutaneous lung biopsies using a 20-gauge cutting needle and automated biopsy gun (ABG) were performed under CT guidance in 25 patients with thoracic lesions. This procedure was compared with that using a 21-gauge manual aspiration needle in 36 patients (40 examinations, 37 lesions) in terms of success rate, rate of correct diagnosis, mean examination time and rate of complications. Specimens obtained from lung biopsy were graded by a histopathologist according to quality and quantity from 0 to 4 (pathological score). There were no statistically significant differences between the two procedures in terms of success rate, rate of correct diagnosis and rate of complications; only the time required was significantly different. However, sufficient biopsy material and a mean pathological score of G-II 2.8 (that of G-I was 1.9, p less than 0.05) could be obtained by the biopsy procedure using the cutting needle. The above results indicated that aspiration needle biopsy was adequate for lung biopsy, but that a cutting needle and ABG should be used when a good biopsy specimen is needed for tissue diagnosis.