Nobuhiro Uwa

CD44 expression is related to poor prognosis of hypopharyngeal squamous cell carcinoma

Abstract Conclusions: CD44 expression in hypopharyngeal squamous cell carcinomas (SCCs) is closely associated with poor prognosis for patients. CD44 may serve as a prognostic marker for hypopharyngeal SCCs. Objectives: CD44, an adhesion molecule binding to extracellular matrix, is believed to participate in the progression of malignancies. To clarify the role of CD44 in the progression of hypopharyngeal SCCs, we examined CD44 expression in relation to clinical parameters in hypopharyngeal SCCs. Methods: Biopsy specimens of hypopharyngeal SCCs were collected from 40 untreated patients, and their CD44 expression was examined immunohistochemically. Hypopharyngeal SCCs were classified into two groups: CD44-low SCCs comprising < 50% CD44-positive tumor cells and CD44-high SCCs comprising ≥ 50% CD44-positive tumor cells. The relation between CD44 expression and various parameters (clinical T and N stages, distant metastasis, and pathological T and N stages) was analyzed by Fishers exact test. The relation between CD44 expression and the 5-year disease-free survival (DFS) rate was also analyzed by log rank test. Results: The CD44 expression in hypopharyngeal SCCs was related to pathological N stage, but not to clinical T and N stages and pathological T stage, of the patients. Distant metastasis during the follow-up occurred more frequently in patients with CD44-high SCCs than those with CD44-low SCCs. The 5-year DFS was significantly lower in the former than in the latter.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers.

Clinical features of 5 patients with descending necrotizing mediastinitis originating from deep neck infection.

Descending necrotizing mediastinitis originating from deep neck infection is one of the most serious diseases in the head and neck region. Delayed diagnosis leads to death. We examined 5 cases of descending necrotizing mediastinitis, successfully treated with antibiotics and surgical drainage. Abscess was found in the lower part of the anterior mediastinum in 3 cases and the posterior mediastinum in 2 cases. We first conducted transcervical mediastinal drainage for 3 cases, however, thoracotomy was eventually required in all cases. For cases of abscess in the lower part of the anterior mediastinum, early and aggressive surgical drainage in collaboration with thoracic surgeons is very important and can improve survival.

Arterial chemoradiotherapy for carcinomas of the external auditory canal and middle ear

The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear.

Combined small cell carcinoma of the hypopharynx.

We report an extremely rare case of combined small cell carcinoma (combined SmCC) of the hypopharynx. A 73-year-old male presented with multiple left neck swellings for 1 month. A tumorous lesion was found in the left pyriform sinus, and biopsy revealed that the lesion was squamous cell carcinoma (SqCC). Surgery was performed and pathological examination led to a diagnosis as combined SmCC, composed of SqCC and small cell carcinoma (SmCC). One month after surgery, a contrast-CT indicated metastases to the cervical lymph node (LN), mediastinum and liver. We performed 5 courses of chemotherapy with the use of cisplatin (CDDP) and irinotecan (CPT-11). The patient temporarily showed a favorable response to the chemotherapy; however, eventually he died of regrowth of the tumor. Combined SmCC is a disease with a poor prognosis. Although biopsy sometimes fails to detect the SmCC component, intensive diagnosis and treatment are necessary.

Utility of real-time diagnosis using contact endoscopy for oral and lingual diseases.

OBJECTIVE In this study, we prospectively investigated the diagnostic accuracy of CE findings in oral and lingual diseases. METHODS Between January 2004 and December 2009, CE was used to examine 66 patients with oral and lingual diseases at Hyogo College of Medicine Hospital. Blood vessel networks and superficial cell layers in the mucosal epithelium of normal and lesion sites were observed after staining with 1% methylene blue. Endoscopic diagnoses (CE diagnosis) were compared with subsequent definitive diagnoses based on pathological findings. The sensitivity and specificity for CE diagnosis were calculated. RESULTS On CE findings, SCC showed the characteristics of absent and tortuous blood vessels, heterogeneous distribution, and increased nucleus/cytoplasm (N/C) ratio. Leukoplakia showed no atypical cells, abundant cornified layers, or cytoplasm without nuclei. Lesions were pathologically classified into three groups: 46 squamous cell carcinomas (SCC), 10 leukoplakias, and 10 other benign lesions (n=66). In 4 patients with SCC, malignancy was underestimated by CE findings. The overall diagnostic rate of the CE was 93.9% (62/66 patients). The sensitivity and specificity of SCC were 0.913 (42/46 patients) and 1.0 (20/20 patients), respectively. CONCLUSION The usefulness of contact endoscopy (CE) as an in vivo real-time diagnostic instrument that can deliver results prior to pathological confirmation was suggested.

Factors Affecting Recurrence of T1 and T2 Tongue Cancer Undergoing Intraoral Resection

1.1. Background: Intraoral resection of early tongue cancer minimally affects the quality of life (QOL) of patients; however, local recurrence of the tumor requires radical resection and negatively affects QOL as well as patient prognosis. The present study was performed to clarify factors affecting recurrence of tongue cancers undergoing intraoral resection. 1.2. Methods: In total, 174 patients (T1: 105 patients and T2: 69 patients) with squamous cell carcinoma of the tongue receiving intraoral resection were enrolled in the study, including 106 male patients and 68 female patients (aged 27-88 years, mean 58 years). Tumor recurrence was observed in 10 of 105 patients with T1 stage cancer (9.5%) and in 6 of 69 patients with T2 stage cancer (8.7%). The clinicopathological factors, including immunohistochemistry for p53, Ki67, and vimentin, were analyzed. 1.3. Results: An infiltration pattern and vimentin expression were associated with tongue cancer recurrence. Specifically, tumors with positive vimentin expression exhibited a higher ratio of endophytic growth, and multivariate analysis revealed that the Ki67 labeling index and vimentin expression were independent factors affecting tumor recurrence. 1.4. Conclusion: The mode of tumor invasion and the epithelial-to-mesenchymal transition, as evidenced by vimentin immunohistochemistry, assisted the identification of high-risk patients with tongue cancer undergoing intraoral resection. Intense follow-up with the aid of multimodal therapies after surgery is necessary in this group of high-risk patients.

An unexpected skin ulcer and soft tissue necrosis after the nonconcurrent combination of proton beam therapy and pazopanib: A case of myxofibrosarcoma

We herein report the case of a patient presenting with myxofibrosarcoma (MFS) who underwent treatment with surgery, proton beam therapy (PBT), and pazopanib. A 64-year-old male was diagnosed with MFS, which ranged from the posterior neck to the shoulder. Surgery was performed as an initial treatment; however, the primary tumor recurred 83 months after the initial treatment. We, therefore, administered PBT. Although most of the recurrent tumor disappeared after PBT, multiple lung metastases were identified 3 months after the completion of PBT. We initiated antiangiogenic treatment with pazopanib. Although long-term survival was achieved with the treatments, the patient suffered from a skin ulcer and soft tissue necrosis and eventually died of general prostration caused by infection, and complicated by pneumonia. Although PBT and pazopanib were effective for treating the local recurrence and lung metastases of MFS, respectively, clinicians must be cognizant of the fact that the combination of high-dose irradiation and angiogenesis inhibitors, even in nonconcurrent cases, can result in a severe skin ulcer and soft tissue necrosis.

Expression of CD44 variant isoforms, CD44v3 and CD44v6, are associated with prognosis in nasopharyngeal carcinoma.

OBJECTIVE The clinical and prognostic significance of CD44 variant isoform expression in nasopharyngeal carcinoma is not well known. This study aimed to clarify whether CD44 variant isoform expression serves as a prognostic factor in nasopharyngeal carcinoma. METHODS Forty-two nasopharyngeal carcinoma patients, who underwent concurrent chemoradiotherapy as the initial treatment, were the subjects of investigation. Expression of CD44 variant isoforms, CD44v3, CD44v4, CD44v5, CD44v6 and CD44v7, in nasopharyngeal carcinoma was assessed in relation to concurrent chemoradiotherapy resistance and disease-specific survival of the patients. RESULTS AND CONCLUSION The patients with CD44v6 high expression showed a clinically incomplete response to concurrent chemoradiotherapy at the primary site. The disease-specific survival rate was lower in patients with high expression of CD44v3 than in those with low expression. These results suggest that analysis of CD44v6 and CD44v3 expression is useful in estimating prognosis and determining effective treatment strategies in nasopharyngeal carcinoma.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery

Background/Aim: Prognostic impact of p16 expression in patients with oropharyngeal squamous cell carcinoma (OSCC) undergoing surgery is not fully examined. The aim of this study was to clarify these issues. Patients and Methods: Sixty-four OSCC subjects were analyzed. Immuno-histochemical staining of p16, a surrogate marker for human papillomavirus (HPV), was performed histopathologically. Data were retrospectively analyzed according to p16 positivity and factors linked to prognosis were also analyzed. Results: No significant difference was observed in the prognosis between the p16-positive group (n=28) and the p16-negative group (n=36). In patients undergoing post-operative radiation, the p16-positive group (n=18) had a significantly better prognosis than the p16-negative group (n=6). On multivariate analysis, transoral surgery was a significant predictor of overall survival (p=0.0173). Conclusion: Prognostic impact of p16 can be emphasized in a subgroup of OSCC patients undergoing surgery. Surgery with sufficient surgical margin may be chosen as the first treatment for HPV-negative OSCC in some cases.