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.

Assessment of tumor response to chemoradiotherapy and predicting prognosis in patients with head and neck squamous cell carcinoma by PERCIST.

PURPOSE: To evaluate therapeutic response to chemoradiotherapy and prediction of recurrence and death in patients with head and neck squamous cell carcinoma (HNSCC) using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). MATERIALS AND METHODS: Forty-two patients (mean 63.4, range 20-79 years) with nasopharyngeal (n = 10), oropharyngeal (n = 13), hypopharyngeal (n = 11), or laryngeal (n = 8) cancer underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and approximately 3 months (mean 95.0, range 70-119 days) after undergoing concurrent chemoradiotherapy. The effect of PERCIST regarding progression-free survival (PFS) and overall survival (OS) was examined using log-rank and Cox methods. RESULTS: Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease shown by PERCIST were seen in 30 (71.4%), 9 (21.4%), 3 (7.1%), and 0 patients, respectively. Fourteen (33.3%) developed recurrent disease (median follow-up 27.2, range 8.7-123.1 months) and 9 (21.4%) died (median follow-up 43.6, range 9.6-132.6 months). Furthermore, 4 (13.3%) of 30 patients with CMR developed recurrence, while 7 (77.8%) of 9 with PMR and all 3 (100%) with SMD developed recurrence. Two (6.7%) of 30 patients with CMR, 4 (44.4%) of 9 with PMR, and all 3 (100%) with SMD died. Patients who achieved CMR showed significantly longer PFS and OS as compared to those who did not (PMR and SMD) (both, p < 0.0001). CONCLUSION: PERCIST is useful for evaluating therapeutic response to chemoradiotherapy and predicting recurrence and death in HNSCC 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.

[A Case of Tongue Carcinoma Resection and Reconstruction with Microsurgical Free Flap during Pregnancy].

Malignant tumors during pregnancy are rarely seen by otolaryngologists, and they cause various problems which require special treatment with careful consideration of both the mother and fetus. Cases of tongue carcinoma resection and reconstruction with a microsurgical free flap during pregnancy have not previously been reported in Japan. We report herein on a case, in which the mother and her child made satisfactory progress after surgery. A-33-year-old female at 25 weeks and 4 days of pregnancy was referred to our department for the treatment of a tumor on the right edge of her tongue. Examinations including biopsy revealed SCC (T2N0M0). We performed an operation to remove the tongue carcinoma with the pull-through method and reconstruct the tongue with an ALT flap at just 28 weeks of pregnancy. The postoperative recovery was favorable, and she gave natural birth to a girl safely at 38 weeks and 6 days of pregnancy. She is currently free of disease and her child is growing normally, at 2 years and 10 months after surgery.

[A Clinical Study of 109 Cases of Glottic Squamous Cell Carcinoma].

A total of 109 patients with glottic squamous cell carcinoma were retrospectively evaluated at Hyogo College of Medicine Hospital between 2003 and 2010; 106 patients were male and 3 patients were female, with a median age of 69 years (range, 51-90 years). According to the 7th edition of the Union for International Cancer Control TNM classification, the clinical TN stages were T1aN0 in 47 cases, T1aN1 in 1 case, T1aN2a in 1 case, T1bN0 in 19 cases, T3N0 in 11 cases, T4aN in 5 cases, and T4aN2b in 1 case. No distant metastasis was observed in any cases at initial treatment. Treatments were radiotherapy alone in 75 cases, concurrent chemo-radiotherapy in 20 cases, supra-cricoid laryngectomy in 1 case, and total laryngectomy in 13 cases. Salvage surgery was performed for 14 patients who had undergone radiotherapy or concurrent chemo-radiotherapy. Salvage surgeries included frontolateral partial laryngectomy in 8 cases, supra-cricoid laryngectomy in 2 cases, and total laryngectomy in 4 cases. The 5-year overall survival rate was 77.6%, and the 5-year disease-specific survival rate was 92.5%. The 5-year laryngeal preservation rate was 82.9%. With regard to T-stages, the laryngeal preservation rates were 100% for T1a, 89.5% for T1b, 91.5% for T2, 18.2% for T3, and 16.7% for T4a.

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.

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

OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. METHODS: Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. RESULTS: The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. CONCLUSIONS: These results suggest that superselective arterial chemoradiation can be a treatment option 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.

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

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 Fisher's 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.

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.

[Voice restoration and long-term progress in voice rehabilitation using the Provox2 voice prosthesis after total laryngectomy].

From January 2000 to December 2008, we conducted voice rehabilitation using the Provox2 voice prosthesis total-laryngectomy subjects. Of these, 36 attained restoration of 90.0%. Mean maximum phonation time (MPT) was 14.5s, ranging from MPT was not influenced by age, radiotherapy use, primary tumor site, or reconstructive surgery use. Voice prosthesis replacement averaged 25 weeks (5.8 months), ranging from 9 to 74 weeks. Complications occurred in 16 caces (40.0%), mainly granulation tissue formation and prosthesis-site infection, also aspiration pneumonia, prosthesis-site salivary leakage, inability to replace the prosthesis, tracheomalacia, bodies in the trachea. Management rather than medical problems included cost, frequent hospital visits, and lack of motivation to use a prosthesis. The Provox2 voice prosthesis speech provides a higher rate of speech restoration, longer phonatory better intelligibility. Management problems, however, require that we work to understand subjects' living environments and family situations better for evaluating Provox2 voice prosthesis indication more effectively.

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.

Epithelial-myoepithelial carcinoma arising in the nasal cavity.

This study documents a case of an epithelial-myoepithelial carcinoma (EMC) in the left nasal cavity. A 70-year-old woman who presented with recurrent epistaxis of the left nasal nostril of 3 months duration was found to have a polypoid tumor in the left nasal cavity. A computed tomography (CT) scan revealed a tumor to occupy the left inferior and middle nasal cavity which had destroyed the inferior nasal turbinate, and a horizontal scan showed the tumor to occupy the middle and posterior nasal cavity. Since the tumor was connected to the lateral wall of the left nasal cavity with a narrow stalk, the tumor was excised by peeling the mucosa from the wall of the left nasal cavity. Based on the histological and immunohistochemical findings, the tumor was diagnosed to be an EMC. The follow-up at 12 months after the operation showed no evidence of recurrence.

Primary malignant melanoma of the larynx: a case report and literature review.

A 56-year-old Japanese man presented with hoarseness and left sided neck swelling in June 2003. Endoscopy showed an irregular tumor extending from the anterior commissure to the left ventricle with dark pigmentation. A biopsy showed malignant melanoma. A total laryngectomy with left radical neck dissection was performed in July 2003, followed by chemohormonal therapy and radiotherapy to the neck. Multiple bone metastases were diagnosed in May 2004, and the patient died with disseminated disease in April 2005, 21 months after initial treatment. The medical literature on laryngeal malignant melanoma was reviewed, and suggested a very poor prognosis despite therapy with surgery, radiotherapy, and chemotherapy.

Voice rehabilitation with Provox2 voice prosthesis following total laryngectomy for laryngeal and hypopharyngeal carcinoma.

OBJECTIVE: To analyze the effectiveness of the Provox2 voice prosthesis for voice rehabilitation following total laryngectomy. METHODS: From September 2000 to December 2004, the Provox2 voice prosthesis was used for voice rehabilitation in 32 patients following total laryngectomy. The quality of speech with the Provox2 voice prosthesis was analyzed using the HRS rating scale, the maximum phonation time (MPT), incidence of complications and the in situ lifetime. The rate of speech restoration was further analyzed in 129 patients with total laryngectomy from 1996 to 2004. RESULT: Twenty-nine of 32 patients were able to restore speech using the Provox2 voice prosthesis, a speech restoration rate of 90.6%. The maximum phonation time (MPT) was measured in 18 patients using the Provox2 voice prosthesis. The mean MPT was 15.1 s, with a range of 8-28 s. MPT was not influenced by age, concurrent radiotherapy treatment, the location of the primary tumor or use of reconstructive surgery. The average lifetime of the Provox2 in patients with laryngeal carcinoma (12 patients) and hypopharyngeal carcinoma (17 patients) was 27.2 and 16.6 weeks, respectively, which was significantly different (P=0.024, non-parametric Mann-Whitney's U-test). The rate of speech restoration by the use of esophageal speech, and insertion of an artificial larynx was 62.7% for laryngeal carcinoma (59 cases) and 38.6% for hypopharyngeal carcinoma (70 cases), which was also significantly different (P<0.01, chi-square test). CONCLUSION: Provox2 voice prosthesis speech was very useful due to the higher rate of speech restoration, longer phonatory time, and better intelligibility. It was also thought that voice prosthesis speech was useful in conjunction with esophageal speech and an artificial larynx depending on the patient's condition or wishes.