Acquired tracheobronchomalacia developed following voice prosthesis implantation.

Acquired tracheobronchomalacia (ATBM) is a condition in which the tracheobronchial wall and cartilage progressively lose their rigidity, resulting in dynamic collapse during exhalation. In this report, we present a case of ATBM that developed following voice prosthesis implantation. To the best of our knowledge, this is the first documented case of such a condition in the medical English literature based on a PubMed search. A 63-year-old man was referred to National Kyushu Cancer Center in Japan with complaints of pharyngeal pain and a laryngeal tumor. The tumor was diagnosed as laryngeal cancer, and the patient underwent laryngectomy. Three months after the surgery, we implanted a voice prosthesis through a tracheoesophageal puncture. Two months after implantation, the patient experienced dyspnea. This condition was subsequently diagnosed as ATBM through computed tomography and bronchofiberscope examinations. After the removal of the voice prosthesis, there has been no progression of ATBM for over five years. While ATBM may not be a common occurrence in the practice of head and neck surgeons, it should be considered as a potential complication when patients report dyspnea following voice prosthesis implantation.

Efficacy of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine for the prevention of mucositis induced by platinum-based chemoradiation in head and neck cancer: A phase II study.

BACKGROUND & AIMS: The current standard treatment modality for advanced head and neck squamous cell carcinoma (HNSCC), namely platinum-based (PB) concurrent chemoradiotherapy (CRT), is associated with frequent severe mucositis which is responsible for the multiple acute and late adverse events. So far, effective preventive methods for this CRT-induced mucositis are not identified. In the current study, we examined the prophylactic effects of beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) (HMB/Arg/Gln) mixture. METHODS: Patients with HNSCC who were subject to PBCRT were randomly assigned to HMB/Arg/Gln intervention (Group I) and non-intervention (Group NI) cohort. The incidences of ≧ grade 3 mucositis (primary endpoint), ≧ grade 2 mucositis, and opioid usage and the degree of body weight loss (secondary endpoints) were compared between Group I and Group NI. RESULTS: A total of 75 patients were enrolled to this study and 38 patients were assigned to Group I, while 37 patients were to Group NI. After excluding patients who failed to complete CRT (3 in Group I and 2 in Group NI) or withdrew consents (11 in Group I and 1 in Group NI), 24 patients in Group I and 34 patients in Group NI were evaluated. HMB/Arg/Gln failed to reduce the incidences of ≧ grade 2 mucositis, but significantly (p = 0.0003) inhibited grade 3 mucositis in the late phase CRT, reducing the incidence from 64.6% (Group NI) to 25% (Group I) at 70Gy. The degree of body weight loss was significantly (p = 0.0038) lower in Group I (5.6%) compared to Group NI (8.9%), preventing the progression of PBCRT-induced cachexia. CONCLUSIONS: HMB/Arg/Gln administration demonstrated inhibitory effects on the progression of grade 3 mucositis and cancer cachexia in HNSCC patients treated with PBCRT. A larger scale phase III study is encouraged. CLINICAL TRIAL REGISTRATION: This study is registered to the UMIN Clinical Trial Registry: UMIN000050011.

Is chemoimmunotherapy a game changer in the treatment of locally advanced head and neck squamous cell carcinoma?

Pembrolizumab and chemotherapy (chemoimmunotherapy) were administered to 2 head and neck squamous cell carcinoma (HNSCC) patients with extremely advanced local tumors and distant metastases with palliative intent. However, they demonstrated strikingly good responses and achieved remission. Expanded application of induction chemoimmunotherapy may be useful for locally advanced HNSCC.

Genetic and transcriptomic analyses in a rare case of human papillomavirus-related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma.

Human papillomavirus (HPV)-related oropharyngeal small-cell carcinoma (OPSmCC) is a rare malignancy with aggressive behavior, whereas HPV-related oropharyngeal squamous-cell carcinoma (OPSqCC) displays a favorable prognosis. Notably, these two malignancies occasionally arise in an identical tumor. In this case study, we explored the molecular characteristics that distinguishes these two carcinomas using a rare case of HPV-related oropharyngeal carcinoma (OPC) with the combined histology of SmCC and SqCC. Immunohistochemical analysis and HPV-RNA in situ hybridization (ISH) suggested that both SmCC and SqCC were HPV-related malignancies. Targeted exome sequencing revealed that SmCC and SqCC had no significant difference in mutations of known driver genes. In contrast, RNA sequencing followed by bioinformatic analyses suggested that aberrant transcriptional programs may be responsible for the neuroendocrine differentiation of HPV-related OPC. Compared to SqCC, genes up-regulated in SmCC were functionally enriched in inflammatory and immune responses (e.g., arachidonic acid metabolism). We then developed a SmCC-like gene module (top 10 up-regulated genes) and found that OPC patients with high module activity showed poor prognosis in The Cancer Genome Atlas (TCGA) and GSE65858 cohort. Gene set enrichment analysis of the SmCC-like gene module suggested its link to MYC proto-oncogene in the TCGA data set. Taken together, these findings suggest that the SmCC-like gene module may contribute to acquisition of aggressive phenotypes and tumor heterogeneity of HPV-related OPC. The present case study is the first report of genetic and transcriptomic aberrations in HPV-related OPSmCC combined with SqCC.

Successful management of recurrent adenoid cystic carcinoma in the deep infratemporal fossa by maxillo-orbito-zygomatic approach.

OBJECTIVE: In the case of deep invasion of an infratemporal fossa (ITF) tumor, surgeons find it difficult to gain sufficient visualization and working space by conventional surgical approaches. To overcome these limitations, we have developed a novel surgical technique, maxillo-orbito-zygomatic (MOZ) approach, by combining partial lateral maxillectomy with the conventional orbito-zygomatic approach. METHODS: A 63-year-old male presented with the fifth recurrent adenoid-cystic carcinoma in the right deep ITF. Using a Weber-Ferguson-type incision and partial dismasking, we elevated the skin and scalp flap, while preserving the facial nerve and orbicularis oculi muscle intact in the flap. Then, we performed MOZ osteotomy using three cut lines, the zygomatic arch, the frontozygomatic suture, and from the inferior orbital fissure to the anterolateral wall of the maxilla. Following this, we temporarily elevated the bone flap by partially opening the lateral maxillary sinus. We obtained an excellent surgical view of the ITF, middle skull base, and pterygopalatine fossa with this technique, which facilitated the safe removal of the tumor. RESULTS: The postoperative course remained almost uneventful, and we obtained favorable cosmetic results. CONCLUSIONS: Our novel MOZ approach could be a robust approach to remove deep ITF tumors.

Transmanubrial Approach for Removing a Head and Neck Tumor Located at the Upper Lateral Mediastinum.

BACKGROUND: When a head and neck tumor invades the upper lateral mediastinum, the transmanubrial approach (TMA), in which the sternoclavicular joint is temporary mobilized and replaced back to the physiological position, appears to be an excellent method. However, there have been only a few reports about the application of this approach to head and neck tumors. MATERIALS AND METHODS: We recently adopted this technique for the removal of 2 head and neck tumors that required handling of the subclavian and innominate veins around the venus angle. RESULTS: We could safely remove the tumors under good surgical view and obtained excellent cosmetic and functional results. CONCLUSIONS: TMA is a useful technique for the removal of head and neck tumors, which invade the upper lateral mediastinum. More frequent applications of this method are encouraged in combination with head and neck tumor surgery.

Massive internal jugular vein tumor thrombus derived from squamous cell carcinoma of the head and neck: two case reports.

PURPOSE: Tumor thrombosis of the internal jugular vein (IJV) is an extremely rare disease, and the reported cases have been exclusively associated with differentiated thyroid cancer. In the present study, we describe two cases of IJV tumor thrombosis originated from squamous cell carcinoma (SCC), which is the first case report. METHODS: Case 1 was a 67-year-old man diagnosed with advanced supraglottic SCC with a massive tumor thrombus in the IJV. He was treated with bio-radiotherapy followed by radical surgery. Case 2 was a 65-year-old woman who underwent radical surgery for SCC of thyroid with tumor thrombosis in the IJV. RESULTS: These cases rapidly developed local recurrences and distant metastases and died within 10 months after surgery. CONCLUSIONS: IJV tumor thrombosis originated from SCC apparently reflects extremely aggressive state of the tumor. Recognition and precaution to this condition is essential for the development of a clinically effective treatment strategy.

A case of peritoneal metastasis during treatment for hypopharyngeal squamous cell carcinoma.

BACKGROUND: Advanced head and neck squamous cell carcinomas frequently develop distant metastases to limited organs, including the lungs, bone, mediastinal lymph nodes, brain, and liver. Peritoneal carcinomatosis as an initial distant metastasis from hypopharyngeal squamous cell carcinoma is quite rare. CASE PRESENTATION: A 75-year-old man diagnosed with hypopharyngeal squamous cell carcinoma and his clinical stage was determined as T2N2cM0. Notably, the right retropharyngeal lymph node surrounded more than half of the right internal carotid artery. Concomitant conformal radiation therapy was administered for the primary hypopharyngeal lesion, and the whole neck and tumor response was evaluated at this point according to our algorithm-based chemoradioselection protocol. As the tumor responses at both the primary and lymph nodes were poor, with the right retropharyngeal lymph node in particular demonstrating mild enlargement, we performed a radical surgery: pharyngolaryngectomy, bilateral neck dissection, and reconstruction of the cervical esophagus with a free jejunal flap. Then, postoperative CRT was performed. During these therapies, the patient developed a fever and mild abdominal pain, which was associated with an increased C-reactive protein level. Contrast-enhanced computed tomography from the neck to the pelvis demonstrated mild peritoneal hypertrophy and ascites with no evidence of recurrent and/or metastatic tumor formation. We initially diagnosed acute abdomen symptoms as postoperative ileus. However, cytological examination of the refractory ascites resulted in a diagnosis of peritoneal carcinomatosis. Owing to rapid disease progress, the patient died 1.5 months after abdominal symptom onset. CONCLUSIONS: The present case is the second reported case of head and neck squamous cell carcinoma with peritoneal carcinomatosis as an incipient distant metastasis. Therefore, peritoneal carcinomatosis should be considered a differential diagnosis when acute abdomen is noted during treatment for head and neck cancers.

A case of hypopharyngeal cancer with stenosis, perforation, and pyogenic spondylitis development after chemoradiotherapy.

INTRODUCTION: Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. PRESENTATION OF CASE: A 65-year-old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. DISCUSSION: Chemoradiotherapy-induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. CONCLUSION: Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case.

[Spindle Cell Carcinoma of the Head and Neck: A Report of 6 Cases].

Spindle cell carcinoma of the head and neck is a rare neoplasm. We at Kyushu Cancer Center experienced 6 cases of spindle cell carcinoma which accounted for 0.9% of all cases of head and neck squamous cell carcinoma. These cases presented with the characteristic clinical presentation, such as a particular form (polypoid and exophytic) and difficulty of pathological diagnosis. For treatment, surgery was performed in the main, but in one case of hypopharyngeal cancer chemoradiotherapy was undertaken. Spindle cell carcinoma exhibits a poor prognosis, compared with the other squamous cell carcinomas. However for the moment, 4 of 6 cases are surviving, and disease free. We will require long-term monitoring of these cases.

Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

BACKGROUND: At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies. RESULTS: The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group. CONCLUSIONS: CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival.

Utility of algorithm-based chemoradioselection in the treatment for advanced hypopharyngeal carcinoma.

BACKGROUND: Current organ-preserving dose-intensified modalities have apparently reached the limit of human tolerance. To optimize the therapeutic ratio, we evaluated the utility of a chemoradioselection strategy for the treatment of advanced hypopharyngeal carcinoma. METHODS: Fifty-five patients with advanced hypopharyngeal carcinoma were enrolled in our algorithm-based protocol. After 40 Gy of concurrent chemoradiation therapy (CCRT), patients who were chemoradioselected (chemoradioselected group, complete response [CR] at the primary site) received further 30 Gy of CCRT up to 70 Gy, whereas the remaining nonchemoradioselected (nonchemoradioselected group) patients underwent radical surgery. RESULTS: Based on this algorithm, 27 patients were chemoradioselected and 28 nonchemoradioselected. The 5-year cumulative disease-specific and overall survival (OS) rates were 76% and 65%, respectively. The chemoradioselected group demonstrated favorable laryngoesophageal dysfunction-free survival (77% at 3 years). CONCLUSION: Although preliminary, our results indicate that algorithm-based chemoradioselection may provide a novel platform for improving the treatment of advanced hypopharyngeal carcinoma by providing the complete advantages of CCRT and radical surgical resection.

[A case of squamous cell carcinoma of the hard palate in a patient with basal cell nevus syndrome].

Basal cell nevus syndrome is an autosomal dominant disorder characterized by the developmental malformations and its carcinogenic nature. This syndrome shows various symptoms of multiple cutaneous basal cell carcinoma, ketatocystic odontogenic tumors, and inborn abnormalities in the bone and skin. Although basal cell nevus syndrome itself is a rare disorder, we experienced a very rare case in which squamous cell carcinoma of the oral cavity developed, and not cutaneous basal cell carcinoma. Only 4 similar cases have been reported in the English literature. The patient was a 33-year-old woman. She was diagnosed as having squamous cell carcinoma of the hard palate, and basal cell nevus syndrome in our hospital. The patient underwent surgery for squamous cell carcinoma of the hard palate, with postoperative chemoradiothetrapy. Since patients with this syndrome tend to form basal cell carcinoma when exposed to X-ray radiation, we perform radiotherapy with care.

[Clinical study on 72 cases of adenoid cystic carcinoma].

We reviewed 72 cases treated in our hospital for adenoid cystic carcinoma of the head and neck during the 37 years between 1972 and 2009. The disease-specific survival rate at 3, 5, 10, 15, and 20 years was 76%, 70%, 46%, 33%, and 33%, respectively so survival rate had decreased gradually to 15 years. There was no significant difference in the survival rate of primary site, but T3 & T4 disease indicated a worse prognosis, and patients with lymph node positive findings tended to have a worse prognosis. The loco-regional control rate was 65% at 5 years, but after that, it continued to decrease, and the loco-regional control rate at 15 years was 31%. In addition, the median of the period for loco-regional recurrence was 93 months, with the longest time being 168 months. The relatively long lapse was traced to recurrence. The rate of absence of distant metastasis was 54% at 5 years, but after that, it continued to decrease, with the rate at 20 years was being 22%. The median time of survival after patients tested positive for distant metastasis was 25 months, with longest recognized period being 216 months. The long-term prognosis of adenoid cystic carcinoma is generally poor, so a long-term follow-up is necessary.

[Clinical analysis of mandibular osteoradionecrosis].

Radiotherapy thought vital in treating head and neck cancer, occasionally causes seriously local complications such as mandibular osteoradionecrosis (ORN). An analysis of mandibular ORN cases showed 16 in 638 subjects treated by radiotherapy, for an ORN rate of 2.5%. This rate was highest in subjects with oral cancer excluding the tongue, administered 81 Gy radiation dose, using X-ray plus electronic beams. 8 cases of ORN occurred within 1 year following radiation, and the 8 others within 5 years. Preservation treatment was successful in 44% of ORN cases, including surgery, for which the rate of final cure was 63%. With case of cancer recurrence, the rate was 25%. In 2 subjects dying of aspiration pneumonia, the cause should be a particular point for reflection. Radiotherapy involving mandibular bone should include special consideration related to the radiation source, radiation dose. Once ORN occurred, we should take care of the mixed cancer and dysphagia in the treatment.

[A clinical study of nonsquamous cell carcinoma of the nasal and paranasal sinuses].

We evaluated the efficacy of multimodality therapy for nonsquamous cell carcinoma (salivary carcinoma) of the nasal and paranasal sinuses. We retrospectively analyzed 28 patients with nonsquamous cell carcinoma of the nasal cavity and paranasal sinuses between 1972 and 2005. Primary sites were the maxillary sinus in 20 patients, ethmoidal sinus in 1, and the nasal cavity in 7. Pathology included adenocarcinoma in 5, mucoepidermoid carcinoma in 4, adenoid cystic carcinoma in 18, and adenosquamous carcinoma in 1. Five-year survival was 55% in all cases, 50% in the maxillary and ethmoidal sinuses, and 71% in the nasal cavity. Adenoid cystic carcinoma recurrence persisted over the five years following primary treatment and salvage after recurrence was 0%. Multimodality therapy decreased primary-site recurrence more than nonmultimodality therapy. Multimodality therapy thus appears useful in the primary treatment of nonsquamous cell carcinoma in the nasal cavity and paranasal sinuses.

[The present situation of neoadjuvant therapy for head and neck carcinoma].

Cisplatin and infusional 5-fluorouracil were most commonly used as neoadjuvant chemotherapy or induction chemotherapy for squamous cell carcinoma of head and neck (SCCHN). But current analysis of neoadjuvant chemotherapy trials in head and neck cancer have not demonstrated a survival benefit for the use of induction therapy. Taxanes are an effective anti-cancer drug for SCCHN. New regimens including Taxanes as neoadjuvant chemotherapy for SCCHN are recommended.

Electroencephalographic changes during intravenous olfactory stimulation in humans.

The intravenous olfaction test with thiamin propyl disulfide (TPD) is a simple procedure widely used in Japan. An olfactory stimulus is provided by intravenous injection of TPD (2 ml) over the course of 20 sec. The subject smells n-propyl mercaptan (a decomposition product of TPD discharged from the blood into alveoli) in expired air after treatment. In this preliminary study we recorded electroencephalograms (EEGs) in normal subjects during three stages: 1) eyes-closed rest (prestimulus), 2) olfactory sensation after TPD injection, and 3) disappearance of sensation. In each of these stages, we calculated and compared EEG powers according to the band components of each electrode position. This study was designed a) to evaluate by frequency analysis EEG changes during olfactory sensation after TPD injection, and b) to identify the most significant changes in EEG power according to frequency band and electrode location. During the intravenous olfactory stimulation, alpha 2 and beta 2 waves were activated over the frontal and temporal regions. After disappearance of olfactory sensation, these waves decreased in the same regions. EEG powers returned to prestimulus levels.