Early Predictors of Fistula Formation Following Head and Neck Reconstruction.

BACKGROUND: Salivary fistula formation is a common and serious complication following head and neck reconstruction. Because it can cause delayed wound healing and infection and carotid artery rupture in severe cases, hence, early detection and treatment are crucial. This study was designed to identify early predictors of postoperative fistula formation. METHODS: We conducted a retrospective analysis of patients who underwent head and neck reconstruction between 2015 and 2022. Body temperature, serum white blood cell (WBC) count, and serum C-reactive protein (CRP) levels were assessed until postoperative day (POD) 14 and compared between patients with and without fistula. RESULTS: In this study, 200 patients were included. No significant differences in body temperature and WBC count were observed between the two groups during the entire study period. CRP levels after POD2 were higher in the fistula group than in the without fistula group. From the receiver operating characteristic curves comparing the two groups, the best cutoff level for CRP was 6.27 mg/dL from POD7 to POD8, with 77.1% sensitivity, 69.8% specificity, and 90.1% negative predictive value. CONCLUSION: CRP is a valuable predictor of fistula formation following head and neck reconstruction. The course of CRP levels in patients with fistulas remains consistently elevated compared to patients without fistulas, and it is particularly useful for the exclusion diagnosis of fistula.

Platinum resistance and sensitivity in recurrent/metastatic head and neck squamous cell carcinoma.

OBJECTIVE: For patients with recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), platinum-free interval (PFI)-based differences in the effectiveness of rechallenge with platinum-based chemotherapy (PBCT) remain unknown. We aimed to evaluate the difference in platinum sensitivity based on PFI in R/MHNSCC. METHODS: We retrospectively examined 80 patients with R/MHNSCC who underwent PBCT between 2001 and 2020. Treatment efficacy was compared between patients with prior PBCT for treatment of recurrence/metastasis or concurrent chemoradiotherapy during radical treatment (rechallenge group) and those without (control group). Patients with prior PBCT (rechallenge group) were stratified by PFI. PFI was defined as the period from the last dosing date with the previous platinum agent to rechallenge with PBCT. RESULTS: Of 80 patients, 55 had been with prior PBCT (rechallenge group) and 25 had been without prior PBCT (control group). The rechallenge group was divided into three groups: PFI <6 months (10), PFI 6-11 months (17), and PFI ≥12 months (28). The PFI <6-month group had shorter overall survival (p=0.047, the log-rank test) and lower disease control rate (p=0.02, Fisher's exact test) than the control group. The PFI 6-11- and ≥12-month group outcomes did not significantly differ from those of the control group. CONCLUSIONS: Patients with PFI <6 months tend to have a poorer prognosis after rechallenge with PBCT than patients without prior PBCT, suggesting that PFI 6 months may be considered as a threshold of platinum resistance and rechallenge with PBCT may be a valid option in PFI ≥6 months.

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial.

PURPOSE: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.

Pathological Level VI Lymph Node Metastasis in Clinical N3b Pyriform Sinus Squamous Cell Carcinoma.

OBJECTIVE: The frequency of metastasis to level VI lymph nodes in advanced pyriform sinus squamous cell carcinoma (PSSCC) is unknown. We intended to analyze the clinical features and pathological presence or absence of level VI lymph node metastasis in patients with PSSCC. METHODS: The data of 270 patients with previously untreated hypopharyngeal squamous cell carcinoma from 2006 to 2016 were obtained. Patients who underwent pharyngolaryngectomy for the pyriform sinus subsite with a curative intent with level VI dissection were included. We retrospectively analyzed the clinical Tumor-Node (TN) status (TNM classification of malignant tumors, eighth edition) and the presence or absence of pathological level VI lymph node metastasis. RESULTS: A total of 34 patients were included. Eight patients (24%) had pathological level VI lymph node metastasis. The rate of pathological level VI lymph node metastasis was directly proportional to the clinical N status (P = .0002, Chi-square test for trend). In all, 5 patients with cN2b- 3 were classified as cN3b. Ipsilateral pathological level VI lymph node metastasis was observed in 1 patient, and bilateral metastasis was observed in 3 patients. There was no association between clinical T status or pyriform sinus apex invasion and pathological level VI metastasis (both P > .99, Fisher's exact test). CONCLUSIONS: PSSCC with cN3b is prone to bilateral level VI metastasis. We recommend that patients with PSSCC with cN3b should undergo bilateral level VI lymph node dissection.

Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0-1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24-68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options.This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

Sites of invasion of cancer of the external auditory canal predicting oncologic outcomes.

BACKGROUND: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor. METHODS: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan-Meier method were used to focus on the tumor invasion sites and overall survival of the patients. RESULTS: The 3-year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan-Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes. CONCLUSION: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes.

Closing an Intractable Tracheoesophageal Fistula Caused by a Tracheoesophageal Shunt Using a Myocutaneous Flap and a Hinged Flap With Skin Graft in a Two-Step Procedure.

Total laryngectomy involves removal of the vocal cords resulting in the loss of vocal function. After laryngectomy, the patient's vocal function can be restored in several ways, including the insertion of a tracheoesophageal (TE) shunt. A TE shunt is considered an effective means of restoring speech due to its high efficacy, low requirement for training, and no need for any equipment while speaking. However, complications such as saliva inflow into the trachea, caused by the widening of the shunt opening, have also been reported. Moreover, the optimal treatment for an enlarged fistula has not yet been established. A fistula may also form at sites of hypopharyngeal reconstruction with free jejunal transplantation. Following its formation, the influx of saliva, infections, and pressure exerted by the act of swallowing make a fistula resistant to closure, and most patients require closure surgery using myocutaneous flaps. We encountered a case where an intractable TE fistula formed due to a TE shunt after the patient underwent total pharyngolaryngeal resection for hypopharyngeal cancer and hypopharyngeal reconstruction with a free jejunum flap. Since the optimal method for the TE fistula closure remains uncertain, we attempted to close the fistula according to the fistula closure of the free jejunal transplantation. Failure to close a TE fistula using a myocutaneous flap necessitates a re-closure procedure. However, because the surgical field around the trachea can be limited in such patients, creating an additional myocutaneous flap may not be feasible. In addition to the myocutaneous flap, ventilation control using a conventional intubation tube may further narrow the surgical field during the re-closure surgery. Based on our experience and existing literature, in this article, we summarize several ways of managing TE fistula when the surgical field around the trachea is limited.

Multi-institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal in Japan.

OBJECTIVES: This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients. METHODS: This is a multi-institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent. RESULTS: Overall 5-year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5-fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups. CONCLUSION: Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E870-E874, 2021.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator's choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141).

BACKGROUND: The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial. METHODS: The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed. RESULTS: The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs. CONCLUSIONS: Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy. CLINICAL TRIAL REGISTRATION: NCT02105636.

Nutritional support dependence after curative chemoradiotherapy in head and neck cancer: supplementary analysis of a phase II trial (JCOG0706S1).

OBJECTIVES: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272). METHODS: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome. RESULTS: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose. CONCLUSIONS: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.

A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition).

A number of major modifications were made to the classification of head and neck carcinomas in the eighth edition of the American Joint Committee on Cancer, Cancer Staging Manual and Union for International Cancer Control TNM classification of Malignant Tumors. These modifications were aimed at improving the prognosis prediction accuracy of the system. In this article, we review the new edition of the TNM classification system. Among the several changes in the new system, a separate algorithm for p16-positive oropharyngeal carcinoma was included, as were new chapters on 'Head and Neck Skin Carcinoma' and 'Unknown Primary Carcinoma-Cervical Nodes.' Changes to Tumor (T) classification were made by introducing the depth of invasion of oral carcinoma, whereas changes to Node (N) classification were made by adding extra-nodal extension. It is believed that these changes will help improve the accuracy of the system in the prediction of prognosis. However, it is necessary to verify their validity through further clinical research.

Clinical impact of cachexia in unresectable locally advanced head and neck cancer: supplementary analysis of a phase II trial (JCOG0706-S2).

OBJECTIVES: To evaluate the clinical impact of cachexia, defined by the combination of albumin and C-reactive protein levels, in patients with unresectable locally advanced head and neck squamous cell carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706. METHODS: Forty-five patients received radiation for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. The present analysis was conducted in 44 patients with available data. The association between treatment efficacy and cachexia was investigated. Pretreatment cachexia was defined as a serum albumin level of less than 3.5 mg/dl and C-reactive protein level of more than 0.5 mg/dl. RESULTS: Among the 44 patients, 5 patients had cachexia. On comparison with the cachexic and non-cachexic patients, the percentage of clinical complete remission (20% vs 72%), time to treatment failure at 3 years, (20% vs 53%) and proportion of treatment completion (20% vs 79%) were statistically worse in the cachexic patients, while overall survival, progression-free survival and local progression-free survival at 3 years tended to be worse in cachexic patients. CONCLUSIONS: This supplementary analysis from a prospective study suggests that a pretreatment status of cancer cachexia is a prognostic factor for treatment outcomes and compliance in patients with locally advanced head and neck squamous cell carcinomas treated with chemoradiotherapy, and a candidate stratification factor in future prospective trials in this population.

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study.

BACKGROUND: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

Long-term results of Amatsu tracheoesophageal shunt: Follow-up of more than 5 years.

BACKGROUND/OBJECTIVE: The Amatsu tracheoesophageal shunt (ATES) represents a nonprosthesis surgical option for voice restoration in laryngectomized patients. However, data regarding the long-term efficacy of ATES are lacking. STUDY DESIGN: Retrospective, single-institution study. METHODS: Between 2001 and 2010, 16 patients with laryngeal cancer underwent total laryngectomy with ATES at the Hyogo Cancer Center (Akashi, Hyogo, Japan). Of these, 11 achieved long-term tracheoesophageal speech that was maintained for a follow-up exceeding 5 years (range 75-161 months; median 95 months). All patients were male and ranged from 46 to 74 years of age at the time of ATES surgery. RESULTS: Of 11 eligible patients, eight were able to speak intelligibly with ATES at last follow-up. Regarding aspiration, three patients experienced no leakage, and six experienced mild leakage of saliva without medical intervention at last follow-up. Almost all patients maintained an unchanged degree of voice quality (9 of 11) and leakage (8 of 11). CONCLUSION: The favorable voice restoration and low aspiration rates achieved in this study appear to support the long-term efficacy of ATES. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1395-1397, 2018.

A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141.

OBJECTIVES: To assess efficacy and safety of nivolumab versus investigator's choice of therapy (IC) in Asian patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Thirty-four patients from Japan, Taiwan, Hong Kong, and Korea received nivolumab 3mg/kg (n=23) every 2weeks or IC (n=11), as part of a global trial (n=361), until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS). RESULTS: Median OS was 9.5months (95% confidence interval [CI] 9.1-NR) with nivolumab and 6.2months (95% CI 2.6-NR) with IC. Seven (30.4%) patients receiving nivolumab and six (54.5%) receiving IC died. The hazard ratio (HR) for risk of death (nivolumab vs. IC) was 0.50 (95% CI 0.17-1.48). Median progression-free survival was 1.9months (95% CI 1.6-7.5) with nivolumab and 1.8months (95% CI 0.4-6.1) with IC (HR 0.57 [95% CI 0.25-1.33]). Objective response rates (complete+partial responses) were 26.1% (6/23 patients; 95% CI 10.2-48.4) for nivolumab and 0% (0/11 patients; 95% CI 0.0-28.5) for IC. Sixteen (69.6%) nivolumab-treated patients and 10 (90.9%) patients receiving IC had a treatment-related adverse event, most commonly decreased appetite (21.7%), pruritus, rash, and fatigue (17.4% each) with nivolumab, and nausea, stomatitis, and decreased appetite (27.3% each) with IC. CONCLUSION: Nivolumab demonstrated a survival advantage compared with conventional treatments in Asian patients with platinum-refractory recurrent or metastatic SCCHN, and was well tolerated. Clinical trial registration NCT02105636.

Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy.

BACKGROUND: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. METHODS: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. RESULTS: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. CONCLUSIONS: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

Bazex Syndrome with Hypoalbuminemia and Severe Ascites.

Bazex syndrome is a rare paraneoplastic dermatosis. The underlying malignancy frequently is squamous cell carcinoma of the upper aerodigestive tract or cervical lymph nodes from an unknown primary site. We report a 63-year-old man with squamous cell carcinoma of cervical lymph nodes from an unknown primary site. He developed a mass on the right side of his neck, cutaneous lesions diagnosed as Bazex syndrome, hypoalbuminemia, and severe ascites. Right neck dissection was performed. After neck dissection, not only the cutaneous lesions, but also the severe hypoalbuminemia and severe ascites were improved. Bazex syndrome may be associated with hypoalbuminemia and ascites.

Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study.

In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion-positive and fusion-negative MEC of the major salivary gland. The AREG and EGFR expression were studied by immunochemistry in 33 MEC cases of the major salivary glands. CRTC1-MAML2 fusion was tested by reverse-transcription polymerase chain reaction (23 CRTC1-MAML2 fusion-positive, 10 fusion-negative). Of 23 fusion-positive cases, AREG and EGFR overexpression were detected in 17 (73.9%) and 14 (60.9%) cases, respectively. Of 10 fusion-negative cases, AREG and EGFR overexpression were detected in 1 (10%) and 3 (30.0%) cases, respectively. There was a positive correlation between CRTC1-MAML2 fusion and AREG overexpression (P < .01), but not between CRTC1-MAML2 fusion and EGFR overexpression. The AREG overexpression was associated with a longer disease-free survival of the MEC patients (P = .042), but EGFR overexpression was not. In this study, we showed that AREG overexpression was detected more frequently in the CRTC1-MAML2 fusion-positive tumors than in fusion-negative tumors. Detection of AREG expression may be useful for identifying CRTC1-MAML2-positive MECs and as a marker for favorable prognosis.