Preoperative S-1 Therapy for Head and Neck Carcinoma During the Waiting Period Before Surgery.

BACKGROUND/AIM: In patients with squamous cell carcinoma of the head and neck (SCCHN), delayed surgery can result in poorer postoperative function and prognosis due to the growth of the tumor and extended surgery. Further, delay may even make the tumor unresectable. To prevent tumor growth during the waiting period before surgery, S-1 has been administrated preoperatively at several facilities in Japan. To date, however, the safety and efficacy of preoperative S-1 remain unclear. PATIENTS AND METHODS: We conducted a retrospective cohort study of 118 patients with SCCHN treated with S-1 before radical surgery at 2 institutions in Japan. We evaluated the safety of S-1 therapy, which was evaluated by the incidence of grade 3 or greater adverse events (AEs). The rate of achievement of non-growth of tumors was also calculated. RESULTS: Regarding safety, 125 AEs of all grades were recorded in 71 patients (60%). Of these, grade 3 AEs were detected in 3 patients (3%), and no grade 4 or 5 AEs occurred. The nongrowth rate of primary lesions and lymph node metastases was 89% and 85%, respectively. CONCLUSION: Preoperative S-1 therapy might be useful, with acceptable toxicity, on an outpatient basis in patients with SCCHN.

Resection of Parapharyngeal Space Tumors Located in the Prestyloid Compartment: Efficacy of the Cervical Approach.

BACKGROUND: Parapharyngeal space tumors are rare. Among them, tumors in the prestyloid compartment are particularly suitable for surgery; however, there are no detailed reports of such surgery and their features remain unknown. METHODS: We conducted a retrospective cohort study. For 67 surgical cases of benign tumors in this compartment, we examined the patient and tumor characteristics, fine-needle aspiration cytology (FNAC), and intraoperative details such as surgical approach, use of complete excision, and postoperative complications. RESULTS: Pleomorphic adenomas (PAs) comprised 73.1% of the lesions. The diagnostic accuracy of FNAC to differentiate benign and malignant tumors was 97.7%. Of the treated lesions, 94.0% were removed via the cervical approach alone, including all PAs. The remaining 6.0% were resected via the cervical-parotid approach. The median operative time and bleeding volume were 89 min and 50 mL, respectively. Operative time using the cervical approach was significantly shorter (p = 0.021). All cases could be treated via complete surgical excision. Postoperative complications occurred in 32.8% of patients, with transient slight facial palsy being the most common. No fatal complications occurred and 92.5% of patients had no sequelae. There was no significant association between complications and surgical approach. CONCLUSION: Based on diagnosis by FNAC, with a high accuracy rate, most benign prestyloid tumors, especially PAs, were resected using the cervical approach alone, with a shorter operative time and without severe complications.

A novel technique of arterial blood flow modification in intra-arterial chemoradiotherapy of maxillary sinus squamous cell carcinoma.

OBJECTIVES: Intra-arterial chemoradiotherapy via a superficial temporal artery is reportedly a useful organ-preserving treatment for maxillary sinus squamous cell carcinoma. This study aimed to determine whether blood flow modification facilitates sufficient drug delivery to the entire carcinoma via the maxillary artery alone, even for advanced tumors. MATERIALS AND METHODS: A retrospective study of 10 patients who were diagnosed with locally advanced carcinoma (4 [40%] at stage T3, 5 [50%] at T4a, and 1 [10%] at T4b) from August 2016 to July 2018, with tumor blood flow from both the maxillary and facial arteries, was conducted. Patients underwent intra-arterial chemoradiotherapy, which involved chemotherapy with weekly cisplatin administration (40 mg/m2) and radiotherapy (70 Gy/35 fr), with facial artery ligation. The success rate of blood flow modification, as well as its therapeutic effects and safety, were evaluated, with a median follow-up period of 14.4 months (range: 12.3-35 months). RESULTS: The blood flow surrounding the tumor was changed from both the maxillary and facial arteries to the maxillary artery alone in all patients. A median of 9 chemotherapy courses (range: 8-10) were administered; the median total cisplatin dose was 350 mg/m2 (range: 320-360 mg/m2). Radiotherapy of 70 Gy/35 fr was used to treat all patients. Grade 3 oral mucositis (80%) and irradiation field dermatitis (40%) were observed. In all patients, complete response was achieved, and local recurrence was not observed for at least 1 year. CONCLUSION: Simplifying the blood flow around the tumor facilitates more standardized intra-arterial chemoradiotherapy via a superficial temporal artery procedure.

Classification of tumors by imaging diagnosis and preoperative fine-needle aspiration cytology in 120 patients with tumors in the parapharyngeal space.

BACKGROUND: Tumors in the parapharyngeal space are rare, and preoperative diagnosis is difficult because of anatomical and histological complexity. METHODS: To evaluate the usefulness of preoperative diagnosis, we compared the classification of tumor localization in the prestyloid and retrostyloid compartments by imaging and preoperative cytological diagnosis by fine-needle aspiration cytology with the postoperative histopathological diagnosis in 120 patients with tumors in the parapharyngeal space. RESULTS: Tumors were located in the prestyloid and retrostyloid compartments in 68 and 52 patients, respectively. The majority of histopathological diagnoses in the prestyloid and retrostyloid compartments were pleomorphic adenoma and schwannoma, respectively. All malignant tumors were in the prestyloid compartment. The preoperative cytological diagnostic rate for benign or malignant tumor was 95.2%, which was not inferior to that for other head and neck lesions. CONCLUSION: Our results suggested that the preoperative classification of tumor localization and cytological diagnosis improved the accuracy of presumptive diagnosis.

Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma.

PURPOSE: Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease's rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2-positive SDC. PATIENTS AND METHODS: This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). RESULTS: Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. CONCLUSION: Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2-positive SDC, with a manageable toxicity profile.

Hypofractionated Stereotactic Radiotherapy for Auditory Canal or Middle Ear Cancer.

BACKGROUND: Stereotactic radiotherapy (SRT) may represent a new treatment option for individuals with auditory canal or middle ear cancer. METHODS: Study participants with pathologically proven ear cancer were treated with SRT (35 Gy for 3 fractions or 40 Gy for 5 fractions) as first-line therapy. When local tumor recurrence developed following SRT, subtotal temporal bone resection and postoperative chemoradiotherapy were performed as salvage treatment. Boluses were used for the initial 14 study patients. RESULTS: Twenty-nine study participants were enrolled and staged with T1 (n = 3), T2 (n = 7), T3 (n = 14), or T4 disease (n = 5). Three-year overall survival rates were 69% for T1/2 disease, 79% for T3 disease, and 0% for T4 disease. Three-year local control rates were 70% for T1/2 disease, 50% for T3 disease, and 20% for T4 disease. Grade 2 or higher dermatitis or soft-tissue necrosis occurred more frequently in study patients treated with boluses (8/14 vs 2/15; P = .02). Salvage treatment was safely performed for 12 recurrent cases. CONCLUSIONS: These results suggest that SRT outcomes are promising for patients with ear cancer (? T3 disease). The rate of toxicity was acceptable in the study patients treated without boluses. Outcomes of salvage surgery and postoperative radiotherapy following SRT were also encouraging.

Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a highly aggressive disease which often metastasizes to distant sites, and there is no established standard therapy for this systemic disease. Given that SDC is biologically similar to breast and prostate cancer, anti-androgenic receptor (AR) and anti-human epidermal growth factor receptor 2 (HER2) therapies have the potential to exert effects, not only on patients with breast and prostate cancer but also on those with SDC. METHODS: The expression levels of HER2, epidermal growth factor receptor (EGFR), Ki-67, and AR were assessed in 32 patients with SDC, and their correlations with overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively. SDC was classified into five subtypes using a method similar to that used for breast cancer. RESULTS: Anti-AR, HER2, and EGFR were positive in 23 (71.9 %), 14 (43.8 %), and 26 (81.3 %) cases, respectively. One or more of these 3 factors were positive in 30 (93.8 %) cases. The Ki-67 labeling index was greater than 15 % in all cases. While molecular status did not correlate with OS, EGFR and AR positivity were significantly associated with DFS in univariate analysis. Multivariate analysis revealed that EGFR was the only independent predictor of DFS. CONCLUSIONS: The statuses of some molecules are useful to predict DFS in patients with SDC. Ki-67 overexpression suggests that cytotoxic agents are effective for SDC. Since the majority of SDCs express AR, HER2, and/or EGFR, assessing and targeting these molecules are promising strategies to improve the prognosis of unresectable, metastatic or recurrent SDC, and a classification system according to the molecular expression status may be useful to select appropriate therapy.

Japanese Board Certification System for head and neck surgeons.

The Japan Society for Head and Neck Surgery (JSHNS) started a board certification system for head and neck surgeons in 2010. To become certified, the following qualification and experiences are required: (1) board certification as otorhinolaryngologist, (2) 2 years of clinical experience in a board-certified training facility, (3) clinical care of 100 patients with head and neck cancer under the supervision of board-certified faculty and (4) surgical experience in 50 major head and neck surgical procedures, including 20 neck dissections, under the supervision of board-certified faculty. The following scientific activities are also required during the preceding 5 years: (1) two clinical papers on head and neck cancers presented at major scientific meetings, (2) one clinical paper on head and neck cancer published in a major journal, (3) attendance at two annual meetings of JSHNS and (4) enrolment in three educational programs approved by JSHNS. The qualifying examination consists of multiple choice tests and oral examinations. A total of 151 head and neck surgeons were certified in 2010 followed by 43 in 2011 and 34 in 2012, while the membership of JSHNS dramatically increased from 1201 in 2007 to 1748 in 2013. Although the board certification system for head and neck surgeons was started only recently, it has encouraged many residents and fellows as well as established head and neck surgeons. We believe that this system will contribute to further advancement in the clinical practice for head and neck cancers in Japan.

[A site of origin histopathological study on parapharyngeal space tumors. A review of 76 cases].

Tumors of the parapharyngeal space are said to account for 0.5% of all head and neck tumors, and are thus relatively rare. We performed histopathological examination of 76 tumors of the parapharyngeal space in patients hospitalized at the International University of Health and Welfare, Mita Hospital Head and Neck Oncology and Surgery center for 6 years from July 2005 to June 2011. There were 35 men and 41 women; the patients ranged in age from 15 to 78 years with a median age of 44. We performed preoperative CT and MRI, aspiration biopsy cytology (fine needle aspiration [FNA]) and postoperative histopathology diagnosis. There were 69 benign tumors (90.8%), and 7 malignant tumors (11.8%). Among the benign tumors were 32 schwannomas (42.1%) and 28 pleomorphic adenomas (36.8%). A total of 26 tumors of prestyloid origin were pleomorphic adenomas (93.8%), and 28 tumors of poststyloid origin were schwannomas (87.5%); all 7 malignant tumors (100%) were of prestyloid origin. There were 55 patients who underwent preoperative FNA, and the proper diagnosis rate was 70.9% (39/55 case). Preoperative imaging seemed to be very useful for predicting the histopathology. Furthermore, it would be desirable for FNA to be performed preoperatively for tumors of prestyloid origin, in consideration of the likelihood of such tumors being malignant. We think that there is room for improvement in the accurate FNA diagnosis rate.

Efficacy of a new instrument for dural defect repair in anterior skull base reconstruction: a technical note.

BACKGROUND: The anterior skull base is a deep and narrow area, which makes dural repair technically challenging. The goal of this study was to demonstrate the efficacy of a new instrument for anterior skull base dural repair. METHODS: Ten patients underwent surgery via the transbasal approach, combined with either a transfacial or a transnasal endoscopic resection. The dural repair was performed prior to tumor resection, and the new instrument was used to suture the fascia lata in an underlay fashion. The repaired dural defect was then covered with a pericranial flap. RESULTS: The follow-up period ranged from 2 to 18 months, with an average follow-up time of 8.7 months. During this period, none of the patients experienced cerebrospinal fluid leakage, meningitis, tension pneumocephalus, abscess formation, or flap necrosis. CONCLUSIONS: Our findings suggest that the use of this instrument combined with the technique of suturing the fascia lata in an underlay fashion and covering it with a pericranial flap, may be an effective alternative approach to anterior skull base reconstruction.

Phase I/II study of docetaxel, cisplatin and S-1 in locally advanced, recurrent and metastatic head and neck squamous cell carcinoma.

The purpose of this study was to evaluate the maximum tolerated dose, dose-limiting toxicities and preliminary efficacy of chemotherapy with cisplatin, docetaxel and S-1 (TPS) to treat advanced head and neck squamous cell cancer. S-1 was administered orally twice daily on days 1-14 and docetaxel and cisplatin were injected intravenously on day 8, with one course lasting 4 weeks. The recommended dose obtained from a phase I study was set at docetaxel 60 mg/m(2), cisplatin 60 mg/m(2) and S-1 80 mg/m(2)/day. The phase II study revealed that the overall response rate was 81%, comprising 95% in untreated patients with localized advanced cancer and no distant metastases, 50% in untreated patients with distant metastases and 33% in previously treated patients with recurrence. The overall survival rate of untreated patients with localized advanced cancer and no distant metastases was 95% at 1 year and 64.33% at 2 years. In terms of grade 3 or higher hematotoxicity, neutropenia occurred in 100%, thrombocytotopenia in 4% and anemia in 4%. Febrile neutropenia occurred in 46%, with the rate rising to 57% in elderly patients ≥66 years. Grade 3 or higher non-hematotoxicity consisted of loss of appetite in 8%, diarrhea in 8%, hyponatremia in 13% and hypokalemia in 13%. This TPS therapy may be recommended for use as induction chemotherapy. For patients ≤65 years, the appropriate dose was docetaxel 60 mg/m(2), cisplatin 60 mg/m(2) and S-1 80 mg/m(2), whereas for those ≥66 years, it was docetaxel 60 mg/m(2), cisplatin 60 mg/m(2) and S-1 60 mg/m(2).

Craniofacial surgery for esthesioneuroblastoma: report of an international collaborative study.

Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB. Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients. Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.

[Investigation of how to prevent mucositis induced by chemoradiotherapy].

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using PA solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3. 0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44 ± 8. 0 days for the R solution group, 52 ± 18. 8 days for the P-A solution group, and 61 ± 19. 5 days for the S solution group, indicating that the R solution group significantly shortened the length of hospital stay compared to the S solution group. These results suggested that the use of an R or P-A solution may be effective in preventing oral mucositis and impaired nutrition of those undergoing chemoradiotherapy for head and neck cancer.

En bloc temporal bone resection using a diamond threadwire saw for malignant tumors.

The purpose of this study is to describe a new technique for en bloc temporal bone resection using a diamond threadwire saw (T-saw) as an alternative to cutting the temporal bone with an osteotome. This technique has been performed in 10 patients with external auditory canal and middle ear cancers without any injury to the internal carotid artery or jugular vein. The authors conclude that the use of a diamond threadwire saw after transposing the internal carotid artery anteriorly is a safe, simple, and reliable technique for en bloc temporal bone resection.

Operative management of skull base malignant tumors arising from the nasal cavity and paranasal sinus: recent strategies used in 25 cases.

Cancers of the paranasal sinuses and nasal cavity are the most common malignant tumors of the anterior and anterolateral skull base. The treatment of these tumors affecting the skull base is complex due to the significant anatomical features. We examined 25 patients, 17 males and 8 females with mean age 61 +/- 2 years. En bloc resections using anterior skull base resection, orbital resection, middle fossa resection, and combined procedures of these three resections were performed. Using a combination of adjuvant radiation and chemotherapy, we have achieved a 2-year disease-free survival rate of 90% in these cases. However, potential complications include cerebrospinal fluid leakage, meningitis, abscess formation, pneumocephalus, frontal brain contusion, trismus, and dysphagia as a functional complication. We believe that the optimal management of such malignant tumors involves a multimodal and multidisciplinary team approach. Here we present our recent institutional experience and treatment policy employed during the past 3 years.

Inflammatory pseudotumor of the parapharyngeal space: a case report.

Inflammatory pseudotumor is an idiopathic granuloma characterized by infiltrative proliferation of inflammatory cells and myofibroblastic cells, as well as locally aggressive features, clinically and radiologically mimicking a neoplastic process. The occurrence of inflammatory pseudotumor in the head and neck area is uncommon, especially in the parapharyngeal space. The case of a 54-year-old female with inflammatory pseudotumor of the parapharyngeal space is presented. The patient initially complained of hoarseness, dysarthria, aspiration, and hearing impairment. MRI disclosed an expansive soft mass in the parapharyngeal space encompassing the carotid arteries. Histopathologically, the lesions were composed of numerous plasma cells, lymphocytes, histiocytes, and spindle myofibroblastic cells, showing perineural infiltration of inflammatory cells. The patients' symptoms, including conductive hearing loss, improved dramatically with reduction in lesion size after corticosteroid treatment.

Surgical management of giant trigeminal schwannomas extending into the parapharyngeal space.

PURPOSE: Trigeminal schwannomas extending into the deep parapharyngeal space are relatively rare, and a surgical approach to such tumors has not been well established. We report four cases in which the tumors were completely removed by using a combination of three approaches. METHODS: Four patients with trigeminal schwannomas extending into the extracranial space were surgically treated using a combination of the transcervical approach, anterolateral retromaxillar pathway via gingivobuccal sulcus, and epi and interdural middle fossa approach. RESULTS: The maximum diameters of the tumors ranged from 4 to 7 cm. Three tumors extended beyond the lower end of the maxillary sinus. All tumors were completely excised. The Karnofsky performance scales after surgery were more than 90% in all patients. CONCLUSION: Although the tumors extending to the deep parapharyngeal space are difficult to completely remove via a single approach, a combined approach is useful in these huge extracranial extensions.

Outcome of craniofacial surgery in children and adolescents with malignant tumors involving the skull base: an international collaborative study.

BACKGROUND: The aim of the study was to characterize the distribution of anterior skull base (ASB) cancers in the pediatric population and to identify predictors of outcome. METHODS: This was an international study of 1307 patients undergoing craniofacial surgery for malignant tumors; 6.4% (n = 84) among these were

Craniofacial surgery for nonmelanoma skin malignancy: report of an international collaborative study.

BACKGROUND: This study examined the efficacy of craniofacial surgery (CFS) in treating locally advanced nonmelanoma skin cancer (NMSC). METHODS: One hundred twenty patients who underwent CFS for NMSC were identified from 17 participating institutions. Patient, tumor, and treatment information was analyzed for prognostic impact on survival. RESULTS: Surgical margins were negative in 74%, close in 3%, and involved in 23% of patients. Complications occurred in 35% of patients, half of which were local wound problems. Operative mortality was 4%. Median follow-up interval after CFS was 27 months. The 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were 64%, 75%, and 60%, respectively. Squamous cell histology, brain invasion, and positive resection margins independently predicted worse OS, DSS, and RFS. CONCLUSION: CFS is an effective treatment for patients with NMSC invading the skull base. Histology, extent of disease, and resection margins are the most significant predictors of outcome.