Surgical approach through the anterior scalene muscle resection for invasive tumours in the supraclavicular fossa (with video).

BACKGROUND: The supraclavicular fossa contains many vital organs to be preserved, such as the brachial plexus, subclavian artery and vertebral artery. Various surgical methods have been reported. However, no well-standardized surgical procedure has been established. METHODS: Between 2010 and 2020, we performed 28 surgical treatments of the superior mediastinum and supraclavicular fossa. Of these, we retrospectively reviewed seven cases of supraclavicular invasion using a unified surgical technique in which the anterior scalene muscle was resected, and the inter-scalene triangle was approached. RESULTS: We performed claviculectomy in four cases and a transmanubrial approach in three cases. In all cases, by resecting the anterior scalene muscle, the brachial plexus, subclavian artery and vertebral artery were preserved. There were no critical postoperative complications other than tracheostomy and lymphatic leakage. Median bleeding amount and operative time were 438 (range; 76-1144) ml and 328 (range; 246-615) minutes, respectively. CONCLUSIONS: The anterior scalene muscle resection method might be a safe and standardized method for preserving the brachial plexus, subclavian artery and vertebral artery.

Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland.

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes-a case of "high-grade transformation" and 1 "possessing a novel partner gene for EWSR1." We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the "high-grade transformation," harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4-fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1-fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the "whole-genome doubling" and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with "high-grade transformation." Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, "high-grade transformation" and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

BACKGROUND: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. METHODS: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. RESULTS: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. CONCLUSION: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan.

BACKGROUND: Head and neck mucosal melanomas are rare malignancies. Although the prognosis is poor owing to the high incidence of distant metastases, locoregional control remains important. It is difficult to obtain results in a large cohort because of its rarity. This study aimed to elucidate the survival outcomes of patients with head and neck mucosal melanoma treated with surgery in Japan. METHODS: Patients with head and neck mucosal melanoma who were surgically treated between 2007 and 2021 at the National Cancer Center Hospital were retrospectively analyzed. RESULTS: A total of 47 patients were included in this study. The 5-year overall survival, disease-specific survival, locoregional control and relapse-free survival rates were 42%, 50%, 79% and 13%, respectively. The disease-specific survival of the oral mucosal melanoma group was significantly better than that of the sinonasal mucosal melanoma group (5-year disease-specific survival rate: 70% versus 37%, respectively; P = 0.04). Multivariate analyses revealed that sinonasal mucosal melanoma were independently significant adverse prognostic factor, for overall survival and disease-specific survival. Patients with oral mucosal melanoma patients had a higher incidence of lymph node metastasis than those with sinonasal mucosal melanoma patients (P < 0.0001). CONCLUSION: This study demonstrated the survival outcomes of the largest cohort of patients with head and neck mucosal melanomas treated surgically at a single institution within the past 20 years in Japan. We found that survival outcomes and incidence of nodal metastases varied by site.

Comparison of survival outcomes between adolescent and young adults and older adults with tongue squamous cell carcinoma: a nationwide database study using the head and neck cancer registry of Japan.

BACKGROUND: This study aimed to evaluate the prognostic outcome for adolescent and young adult (AYA) generation patients with tongue squamous cell carcinoma (TSCC). METHODS: Data were obtained from the Head and Neck Cancer Registry of Japan, and patients who were newly diagnosed with TSCC from 2011 to 2014 were extracted. We compared the clinical parameter and survival of the ≤ 39 years old (AYA) patient group with the 40-79 (non-AYA) group. Propensity score matching (PSM) was used for survival analyses. RESULTS: Our cohort included 2221 patients with TSCC. AYA and non-AYA groups consisted of 258 and 1963 patients, respectively. The AYA group has a larger proportion of females than the non-AYA group (P < 0.001). Following PSM, both overall and disease-specific survival of the AYA group was significantly longer than those of the non-AYA group (P = 0.009 and P = 0.04, respectively). CONCLUSION: We demonstrated the survival superiority of AYA patients with TSCC compared to older adult patients. Therefore, our study results may reduce this anxiety by providing patients with appropriate information of prognosis for AYA patients with TSCC.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.

Uniform infection screening allowed safe head and neck surgery during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: The purpose of this study was to determine whether a uniform infection screening protocol could be used to safely perform head and neck cancer surgery during the coronavirus disease 2019 pandemic and clarify how surgical treatment changed compared with the pre-pandemic period. MATERIALS AND METHODS: During the unprecedented coronavirus disease 2019 pandemic in Tokyo, we continued providing head and neck cancer care, guided by our own uniform screening protocol. In this study, medical records of 208 patients with head and neck malignancy, who underwent surgical treatment at our hospital during the first and second wave of pandemic for each 2-month period (first wave: 30 March 2020-30 May 2020, second wave: 14 July 2020-14 September 2020) and the 2-month pre-pandemic period (30 October 2019-30 December 2020), were analysed. RESULTS: A total of 133 patients were admitted for surgical treatment and all, except six patients with emergency tracheostomy, were screened according to the protocol. As a result, all 127 patients received surgical treatment as planned, and all 1247 medical staff members involved in the surgeries were uninfected by severe acute respiratory syndrome coronavirus 2. During the first wave of pandemic, 20% reduction of head and neck surgery was requited; however, restrictions of surgery were not necessary during the second wave. Surgical procedure, length of hospitalization, postoperative complications and number of medical staff were unchanged compared with pre-pandemic period. CONCLUSION: Our data indicate that continuation of head and neck anticancer surgical treatment in an epidemic area during the coronavirus disease 2019 pandemic were safe and feasible, if adequate and strict preventive measures are vigorously and successfully carried out.

Pull-through resection without free-flap reconstruction for lateral wall oropharyngeal cancer.

BACKGROUND: While transoral robotic surgery (TORS) is widely used for the management of lateral wall oropharyngeal carcinomas (OPC), open surgical techniques are still used in some cases. A pull-through method for open surgical resections of OPC has recently been introduced. We improved on this method by eliminating the need for subsequent free-flap reconstruction. METHODS: 16 patients with lateral wall OPC underwent pull-through resections. After resection, we used the digastric muscle, stylohyoid muscles, submandibular gland and the surrounding tissues to block the neck and oral cavity and to avoid reconstruction. RESULTS: This novel technique was performed without major complications or morbidities. The average post-operative hospital stay was 14.6 ± 6.1 days, and the average duration until initiation of oral intake post-operation was 6.5 ± 2.9 days. Oncological outcomes, post-operative course and function were acceptable. CONCLUSIONS: Our novel method provides an efficient and less invasive surgical technique than conventional open approaches.

All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. METHODS: Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as "p53 adverse function" and "p53 favorable function" based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher's exact test. RESULTS: Multivariate analysis identified "p53 adverse function" as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the "p53 adverse function" group demonstrated significantly higher local recurrence rate than the "p53 favorable function" group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. CONCLUSIONS: All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.

Common carotid artery ligation at the proximal side before rupture in patients with ligation or occlusion of the external carotid artery at risk of carotid blowout syndrome.

BACKGROUND: Carotid blowout syndrome (CBS) is among the fatal complications in head and neck cancer treatment. However, the optimal treatment for CBS has not been established yet. This study aimed to describe our experience with two patients at high risk of CBS who underwent common carotid artery (CCA) ligation at the proximal side of the bleeding point under local anesthesia and before CCA rupture, and to review and compare the medical records of these two patients against 10 CBS cases treated in our department. METHODS: The institutional electronic medical record was searched, and clinical information was extracted for all patients who showed CBS from 2007 to 2017. Our treatment method was performed as follows. Ligation of the proximal side of the CCA was performed under local anesthesia. The CCA was identified and clamped with two bulldog forceps for 10 minutes to check for any adverse neurological symptoms. Subsequently, the CCA was ligated using 2-0 silk threads and sutured with an absorbable suture between the silk threads. However, ligation or occlusion of the external carotid artery by previous treatment is a prerequisite for this method. RESULTS: Eight patients received interventions, with six patients undergoing prophylactic interventions before rupture. Four patients who did not undergo treatment died owing to CBS. Two patients who underwent treatment with the novel method did not experience re-bleeding, but their conditions deteriorated owing to cancer progression. CONCLUSION: The present method is one of the treatment choices for CBS, especially in patients with an 'impending' risk of CBS.

The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma.

BACKGROUND: TP53 is the most frequently mutated gene in human cancers. Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). However, the relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. The current study aimed to evaluate TP53 mutation status as a predictive biomarker in patients with HPSCC. METHODS: We retrospectively reviewed the clinical charts of 57 HPSCC patients treated with initial surgery between 2008 and 2014. TP53 mutation status was determined by Sanger sequencing, and patients were classified into wild-type, missense mutation, and truncating mutation groups. Additionally, p53 expression was determined using immunohistochemistry in surgical specimens. RESULTS: TP53 mutations were identified in 39 (68%) patients. The 3-year disease-specific survival (DSS) rate of wild-type, missense mutation, and truncating mutation group were 94%, 61%, and 43%, respectively. The TP53 mutation group displayed significantly worse DSS and overall survival rates than the wild-type group (P = 0.01 and P = 0.007, respectively). Multivariate analyses revealed that the presence of TP53 mutations and ≥4 metastatic lymph nodes were independent adverse prognostic factors for HPSCC. p53 immunopositivity was detected in 22 patients, including 5 (28%) and 17 (71%) patients in the wild-type and missense mutation groups, whereas none of the patients with truncating mutation exhibited p53 immunopositivity (P = 0.0001). CONCLUSION: The TP53 mutation status correlated with poor prognosis in surgically treated HPSCC patients. Specifically, truncating mutations which were not detected by p53 immunohistochemistry were predictive of worst survival.

Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma.

OBJECTIVES: Temporal bone squamous cell carcinoma (TSCC) is a rare malignancy. Due to its low incidence rate, studies involving TSCC treatment are limited. The aim of this study is to define the prognostic factors of surgery for TSCC by evaluating our clinical experience. METHODS: We reviewed the clinical charts of patients presenting at the University of Tokyo Hospital between 2001 and 2014 and identified 33 patients with TSCC who had been treated with surgery as initial curative treatment. RESULTS: Lateral and subtotal temporal bone resections were performed in 17 and 16 patients, respectively. The 5-year disease-specific and overall survival rate were 71 and 62%, respectively. The significant poor prognostic factors were pathological T4 (P = 0.03), dural invasion (P = 0.008), temporomandibular joint invasion (P = 0.04), and a positive surgical margin (P = 0.009). CONCLUSION: We demonstrated that the outcome of curative surgery for TSCC as initial treatment was favorable. However, because of the difficulty to ensure an adequate or clear surgical margin due to anatomical complexity, the surgical indication for T4 TSCC with temporomandibular joint invasion should be reconsidered.

Clinical Value of the Epstein-Barr Virus and p16 Status in Patients with Nasopharyngeal Carcinoma: A Single-Centre Study in Japan.

BACKGROUND: The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC). METHODS: We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA. RESULTS: Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically >60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (<60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival. CONCLUSION: In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous.

Human Papillomavirus 16 Physical Status and the TP53 Codon 72 Polymorphism in Japanese HPV-Positive Oropharyngeal Cancer Patients.

BACKGROUND: In human papillomavirus (HPV)-induced carcinogenesis, the arginine (Arg) allele of the TP53 codon 72 polymorphism binds more efficiently to the HPV E6 oncoprotein than the proline (Pro) allele. We investigated the physical status of HPV-16 DNA and the TP53 codon 72 polymorphism in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Tumor samples from 70 p16-positive OPSCC patients were tested for HPV-16 physical status by examining the E2 and E6 open reading frames. The TP53 codon 72 polymorphism was screened by direct sequencing. RESULTS: Of 70 patients, 53 were E6 positive, 29 had integrated forms of HPV-16 DNA, and 24 had mixed or episomal forms. Furthermore, 44 carried the Arg/Arg or Arg/Pro genotype, 3 carried the Pro/Pro genotype, and in 6 patients we were unable to obtain sequencing data. CONCLUSIONS: HPV-16 physical status was heterogeneous in our OPSCC patients. Most OPSCC patients had the TP53 Arg/Arg or Arg/Pro genotype.

Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.

OBJECTIVE: In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan. METHODS: Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus. RESULTS: In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status. CONCLUSION: p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status.

Disease control and clinicopathological prognostic factors of total pharyngolaryngectomy for hypopharyngeal cancer: a single-center study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is a conventional and standard surgical method for locoregional control of advanced hypopharyngeal cancer (HPC). This study aimed to define the clinicopathological prognostic factors of TPL by evaluating our surgical experience of TPL in the treatment of HPCs. METHODS: We retrospectively reviewed the clinical charts of patients with HPC who were treated between 1995 and 2011 at the University of Tokyo Hospital and enrolled 119 patients who underwent TPL as an initial curative treatment. RESULTS: The mean follow-up period was 46 months (range, 2-164 months). The 5-year overall survival (OS), disease-specific survival (DSS), locoregional control rates, and relapse-free survival for all patients were 44, 53, 76, and 50 %, respectively. In multivariate analysis, the number of ≥4 metastatic lymph nodes (LNs) was a significant poor prognostic factor for both OS and DSS (p = 0.03 and p = 0.01). Patients with moderate to severe comorbidities had poor prognoses for OS (p = 0.002). In addition, patients with the number of ≥4 metastatic LNs had a higher incidence of distant metastases (p < 0.0001). CONCLUSIONS: The locoregional control rate following TPL was acceptable and the number of metastatic LNs was associated with the incidence of distant metastases.

[Retrospective Study of Laryngeal Preservation Treatment for Hypopharyngeal Carcinoma with Transoral Resection or Induction Chemotherapy].

We have performed transoral surgical resection for patients with T1/T2 hypopharyngeal cancer and induction chemotherapy with docetaxel for patients with T2/T3 disease. The patients were analyzed in order to determine the current situation of larynx preservation in patients with hypopharyngeal cancer. The data of a total of 83 patients with hypopharyngeal cancer were analyzed retrospectively. The primary subsites were : pyriform sinus (PS) in 61 patients, posterior wall (PW) in 13 patients, and postcricoid (PC) in 9 patients. The number of patients classified as having T1, T2, T3 and T4 disease were 14, 29, 23 and 17, respectively. The main therapies employed in the patients were as follows: transoral surgical resection plus radiation therapy for T1 disease, radiation therapy, induction chemotherapy, and partial resection for T2 disease, induction chemotherapy, radiation therapy, and pharyngo-laryngoesophagectomy for T3 disease, and pharyngo-laryngoesophagectomy plus induction chemotherapy for T4 disease. The 5-year larynx preservation rates in the patients with T1, T2, T3 and T4 disease were 100%, 73%, 39% and 35%, respectively. Our method was able to improve the larynx preservation rate without having any adverse effect on the survival rate. However, the strength of treatment for T 3 disease needs to be improved, because a large number of recurrences and deaths due to the primary disease were encountered in this patient group.

[Retrospective Study of Induction Chemotherapy and Concurrent Chemoradiation Therapy for Oropharyngeal Cancer].

We carried out this study to clarify the treatment outcomes and problems associated with induction chemotherapy (using taxotere, cisplatin and 5-FU [TPF therapy]) and chemoradiotherapy in patients with oropharyngeal cancer. The data of 44 patients receiving their initial treatment for oropharyngeal cancer (including 2, 9 and 33 patients with stage II, stage III and stage IV disease, respectively, and 31, 8 and 3 patients with side wall, front wall and upper wall (soft palate and uvula) involvement) were examined. Of the 44 patients, 33 received induction chemotherapy and 11 received chemoradiotherapy. The feasibility, incidence of neutropenia, response rate, and 3 year disease-specific survival rate in the induction chemotherapy group vs. chemoradiotherapy group were 70%, 88%, 82% and 73%, respectively, vs. 63%, 91%, 82% and 55%, respectively. A statistically significant difference in the 3-year disease-specific survival rate was seen between the p16-positive and p16-negative patients in the induction chemotherapy group: while the rate was 100% in the p16-positive patients, it was only 51% in the p16-negative patients (p=0.004). Of the patients undergoing chemoradiotherapy, 3 developed mandibular osteomyelitis, which was considered as one of the important problems associated with this therapy.

Negative human papillomavirus status and excessive alcohol consumption are significant risk factors for second primary malignancies in Japanese patients with oropharyngeal carcinoma.

OBJECTIVE: To determine the clinical significance of human papillomavirus subclinical infection in patients with oropharyngeal squamous cell carcinoma in Japan. METHODS: Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify samples of oropharyngeal squamous cell carcinoma. We performed in situ hybridization for human papillomavirus-DNA to identify subclinical human papillomavirus infections among patients with oropharyngeal squamous cell carcinoma. Second primary malignancies were classified as synchronous, if identified within 6 months of the diagnosis of the first tumor, or metachronous, if identified after this 6-month period. Univariate and multivariate analyses using logistic stepwise regression models were performed to identify factors associated with synchronous and metachronous second primary malignancy. RESULTS: Of the 150 patients with oropharyngeal squamous cell carcinoma, 14% (21/150) and 20.7% (31/150) developed synchronous and metachronous second primary malignancies, respectively. Esophageal carcinoma was the most frequent second primary malignancy (10/21 for synchronous and 10/31 for metachronous second primary malignancies). The prevalence of oropharyngeal squamous cell carcinoma positive for human papillomavirus was 31% (47/150). Multivariate analysis identified alcohol consumption as a significant unfavorable risk factor for the occurrence of synchronous second primary malignancy, and either a human papillomavirus-negative status or N0 classification was a significant unfavorable risk factor for the occurrence of metachronous second primary malignancy. CONCLUSIONS: Evaluation of the human papillomavirus status may help identify patients at risk for metachronous second primary malignancy. Upper gastrointestinal endoscopy is very important in the diagnosis of oropharyngeal squamous cell carcinoma among heavy drinkers in Japan.