Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English  

DOI： 10.21873/cdp.10378

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancers  

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.

DOI： 10.3390/cancers16142527

Web of Science

Scopus

PubMed

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Language：English  

DOI： 10.21873/cdp.10294

PubMed

Language：Others   Publishing type：Research paper (scientific journal)  

Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. Methods: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. Results: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. Conclusion: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

DOI： 10.1186/s12885-023-11528-4

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/invivo.13318.

Language：Others   Publishing type：Research paper (scientific journal)  

Background/Aim: In recent years, individual patient cancer genomic profiling (CGP) has become more accessible, allowing determination of therapeutic strategies using driver gene mutations in cancer therapy. However, this precision oncology approach, tailored to specific patients, remains experimental. In this study, we verified the feasibility and benefit of using CGP to guide treatment of malignant head and neck tumors. We aimed to evaluate the profiling and clinical courses of patients with head and neck malignancies who underwent CGP and determine the extent to which CGP for head and neck malignancies has resulted in beneficial drug administration. Patients and Methods: We analyzed CGP results, prognosis, and drug administration status in 27 patients. These patients had completed (or were expected to complete) standard therapy or had rare cancers without standard therapy. Results: At least one somatic actionable gene alteration was seen in 25 (92.6%) patients, with a median number of actionable alterations per patient of 4 (range=0-11). Drugs in clinical trials were recommended to 22 (81.5%) patients, but none could participate. However, 3 patients (11.1%) could use approved drugs off-label based on CGP results. The most common genetic abnormality was TP53 (66.7%), with TP53 mutations leading to poor prognosis. Conclusion: CGP is clinically useful and serves as a bridge to increase the number of therapeutic options. However, candidate drugs confirmed using CGP may be ineffective when administered. Therefore, oncologists should not blindly accept CGP therapeutic recommendations but should make recommendations that lead to optimal therapies after proper verification.

DOI： 10.21873/invivo.13312

Language：Others  

Abstract

BACKGROUND

Nivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.

METHODS

Pre-treatment plasmas (N= 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N= 20) were assayed to elucidate biological implications of the PEX mRNA signature.

RESULTS

A combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%;P= 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055;P= 0.0002348). In paired samples, PEXHLA-EmRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P= 0.0191) and the dense population of tumor-infiltrating NK cells (P= 0.024) in the corresponding tumor, suggesting the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade in patients with high PEXHLA-EmRNA.

CONCLUSION

The PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs.

TRIAL REGISTRATION

This study is registered to the UMIN Clinical Trial Registry: UMIN000037029.

FUNDING

This study is partly funded by JSPS KAKENHI (Grant number JP 21436707 to MM) and Sota memorial fund to MM. PEXmRNA analyses were conducted by Showa Denko America Materials. CReS Kyushu organized sample collection and transfer, and conducted clinical data management with funding provided by Ono and Bristol-Myers Squibb.

Graphical abstract

DOI： 10.1101/2023.09.05.23295051

Language：Others   Publishing type：Research paper (scientific journal)  

The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis (P=0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis (P=0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.

DOI： 10.1097/PAS.0000000000002086

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/invivo.13198.

Language：Japanese   Publisher：耳鼻と臨床会  

上咽頭癌は、ほかの頭頸部癌とは異なる側面を持つことから、予後因子も通常の頭頸部扁平上皮癌とは異なる。2018年にTNM分類が改訂され、上咽頭癌も変更されたため、今回われわれは、新TNM分類を用いて、当科で加療を行った上咽頭癌症例について予後の検討を行った。対象は、2010年1月から2020年1月に九州大学病院耳鼻咽喉・頭頸部外科で一次療法を施行した上咽頭癌45例である。男性31例、女性14例、年齢は12-88歳、中央値59歳であった。これらのうち、上咽頭扁平上皮癌であった40例における5年全生存率(以下OS)、無増悪生存率(PFS)、予後関連因子などについて後方視的に解析を行った。その結果、5年OSは75.5%、5年PFSは64.3%であった。予後関連因子として、Stage別や組織型、Epstein-Barr Virus陽性か否かによる有意差は認められなかった。また、上咽頭癌治療の軸となるシスプラチン併用化学放射線療法については、シスプラチンの至適投与量についてさらなる検討が必要と考えられた。(著者抄録)

Language：Others   Publishing type：Research paper (scientific journal)  

Background/Aim: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. Patients and Methods: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. Results: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. Conclusion: 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.

DOI： 10.21873/anticanres.16148

Language：Others   Publishing type：Research paper (scientific journal)  

Background: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. Case presentation: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. Conclusions: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

DOI： 10.1186/s13256-022-03621-2

Language：Japanese  

杙創は,先端の鈍な棒状の物体が身体に突き刺さる外傷形態の一つである。口腔・咽頭外傷は、器具を口腔内に挿入したまま,転倒した際に発症することが多く、原因器具は、歯ブラシが最多とされる。今回、われわれは、副咽頭間隙を貫通した歯ブラシ杙傷の1例を経験した。症例は67歳の女性で、歯ブラシをくわえたまま転倒した。歯ブラシは中咽頭左側壁から副咽頭間隙を貫通し、左後頸部の筋間に刺入していた。また異物によって内頸動脈は著しく狭窄していた。頸部外切開によって歯ブラシのヘッド側から異物を摘出したが、抜去による出血はなく、その後の感染症の併発もなく治癒した。咽頭杙創の場合、不用意な抜去は血管損傷による大出血や神経障害の可能性があるため、造影CTや血管造影等で正常構造物との関係を把握した上で、適切な抜去法を選択する必要がある。また杙創は受傷後数日経過してから、膿瘍等の感染症や外傷性内頸動脈閉塞症などの重篤な合併症を来すこともあり、適切な抗菌薬治療や神経学的所見の経過観察などを怠らないことが重要であると考えられた。(著者抄録)

Language：Others   Publishing type：Research paper (scientific journal)  

Objectives The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. Materials and methods We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). Results The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. Conclusion Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DIIP, is recommended.

DOI： 10.1371/journal.pone.0271907

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. PATIENTS AND METHODS: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. RESULTS: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). CONCLUSION: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.

DOI： 10.21873/anticanres.15854

Language：Others   Publishing type：Research paper (scientific journal)  

Background/Aim: A long-term effect has been confirmed in clinical practice since the introduction of nivolumab for treating various malignant tumors. A similar phenomenon is speculated to occur in head and neck cancer; however, details remain unclear due to the lack of long-term reports. We aimed to investigate the five-year outcomes in long-term responders for over two years, and evaluate the optimal duration of therapy with nivolumab. Patients and Methods: In this retrospective observational study, we analyzed 203 cases of recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), including 33 long-term responders. Results: The median overall survival (OS), 5-year OS, median progression-free survival (PFS), and 5-year PFS values in the 203 cases were 13.1 months, 19.2%, 3.1 months, and 13.2%, respectively. Of the 33 long-term responders, 14 (42.4%) continued using nivolumab for more than 2 years. The remaining 19 patients (57.6%) discontinued nivolumab. The most common reason for discontinuation was severe immune-related adverse events (irAEs) (9 cases; 27.3%); in these 9 cases, the median disease-free survival was 33.2 (range=10.7-44.3) months. Nine patients (21.2%) were considered to have progressive disease (PD) after at least 2 years of administration, and 3 patients (9.1%) requested to discontinue treatment because a complete response (CR) was achieved. Conclusion: This study demonstrated the durable and long-term benefit of nivolumab in R/MHNSCC. In the future, we aim to accumulate real-world data for the establishment of criteria for completion of nivolumab treatment in long-term responders.

DOI： 10.21873/invivo.12907

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/invivo.12790

Language：Others   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. PATIENTS AND METHODS: Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. RESULTS: Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. CONCLUSION: Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.

DOI： 10.21873/invivo.12780

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00405-021-07236-z

Language：English   Publishing type：Research paper (scientific journal)  

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

DOI： 10.1097/PAS.0000000000001857

Language：Others   Publishing type：Research paper (scientific journal)  

The antitumor efficacies of immune checkpoint inhibitors (ICIs) and the usefulness of potential predictive markers such as programmed death-ligand 1 (PD-L1) expression, density of tumor-infiltrating lymphocytes (TILs) and microsatellite instability (MSI) in sinonasal squamous cell carcinoma (SNSCC) have not been fully elucidated. We retrospectively analyzed 131 SNSCCs with immunohistochemistry for PD-L1 expression, TIL subpopulations and loss of mismatch repair (MMR) proteins as a surrogate for MSI-high. We also comprehensively evaluated the mutual relationships among these immuno-markers, high-risk human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) gene status, and KRAS mutation. PD-L1 expression (tumor proportion score ≥ 1%) was detected in 60 (45.8%) SNSCC cases and was significantly associated with worse overall survival (OS) (p = 0.0240). High density of cluster of differentiation 8 (CD8)-positive TILs was significantly associated with better progression-free survival (PFS) (p = 0.0368), and high density of forkhead box protein P3-positive TILs was significantly associated with better PFS and OS (p = 0.0007 and 0.0143, respectively). With respect to the combination of CD8 + TIL and PD-L1 expression, the high-CD8/PD-L1-negative group showed the most favorable prognosis, whereas the low-CD8/PD-L1-positive group showed the worst prognosis. MMR loss was detected in 3 (2.3%) of the 131 cases. HPV infection (6.1%), EGFR mutation (14.5%), EGFR copy number gain (26%), and MMR loss were essentially mutually exclusive; patients in these molecular groups showed significant differences in prognosis but not in the degree of PD-L1 expression or TILs. Among the nine ICI-treated patients, three (33.3%) were responders, and the EGFR-wild type cases (n = 7) showed better clinical responses to an ICI compared to the EGFR-mutant cases (n = 2). Among the patients with residual/recurrent EGFR-wild type tumors (n = 43), ICI treatment significantly improved OS (p = 0.0281). The results suggest that the evaluation of immuno-markers and molecular subclassification may be helpful for prognostic prediction and selecting an individualized therapeutic strategy for patients with SNSCC.

DOI： 10.1038/s41379-021-00868-w

Language：Others   Publishing type：Research paper (scientific journal)  

Aims: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC), but it is not sufficient in all clinical settings. Methods and results: We examined the p16 and Rb expression status in 177 OPSCC cases by immunohistochemistry and the presence of transcriptionally active HR-HPV infection by mRNA in-situ hybridisation. The 177 cases were divided into p16+/HPV+ (n = 105, 59.3%), p16+/HPV− (n = 8, 4.5%) and p16−/HPV− (n = 64, 36.2%) groups. The p16+/HPV− and p16−/HPV− groups had a trend towards worse overall survival (OS) or significantly worse OS than the p16+/HPV+ group (n = 105) (P = 0.0610, P = 0.0004, respectively). We divided the Rb status into preserved expression (> 90%, n = 68), partial loss (PL) (10–90%, n = 97) and complete loss (CL) (< 10%, n = 12). Among the HPV-positive cases (n = 105), the Rb pattern was typically PL (n = 97, 92.4%) and rarely CL (n = 8, 7.6%), but never preserved expression (0%). In contrast, among the HPV-negative cases (n = 72), the Rb pattern was typically preserved expression (n = 68, 94.4%) and rarely CL (n = 4, 5.6%), but never PL (0%). Compared to p16 alone, the combination of p16 overexpression and Rb-PL/CL showed equally excellent sensitivity (each 100%) and improved specificity (97.2 versus 88.9%) and positive predictive values (98.1 versus 92.9%). Conclusions: These results suggest that the combined use of p16 and Rb immunohistochemistry could be a reliable, cost-effective method to predict HR-HPV infection in OPSCCs; however, HPV specific testing is necessary on inconclusive cases. We propose a diagnostic algorithm for practical use of these markers.

DOI： 10.1111/his.14337

Language：Japanese  

BCGは、抗酸菌の結核菌群の一つであるBacillus Calmette-Guerin菌を弱毒化したワクチンである。結核発病予防や膀胱癌治療に広く使用され、有効性は高く有害事象は少ない薬剤であるが、まれに重篤な感染症を引き起こし、診断や治療に難渋することがある。本症例は84歳の男性で、BCG膀胱内注入治療から約1年後に左頸部にBCGリンパ節炎を発症した。2ヵ月間の抗結核剤投与を行ったが、徐々に皮膚が自壊し深頸部膿瘍となったため、デブリードメントを行った。その後も抗結核剤の投与を持続していたが、デブリードメントから約2ヵ月後に感染性頸動脈瘤にまで発展した。BCG感染症は、そのまれさ故、確定診断がつけにくく、その上治療法も確立していないため、治療にも難渋することがある。今回われわれは、BCG感染症を経験し、その診断方法と治療方法について若干の文献とともに報告する。(著者抄録)

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Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1–4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient. Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1–4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient.

DOI： 10.1016/j.amjoto.2021.103081

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Re-irradiation with X-rays and particle beams can be used to treat localized recurrence of unresectable head and neck cancer after initial irradiation therapy. However, re-irradiation therapy increases the risk of severe and late sequelae by 4-to 8-fold. It can also result in fatal outcomes, such as rupture of the carotid artery and cerebral necrosis or abscess. A 41-year-old woman was diagnosed with squamous cell carcinoma of the external auditory canal. The patient was initially treated with X-ray irradiation. However, the patient underwent re-irradiation with heavy particle beams and neutron rays for a recurrent tumor. The patient developed necrosis of the skull base involving the facial skin and temporal bone 2 months after the last session of re-irradiation therapy. The tissue in the parapharyngeal and masticatory regions also became completely necrotic, resulting in extensive exposure of the brain parenchyma. Although the patient underwent conservative and surgical treatment, necrosis of the tissue progressed, and a large part of the brain was exposed. Approximately 2.5 years later, although the brain is still exposed, the patient is alive without disease. Although the tumor had subsided and long-term survival was achieved, our patient developed serious osteoradionecrosis of the skull base with extensive brain exposure. For patients who are not candidates for surgery, re-irradiation alone is an option, albeit with poor prospects. This approach should be discussed with the patient while balancing the potential survival gain against the burden of treatment and the risk of complications.

DOI： 10.1159/000516801

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DOI： 10.1177/01455613211013084.

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© 2020 Elsevier Inc. Salivary secretory carcinoma (SASC) is frequently associated with ETV6-neurotrophic tyrosine receptor kinase (NTRK) 3 fusion and more rarely with RET, MET, or ALK rearrangement. We aimed to elucidate the potential diagnostic utility of pan-tropomyosin receptor kinase (Trk) immunohistochemistry and its relationship with the fusion gene subtype in SASC. We examined 33 cases of SASC for immunoexpression of pan-Trk, ALK and ROS1, and gene rearrangement of the ETV6, NTRK3, and RET genes using fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Thirty (90.9%) of 33 SASCs harbored ETV6-NTRK3 fusion gene transcripts by RT-PCR and/or both ETV6 and NTRK3 gene rearrangements by FISH, and 3 cases (9.1%) had RET gene rearrangement. Most NTRK3-rearranged SASCs (27/33 cases; 81.8%) had conventional ETV6 exon 5-NTRK3 exon 15 fusion, whereas 2 cases (6.1%) had both the conventional fusion and a novel ETV6 exon 4-NTRK3 exon 15 fusion variant. In the remaining one case (3%), only FISH revealed both ETV6 and NTRK3 rearrangements, suggesting an ETV6-NTRK3 fusion with an as yet undetermined break point. All 30 SASCs with ETV6-NTRK3 fusion and/or NTRK3 rearrangement showed nuclear and cytoplasmic immunoreactivity for pan-Trk. In contrast, 3 SASCs with RET rearrangement showed negative or only weak cytoplasmic staining for pan-Trk. There was no case harboring ALK and ROS1 rearrangements. All 17 non-SASC tumors were negative for pan-Trk. The results suggest that nuclear and cytoplasmic immunoreactivity for pan-TRK may be helpful to identify ETV6-NTRK3–fused SASCs and to distinguish them from RET-rearranged SASCs and morphological mimics.

DOI： 10.1016/j.humpath.2020.11.017

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© 2020 Elsevier Ltd Background: Drug-induced interstitial lung disease (DI-IP) is one of the most serious adverse reactions associated with the use of anticancer drugs. DI-IP prevalence among molecular-targeting drugs and immune checkpoint inhibitors (ICIs) is relatively high in Japanese patients. To assess the risk of cetuximab and/or nivolumab-related IP is important. Patients and Methods: The medical records of 138 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with cetuximab-containing chemotherapy and/or nivolumab monotherapy were retrospectively reviewed. Results: The incidence of DI-IP with R/M HNSCC was 7.2%. DI-IP occurred more frequently in patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy than in patients with other regimens. However, tumor suppression was detected in all patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy, and two achieved a complete response. Conclusions: Although patients treated with cetuximab-containing chemotherapy following nivolumab showed dramatic efficacy, careful monitoring should be recommended.

DOI： 10.1016/j.oraloncology.2020.105129

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© 2020 Wolters Kluwer Health, Inc. All rights reserved. Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.

DOI： 10.1097/PAS.0000000000001566

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DOI： 10.21873/anticanres.14752.

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DOI： 10.1080/00016489.2020.1807601.

Language：Japanese  

頸部リンパ漏は、頭頸部領域の手術後に発症し得る合併症の一つであるが、時に難治性となり対応に苦慮することがある。今回われわれの施設では、無脂肪消化態流動食(ペプチーノ)の経管投与にてリンパ漏を治療した8例を経験した。8例中5例で創処置や薬物療法との併用となったが、5-12日間のペプチーノの投与でいずれの症例もリンパ漏は停止した。無脂肪消化態流動食(ペプチーノ)は比較的安価で投与方法も簡便であるため、臨床的にリンパ漏を疑った場合、積極的に投与開始を検討すべきであると考えられた。(著者抄録)

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© 2019 Wolters Kluwer Health, Inc. All rights reserved. The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV+ cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16+ SNSCCs were HPV-. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV+/EGFR CNG- group had significantly better overall survival than the HPV-/EGFR CNG- and HPV-/EGFR CNG+ groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.

DOI： 10.1097/PAS.0000000000001410

Language：Japanese  

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© 2019 Elsevier Ltd Objectives: Immune-related adverse events (irAEs) have been shown to be associated with higher antitumor responses and a clinical benefit in non-small cell lung carcinoma, renal cell carcinoma, and melanoma patients. However, little is known regarding the association between irAEs and the clinical effect of nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC). Materials and methods: We evaluated 108 patients treated with nivolumab for R/MHNSCC at 2 participating institutions. IrAEs were identified and profiled. We analyzed the association of each immune-related adverse effect with the clinical outcome of the patients. Results: Among 108 patients, the objective response rate (ORR) was 29.6% (32/108 patients), and the disease control rate (DCR) was 50.0% (54/108 patients). IrAEs were observed in 41 patients (38.0%). Patients with irAEs had a significantly higher ORR and DCR than those without irAEs (46.3% vs. 19.4%, P = 0.004 and 75.6% vs. 34.3%, P < 0.001, respectively). The median progression-free and overall survival rates in patients with irAEs were significantly longer than in those without irAEs. Conclusions: There was a significant relationship between irAEs and efficacy in R/MHNSCC patients treated with nivolumab. Our results indicate that the development of irAEs may aid in the earlier prediction of anticancer effects in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.

DOI： 10.1016/j.oraloncology.2019.104525

Language：Japanese  

当科において遠隔転移病変に対して外科的切除を行った頭頸部扁平上皮癌症例に関して検討を行った。対象は、2000年1月から2016年12月までに九州大学耳鼻咽喉・頭頸部外科で一次根治治療を施行した頭頸部扁平上皮癌症例のうち、肺転移、肝転移に対して外科的切除を施行した26例である。原発巣の内訳は上咽頭3例、中咽頭6例、下咽頭8例、喉頭5例、口腔3例、顎下腺1例であった。転移臓器は肺が22例、肝臓が4例であった。遠隔転移巣切除後の1年全生存率は78%、2年全生存率は70.9%であり、遠隔転移巣に対する外科的切除が予後の改善に寄与する可能性が示された。初回治療から遠隔転移再発までが短期間であった症例では、転移巣の切除後も予後不良な傾向を認めた。遠隔転移に対する外科的切除後も慎重なフォローアップが必要と考えられる。(著者抄録)

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© 2019 Wiley Periodicals, Inc. Background: Predicting the response to treatment with nivolumab and the survival in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) remains a challenge. We investigated whether or not the neutrophil-to-lymphocyte ratio (NLR) kinetics could be used to predict the anticancer effect of nivolumab. Patients and Methods: Forty-one patients with recurrent or metastatic HNSCC who had been treated with nivolumab were retrospectively analyzed. The NLR was calculated using pretreatment blood test results until the end of the treatment. Results: The posttreatment NLR was higher than the pretreatment value in 13 of 17 patients (76%) patients with progressive disease within the first 3 months, whereas the posttreatment NLR was lower than the pretreatment value in 10 of 11 patients (91%) with stable disease or partial response during the follow-up period. Conclusion: Our results indicate that monitoring the NLR may aid in the earlier confirmation of treatment failure in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.

DOI： 10.1002/hed.25737

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© 2019 JLO (1984) Limited. Background Parotid gland carcinoma is a rare and complicated histopathological classification. Therefore, assembling a sufficient number of cases with long-term outcomes in a single institute can present a challenge.Method The medical records of 108 parotid gland carcinoma patients who were treated at Kyushu University Hospital, Fukuoka, Japan, between 1983 and 2014 were reviewed. The survival outcomes were analysed according to clinicopathological findings.Results Forty-six patients had low clinical stage tumours (I-II), and 62 patients had high clinical stage tumours (III-IV). Fifty-two, 10 and 46 patients had low-, intermediate-and high-grade tumours, respectively. Twenty-seven of 65 cases had positive surgical margins. In high clinical stage and intermediate-to high-grade tumours, adjuvant radiation therapy was correlated with local recurrence-free survival (p = 0.0244). Intermediate-to high-grade tumours and positive surgical margins were significantly associated with disease-specific survival in multivariate analysis (p = 0.0002 and p = 0.0058).Conclusion The results of this study show that adjuvant radiation therapy is useful for improved local control in patients with high clinical stage and intermediate-to high-grade tumours.

DOI： 10.1017/S0022215119001130

Language：Japanese  

UICC/AJCC TNM分類第8版による中咽頭癌TNM分類では、(1)HPV関連の有無 (2)N節外浸潤の有無が、重要な要素となった。本邦の症例でも検証が必要であり、今回の改定に含まれない喫煙の予後への影響も含めて後方視的検討を行った。2010年1月から2015年12月に当科で根治治療を行ったHPV検索済の中咽頭扁平上皮癌110例を対象とした。HPV関連癌は52例だった。旧分類ではStage IVが全体の60%を占めていたが、新分類ではStage IおよびIIが倍増しStage IVが減ったことで各病期症例数のバランスが改善した。粗生存率解析では新分類のほうが病期毎予後をより反映しており、喫煙の予後に対する影響も示唆された。(著者抄録)

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© 2018 Elsevier B.V. Objective: The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC. Methods: Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA. Results: Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15. Conclusion: The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.

DOI： 10.1016/j.anl.2018.07.010

Language：Japanese  

近年増加傾向にある高齢者頭頸部扁平上皮癌患者の手術症例についてPOSSUMを用いて検討した。対象は、過去5年間(2011年9月-2016年8月)の当科における80歳以上頭頸部扁平上皮癌の手術症例21例とした。術後合併症群8例、非合併症群13例とで検討を行い、POSSUM予測合併症率は、術後合併症群で平均65%、非合併症群で平均48%となり、両群間には有意差は認めなかったものの術後合併症群で高い傾向を認めた。また、死亡など重篤な合併症を生じた例ではPOSSUM予測合併症率は高値を示した。POSSUM予測合併症率が高い症例では、術前に全身状態の改善や手術侵襲等を再検討し合併症率を下げるための予防策を立てることが重要であると考えられた。(著者抄録)

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© 2018 Wiley Periodicals, Inc. Background: Differentiating inverted papilloma from squamous cell carcinoma (SCC) is sometimes difficult. We evaluated the clinical usefulness of serum SCCA1 and SCCA2 in the management of patients with inverted papilloma or SCC. Methods: Serum and tissue samples for the analysis of SCCA1, SCCA2, and SCC antigen were taken from 18 patients with sinonasal inverted papilloma and 23 cases with sinonasal SCC. The SCCA1, SCCA2, and SCC antigen levels were determined. Results: The serum SCCA1 concentration was significantly higher in the inverted papilloma group than in the SCC group, whereas the serum SCCA2 level was significantly higher in the SCC group than in the inverted papilloma group. Conclusion: Patients with sinonasal inverted papilloma predominantly express SCCA1 protein, whereas those with SCC predominantly express SCCA2. This suggests that combined measurements of both serum SCCA1 and SCCA2 concentrations can be very useful for distinguishing sinonasal inverted papilloma from SCC.

DOI： 10.1002/hed.25351

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© 2017 Elsevier B.V. Objectives: Primary squamous cell carcinoma (SCC) of the thyroid is a rare disease. It usually presents with locally advanced disease and has an overall poor prognosis. In this study, we investigated the characteristics and outcomes of patients with SCC of the thyroid, and reported our experience with chemotherapy with lenvatinib in the treatment of SCC of the thyroid. Methods: The management outcome of 10 patients who had SCC of the thyroid between January 2000 and 2015 at Kyushu University Hospital or associated facilities was reviewed. Results: There were 3 males and 7 females, ranging in age from 53 to 77 years. Extent of disease was staged as follows: stage IVA, 3 cases; stage IVB, 3 cases; stage IVC, 4 cases. Only tracheostomy was applied for 2 cases, surgical resection, such as total thyroidectomy and neck dissection, for the other 8 cases. Radiotherapy following surgical treatment was applied for 9 cases. Four patients started on oral lenvatinib due to recurrent or progressive SCC of the thyroid. The one year actuarial survival rate of patients was 22.7%. There was no 2-year survivor of all patients. Conclusions: Treatment should primarily be targeted at surgical resection with negative margins in patients with resectable disease. Lenvatinib may show promise to potentially extend survival.

DOI： 10.1016/j.anl.2017.07.009

Language：Japanese  

症例は50歳、女性。1年前から嚥下時違和感を認め、画像検査の結果、食道粘膜下腫瘍と診断した。腫瘍の増大傾向があること、乳癌治療歴があり転移が否定できないこと、嚥下時違和感などの自覚症状を有していたことから、治療目的に腫瘍摘出術を行う方針とした。腫瘍は食道筋層内に局在しており、摘出標本は37×31mm大であった。術中所見および病理組織所見から頸部食道より発生した神経鞘腫と診断した。術後経過は良好で術後10日目に退院となった。術後10ヵ月が経過した現在、再発所見は認めていない。今回まれな頸部食道神経鞘腫に対して文献的考察を行ったところ、上縦隔にとどまっている腫瘍については頸部切開のみで摘出可能であり、上縦隔から中縦隔にまたがる頸胸部境界部腫瘍の場合は症例ごとにアプローチ法が選択する必要があると考えられた。(著者抄録)

Language：Japanese  

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© 2016 Elsevier Ireland Ltd Objective The aim of this study was to investigate the clinical features and prognosis of patients with squamous cell carcinoma (SCC) associated with sinonasal inverted papilloma (IP). Methods The medical records of 95 patients who were diagnosed with IP or SCC associated with IP were retrospectively reviewed. Out of 95 patients, 15 were diagnosed with SCC associated with IP. The clinical characteristics, treatment modalities, and survival outcomes of the patients were analyzed. Results The incidence of SCC associated with IP was 15.8%. Although differential diagnosis between IP and SCC associated with IP is difficult, epistaxis may be the specific symptom in SCC associated with IP cases. The 3-year disease-specific survival rate was higher in cases with T1, 2 and 3 than in cases with T4. There was no significant difference in survival rate between maxillary sinus and other primary sites. On the other hand, there was a significant difference in survival rate between the microscopic SCC with IP cases and the other cases. In addition, the patients with <70 years old better than those with >70 years old with a 3-year disease free survival of 80% versus 0%. Conclusions Some T4 patients were found to have a highly aggressive disease. Therefore, complete surgical resection followed by chemo-radiation therapy is the recommended treatment for patients with T4 disease to control of the primary tumor site.

DOI： 10.1016/j.anl.2016.04.004

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Language：Japanese  

中咽頭癌の発癌メカニズムとして、近年ヒトパピローマウイルス(HPV)の関与が示唆されている。HPVはその発癌性からHPV16、HPV18などの高リスク群と、HPV6、HPV11などの低リスク群に分けられる。これまで本邦では低リスク群が陽性であった中咽頭癌症例の報告はなく、海外の文献でも非常に少数である。今回われわれは、HPV6陽性中咽頭後壁癌の1例を経験した。術前化学療法が著効し、摘出標本に癌細胞を認めなかった。病理組織学的検討を行ったところ、p16は基底層を含む一部の細胞で局在を認めたが、高リスク群のような高発現は認めなかった。発癌の原因は不明であるが、まれな症例であり今後症例を蓄積した上で詳細な検討が必要と考えられる。(著者抄録)

Language：Japanese  

精神疾患を有する頭頸部癌症例においては、しばしば標準治療の遂行が困難となる。今回2008年1月から2013年6月の間に当院にて入院加療を行った精神疾患を合併する頭頸部癌症例27例について、治療経過や合併症に関する検討を行った。高度の認知障害を有する6例では治療を開始できなかった。放射線治療症例においては、治療の長期化に伴い精神疾患の増悪や身体合併症の出現がみられ、治療中断となる症例もみられた。手術を施行した症例では術後せん妄が多く、再建症例では皮弁に関連した合併症率が高い傾向を認めた。精神疾患合併頭頸部癌症例においては、進行度や全身状態、また精神社会的背景を十分に考慮した上での治療適応検討が重要と考える。(著者抄録)

Language：Japanese  

当科にて2009年から2012年の4年間に原発性副甲状腺機能亢進症(pHPT)と診断、手術を行った症例について検討を行った。対象は27例、年齢は23-82歳、性別は男性4例、女性23例であった。最終病理診断は26例が腺腫、1例が過形成であった。術前検査として頸部エコー、CTに99mTcMIBIシンチグラフィ、TL201-Tc99mサブトラクションシンチグラフィを組み合わせることで局在診断が可能であった。手術は22例で副甲状腺1腺摘出、1例で両側副甲状腺2腺摘出、4例で甲状腺半切とともに2腺を摘出した。16例で、術中にintact PTHを測定しその低下を確認した。術後26例では速やかに血清カルシウム(Ca)値の正常化が認められたが、1例では正常化には至らなかった。合併症として、反回神経麻痺は認めなかったが、6例で術後にテタニー症状と血清Ca値の低下を認めた。pHPTの手術において、責任病巣が特定可能であれば、病巣を摘出した上で術中intact PTHを測定し、その低下を確認することが有用であると考えられた。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

Language：Others   Publishing type：Research paper (scientific journal)  

Aims: In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). Methods and results: In 31 cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC. Conclusions: These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status. © 2013 John Wiley & Sons Ltd.

DOI： 10.1111/his.12183

Language：Others   Publishing type：Research paper (scientific journal)  

Objective: The aim of this study was to describe the CT,MRI and ultrasonography findings of five cases of neurogenic tumours in the head and neck region. Methods: Five neurogenic tumours were analysed with respect to their CT value, the presence of cystic change, target sign, lobulation, connection to the nerve and vascularity. Results: The contrast-enhanced CT (ECT) of the schwannomas demonstrated either a mass with low enhancement (two out of three cases), which reflected the predominant Antoni B components, or a mass with cystic changes, which was an Antoni A-based schwannoma displaying cystic changes (one out of three cases). On MRI, all tumours showed homogeneous and isointense signals for muscle on T1 weighted images (T 1 WIs). T 2 weighted images (T 2WIs) and gadolinium (Gd)-enhanced T 1 WIs demonstrated target sign in both schwannomas. Ultrasound examination showed a well-defined, ovoid or round hypoechoic mass. The direct connection to the nerve was demonstrated in two of the five cases. Lobulation was observed in only one of the five cases and cystic changes were observed in one of the five cases. In all of the cases, no vascularity was seen in power Doppler images (PDIs) obtained percutaneously. Conclusions: Low-enhanced areas on ECTs can be specific for schwannomas, which suggests the predominance of Antoni B components. The target sign on T 2 WIs and Gdenhanced T 1 WIs can be specific, which can be used to differentiate the two different components (Antoni A and Antoni B). The direct connection to the nerve can be a specific finding for neurogenic tumours; however, at present the sensitivity is 40%. © 2012 The British Institute of Radiology.

DOI： 10.1259/dmfr/81000210

Language：Japanese  

症例は70歳男性で、50年前から右鼻閉・鼻出血があり、近医で白色腫瘍を指摘された。頭部・副鼻腔造影MRIで、左鼻腔奥から上咽頭に突出する3.5×2.5×3.5cmの腫瘤を認め、T1で軽度高信号、T2で軽度低信号を呈し、造影後は強く増強された。FDG-PETで腫瘤の他に左上顎歯肉、左耳・顎下部に高集積を認め、両側の傍咽頭、深頸部、副神経リンパ節にも淡い集積が認められた。生検所見とあわせて左鼻腔悪性腫瘍(T2N2bM0)と診断し、重粒子線単独治療を開始した。原発巣に60.8GyE/16fr、左頸部リンパ節に56GyE/8fr照射し、それぞれCR、PRを得た。以後原発巣はコントロールされたが、照射部位の壊死によって引き起こされた様々な合併症(Grade 1～3)を来たし、治療3ヵ月以内では口内炎、皮膚炎、3ヵ月以降は皮膚そう痒感、軟口蓋痛、鼻出血、口内炎、開口障害が認められた。更に約1年3ヵ月後には眼窩内膿瘍が生じて開放・排膿術を要し、2年経過時点で上咽頭後壁に潰瘍が出現している。

Language：Others   Publishing type：Research paper (scientific journal)  

Cancer-to-cancer metastasis into a thyroid neoplasm is an uncommon phenomenon with possible diagnostic difficulties. Here, we describe a case of lung adenocarcinoma metastatic into a follicular variant of papillary thyroid carcinoma (FVPTC). A 60-year-old woman with no prior history of malignant neoplasm presented with a nodule in the right lobe of the thyroid gland, some masses in the left lung were found by radiological examination. Histopathological examination of the thyroidectomy specimen demonstrated two different components of carcinoma in a single thyroid nodule; one was FVPTC and the other was high-grade adenocarcinoma. Although both components shared the TTF-1+/CK7+/CK19+/CK20-/SP-A- immunoprofile, only the former was positive for thyroglobulin, and only the latter was positive for CEA. The epidermal growth factor receptor (EGFR) gene mutation at exon21 (L858R) was present only in the latter. The lung biopsy specimen showed cytological, immunohistochemical, and EGFR genotypic features similar to those of the high-grade adenocarcinoma component of the thyroid nodule. These findings resulted in a reliable diagnosis of lung adenocarcinoma metastasizing into an FVPCT and treatment with EGFR-targeted therapy. These results demonstrate that a panel of immunohistochemical staining and molecular analysis is helpful for both diagnosis and appropriate postoperative treatment for a patient with cancer-to-cancer metastasis. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

DOI： 10.1111/j.1440-1827.2011.02679.x

Language：Japanese  

上顎に発症した脱分化型腺様嚢胞癌の1例を経験した。症例は72歳男性。左上顎洞から骨破壊を伴って鼻腔、口腔内へと進展する腫瘍を認め、上顎洞試験開窓術が施行された。腫瘍は組織学的に異なった二つの成分から構成されており、定型的腺様嚢胞癌成分と核異型、核分裂像が著明な高悪性度の癌腫成分が一部で移行像を伴って併存してみられ、脱分化型腺様嚢胞癌と診断された。脱分化型腺様嚢胞癌は発症頻度が低く、予後が悪い傾向にあるため正確な病理学的診断が必要と考えられる。(著者抄録)

Language：Japanese  

孤立性線維性腫瘍は間葉系由来の腫瘍であるが鼻、副鼻腔での報告はまれである。中鼻甲介を基部とした孤立性線維性腫瘍の1例を経験したので報告する。症例は59歳、女性で徐々に出現した鼻背部の腫脹を主訴に当科を受診した。生検で孤立性線維性腫瘍の診断であった。易出血性であったがDenker法に内視鏡を併用することによって安全に摘出可能であった。術後病理で悪性所見を認めず、12ヵ月経過した。現在再発は認めていない。(著者抄録)

Language：Japanese  

唾液腺腫瘍は組織像や生物学的態度が多彩である。適切な診断、治療の発展の基礎となることを目的とし、我々の施設で1983年～2007年の約24年間に手術された大唾液腺原発性腫瘍551例を収集・解析した。その内訳は、上皮性腫瘍537例(97.5%)、血液・リンパ系腫瘍10例、間葉系腫瘍4例であった。上皮性腫瘍537例(耳下腺475例、顎下腺62例)中、悪性は123例(22.9%)であったが、悪性の占める割合は、耳下腺20%に対し、顎下腺は45.2%と高率であった。組織型別では多形腺腫285例(53.1%)、ワルチン腫瘍104例(19.4%)の順に多く、悪性では、腺様嚢胞癌(25例)、粘表皮癌(17例)、多形腺腫由来癌(15例)が多かった。また、多形腺腫の癌化は5%(15/300例)程度と推定された。また、多形腺腫由来癌の悪性成分は多彩だったが、高悪性度である唾液腺導管癌も少なくなく、注意が必要である。(著者抄録)

Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2018.6

Language：Japanese  

Venue：東京   Country：Japan  

Event date： 2017.6

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Venue：京都   Country：Japan  

Event date： 2017.2

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Event date： 2016.2

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Event date： 2015.9

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Event date： 2015.1

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Event date： 2014.6

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Event date： 2014.1

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Venue：香川   Country：Japan  

Event date： 2013.1

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Venue：鹿児島   Country：Japan  

Event date： 2012.10

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Event date： 2011.7

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Venue：福岡   Country：Japan  

Event date： 2011.6

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Venue：愛知   Country：Japan  

Event date： 2011.2

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Event date： 2010.12

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Event date： 2009.5

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Venue：福岡   Country：Japan  

Event date： 2008.9

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Venue：長崎   Country：Japan  

Event date： 2008.4

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Venue：福岡   Country：Japan  

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Venue：福岡   Country：Japan  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：3

Number of peer-reviewed articles in Japanese journals：2

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1

Number of peer-reviewed articles in Japanese journals：1

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：3