Single-cycle induction chemotherapy for resectable advanced hypopharyngeal cancer.

BACKGROUND: The role of induction chemotherapy (IC) in the treatment of resectable advanced head and neck squamous cell carcinoma has not been elucidated, and the most effective IC regimen for chemoselection is still unknown. At our institute we have not used the triple combination of docetaxel, cisplatin, fluorouracil (TPF) for chemoselection, but rather the double combination of docetaxel + cisplatin (TP). The aim of this study is to report the outcome of patients with advanced hypopharyngeal cancer treated by single cycle of IC with TP followed by chemoradiation (CRT) or surgery. METHODS: A total of 29 patients with resectable advanced hypopharyngeal cancer who were treated with a single cycle of IC were entered into the study. Responders were treated by CRT while nonresponders underwent surgery. Outcomes were analyzed using the Kaplan-Meier method. RESULTS: A single cycle of IC with TP achieved response in 21 of the 29 patients. The major side effect was neutropenia which could be managed without delaying the sequential treatment. The 2-year overall survival and disease-specific survival were both 74.0% (stage III 100%, stage IVA 69.1%). The cumulative 2-year laryngeal preservation rate was 100% for stage III and 53.6% for stage IVA. CONCLUSION: A single cycle of IC with the combination of docetaxel + cisplatin may be sufficient to select advanced hypopharyngeal cancer patients with radio-sensitivity. IC intended for organ preservation strategies should be low toxic. Our strategy may be a useful for providing the benefits of IC and the opportunity for curative surgery without delay.

[A Case of Pneumocystis Pneumonia after Cetuximab-based Bioradiotherapy].

Reports of drug-induced interstitial pneumonia caused by Cetuximab have been increasing. Pneumocystis pneumonia is important as a differential diagnosis of drug-induced interstitial pneumonia. We report herein on a 64-year-old man with pneumocystis pneumonia after cetuximab-based bioradiotherapy for laryngeal cancer. After radiotherapy, the patient developed multi-drug resistant pneumonia. Chest CT imaging revealed diffuse ground-glass opacities in the lung field. He was diagnosed as having pneumocystis pneumonia based on the bronchoalveolar lavage (BAL) findings, and then his symptoms improved after treatment with Trimethoprim/Sulfamethoxazole. It is important to assess the risk factor for pneumocystis pneumonia for early its detection and treatment.

Removal of a Metallic Stent after 9 Years of Placement That Caused Tracheal Stenosis: A Rare Case Report.

Introduction: Metallic stents are widely used to prevent airway obstruction for tracheal stenosis caused by malignant diseases. Although their efficacy has been recognized, there is no established evidence surrounding their long-term safety. We report a case of airway stenosis caused by a metallic tracheal stent. Removal of the stent to secure the airway was difficult and extremely complicated. Case Presentation: A 50-year-old male suffering from dyspnea caused by malignant lymphoma (diffuse large B-cell lymphoma) of the thyroid gland was treated with a metallic tracheal stent. After remission of the lymphoma, stenosis of the stent lumen developed gradually, and the patient complained of dyspnea. Tracheostomy could not be performed due to the metallic stent. Since the patient was unable to intubate, the stent was removed under general anesthesia with partial percutaneous cardiopulmonary support 9 years after the stent placement. Conclusion: Otolaryngologists should be aware of the possibility of severe stenosis following the long-term placement of a metallic tracheal stent.

Efficacy of anti-PD-1 monotherapy for recurrent or metastatic olfactory neuroblastoma.

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear. Methods: We retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy. Results: Of the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity. Conclusion: ICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB.

Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx.

PURPOSE: The significance of epidermal growth factor receptor (EGFR) signaling has been recognized in various cancers and anti-EGFR therapies in Japan are currently under consideration in squamous cell carcinoma of the head and neck (SCCHN) similar to colorectal cancer. However, there was no established survey regarding heterogeneous EGFR protein expression in Japanese SCCHN patients. The purpose of this study is to examine the relationship between EGFR expression or KRAS mutation (related to the alteration of EGFR pathway) and the clinicopathological characteristics of SCCHN. MATERIALS AND METHODS: We retrospectively examined the expression of EGFR protein by immunohistochemistry and KRAS gene mutation at codons 12 and 13 by using paraffin-embedded and formalin-fixed primary tumor tissues from 205 patients with SCCHN who underwent surgery at National Cancer Center Hospital East. RESULTS: In 200 of the 205 patients (97.6 %), EGFR protein was expressed despite intratumoral heterogeneity. No patients had KRAS mutation at codons 12 or 13, and all 183 tumors showed wild-type KRAS. Positive rate of EGFR protein expression was significantly associated with better disease free survival (DFS) (P = 0.0471) and the intensity of EGFR protein expression showed a tendency for better DFS (P = 0.1034). Both higher EGFR positive rate and more intense EGFR expression were significantly associated with well differentiated subtype of squamous cell carcinoma (P = 0.0003 and P = 0.0007, respectively). CONCLUSION: Most SCCHN patients may be good candidates for the anti-EGFR therapies.

An invasive presentation of parotid lymphadenoma: A first reported case.

Lymphadenoma, a rare benign tumor recognized in the WHO salivary gland tumor classification of 2005, poses diagnostic and treatment challenges due to its rarity and distinct histopathological characteristics. We report a unique case of lymphadenoma in a 45-year-old male patient who presented with a hard, painless tumor in the right parotid gland that had been present since he was 15 years old. Distinctively, MRI and CT imaging revealed signs of infiltration into the surrounding muscle tissues, challenging the traditional notion of lymphadenomas as tumors with clear boundaries. The histopathological examination identified the characteristic epithelial and lymphoid cell proliferation, suggestive of a lymphadenoma. However, the possibility of sebaceous differentiation due to faintly pale cells within the epithelial component was inconclusive. The tumor's invasive nature and the high risk of facial nerve paralysis associated with surgical resection led to the patient's decision against treatment. Findings from this case underline the need for caution in diagnosing lymphadenoma, given its potential to show invasive images and the risks associated with a malignant diagnosis based solely on these images. Furthermore, the observations from this case present new insights into the FDG-PET findings of lymphadenoma, contributing to the overall understanding of this rare tumor's clinical implications. Future studies are warranted to provide more clarity on this condition.

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma.

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer.

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC. METHODS: An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FU cytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients. RESULTS: Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cells in vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC. CONCLUSIONS: These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy.

Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland.

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.

Combined transcervical and orbitozygomatic approach for the removal of a nasopharyngeal adenocarcinoma.

OBJECTIVE: In some cases, the exposure and safeguarding of the internal carotid artery (ICA) are not easy by the maxillary swing approach that is used as a mainstay for the removal of nasopharyngeal tumors. To address this issue, we have developed a new combined transcervical and orbitozygomatic approach. METHODS: A nasopharyngeal adenocarcinoma arose in a 52-year-old patient and occupied the right middle skull base extending to the ICA. We first identified and dissected the ICA from the posterolateral part of the tumor using a transcervical approach. Then, the tumor was approached and removed by an orbitozygomatic technique with hemifacial dismasking. The surgical defect was filled using a temporal muscle flap, which was divided into two parts according to the blood supply from either the anterior or the posterior deep temporal artery. RESULTS: The postoperative course was uneventful and favorable cosmetic results were obtained. The patient has been free of carcinoma for more than 40 months after the surgery. CONCLUSION: Our new combined approach might be a good option for selected patients with nasopharyngeal tumors.

Microsatellite instability and proliferating activity in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma.

Sinonasal carcinomas arise from the respiratory epithelium that lines the nasal and paranasal cavities, and are histologically composed of either squamous or cylindrical cell carcinoma. However, molecular analysis with the purpose of distinguishing sinonasal carcinomas from other head and neck squamous cell carcinomas (HNSCCs), which arise from squamous epithelium, has been limited. Moreover, a wide range of frequency of microsatellite instability (MSI) in HNSCC has been reported. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 34 patients with sinonasal carcinoma. As a control, 24 oral squamous cell carcinomas were used. MSI was detected in 14 patients with sinonasal carcinoma (41%), but not in any with oral squamous cell carcinoma (p=0.002). Furthermore, in sinonasal carcinoma, 11 out of 17 (65%) T1-T3 sinonasal carcinomas demonstrated MSI, whereas only 3 out of 15 (20%) T4 tumors demonstrated MSI. Immunohistochemically, sinonasal carcinoma showed a higher MIB-1-labeling index and more frequently showed cytokeratin 18 expression when compared with oral squamous cell carcinoma. These findings suggest that sinonasal carcinoma and HNSCC have quite different molecular backgrounds regarding carcinogenesis, and the role of MSI is relatively minor in cases of advanced sinonasal carcinoma.

A rare case of idiopathic hypereosinophilic syndrome involving the oral cavity associated with the esophagus and gastrointestinal tract.

We report the rare case of HES involving oral cavity associated with esophagus, and gastrointestinal tract, which we succeeded in diagnosing precisely through a biopsy specimen obtained from the lip. A 64-year-old man had dysphagia, swelling of the oral mucosa and the posterior cervical muscles, accompanied by an abdominal pain and diarrhea. Peripheral blood cell count showed marked eosinophilia. Computed tomography showed thickening of posterior wall of the pharynx, esophagus, and gastrointestinal tract. Histologic specimen obtained from the lower lip demonstrated a moderate infiltration of eosinophils. His clinical condition was improved by oral prednisolone therapy.

Tracheal reconstruction with a modified infrahyoid myocutaneous flap.

Reconstruction of a tracheal defect is a challenge because it often requires invasive surgery associated with relatively high morbidity. We recently invented a less-invasive method using a modified infrahyoid myocutaneous (IHMC) flap for the reconstruction of a tracheal defect in an 83-year-old male. A tracheal defect, the right half of the cricoid cartilage plus the right three quarters of the I-IV tracheal cartilage (about 3 × 4 cm), was reconstructed with a modified IHMC flap composed of the sternohyoid and platysma muscles and a skin pedicle. Considering the age of patient, we avoided rigid reconstruction and used a soft silicone tracheal opening retainer (Koken Co., Ltd., Tokyo, Japan) as an anterior wall dilator after surgery and waited for the scarring of the flap until it become rigid enough. The postoperative course was uneventful and the trachea was reconstructed safely. Tracheal reconstruction with an IHMC flap is a useful and less-invasive alternative compared to end-to-end anastomosis or reconstruction with a forearm flap, which is currently used as a mainstay.

The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.