Maxillary Sinus NUT Carcinoma: A Case Report.

Background/Aim: Nuclear protein in testis (NUT) carcinoma is extremely rare, occurs in the midline of the body, progresses rapidly and is refractory to treatment; most patients die within a year. Here, we describe a case of maxillary sinus NUT carcinoma presenting with epistaxis and nasal obstruction that was treated as a standard head and neck carcinoma. Case Report: The patient was a 41-year-old male with a left buccal swelling; the diagnosis was made of primary NUT carcinoma of the left maxillary sinus and bone metastasis in the cervical spine. After induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil, the tumor decreased in size, and the patient was further treated with cisplatin and radiation therapy. One month after that, the tumor remained small, however, lung metastasis was observed. Therefore, nivolumab was administered. Cetuximab and paclitaxel were administered after the lung metastasis worsened, but the patient developed progressive disease and died 11 months after diagnosis. Conclusion: Effective treatments for NUT carcinoma have not yet been established. However, early testing to establish the diagnosis may provide useful insights to guide clinical decisions to improve patient outcomes.

Parotid Gland Cancer With First Bite Syndrome Detected via CT-Guided Fine Needle Aspiration Cytology.

BACKGROUND/AIM: First bite syndrome (FBS) is a symptom of severe pain at the beginning of a meal that lessens as the meal progresses. It is a common postoperative complication of parapharyngeal space tumors and is rarely reported as the first symptom of parotid carcinoma. The parapharyngeal space is considered a difficult area for approach; hence, preoperative histopathology is often challenging. However, there are hardly any reports on the approach of performing biopsies under computerized tomography (CT) guidance. CASE REPORT: A 28-year-old woman presented to our hospital with the chief complaint of pain in the left parotid region since the past year. Contrast-enhanced magnetic resonance imaging of the parotid gland revealed a 10-mm high-signal area on T2-weighted images extending from the deep lobe of the left parotid gland to the parapharyngeal space, which could not be visualized on ultrasound. She was suspected to have a malignant tumor because of the presence of a parotid tumor with FBS. Therefore, she underwent CT-guided fine-needle aspiration cytology (FNAC) and was diagnosed with adenoid cystic carcinoma. The patient underwent left parotid tumor resection and left cervical dissection, and her pain during feeding improved postoperatively. CONCLUSION: In a patient with parotid tumor extending into the parapharyngeal space with FBS as the initial symptom, CT-guided FNAC was successfully used to diagnose parotid carcinoma. Symptoms of pain, including FBS, should be considered in cases of malignancy. CT-guided FNAC is effective for lesions that cannot be visualized by ultrasound, such as those in the parapharyngeal space.

Pregnancy and delivery in an advanced cancer survivor with immune checkpoint inhibitor-induced type 1 diabetes: a case report.

PURPOSE: Given the rarity and elderly onset of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (ICI-T1DM), cases leading to delivery are rare. METHOD: To our knowledge, this is the first case report of childbirth in a patient with ICI-T1DM after cancer survival. A 32-year-old woman was started on Nivolumab for metastatic parotid cancers one year after total parotidectomy. RESULT: The patient developed ICI-T1DM after 43 cycles and started multiple daily insulin therapy and self-monitoring of blood glucose. Complete response was maintained for 2 years by nivolumab, and she finished nivolumab in 77 cycles to attempt pregnancy. During the follow-up period, she began using a sensor-augmented pump (SAP). She had undetectable serum and urinary C-peptide when she started SAP. Her HbA1c level decreased from 7.8 to 6.6% without increasing hypoglycemia in one year. The patient remained in complete response after ICI discontinuation, and embryo transfer was initiated. Pregnancy was confirmed after a second embryo transfer (21 months after ICI discontinuation). At 36 weeks and 6 days, an emergency cesarean section was performed due to the onset of preeclampsia. The baby had hypospadias and bifid scrotum but no other complications or neonatal intensive care unit admission. CONCLUSION: Because ICI discontinuation and ICI-T1DM carry risks for the patient and child, the decision regarding pregnancy warrants careful consideration. Diabetologists should collaborate with patients and other clinical departments to develop a treatment plan for childbirth.

Brain metastases in patients with salivary duct carcinoma: A retrospective study.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.

Lemierre's Syndrome after Head and Neck Photoimmunotherapy for Local Recurrence of Nasopharyngeal Carcinoma.

Introduction: Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre's syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre's syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma. Case Presentation: A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy. Three months after HN-PIT, the patient developed fever and neck pain, which led to a diagnosis of Lemierre's syndrome. The patient was treated with antibiotics and anticoagulants for at least 1 month. The patient's general condition and inflammatory findings on blood sampling showed gradual improvement, and a follow-up cervicothoracic computed tomography imaging showed that the venous thrombus had been obscured and the patient was doing well. Conclusion: HN-PIT is a high-risk procedure for the development of Lemierre's syndrome due to irradiation-induced mucositis, and anticipating the development of Lemierre's syndrome during HN-PIT is important.

Two Cases of Emergency Tracheostomy After Head and Neck Photoimmunotherapy.

Background/Aim: Head and neck photoimmuno-therapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023. Of these, we experienced two cases in which preventive tracheostomy was not performed because the risk of laryngeal edema was considered low; however, laryngeal edema developed after treatment, and an emergency tracheostomy had to be performed. Case Report: Case 1 was a patient in his 70s with a local recurrence of mandibular gingival carcinoma. HN-PIT using cylindrical diffusers was performed on the target lesion, extending from the lateral wall of the oropharynx to the soft palate. Case 2 was also a patient in his 70s with carcinoma of the mid-pharynx. HN-PIT was performed using a frontal diffuser to target lesions extending from the soft palate to the buccal mucosa. Notably, both patients developed laryngeal edema after HN-PIT, and an emergency tracheostomy had to be performed. Conclusion: HN-PIT treatment is still being established through a trial-and-error method and is still incomplete.

A Case of Successful Treatment with an Immune Checkpoint Inhibitor after Head and Neck Photoimmunotherapy.

Introduction: Head and neck photoimmunotherapy (HN-PIT) has been conditionally approved by the Japanese government for the treatment of unresectable locally advanced or locally recurrent head and neck cancer since January 2021. HN-PIT makes local treatment of locally recurrent disease possible in cases where systemic drug therapy would have previously been the only option. However, when treatment is ineffective and the disease progresses, it is necessary to shift to conventional drug therapies. We report a case in which an immune checkpoint inhibitor (ICI) was successfully administered to a patient with advanced disease following HN-PIT. Case Presentation: A 75-year-old male patient presented with local recurrence of mandibular gingival cancer. The primary treatment consisted of mandibular segmentectomy and reconstruction with a scapulohumeral and vastus lateralis skin valve. Post-operative radiotherapy was administered. Local recurrence was found in the mid-pharynx adjacent to the reconstruction. HN-PIT was performed for the local recurrence. After three cycles of HN-PIT, the local lesion increased, and the disease was evaluated as advanced. Therefore, the patient was switched to pembrolizumab, an ICI. Conclusion: The recurrent lesions disappeared 2 months after the first dose of pembrolizumab, and the patient remained in clinical remission at 1 year. To the best of our knowledge, there are no other reports of successful ICI therapy after HN-PIT.

Transoral robotic surgery (TORS) in Japan: procedures, advantages and current status.

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan.

Tracheostomy in otorhinolaryngology education and training programs: A Japanese nationwide survey.

OBJECTIVE: Surgical airway management is one of the most effective techniques for safe airway management. Within the training programs relating to knowledge and skills required by otorhinolaryngologists, tracheostomy and postoperative management are important items that must be fully understood by airway surgeons. We performed a nationwide survey to identify problems within tracheostomy and postoperative management in Japan in order to establish practical and safe guidelines for surgical airway management. METHODS: We conducted a questionnaire survey of the current status of tracheostomy and postoperative management at core institution of otorhinolaryngology training programs in Japan. RESULTS: Responses were obtained from all 101 core training institutions in Japan. Tracheostomy was performed in the operating room at 61.4% of institutions and in the ICU at 26.7%. 89.1% of them performed surgical tracheostomy (ST) in all cases. Even in the remaining 10.9%, percutaneous dilatational tracheostomy (PDT) was performed in less than 10% of cases. The primary surgeon was an otorhinolaryngology resident at 89.1% of institutions. The method of securing the tube immediately after surgery was by securing it with an attached cord at 48.5% of institutions, by suturing to the skin at 25.7%, and using a Velcro band at 24.8%. The first tube change after tracheostomy was performed on the seventh postoperative day at 81.2% of institutions. 87.1% had more than one person performing the first tube change. The tracheostomy postoperative complications within the past year were as follows: tracheostomal granulation: 89.1%; subcutaneous and/or mediastinal emphysema: 62.4%; tube stenosis: 55.4%; accidental tube removal: 50.5%; incorrect tube insertion or misplacement: 15.8%; hemorrhage from tracheal foramen requiring hemostasis in the operating room: 14.9%; pneumothorax: 4.0%; tracheo-innominate arterial fistula: 2.0%; and tracheoesophageal fistula: 1.0%. The method for educating otorhinolaryngology residents about tracheostomy was on-the-job training at 98.0% of institutions. CONCLUSIONS: For airway management in otorhinolaryngology training programs, after learning the basics of ST, PDT should also be well understood. Furthermore, in order to create safe educational programs for intraoperative and postoperative management, it is necessary to train otorhinolaryngologists with accurate knowledge and skills, and to strengthen collaboration with multiple professions in their leadership roles as airway surgeons.

Useful combination of Gehanno method, polyglycolic acid sheet and fibrin glue for prevention of postoperative dysfunction after soft palate resection with TORS.

Oropharyngeal cancer requiring combined resection of the soft palate is relatively out of indication for transoral robotic surgery (TORS) due to postoperative functional problems. We report the case of a patient with oropharyngeal cancer in which half of the soft palate was resected, and good function was maintained using the Gehanno method, polyglycolic acid (PGA) sheet and fibrin glue. The patient was a woman in her 50 s with oropharyngeal squamous cell carcinoma (p16-positive, T2N1M0 stage I). TORS and right neck dissection were performed the same day. About half of the soft palate was resected cranially. After closing the right nasopharynx with the Gehanno method, the sutured part was reinforced by covering with a PGA sheet of about 10 mm on a side and fibrin glue. Oral feeding was started on postoperative day 4, but no nasal reflux was observed. Three weeks postoperatively, no nasal reflux was evident, normal food intake was possible, and nasal breathing was maintained. This technique may be effective after TORS surgery that requires soft palate resection.

A Case of Oropharyngeal Carcinoma with an Oblique Neck that Benefited from Transoral Robotic Surgery.

Transoral robotic surgery (TORS) and transoral videolaryngoscopic surgery (TOVS) are minimally invasive procedures for early-stage head and neck cancers. However, due to its unique nature, transoral resection often leads to skeletal and anatomical disorders. We describe a case in which TORS was used in a 71-year-old man with a skeletal disorder, spastic stridor, and a T2N1M0 stage I p16-positive oropharyngeal carcinoma. Prior to the procedure, he underwent right cervical dissection (levels II-IV). Although he had an oblique neck, the right side of his neck was naturally hyperextended because the dissection was performed on the right side. The right facial, lingual, and external carotid arteries were ligated in preparation for TORS. Postoperative pathological examination revealed no extranodal involvement of the metastatic lymph nodes. A two-stage TOVS procedure was performed for the oropharyngeal tumor, in which the surgeon was required to be positioned at the patient's head to allow direct manipulation. This makes the neck and oral cavity more susceptible to the skeletal effects. In contrast, in TORS, the da Vinci insertion angle can be set to match the angle of the neck, allowing surgeons to operate with less skeletal influence. TORS is more useful in this setting.

Postoperative Pharyngeal Fistula Diagnosed by Prone Position Computed Tomography With Oral Contrast Agent: A Case Report.

BACKGROUND/AIM: A pharyngeal fistula is the most common complication of total laryngectomy; thus, accurate diagnosis and treatment are important. Diagnosis is usually made by the finding of leakage of the contrast agent outside the pharynx during swallowing contrast examination. Herein, we encountered a case in which fine leaks not detected on contrast examination during swallowing were visualized and diagnosed by computed tomography (CT) imaging with oral contrast media with the patient in a prone position. CASE REPORT: During imaging in a prone position, the contrast agent entered the sutures on the cephalocaudal and ventral sides of the surgical site, which were particularly prone to leaks due to gravity, and it was possible to diagnose minute leaks. When there is a high risk of postoperative pharyngeal fistula, such as in reconstructive cases with a pedunculated flap or with overlapping risk factors such as preoperative irradiation, CT imaging with contrast medium in a prone position is considered useful when swallowing contrast examination does not provide a clear diagnosis. However, suture failure is possible, and this should be evaluated. CONCLUSION: This case suggests that routine prone CT may lead to the early detection of postoperative pharyngeal fistula in high-risk cases. Further accumulation of cases is required to confirm our findings.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC). PATIENTS AND METHODS: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases. RESULTS: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively. CONCLUSION: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future.

Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis.

Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy.

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study.

BACKGROUND/AIM: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities. PATIENTS AND METHODS: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared. RESULTS: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02). CONCLUSION: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors.

Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.

A Case of Laryngeal Cryptococcosis that Responded to Itraconazole.

Laryngeal cryptococcosis is a rare condition. While there is no reliable evidence regarding the treatment of laryngeal cryptococcosis, oral fluconazole was successful in most previous cases. We experienced a case where we could not continue fluconazole because of adverse drug effects. An 88-year-old female was referred to our department with a 5-month history of sore throat and cough. She had used oral steroids and a corticosteroid inhaler for poorly controlled asthma. Flexible laryngoscopy showed leukoplakia of the vocal cords and subglottic mucosa, and biopsy revealed cryptococcal infection. We started the treatment with fluconazole but changed to itraconazole because of adverse events. Since laryngoscopy performed 6 months later was unremarkable and drug interactions had occurred, we stopped the itraconazole use at 6 months. Our experience suggests that itraconazole is also useful for treating laryngeal cryptococcosis.

Macroscopic and multiple metastases in sentinel lymph node biopsy are respectively associated with poor prognosis in early oral cancer.

BACKGROUND: A multicenter, randomized controlled phase III trial was conducted on sentinel lymph node biopsy (SLNB) and elective neck dissection for T1 (depth of invasion ≥ 4 mm)-T2N0M0 oral cavity squamous cell carcinoma. This study identified factors associated with poor prognosis in patients who underwent SLNB based on a subgroup analysis of this trial. METHODS: We analyzed 418 sentinel lymph nodes (SLNs) from 132 patients who underwent SLNB. The metastatic SLNs were classified into three categories based on size-isolated tumor cells: < 0.2 mm, micrometastasis: ≥ 0.2 mm and < 2 mm, and macrometastasis: ≥ 2 mm. Three groups were formed based on the number of metastatic SLNs: no metastasis, 1 metastatic node, and ≥ 2 metastatic nodes. The size and number of metastatic SLNs on survival were evaluated using Cox proportional hazard models. RESULTS: Patients with macrometastasis and ≥ 2 metastatic SLNs had worse overall survival (OS) and disease-free survival (DFS) after adjustment for potential confounders (HR for OS: macrometastasis, 4.85; 95% CI 1.34-17.60; ≥ 2 metastatic SLN, 3.63; 95% CI 1.02-12.89; HR for DFS: macrometastasis, 2.94; 95% CI 1.16-7.44; ≥ 2 metastatic SLN, 2.97; 95% CI 1.18-7.51). CONCLUSIONS: In patients who underwent SLNB, a poorer prognosis was associated with macrometastasis or having ≥ 2 metastatic SLNs.