Satoshi Yamada

Key Clinical Message: A 35‐year‐old male presented with recurrent respiratory papillomatosis. Human papillomavirus type 11 was detected from all sites of tumor tissue DNA by PCR. The pre‐surgery cell‐free DNA (cfDNA) viral load (3.33 × 10³ copies/ng DNA) fell below the post‐surgical detection limits on achieving remission, suggesting cfDNA's potential as a biomarker.

Sudden sensorineural hearing loss (SSNHL) is routinely encountered and is one of the most common emergent diseases in otolaryngology clinics. However, the etiology of SSNHL remains unclear. Due to the inaccessibility of the living human inner ear for biopsy, studies investigating the etiology of SSNHL have been performed by analyzing data obtained from examinations using peripheral blood or imaging. We updated the findings obtained from serological, magnetic resonance imaging, genetic, and viral examinations to reveal the etiology of SSNHL. Regarding viral examination, we focused on sensorineural hearing loss associated with coronavirus disease (COVID-19) because the number of correlated reports has been increasing after the outbreak. The updated findings revealed the following three possible mechanisms underlying the development of SSNHL: thrombosis and resulting vascular obstruction in the cochlea, asymptomatic viral infection and resulting damage to the cochlea, and cochlear inflammation and resulting damage to the cochlea. Thrombosis and viral infection are predominant, and cochlear inflammation can be secondarily induced through viral infection or even thrombosis. The findings about sensorineural hearing loss associated with COVID-19 supported the possibility that asymptomatic viral infection is one of the etiologies of SSNHL, and the virus can infect inner ear tissues and directly damage them.

Ion-exchange resins are commonly used to treat complications such as hyperkalemia, hyperphosphatemia, and hypercholesterolemia. Gastrointestinal complications may occur as side effects of such treatments. Sodium and calcium polystyrene sulfonate (PS-Ca) are cation-exchange resins comprising an insoluble structure that binds to potassium ions in the digestive tract and exchanges them with sodium and calcium ions, respectively, to promote their elimination. PS crystals are rhomboid, refractive, and basophilic in hematoxylin and eosin staining. To differentiate PS crystals from other ion-exchange resin crystals such as sevelamer and cholestyramine, periodic acid–Schiff, Ziehl–Neelsen, and Congo red staining are usually performed. Here, correlative light and electron microscopy (CLEM)-energy-dispersive X-ray spectroscopy and the NanoSuit method (CENM) was applied to perform a definitive identification of ion-exchange resins. CENM could detect sulfur in PS crystals without destroying the glass slides. Notably, PS retained its ion-exchange ability to bind potassium in paraffin sections. Differential diagnosis of anion-exchange resins, such as sevelamer and cholestyramine, was possible using these characteristics. The phosphorus:carbon ratio was higher in sevelamer than in cholestyramine after soaking paraffin sections in a phosphate solution. Therefore, CENM may be used for the differential pathological diagnosis of ion-exchange resins in paraffin sections.

Behcet’s disease is a chronic relapsing systemic inflammatory disease with four characteristic symptoms, including oral aphthous ulcers. In general, oral aphthous ulcers in Behcet’s disease are often confined to the oral cavity, but there have been reports of cases in which the aphthous ulcers have extended to the pharynx and larynx. Because there are no specific laboratory findings for the diagnosis of this disease, it is often difficult to diagnose. Herein, we report four cases of Behcet’s disease with intractable aphthous ulcers in the pharynx and larynx, including the epiglottis.

Small bowel perforation caused by metastasis from head and neck carcinomas is rare. We report a case of oropharyngeal carcinoma with metastasis to the small bowel. A 64-year-old woman who had received radiotherapy for oropharyngeal carcinoma presented to us complaining of abdominal pain. CT revealed free air in the abdomen, and emergency surgery was performed. During explorative laparotomy, many tumors were detected in the mesentery; one of them had caused a free perforation and another had caused stricture of the small bowel. The tumors were resected, and the postoperative diagnosis was metastatic squamous cell carcinoma (p16 positive). The patient could eventually resume oral intake and was discharged from the hospital. However, 27 days after the operation, she presented again with abdominal pain. CT showed free air, and there was evidence of panperitonitis. She died 4 hours later. Small bowel metastasis accounts for less than 10% of malignant tumors of the small bowel, and metastases to the small bowel secondary to head and neck SCC are very rare. Furthermore, they are rarely symptomatic and carry a very poor prognosis. Bowel perforation by metastasis is thought to occur in the terminal stages of cancer.

Liquid biopsy has the alternative utility, besides being a diagnostic tool, as a minimally invasive monitoring tool for disease profiling and prognostication. Recently, the incidence of HPV-associated oropharyngeal cancer has been increasing. Also, the choices of chemotherapy, including immune checkpoint inhibitor therapy, has been increasing. A minimally invasive diagnostic tool is desired. Herein, we demonstrate the usefulness of liquid biopsy, not only for HPV ctDNA monitoring, but also for diagnosis of recurrence, in a patient with HPV-OPC. The ctDNA concentrations decreased and serum HPV-DNA became negative after surgery for the primary tumor. When the patient developed a pulmonary lesion during the follow-up after initial treatment, we initially suspected primary lung cancer clinically. The operated lesion turned out to be a metastatic lesion. The test for HPV-DNA, which had become negative before, had become positive before the pulmonary surgery, suggesting recurrent disease. Liquid biopsy for monitoring of the ctDNA has the potential to allow the disease status to be monitored in patients with HPV-OPC.

Laryngeal papillomatosis is caused by infection with human papillomavirus (HPV) type 6 and/or 11. Laryngeal papillomatosis recurs frequently, and malignant transformation occurs in 1.6%-4% of the cases. Surgery is the treatment of first choice. While adjuvant therapies such as interferon, Chinese medicines, proton pump inhibitors, indole 3 carbinol, cidofovir and vaccines have been tried, none has come to be positioned as the standard of care. We report seven patients with laryngeal papillomatosis who underwent multiple surgeries. All were men. The surgery was performed in combination with two or three of the following: use of an electric scalpel, CO₂ laser, YAG laser, sharp resection, and intralesional injection of cidofovir. Intralesional injection of cidofovir after resection was performed in four cases, and remission was achieved in three of these cases. Cidofovir is an unapproved drug in Japan and is not yet approved for use in cases of laryngeal papillomatosis in other countries. However, the outcomes in our cases and other reports suggest that intralesional injection of cidofovir is effective. HPV6 (n=5), HPV11 (n=1) and HPV negative (n=1) detected respectively. Malignant transformation occurred in one case and HPV negative. Moreover, p16 immunohistochemistry was performed in all cases. However, no relation with number of operations and HPV status was found. The life cycle of HPV in laryngeal papillomatosis is largely unknown, and there is no consensus on methods of treatment other than surgery. More research is needed to elucidate the life cycle of HPV and the pathophysiology of laryngeal papillomatosis.

Superselective Intra-arterial Cisplatin Infusion and Concomitant Radiotherapy (RADPLAT) is adopted at multiple centers as treatment for advanced maxillary sinus cancer, and favorable results have been reported. We examined the treatment results and adverse effects of RADPLAT at our hospital. From January 2004 to February 2019, we examined the data of 58 patients with maxillary sinus cancer who underwent RADPLAT. Of the 58 patients, 48 were male, 10 were female, the median age was 68 years (38-87 years), and the histopathological diagnosis was squamous cell carcinoma in 56 cases and transitional cell carcinoma and undifferentiated carcinoma in 1 case each. The criteria for treatment completion were as follows: six cycles of CDDP administered at 100 to 120 mg/m² weekly, with irradiation at 60 to 70 Gy. The treatment was completed in 84.5% of cases (49/58 cases), and in the group in which the treatment was completed, the response rate (CR or PR) was 98%, the 5-year local control rate was 69.1%, and the 5-year crude survival rate was 71. 8%. The serious adverse events were blindness in 5 cases (of which 4 had received intra-arterial injection into the ophthalmic artery) and cerebral infarction in 2 cases, while no sequelae were observed after conservative treatment. There were no cases with severe renal impairment. The high response rate, 5-year local control rate and 5-year crude survival rate were consistent with previously reported treatment results. As compared to systemic chemotherapy, there were fewer adverse events, and this treatment may be particularly indicated for elderly patients and mild renal impairment. However, it is necessary to carefully consider the indication of treatment, provide information to the patients and their families about this treatment, including the risks, and obtain their informed consent.