Evaluation of usefulness of tongue pressure measurement device for dysphagia associated with treatment of patients with head and neck cancer (ELEVATE).

INTRODUCTION: Dysphagia is often caused by radiotherapy (RT) in patients with head and neck cancer (HNC), and reduced tongue pressure (TP) is often associated with swallowing dysfunction in the oral stage. However, the evaluation of dysphagia by measuring TP has not yet been established in HNC patients. Herein, we conducted a clinical trial to evaluate the usefulness of TP measurement using a TP-measuring device as an objective indicator of dysphagia induced by RT in HNC patients. METHODS AND ANALYSIS: This ELEVATE trial is a prospective, single-center, single-arm, non-blind, non-randomized trial to evaluate the usefulness of a TP measurement device for dysphagia associated with the treatment of HNC. Eligible participants include patients with oropharyngeal or hypopharyngeal cancer (HPC) undergoing RT or chemoradiotherapy (CRT). The TP measurements are conducted before, during, and after RT. The primary endpoint is the change in the maximum TP values from before RT to 3 months after RT. Moreover, as secondary endpoints, the correlation between the maximum TP value and the findings of video-endoscopic and video-fluoroscopic examinations of swallowing will be analyzed at each evaluation point, as well as changes in the maximum TP value from before RT to during RT and at 0, 1, and 6 months after RT. DISCUSSION: This trial aimed to investigate the usefulness of evaluation by measuring TP for dysphagia associated with HNC treatment. We expect that an easier evaluation for dysphagia will improve rehabilitation programs for dysphagia. Overall, we expect this trial to contribute to the improvement of patients' quality of life (QOL).

Comparison of the efficacy of the Epley maneuver and repeated Dix-Hallpike tests for eliminating positional nystagmus: A multicenter randomized study.

Background and objectives: Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix-Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week. Methods: This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%. Results: Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin. Discussion: This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living. Classification of evidence: This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week. Registration number: UMIN000016421.

An extremely rare case of interdigitating dendritic cell sarcoma of the parotid gland with a 40­month disease­free survival time after only surgery: A case report.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from dendritic cells and is mainly located in the lymph nodes. To the best of our knowledge, no treatment strategy has yet been established for IDCS, despite its aggressive clinical features. The present study presents the case of a patient with IDCS who experienced a 40-month disease-free survival time after surgery alone. The patient, a 29-year-old woman, presented with a painful right subaural swelling. Diagnostic MRI and 18F-fludeoxyglucose positron emission tomography/computed tomography revealed a right parotid gland tumour and ipsilateral cervical lymph node. The patient underwent surgical resection, and histological examination of the resected tissue specimens confirmed IDCS diagnosis. To the best of our knowledge, this is only the fifth report of an IDCS located in the parotid gland, with the longest follow-up period among cases of IDCS reported in this region. The positive outcome of this patient suggests that surgical resection may be an effective treatment option for local IDCS. Nonetheless, further studies are required to establish a definitive diagnosis and treatment strategy for IDCS.

Resection of brachial plexus schwannomas while monitoring transcranial motor evoked potentials: report of two cases.

A schwannoma is a benign nerve sheath tumor treated by enucleation, which carries the risk of intraoperative nerve injury that is observed after awakening. Transcranial motor evoked potential (TcMEP) monitoring has been established as an effective method to predict and prevent intraoperative neurological complications during brain and spinal surgery. However, there have been few reports on its application in head and neck surgeries. We performed enucleation to relieve the symptoms due to schwannomas in the neck of two women, aged 25 years and 70 years. Both women presented with a left cervical mass, paresthesia of the left upper limb, and a Tinel-like sign without muscle weakness. TcMEPs were recorded before beginning surgery, during surgery, and immediately before completing surgery. The dissecting lines were decided using the stimulator attached to the dissecting instrument, which helped warn the surgeon regarding risky areas. Histopathological examinations confirmed the diagnosis of schwannoma. There was no significant difference in the pre- and postoperative TcMEP recordings, and no postoperative motor deficits were identified. Intraoperative TcMEP monitoring is expected to be useful in preventing operative complications while treating head and neck schwannomas.

Intraoperative Transcranial Motor-Evoked Potential Monitoring During Head and Neck Surgeries: A Case of Cervical Vagus Nerve Schwannoma With Laryngeal Paralysis.

Intraoperative transcranial motor-evoked potential (TcMEP) monitoring can effectively prevent neurological complications by enabling the evaluation of neurological deficits in all pathways from the motor cortex to the periphery. However, studies regarding its applicability in head and neck surgery are insufficient. This case report discusses a patient who was intraoperatively diagnosed with a right cervical vagus nerve schwannoma previously at another hospital. The patient then developed right laryngeal paralysis after the surgery without neuromonitoring. No significant recovery of the paralysis was observed, and after eight months of being referred to our institution, the patient opted for surgical retreatment following tumor growth and accompanying symptoms such as cervical swelling and discomfort. The patient was examined to evaluate the nerve damage in his previous surgery TcMEP monitoring as well as direct stimulation (DS). The right vagus nerve (RVN) showed no response on TcMEP monitoring throughout the surgery despite a significant response to DS at the tumor site. These findings suggest that the RVN had been damaged medial to the tumor site, and the damage occurred because of traction and ischemia during the previous surgery. Thus, contrary to our belief, medial nerve damage may be present even when local and peripheral nerve preservation is observed through peripheral neuromonitoring. This suggests that DS alone during neuromonitoring in head and neck surgery is insufficient. A multimodal evaluation approach, including TcMEP monitoring, is effective in not only preventing neurological complications but also in evaluating neurological deficits in all pathways from the motor cortex to the periphery.

A survey of feeding and swallowing function after free jejunal flap reconstruction in cases of head and neck cancer.

Reconstructive surgery using the free jejunum flap for locally advanced head and neck cancer is effective in preserving the swallowing function; however, it does not allow normal oral intake in all patients. A total of 47 patients underwent surgery at Nara Medical University between Jan 2010 and Dec 2019. The patients' ages ranged from 48 to 86 years. Sites were the hypopharynx (33 cases), larynx and cervical esophagus (5 cases each) and oropharynx (4 cases). Swallowing function was assessed using videofluorography, from the start of oral intake to discharge, as well as meal form at discharge. Lateral-retropharyngeal-lymph node dissection (LRPLND), preoperative radiation therapy, extended resection to the nasopharynx and incidence of stenosis in the jejuno-esophageal anastomosis were examined. Significant differences were revealed in the scores of pharyngeal residues of contrast medium and pharyngeal contraction, with and without preoperative radiotherapy. LRPLND did not affect swallowing function; dissection group cases had lower scores for soft palate elevation. Overall, resection extended to the nasopharynx, and the anastomosis method did not affect scores of swallowing function.

Four cases of medullary thyroid carcinomas associated with multiple endocrine neoplasia 2B with rearranged during transfection codon M918T mutation in the same family.

Multiple endocrine neoplasia (MEN) with medullary thyroid carcinoma (MTC) is associated with rearranged during transfection (RET) mutations. The authors encountered four cases of MTC-related MEN type 2B (MEN2B) with RET codon M918T mutation in one family. Case 1 included a 19 year-old male diagnosed with MTC with lung metastases. Genetic testing revealed an RET codon M918T mutation, which indicated MEN2B. The patient responded partially to vandetanib and the disease has shown no progression in 25 months. Case 2 involved the mother of the patient in Case 1. She underwent total thyroidectomy (TT) when diagnosed with MTC-related MEN2B at 12 years of age, but was not counseled adequately. Cases 3 and 4 involved the sisters of the Case 1 patient and were assessed after Case 1 was diagnosed. Genetic testing revealed the same mutation. Case 3 was diagnosed with MTC and underwent TT. Case 4 was asymptomatic but underwent prophylactic TT; histopathologic examination revealed MTC tissue. Prophylactic TT prevented MTC from being detected at an advanced state. Genetic counseling is essential in treating MEN2B. The mother was uninformed about the genetic characteristics of MEN2B, delaying the detection of MTC in her children. The present study reaffirms the importance of family history and screening.

COVID­19 and peritonsillar abscess co­infection: A case report.

Coronavirus disease 2019 (COVID-19) generally presents with fever, shortness of breath and a sore throat. These symptoms are also common in oral and pharyngeal infections, such as peritonsillar abscess (PA). The present study describes a case of PA and COVID-19 co-infection. Although COVID-19 was initially suspected in the patient due to the presenting symptoms of fever, sore throat, dysgeusia and dysosmia, an oral examination and computed tomography scan detected PA. The patient was conservatively managed with intravenous antibiotics without transoral drainage of the abscess. Anti-COVID-19 medication was not administered as the COVID-19 infection in the patient was not severe. Laboratory findings revealed high levels of leukocytes, C-reactive protein (CRP) and procalcitonin. On the whole, the association between laboratory findings (including leukocyte count, CRP and procalcitonin levels) and bacterial co-infection with COVID-19 remains unclear, and further studies are warranted. Oral examinations and transoral procedures are often avoided due to the high risk of the aerosolisation of COVID-19 viral particles. However, an appropriate evaluation is essential in order to avoid the underdiagnosis of life-threatening bacterial infections that co-exist with COVID-19.

Anaplastic thyroid cancer with long-term survival with lenvatinib therapy and preservation of laryngeal function after one-stage reconstruction: A case report.

Laryngotracheal reconstruction is performed to treat locally advanced thyroid carcinoma invading the larynx and/or trachea. The reconstructive technique varies. The present report describes the case of a 71-year-old female patient who underwent surgery for thyroid carcinoma involving the larynx. Reconstructive surgical techniques were employed to maintain laryngeal structure and function. An anterolateral thigh flap with free rib cartilage grafts was used to compensate for laryngeal defects. Although a temporary tracheal stoma was constructed, it closed spontaneously after decannulation. Therefore, one-stage laryngeal reconstruction was accomplished. Post-operative histopathological examination revealed focal anaplastic changes in the lesion, which mainly consisted of papillary components. Post-operative positron emission tomography/computed tomography indicated early recurrence in the left side of the neck. Therefore, lenvatinib was started as adjuvant therapy. Complete response was observed with lenvatinib therapy. The patient was alive and had good laryngeal function 26 months after the operation. One-stage laryngeal reconstruction can reduce burden and improve quality of life in patients with thyroid carcinoma involving the larynx. Lenvatinib may be useful for treating early recurrence of anaplastic thyroid carcinoma after reconstructive surgery with a free flap.

Surgical technique for the prevention of tracheal necrosis following total pharyngolaryngectomy.

Total pharyngolaryngectomy with cervical esophagectomy (TPLCE) is an invasive procedure with various post-operative complications. Tracheal necrosis (TRN) is a fatal complication of TPLCE. The present study aimed to identify a surgical technique which may be used to prevent TRN. The post-operative complications of 48 patients who underwent TPLCE from January, 2010 to December, 2019 were retrospectively investigated. The incidence of TRN was examined and measures against TRN were reviewed. The results revealed that 3 patients (6%) experienced TRN within 1 week following surgery. In addition, 2 patients required the surgical debridement of the necrotic tissue and tracheoplasty. The other patient underwent conservative treatment. Stomal recurrence developed in 1 patient (2%). On the whole, the present study demonstrates that the incidence of TRN following TPLCE is lower than that observed in previous reports, and only one stomal recurrence was reported. Preserving the blood supply to the trachea is essential for the prevention of TRN. The eight surgical processes used herein effectively preserved the blood supply. Further investigations however, are necessary in order to confirm the present findings and to ensure effective measures are found with which to prevent TRN following TPLCE.

Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection.

Reactivation of a former hepatitis B virus (HBV) infection can be triggered by immunosuppressive therapy, diseases associated with an immunocompromised state, organ transplantation or the withdrawal of antiviral drugs. Despite the absence of such risk factors, a spontaneous reactivation of HBV replication occurred in two elderly patients with resolved or occult HBV infection. A 73-year-old male underwent coronary artery bypass grafting in October 2008, and was negative for HBsAg but positive for anti-HBs. In July 2009, his serum became positive for HBsAg, HBeAg and HBV DNA (6.4 log copies/ml; genotype C), but negative for anti-HBc IgM, with abrupt elevation of the liver enzymes. The entire genomic sequence of HBV recovered from this patient revealed no mutations in the core promoter and precore regions that interfere with HBeAg production. A 76-year-old male with a history of endoscopic mucosal resection for esophageal cancer in 2002 and an initial diagnosis of diabetes mellitus in 2009, at which time he was negative for HBsAg. He was found to be positive for HBsAg in September 2012 during a laboratory examination performed prior to the resection of recurrent esophageal cancer, despite a low HBV load (2.1 log copies/ml). Three months later, without the administration of any anticancer drugs, the HBV DNA (genotype B) level increased to 5.1 log copies/ml. A precore G1896A variant with high quasispecies diversity was recovered from the patient. Aging, surgical stress and complication of disease(s) associated with compromised immunity, such as cancer, arteriosclerosis and diabetes mellitus may trigger spontaneous HBV reactivation.

Re-evaluation of the serum alanine aminotransferase upper normal limit in chronic hepatitis C patients.

OBJECTIVE: The aim of this study was to re-evaluate the upper limit of normal range (ULN) for serum alanine aminotransferase (ALT) in chronic hepatitis C (CH-C) patients who achieved sustained virological response (SVR) to interferon therapy. METHODS: Enrolled in this study were 136 consecutive patients, 84 males and 52 females, mean age 52.1+/-14.8 years, with CH-C who received interferon therapy during 1992 to 2008 and achieved SVR. AST and ALT levels (3 serial measurements) were measured every 3 to 4 months over one year after termination of interferon therapy and then the measurements were averaged for each patient. RESULTS: The distribution of AST and ALT showed normal distribution. Overall, AST levels were 19.7+/-3 IU/L and ALT levels were 13.8+/-3.1 IU/L in all patients, AST levels were 19.8+/-3 IU/L and 12.9+/-2.9 IU/L and ALT levels were 14.4+/-3.2 IU/L and 9.9+/-3.5 IU/L in male and female patients, respectively. AST level was the highest in the 6th decade and ALT level was in the 5th decade. CONCLUSION: In this study on CH-C patients with SVR to interferon therapy, ULN of serum ALT and AST were far lower than the current accepted value. We propose that a suitable ULN of serum AST is <25 IU/L and ALT is <20 IU/L in CH-C patients.

Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts.

BACKGROUND/AIMS: To estimate hepatocarcinogenesis rates in patients with hepatitis C virus (HCV)-related cirrhosis, an accurate prediction table was created. METHODS: A total of 183 patients between 1974 and 1990 were assessed for carcinogenesis rate and risk factors. Predicted carcinogenesis rates were validated using a cohort from the same hospital between 1991 and 2003 (n=302) and an external cohort from Tokyo National Hospital between 1975 and 2002 (n=205). RESULTS: The carcinogenesis rates in the primary cohort were 28.9% at the 5th year and 54.0% at the 10th year. A proportional hazard model identified alpha-fetoprotein (>or=20 ng/ml, hazard ratio 2.30, 95% confidence interval 1.55-3.42), age (>or=55 years, 2.02, 95% CI 1.32-3.08), gender (male, 1.58, 95% CI 1.05-2.38), and platelet count (<100,000 counts/mm3, 1.54, 95% CI 1.04-2.28) as independently associated with carcinogenesis. When carcinogenesis rates were simulated in 16 conditions according to four binary variables, the 5th- and 10th-year rates varied from 9 to 64%, and 21-93%, respectively. Actual carcinogenesis rates in the internal and external validation cohorts were similar to those of the simulated curves. CONCLUSIONS: Simulated carcinogenesis rates were applicable to patients with HCV-related cirrhosis. Since, hepatocarcinogenesis rates markedly varied among patients depending on background features, we should consider stratifying them for cancer screening and cancer prevention programs.

Factors regarding increase of platelet counts in chronic hepatitis C patients with sustained virological response to interferon-Relation to serum thrombopoietin levels.

UNLABELLED: Thrombocytopenia is frequently found in patients with chronic liver disease, and associated with advanced fibrosis stage and with decreased liver function. Serum thrombopoietin (TPO) levels also decrease as the disease progresses from mild fibrosis to cirrhosis. On the other hand, platelet counts increase associated with improvement of fibrosis in chronic hepatitis C (CH-C) patients with sustained virological response (SVR) to interferon (IFN) therapy. Then, we studied if the increase of platelet counts in SVR associate with elevated TPO production or a reduction of spleen size. Liver fibrosis, spleen size, serum TPO levels, albumin, zinc turbidity test (ZTT), platelet counts were compared in fifteen CH-C patients with SVR before and after IFN therapy. RESULTS: Albumin increased from 4.2+/-0.3 to 4.3+/-0.3g/dl (p=0.067), ZTT decreased from 17.7+/-5.9 to 8.9+/-3.9K-U (p<0.001), platelet counts increased from 15.5+/-6.8x10(4) to 19.9+/-5.8x10(4)/mul (p<0.01) and serum TPO levels increased from 1.65+/-0.94 to 2.06+/-1.22fmol/ml (p=0.073). Spleen size was measured by ultrasonography, and the spleen index was calculated by multiplication of the long and short axes from hilus, which decreased from 14.6+/-5.0 to 10+/-3.1 (p<0.001) after IFN therapy. In conclusion, increase of platelet counts in SVR may be related to the reduction of spleen size and increased serum TPO levels associated with improvement of fibrosis after IFN therapy.

Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy.

BACKGROUND AND AIM: Hepatitis C virus (HCV)-infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients. METHODS: In total, 126 patients with chronic hepatitis C (CHC) who achieved a sustained virological response (SVR) to IFN monotherapy, which was defined as the absence of detectable HCV RNA in the serum at 6 months after completion of treatment, were enrolled and possible risk factors for HCC were analyzed. RESULTS: During the observation period of 66 +/- 36 months after cessation of IFN treatment, five (4.0%) of the 126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of HCC was significantly higher among patients with severe fibrosis (F3 or F4) than among patients with no or mild fibrosis (F0 to F2) in the liver before treatment (P = 0.007); among patients with alcohol intake of > or = 27 g/day than among patients with that of < 27 g/day (P = 0.015); and among patients who were > or = 65 years old than among patients who were < 65 years old at the start of treatment (P = 0.026). CONCLUSIONS: Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were > or = 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV.

Circulating KL-6 level at baseline is a predictive indicator for the occurrence of interstitial pneumonia during interferon treatment for chronic hepatitis C.

Interstitial pneumonia (IP) is a serious adverse event of interferon alpha (IFNalpha) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who received IFNalpha treatment with or without ribavirin between January 1992 and June 2002, six patients (1.1%) developed IP, including one patient who developed IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D levels were within the normal range in all seven cases, but the serum KL-6 level was elevated in five of the seven cases, contrasting with that in three of 48 age-adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%; P=0.0003). Furthermore, the circulating KL-6 level at baseline was significantly higher among the seven cases than among the controls (543+/-105 vs. 304+/-98 U/ml, P=0.0001). These results indicate that measurement of the circulating KL-6 level in CH-C patients before IFN treatment may be useful for predicting the occurrence of IP during IFN treatment.