Surgical indications for upper mediastinal dissection by sternotomy in patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a relatively indolent disease, despite the high incidence of lymph node metastases. Although less frequent, some upper mediastinal metastases of PTC cannot be removed without sternal resection. In this study, we investigated the prognostic impact of upper mediastinal dissection (UMD) by sternotomy on patients with mediastinal metastases of PTC. Charts of patients with PTC who underwent surgical treatment at our institution between 2006 and 2018 were retrospectively reviewed. Fifty-eight patients with upper mediastinal metastases were enrolled. Kaplan-Meier survival curves were compared, and Cox hazard regression models were used for analyses. Of the 58 patients with mediastinal metastasis, 12 (20.7%) underwent dissection of the prevascular nodes, 51 (87.9%) underwent dissection of the upper paratracheal nodes, and 14 (24.1%) underwent dissection of the lower paratracheal node. The preferred site of mediastinal metastasis was the upper paratracheal nodes. The 5 and 10-year disease-specific survival rates for patients after UMD were 74.6% and 58.7%, respectively. Among 25 patients (43.1%) with locoregional recurrence, 12 (20.7%) had mediastinal recurrence and 7 were eligible for additional UMD. Although distant metastasis was the predominant poor prognostic factor, mediastinal recurrences were more frequently unresectable than cervical recurrences, suggesting that mediastinal recurrence is a poor prognostic factor. Mediastinal metastases larger than 30 mm or metastases to the lower paratracheal nodes are considered a risk factor for mediastinal recurrence. UMD by sternotomy for patient with upper mediastinal metastases which are difficult to resect via transcervical approach is an effective treatment option to improve patient prognosis.

Novel surgical methods for reconstruction of the recurrent laryngeal nerve: Microscope-guided partial layer resection and intralaryngeal reconstruction of the recurrent laryngeal nerve.

BACKGROUND: The optimal strategy for surgical management of papillary thyroid carcinoma invasion of the recurrent laryngeal nerve remains controversial. Our aim was to evaluate the efficacy of 2 surgical methods and provide detailed descriptions of microscope-guided partial layer resection and intralaryngeal reconstruction of the recurrent laryngeal nerve. METHODS: This retrospective study enrolled 85 patients with papillary thyroid carcinoma who underwent initial surgical excision for invasion of the recurrent laryngeal nerve. Twenty-seven patients (28 recurrent laryngeal nerve sites) underwent partial layer resection, and 11 patients (11 recurrent laryngeal nerve sites) underwent intralaryngeal reconstruction of the recurrent laryngeal nerve. The remaining patients underwent either only resection or resection with immediate reconstruction of the recurrent laryngeal nerve. Pre and postoperative phonetic function and rates of locoregional recurrence were extracted from medical charts for analysis. RESULTS: Isolated locoregional recurrence specific to the aerodigestive tract was identified in 1 patient (3.7%) in the partial layer resection group and 1 patient (9.1%) in the intralaryngeal reconstruction group. Seventy-five percent of patients in the partial layer resection group recovered or had preserved vocal cord function, and the mean maximum phonation time of the patients with postoperative complete vocal cord palsy was 15.3 seconds. The mean maximum phonation time of the patients, excluding 4 patients with permanent stoma in the intralaryngeal reconstruction group, was 22.3 seconds. The mean maximum phonation time of either group was longer than that of patients with recurrent laryngeal nerve resection only and comparable with that of patients with recurrent laryngeal nerve resection and immediate reconstruction. CONCLUSION: Patients who underwent either partial layer resection or intralaryngeal reconstruction had low rates of locoregional recurrence specific to the aerodigestive tract and good postoperative functional outcomes.

Parathyroid carcinoma coexisting with multiple parathyroid adenomas: a case report.

Primary hyperparathyroidism is usually caused by parathyroid adenoma; however, parathyroid carcinoma is a rare cause. We report a rare case of 74-year-old female of primary hyperparathyroidism caused by parathyroid carcinoma (PC) and coexisting multiple parathyroid adenomas. She was referred to our hospital for primary hyperparathyroidism and a suspected thyroid tumor. She had no family history of malignant tumor. Computed tomography (CT) and ultrasonography of the neck revealed some masses posterior to both thyroid lobes. Those masses were believed to be parathyroid lesions. However, another mass located posterior to the right upper thyroid lobe seemed to be heterogeneous, which indicated a malignant thyroid tumor as well as parathyroid tumor. The preoperative diagnosis was multiple parathyroid adenoma and suspicious incidental thyroid carcinoma. Therefore, the patient underwent total parathyroidectomy and thyroidectomy. The histopathological diagnosis was parathyroid carcinoma coexisting with multiple parathyroid adenomas. There was no evidence of recurrence at 1 year after the surgery. It was difficult to diagnose PC preoperatively. Few rare cases of PC coexisting with parathyroid adenoma in multiple endocrine neoplasia type 1 (MEN1) have been reported. Therefore, careful follow-up was necessary considering the possibility of MEN1, though she did not wish for a genetic examination.

A novel reflex cough testing device.

BACKGROUND: The reflex cough test is useful for detecting silent aspiration, a risk factor for aspiration pneumonia. However, assessing the risk of aspiration pneumonia requires measuring not only the cough reflex but also cough strength. Currently, no reflex cough testing device is available that can directly measure reflex cough strength. We therefore developed a new testing device that can easily and simultaneously measure cough strength and the time until the cough reflex, and verified whether screening with this new instrument is feasible for evaluating the risk of aspiration pneumonia. METHODS: This device consists of a special pipe with a double lumen, a nebulizer, and an electronic spirometer. We used a solution of prescription-grade L-tartaric acid to initiate the cough reflex. The solution was inhaled through a mouthpiece as a microaerosol produced by an ultrasonic nebulizer. The peak cough flow (PCF) of the induced cough was measured with the spirometer. The 70 patients who participated in this study comprised 49 patients without a history of pneumonia (group A), 21 patients with a history of pneumonia (group B), and 10 healthy volunteers (control group). RESULTS: With the novel device, PCF and time until cough reflex could be measured without adverse effects. The PCF values were 118.3 ± 64.0 L/min, 47.7 ± 38.5 L/min, and 254.9 ± 83.8 L/min in group A, group B, and the control group, respectively. The PCF of group B was significantly lower than that of group A and the control group (p < 0.0001), while that of group B was significantly lower than that of the control group (p < 0.0001). The time until the cough reflex was 4.2 ± 5.9 s, 7.0 ± 7.0 s, and 1 s in group A, group B, and the control group, respectively. This duration was significantly longer for groups A and B than for the control group (A: p < 0.001, B: p < 0.001), but there was no significant difference between groups A and B (p = 0.0907). CONCLUSION: Our newly developed device can easily and simultaneously measure the time until the cough reflex and the strength of involuntary coughs for assessment of patients at risk of aspiration pneumonia.

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland.

Background: Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. Methods: We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. Results: While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. Conclusion: Our novel classification system based on anechoic area patterns demonstrated by the tumors had high sensitivity, specificity and diagnostic accuracy for differentiating Warthin tumors from pleomorphic adenomas.

Submucosal Abscess of the Esophagus Caused by Piriform Sinus Fistula Treated with Transoral Video Laryngoscopic Surgery.

Piriform sinus fistula (PSF) is a rare branchial anomaly that causes repetitive acute suppurative thyroiditis or deep neck abscess. The definitive treatment of PSF is open neck surgery. However, such surgery has a cosmetic problem and a high risk of recurrence. Furthermore, identifying the fistula is difficult due to previous repetitive infections. We report a case of esophageal submucosal abscess caused by PSF treated with endoscopic mucosal incision. The patient underwent transoral video laryngoscopic surgery (TOVS), and endoscopy as well as fluoroscopy revealed complete closure of PSF without any complication. TOVS is a novel surgical technique for the definitive treatment of PSF with esophageal submucosal abscess.

Dietary glucosylceramides suppress tumor growth in a mouse xenograft model of head and neck squamous cell carcinoma by the inhibition of angiogenesis through an increase in ceramide.

BACKGROUND: We previously reported that dietary glucosylceramides show cancer-prevention activity in a mouse xenograft model of human head and neck cancer cells (SCCKN). However, the mechanism was unclear. Ceramides, metabolites of glucosylceramides, induce apoptotic cell death in various malignancies. Here, we investigated the inhibitory effects of dietary glucosylceramides on tumor growth in vivo and in vitro. METHODS: SCCKN were subcutaneously inoculated into the right flanks of NOD/SCID mice. Mice were treated with or without dietary glucosylceramides (300 mg/kg) daily for 14 consecutive days after confirmation of tumor progression. Microvessel areas around the tumor were assessed by hematoxylin-eosin staining and immunohistochemistry of CD31, and, as markers for angiogenesis, protein levels of VEGF, VEGF receptor-2, and HIF-1α were assessed by Western blotting. Mass spectrometry was performed to measure the levels of sphingolipids in mouse serum after treatment with dietary glucosylceramides. RESULTS: Oral administration of glucosylceramides significantly decreased SCCKN growth in the xenograft model with inhibition of angioinvasion. In tumor-invasive areas, VEGF and HIF-1α in the tumor cells, and VEGF receptor-2 in endothelial cells decreased after treatment with dietary glucosylceramides. Dietary glucosylceramides increased serum levels of sphingosine-based ceramides as compared to the control. In SCCKN and UV♀2 cells, C6-ceramide suppressed the expressions of VEGF, VEGF receptor-2, and HIF-1α in vitro. CONCLUSION: These results suggest that dietary glucosylceramides trigger the de novo pathway of ceramide synthesis, indicating that sphingosine-based ceramide suppresses the growth of head and neck tumors through the inhibition of pro-angiogenic signals such as VEGF, VEGF receptor-2, and HIF-1α.

Subglottic laryngeal closure: a unique modified method of laryngotracheal separation to prevent aspiration.

OBJECTIVES: Laryngotracheal separation (LTS) is an ideal surgical method for intractable aspiration; however, the oral side of the tracheal stump can easily disintegrate. Therefore, we developed a modified LTS method. We performed subglottic laryngeal closure (SGLC) as a new surgical method and evaluated the outcomes. METHODS: We retrospectively analyzed the medical records of 36 patients (28 male and 8 female; 15 to 91 years of age) who underwent SGLC between 2007 and 2011 at Tottori University Hospital, Japan. Operative data (operative time, intraoperative bleeding, and time to drain removal), outcomes (aspiration and changes in nutritional status), and complications with regard to the surgical method were examined. The occurrence of a subcutaneous proximal laryngeal stump fistula was evaluated by videofluoroscopy. RESULTS: The SGLC was performed safely in all patients. Fistulization was observed in only 1 of the patients (2.8%), and major bleeding after surgery was observed in 1 patient (2.8%). The procedure relieved aspiration pneumonia in all patients. CONCLUSIONS: We conclude that SGLC is effective for treating and preventing pulmonary aspiration. The incidence of postoperative complications, particularly that of subcutaneous fistulas, was very low. Therefore, this method may be useful for patients in poor condition.

Capsule of parotid gland tumor: evaluation by 3.0 T magnetic resonance imaging using surface coils.

BACKGROUND: magnetic resonance (MR) imaging of parotid gland tumors has been widely reported, although few reports have evaluated the capsule of parotid gland tumors in detail. PURPOSE: to evaluate the diagnostic usefulness of 3.0 T MR imaging with surface coils for detection of the parotid gland tumor capsule, and to clarify the characteristics of the capsules. MATERIAL AND METHODS: seventy-eight patients with parotid gland tumors (63 benign and 15 malignant) were evaluated. Axial and coronal T2-weighted and contrast-enhanced T1-weighted images were obtained using a 3.0 T MR scanner with 70 mm surface coils. It was retrospectively assessed whether each parotid gland tumor was completely surrounded by a capsule. The capsule was classified as regular or irregular in terms of capsular thickness, and as none, mildly, or strongly enhancing in terms of contrast enhancement. Visual interpretations were compared with histopathological findings to evaluate the diagnostic ability of MR imaging to detect parotid gland tumor capsules. Statistical evaluation was conducted concerning the presence of capsules, capsular irregularity, and the difference in contrast enhancement between benign and malignant tumors, and that between pleomorphic adenomas and Warthin's tumors. RESULTS: capsules completely surrounding the tumor on MR imaging yielded a sensitivity of 87.7% (50/57), specificity of 90.5% (19/21), and accuracy of 88.5% (69/78). Benign tumors had a capsule completely surrounding the tumor significantly more often than malignant tumors (P = 0.009). Concerning capsular irregularity, malignant tumors tended to have more irregular capsules than benign tumors, although there were no significant differences. The capsules of malignant tumors enhanced significantly more strongly than those of benign tumors (P = 0.018). CONCLUSION: 3.0 T MR imaging using surface coils could correctly depict parotid gland tumor capsules in most cases. Most benign and some malignant tumors had capsules completely surrounding the tumors. Malignancy should be considered in tumors with irregular and strongly enhancing capsules.

The ability to identify the intraparotid facial nerve for locating parotid gland lesions in comparison to other indirect landmark methods: evaluation by 3.0 T MR imaging with surface coils.

INTRODUCTION: It is important to know whether a parotid gland lesion is in the superficial or deep lobe for preoperative planning. We aimed to investigate the ability of 3.0 T magnetic resonance (MR) imaging with surface coils to identify the intraparotid facial nerve and locate parotid gland lesions, in comparison to other indirect landmark methods. METHODS: We retrospectively evaluated 50 consecutive patients with primary parotid gland lesions. The position of the facial nerve was determined by tracing the nerve in the stylomastoid foramen and then following it on sequential MR sections through the parotid gland. The retromandibular vein and the facial nerve line (FN line) were also identified. For each radiologist and each method, we determined the diagnostic ability for deep lobe lesions and superficial lobe lesions, as well as accuracy. These abilities were compared among the three methods using the Chi-square test with Yates' correction. RESULTS: Mean diagnostic ability for deep lobe lesions, the diagnostic ability for superficial lobe lesions, and accuracy were 92%, 86%, 87%, respectively, for the direct identification method; 67%, 89%, 86%, respectively, for the retromandibular vein method; and 25%, 99%, 90% , respectively, for the FN line method. The direct identification method had significantly higher diagnostic ability for deep lesions than the FN line method (P < 0.01), but significantly lower diagnostic ability for superficial lobe lesions than the FN line method (P < 0.01). CONCLUSION: Direct identification of the intraparotid facial nerve enables parotid gland lesions to be correctly located, particularly those in the deep lobes.

Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy.

INTRODUCTION: To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. CASE REPORT: A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m(2)) on days 1, 8 and 15 in combination with docetaxel (60 mg/m(2)) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. CONCLUSION: The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities.

[Omohyoid muscle syndrome in a patient with Parkinson's disease].

A 49-year-old man noticed a resting tremor in his right hand and was diagnosed with Parkinson's disease (PD) at the age of 43. Soon thereafter, he noticed a right neck mass that only appeared when he swallowed and was accompanied by an uncomfortable sensation. At the age of 49, he was admitted to our hospital to adjust his medication for PD and to examine the neck mass. The subcutaneous mass was round, soft, and approximately 3 cm in diameter. The symptoms in his neck showed no progression. Resting tremors and rigidity due to his PD were predominantly observed on his right side, but his postural reflex was intact. Cervical echogram revealed that the mass was the belly of the OM itself. Thus, the patient was diagnosed with omohyoid muscle syndrome (OMS). It can be surmised that some susceptibility of the OM itself and/or structural fragility in the surrounding tissues would be involved in the pathogenesis of OMS. In this case, considering that OMS occurred soon after symptoms of PD appeared, we speculated that muscle tone abnormalities due to PD played a role in the development of OMS.

Lower brainstem dysfunction in an infant with persistent primitive trigeminal artery.

A 6-month-old boy with persistent primitive trigeminal artery (PPTA) presented with stridor, dysphagia, delayed motor development and postural neck and shoulder dystonia. Magnetic resonance imaging/angiography and ultrasonography revealed PPTA, with flow from the dilated basilar artery to the right internal carotid artery, lower brainstem compression by the dilated basilar artery, and cerebellar vermis hypoplasia. Evoked potentials showed lower pons and medulla oblongata functional disruption. These lesions may be related to vascular etiology in the lower brainstem or to congenital malformation syndrome involving infratentorial structures. The relationship of this condition to Möbius syndrome is discussed.

Sequence variability and candidate gene analysis in two cancer patients with complex clinical outcomes during morphine therapy.

In this case report, we present genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and mu opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different [i.e., sensitive (patient 1) and low responder (patient 2)]. In addition, allelic variants in the UGT2B7 gene were analyzed in 46 Japanese individuals. Amplified DNA fragments for the two genes of interest were screened using single strand conformation polymorphism and then sequenced. In the UGT2B7 gene, 12 single nucleotide polymorphisms (SNPs) were newly identified with an allelic frequency ranging from 0.022 to 0.978. Six SNPs in the promoter region (A-1302G, T-1295C, T-1111C, G-899A, A-327G, and T-125C) and two coding SNPs (UGT2B7*2 in exon 2 and C1059G in exon 4) appeared to be consistently linked. Remarkable differences in the nucleotide sequence of UGT2B7 were observed between the two patients; in contrast to patient 1 who had "reference" alleles at almost SNP positions, but a rare ATTGAT*2(AT)C haplotype as homozygosity, patient 2 was a homozygous carrier for the predominant GCCAGC*1(TC)G sequence. Serum morphine and two glucuronide concentrations in patient 2 suggest that the predominant GCCAGC*1G sequence was not associated with a "poor metabolizer" phenotype. In the MOR1 gene, patient 1 had no SNPs, whereas patient 2 was a heterozygous carrier for both the G-1784A and A118G alleles. The present study describes substantial differences in genotype patterns of two genes of interest between the two patients. The results necessitate larger trials to confirm these observations in larger case control studies.