鈴木 猛司

Background/Aims: The Lyon Consensus defined parameters based on upper endoscopy and 24-hour combined multichannel intraluminal impedance-pH (MII-pH), that conclusively establish the presence of gastroesophageal reflux disease (GERD). However, the true role of upper endoscopy and MII-pH to evaluate patients with extraesophageal symptoms (EES) has not been well established. Hypopharyngeal MII (HMII), which directly measures laryngopharyngeal reflux (LPR) events, has been utilized to evaluate patients with EES suggestive of LPR. Methods: This was a retrospective study involving patients with EES for > 12 weeks despite proton pump inhibitor therapy, and had no endoscopic confirmatory evidence for GERD and negative MII-pH. All patients were subsequently referred for further evaluation of EES with "unknown" etiology and underwent laryngoscopy and HMII. Based on HMII, abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (reflux 2 cm distal to the upper esophageal sphincter) > 4/day. Patients with APE were offered antireflux surgery (ARS) and the outcome of ARS was objectively assessed using Reflux Symptom Index. Results: Of 21 patients with EES which was thought to be GERD-unrelated based on endoscopy and MII-pH, 17 patients (81%) had APE. Eight patients with APE who had undergone ARS had significant symptomatic improvement in the Reflux Symptom Index score (19.6 ± 4.9 pre-ARS to 5.8 ± 1.4 post-ARS, P = 0.008). Conclusions: A conventional diagnostic approach using endoscopy and MII-pH may not be sufficient to evaluate patients with EES suggestive of LPR. HMII is essential to evaluate patients with EES, and APE could be a reliable indicator for successful treatment outcomes.

Hypopharyngeal multichannel intraluminal impedance (HMII) that can measure laryngopharyngeal reflux (LPR) events has supported the causal relationship between chronic cough (CC) and LPR containing liquid. However the role of "gas" LPR associated with CC has been poorly understood. We present two cases of patients with CC who had negative LPR containing liquid but had multiple episodes of "gas" LPR on HMII. The majority of "gas" LPR events had a minor pH drop at hypopharynx. Since any etiology of CC was excluded and medical therapy failed, both patients underwent laparoscopic antireflux surgery (LARS). Both of the patients had complete resolution of cough postoperatively. The present cases demonstrated successful outcome of LARS to treat the patients with CC who had documented "gas" LPR on HMII, thus suggesting the causal relationship between CC and "gas" LPR. The number of "gas" LPR events may need to be considered as an important diagnostic parameter.

保存的治療抵抗性の咽喉頭逆流症(LPRD)28例(男性16例、女性12例、年齢中央値51歳)に対し腹腔鏡下逆流防止術(LARS)を施行し、治療効果について検討した。術後経過観察期間12ヵ月(中央値)の結果、LPRD主症状は26例(93%)で改善が認められ、うち16例(57%)は症状の完全な消失が得られていた。LARS後3ヵ月の時点でFSSG、RSIスコアは有意に低下するも、RSIスコアは正常値であった。一方、2例は症状不変であった。また、2例で症状再発が認められたが、いずれもwrapの縦隔内逸脱を腹腔鏡下に整復し、再手術後は症状の改善が得られた。尚、LARSの有害事象である3ヵ月以上継続する食事時の心窩部のつまり感は5例(18%)で確認された。

慢性咳嗽の原因としてGERDは鑑別の一つとなりうるが、本邦では欧米に比較し、その割合は低いと考えられている。しかし、PPI抵抗性のGERDや食道粘膜障害を伴わないNERDの存在、また、日本人の肥満率は欧米のそれと比べ低いことから日本人のGERD罹患率が低く見積もられている可能性がある。近年、24時間下咽頭食道多チャンネルpHインピーダンス検査(HMII)が開発され、確定診断が難しかった咽喉頭逆流(LPR)を測定することができるようになった。本研究は、本邦で初めてHMIIを用い、日本人の原因不明慢性咳嗽患者における咽喉頭逆流症(LPRD)の関与を検討する目的で行った。日本人原因不明慢性咳嗽患者の73%にabnormal proximal exposure(APE)を認め、難治性慢性咳嗽はLPRを含めた胃内容物の高位逆流が原因である可能性が示唆された。また、DeMeester scoreは63%が正常であり、約40%のLPRまたは食道高位への逆流は非酸性の逆流であり、24時間pHモニタリングでは診断が難しく、難治性慢性咳嗽の診断にはHMIIが必要であると考えられた。(著者抄録)

Background: Clinical characteristics of laryngopharyngeal reflux (LPR) in Japanese population remain unclear, and its treatment outcome is suboptimal. The objectives of this study were to evaluate Japanese patients with LPR symptoms using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the outcome of antireflux surgery (ARS). Methods: Subjects included patients who had LPR symptoms for &gt 12 weeks or laryngoscopic findings suggestive of LPR and underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (FCR) (reflux 2 cm distal to the upper esophageal sphincter) ≥ 5/day on HMII. Patients with APE were offered ARS and the outcome of ARS was objectively assessed using Reflux Symptom Index (RSI). Results: From July 2015 to September 2016, 52 patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII, and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI &lt 25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third of LPR and FCR events were non-acid in the distal esophagus. A positive symptom-association probability was seen only in 18 patients (35%). Mild esophagitis and hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12 patients (100%) who had undergone ARS were able to discontinue PPI and had a significant improvement in the RSI scores postoperatively (22.9 ± 10.0 vs. 6.8 ± 6.8, p &lt  .001). Conclusions: APE was frequently observed in Japanese patients with LPR symptoms. Obesity and esophagitis were uncommon in this population. Since a large number of patients with APE had negative DeMeester score and proximal reflux events were often non-acid, a conventional pH monitoring is insufficient. HMII is crucial to evaluate patients with LPR symptoms as the documentation of APE is a key for successful outcome of ARS.

Background: People with allergic rhinitis often have laryngeal symptoms (LSs) in addition to nasal symptoms during the pollen-scattering season. Objective: To clarify the characteristics of the LSs induced by pollen exposure using an environmental challenge chamber. Methods: Cypress pollen exposure using an environmental challenge chamber for 25 participants with cypress polleneinduced allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study courses: namely, pollen exposure under normal nasal breathing and pollen or sham pollen exposure with nasal blockage, which eliminated any allergic reactions in the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal examinations and physiologic lung tests were also conducted. Results: Various LSs were reported, and these LSs were significantly elevated during pollen exposure and even under sham exposure with artificial nasal blockage. The pollen exposure with artificial nasal blockage exaggerated the LSs in 32% of the participants and also increased the serum ECP levels. The serum ECP levels did not change after sham exposure. The findings of both laryngeal examinations and lung tests failed to reveal any significant changes. Conclusion: Nasal obstruction could induce significant LSs even without pollen exposure. LSs were enhanced by pollen exposure and allergic reactions in the larynx could thus be involved in this enhancement. Trial Registration: clinicaltrials.gov Identifier: UMIN000015667. (C) 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Suzuki T, Sugiyama Y, Yates BJ. Integrative responses of neurons in parabrachial nuclei to a nauseogenic gastrointestinal stimulus and vestibular stimulation in vertical planes. Am J Physiol Regul Integr Comp Physiol 302: R965-R975, 2012. First published January 25, 2012; doi: 10.1152/ajpregu.00680.2011.-The parabrachial and adjacent Kolliker-Fuse (PBN/KF) nuclei play a key role in relaying visceral afferent inputs to the hypothalamus and limbic system and are, thus, believed to participate in generating nausea and affective responses elicited by gastrointestinal (GI) signals. In addition, the PBN/KF region receives inputs from the vestibular system and likely mediates the malaise associated with motion sickness. However, previous studies have not considered whether GI and vestibular inputs converge on the same PBN/KF neurons, and if so, whether the GI signals alter the responses of the cells to body motion. The present study, conducted in decerebrate cats, tested the hypothesis that intragastric injection of copper sulfate, which elicits emesis by irritating the stomach lining, modifies the sensitivity of PBN/KF neurons to vertical plane rotations that activate vestibular receptors. Intragastric copper sulfate produced a 70% median change in the gain of responses to vertical plane rotations of PBN/KF units, whose firing rate was modified by the administration of the compound; the response gains for 16 units increased and those for 17 units decreased. The effects were often dramatic: out of 51 neurons tested, 13 responded to the rotations only after copper sulfate was injected, whereas 10 others responded only before drug delivery. These data show that a subset of PBN/KF neurons, whose activity is altered by a nauseogenic stimulus also respond to body motion and that irritation of the stomach lining can either cause an amplification or reduction in the sensitivity of the units to vestibular inputs. The findings imply that nausea and affective responses to vestibular stimuli may be modified by the presence of emetic signals from the GI system.

Objective It is important to identify and save the normal parathyroid glands during head and neck surgery because of their role in regulating the blood calcium level, yet it is often difficult to localize normal parathyroid glands during surgery. Fluorescence-guided parathyroidectomy in patients with hyperparathyroidism has already proved useful. However, there are few reports of fluorescence-guided localization of normal parathyroid glands in humans. We investigated the utility of fluorescence-guided localization of normal parathyroid glands during thyroidectomy and completed a spectral fluorescence analysis of the accumulation of 5-aminolevulinic acid metabolites in the parathyroid glands. Methods Eight patients with benign thyroid disease and five with malignant thyroid tumors were given 20 mg/kg body weight of 5-aminolevulinic acid orally 5 hours before surgery. After the posterior surface of the thyroid gland was exposed and the recurrent laryngeal nerve was identified, we illuminated the area with a violet-blue light of 405 nm. Tissues showing red fluorescence were biopsied to analyze the spectral fluorescence. Results Under the violet-blue light, normal parathyroid glands showed red fluorescence, while the surrounding structures such as the thyroid gland, muscles, and fat remained nonfluorescent. The spectral peak was observed at 635 nm indicating 5-aminolevulinic acid metabolites. Histopathologically, the biopsied tissue corresponded to normal parathyroid glands. Conclusions 5-Aminolevulinic acid is useful to localize the normal parathyroid glands during thyroid surgery in humans.

甲状腺腫瘍などの手術において正常副甲状腺を同定し確実に温存することは、術後の血中カルシウム維持のために重要である。これまで、病的副甲状腺の染色方法の報告はあるものの、正常副甲状腺の術中同定法の報告は少ない。今回、アミノレブリン酸(5-ALA)を用い、正常副甲状腺の術中光線力学的同定を行った。甲状腺良性腫瘍患者9例において、副甲状腺を露出する約5時間前に5-ALA20mg/kgを経口投与した。甲状腺裏面露出後、周囲組織を波長405nmの青紫色光で励起させ、赤色発光し副甲状腺と考えられる組織を一部生検し病理組織検査を行った。全例が赤色蛍光発光し容易に確認でき、病理組織学的にも正常副甲状腺と確認された。(著者抄録)

Inhibitory postsynaptic potentials (IPSPs) of laryngeal motoneurons (LMs) are essential for narrowing the glottis at just the right time during swallowing, which prevents aspiration. To examine the property of IPSPs of LMs during swallowing, we monitored the effects of intracellular application of chloride ion and extracellular application of inhibitory neurotransmitter antagonists on the membrane potential trajectories of LMs during fictive swallowing in decerebrate, paralyzed cat. Adductor LMs hyperpolarized briefly at the beginning of the pharyngeal stage of swallowing (PS) and then depolarized explosively during the remaining part of the PS. Abductor LMs exhibited various patterns during swallowing; hyperpolarization during the PS followed by depolarization at the offset of the PS, slight depolarization, or plateau potentials. Chloride-dependent IPSPs were revealed during the initial part of PS in adductor LMs and during the whole PS in abductor LMs. The swallow-related IPSPs were depressed by iontophoretic extracellular application of bicuculline in both adductor and abductor LMs, but they were not modified by strychnine application. It is concluded that the swallow-related inhibition of both adductor and abductor LMs is chloride-dependent IPSPs mediated through GABA(A) receptors, not through glycine receptors. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.