Publications by authors named "Yoshiyuki Kawashima"

96 Publications

Optimal Region of Lymph Node Dissection in Distal Pancreatectomy for Left-Sided Pancreatic Cancer Based on Tumor Location.

Ann Surg Oncol 2021 Nov 26. Epub 2021 Nov 26.

Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.

Background: The optimal lymph node (LN) dissection for left-sided pancreatic cancer based on tumor location has remained unknown. In particular, the efficacy of LN dissection around the common hepatic artery and the celiac axis for distal tumors has not been established. This study was designed to elucidate the frequency and prognostic impact of LN metastasis, focusing on tumor location.

Methods: Data from 110 patients with invasive pancreatic cancer who underwent distal pancreatectomy between 2007 and 2020 were collected. We used a quantitative value-the distance between the left side of the portal vein and the right side of tumor (DPT)-to define the tumor location. LN stations were divided into two groups: peripancreatic lymph nodes (PLN) and non-PLN. We then analyzed the frequency of LN metastasis based on the tumor location and prognostic factors.

Results: Non-PLN metastasis was observed in 7.3% of patients. Non-PLN metastasis was found only in patients with a DPT < 20 mm. Patients with non-PLN metastasis exhibited a significantly worse prognosis than those with only-PLN metastasis (median survival time: 20.3 vs. 42.5 months, p = 0.048). Multivariate analysis for survival indicated that tumor size > 4 cm (hazard ratio [HR]: 2.23, p = 0.012) and metastasis in the non-PLN region (HR: 3.02, p = 0.015), and inability to undergo adjuvant chemotherapy (HR: 2.81, p = 0.0018) were also associated with poor prognosis.

Conclusions: Dissection of the non-PLN region can be avoided in selected patients with DPT ≥ 20 mm.
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http://dx.doi.org/10.1245/s10434-021-11108-5DOI Listing
November 2021

Application of a virtual and mixed reality-navigation system using commercially available devices to the lateral temporal bone resection.

Ann Med Surg (Lond) 2021 Dec 16;72:103063. Epub 2021 Nov 16.

Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Lateral temporal bone resection (LTBR) is performed for stage T1-2 external ear malignant tumors and requires spatial anatomical knowledge of the rare surgical field.

Objective: This paper presents a novel virtual reality (VR) based surgical simulation and navigation system using only commercially available display device and an online software, to assist in the understanding of the anatomy pre and intraoperatively.

Result And Conclusion: VR model created by 3D Slicer modules and visualized on head mounted display enabled users to simulate and learn surgical techniques of a rare surgical case. 3D hologram through HoloLens assisted the surgeon in comprehending the spatial relationship between crucial vital structures and the pathological lesion during the operation. This platform does not require the users to possess specific programming skill or knowledge, and is therefore applicable in daily clinical usage.
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http://dx.doi.org/10.1016/j.amsu.2021.103063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604738PMC
December 2021

Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice.

J Assoc Res Otolaryngol 2021 12 7;22(6):681-691. Epub 2021 Oct 7.

Department of Otorhinolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan.

Incomplete partition type II (IP-II) is frequently identified in ears with SLC26A4 mutations. Cochleae with IP-II are generally observed to have 1½ turns; the basal turns are normally formed, and the apical turn is dilated or cystic. The objective of this study was to characterize the pathomorphogenesis of the IP-II cochlear anomaly in Slc26a4-null mice. Otic capsules were dissected from Slc26a4 and Slc26a4 mice at 1 and 8 days of age and at 1 and 3 months of age. X-ray micro-computed tomography was used to image samples. We used a multiplanar view and three-dimensional reconstructed models to calculate the cochlear duct length, cochlear turn rotation angle, and modiolus tilt angle. The number of inner hair cells was counted, and the length of the cochlear duct was measured in a whole-mount preparation of the membranous labyrinth. X-ray micro-computed tomography mid-modiolar planar views demonstrated cystic apical turns in Slc26a4 mice resulting from the loss or deossification of the interscalar septum, which morphologically resembles IP-II in humans. Planes vertical to the modiolus showed a similar mean rotation angle between Slc26a4 and Slc26a4 mice. In contrast, the mean cochlear duct length and mean number of inner hair cells in Slc26a4 mice were significantly smaller than in Slc26a4 mice. In addition, there were significant differences in the mean tilt angle and mean width of the modiolus. Our analysis of Slc26a4-null mice suggests that IP-II in humans reflects loss or deossification of the interscalar septum but not a decreased number of cochlear turns.
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http://dx.doi.org/10.1007/s10162-021-00812-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599553PMC
December 2021

Colloid carcinoma derived from intraductal papillary mucinous neoplasm of the pancreatic head with calcification: A case report and literature review.

Surg Case Rep 2021 Sep 6;7(1):202. Epub 2021 Sep 6.

Department of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-Adachi-gun, Saitama, 362-0806, Japan.

Background: Colloid carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreatic head with prominent calcification is exceedingly rare. Only a few studies about this entity have been reported in the literature. Therefore, its biological behavior, appropriate treatment modalities, and overall patient prognosis remain largely unclear. In this report, we present a case of a resected colloid carcinoma derived from IPMN with prominent calcification. In addition, we review the relevant literature and discuss the clinical management of colloid carcinoma derived from IPMN with prominent calcification, including the histopathological features.

Case Presentation: A 75-year-old man presented with a pancreatic tumor measuring 58 mm on the head of the pancreas that was incidentally detected by abdominal ultrasonography. Abdominal computed tomography and endosonography revealed a multilobular cystic lesion with a 17 mm mural nodule in the pancreatic head. Furthermore, prominent calcification was observed on part of the cyst wall. Magnetic resonance cholangiopancreatography showed a multilobular cyst in the branch duct lacking communication between the cystic lesion and the main pancreatic duct. Thus, the lesion was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with a preoperative classification of T1N0M0 stage IA according to the 8th Union for International Cancer Control (UICC) guidelines, and the patient underwent conventional pancreatoduodenectomy. The resected specimen was microscopically found to contain colloid carcinoma, probably derived from IPMN. In addition, marked calcification was confirmed in the partition wall of the cystic mass. The postoperative course was uneventful, and no evidence of recurrence or metastasis was observed after 10 months of follow-up.

Conclusions: We consider that colloid carcinoma derived from IPMN should be differentially diagnosed as a pancreatic multilobular cystic lesion with prominent calcification that shows no sign of systemic chronic pancreatitis.
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http://dx.doi.org/10.1186/s40792-021-01286-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421485PMC
September 2021

Four-Hour Delayed Gadolinium-Enhanced 3D-FLAIR MR Imaging Highlights Intralabyrinthine Micro-Schwannomas.

Otol Neurotol 2021 Dec;42(10):e1444-e1448

Department of Otolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.

Objective: To demonstrate the clinical significance of 4-hour delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (delayed 3D-FLAIR) in patients with intralabyrinthine schwannoma (ILS).

Patients: Three patients who were clinically diagnosed with ILS.

Interventions: All patients underwent audiological examinations and magnetic resonance imaging (MRI) scans. The MR-protocol included axial MR cisternography, immediate gadolinium-enhanced T1-weighted sequence, and heavily T2-weighted 3D-FLAIR prior to and 4 hours after the intravenous administration of gadolinium contrast medium.

Main Outcome Measures: All MR images were visually inspected.

Results: In all three patients with ILS, delayed 3D-FLAIR MRI demonstrated a strong signal of cochlear fluid surrounding the tumor, which highlighted a tumor region that lacked signals.

Conclusions: Delayed 3D-FLAIR MRI may serve as a novel diagnostic tool for the early detection of intralabyrinthine micro-schwannoma. The findings also shed light on the pathophysiology of ILS.
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http://dx.doi.org/10.1097/MAO.0000000000003310DOI Listing
December 2021

Comparison of effects of six main gastrectomy procedures on patients' quality of life assessed by Postgastrectomy Syndrome Assessment Scale-45.

World J Gastrointest Surg 2021 May;13(5):461-475

Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Background: The effects of various gastrectomy procedures on the patient's quality of life (QOL) are not well understood. Thus, this nationwide multi-institutional cross-sectional study using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45), a well-established questionnaire designed to clarify the severity and characteristics of the postgastrectomy syndrome, was conducted.

Aim: To compare the effects of six main gastrectomy procedures on the postoperative QOL.

Methods: Eligible questionnaires retrieved from 2368 patients who underwent either of six gastrectomy procedures [total gastrectomy with Roux-en-Y reconstruction (TGRY; = 393), proximal gastrectomy (PG; = 193), distal gastrectomy with Roux-en-Y reconstruction (DGRY; = 475), distal gastrectomy with Billroth-I reconstruction (DGBI; = 909), pylorus-preserving gastrectomy (PPG; = 313), and local resection of the stomach (LR; = 85)] were analyzed. Among the 19 main outcome measures of PGSAS-45, the severity and characteristics of postgastrectomy syndrome were compared for the aforementioned six gastrectomy procedures using analysis of means.

Results: TGRY and PG significantly impaired the QOL of postoperative patients. Postoperative QOL was excellent in LR (cardia and pylorus were preserved with minimal resection). In procedures removing the distal stomach, diarrhea subscale (SS) and dumping SS were less frequent in PPG than in DGBI and DGRY. However, there was no difference in the postoperative QOL between DGBI and DGRY. The most noticeable adverse effects caused by gastrectomy were meal-related distress SS, dissatisfaction at the meal, and weight loss, with significant differences among the surgical procedures.

Conclusion: Postoperative QOL greatly differed among six gastrectomy procedures. The severity and characteristics of postgastrectomy syndrome should be considered to select gastrectomy procedures, overcome surgical shortcomings, and enhance postoperative care.
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http://dx.doi.org/10.4240/wjgs.v13.i5.461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167845PMC
May 2021

Patient-specific virtual and mixed reality for immersive, experiential anatomy education and for surgical planning in temporal bone surgery.

Auris Nasus Larynx 2021 Dec 29;48(6):1081-1091. Epub 2021 May 29.

Department of Otorhinolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113 - 8510, JAPAN.

Objective: The recent development of extended reality technology has attracted interest in medicine. We explored the use of patient-specific virtual reality (VR) and mixed reality (MR) temporal bone models in anatomical teaching, pre-operative surgical planning and intra-operative surgical referencing.

Methods: VR and MR temporal bone models were created and visualized on head-mounted display (HMD) and MR headset respectively, by a novel webservice that allows users to convert computed tomography images to VR and MR images without specific knowledge of programming. Eleven otorhinolaryngology trainees and specialists were asked to manipulate the healthy VR temporal bone model and to assess its validity by filling out a questionnaire. Additionally, VR and MR pathological models of petrous apex cholesteatoma were utilized for surgical planning pre-operatively and for referring to the anatomy during the surgery.

Results: Most participants were favorable about the VR model and considered HMD as superior to a flat computer screen. 91% of the participants agreed or somewhat agreed that VR through HMD is cost effective. In addition, the VR pathological model was used for planning and sharing the surgical approach during a pre-operative surgical conference. The MR headset was worn intra-operatively to clarify the relationship between the pathological lesion and vital anatomical structures.

Conclusion: Regardless of the participants' training level in otorhinolaryngology or VR experience, all participants agreed that the VR temporal bone model is useful for anatomical education. Furthermore, the creation of patient-specific VR and MR models using the webservice and their pre- and intra-operative usages indicated the potential of innovative adjunctive surgical instrument.
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http://dx.doi.org/10.1016/j.anl.2021.03.009DOI Listing
December 2021

Conformations and Low-Frequency Intramolecular Motions of 1-Butanol, 1-Butanethiol, -butanol, and -butanethiol Investigated by Fourier Transform Microwave Spectroscopy Combined with Quantum Chemical Calculations.

J Phys Chem A 2021 Feb 27;125(5):1166-1183. Epub 2021 Jan 27.

The Graduate University for Advanced Studies, Hayama, Kanagawa 240-0193, Japan.

The rotational spectra of 1-butanol (1-BuOH), 1-butanethiol (1-BuSH), 2-methyl-1-propanol (-BuOH), and 2-methyl-1-propanethiol (-BuSH) were measured by Fourier transform microwave spectroscopy in the frequency region from 3.7 up to 25 GHz. The observed spectral lines were assigned by observation of the deuterium substitution effect and by ab initio or density functional theory calculations at the levels of MP2/6-311++G(d,p) or B3LYP and -B3LYP, respectively. For 1-BuOH and 1-BuSH, seven of the 14 conformations, anticipated to exist as stable, were detected, whereas four and three among the five possible conformations were identified for -BuOH and -BuSH, respectively. We further found that, of the seven conformers of 1-BuOH, five were and two , with respect to the internal rotation axis: the C2-C3 bond, while three of -BuOH existed in and one in . The most stable conformer of the two BuOH molecules was with respect to the C-O bond, while all the sulfur analogues were to the C-S axis. The rare isotopomers examined included C and OD of 1-BuOH and OD of -BuOH, S, C, and SD of the two sulfur molecules, and the rotational constants obtained on these isotopomers were employed in the molecular structure derivation. The potential barrier to CH internal rotation and the deuterium quadrupole coupling constant, where available, were also derived from the spectral analysis, and the molecular parameters thus obtained were compared with those derived using quantum-chemical calculations; the values derived using -B3LYP/6-311++G(d,p) were in better agreement with the observed than those derived using MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p). The form of 1-BuOH and of 1-BuSH and the form of -BuSH exhibited additional spectral splittings, which were interpreted as caused by the OH or SH group tunneling between the symmetric and antisymmetric states. Some of the = 8 rotational levels of 1-BuSH happened to be near-degenerate with others, and the splittings in them caused by mutual repulsion could be precisely determined by the observation of the transitions involving those split levels. Such splittings were determined for 1-BuSH, 1-BuSD, and -BuSH to be 1694.1731 (22), 56.3174 (16), and 6.4678 (14) MHz, respectively. A natural bond orbital analysis was performed to show that the most stable conformation of the primary and secondary alcohols is because of the charge transfer from the lone-pair electron of the oxygen atom to the antibonding orbital of the C-H bond in 1-BuOH, whereas in -BuOH, the charge transfer to the antibonding orbital of the C1-C2 bond.
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http://dx.doi.org/10.1021/acs.jpca.0c09687DOI Listing
February 2021

Indications for and extent of elective neck dissection for lymph node metastasis from external auditory canal carcinoma.

Auris Nasus Larynx 2021 Aug 30;48(4):745-750. Epub 2020 Dec 30.

Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.

Objectives: We aim to clarify the frequency of lymph node metastasis of external auditory canal (EAC) carcinoma, including susceptible locations, adequate extent of elective neck dissection, and the relationship between the tumor infiltration site and lymph node metastasis.

Patients And Methods: From 2003 to 2018, 63 patients with EAC carcinoma at Tokyo Medical and Dental University Hospital were enrolled in this study. The T and N stages, locations of clinically positive lymph nodes, prognoses, and anatomic site of tumor infiltration were analyzed after treatment.

Results: Clinically positive lymph node metastasis (cN+) was detected in 18 patients (28.6%), consisting of T1, T2, T3, and T4 disease in 1 (6%), 2 (22%), 8 (38%), and 7 (41%) patients, respectively. The metastatic locations were at level II in 10 patients, parotid gland nodes in 7, preauricular nodes in 5, level Ib in 3, level Va in 3, level III in 1, and superficial cervical nodes in 1. Neck recurrence was determined in two of 45 patients with clinically negative lymph nodes (cN0), with the metastatic locations being levels II, Ib, and III. Among 18 cN+ cases, neck recurrence was noted in 2 of 9 patients who underwent neck dissection. Neck lesions were found to be manageable in all five patients who underwent docetaxel, cisplatin, 5-fluorouracil, and radiation therapy (TPF-RT). No relationship was noted between the tumor infiltration site and lymph node metastasis among T3/4 canrcinoma patients.

Conclusions: Elective neck dissection could be indicated only in T3/4 patients with free flap reconstruction. Levels Ib to III are considered appropriate for elective neck dissection in cN0 cases. Levels Ib to III and Va indicated favorable sites, even in cases with metastasis in the parotid gland or preauricular area. Furthermore, TPF-RT could be a useful option even in cN+ cases.
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http://dx.doi.org/10.1016/j.anl.2020.12.002DOI Listing
August 2021

Enhanced fallopian canal as a potential marker for temporal bone vasculitis.

Laryngoscope Investig Otolaryngol 2020 Dec 4;5(6):1168-1175. Epub 2020 Nov 4.

Department of Otolaryngology Tokyo Medical and Dental University Tokyo Japan.

Objectives: This study aimed to test the hypothesis that contrast-enhanced 3D MRI with gradient-echo sequences (CE-3D-GRE) can detect signs of vasculitis in the fallopian canal, which may cause otologic involvement, in four patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: CE-3D-GRE acquired at 3.0 Tesla was performed on four patients diagnosed with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis, at onset or relapse of the disease, and in remission. Clinical correlations between otologic symptoms and radiological findings were examined for each patient. Furthermore, signal intensity of the mastoid segment of the fallopian canal was compared between the ears with active disease (n = 3) and those in remission or without vasculitis (n = 3).

Results: Intense enhancement in the tympanic and mastoid segments of the fallopian canal was associated with development of external otitis, otitis media, and sensorineural hearing loss, and was unrelated to the presence of facial paresis. Maximal intensity projection images visualized the close relationship between the enhanced fallopian canal and middle ear inflammation. The findings were absent in remission. Signal intensity of the mastoid segment of the fallopian canal was higher in ears with active disease than in normal ears ( < .001) and decreased to normal levels during remission ( = .597).

Conclusion: CE-3D-GRE can demonstrate vasculitis in the temporal bone, reflecting disease activity and the severity of otologic manifestations, including cochlear involvement, in AAV patients. Intense enhancement of the fallopian canal on CE-3D-GRE can be a potential marker for vasculitis of the temporal bone.

Level Of Evidence: 5.
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http://dx.doi.org/10.1002/lio2.489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752078PMC
December 2020

Denosumab-induced osteonecrosis of external auditory canal.

Auris Nasus Larynx 2021 Dec 23;48(6):1199-1203. Epub 2020 Jul 23.

Department of Otolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address:

Denosumab is the world's first human monoclonal antibody for the treatment of osteoporosis and shares an active pathway with bisphosphonates, strongly suppressing osteoclast activities. This is the first case report describing a possible relationship between the development of osteonecrosis of external auditory canal and denosumab administration. We herein report an 81-year-old woman diagnosed with left osteonecrosis of external auditory canal who had a history of denosumab administration. She underwent left radical mastoidectomy due to being refractory to conservative treatment. No major complications or recurrence were observed in the left ear after surgery, but bone erosion in the right ear has continued to progress slowly despite the cessation of denosumab administration. Otolaryngologists should be aware of the association between osteonecrosis of external auditory canal and denosumab administration and consider performing long-term observation even after cessation.
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http://dx.doi.org/10.1016/j.anl.2020.07.007DOI Listing
December 2021

Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Sensory Mechanoelectrical Transduction Channels.

J Assoc Res Otolaryngol 2020 04 9;21(2):137-149. Epub 2020 Mar 9.

Department of Otolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Systemically administered aminoglycoside antibiotics can enter inner ear hair cells and trigger apoptosis. However, the in vivo route(s) by which aminoglycoside antibiotics enter hair cells remains controversial. Aminoglycosides can enter mouse hair cells by endocytosis or by permeation through transmembrane ion channels such as sensory mechanoelectrical transduction (MET) channels, transient receptor potential (TRP) channels, P2X channels, Piezo2-containing ion channels, or a combination of these routes. Transmembrane channel-like 1 (TMC1) and TMC2 are essential for sensory MET and appear to be the pore-forming components of sensory MET channels. The present study tested the hypothesis that systemic fluorescent gentamicin enters mouse hair cells predominantly through sensory MET channels. We employed Tmc1, Tmc2, and Tmc1::mCherry mice. In Tmc1::mCherry mice, the transgene was integrated on the X chromosome, resulting in mosaic expression of TMC1-mCherry in the hair cells of female heterozygous mice. After systemic administration of gentamicin-conjugated Texas Red (GTTR) into Tmc1;Tmc2 mice and wild-type mice at postnatal day 4 (P4), robust GTTR fluorescence was detected in wild-type hair cells, whereas little or no GTTR fluorescence was detected in Tmc1;Tmc2 hair cells. When GTTR was injected into developing mice at P0, P2, P4, or P6, the GTTR fluorescent intensity gradually increased from P0 to P4 in wild-type hair cells, whereas the intensity was stably low from P0 through P6 in Tmc1;Tmc2 hair cells. The increase in the GTTR intensity coincided with the spatio-temporal onset of sensory MET in wild-type hair cells. In Tmc1::mCherry cochleae, only hair cells that showed a significant uptake of systemic GTTR took up FM1-43. Transmission electron microscopy could detect no disruption of normal endocytosis at the apical surface of Tmc1;Tmc2 hair cells in vitro. These results provide substantial novel evidence that in vivo gentamicin enters neonatal mouse hair cells predominantly through sensory MET channels and not via endocytosis.
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http://dx.doi.org/10.1007/s10162-020-00746-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270392PMC
April 2020

Potential Confounding Factors May Influence the Association Between Configurations of the Vertebrobasilar System and the Incidence of Idiopathic Sudden Sensorineural Hearing Loss and Canal Paresis.

Otol Neurotol 2020 Jun;41(5):e548-e555

Department of Otolaryngology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Objective: To investigate the impact of configurations of the vertebrobasilar system on the incidence of idiopathic sudden sensorineural hearing loss (ISSNHL) and canal paresis (CP).

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Two hundred and forty-eight consecutive patients diagnosed with ISSNHL and 152 patients with unilateral CP of an uncertain cause who were managed between January 2011 and December 2017. The contralateral side of 144 patients with Bell's palsy or cerebellopontine angle tumor served as a control.

Interventions: All patients underwent magnetic resonance cisternography. CP was diagnosed based on caloric testing.

Main Outcome Measures: 1) Branching patterns of the anterior/posterior inferior cerebellar artery (AICA/PICA) in the cerebellopontine angle area. 2) The direction of the basilar artery (BA) curvature. 3) Vertebral artery (VA) dominance.

Results: The incidence of vascular loops of the AICA/PICA entering the internal acoustic canal was significantly higher on both the affected and unaffected sides in patients with ISSNHL and CP in comparison to controls (p < 0.05). The curved BA was observed more frequently in the ISSNHL and CP groups than in the control group (p < 0.05), whereas the direction of the BA curvature was not associated with the laterality of ISSNHL or CP. The incidence of asymmetric VA in CP patients was significantly higher than that in controls (p = 0.0304), while no significant difference was observed between ISSNHL patients and controls. Remarkably, while the incidence rate of irregular vascular configurations was high in both the ISSNHL and CP groups, there was no marked difference between the affected and unaffected ears of the ISSNHL and CP groups.

Conclusions: Our results indicate that the vascular configurations of the vertebrobasilar system do not directly cause ISSNHL and CP. Instead, they suggest the presence of confounding factors that influence the vascular configurations and the development of ISSNHL and CP.
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http://dx.doi.org/10.1097/MAO.0000000000002605DOI Listing
June 2020

Anomalies of the right vertebral vein increasing the difficulty of lymph-node dissection along the right recurrent laryngeal nerve: a single-institution, retrospective study.

Esophagus 2020 07 22;17(3):257-263. Epub 2020 Feb 22.

Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, 780 Komuro Inamachi, Kitaadachi-gun, Saitama, 362-0806, Japan.

Background: Radical lymph-node dissection along the recurrent laryngeal nerves (RLN) improves the prognosis of patients with esophageal cancer. The RLN is a landmark for achieving adequate lymph-node dissection. However, the right RLN is sometimes covered by the right vertebral veins (VVs), making it undetectable. We investigated the relationship between this anomaly of the right VVs and the challenges of performing lymphadenectomy along the right RLN.

Methods: Patients with esophageal cancer, who underwent thoracoscopic esophagectomy with radical lymph-node dissection, were registered. The patterns of the right VVs were evaluated by preoperative computed tomography. The time required for identifying the right RLN or completing the lymphadenectomy was determined by reviewing surgical videos.

Results: In total, 178 patients were enrolled. Eighty patients (45%) had right VVs passing dorsal to the right subclavian artery (Dorsal group). More time was required to detect the right RLN in these cases (11 vs 9.5 min for the other cases, p = 0.034). In the Dorsal group, there were 15 patients who had specific VV patterns: The right VV converged on the lower portion of the right brachiocephalic vein (BCV), or passed through to the more medial side of the mediastinum. These patients required more time for detecting the right RLN (25 vs 9 min, p < 0.0001) and for completing the lymphadenectomy (41 vs 32 min, p = 0.048) than the other cases.

Conclusion: The right VVs behind the subclavian artery, joining the lower part of the BCV or passing through the medial side, made it difficult to identify the right RLN and complete the lymphadenectomy.
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http://dx.doi.org/10.1007/s10388-020-00723-yDOI Listing
July 2020

The Risk of Developing Multiple Primary Cancers among Long-Term Survivors Five Years or More after Stomach Carcinoma Resection.

Tohoku J Exp Med 2020 01;250(1):31-41

Department of Gastroenterological Surgery, Saitama Cancer Center.

Recently, the number of long-term survivors of ≥ 5 years after stomach carcinoma resection is increasing in Japan. The clinical courses of 4,883 patients who underwent stomach carcinoma resection were retrospectively reviewed to investigate the cause of death including multiple primary cancers (MPC) and delayed stomach carcinoma recurrence among long-term survivors of ≥ 5 years. Of 3,061 patients who survived for ≥ 5 years, 1,203 patients (39.3%) were dead after 5 years survival, including 299 patients (24.9%) who died of MPC. Of 84 patients (7.0%) who died of recurrent stomach carcinoma, 25 patients were newly diagnosed ≥ 5 years postoperative. The most common site of MPC was lung in 124 patients, and 347 patients (44.7%) had a smoking-related MPC, including 124 lung, 63 esophagus, 62 head and neck, and 98 other cancers. We examined the prognostic differences in 527 patients with MPC according to the diagnosis time. In 325 patients of long-term survivors in whom MPC was diagnosed ≥ 5 years postoperative, 5-year survival rate and the median survival time after diagnosis were 35.1% and 17.7 months, respectively. This outcome was significantly poorer than that of 160 patients in whom MPC was diagnosed within 5 years postoperative (58.5% and 62.7 months, P < 0.0001). In conclusion, MPC accounted for approximately a quarter of the cause of death in long-term survivors. Lifestyle instructions including smoking cessation are important. Periodical cancer screening allows the early asymptomatic diagnosis and may contribute to a decrease in cancer mortality of MPC in long-term cancer survivors.
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http://dx.doi.org/10.1620/tjem.250.31DOI Listing
January 2020

Rapid screening of copy number variations in C by droplet digital PCR in patients with mild-to-moderate hearing loss.

Hum Genome Var 2019 30;6:41. Epub 2019 Aug 30.

1Department of Otorhinolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.

Copy number variations (CNVs) are commonly reported in , the causal gene for DFNB16. Various techniques are used clinically for CNV detection, and droplet digital PCR (ddPCR) provides highly precise absolute quantification of DNA copy number. We aimed to validate the feasibility and efficiency of ddPCR in combination with long-range PCR (LR-PCR) in identifying CNVs and mutations in . Additionally, we determined the frequency of CNVs and mutations in in Japanese patients with mild-to-moderate hearing loss. We evaluated 84 unrelated Japanese patients with mild-to-moderate bilateral idiopathic or autosomal recessive nonsyndromic sensorineural hearing loss. The ratio of copy number to the copy number of the internal control ranged from 0.949 to 1.009 (0.989 ± 0.017) in 77 patients; it ranged from 0.484 to 0.538 (0.509 ± 0.024) in five patients and was 0.000 in two patients, indicating heterozygous and homozygous deletions, respectively. The copy number deletion prevalence rates were 7.7% and 0.9% in the patients and healthy controls, respectively. In combination with LR-PCR, ddPCR revealed that at least three patients (3.6%) had -related hearing loss. Detecting CNVs by ddPCR was rapid, precise, and cost-effective and facilitated the identification of CNVs.
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http://dx.doi.org/10.1038/s41439-019-0075-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804619PMC
August 2019

G-CSF-producing Undifferentiated Pleomorphic Sarcoma Adjacent to the Ascending Colon and in the Right Iliopsoas Muscle: A Case Report and Review of the Literature.

Intern Med 2019 Oct 27;58(19):2783-2789. Epub 2019 Jun 27.

Department of Gastroenterological Surgery, Saitama Cancer Center, Japan.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.
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http://dx.doi.org/10.2169/internalmedicine.2762-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815886PMC
October 2019

Effects of perioperative Eicosapentaenoic acid-enriched oral nutritional supplement on lean body mass after total gastrectomy for gastric cancer.

J Cancer 2019 29;10(5):1070-1076. Epub 2019 Jan 29.

Department of Upper Gastrointestinal Surgery Kitasato University School of Medicine, Sagamihara, Japan.

: In previous our phase III study to compare perioperative standard diet with or without Eicosapentaenoic acid (EPA)-enriched oral nutritional supplement (EPA-ON), additional EPA-ON did not contribute to prevent body weight loss after total gastrectomy. This report clarified whether EPA-ON could prevent loss of lean body mass (LBM) after total gastrectomy, a key secondary endpoint, in our phase III trial. : This phase III study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA-ON body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either Standard-diet group or EPA-ON group by a centralized dynamic method. Standard-diet group was given no additional nutritional supplementation perioperatively (standard diet), while EPA-ON group was given an EPA-enriched supplement (ProSure, Abbott Japan, Tokyo, Japan) in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. For both groups, patients underwent total gastrectomy with Roux-en Y reconstruction. : A total of 123 patients (Group A: 60, Group B: 63) were analyzed in the study. All background factors were well balanced between the both groups. Median loss of LBM was 6.74% (range -3.91% to 20.27%) in the Standard-diet group and 6.89% (range -5.11% to 20.04%) in the EPA-ON group at 1 month after surgery and was 8.59% (range -4.40% to 20.27%) in the Standard-diet group and 7.77% (range -5.57% to 23.35%) in the EPA-ON group at 3 months after surgery, which was not significantly different at the both (p=0.794 and p=0.393, respectively). : The perioperative EPA-ON could not be recommended to prevent loss of LBM after total gastrectomy.
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http://dx.doi.org/10.7150/jca.29632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400678PMC
January 2019

[Three Long-Surviving Cases of Recurrent Rectal Carcinomas Treated Non-Surgically and Cured].

Gan To Kagaku Ryoho 2018 Dec;45(13):2453-2455

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

Few cases of recurrent colorectal carcinomas were treated non-surgically and cured. Here, we report 3 such cases. Case No. 1 was of a 66-year-old woman, who underwent ISR for very low rectal cancer. Her disease Stage was tub2, T2N0M0. Two years and 6 months later, she developed intrapelvic recurrence involving sacral bones(S1-S3). Radiotherapy of 50 Gy followed by mFOLFOX6 with bevacizumab was administered for a year. She has been cancer-free for 6 years. Case No. 2 was of a 47-year-old man who underwent preoperative CRT of 40 Gy with 5-FU plus Leucovorin, and LAR was performed for very low rectal cancer. The disease Stage was tub2, T3N2M0. One year later, he was diagnosed with recurrent aortic lymph node metastasis. After 7 months of mFOLFOX6 with bevacizumab, he developed an anastomotic fistula. His chemotherapy was discontinued; he was cancer-free for 6 years. Case No. 3 was of a 56-year-old man who underwent TPE for low rectal cancer. The disease Stage was muc, T4b(urinary bladder)N0M1a(perianal skin). One year and 6 months later, he developed ileus and was diagnosed with intrapelvic recurrence. He underwent intestinal bypass operation, and CRT of 46 Gy with capecitabine was administered. He attained CR quickly, and was cancer-free for 5 years. Collecting similar cases to analyze the key to successful treatment is important.
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December 2018

Survival Outcomes of Two Phase 2 Studies of Adjuvant Chemotherapy with S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Patients with Gastric Cancer After D2 Gastrectomy.

Ann Surg Oncol 2019 Feb 19;26(2):465-472. Epub 2018 Nov 19.

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Background: Two phase 2 trials of oxaliplatin-containing adjuvant therapy for patients with gastric cancer (GC) after D2 gastrectomy were conducted in Japan. The SOXaGC trial evaluated the tolerability and safety of adjuvant therapy with S-1 plus oxaliplatin (SOX), whereas the J-CLASSIC trial evaluated the feasibility of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX). Because both were studies that did not evaluate survival results as study end points, the authors evaluated the survival outcomes for the patients in the two trials.

Methods: All 62 and 100 patients in the full analysis set of the SOXaGC and J-CLASSIC trials, respectively, were included in the current study. Their information about survival outcome was collected. The primary end point was relapse-free survival (RFS), and the secondary end point was overall survival (OS).

Results: For the pathologic stage (pStage 2) patients treated with CAPOX, the 3-year RFS rate was 87.8% and the 3-year OS rate was 92.7%. For the pStage 3 patients treated with SOX and CAPOX, the 3-year RFS rates were respectively 70.9% and 67.8% (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.50-1.72), whereas the 3-year OS rates were respectively 75.7% and 79.3% (HR, 1.10; 95% CI, 0.54-2.26). Subgroup analysis showed significant interactions between the treatment (SOX vs. CAPOX) and both sex (male vs. female; P = 0.024) and histologic type (diffuse vs. other, P = 0.069).

Conclusions: This exploratory analysis demonstrated that SOX and CAPOX are suggested to have similar efficacy for pStage 3 GC patients after D2 gastrectomy. Differences in the treatment effect according to sex and histologic type warrant further evaluation.
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http://dx.doi.org/10.1245/s10434-018-7063-8DOI Listing
February 2019

Fourier Transform Microwave Spectra of the Nitrogen Molecule-Ethylene Sulfide and Nitrogen Molecule-Dimethyl Sulfide Complexes.

J Phys Chem A 2018 Dec 28;122(49):9454-9463. Epub 2018 Nov 28.

The Graduate University for Advanced Studies , Hayama , Kanagawa 240-0193 , Japan.

We recorded the rotational spectra of N-ethylene sulfide (ES) and N-dimethyl sulfide (DMS) including the N and NN isotopomers in the frequency range of 5-25 GHz by using a Fourier transform microwave spectrometer. The b-type transitions for the ortho and para states of N-ES and N-ES and c-type transitions of N-DMS and N-DMS were observed. The NN-ES and NN-DMS species were found to exist in two isomeric forms: inner (NN-ES and NN-DMS) and outer (NN-ES and NN-DMS). Neither the -ES nor -DMS complexes showed weak accompanying spectra, which had been observed for N-ethylene oxide (EO). This is because the potential barriers to internal rotation of ES and DMS are higher than that of EO. The spectra were analyzed by an A-reduced asymmetric-top rotational program with less than 4 kHz standard deviation, except for the NN-DMS and NN-DMS complexes. Rotational, centrifugal distortion, and nuclear electric quadrupole coupling constants were determined by the spectral analysis. The V potential barrier to internal rotation of the two equivalent methyl groups of DMS in the ortho and para states of the N-DMS complex was determined to be about 740 cm. We performed ab initio calculations in order to complement the information on the intracomplex motions obtained from the experimental spectra.
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http://dx.doi.org/10.1021/acs.jpca.8b08647DOI Listing
December 2018

Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps.

Braz J Otorhinolaryngol 2019 Nov - Dec;85(6):760-765. Epub 2018 Aug 7.

Tokyo Medical and Dental University, Department of Otolaryngology, Tokyo, Japan.

Introduction: Chronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment.

Objective: The purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis.

Methods: A total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups.

Results: Thirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund-Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis.

Conclusion: Increased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.
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http://dx.doi.org/10.1016/j.bjorl.2018.07.005DOI Listing
December 2019

Vestibular Dysfunction in Patients With Superficial Siderosis of the Central Nervous System.

Otol Neurotol 2018 07;39(6):e468-e474

Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.

Objective: To describe the vestibular function in patients with superficial siderosis of the central nervous system (SSCN).

Study Design: Retrospective analysis.

Setting: Tertiary referral center.

Patients: Ten consecutive patients with SSCN. This study is the largest case series of SSCN in which detailed neuro-otological findings, including electronystagmography recording, video head impulse test (vHIT), and posturography, were described.

Interventions: Audiological and neuro-otological examinations, including pure-tone audiometry, distortion product otoacoustic emissions, speech audiometry, auditory brainstem responses, electronystagmography recording, vHIT, and posturography.

Main Outcome Measures: Pure-tone average, DP level, maximum speech discrimination score, interpeak latency between auditory brainstem responses waves I and V, eye tracking test, examination of optokinetic nystagmus, caloric response, visual suppression, vestibulo-ocular reflex gains, total center of pressure path length, and Romberg's ratio.

Results: Audiological examinations suggested that the sensorineural hearing loss was of a cochlear etiology in 3 ears, a retrocochlear etiology in 11 ears, and a combined cochlear and retrocochlear etiology in 6 ears. Neuro-otological examinations revealed that eight out of nine patients had cerebellar disorders, while all patients also had peripheral vestibular dysfunction.

Conclusion: In addition to cerebellar disorders, SSCN patients suffer from severe peripheral vestibular dysfunction, which can exacerbate the patient's imbalance. When otolaryngologists encounter patients with distinctly progressive sensorineural hearing loss and imbalance, they should include SSCN in the differential diagnosis and perform neuro-otological examinations, including an electronystagmography recording and vHIT and brain magnetic resonance imaging.
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http://dx.doi.org/10.1097/MAO.0000000000001844DOI Listing
July 2018

Three-dimensional computed tomography analysis of the vascular anatomy of the splenic hilum for gastric cancer surgery.

Surg Today 2018 Sep 1;48(9):841-847. Epub 2018 Jun 1.

Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina, Kita-adachi gun, Saitama, Saitama Prefecture, 362-0806, Japan.

Purpose: Splenic infarction may occur if the splenic branches are injured or ligated accidentally during gastrectomy. We used three-dimensional computed tomography (3D-CT) imaging to distinguish the vascular anatomy of the splenic hilum in individual patients, focusing on the splenic polar branches and the gastric branches.

Methods: The subjects of this study were 104 patients who underwent computed tomography (CT) with intravenous contrast before gastrectomy. SYNAPSE 3D® (Fujifilm Medical, Tokyo, Japan) was used to generate the 3D-CT images. The total spleen volume and the area supplied by the superior polar artery (SPA) in each patient were estimated using the "liver analysis" function.

Results: The SPA without the gastric branch (supplying only the spleen), the SPA with the gastric branch (supplying both the stomach and the spleen), and the posterior gastric artery (supplying only the stomach) were present in 14, 45, and 18% of the patients, respectively. The SPA supplied 12% of the total spleen volume on average; however, it supplied over 30% in two patients.

Conclusion: We identified the vascular anatomy around the splenic hilum in over 100 patients. Based on our findings, we recommend preservation of the SPA when it is supplying a large area of the spleen. Preoperative 3D-CT analysis provides useful information to optimize safe gastrectomy.
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http://dx.doi.org/10.1007/s00595-018-1679-yDOI Listing
September 2018

[Three Long-Surviving Cases of Peritoneal Metastasis after Colorectal Cancer Resection].

Gan To Kagaku Ryoho 2018 Feb;45(2):356-358

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

We experienced 3 impressive colorectal cancer patients who developed peritoneal recurrences and underwent surgery several times and survived for more than 5 years. Case No. 1 was of a 44-year-old woman who underwent right hemicolectomy for her stage II A ascending colon cancer. She developed left ovarian metastasis, which was resected 3 years later. Five years later, she developed a pelvic peritoneal recurrence, which was resected successfully. Thirteen years later, she is doing well. Case No. 2 was of a 61-year-old man who underwent transverse colectomy for his stage II B colon cancer. He developed ileus 2 years 9 months later due to peritoneal recurrence, which was removed successfully. He underwent another resection for peritoneal metastasis 2 years 6 months later. He was administered 15 courses of FOLFOX6. He has remained cancer-free since 2009. Case No. 3 was of a 62-year-old man who underwent sigmoidectomy for his stage II A colon cancer. One year 8 months later, he underwent resection for a painful abdominal wall metastasis. Eight months later, he developed another abdominal wall recurrence, which was resected successfully. He underwent thoracoscopic resection 4 times for lung metastases and was given 16 courses of FOLFOX6. In 2009, he developed pelvic peritoneal nodules, which were resected. He later needed lymphadenectomy twice. He has remained cancer-free for the last 5 years and 6 months. Curative resection must be performed for a patient with peritoneal recurrence of colorectal cancer when surgery is indicated.
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February 2018

[Laparoscopic Total Gastrectomy(LTG)in Patient with Multiple Gastric Neuroendocrine Tumor Related to Multiple Endocrine Neoplasia Type 1 - Two Case Reports].

Gan To Kagaku Ryoho 2017 Nov;44(12):1114-1116

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

We herein report 2 cases of laparoscopic total gastrectomy(LTG)in patient with multiple gastric neuroendocrine tumor (NET)related to multiple endocrine neoplasia type 1(MEN1). Case 1: A 66-year-old female was diagnosed with multiple gastric NET. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. Case 2: A 58-year-old female was diagnosed with multiple gastric NET. The patient had a previous history of surgery for pituitary gland tumor. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. In our cases, we could perform complete resection of gastric NET by laparoscopic surgery. Multiple gastric NET is a good indication of laparoscopic gastrectomy.
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November 2017

Gradual Symmetric Progression of DFNA34 Hearing Loss Caused by an NLRP3 Mutation and Cochlear Autoinflammation.

Otol Neurotol 2018 03;39(3):e181-e185

Molecular Biology and Genetics Section.

Objective: To characterize the audiometric phenotype of autosomal-dominant DFNA34 hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3 encodes a critical component of the NLRP3 inflammasome that is activated in innate immune responses.

Study Design: This study was conducted under protocol 01-DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and developmental history interviews and physical and audiological examinations of affected individuals with DFNA34 HL caused by the p.Arg918Gln mutation of NLRP3. We retrospectively reviewed audiological reports, when available, from other health care centers.

Setting: Federal biomedical research facility.

Subjects: Eleven members of a North American family segregating p.Arg918Gln.

Main Outcome Measures: Pure-tone thresholds, rates of pure-tone threshold progression, and speech discrimination scores.

Results: Eight subjects had bilateral sensorineural HL with an onset in the late 2nd to 4th decade of life. Slowly progressive HL initially primarily affected high frequencies. Low and middle frequencies were affected with advancing age, resulting in moderate HL with a downsloping audiometric configuration. The average annual threshold deterioration was 0.9 to 1.5 dB/yr. Speech recognition scores ranging from 60 to 100% were consistent with cochlear, but not retrocochlear, etiology. Three subjects (16, 22, and 32 yr old) had normal hearing thresholds.

Conclusion: DFNA34 HL has an onset during early adulthood and progresses approximately 1.2 dB/yr.
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http://dx.doi.org/10.1097/MAO.0000000000001715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807171PMC
March 2018

mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy.

Proc Natl Acad Sci U S A 2017 09 28;114(37):E7766-E7775. Epub 2017 Aug 28.

Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;

The NLRP3 inflammasome is an intracellular innate immune sensor that is expressed in immune cells, including monocytes and macrophages. Activation of the NLRP3 inflammasome leads to IL-1β secretion. Gain-of-function mutations of result in abnormal activation of the NLRP3 inflammasome, and cause the autosomal dominant systemic autoinflammatory disease spectrum, termed cryopyrin-associated periodic syndromes (CAPS). Here, we show that a missense mutation, p.Arg918Gln (c.2753G > A), of causes autosomal-dominant sensorineural hearing loss in two unrelated families. In family LMG446, hearing loss is accompanied by autoinflammatory signs and symptoms without serologic evidence of inflammation as part of an atypical CAPS phenotype and was reversed or improved by IL-1β blockade therapy. In family LMG113, hearing loss segregates without any other target-organ manifestations of CAPS. This observation led us to explore the possibility that resident macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The NLRP3 inflammasome can indeed be activated in resident macrophage/monocyte-like cells in the mouse cochlea, resulting in secretion of IL-1β. This pathway could underlie treatable sensorineural hearing loss in DFNA34, CAPS, and possibly in a wide variety of hearing-loss disorders, such as sudden sensorineural hearing loss and Meniere's disease that are elicited by pathogens and processes that stimulate innate immune responses within the cochlea.
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http://dx.doi.org/10.1073/pnas.1702946114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604003PMC
September 2017

[Three Successful TUR Treatments of Urinary Bladder Recurrence of Colorectal Carcinoma].

Gan To Kagaku Ryoho 2016 Nov;43(12):1638-1640

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

We analyzed whether TUR was feasible in 4 cases of urinary bladder recurrence of sigmoid colon cancer that invaded into the bladder. Case No. 1 involved a 66-year-old male who presented with sigmoid colon cancer that had invaded the urinary bladder; he underwent sigmoidectomy with partial bladder resection. Six months after the operation, a small, protruded lesion in his urinary bladder was detected and TUR was performed. He has been cancer free for 10 years. Case No. 2 involved a 53- year-old female who underwent sigmoidectomy and hepatectomy for her sigmoid colon cancer and liver metastasis. She developed bladder and liver metastases, which were resected. Four months later, she underwent TUR because she developed a small recurrent tumor in the bladder. Since then, she has had no intrapelvic recurrence for 6 years. Case No. 3 was a 44- year-old male who underwent bladder-preserving resection for a sigmoid colon cancer that had invaded his bladder. He developed a relatively large bladder tumor 1 year 6 months later. TUR was performed and he was administered CRT. He has had no recurrences for 2 years 5 months. Case No. 4 was a 68-year-old male who underwent bladder-preserving surgery for a sigmoid colon cancer that had invaded his bladder. Because he developed a recurrence in the bladder, he underwent TUR 3 months later. He developed a recurrence in the bladder again 1 year 7 months later, and he underwent TUR again. Multiple organ metastases became evident and was prescribed chemotherapy for 2 years. From these cases, we conclude that TUR may be a feasible option for small, protruded recurrences in the bladder, but we should not hesitate to perform total cystectomy if the first TUR is unsuccessful.
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November 2016

Factors affecting the quality of life of patients after gastrectomy as assessed using the newly developed PGSAS-45 scale: A nationwide multi-institutional study.

World J Gastroenterol 2016 Oct;22(40):8978-8990

Koji Nakada, Department of Laboratory Medicine, Daisan Hospital Jikei University School of Medicine, Tokyo 201-8601, Japan.

Aim: To identify certain clinical factors other than the type of gastrectomy which affect the postoperative quality of life (QOL) of patients after gastrectomy.

Methods: The postgastrectomy syndrome assessment scale (PGSAS)-45 was designed to assess the severity of symptoms, the living status and the QOL of gastrectomized patients. It consists of 45 items, of which 22 are original items while 23 were retrieved from the SF-8 and Gastrointestinal Symptoms Rating Scale questionnaires with permission. A nationwide surveillance study to validate PGSAS was conducted and 2368 gastric cancer patients who underwent various types of gastrectomy at 52 medical institutions were enrolled. Of these, 1777 patients who underwent total gastrectomy (TG) reconstructed with Roux-Y ( = 393), distal gastrectomy (DG) reconstructed with Billroth-I ( = 909), or DG reconstructed with Roux-Y ( = 475) were evaluated in the current study. The influence of the type of gastrectomy and other clinical factors such as age, sex, duration after surgery, the symptom severity, the degree of weight loss, dietary intake, and the ability for working on the postoperative QOL (., dissatisfaction for daily life subscale, physical component summary and mental component summary of the SF-8) were examined by multiple regression analysis (MRA). In addition, importance of various symptoms such as esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation and dumping on the postoperative living status and QOL were also appraised by MRA.

Results: The postoperative QOL were significantly deteriorated in patients who underwent TG compared to those after DG. However, the extent of gastrectomy was not an influential factor on patients' QOL when adjusted by the MRA. Among various clinical factors, the symptom severity, ability for working, and necessity for additional meals were the most influential factors to the postoperative QOL. As for the individual symptoms, meal-related distress, dumping, abdominal pain, and esophageal reflux significantly affected the postoperative QOL in that order, while the influence of indigestion, diarrhea and constipation was insignificant.

Conclusion: Several clinical factors such as the symptom severity (especially in meal-related distress and dumping), ability for working and necessity for additional meals were the main factors which affected the patients' well-being after gastrectomy.
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http://dx.doi.org/10.3748/wjg.v22.i40.8978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083803PMC
October 2016
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