Publications by authors named "Akira Sasaki"

418 Publications

High frequency and long persistency of ballooning hepatocyte were associated with glucose intolerance in patients with severe obesity.

Sci Rep 2021 Jul 28;11(1):15392. Epub 2021 Jul 28.

Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 1-1-1 Idaidori, Yahaba-cho, Iwate, 0283694, Japan.

Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance-demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test-and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.
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http://dx.doi.org/10.1038/s41598-021-94937-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319304PMC
July 2021

Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment.

Diagnostics (Basel) 2021 Jun 7;11(6). Epub 2021 Jun 7.

Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.

Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction.
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http://dx.doi.org/10.3390/diagnostics11061044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229468PMC
June 2021

A case of langerhans cell histiocytosis of the mandible that spontaneously regressed after biopsy in a child.

Clin Case Rep 2021 Jun 24;9(6):e04321. Epub 2021 Jun 24.

Department of Oral and Maxillofacial Surgery Dentistry and Pharmaceutical Sciences Okayama University Graduate School of Medicine Okayama Japan.

In younger patients of LCH, we should consider that the effectiveness of follow-up without aggressive treatment for SS-type LCH in the oral and maxillofacial bone. However, there are very rare case in which an SS-type LCH recurred after showing a healing tendency. Regular follow-up must be performed even after healing.
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http://dx.doi.org/10.1002/ccr3.4321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223692PMC
June 2021

Invention of novel scoring system for reduced port laparoscopic colorectal surgery to secure surgical safety and quality: A prospective clinical trial.

Asian J Surg 2021 Aug 23;44(8):1120-1122. Epub 2021 Jun 23.

Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, 028-3695, Japan.

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http://dx.doi.org/10.1016/j.asjsur.2021.05.034DOI Listing
August 2021

Background characteristics and diabetes remission after laparoscopic sleeve gastrectomy in Japanese patients with type 2 diabetes stratified by BMI: subgroup analysis of J-SMART.

Diabetol Int 2021 Jul 2;12(3):303-312. Epub 2021 Jan 2.

Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741 Japan.

Aim: The J-SMART study was the first national survey of Japanese patients undergoing laparoscopic sleeve gastrectomy (LSG). We performed a subgroup analysis of J-SMART focusing on the differences in patient background and diabetes remission between patients with BMI 32-34.9 kg/m and those with higher BMI.

Methods: In this multi-institutional retrospective study at 10 certified bariatric institutions, 203 Japanese with type 2 diabetes (T2D) and BMI of 32 kg/m or higher were analyzed (mean age: 49.2 years, BMI: 43.8 kg/m, HbA1c: 7.6%). Patients were stratified into five groups according to preoperative BMI.

Results: Background characteristics in BMI 32.0-34.9 group were higher adjusted HbA1c, higher visceral/subcutaneous fat area ratio, higher prevalence of diabetic retinopathy, higher frequency of insulin use and lower serum C-peptide. Although 2-year percent total weight loss (21.7%) and diabetes complete remission (CR) rate (52.4%) were lower in BMI 32.0-34.9 group, diabetes improvement rate was 81.0%, and the decrease in HbA1c and number of antidiabetic drugs were comparable or greater than those with higher BMI. Higher BMI and no insulin use were significant independent predictors of diabetes CR. No significant independent predictor was identified for diabetes improvement.

Conclusion: The patients with 32-34.9 kg/m were characterized by more severe visceral obesity, T2D and the complications, and lower intrinsic insulin secretion capacity. LSG should be considered as a treatment option for patients with BMI 32-34.9 kg/m, to improve diabetes control.
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http://dx.doi.org/10.1007/s13340-020-00487-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172703PMC
July 2021

Crystal structures of a nicotine MATE transporter provide insight into its mechanism of substrate transport.

FEBS Lett 2021 07 16;595(14):1902-1913. Epub 2021 Jun 16.

Nara Institute of Science and Technology, Ikoma, Japan.

A transporter of the multidrug and toxic compound extrusion (MATE) family, Nicotiana tabacum MATE2 (NtMATE2), is located in the vacuole membrane of the tobacco plant root and is involved in the transportation of nicotine, a secondary or specialized metabolic compound in Solanaceae. Here, we report the crystal structures of NtMATE2 in its outward-facing forms. The overall structure has a bilobate V-shape with pseudo-symmetrical assembly of the N- and C-lobes. In one crystal structure, the C-lobe cavity of NtMATE2 interacts with an unidentified molecule that may partially mimic a substrate. In addition, NtMATE2-specific conformational transitions imply that an unprecedented movement of the transmembrane α-helix 7 is related to the release of the substrate into the vacuolar lumen.
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http://dx.doi.org/10.1002/1873-3468.14136DOI Listing
July 2021

Pure Laparoscopic Living Donor Left Lateral Sectionectomy Using Glissonean Approach and Original Bridging Technique.

Surg Laparosc Endosc Percutan Tech 2021 Feb 12;31(3):389-392. Epub 2021 Feb 12.

Department of Surgery, Iwate Medical University, Yahaba, Japan.

Background: Living donor liver transplantation (LDLT) is the final treatment for children with end-stage liver disease. Congenital biliary atresia (CBA) is the most common disease requiring LDLT in Japan, and a left lateral sector graft is preferably procured owing to its anatomic predictivity and identical graft volume for preschool recipients. Laparoscopic left lateral sectionectomy (L-LLS) for LDLT has been recently established; however, there is no report about the innovative technique in L-LLS. The aim of this study was to introduce our L-LLS using the Glissonean approach and bridging technique for pediatric LDLT.

Materials And Methods: From September 2017 to September 2020, 5 cases of L-LLS for pediatric LDLT because of CBA were performed and we performed L-LLS using the original technique on their donors. In this novel procedure, the left Glissonean pedicle was encircled at the parenchymal side of the Laennec capsule after mobilization of the lateral sector and visualization of the left hepatic vein. Then, we passed 2 tapes through the encircled Glissonean pedicle at the hepatic side and the duodenal side, as the caudate lobe branch is enclosed like a bridge. By virtue of this bridging technique, we encircled the caudate lobe branch alone by switching the tape, and we clipped and divided it; this technique secured an adequately long hepatic duct on the graft side to perform a hepaticojejunostomy. The left hepatic duct was divided after indocyanine green fluorescence cholangiography, and the left hepatic artery and portal vein were divided as well. Finally, the left hepatic vein was transected and procured from an extended intraumbilical incision.

Results: We achieved L-LLS by using the Glissonean approach and the bridging technique in the 5 donors. The median operating time and blood loss were 282 (268 to 332) minutes and 34 (25 to 75) mL, respectively. There was no conversion to hybrid or open LLS and no postoperative complications. Regarding recipient outcomes, hepatic artery thrombosis occurred on postoperative day 4 in a 5-year-old female. All grafts function well and all recipients are alive after discharge (range of observation period, 3 to 26 mo).

Conclusions: We herein present standardized L-LLS using the Glissonean approach and bridging technique for pediatric LDLT. Our technique can secure a longer margin of the left hepatic duct for recipients' hepaticojejunotomy. Our results have demonstrated the advantage in pediatric LDLT, especially in patients with CBA after the Kasai procedure.
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http://dx.doi.org/10.1097/SLE.0000000000000926DOI Listing
February 2021

Weight Gain After 20 Years of Age is Associated with Unfavorable Lifestyle and Increased Prevalence of Metabolic Disorders.

Diabetes Metab Syndr Obes 2021 20;14:2065-2075. Epub 2021 May 20.

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan.

Purpose: It is unclear what kind of modifiable lifestyle factors are associated with long-time weight gain in adulthood. To clarify the lifestyle behavior related to body weight gain since the age of 20 years, we explored the lifestyle risk factor, independently associated with excessive weight gain after 20 years of age as compared to those in subjects with a stable weight, with matching of age, gender, and the current body mass index (BMI).

Patients And Methods: From baseline data of a general population-based cohort study, we designed a cross-sectional analysis collecting individual data of medical health check-ups and a questionnaire related to lifestyle, including amount of sleep, frequency of eating breakfast, average times per day engaged in walking and sitting in the prior year, and smoking habits. These data were compared between the subjects with weight gain ≥10kg (n=3601) and <10kg (n=3601) after age 20, matched by a propensity score model which included current BMI, age and gender. We used multivariable logistic regressions to assess the lifestyle factor's association with high weight gain.

Results: Participants who gained ≥10 kg were significantly more likely to sleep <5 hours or ≥9 hours per night, skip breakfast, engage in walking <1 hour per day, and sit ≥5 hours per day than those who gained <10kg. Multivariable logistic regressions analyses showed that, with adjusting for potential confounder, the lifestyles with the positive association with high weight gain were skipping breakfast (OR 1.252; 95% CI 1.053-1.489, vs regularly), long sleeping duration (9 hours/day≤ OR 1.613; 95% CI 1.018-2.557 vs 5≤-<7 hours/day), and former smoker (OR 1.163; 95% CI 1.008-1.343 vs never smoker), while walking duration was negatively associated with high weight gain. Furthermore, despite similar current BMI, participants with weight gain ≥10kg had significantly higher values for waist circumference, blood pressure, HbA1c, LDL-C, triglycerides, and hepatic enzyme levels than those with weight gain <10kg. Similarly, the prevalence rates of hypertension, dyslipidemia, metabolic syndrome (MetS), and former smoker were higher in the participants with weight gain ≥10kg.

Conclusion: Major weight gain after 20 years of age was associated with unfavorable lifestyle factors and greater waist circumference, possibly leading to elevated risk for MetS and other non-communicable diseases. These findings highlight the importance of maintaining both weight at age 20 and a favorable lifestyle throughout adulthood.
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http://dx.doi.org/10.2147/DMSO.S300250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143959PMC
May 2021

A Right Angle Guide for Distal Tuberosity Osteotomy With Medial Open Wedge High Tibial Osteotomy for Varus Knee Osteoarthritis.

Arthrosc Tech 2021 Apr 12;10(4):e1007-e1016. Epub 2021 Mar 12.

Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai City, Japan.

Medial open wedge high tibial osteotomy (OWHTO) is usually performed with proximal tuberosity osteotomy or setting the osteotomy line proximal to the tuberosity. However, OWHTO can result in patellofemoral complications due to postoperative patella infera. A new OWHTO technique, biplanar osteotomy with a distal tuberosity osteotomy, was reported in 2004 to prevent postoperative patella infera. To ensure that the 2 osteotomy lines maintain perpendicular, we describe the OWHTO procedure with a distal tuberosity osteotomy technique using a TriS Medial HTO Plate System (Olympus Terumo Biomaterials Corp., Tokyo, Japan) and a right angle guide we developed. In this Technical Note, we describe the procedure and advantages, risks, and limitations, as well as the pearls and pitfalls based on our experience.
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http://dx.doi.org/10.1016/j.eats.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084846PMC
April 2021

Incidence and characteristics of medical emergencies related to dental treatment: a retrospective single-center study.

Acute Med Surg 2021 Jan-Dec;8(1):e651. Epub 2021 May 1.

Department of Emergency, Critical Care and Disaster Medicine Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan.

Aim: Although uncommon, medical emergencies arise in general dental practice. Inadequate data on their severity and frequency makes targeting medical education for general dental practitioners difficult. This also makes planning for unexpected events challenging for practitioners and makes collaborating with emergency physicians burdensome. We aimed to clarify the incidence and characteristics of a dental outpatient department's medical emergencies.

Methods: This single-center, retrospective, observational study was undertaken with patients who visited the dental outpatient department of Okayama University Hospital during the 8-year period. The primary outcome of the study was to identify the incidence and characteristics of medical emergencies in the dental outpatient department. Then we examined the timing of medical emergencies, administered medications, and final disposition (home/admission).

Results: During the period, 1,146,929 patients were enrolled. Forty-two patients (0.0037%) were consulted as medical emergencies. More than 60% of the incidents were vasovagal syncope, and dehydration and hypoglycemia were the second most prevalent at 9.5%. The most common types of dental treatments were tooth extraction (45.2%), followed by general dental treatment (28.6%), and other dental surgery such as implant placement (14.3%). Types of medical emergencies occurred equally before, during, and after dental treatment. Antihypertensive agents, sedatives, or glucose were used. For patients with emergencies, 90.5% recovered during the day and returned home, and 9.5% were hospitalized.

Conclusion: The incidence of medical emergencies was low in our dental outpatient department. Knowledge of basic management principles, regular education for emergency care, and practicing first aid skills are mandatory for safe patient management.
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http://dx.doi.org/10.1002/ams2.651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088391PMC
May 2021

Aggressive Laparoscopic Cholecystectomy in Accordance with the Tokyo Guideline 2018.

JSLS 2021 Jan-Mar;25(1)

Department of Surgery, Iwate Medical University, Iwate Prefecture, Japan.

Objectives: The Tokyo Guidelines 2018 have been widely adopted since their publication. However, the few reports on clinical outcomes following laparoscopic cholecystectomy have not taken into account the severity of the acute cholecystitis and the patient's general condition, as estimated by the Charlson comorbidity index. This study aimed to assess the relationships between severity, Charlson comorbidity index, and clinical outcomes subsequent to laparoscopic cholecystectomy.

Methods: We extracted the retrospective data for 370 Japanese patients who underwent emergency or scheduled early laparoscopic cholecystectomy within 72 hours from onset between February 2015 and August 2018. We compared postoperative factors in relationship to severity (grade I versus grade II/III). Then, we made a similar comparison between those with low (< 4) and high Charlson comorbidity index (≥ 4).

Results: According to the Tokyo guideline 2018 levels of severity, there were 282 (76.2%), 61 (16.5%), and 27 (7.3%) patients in grades I, II, and III, respectively. With regards to surgical outcomes, the mean operating time was 62.3 minutes and the mean blood loss was 24.4 mL. The mean hospital stay was 3.6 days, with no mortalities. Blood loss was the only factor affected by severity (20.9 mL versus 60.1 mL, = 0.0164), and operating time was the only factor affected by high Charlson comorbidity index (53.4 versus 67.8 minutes, = 0.0153).

Conclusion: Our aggressive strategy is acceptable, and severity and Charlson comorbidity index are not critical factors suggesting the disqualification of early laparoscopic cholecystectomy in patients with any grade acute cholecystitis.
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http://dx.doi.org/10.4293/JSLS.2020.00116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035821PMC
July 2021

A case of intramandibular neurofibroma resembling a radicular cyst in a neurofibromatosis type 1 patient.

Int J Surg Case Rep 2021 May 10;82:105883. Epub 2021 Apr 10.

Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Introduction: Neurofibromatosis is a disease that causes various abnormalities such as neurofibroma, mainly in the skin and nerves. The common sites in the oral cavity are the palate, gingiva, tongue, buccal mucosa, and lips but, occurrence in the mandible is rare.

Presentation Of Case: A 26-year-old woman was referred to our clinic because of percussion pain. Radiographic findings showed a radiolucent area. The patient was clinically diagnosed with a radicular cyst by a previous doctor. Multiple café-au-lait spots were found disseminated on her body, and she had already been prenatally diagnosed with neurofibromatosis type 1 (NF1). We performed a biopsy and suggested a neurofibroma. Tumor extirpation was performed under general anesthesia. The histopathological diagnosis showed a neurofibroma.

Clinical Discussion And Conclusion: NF1 is a systemic nevus that causes abnormalities in melanocytes and Schwann cells, and various lesions appear, but intramandibular lesions are extremely rare. Diagnosis of NF1 and radicular cysts in the mandible is difficult due to their image resemblance. However, it should be kept in mind if the underlying disease is NF1. In our case, it was easy to detach and may have originated from small peripheral nerve endings in the mandible.
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http://dx.doi.org/10.1016/j.ijscr.2021.105883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081929PMC
May 2021

Central hepatic bisectionectomy with hepatic artery and biliary tracts reconstruction for the patient with nodular type intrahepatic hilar cholangiocarcinoma: A case report.

Int J Surg Case Rep 2021 May 6;82:105868. Epub 2021 Apr 6.

Department of Surgery, Iwate Medical University, Japan.

Introduction And Importance: A central hepatic bisectionectomy (CHBS) for a hilar cholangiocarcinoma (CCA) is technically challenging because bilateral biliary reconstruction is required after resection. On the other hand, hepatic artery resection and reconstruction in a major liver resection are also technical procedures. In this report, we describe our radical CHBS with hepatic artery and biliary tracts reconstruction for a patient with nodular type intrahepatic hilar CCA.

Case Presentation: A 76-year-old man was referred for further investigation of an incidental hepatic tumor. The hepatic tumor was located from medial sector to anterior sector with encasement of the anterior branch of the right hepatic artery. Based on these findings, we performed a CHBS with right hepatic artery and biliary tracts reconstruction. The histopathological findings revealed that the tumor consisted of moderately differentiated tubular adenocarcinoma with tumor necrosis without a fibrous capsule. In this area, tumors cells had invaded branches of the hepatic vein; however, there was no destructive invasion to the hepatic artery. Consequently, he was diagnosed with a nodular type intrahepatic hilar CCA with pT2aN0M0.

Clinical Discussion: A CHBS is usually performed with the intent of anatomically preserving a patient's liver as much as possible. Concomitant resection and reconstruction of the hilar vessels and biliary tracts with CHBS is one of the most technically challenging procedures in liver resections.

Conclusion: A CHBS with hepatic artery and biliary reconstruction may be a promising alternative if expert surgeons perform it on strictly selected patients.
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http://dx.doi.org/10.1016/j.ijscr.2021.105868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055599PMC
May 2021

Predictive scoring system for advanced liver fibrosis in Japanese patients with severe obesity.

Surg Today 2021 Apr 7. Epub 2021 Apr 7.

Division of Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba, 028-3695, Japan.

Purpose: The aim of this study was to examine the predictive scoring system of advanced liver fibrosis in severely obese Japanese patients.

Methods: Seventy-two patients underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies. We classified these patients into two groups: Brunt stage ≥ 2 (advanced fibrosis) and 0/1 (none/mild fibrosis). A logistic regression analysis was performed to identify the predictors of advanced fibrosis.

Results: Sixteen patients had advanced fibrosis, while 56 had no/mild fibrosis. The prevalence of type 2 diabetes mellitus (T2DM) in advanced fibrosis group was significantly higher than in none/mild fibrosis. An univariate analysis of the factors predicting advanced fibrosis showed significant differences in AST/ALT ratio, serum insulin levels, HOMA-IR, and type IV collagen 7S in the T2DM group. According to a multivariate analysis, type IV collagen 7S was an independent predictor and the cutoff value was 5.6 ng/mL. We created a flow chart; high risk (T2DM and type IV collagen 7S ≥ 5.6 ng/mL), moderate risk (T2DM and type IV collagen 7S < 5.6 ng/mL), and low risk (non-DM). For those at high risk, the sensitivity, specificity, positive predictive value, and negative predictive value were 56.2%, 94.4%, 75.0%, and 87.9%, respectively.

Conclusion: This classification system has the potential to accurately categorize the risk of liver fibrosis.
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http://dx.doi.org/10.1007/s00595-021-02266-wDOI Listing
April 2021

Multicenter Study of Congenital Middle Ear Anomalies. Report on 246 Ears.

Laryngoscope 2021 07 1;131(7):E2323-E2328. Epub 2021 Mar 1.

Department of Otolaryngology, Fukushima Medical University, Fukushima, Japan.

Objectives/hypothesis: Congenital middle ear anomalies represent a relatively rare condition. This study aimed to describe the characteristics and the surgical outcomes for patients with middle ear anomalies.

Methods: A multicenter study was conducted of consecutive patients with congenital middle ear anomalies who underwent primary surgical treatment between January 2008 and December 2017. Demographics, surgical procedures, and audiometric data were registered into the institutional database. Hearing changes and postoperative air-bone gap (ABG) were evaluated 1 year after surgery.

Results: A total of 246 patients (246 ears) (median age: 14 years, range: 4-75 years old) were included in this study. Anomalies were subdivided using the Teunissen and Cremers classification: 53 ears (22%) were categorized as class I, comprising only stapes ankylosis; 35 ears (14%) as class II, having ossicular chain anomalies with stapes ankylosis; 139 ears (57%) as class III, having ossicular chain anomalies with a mobile stapes-footplate; and 19 ears (8%) as class IV, with aplasia of the oval window. Evaluation of hearing outcomes for 198 ears with more than 1 year of follow-up revealed that good postoperative ABG (≤20 dB) was achieved in 82% of class I, 68% of class II, 74% of class III, and 23% of class IV anomalies. The postoperative ABG in class IV was significantly worse than in class I (P < .001) or class III (P < .01).

Conclusions: This study demonstrated that class III anomalies comprised the majority of middle ear anomalies and surgical outcomes for class IV anomalies are unfavorable.

Level Of Evidence: 4 Laryngoscope, 131:E2323-E2328, 2021.
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http://dx.doi.org/10.1002/lary.29482DOI Listing
July 2021

Laparoscopic Left Hepatectomy with Middle Hepatic Vein Resection for Hepatocellular Carcinoma with Extrahepatic Portal Vein Obstruction.

Am J Case Rep 2021 Mar 1;22:e928801. Epub 2021 Mar 1.

Department of Surgery, Iwate Medical University, Morioka, Iwate, Japan.

BACKGROUND Extrahepatic portal vein obstruction (EHPVO) is one of the most important diseases that causes pre-hepatic portal hypertension, and EHPVO sometimes develops cavernous transformation to maintain hepatopetal flow. In this report, we describe the first case of hepatocellular carcinoma (HCC) with EHPVO having underwent pure laparoscopic left hepatectomy with middle hepatic vein (MHV) resection. CASE REPORT A 70-year-old woman with a diagnosis of mixed-type HCC or cholangiocarcinoma located in segment 4b was referred to our hospital, and computed tomography revealed EHPVO with cavernous transformation. We successfully performed pure laparoscopic left hepatectomy with MHV resection by using the individual hilar approach, frequent intraoperative sonography, and indocyanine green imaging. In this case, the routine Glissonian approach was impossible due to cavernous transformation growth and the absence of a portal vein. Therefore, frequent confirmation of intrahepatic flow was crucial to avoid intraoperative complications. The patient was discharged with no complications on postoperative day 7. A histopathological examination revealed that the moderately differentiated HCC formed a pseudoglandular pattern and cord-like structures, thereby defined as type II according to Edmondson's classification. CONCLUSIONS Currently, difficulty scoring systems for laparoscopic liver resection (LLR) usually contain the procedure and location of the hepatic tumor, but they do not contain the variety of anatomical abnormality due to its rarity. However, the false recognition of hilar vessels and biliary ducts in patients with an anatomical abnormality, including EHPVO, leads to severe injury; therefore, anatomical variety and abnormality are also important factors increasing the difficulty of LLR.
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http://dx.doi.org/10.12659/AJCR.928801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930512PMC
March 2021

Evolution and Maintenance of Mutualism between Tubeworms and Sulfur-Oxidizing Bacteria.

Am Nat 2021 03 19;197(3):351-365. Epub 2021 Jan 19.

AbstractTubeworms and sulfur-oxidizing bacteria mutualism, an essential part of the chemosynthetic ecosystem in the deep sea, has several puzzling features. After acquiring sulfur-oxidizing bacteria from the environment, tubeworms become fully dependent on their symbiont bacteria for nutrient intake. Once ingested by the tubeworm larva, no additional symbionts join from the environment, and no symbionts are released until the host tubeworm dies. Despite this very narrow window to acquire symbionts, some tubeworm species can live for >200 years. Such a restricted release of symbionts could lead to a shortage of symbiont bacteria in the environment without which tubeworms could not survive. In our study, we examine the conditions under which this mutualism can persist and whether the host mortality rate evolves toward a low value using a mathematical model for the tubeworm-symbiont bacteria system. Our model reveals that mutualism can persist only when the host mortality rate is within an intermediate range. With cohabitation of multiple symbionts strains in the same host, host mortality rate evolves toward a low value without driving either host or symbiont to extinction when competition among symbionts is weak and their growth within a host is slow. We also find the parameter conditions that lead to unlimited evolutionary escalation of host mortality rate toward coextinction of both tubeworms and symbionts populations (evolutionary double suicide). The generality of this evolutionary fragility in obligate mutualistic systems as well as the contrasting evolutionary robustness in host-parasite systems are discussed.
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http://dx.doi.org/10.1086/712780DOI Listing
March 2021

Cutaneous metastasis from esophageal basaloid squamous cell carcinoma: A case report.

Int J Surg Case Rep 2021 Mar 5;80:105621. Epub 2021 Feb 5.

Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan. Electronic address:

Introduction And Importance: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a relatively rare histologic variant of squamous cell carcinoma. Here, we reported a case of solitary cutaneous metastasis as the first symptom of esophageal BSCC and was successfully treated with multidisciplinary treatment.

Case Presentation: A 67-year-old man visited a local hospital with symptoms of dysphagia and cutaneous nodules on his left shoulder. Fluorine-18 fluorodeoxyglucose positron emission tomography revealed hypermetabolic accumulations in the middle thoracic esophagus, right recurrent laryngeal nerve lymph node, and epidermis of the left shoulder. Esophagogastroscopy revealed an ulcerative and infiltrating type tumor in the middle thoracic esophagus. Based on histopathologic examination of the endoscopic biopsy and the resected cutaneous tumor, the patient was diagnosed as esophageal BSCC with cutaneous metastasis. The patient was treated with chemotherapy followed by chemoradiotherapy. The therapeutic effect was a complete response, which was sustained for 39 months.

Clinical Discussion: Review of previous literature in the PubMed database revealed only been two case reports on cutaneous metastasis of BSCC. Advanced BSCC of the esophagus with distant metastasis has a poor prognosis. Therefore, in our case, future careful follow-up is required.

Conclusion: Esophageal BSCC with cutaneous metastasis can be successfully managed by multidisciplinary treatment, including local resection of the cutaneous metastasis, systemic chemotherapy, and chemoradiotherapy.
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http://dx.doi.org/10.1016/j.ijscr.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893449PMC
March 2021

Surgical resection of a giant peripheral ossifying fibroma in mouth floor managed with fiberscopic intubation.

Clin Case Rep 2021 Jan 6;9(1):180-184. Epub 2020 Nov 6.

Department of Oral and Maxillofacial Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan.

Tracheal intubation for general anesthesia can sometimes be difficult in patients with a large mass in the mouth floor. Preoperative evaluation of the patient's airway is most important when treating large oral disease.
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http://dx.doi.org/10.1002/ccr3.3494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813068PMC
January 2021

Prediction of Long-Term Diabetes Remission After Metabolic Surgery in Obese East Asian Patients: a Comparison Between ABCD and IMS Scores.

Obes Surg 2021 Apr 7;31(4):1485-1495. Epub 2021 Jan 7.

Weight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo, Japan.

Purpose: Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial.

Methods: Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients.

Results: The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG.

Conclusion: IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.
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http://dx.doi.org/10.1007/s11695-020-05151-6DOI Listing
April 2021

Laparoscopic colectomy for persistent descending mesocolon in sigmoid colon cancer: A case report.

Int J Surg Case Rep 2021 Jan 17;78:307-309. Epub 2020 Dec 17.

Department of Surgery, Iwate Medical University School of Medicine, 2-1-1 idaidori yahaba, Iwate 028-3695, Japan. Electronic address:

A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.
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http://dx.doi.org/10.1016/j.ijscr.2020.12.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779540PMC
January 2021

A case of oral cancer with delayed occipital lymph node metastasis: Case report.

Clin Case Rep 2020 Dec 30;8(12):2469-2475. Epub 2020 Jul 30.

Department of Oral and Maxillofacial Surgery Dentistry and Pharmaceutical Sciences Okayama University Graduate School of Medicine Okayama Japan.

Consideration of unexpected metastasis in patients who have undergone neck dissection with advanced tumors must be anticipated with careful follow-up.
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http://dx.doi.org/10.1002/ccr3.3086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752593PMC
December 2020

Indocyanine green fluorescence imaging via endoscopic nasal biliary drainage during laparoscopic deroofing of liver cysts.

J Minim Access Surg 2021 Jan-Mar;17(1):131-134

Department of Surgery, Iwate Medical University, Iwate, Japan.

Laparoscopic deroofing of liver cysts is widely accepted as the treatment of symptomatic huge liver cysts. As bile leakage is a common complication of this procedure, indocyanine green (ICG) imaging has played an active role in detecting intrahepatic biliary tract. However, infusion ICG imaging needs time rag after injection due to moving from bloodstream to bile, and also, additional injection is needed when the fluorescent imaging is not clear. To cover this weakness of ICG imaging, we first applied ICG imaging via 5-Fr endoscopic nasal biliary drainage (ENBD) during laparoscopic deroofing of liver cysts. This technique promptly gives us ICG imaging after ICG injection from ENBD; in addition, direct ICG imaging sometimes reveals minor leakage from sealing line and staple lines; therefore, we believe that direct ICG imaging via ENBD helps us to prevent post-operative bile leakage.
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http://dx.doi.org/10.4103/jmas.JMAS_26_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945643PMC
December 2020

Plasma lipoprotein profile from nonalcoholic steatohepatitis model rats.

Biomed Res 2020 ;41(6):289-293

Akita Research Institute of Food & Brewing.

We recently revealed that increases in particle sizes of very-low-density lipoproteins (VLDL) are highly correlated with the progression of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and VLDL particle size may be a minimally invasive indicator of these hepatic disorders. Methionine and choline-deficient (MCD) diet fed animals are usually used as a NASH model; however, the application of this minimally invasive biomarker in MCD diet fed animals remains unclear. In the present study, we measured the levels of liver disease markers and plasma lipoprotein profiles in MCD diet fed rats, and compared them with those of normal diet fed rats. Assessing lipoprotein profiles showed marked increases in VLDL particle sizes in MCD diet fed rats with pathologically and biochemically NASH-like features.
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http://dx.doi.org/10.2220/biomedres.41.289DOI Listing
January 2020

A genome-wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors.

Genes Chromosomes Cancer 2021 Apr 24;60(4):250-262. Epub 2020 Dec 24.

Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome-wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22-q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.
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http://dx.doi.org/10.1002/gcc.22924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898915PMC
April 2021

Portal bifurcation reconstruction using own hepatic vein grafts due to portal vein anomaly of the living donor for the patient with portal vein thrombosis.

Ann Hepatobiliary Pancreat Surg 2020 Nov;24(4):533-538

Department of Surgery, Iwate Medical University Hospital, Yahaba, Japan.

A 57-year-old Japanese female was considered for living donor liver transplantation (LDLT) due to end-stage liver cirrhosis caused by primary biliary cholangitis with portal vein thrombosis (PVT) formation. A 26-year-old daughter of the patient was selected as a living donor; however, a computed tomography examination revealed trifurcated-type portal vein anomaly (PVA). Preoperative liver volumetry showed that the right lobe graft was necessary for the recipient; therefore, reconstruction of the portal vein bifurcation during LDLT was necessary. We planned to extract the recipient's own hepatic vein grafts after total hepatectomy, and these would be attached with anterior and posterior portal branches as jump grafts. We performed laparoscopic donor hepatectomy as usual, and the recipient's hepatic vein grafts were anastomosed on the bench. Then, the liver graft was inserted, and the hepatic vein reconstruction was routinely performed. We confirmed the alignment between the recipient's portal vein and the bridged hepatic vein graft of the liver graft's posterior branch, and anastomosed these two vessels. Moreover, we confirmed the front flow and expansion of the reconstructed posterior branch by declamping only the suprapancreatic side of the portal vein. The decision regarding the punch-out location was crucial. We confirmed the alignment between the reconstructed posterior branch and the bridged hepatic vein graft of the anterior branch, and anastomosed these two vessels employing the punched-out technique. In LDLT, liver transplant surgeons occasionally encounter living donors with PVA or recipients with PVT. Our contrivance may be useful when the liver graft needs reconstruction of portal vein bifurcation.
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http://dx.doi.org/10.14701/ahbps.2020.24.4.533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691204PMC
November 2020

The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone.

J Bone Oncol 2021 Feb 28;26:100330. Epub 2020 Oct 28.

Department of Medicine, Hematology Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.

Bone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP.
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http://dx.doi.org/10.1016/j.jbo.2020.100330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649349PMC
February 2021

Rare presentation of De Garengeot hernia treated by transabdominal preperitoneal hernia repair: A case report.

Asian J Endosc Surg 2021 Jul 3;14(3):578-581. Epub 2020 Nov 3.

Department of Surgery, Iwate Medical University, Shiwa, Japan.

We present a rare case of De Garengeot hernia treated with simultaneous laparoscopic appendectomy and transabdominal preperitoneal hernia repair. Our patient was an 85-year-old man with a bulging mass in the right groin. De Garengeot hernia was observed on contrast-enhanced CT. Urgent laparoscopy showed the distal part of the appendix passing through a right-sided femoral hernia. Laparoscopic appendectomy was performed, followed by transabdominal preperitoneal repair of the femoral hernia. Pathological examination revealed ischemic necrosis of the appendix. The patient's postoperative recovery was uneventful.
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http://dx.doi.org/10.1111/ases.12891DOI Listing
July 2021

Triple knockdown of CDC37, HSP90-alpha and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer.

J Extracell Vesicles 2020 May 31;9(1):1769373. Epub 2020 May 31.

Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones - CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial-mesenchymal transition (EMT), although their contribution to EVs-mediated cell-cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer-derived EVs (MEV) were enriched with HSP90α HSP90β and cancer-initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV-driven malignancy events. In metastatic oral cancer patient-derived tumours, HSP90β was significantly accumulated in infiltrating tumour-associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90-enriched MEV-induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA-mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV-driven malignancy events in the tumour microenvironment.

Abbreviations: CDC37: cell division control 37; EMT: epithelial-mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour-associated macrophage.
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http://dx.doi.org/10.1080/20013078.2020.1769373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580842PMC
May 2020

Molecular alterations in gastric cancer and the surrounding intestinal metaplastic mucosa: an analysis of isolated glands.

Gastric Cancer 2021 Mar 3;24(2):382-391. Epub 2020 Nov 3.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwa, Yahaba, Morioka, 028-3695, Japan.

Background: Intestinal metaplasias (IMs) are generally regarded as pre-neoplastic gastric lesions. However, molecular alterations including genetic and epigenetic changes occurring in individual IM glands are not well defined.

Aims: We sought to identify DNA methylation status, microsatellite instability (MSI) and allelic imbalance (AI) occurring in individual IM glands and non-IM glands within the same mucosa.

Methods: We divided examined isolated gland obtained from GC into 4 components: isolated cancer, antral isolated intestinal metaplastic tissue, antral isolated non-metaplastic gland and isolated non-metaplastic gland derived from the greater curvature of the most distant gastric body without mucosal atrophy. We examined AI and microsatellite instability statuses using PCR-based microsatellite analysis. Next, the DNA methylation status (high methylation epigenome [HME], intermediate methylation epigenome [IME], and low methylation epigenome [LME]) was investigated. DNA methylation analysis of CDKN2A, mir34-b/c and MLHI genes was also performed.

Results: Although antral isolated IM glands were characterized by IME, isolated non-IM glands showed LME. In isolated cancer glands, HME was frequently found, compared with isolated non-IM glands. DNA methylation of mir34-b/c was common in isolated cancer and IM glands, whereas DNA methylation of CDKN2A was a rare event in isolated samples. The MLH1 gene was not methylated in isolated non-IM glands. Although multiple AIs were frequently found in isolated cancer glands, a few AIs were detected in isolated IM glands.

Conclusions: We suggest that the DNA methylation status and the status of the mir34-b/c gene among isolated samples of IMs and isolated non-IM glands have an impact on IM development.
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http://dx.doi.org/10.1007/s10120-020-01130-zDOI Listing
March 2021
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