Publications by authors named "Tomoyuki Koike"

167 Publications

The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study.

BMC Neurol 2021 Jun 25;21(1):242. Epub 2021 Jun 25.

Department of Neurology, Fukuoka University, Fukuoka, Japan.

Background: Levodopa-carbidopa intestinal gel (LCIG) treatment, a unique drug delivery system for patients with advanced Parkinson's disease (PD), is covered by health insurance in Japan since September 2016. Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited. This is the first multicenter study to clarify the frequency and timing of device-related AEs.

Methods: Between September 2016 and December 2018, 104 patients introduced to the LCIG treatment for advanced PD in 11 hospitals were included. The patients' characteristics, AEs incidence, AEs time, and tube exchange time were investigated.

Results: The median follow-up period was 21.5 months. Minor AE cases were 29.4%, whereas major AE cases were 43.1%. Majority of major AEs (n = 55, 94.8%) were managed with endoscopic treatment, such as tube exchange. Few severe AEs required surgical treatment (n =3, 5.2%). The mean (range) exposure to percutaneous endoscopic gastrojejunostomy (PEG-J) was 14.7 (0-33) months. One year after the LCIG treatment introduction, 55 patients (54.0%) retained the original PEG-J tube. The mean PEG-J tube exchange time was 10.8 ± 7.0 months in all patients, 11.6 ± 4.7 and 10.5 ± 7.7 months in patients with scheduled exchange and who underwent exchange due to AEs, respectively.

Conclusions: Some device-related AEs occurred during the LCIG treatment; however, only few were serious, most of which could be treated with simple procedures or tube replacement with endoscopy. Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists' understanding and cooperation.
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http://dx.doi.org/10.1186/s12883-021-02269-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228941PMC
June 2021

Risk of metastatic recurrence after endoscopic resection for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa: a multicenter retrospective study.

J Gastroenterol 2021 Jul 21;56(7):620-632. Epub 2021 Apr 21.

National University Corporation Hirosaki University, Hirosaki, Japan.

Background: We aimed to elucidate the risk of metastatic recurrence after endoscopic resection (ER) without additional treatment for esophageal squamous cell carcinomas (ESCCs) with tumor invasion into the muscularis mucosa (pT1a-MM) or submucosa (T1b-SM).

Methods: We retrospectively enrolled patients with pT1a-MM/pT1b-SM ESCC after ER at 21 institutions in Japan between 2006 and 2017. We compared metastatic recurrence between patients with and without additional treatment, stratified into category A (pT1a-MM with negative lymphovascular invasion [LVI] and vertical margin [VM]), B (tumor invasion into the submucosa ≤ 200 µm [pT1b-SM1] with negative LVI and VM), and C (others). Subsequently, using multivariate Cox analysis, we evaluated risk factors for metastatic recurrence after ER without additional treatment.

Results: We enrolled 593 patients, and metastatic recurrence occurred in 38 patients. Metastatic recurrence after additional treatment was significantly lower than that after no additional treatment in category C (9.1% vs. 23.6% in 5 years, p = 0.001), whereas no significant difference was noted in categories A (0.0% vs. 2.6%) and B (0.0% vs. 4.3%). In patients without additional treatment after ER, risk factors for metastatic recurrence were lymphatic invasion (hazard ratio [HR], 5.61), positive VM (HR, 4.55), and tumor invasion into the submucosa > 200 μm (HR, 3.25), and, but near half of the patients with metastatic recurrence had no further recurrence after salvage treatment, resulting in excellent 5-year disease-specific survival in categories A (99.6%) and B (100.0%).

Conclusions: Closed follow-up with no additional treatment may be an acceptable option after ER in pT1a-MM/pT1b-SM1 ESCC with negative LVI and VM.
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http://dx.doi.org/10.1007/s00535-021-01787-yDOI Listing
July 2021

Prevention of delayed bleeding with vonoprazan in upper gastrointestinal endoscopic treatment.

J Gastroenterol 2021 Jul 19;56(7):640-650. Epub 2021 Apr 19.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Background: Delayed bleeding is the major adverse event in upper gastrointestinal endoscopic treatment (UGET). We aimed to investigate the efficacy of vonoprazan, which is the novel strong antisecretory agent, to reduce the risk for delayed bleeding in comparison with proton pump inhibitors (PPIs) in UGET.

Methods: This retrospective population-based cohort study used the Diagnosis Procedure Combination database in Japan. We included patients on vonoprazan or PPI in UGET between 2014 and 2019. The primary outcome was delayed bleeding. We conducted propensity score matching to balance the comparison groups, and logistic regression analyses to compare the bleeding outcomes.

Results: We enrolled 124,422 patients, in which 34,822 and 89,600 were prescribed with vonoprazan and PPI, respectively. After propensity score matching, the risk for delayed bleeding was lower in vonoprazan than in PPI (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.71-0.80), consistent with sensitivity analysis results. In the subgroup analyses of seven UGET procedures, vonoprazan was significantly advantageous in esophageal endoscopic submucosal dissection (E-ESD) (OR, 0.71; 95% CI, 0.54-0.94) and gastroduodenal endoscopic submucosal dissection (GD-ESD) (OR, 0.70; 95% CI, 0.65-0.75), although correction for multiple testing of the outcome data removed the significance in E-ESD. These results were also consistent with sensitivity analysis results. In the five other procedures, no significant advantage was found.

Conclusions: This nationwide study found that, compared with PPI, vonoprazan can reduce delayed bleeding with approximately 30% in GD-ESD. Vonoprazan has the possibility to become a new treatment method for preventing delayed bleeding in this procedure.
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http://dx.doi.org/10.1007/s00535-021-01781-4DOI Listing
July 2021

A rare case of penetration related to ischemic duodenitis after ventricular assist device implantation for dilated cardiomyopathy.

Clin J Gastroenterol 2021 Aug 24;14(4):1186-1190. Epub 2021 Mar 24.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Tohoku University Hospital, 1-1, Seiryo-Cho, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.

A 66-year-old man with a history of diabetes and dilated cardiomyopathy underwent the implantation of a ventricular assist device (VAD) at the age of 62. He suffered from epigastralgia for a month and then visited our hospital with complaints of severe epigastralgia and hematemesis. A physical examination revealed abdominal distension without rigidity. Laboratory data showed severe systemic inflammation, multiple organ failure, and disseminated intravascular coagulation. Computed tomography showed multifocal thickness of the gastroduodenal wall with surrounding panniculitis, gas in a portal vein and a perigastric vein. Emergency esophago-gastro duodenoscopy (EGD) demonstrated a large erosion in the antrum of the stomach, and penetration surrounded by circumferentially ischemic mucosa in the second and third portions of the duodenum. Based on informed consent, conservative therapy was performed, and his condition improved enabling the start of oral intake on the 37th hospital day. However, 7 days later, there was a relapse of epigastralgia after a meal. Gastrointestinal series and EGD revealed a 10-mm-long pinhole-like stricture at the site. After laparoscopic gastro-jejunal bypass surgery, he has remained in a good condition for 2 years. We demonstrated a rare case of penetration due to severe ischemic duodenitis 4 years after VAD implantation.
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http://dx.doi.org/10.1007/s12328-021-01346-1DOI Listing
August 2021

Combination of Dermal fat Grafting and Frontalis Suspension Using Polytetrafluoroethylene Sheet for Blepharoptosis With a Deep Sulcus.

J Craniofac Surg 2021 Feb 18. Epub 2021 Feb 18.

Department of Plastic Surgery, Fujisawa Shounandai Hospital, Fujisawa-shi Department of Ocular Plastic & Orbital Surgery, Seirei Hamamatsu General Hospital, Hamamatsu-shi Yokohama Sakuragicho Eye Clinic Department of Plastic and Reconstructive Surgery, Yokohama City University Hospital Department of Plastic and Reconstructive Surgery, Yokohama City University Medical Center, Yokohama-shi, Japan.

Abstract: The frontalis suspension procedure is a common surgical method for patients with severe blepharoptosis. While frontalis suspension is a very effective method, the transplant material may be visualized after surgery in patients with a deep sulcus and severe blepharoptosis. To prevent this complication, we performed a combination of dermal fat grafting and frontalis suspension using a polytetrafluoroethylene sheet in 5 patients (6 eyelids). We followed-up the patients for at least 6 months postoperatively (mean: 6.8 months) and observed no transplant material visualization or occurrence of infection. The mean pre- and postoperative margin reflex distance-1 was -3.75 (-5 to -2) and 2.10 (1-3), respectively. Bulky upper eyelids were observed 6 months postoperatively in 1 patient (2 eyelids). None of the patients underwent reoperation. In conclusion, the combination of frontalis suspension using a polytetrafluoroethylene sheet and dermal fat grafting for severe blepharoptosis and a deep upper eyelid sulcus was effective in preventing visualization of the transplant material.
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http://dx.doi.org/10.1097/SCS.0000000000007556DOI Listing
February 2021

Predictors of Early and Late Mortality after Endoscopic Resection for Esophageal Squamous Cell Carcinoma.

Tohoku J Exp Med 2021 01;253(1):29-39

Division of Gastroenterology, Tohoku University Graduate School of Medicine.

In esophageal squamous cell carcinoma (ESCC) comprising 90% of cases with esophageal cancer, endoscopic resection (ER) is recommended for patients with negligible risk of ESCC-related mortality. In fact, a main cause of death in patients underwent ER is not ESCC. We thus aimed to clarify the predictors for early and late mortality among patients underwent ER of ESCC between 2005 and 2018 at our institution. In this retrospective cohort study, we investigated the prognosis and predictors of early and late mortality with the cut-off value of 3 years. We enrolled 407 patients with a median 69 months follow-up. The 5-year overall survival and disease-specific survival, an indicator of ESCC-related mortality, were 83.4% and 98.4%, respectively. In multivariate Cox analyses, Eastern Cooperative Oncology Group performance status (ECOG-PS), consisting of six grades by a patient's level of activity, ≥ 2 was a predictor for early and late morality [hazard ratio (HR), 7.21 (P = 0.007) and 15.62 (P = 0.021), respectively]. Charlson comorbidity index (CCI), which is an index for predicting mortality by comorbid conditions, ≥ 2 was also a predictor for both mortality [HR, 2.97 (P = 0.017) and 1.90 (P = 0.019), respectively]. However, age was a predictor only for late mortality [HR, 3.08 (P = 0.010) in 80-84 years and 8.38 (P < 0.001) in ≥ 85 years]. Considering the predictive ability for early mortality, we propose that ECOG-PS and/or CCI are better indices compared with age in deciding treatment strategy after ER for ESCC.
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http://dx.doi.org/10.1620/tjem.253.29DOI Listing
January 2021

A Rare Case of Localized Esophageal Amyloidosis.

Intern Med 2021 May 7;60(10):1529-1532. Epub 2020 Dec 7.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan.

A 72-year-old man without any symptoms was referred to our hospital. Esophagogastroduodenoscopy revealed an elevated esophageal lesion that was covered with normal mucosa. The examination of biopsy specimens from the lesion revealed amyloid light-chain (AL) (λ) type amyloid deposits, but there were no amyloid deposits elsewhere in the gastrointestinal tract. Further examinations did not indicate systemic amyloidosis. Thus, this case was diagnosed as a localized esophageal amyloidosis. As the clinical outcome of localized amyloidosis is favorable, this case was scheduled for close follow-up. Localized amyloidosis should be considered in the differential diagnosis of esophageal submucosal tumors.
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http://dx.doi.org/10.2169/internalmedicine.6321-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188021PMC
May 2021

Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study.

Dig Endosc 2020 Dec 4. Epub 2020 Dec 4.

Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.

Objects: Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort.

Methods: A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year.

Results: Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC.

Conclusion: This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).
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http://dx.doi.org/10.1111/den.13910DOI Listing
December 2020

Linked Color Imaging Focused on Neoplasm Detection in the Upper Gastrointestinal Tract : A Randomized Trial.

Ann Intern Med 2021 01 20;174(1):18-24. Epub 2020 Oct 20.

National Hospital Organization Hakodate National Hospital, Hakodate, Japan (M.K.).

Background: Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color.

Objective: To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract.

Design: A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863).

Setting: 16 university hospitals and 3 tertiary care hospitals in Japan.

Patients: 1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer.

Intervention: WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group).

Measurements: Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome).

Results: 752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50;  = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]).

Limitation: Endoscopists were not blinded.

Conclusion: LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach.

Primary Funding Source: Fujifilm Corporation.
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http://dx.doi.org/10.7326/M19-2561DOI Listing
January 2021

Localized Gastric Amyloidosis that Displayed Morphological Changes over 10 Years of Observation.

Intern Med 2021 Feb 30;60(4):539-543. Epub 2020 Sep 30.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan.

We herein report an extremely rare case of localized gastric amyloidosis (LGA) with morphological changes during the follow-up. A 71-year-old woman who had a depressed lesion with central elevation in the gastric lower body was diagnosed with LGA. Esophagogastroduodenoscopy at 10 years after the initial examination showed that the lesion had grown and changed morphologically, exhibiting a submucosal tumor-like appearance. Since the lesion was confined to the submucosa, the patient underwent endoscopic submucosal dissection. The final pathological diagnosis was amyloid light-chain (AL)-type LGA. This case may provide useful information regarding the natural history of AL-type LGA.
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http://dx.doi.org/10.2169/internalmedicine.5031-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946503PMC
February 2021

The Development of Foveolar-type Gastric Adenocarcinoma during Maintenance Therapy of Vonoprazan for Reflux Esophagitis.

Intern Med 2021 Feb 29;60(3):391-396. Epub 2020 Aug 29.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan.

We herein report the first case of foveolar-type gastric adenocarcinoma that developed after the initiation of vonoprazan (VPZ). A 51-year-old man had heartburn at the first visit and reflux esophagitis endoscopically, so he started taking VPZ. An approximately 5-mm-sized reddish polyp with a raspberry-like morphology was detected at the anterior wall of the upper body of the stomach 156 weeks after starting maintenance therapy with VPZ 10 mg/day. It was diagnosed as foveolar-type gastric adenocarcinoma based on a biopsy. Another approximately 4-mm-sized foveolar-type gastric adenocarcinoma was also detected at the posterior wall of the middle body of the stomach.
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http://dx.doi.org/10.2169/internalmedicine.5431-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925268PMC
February 2021

Using Polyethylene Glycol 3350 Plus Electrolytes in Constipated Hemodialysis Patients: A Case Series.

Intern Med 2021 Feb 29;60(3):379-384. Epub 2020 Aug 29.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan.

Appropriate management of constipation in hemodialysis patients has not been established, although constipation is the most frequent gastrointestinal complication in dialysis patients. We herein report the efficacy and safety of polyethylene glycol in constipated hemodialysis patients assessed prospectively. Seven patients using stimulant laxatives participated in this study. Polyethylene glycol was administered to reduce stimulant laxatives during the six-week intervention period. The amount of stimulant laxatives decreased and spontaneous bowel movements with ideal stool consistency increased significantly after the intervention. No serious adverse effects were observed throughout this study. In conclusion, polyethylene glycol can be a useful tool for managing constipated hemodialysis patients.
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http://dx.doi.org/10.2169/internalmedicine.5231-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925282PMC
February 2021

Supragastric belching in Japan: lower prevalence and relevance for management of gastroesophageal reflux disease compared to United Kingdom.

J Gastroenterol 2020 Nov 24;55(11):1046-1053. Epub 2020 Aug 24.

Barts and The London School of Medicine and Dentistry, Wingate Institute of Neurogastroenterology, Blizard Institute, Upper GI Physiology Unit Royal London Hospital, Queen Mary University of London, 26 Ashfield Street, London, E12AJ, UK.

Background: Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK.

Methods: We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries.

Results: Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09-7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0-4.9)] compared to the UK [35% (0-54.1)] (P = 0.071).

Conclusions: The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.
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http://dx.doi.org/10.1007/s00535-020-01720-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567718PMC
November 2020

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease.

Digestion 2021 12;102(3):404-414. Epub 2020 Aug 12.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background And Objective: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients' mucosal integrity of the proximal esophagus.

Methods: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis.

Results: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1β mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules.

Conclusions: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.
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http://dx.doi.org/10.1159/000508661DOI Listing
August 2020

Duodenal Obstruction Caused by the Long-term Recurrence of Appendiceal Goblet Cell Carcinoid.

Intern Med 2020 Dec 4;59(23):3001-3007. Epub 2020 Aug 4.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan.

A 38-year-old Japanese man who had been diagnosed with appendiceal carcinoid and undergone ileocecal resection 8 years before presented with duodenal obstruction caused by a submucosal tumor-like appearance. He was diagnosed with long-term recurrence of appendiceal goblet cell carcinoid (GCC) with a multi-morphological pattern based on the histological assessment of a duodenal biopsy and his previously resected appendix. He underwent subtotal stomach-preserving pancreaticoduodenectomy combined with resection of an ileo-colic anastomotic lesion. The GCC recurred at the nearby ileo-colic anastomosis and invaded the duodenum. This late recurrence might have resulted from the unique features of his GCC, which contained cells with different degrees of malignancy.
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http://dx.doi.org/10.2169/internalmedicine.4548-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759692PMC
December 2020

A rare case of gastric squamous-cell carcinoma metastasized from the cervix.

Clin J Gastroenterol 2020 Dec 25;13(6):1062-1065. Epub 2020 Jul 25.

Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo-Cho Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.

Gastric squamous-cell carcinoma (SqCC) metastasized form the cervix is rarely detected in endoscopic examination, although cervical carcinoma is the second most common in gynecologic malignancy. A 59-year-old female visited a clinic for anorexia, and an esophago-gastro-duodenoscopy (EGD) revealed multiple submucosal tumors (SMTs) of the stomach. After she was referred, an image-enhanced endoscopy enhanced multiple SMTs with white spots, whose findings were irregular micro-vascular patterns in the mucosa with irregular/absent micro-surface pattern. We took endoscopic biopsies, whose histological diagnoses were SqCC in the layer of the lamina propria under normal epithelium. Positron emission tomography-CT, CT and magnetic resonance imaging revealed an irregularly enhanced mass of the cervix, the irregularly thickening wall of the stomach and peritoneal nodules. Palliative care alone was administered based on poor condition associated with the Stage IV cervical carcinoma. In this case, endoscopic detection of gastric SqCC might provide a tip to make final diagnosis of primary site of cervical SqCC. The numbers of endoscopic examination become increasing, so further deep awareness of such patterns of metastasis in cervical cancer are required.
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http://dx.doi.org/10.1007/s12328-020-01191-8DOI Listing
December 2020

Novel device for preventing diffusion of aerosol droplets from subjects undergoing esophagogastroduodenoscopy during COVID-19 pandemic.

Dig Endosc 2020 Sep 22;32(6):e140-e141. Epub 2020 Jul 22.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan.

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http://dx.doi.org/10.1111/den.13772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405108PMC
September 2020

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

Endoscopy 2020 11 24;52(11):967-975. Epub 2020 Jun 24.

Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.

Background: Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study.

Methods: Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC.

Results: 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %.

Conclusions: Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.
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http://dx.doi.org/10.1055/a-1185-9329DOI Listing
November 2020

Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score.

Gut 2021 Mar 4;70(3):476-484. Epub 2020 Jun 4.

Division of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.

Objective: Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC.

Design: This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration.

Results: A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a -statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01).

Conclusions: In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.
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http://dx.doi.org/10.1136/gutjnl-2019-319926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873424PMC
March 2021

[Relationship between lifestyle and esophageal disease].

Nihon Shokakibyo Gakkai Zasshi 2020;117(5):365-374

Division of Gastroenterology, Tohoku University Graduate School of Medicine.

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http://dx.doi.org/10.11405/nisshoshi.117.365DOI Listing
September 2020

Gastric Duplication Cyst With Occult GIST Component.

ACG Case Rep J 2020 Feb 7;7(2):e00260. Epub 2020 Feb 7.

Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyagi, Japan.

A 37-year-old man underwent screening examinations, and a pale-colored submucosal tumor was detected on gastric cardia. Endosonography showed a 15-mm cyst with hypoechoic nodules in the muscularis propria, and endoscopic ultrasound-guided fine-needle aspiration obtained mucinous fluid with atypical spindle cells positive for , indicating a gastrointestinal stromal tumor. Surgical resection was recommended, but he initially agreed to surveillance. After becoming larger for 8 years, partial gastrectomy was performed for the 22 × 22 × 15-mm capsulized lesion. Surprisingly, its histology was gastric duplication cyst without gastrointestinal stromal tumor. Gastric duplication cyst is a rare entity with the possibility of malignant complications, but careful assessment of endoscopic ultrasound-guided fine-needle aspiration might also be required.
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http://dx.doi.org/10.14309/crj.0000000000000260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145172PMC
February 2020

Prevalence and risk factors for lymph node metastasis after noncurative endoscopic resection for early gastric cancer: a systematic review and meta-analysis.

J Gastroenterol 2020 Aug 10;55(8):742-753. Epub 2020 Apr 10.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Background: Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies.

Methods: We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible.

Results: We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88-6.19]), lymphovascular invasion (LVI) (4.17 [2.90-5.99]), vascular invasion (2.38 [1.65-3.44]), positive vertical margin (2.16 [1.59-2.93]), submucosal invasion depth of ≥ 500 μm (2.14 [1.48-3.09]), and tumor size > 30 mm (1.77 [1.31-2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance.

Conclusions: Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).
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http://dx.doi.org/10.1007/s00535-020-01685-9DOI Listing
August 2020

Photocrosslinking of cDNA Display Molecules with Their Target Proteins as a New Strategy for Peptide Selection.

Molecules 2020 Mar 24;25(6). Epub 2020 Mar 24.

Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan.

Binding peptides for given target molecules are often selected in vitro during drug discovery and chemical biology research. Among several display technologies for this purpose, complementary DNA (cDNA) display (a covalent complex of a peptide and its encoding cDNA linked via a specially designed puromycin-conjugated DNA) is unique in terms of library size, chemical stability, and flexibility of modification. However, selection of cDNA display libraries often suffers from false positives derived from non-specific binding. Although rigorous washing is a straightforward solution, this also leads to the loss of specific binders with moderate affinity because the interaction is non-covalent. To address this issue, herein, we propose a method to covalently link cDNA display molecules with their target proteins using light irradiation. We designed a new puromycin DNA linker that contains a photocrosslinking nucleic acid and prepared cDNA display molecules using the linker. Target proteins were also labeled with a short single-stranded DNA that should transiently hybridize with the linker. Upon ultraviolet (UV) light irradiation, cDNA display molecules encoding correct peptide aptamers made stable crosslinked products with the target proteins in solution, while display molecules encoding control peptides did not. Although further optimization and improvement is necessary, the results pave the way for efficient selection of peptide aptamers in multimolecular crowding biosystems.
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http://dx.doi.org/10.3390/molecules25061472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146492PMC
March 2020

The Alcohol Use Disorders Identification Test and the risk of metachronous cancer after endoscopic resection of esophageal cancer.

Carcinogenesis 2020 08;41(8):1049-1056

Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Kyoto, Japan.

Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8-14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0-7, 1.2 for 8-14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC [multivariate hazard ratio (95% confidence interval) = 6.98 (1.31-37.09) and 3.19 (1.19-8.54), respectively]. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676.
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http://dx.doi.org/10.1093/carcin/bgaa022DOI Listing
August 2020

The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease.

Digestion 2021 14;102(3):480-488. Epub 2020 Feb 14.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Introduction: Weakly acidic reflux has been reported to be the major cause of symptoms in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) undergoing PPI treatment. We previously reported that reflux at pH 4-5 was the main factor that induced symptoms in such patients. The present study aimed to elucidate the symptom-ameliorating effect of vonoprazan (VPZ) by evaluating the change in the pH value of the refluxate using multichannel intraluminal impedance and pH (MII-pH) monitoring.

Methods: We retrospectively evaluated the records of MII-pH monitoring in 29 symptom index (SI) and/or symptom association probability (SAP)-positive patients with PPI-refractory NERD. After switching to VPZ 20 mg/day, we performed MII-pH monitoring again. We assessed the change in the score of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the pH value of the refluxate, and the percent times of intragastric pH <4 or <5 before and after switching. We divided the patients into the following 2 groups according to the FSSG score after switching: effective and noneffective groups.

Results: Among of the 29 SI/SAP-positive patients, 16 underwent switching to VPZ. Furthermore, of these 16 patients, 10 underwent MII-pH monitoring again after switching. The FSSG score decreased, the pH value of the refluxate increased, and the percent times of intragastric pH <4 or <5 reduced after switching when compared with the findings before switching. In the effective group, both the proportion of reflux at pH <4 and that of reflux at pH 4-5 decreased while taking VPZ when compared with the findings while taking double-dose PPI. In the noneffective group, the proportion of reflux at pH <4 decreased but that of reflux at pH 4-5 increased and that of reflux at pH <5 did not change overall while taking VPZ. In addition, the percent times of intragastric pH <5 values were low in the effective group.

Conclusion: Symptom suppression appears to be inadequate in patients with persistent reflux at pH 4-5 even with VPZ 20 mg/day. Strong acid suppressive therapy with VPZ to increase the pH value of the refluxate to ≥5 is useful for symptom improvement.
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http://dx.doi.org/10.1159/000506152DOI Listing
February 2020

Sox2 induces tumorigenesis and angiogenesis of early-stage esophageal squamous cell carcinoma through secretion of Suprabasin.

Carcinogenesis 2020 11;41(11):1543-1552

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Early stage of esophageal squamous cell carcinoma (ESCC) is known to be accompanied by angiogenesis and morphological changes of microvessels. Transcription factor Sox2 is amplified in various cancers including ESCC, but the role of Sox2 in the carcinogenesis and angiogenesis has not been determined. Hence, we aimed to investigate the role of Sox2 in the early stage of ESCC. We found that the expression of Sox2 was significantly higher in early-stage ESCC tissues than that in their adjacent normal tissues. We then established Sox2-inducible normal human esophageal squamous cell line (HetSox2) to investigate the role of Sox2 in esophageal carcinogenesis and angiogenesis in vitro. Sox2 overexpression led to increased cell proliferation and spheroid formation. The culture supernatant of Sox2-overexpressing HetSox2 induced migration and sprouting of endothelial cell line HUVEC (human umbilical vein endothelial cell). As for the mechanism, we found that the expression of secreted protein Suprabasin was directly induced by Sox2. Suprabasin enhanced proliferation of normal human esophageal squamous cells when added to the culture. Moreover, Suprabasin enhanced migration and sprouting of HUVEC cells, which were observed with the culture supernatant of Sox2-overexpressing HetSox2. This angiogenic effect of Suprabasin was abolished by inhibiting AKT phosphorylation, which suggested its dependence on AKT signaling. Finally, we showed that Suprabasin expression and the density of microvessels were significantly higher in ESCC tissues with high Sox2 expression. Our study suggested that increased Sox2 expression in esophageal squamous cells induced Suprabasin expression, and as a result initiated the carcinogenesis via increased cell proliferation and angiogenesis.
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http://dx.doi.org/10.1093/carcin/bgaa014DOI Listing
November 2020

Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions.

Dis Esophagus 2020 Sep;33(9)

Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.

This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC.
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http://dx.doi.org/10.1093/dote/doz110DOI Listing
September 2020

Management following endoscopic resection in elderly patients with early-stage upper gastrointestinal neoplasia.

Dig Endosc 2020 Sep 22;32(6):861-873. Epub 2020 Jan 22.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan.

With the ongoing increase in the aging population in Japan, the number of elderly patients among the total population with upper gastrointestinal (GI) neoplasia has also been increasing. As elderly patients present unique age-related variations in their physical condition, the therapeutic approach for upper GI neoplasia should be differentiated between elderly and nonelderly patients. According to the existing guidelines, additional treatment is the standard therapy in patients who undergo endoscopic resection (ER) with a possible risk of lymph node metastasis (LNM) for upper GI neoplasia. However, due to the relatively low rate of LNM, applying additional treatment in all elderly patients may be excessive. Although additional treatment has the advantage of reducing cancer-specific mortality, its disadvantages include deteriorated quality of life, complications, and mortality in surgery. In patients with early gastric cancer, we propose treatment decisions be made using a risk-scoring system for LNM and upon considering the physical condition of the patient after ER with curability C-2. In those with superficial esophageal squamous cell carcinoma with a possible risk of LNM after ER, selective chemoradiotherapy may be a less-invasive treatment option, although the present standard treatment is esophagectomy. When considering the treatment decision, achieving a "cure" of the tumor has been regarded as critical. However, as the main cause of mortality in elderly patients with ER for upper GI neoplasia is noncancer-related death, both achieving a "cure" and also a good level of "care" is important in the management of elderly patients.
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http://dx.doi.org/10.1111/den.13592DOI Listing
September 2020

Difficult Preoperative Diagnosis of Lymphoepithelioma-Like Carcinoma of the Esophagus.

ACG Case Rep J 2019 Aug 30;6(8):e00163. Epub 2019 Aug 30.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

A 60-year-old man with a medical history of diabetes, liver cirrhosis, and distal gastrectomy was referred for further examination of a 10-mm pale-colored submucosal tumor around 40 cm from the incisors. Narrow band imaging-magnifying endoscopy revealed the lesion covered by smooth epithelium with irregular microvascular architecture in a sparse distribution. Endosonography showed an irregular-shaped hypoechoic lesion in the submucosa. With no evidence of metastases, we performed en bloc endoscopic submucosal dissection, whose specimen revealed esophageal lymphoepithelioma-like carcinoma invading up to 500 μm in the submucosa, a rare disease entity. Despite no additional treatment, he was alive without recurrence for longer than 88 months.
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http://dx.doi.org/10.14309/crj.0000000000000163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791625PMC
August 2019

Modified Hemihamate Arthroplasty With Oblique Osteotomy of the Middle Phalanx Base to Reconstruct Proper Contour of the Articular Surface.

Tech Hand Up Extrem Surg 2020 Jun;24(2):79-84

Hand Surgery Center, National Hospital Organization Murayama Medical Center, Musashimurayama City, Tokyo, Japan.

Treatments of unstable dorsal fracture dislocations of the proximal interphalangeal (PIP) joint are very challenging. The authors performed modified hemihamate arthroplasty for these injuries in 13 patients (13 fingers). Our surgical technique was unique in the point that we put volarly oblique osteotomy in the coronal plane at the recipient site to create an adequate reconstruction of the volar lip of the articular surface of the middle phalanx. Affected fingers are index in 2, middle in 4, ring in 3, and little in 3, and the mean duration of follow-up was 14 months. Hemihamate arthroplasty was indicated if >30% to 50% of the volar articular surface of the middle phalangeal base showed comminuted fracture which was not large enough to allow open reduction and internal fixation. The average range of motion of the PIP joint was 17.7 degrees preoperatively, which was improved significantly to 71.3 degrees at final follow-up. Radiographically, all grafts were united but 1 showed mild graft absorption. Ten patients demonstrated normal joint space and other 3 showed mild degenerative change of PIP joints. Eleven patients showed good congruency of the PIP joint and other 2 demonstrated slight dorsal subluxation. Four patients complained of mild pain in flexion, but other 9 had no pain at all. The modified hemihamate arthroplasty is a reliable technique to treat comminuted dorsal fracture dislocations of the PIP joint.
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http://dx.doi.org/10.1097/BTH.0000000000000268DOI Listing
June 2020
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