It was reported that nerve fibers were present in the inner part of lumbar intervertebral discs from patients with discogenic pain. Because there are no nerve fibers in the inner part of annulus fibrosus in normal condition, this finding suggests nerve ingrowth into the disc may be a cause of discogenic pain. Disc degeneration is often asymptomatic, thus, to understand the differences between symptomatic and asymptomatic disc, it is necessary to understand the pathogenesis of discogenic pain. We recently revealed that over 90% of the nociceptive dorsal root ganglion (DRG) neurons innervating the disc are sensitive to nerve growth factor (NGF), which is related to inflammatory pain. This indicates that discogenic pain is closely related to inflammation and NGF may play a key role. The increase of inflammatory mediators in symptomatic discs has been reported; we therefore studied the effects of disc inflammation and found that it induces sensitization of disc-innervating neurons and nerve ingrowth into the disc. More recently, it was shown that annular rupture induces nerve ingrowth, an increase of inflammatory mediators in the disc, and upregulation of calcitonin gene-related peptide, a pain-related molecule in DRGs. These findings led us to believe that annular rupture triggers inflammation and nerve ingrowth, inflammatory mediators then further promote nerve ingrowth into the disc and sensitization of disc-innervating neurons, and discogenic pain finally becomes chronic. NGF, found in symptomatic discs, may act as a key factor in generating chronic discogenic pain by sensitizing disc-innervating neurons and stimulating nerve ingrowth into the disc.
Calcitonin Gene-Related Peptide ; Diagnosis-Related Groups ; Ganglia, Spinal ; Humans ; Inflammation ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Nerve Fibers ; Nerve Growth Factor ; Neurons ; Rupture ; Up-Regulation

PURPOSE: Endoscopic diagnosis of gastric cancer (GC) that emerges after eradication of Helicobacter pylori may be affected by unique morphological changes. Using comprehensive endoscopic imaging, which can reveal biological alterations in gastric mucosa after eradication, previous studies demonstrated that Congo red chromoendoscopy (CRE) might clearly show an acid non-secretory area (ANA) with malignant potential, while autofluorescence imaging (AFI) without drug injection or dyeing may achieve early detection or prediction of GC. We aimed to determine whether AFI might be an alternative to CRE for identification of high-risk areas of gastric carcinogenesis after eradication. MATERIALS AND METHODS: We included 27 sequential patients with metachronous GC detected during endoscopic surveillance for a mean of 82.8 months after curative endoscopic resection for primary GC and eradication. After their H. pylori infection status was evaluated by clinical interviews and ¹³C-urea breath tests, the consistency in the extension of corpus atrophy (e.g., open-type or closed-type atrophy) between AFI and CRE was investigated as a primary endpoint. RESULTS: Inconsistencies in atrophic extension between AFI and CRE were observed in 6 of 27 patients, although CRE revealed all GC cases in the ANA. Interobserver and intraobserver agreements in the evaluation of atrophic extension by AFI were significantly less than those for CRE. CONCLUSIONS: We demonstrated that AFI findings might be less reliable for the evaluation of gastric mucosa with malignant potential after eradication than CRE findings. Therefore, special attention should be paid when we clinically evaluate AFI findings of background gastric mucosa after eradication (University Hospital Medical Information Network Center registration number: UMIN000020849).
Atrophy ; Breath Tests ; Carcinogenesis ; Congo Red ; Diagnosis ; Digestive System ; Endoscopy ; Gastric Mucosa* ; Helicobacter pylori* ; Helicobacter* ; Humans ; Information Services ; Optical Imaging ; Stomach Neoplasms

A special Students' Committee on Medical Education was established by the Student Union of Nippon Medical School. The members of this committee are all volunteers and have carried out several plans to improve the educational environment at our school. In 1999, the Students' Committee on Medical Education proposed holding joint meetings with the Education Committee of Nippon Medical School. The meeting was to allow communication between students and teachers for improving the curriculum. The volunteer faculty members of the Education Committee and students have held joint meetings seven times from November 1999 through February 2001. Discussions between students and teachers have changed ideas on both sides and have led to improvements in some educational programs, such as clinical internship during the summer vacation.

Background/Aims: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA. Methods: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs. Results: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients. Conclusions The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA.

Background/Aims: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA. Methods: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs. Results: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients. Conclusions The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA.

PURPOSE: The optimal method for intracorporeal esophagojejunostomy remains unclear because a purse-string suture for fixing the anvil into the esophagus is difficult to perform with a laparoscopic approach. Therefore, this study aimed to evaluate our novel technique to fix the anvil into the esophagus. MATERIALS AND METHODS: This retrospective study included 202 patients who were treated at our institution with an intracorporeal circular esophagojejunostomy in a laparoscopy-assisted total gastrectomy with a Roux-en-Y reconstruction (166 cases) or a laparoscopy-assisted proximal gastrectomy with jejunal interposition (36 cases). After incising 3/4 of the esophageal wall, a hand-sewn purse-string suture was placed on the esophagus. Next, the anvil head of a circular stapler was introduced into the esophagus. Finally, the circular esophagojejunostomy was performed laparoscopically. The clinical characteristics and surgical outcomes were evaluated and compared with those of other methods. RESULTS: The average operation time was 200.3 minutes. The average hand-sewn purse-string suturing time was 6.4 minutes. The overall incidence of postoperative complications (Clavien–Dindo classification grade ≥II) was 26%. The number of patients with an anastomotic leakage and stenosis at the esophagojejunostomy site were 4 (2.0%) and 12 (6.0%), respectively. All patients with stenosis were successfully treated by endoscopic balloon dilatation. There was no mortality. Regarding the materials and devices for anvil fixation, only 1 absorbable thread was needed. CONCLUSIONS: Our procedure for hand-sewn purse-string suturing with the double ligation method is simple and safe.
Anastomotic Leak ; Classification ; Constriction, Pathologic ; Dilatation ; Esophagus ; Gastrectomy ; Head ; Humans ; Incidence ; Laparoscopy ; Ligation ; Methods ; Mortality ; Postoperative Complications ; Retrospective Studies ; Sutures

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.