Sleep architecture as a candidate for phenotyping sleep bruxism: A narrative physiological review.

BACKGROUND: Sleep bruxism (SB), an oral behaviour in otherwise healthy individuals, is characterised by frequent rhythmic masticatory muscle activity (RMMA) during sleep. RMMA/SB episodes occur over various sleep stages (N1-N3 and rapid eye movement (REM)), sleep cycles (non-REM to REM), and frequently with microarousals. It currently remains unclear whether these characteristics of sleep architecture are phenotype candidates for the genesis of RMMA/SB. OBJECTIVES: This narrative review investigated the relationship between sleep architecture and the occurrence of RMMA as a SB phenotype candidate. METHODS: PubMed research was performed using keywords related to RMMA/SB and sleep architecture. RESULTS: In non-SB and SB healthy individuals, RMMA episodes were most frequent in the light non-REM sleep stages N1 and N2, particularly during the ascending phase of sleep cycles. The onset of RMMA/SB episodes in healthy individuals was preceded by a physiological arousal sequence of autonomic cardiovascular to cortical activation. It was not possible to extract a consistent sleep architecture pattern in the presence of sleep comorbidities. The lack of standardisation and variability between subject complexified the search for specific sleep architecture phenotype(s). CONCLUSION: In otherwise healthy individuals, the genesis of RMMA/SB episodes is largely affected by oscillations in the sleep stage and cycle as well as the occurrence of microarousal. Furthermore, a specific sleep architecture pattern cannot be confirmed in the presence of sleep comorbidity. Further studies are needed to delineate sleep architecture phenotype candidate(s) that contribute to the more accurate diagnosis of SB and treatment approaches using standardised and innovative methodologies.

Understanding the pathophysiology of sleep bruxism based on human and animal studies: A narrative review.

BACKGROUND: Sleep bruxism (SB) is a common sleep disorder that affects approximately 20% of children and 10% of adults. It may cause orodental problems, such as tooth wear, jaw pain, and temporal headaches. However, the pathophysiological mechanisms underlying SB remain largely unknown, and a definitive treatment has not yet been established. HIGHLIGHT: Human studies involving polysomnography have shown that rhythmic masticatory muscle activity (RMMA) is more frequent in otherwise healthy individuals with SB than in normal individuals. RMMA occurs during light non-rapid eye movement (non-REM) sleep in association with transient arousals and cyclic sleep processes. To further elucidate the neurophysiological mechanisms of SB, jaw motor activities have been investigated in naturally sleeping animals. These animals exhibit various contractions of masticatory muscles, including episodes of rhythmic and repetitive masticatory muscle bursts that occurred during non-REM sleep in association with cortical and cardiac activation, similar to those found in humans. Electrical microstimulation of corticobulbar tracts may also induce rhythmic masticatory muscle contractions during non-REM sleep, suggesting that the masticatory motor system is activated during non-REM sleep by excitatory inputs to the masticatory central pattern generator. CONCLUSION: This review article summarizes the pathophysiology of SB based on the findings from human and animal studies. Physiological factors contributing to RMMA in SB have been identified in human studies and may also be present in animal models. Further research is required to integrate the findings between human and animal studies to better understand the mechanisms underlying SB.

Motor representation of rhythmic jaw movements in the amygdala of guinea pigs.

OBJECTIVE: The areas of the amygdala contributing to rhythmic jaw movements and the movement patterns induced remain unknown. Therefore, the present study investigated the areas of the amygdala contributing to rhythmic jaw movements using repetitive electrical microstimulation techniques. DESIGN: Experiments were performed on head-restrained guinea pigs under ketamine-xylazine anesthesia. EMG activities in the masseter and digastric muscles and jaw movements were recorded. Short- and long-train electrical microstimulations of the amygdala were performed and the patterns of jaw movements induced were analyzed quantitatively. RESULT: The short-train stimulation induced short-latency EMG responses in the masseter and/or digastric muscles. The stimulation sites inducing short-latency EMG responses were distributed within the ventral part of the amygdala, which covered the medial, basal, and cortical nuclei. The long-train stimulation induced tonic jaw opening and two types of rhythmic jaw movements: those with or without lateral jaw shifts, which were characterized by a larger jaw gape and ipsilateral jaw excursion, respectively. Rhythmic jaw movements with lateral jaw shifts were characterized by overlapping masseter and digastric EMG activities. However, rhythmic patterns did not differ between the two types of rhythmic jaw movements. The stimulation sites that induced rhythmic jaw movements were more localized to the cortical nucleus. CONCLUSIONS: The present results suggest that the ventral part of the amygdala is involved in the induction of rhythmic jaw movements in guinea pigs. The putative roles of the limbic system in the genesis of functional (e.g., chewing) and non-functional (e.g., bruxism) rhythmic oromotor movements warrant further study.

After-effects of acute footshock stress on sleep states and rhythmic masticatory muscle activity during sleep in guinea pigs.

This study investigated the effects of acute footshock stress (FS) on the occurrence of rhythmic masticatory muscle activity (RMMA) during sleep in guinea pigs. Animals were prepared for chronic recordings from electroencephalogram, electrooculogram and electromyograms of neck and masseter muscles. The signals were recorded for six hours on the two successive days: the first day with stress-free condition (non-FS condition) and the second day with acute FS (FS condition). Sleep/wake states and RMMA were scored visually. Sleep variables and the frequency of RMMA occurring during non-rapid eye movement (NREM) sleep were compared during 6-h periods between the two conditions. Compared to non-FS condition, the amount of total sleep and NREM sleep significantly reduced during 2 h following the acute FS in the FS condition. Similarly, the frequency of RMMA significantly increased during 2 h following the acute FS for the FS condition compared to non-FS condition. During 2-6 h after FS in the FS condition, sleep variables and the frequency of RMMA did not differ from those without FS in the non-FS condition. These results suggest that acute experimental stress can induce transient changes in sleep-wake states and the occurrence of RMMA in experimental animals.

Changes in cortical, cardiac, and respiratory activities in relation to spontaneous rhythmic jaw movements in ketamine-anesthetized guinea pigs.

It has been reported that rhythmic jaw movements (RJMs) spontaneously occur in ketamine-anesthetized animals. The present study investigated the physiological processes that occur during the cortical, cardiac, and respiratory events which contribute to the genesis of RJMs in animals after supplemental ketamine injections. Fourteen guinea pigs were prepared to allow electroencephalographic, electrocardiographic, and electromyographic activities to be recorded from the digastric muscle, measurement of jaw movements, and nasal expiratory airflow under ketamine-xylazine anesthesia. Rhythmic jaw movements spontaneously occurred with rhythmic digastric muscle contractions, 23-29 minutes after injection of supplemental ketamine (12.5 and 25.0 mg kg-1 , intravenously). The cycle length of RJMs did not differ significantly between the two doses of ketamine (mean±SD: 12.5 mg kg-1 , 326.5 ± 60.0 ms; 25 mg kg-1 , 278.5 ± 45.1 ms). Following injection of ketamine, digastric muscle activity, heart and respiratory rates, and cortical beta power significantly decreased, while cortical delta and theta power significantly increased. These changes were significantly larger in animals given 25.0 mg kg-1 of ketamine than in those given 12.5 mg kg-1 . With the onset of RJMs, the levels of these variables returned to pre-injection levels, regardless of the dose of ketamine administered. These results suggest that, following supplemental ketamine injections, spontaneous RJMs occur during a specific period when the pharmacological effects of ketamine wear off, and that these RJMs are characterized by stereotypical changes in cardiac, respiratory, and cortical activities.

Preceding endoscopic submucosal dissection for T1 colorectal carcinoma does not affect the prognosis of patients who underwent additional surgery: a large multicenter propensity score-matched analysis.

BACKGROUND: We analyzed the influence of preceding endoscopic submucosal dissection (ESD) on the prognosis of patients with T1 colorectal carcinoma (CRC) after additional surgery using propensity-score matching. METHODS: 1638 consecutive patients with T1 CRC were retrospectively identified between January 1998 and December 2016 at the Hiroshima GI Endoscopy Research Group. We assessed 602 patients with 602 T1 CRC who underwent additional surgery after ESD (n = 216) or surgery alone (n = 386). The enrolled patients were treated according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016, and were defined as non-endoscopically curable (non-e-curable) when they did not satisfy its curative criteria. We analyzed the pathological characteristics and the prognosis of non-e-curable patients using propensity-score matching between the additional surgery after ESD and surgery alone groups. RESULTS: There were no cases of recurrence and lymph node metastasis among the e-curable patients. The rate of lymph node metastasis and recurrences in the non-e-curable patients were 10.8% and 2.6%, respectively. After propensity-score matching, there were no significant differences in the 5-year overall survival rates (96.9% vs. 92.0%), 5-year disease-free survival rates (96.7% vs. 96.7%) and 5-year disease-specific survival rates (100% vs. 98.6%) after treatment of T1 CRCs between the 2 groups in non-e-curable patients. CONCLUSIONS: Preceding ESD with histological en bloc resection for patients with T1 CRC did not affect their oncologic behavior adversely after additional surgery.

Experimentally induced rhythmic jaw muscle activities during non-rapid eye movement sleep in freely moving guinea pigs.

Rhythmic jaw muscle activities frequently occur during non-rapid eye movement sleep in patients with sleep bruxism. The present study aimed to investigate the response characteristics of the masticatory rhythm generation during non-rapid eye movement sleep in animals. Eleven guinea pigs were surgically prepared for polygraphic recordings by electromyography, electrooculography, electroencephalography and electrocardiography with the implantation of a stimulating electrode. Repetitive electrical microstimulations at three intensities were applied to the corticobulbar tract under freely moving conditions. The rhythmic electro-myographic responses of the digastric and masseter muscles were scored and analysed. Changes in cortical electro-encephalographic power and heart rate in association with these stimulations were quantified. Microstimulations to the corticobulbar tract induced rhythmic jaw muscle activities in digastric muscles, occasionally with masseter activities during wakefulness and non-rapid eye movement sleep. The response rate of rhythmic jaw muscle activities was significantly lower (p < 0.01) and the response latency was significantly longer (p < 0.01) during non-rapid eye movement sleep than during wakefulness. At higher stimulus intensities, the response rate increased and response latency decreased. The mean burst intervals of the digastric and masseter muscles were similar regardless of vigilance states and stimulus intensities. Induced rhythmic jaw muscle activities during non-rapid eye movement sleep were followed by a transient decrease in delta power and increases in beta power and heart rate. During non-rapid eye movement sleep, the masticatory motor system is able to generate rhythmic outputs to the jaw muscles in response to facilitatory inputs although the responsiveness was decreased from wakefulness.

Long-term prognosis after treatment for T1 carcinoma of laterally spreading tumors: a multicenter retrospective study.

PURPOSE: Long-term prognosis of T1 laterally spreading tumors (LSTs) after treatment have not been clarified. This study compared clinicopathological characteristics and long-term prognosis of T1 LSTs. METHODS: We retrospectively assessed 169 patients with 169 T1 LSTs between January 1992 and December 2008 by ten hospitals. Patients who did not meet the Japanese Society for Cancer of the Colon and Rectum (JSCCR) 2016 guidelines for the treatment of colorectal carcinoma (CRC) criteria were defined as non-endoscopically curable. The number of non-endoscopically curable patients with LST-granular/ nodular mixed (LST-G-M) was 61, that with LST-non-granular/ flat elevated (LST-NG-FE) was 23, and that with LST-non-granular/ pseudo depressed (LST-NG-PD) was 23. Clinicopathological variables and long-term prognosis were analyzed. RESULTS: For overall patients, tumor size, number of non-endoscopically curable cases, and rate of submucosal invasion depth ≥ 1000 µm for the LST-G-M group were significantly higher than those in the other groups. For non-endoscopically curable patients, the tumor size for those with LST-G-M was significantly larger than those in the other groups. The rate of submucosal invasion width ≥ 4000 µm and type B/C muscularis mucosae with LST-G-M was higher than that with LST-NG-FE. All recurrences occurred in non-endoscopically curable patients with LST-G-M. Five-year overall and disease-free survivals for non-endoscopically curable patients with LST-G-M were significantly shorter than those for patients with non-endoscopically curable LST-NG-FE and PD. CONCLUSIONS: Our data supported adequacy of the JSCCR guidelines for the treatment of CRC criteria for endoscopically curable patients after T1 LSTs treatment. Patients with T1 LST-G-M should be followed up more carefully.

Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P < 0.05), and greater variabilities were observed (P < 0.05). Rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep [median (interquartile range): 5.2 (2.6-8.9) times per h] was preceded by a transient decrease in RR intervals, and was accompanied by a transient decrease in delta elelctroencephalogram power. In humans, masseter bursts of rhythmic masticatory muscle activity were characterized by a lower activity, longer duration and longer cycle length than those of chewing (P < 0.05). Rhythmic masticatory muscle activity during non-rapid eye movement sleep [1.4 (1.18-2.11) times per h] was preceded by a transient decrease in RR intervals and an increase in cortical activity. Rhythmic masticatory muscle activity in animals had common physiological components representing transient arousal-related rhythmic jaw motor activation in comparison to human subjects.

Clinical outcomes of endoscopic submucosal dissection for colorectal tumors: a large multicenter retrospective study from the Hiroshima GI Endoscopy Research Group.

BACKGROUND AND AIMS: Although advanced high-volume centers have reported good outcomes of colorectal endoscopic submucosal dissection (ESD), a limited number of highly skilled experts in specialized institutions performed these procedures. We undertook a retrospective multicenter survey, which included nonspecialized hospitals, to investigate the clinical outcomes of colorectal ESD. METHODS: We recruited 1233 consecutive patients with 1259 colorectal tumors resected by ESD at 12 institutions. We evaluated the en bloc resection rate, histologic complete resection rate, curative (R0) resection rate, adverse events, and the long-term prognoses, including local recurrence, metachronous tumor development, and survival rate. RESULTS: The en bloc, histologic complete, and R0 resection rates were 92.6%, 87.4%, and 83.7%, respectively. The delayed bleeding, intraoperative perforation, and delayed perforation rates were 3.7%, 3.4%, and .4%, respectively. The long-term outcomes analysis included 1091 patients (88.4%). Local recurrences occurred in 1.7%, and metachronous tumors (>5 mm) developed in 11.0% of the patients. The 3- and 5-year overall survival rates were 95.1% and 92.3%, respectively. The number of colonic tumors, severe submucosal fibrosis, and en bloc resection rates were significantly higher in the high-volume centers (Group H) than those in the low-volume centers (Group L). The average tumor size in Group H was significantly larger than that in Group L. CONCLUSIONS: Colorectal ESDs are feasible, have acceptable adverse event risks, and favorable long-term prognoses. (Clinical trial registration number: UMIN000016197.).

Long-term outcomes after treatment for T1 colorectal carcinoma: a multicenter retrospective cohort study of Hiroshima GI Endoscopy Research Group.

BACKGROUND: We aimed to clarify the long-term outcomes of patients with T1 colorectal carcinoma (CRC) after endoscopic resection (ER) and surgical resection. METHODS: We examined T1 CRC patients treated during 1992-2008 and who had ≥5 years of follow-up. Patients who did not meet the curative criteria after ER according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines were defined as "non-endoscopically curable" and classified into three groups: ER alone (Group A: 121 patients), additional surgery after ER (Group B: 238 patients), and surgical resection alone (Group C: 342 patients). Long-term outcomes and predictors of recurrence were analyzed. RESULTS: Of the 882 patients with T1 CRC, 701 were non-endoscopically curable. Among these patients, recurrence and 5-year overall survival (OS) rates were 0.6 and 91.1%, respectively. In Groups A, B, and C, recurrence rates were 5.0, 5.5, and 3.8%, OS rates were 79.3, 92.4, and 91.5% (p < 0.01), and 5-year disease-free survival (DFS) rates were 98.1, 97.9, and 98.5%, respectively. Thirty-two patients experienced local recurrence or distant/lymph node metastasis (Group A: 6; Group B: 13; Group C: 13) and 14 patients died of primary CRC (Group A: 3; Group B: 7; Group C: 4). Age ≥65 years, protruded gross type, positive lymphatic invasion, and high budding grade were significant predictors of recurrence in non-endoscopically curable patients. CONCLUSIONS: Our findings supported the JSCCR criteria for endoscopically curable T1 CRC. ER for T1 CRC did not worsen the clinical outcomes of patients who required additional surgical resection.

Anatomical organization of descending cortical projections orchestrating the patterns of cortically induced rhythmical jaw muscle activity in guinea pigs.

Repetitive electrical microstimulation to the cortical masticatory area (CMA) evokes distinct patterns of rhythmical jaw muscle activities (RJMAs) in animals. This study aimed to investigate the characteristics of the descending projections from the CMA, associated with distinct patterns of RJMAs, to the thalamus, midbrain, pons and medulla in guinea pigs. RJMAs with continuous masseter and digastric bursts (CB-RJMAs) and stimulus-locked digastric sub-bursts (SLB-RJMAs) were induced from the anterior and posterior areas of the rostral region of the lateral agranular cortex, and chewing-like RJMAs from the rostral region of the granular cortex. Anterograde tracer, biotinylated dextran amine, was injected into the three cortical areas. The cortical area inducing CB-RJMAs had strong ipsilateral projections to the motor thalamus, red nucleus, midbrain reticular formation, superior colliculus, parabrachial nucleus, and supratrigeminal region, and contralateral projections mainly to the lateral reticular formation around the trigeminal motor nucleus (Vmo). The cortical area inducing SLB-RJMAs had moderate projections to the motor thalamus and lateral reticular formation around the Vmo, but few projections to the midbrain nuclei. The cortical area inducing chewing-like RJMAs had strong projections to the ipsilateral sensory thalamus and contralateral trigeminal sensory nuclei, and moderate projections to the lateral reticular formation. The three cortical areas consistently had few projections to the ventromedial reticular formation. The present study demonstrates that multiple direct and indirect descending projections from the CMA onto the premotor systems connecting the trigeminal motoneurons represent the neuroanatomical repertoires for generating RJMAs during the distinct phases of natural ingestive behavior.

Distinct association between the antagonistic jaw muscle activity levels and cardiac activity during chewing and NREM sleep in the freely moving guinea pigs.

The aim of this study was to investigate the changes of the association between cardiac activity and the electromyographic (EMG) level of the antagonistic jaw muscles during chewing and NREM sleep in guinea pigs after systemic clonidine injections. Ten animals were prepared for chronic experiments to monitor sleep, cardiac activity and EMG activity of jaw-closing masseter (MAS) and jaw-opening anterior belly of digastric (ADG) muscles. The recordings were made for ten hours with the injections of saline or clonidine (10 µg/kg, i.p.). Integrated EMG activity of the two muscles and mean heart rate (mHR) were calculated for every 10-s epoch. During the two hours after clonidine injection, the duration of REM sleep and mHR were significantly reduced. During chewing, the high EMG activity level of the two muscles and the activity ratio between the two muscles were not modified although mHR was decreased. During NREM sleep, after clonidine injection, the low EMG activity level at baseline was further decreased by 20-30% in parallel to a decrease of mHR although the heterogeneity of the activity ratio remained unaltered. The results suggest that the maintenance of the activity level for the antagonistic jaw muscles are regulated by the distinct physiological mechanisms reflecting the behavioral states during conscious chewing and unconscious NREM sleep.

Clinical validity of the expanded criteria for endoscopic resection of undifferentiated-type early gastric cancer based on long-term outcomes.

BACKGROUND: According to the Japanese Gastric Cancer Treatment Guidelines, the expanded criteria for endoscopic resection (ER) of undifferentiated-type early gastric cancer (UEGC) is ulcer-negative, intramucosal cancer 20 mm or less in diameter without lymphovascular invasion. The aim of this study was to confirm validity of the expanded criteria for curative ER of UEGC. METHODS: Subjects were 125 patients from whom 125 UEGCs were resected endoscopically between April 1990 and March 2011. Endoscopic mucosal resection (EMR) (28 lesions, 28 patients) or endoscopic submucosal dissection (ESD) (97 lesions, 97 patients) was performed. We determined the complete resection rate, post-ER bleeding rate, perforation rate, and outcome in both groups, and analyzed the survival outcomes of 84 patients who were followed for more than 5 years (mean, 101.9 months) according to the indication for ER [expanded criteria for curative (n = 52) vs. criteria for noncurative (n = 32)]. RESULTS: Complete resection rates for EMR and ESD were 54 % (15 of 28) and 89 % (86 of 97), respectively, with that for ESD being significantly higher (p < 0.01). Outcomes after ER were as follows: among 52 cases of UEGC meeting the expanded criteria, additional surgical resection was performed in 11 cases of incomplete resection. No local recurrence or lymph node metastasis was observed. Forty-eight patients who were simply surveyed clinically (93.6 ± 38.4 months) after ER survived without recurrence; the remaining 7 patients died of other causes. Among the 32 cases of UEGC meeting the criteria for noncurative resection, additional surgical resection was performed in 13 cases. Among the 19 follow-up cases (108.3 ± 38.7 months), death due to metastasis of the primary disease occurred in 3 cases, death from other causes occurred in 5 cases, and local residual submucosal recurrence occurred in 1 case. CONCLUSIONS: ESD is a useful technique for complete resection as a total excisional biopsy compared with EMR and radical cure of UEGCs meeting the expanded criteria.

Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Although recent guidelines for endoscopic submucosal dissection (ESD) as treatment for early gastric cancer (EGC) recommend noninterruption of low-dose aspirin (LDA) perioperatively, this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before to ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. Our purpose in this study was to confirm the validity of noninterrupted use of LDA in patients undergoing ESD for EGC. METHODS: We studied 78 consecutive patients with 94 EGCs who were routinely taking LDA and were treated by ESD at Hiroshima University Hospital between April 2005 and June 2012. The patients were of two groups: those in whom LDA was interrupted perioperatively (53 patients with 66 EGCs) and those in whom LDA was continued perioperatively (25 patients with 28 EGCs). RESULTS: The complete resection rate was 92.4 % (61/66) in the LDA-interrupted group and 100 % (28/28) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after procedure were 10.6 % (7/66) and 4.8 % (3/66), respectively, in the LDA-interrupted group and 7.1 % (2/28) and 3.6 % (1/28) in the LDA-continued group. Two patients in the interrupted-LDA group suffered cerebrovascular infarction before ESD, and 2 patients in this group suffered acute myocardial infarction after ESD. CONCLUSIONS: Our data suggest that continued use of LDA does not increase the risk of bleeding during or after ESD for EGC and does decrease the risk of ischemic events.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in patients with chronic kidney disease.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), and the number of ESD performed for EGC in patients with chronic kidney disease (CKD) is increasing. Although patients undergoing hemodialysis tend to bleed and are at high risk for cardiovascular disease, the effectiveness and safety of ESD for EGC in patients with CKD in particular have not been established. The aim of this study was to evaluate the effectiveness and potential adverse effects of ESD for EGC in patients with CKD undergoing hemodialysis. METHODS: Sixty-three consecutive CKD patients in whom 79 EGCs were treated by ESD between October 2004 and January 2012; 15 of the 63 patients were hemodialysis patients. Complete en bloc resection rate and ESD-related complications in hemodialysis patients versus non-hemodialysis patients were evaluated. RESULTS: The complete en bloc resection rate was 100% (15/15) in the hemodialysis patients and 87.5% (56/64) in the non-hemodialysis patients, respectively. The post-ESD bleeding rate was 33% (5/15) and 9% (6/64), respectively (P < 0.05). Perforation occurred only in non-hemodialysis patients; the incidence was 5% (3/64). Two ESD-related deaths occurred among hemodialysis patients (13%, 2/15); femoral artery infarction triggered post-ESD bleeding in one of these two patients, and alveolar hemorrhage occurred in the other. CONCLUSION: Hemodialysis poses a risk of post-ESD bleeding. We must understand this risk and provide countermeasures for post-ESD bleeding in hemodialysis patients.

Clinical validity of endoscopic submucosal dissection for submucosal invasive gastric cancer: a single-center study.

BACKGROUND: The 2010 Japanese Gastric Cancer Association guidelines for the treatment of submucosal invasive gastric cancer (SM-GC) specify size 30 mm or less, differentiated-dominant histology, lack of vessel involvement, and submucosal invasion of less than 500 µm (SM1) as expanded criteria for curative endoscopic resection. Our purpose in this study was to confirm the validity of the expanded indications for curative endoscopic submucosal dissection (ESD) of SM-GC. METHODS: The study subjects were 173 patients with SM-GC resected by ESD at Hiroshima University Hospital between April 2002 and September 2010, including 99 patients for whom 3-plus years' follow-up information was available. Post-ESD outcomes were compared between cases of SM1-GC that met the expanded ESD criteria, those that did not, and SM2-GC cases. RESULTS: Complete resection was achieved for 93.2% of the SM1-GCs that met the expanded criteria. There was neither metastasis to lymph nodes or other organs nor local recurrence among the SM1-GCs. Disease-specific survival did not differ significantly between patients that were simply followed up after ESD and those that were treated by additional surgical resection. CONCLUSIONS: Our outcome data support the clinical validity of ESD without additional surgical resection for SM1-GCs that meet the expanded criteria.

Risk factors for bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is standard therapy in Japan for gastric epithelial neoplasm, the complication rate is unsatisfactory, with postoperative bleeding as the major complication. The aim of the present study was to determine risk factors for post-ESD bleeding in patients with gastric epithelial neoplasm. PATIENTS AND METHODS: The study included 764 patients in whom 924 gastric epithelial neoplasms were resected endoscopically between June 2005 and December 2009: the period during which preventative coagulation for all exposed vessels on the artificial ulcer with hemostatic forceps upon completion of ESD was performed routinely. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors. RESULTS: The post-ESD bleeding rate was 3.0%. Dialysis (vs no dialysis, P = 0.034), operation time ≥75 min (vs <75 min, P = 0.012) and poor control of bleeding during ESD (vs good control, P = 0.014) were significantly related to post-ESD bleeding. Poor control of bleeding during ESD (vs good control; P = 0.04) and operation time ≥75 min (vs <75 min; P = 0.012) were significantly related to bleeding after second-look endoscopy. CONCLUSIONS: Patients at high risk for post-ESD bleeding in gastric epithelial neoplasm were those undergoing dialysis, those in whom operation time was ≥75 min, and those in whom bleeding during ESD was poorly controlled. The latter two are risk factors for bleeding even after second-look endoscopy.

Improved detectability of small-bowel lesions via capsule endoscopy with computed virtual chromoendoscopy: a pilot study.

OBJECTIVE: Real-time video capsule endoscopy (CE) with flexible spectral imaging color enhancement (FICE) improves visibility of small-bowel lesions. This article aims to clarify whether CE-FICE also improves detectability of small-bowel lesions. PATIENTS AND METHODS: A total of 55 patients who underwent CE at Hiroshima University Hospital during the period November 2009 through March 2010 were enrolled in the study. Five patients were excluded from the study because residues and transit delays prevented sufficient evaluation. Thus, 50 patients participated. Two experienced endoscopists (each having interpreted more than 50 capsule videos) analyzed the images. One interpreted conventional capsule videos; the other, blinded to interpretation of the conventional images, interpreted CE-FICE images obtained at settings 1-3 (setting 1: red 595 nm, green 540 nm, blue 535 nm; setting 2: red 420 nm, green 520 nm, blue 530 nm; setting 3: red 595 nm, green 570 nm, blue 415 nm). Lesions were classified as angioectasia, erosion, ulceration, or tumor. Detectability was compared between the two modalities. Time taken to interpret the capsule videos was also determined. RESULTS: Seventeen angioectasias were identified by conventional CE; 48 were detected by CE-FICE at setting 1, 45 at setting 2, and 24 at setting 3, with significant differences at settings 1 and 2 (p = 0.0003, p < 0.0001, respectively). Detection of erosion, ulceration, and tumor did not differ statistically between conventional CE and CE-FICE, nor did interpretation time (conventional CE 36 ± 6.9 min; CE-FICE setting 1, 36 ± 6.4 min; setting 2, 38 ± 5.8 min; setting 3, 35 ± 6.7 min). CONCLUSIONS: CE-FICE is superior in the lesion detection in comparison with conventional CE and improves detection of angioectasia.

Improved visibility of lesions of the small intestine via capsule endoscopy with computed virtual chromoendoscopy.

BACKGROUND: We can now enhance video capsule endoscopy (CE) images in real time by means of a flexible spectral imaging color enhancement (FICE) digital processing system. Reports on the clinical usefulness of this system are few. OBJECTIVE: To clarify whether visualization of lesions of the small intestine is improved by FICE image analysis. DESIGN: A retrospective study. SETTING: Academic medical center. METHODS: Five physicians compared FICE images with corresponding conventional images of 145 lesions obtained from 122 patients who underwent video CE at our hospital. The lesions were classified as angioectasia (n=23), erosion/ulceration (n=45), or tumor (n=75), and 3 different sets of FICE images were viewed (ie, at 3 different wavelength settings). Physicians rated the visibility of the lesions on FICE images as follows: +2 (improved visibility), +1 (somewhat improved visibility), 0 (visibility equivalent to that of conventional video CE visibility), -1 (somewhat decreased visibility), and -2 (decreased visibility). Scores for each lesion were totaled (per FICE setting) and evaluated. Intraobserver agreement was also examined. RESULTS: With FICE setting 1 (red 595 nm, green 540 nm, blue 535 nm), improvement was achieved for 87% (20/23) of angioectasia images, 53.3% (26/47) of erosion/ulceration images, and 25.3% (19/75) of tumor images. With setting 2 (red 420 nm, green, 520 nm, blue 530 nm), improvement was achieved for 87% (20/23), 25.5% (12/47), and 20.0% (15/75), respectively. With setting 3, only equivalence was achieved. Intraobserver agreement was good to satisfactory at 5.4 or higher. LIMITATIONS: Single-center study. CONCLUSIONS: CE-FICE improves visibility of small-bowel angioectasia, erosion/ulceration, and tumor.