Efficacy of a new enzyme-linked immunosorbent assay system for three islet cell autoantibodies in Japanese patients with acute-onset type 1 diabetes.

To evaluate the clinical efficacy of a new enzyme-linked immunosorbent assay (ELISA) system for simultaneously detecting three islet cell autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) (3 Screen ICA ELISA) in Japanese patients with acute-onset type 1 diabetes (T1D). In addition, clinical factors affecting the 3 Screen ICA ELISA index were investigated. We compared the positivity values of 3 Screen ICA ELISA with that of each autoantibody alone in 97 patients with acute-onset T1D (mean age 48.7 years, 49% male) and 100 non-diabetic subjects (mean age 47.0 years, 50% male). Serum thyroid stimulating hormone receptor antibody, thyroid peroxidase antibody (TPOAb) and thyroglobulin autoantibody levels were also evaluated. The cut-off value of the 3 Screen ICA ELISA was determined based on the 97th percentile of 100 non-diabetic controls (threshold for positivity, ≥14 index). The mean age of disease onset and duration of diabetes were 34.2 years and 14.5 years, respectively. Among all T1D patients, the positivity of 3 Screen ICA ELISA was 71.1%, while that of GADA, IA-2A, and ZnT8A were 59.8%, 25.8%, and 25.8%, respectively. The median 3 Screen ICA index was 121.9 (8.7-468.2) and was associated with titers of each autoantibody, most so with GADA, and was significantly higher in TPOAb-positive patients than in TPOAb-negative patients. Our findings suggests that the 3 Screen ICA ELISA may be a time-saving diagnostic tool for evaluating islet autoantibodies in acute-onset T1D patients.

Risk factors for delayed bleeding after endoscopic resection for large colorectal tumors.

OBJECTIVE: Endoscopic resection techniques for treating colorectal tumors have advanced recently so that large colorectal tumors can now be treated endoscopically, although some patients experience delayed bleeding after endoscopic resection. Our aim was to clarify the risk factors for delayed bleeding after endoscopic resection for colorectal tumors≥20 mm in diameter. Endoscopic submucosal dissection cases were excluded because of the low incidence of delayed bleeding after such procedures. METHODS: This was a retrospective study using a prospectively completed database and patient medical records at a single, national cancer institution. A total of 403 colorectal endoscopic resections were performed on 375 consecutive patients. We analyzed the database and retrospectively assessed patient age, gender, hypertension and current use of anticoagulant (warfarin) or antiplatelet drugs (e.g. aspirin, ticlopidine) as well as tumor location, size, macroscopic type, histopathological findings, resection method and whether or not placement of prophylactic clips was performed during the endoscopic resection. RESULTS: The overall rate of delayed bleeding was 4.2% (17/403) and the median interval between endoscopic resection and the onset of delayed bleeding was 2 days (range, 1-14 days). All delayed bleeding cases were successfully controlled by endoscopic hemostasis involving clipping and/or electrocoagulation without the need for surgical interventions or blood transfusions. Based on our univariate analysis, the delayed bleeding rate was significantly higher in both males (P=0.04) and those patients without prophylactic clip placement (P=0.04). CONCLUSIONS: Our study results indicated that prophylactic clip placement may be an effective method for preventing delayed bleeding after endoscopic resection for large colorectal tumors.

Development and preliminary validation of a machine learning system for thyroid dysfunction diagnosis based on routine laboratory tests.

Background: Approximately 2.4 million patients in Japan would benefit from treatment for thyroid disease, including Graves' disease and Hashimoto's disease. However, only 450,000 of them are receiving treatment, and many patients with thyroid dysfunction remain largely overlooked. In this retrospective study, we aimed to develop and conduct preliminary testing on a machine learning method for screening patients with hyperthyroidism and hypothyroidism who would benefit from prompt medical treatment. Methods: We collected electronic medical records and medical checkup data from four hospitals in Japan. We applied four machine learning algorithms to construct classification models to distinguish patients with hyperthyroidism and hypothyroidism from control subjects using routine laboratory tests. Performance evaluation metrics such as sensitivity, specificity, and the area under receiver operating characteristic (AUROC) were obtained. Techniques such as feature importance were further applied to understand the contribution of each feature to the machine learning output. Results: The results of cross-validation and external evaluation indicated that we achieved high classification accuracies (AUROC = 93.8% for hyperthyroidism model and AUROC = 90.9% for hypothyroidism model). Serum creatinine (S-Cr), mean corpuscular volume (MCV), and total cholesterol were the three features that were most strongly correlated with the hyperthyroidism model, and S-Cr, lactic acid dehydrogenase (LDH), and total cholesterol were correlated with the hypothyroidism model. Conclusions: We demonstrated the potential of machine learning approaches for diagnosing the presence of thyroid dysfunction from routine laboratory tests. Further validation, including prospective clinical studies, is necessary prior to application of our method in the clinic.

Safety of carbon dioxide insufflation for upper gastrointestinal tract endoscopic treatment of patients under deep sedation.

BACKGROUND: It is well known that carbon dioxide (CO(2)) is absorbed faster in the body than air and also that it is rapidly excreted through respiration. This study aimed to investigate the safety of CO(2) insufflation used for esophageal and gastric endoscopic submucosal dissection (ESD) in patients under deep sedation. METHODS: Patients with either early gastric or esophageal cancers that could be resected by ESD were enrolled in this study from March 2007 to July 2008 and randomly assigned to undergo ESD procedures with CO(2) insufflation (CO(2) group) or air insufflation (air group). A TOSCA measurement system and TOSCA 500 monitor were used to measure and monitor both transcutaneous partial pressure of CO(2) (PtcCO(2)) and oxygen saturation (SpO(2)). RESULTS: The study enrolled 89 patients and randomly assigned them to a CO(2) group (45 patients) or an air group (44 patients). The mean CO(2) group versus air group measurements were as follows: PtcCO(2) (49.1 +/- 5.0 vs. 50.1 +/- 5.3 mmHg; nonsignificant difference [NS]), maximum PtcCO(2) (55.1 +/- 6.5 vs. 56.8 +/- 7.0 mmHg; NS), PtcCO(2) elevation (9.1 +/- 5.4 vs. 11.4 +/- 5.6 mmHg; p = 0.054), SpO(2) (99.0 +/- 0.7% vs. 99.0 +/- 1.0%; NS), minimum SpO(2) (96.5 +/- 2.4% vs. 95.4 +/- 3.3%; p = 0.085), and SpO(2) depression (2.4 +/- 2.3% vs. 3.3 +/- 2.9%; NS). The PtcCO(2) and SpO(2) measurements were similar in the two groups, but the CO(2) group was better than the air group in PtcCO(2) elevation and minimum SpO(2). CONCLUSIONS: The findings demonstrated CO(2) insufflation to be as safe as air insufflation for upper gastrointestinal tract ESDs performed for patients under deep sedation without evidencing any adverse effects.

Transcutaneous monitoring of partial pressure of carbon dioxide during endoscopic submucosal dissection of early colorectal neoplasia with carbon dioxide insufflation: a prospective study.

BACKGROUND: The authors have reported that carbon dioxide (CO(2)) insufflation is safe and effective for lengthy endoscopic submucosal dissection (ESD) with the patient under conscious sedation. However, CO(2) monitoring has not been assessed to clarify whether partial pressure of carbon dioxide (PCO(2)) increases during this type of long procedure. This study aimed to monitor CO(2) before, during, and after ESD to investigate whether CO(2) insufflation is safe for patients receiving a lengthy ESD of early colorectal neoplasia under conscious sedation. METHODS: This study prospectively enrolled 35 consecutive patients who underwent ESD at the National Cancer Center Hospital. Transcutaneous PCO(2) (PtcCO(2)) was measured with a noninvasive sensor before, during, and after ESD for patients under conscious sedation using midazolam. RESULTS: The mean size of removed lesions was 44 ± 22 mm (range, 15-100 mm). The operation time was 90 ± 100 min (range, 15-600 mm). The dose of midazolam was 5.7 ± 4.0 mg (range, 2-19 mg). The mean PtcCO(2) was 41 ± 5 mmHg (range, 33-53 mmHg) before ESD and 44 ± 6 mmHg (range, 32-54 mmHg) afterward. The mean peak PtcCO(2) during ESD was 55 ± 7 mmHg (range, 39-78 mmHg), which was significantly higher than before or after ESD (p < 0.0001). However, no complication associated with CO(2) insufflation such as CO(2) narcosis, gas embolism, or arrhythmia needing treatment was seen in any of the cases. CONCLUSIONS: This study suggests that CO(2) insufflation is safe for patients receiving a lengthy colorectal ESD under conscious sedation.

Detectability of colorectal neoplastic lesions using a narrow-band imaging system: a pilot study.

BACKGROUND AND AIM: Flat and depressed colorectal neoplastic lesions can be difficult to identify using conventional colonoscopy techniques. Narrow-band imaging (NBI) provides unique views especially of mucosal vascular network and helps in visualization of neoplasia by improving contrast. The aim of this study was to assess the feasibility of using NBI for colorectal neoplasia screening. METHODS: Forty-seven consecutive patients, who underwent high definition colonoscopy (HDC) screening examinations revealing neoplastic lesions, were enrolled in our prospective study. No biopsies or resections were performed during the initial HDC, but patients in whom lesions were detected underwent further colonoscopies using NBI, with the results of the first examination blinded from the colonoscopist. They then received appropriate treatment. We compared diagnostic detection rates of neoplastic lesions for HDC and NBI procedures using total number of all identified neoplastic lesions as reference standard. RESULTS: Altogether, 153 lesions were detected and analyzed in 43 patients. Mean diagnostic extubation times were not significantly different (P = 0.18), but the total number of lesions detected by NBI was higher (134 vs 116; P = 0.02). Based on macroscopic type, flat lesions were identified more often by NBI (P = 0.04). As for lesion size, only flat lesions < 5 mm were detected more frequently (P = 0.046). Lesions in the right colon were identified more often by NBI (P = 0.02), but NBI missed two flat lesions >or= 10 mm located there. CONCLUSIONS: Narrow band imaging colonoscopy may represent a significant improvement in the detection of flat and diminutive lesions, but a future multi-center controlled trial should be conducted to fully evaluate efficacy for screening colonoscopies.

Characteristic features of abdominal organ injuries associated with gastric rupture in blunt abdominal trauma.

BACKGROUND: Previous studies have investigated the mechanisms of gastric rupture based only on the findings in gastric rupture and excluding gastric lacerations. METHODS: We investigated 14 cases of gastric injury (five with rupture and nine with laceration) from blunt abdominal trauma with or without thoracic trauma. Gastric injuries were caused by a traffic accident in 12 and by a fall in two patients. All of the patients with gastric rupture had had a full stomach at the time of impact. RESULTS: The patients had associated injuries of adjacent solid organs, the thoracic cage, and extremities. The frequency of injury of the hepatoduodenal or gastrohepatic ligament was higher in patients with gastric laceration than in patients with gastric rupture. Eight of nine patients with a gastric laceration had hepatic or pancreatic injury, whereas none of the patients with gastric rupture had such injury. CONCLUSIONS: The results of our study showed that the distended stomach tends to rupture by absorbing the impact from blunt abdominal trauma (i.e., it works like an airbag to protecting adjacent organs such as the liver and pancreas).

Changes in bite force and dentoskeletal morphology in prognathic patients after orthognathic surgery.

OBJECTIVE: We sought to evaluate the changes in bite force and dentoskeletal morphology in prognathic patients after orthognathic surgery. STUDY DESIGN: Twenty-four patients underwent orthognathic surgery to correct Class III skeletal and dental malocclusions. Ten patients who underwent Le Fort I and bilateral sagittal split ramus osteotomy of the mandible (ie, surgical correction of 2 jaws) and 14 patients who underwent only bilateral sagittal split ramus osteotomy (ie, surgical correction of 1 jaw) were compared. Bite force was measured preoperatively and at 3, 6, and 12 months postoperatively. The dentoskeletal morphology was assessed through lateral cephalograms obtained preoperatively and 12 months postoperatively. RESULTS: Twelve months postoperatively, the bite force was significantly greater in the patients who underwent surgery on 1 jaw than in the patients who underwent surgery on 2 jaws. Significant decreases in the gonial angle, occlusal plane angle, and anterior facial height were observed postoperatively in the patients with 1 surgically corrected jaw, but not in the patients with 2 surgically corrected jaws. Patients with 2 surgically corrected jaws experienced a greater increase in the Frankfort mandibular plane angle and a greater decrease in the posterior facial height than did those with 1 surgically corrected jaw. CONCLUSION: The difference in the preoperative-to-postoperative change in dentoskeletal morphology between the 2 groups is one of the factors responsible for the significant difference in postoperative bite force between the 2 groups.

Analysis and comparison of clinical results of bilateral sagittal split ramus osteotomy performed with the use of monocortical locking plate fixation or bicortical screw fixation.

OBJECTIVE: The aim of this study was to compare clinical results of bilateral sagittal split ramus osteotomy (BSSRO) with the use of monocortical locking plate or bicortical screw fixation. STUDY DESIGN: Fifty-five patients underwent BSSRO for prognathism, using either monocortical locking plate (group A; n = 28) or bicortical screw (group B; n = 27) osseofixation. No intermaxillary fixation was done after surgery. Groups were subdivided according to presence or absence of mandibular asymmetry. Time course changes in condylar and skeletal stability were measured on lateral and posteroanterior cephalograms and axial radiographs before surgery and at 3 and 6 months after surgery. RESULTS: In facial symmetry subjects, the change in angle of the longitudinal axis of the condyle in group A was significantly greater than that for group B up to 3 months after surgery, but no significant differences were found in facial asymmetry subjects. CONCLUSIONS: The findings of this study suggest that monocortical fixation using the locking plate system to stabilize SSRO is as reliable as bicortical screw fixation regardless of facial asymmetry.

Comparison of narrowband imaging with autofluorescence imaging for endoscopic visualization of superficial squamous cell carcinoma lesions of the esophagus.

Aim. To compare narrowband imaging (NBI) and autofluorescence imaging (AFI) endoscopic visualization for identifying superficial esophageal squamous cell carcinoma (SCC). Methods. Twenty-four patients with superficial esophageal carcinomas diagnosed at previous hospitals were enrolled in this study. Lesions were initially detected using white-light endoscopy and then observed with both NBI and AFI. Endoscopic images documented each method, and three endoscopists experienced in esophageal imaging retrospectively reviewed respective images of histologically confirmed esophageal SCCs. Images were assessed for quality in identifying superficial SCCs and rated as excellent, fair, or poor by the three reviewers with interobserver agreement calculated using kappa (κ) statistics. Results. Thirty-one lesions histologically confirmed as superficial esophageal SCCs were detected in 24 patients. NBI images of 27 lesions (87%) were rated as excellent, three as fair, and one as poor compared to AFI images of 19 lesions (61%) rated as excellent, 10 as fair and two as poor (P < 0.05). Moderate interobserver agreement (κ = 0.42, 95% CI 0.24-0.60) resulted in NBI while fair agreement (κ = 0.35, 95% CI 0.18-0.51) was achieved using AFI. Conclusion. NBI may be more effective than AFI for visualization of esophageal SCC.

Prospective Case Study on Characterization of Colorectal Adenomas Comparing AFI with NBI.

Aim. Compare the characterization ability of AFI and NBI for colorectal adenomas. Methods. We prospectively enrolled 58 patients with 89 colorectal adenomas detected by white light colonoscopy. Such lesions were subsequently observed with both AFI and NBI and then treated by endoscopic resection. With respect to the 89 lesions, 3 experienced endoscopists retrospectively evaluated the visualization quality of the AFI and NBI images in a blind manner using a three-tier scale based on excellent, fair, and poor criteria. Results. There were 54, 31, and 4 lesions considered as excellent, fair, and poor visualization, respectively, using AFI in comparison to 53, 19, and 17 lesions, respectively, with NBI. The percentage of excellent and fair visualization lesions was 95.5% with AFI and 80.9% with NBI (P < .01). Conclusion. This study indicated that AFI may be more effective for the characterization of colorectal adenomas because of better visualization of such lesions compared to NBI.

Effect of recombinant human fibroblast growth factor-2 on bone formation in rabbit mandibular distraction models using beta-tricalcium phosphate.

This study was designed to evaluate the effect of recombinant human fibroblast growth factor-2 (rhFGF-2) on the amount and period of new bone formation in rabbit mandibular distraction models using beta-tricalcium phosphate (beta-TCP) as a bone graft substitute. Sixteen male Japanese White rabbits were divided into the following four experimental groups: 1, distraction alone; 2, distraction with beta-TCP granules; 3, distraction with rhFGF-2 (25 microg/50 microL) injected into beta-TCP granules; and 4, distraction with rhFGF-2 (100 microg/50 microL) injected into beta-TCP granules. The bones were harvested at 4 weeks after the operation and examined using soft radiography, micro-computed tomography (micro-CT), and peripheral quantitative computed tomography (pQCT). The dissected mandibles were stained using the Villanueva bone staining method, and the amount of new bone formed, bioresorption of beta-TCP, and new blood vessel formation were morphometrically calculated using bone histomorphometry. Radiopaque areas were observed more frequently in the distracted area of groups 3 and 4. Micro-CT analysis revealed partial new bone formation in the central region of the distracted area in groups 3 and 4. pQCT analysis revealed increased bone mineral density in groups 3 and 4. Histomorphometric analysis revealed increased newly formed bone and blood vessel areas in groups 3 and 4. In group 4, the number of osteoclasts around the beta-TCP granules had significantly increased. The present findings suggested that the combined use of rhFGF-2 and beta-TCP reduced the treatment period for distraction osteogenesis and accelerated the formation of a new high-quality bone.

Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer; however, it is not widely used in the colorectum because of its technical difficulty. OBJECTIVE: To determine the feasibility of using ESD for treating large superficial colorectal tumors and to evaluate the clinical outcome. DESIGN AND SETTING: Case series conducted at the National Cancer Center Hospital in Tokyo. PATIENTS: A total of 198 consecutive patients were treated for 200 lesions. INTERVENTIONS: Procedures were performed, before July 2004, by using a monopolar needle knife or an insulation-tipped knife (IT knife). After July 2004, the procedures were performed by using a bipolar needle knife or an IT knife. After injection of glycerol and sodium hyaluronate acid into the submucosal (sm) layer, a circumferential incision was made and sm dissection was performed endoscopically. MAIN OUTCOME MEASUREMENTS: The en bloc resection rate was 84% and the curative resection rate was 83%. RESULTS: Among the 200 ESDs, 51 involved tubular adenomas, 99 intramucosal cancers, 22 minute sm cancers, and 28 sm deep cancers. The median operation time was 90 minutes, and the mean size of resected specimens was 38 mm (range, 20-150 mm). Perforations occurred in 10 cases (5%) and postoperative bleeding in 4 cases (2%), but only 1 perforation case needed emergency surgery, because endoscopic clipping was ineffective. LIMITATIONS: No long-term outcome data yet. CONCLUSIONS: ESD is a feasible technique for treating large superficial colorectal tumors, because it provides a higher en bloc resection rate and is less invasive than surgical resection.

A pilot study to assess the safety and efficacy of carbon dioxide insufflation during colorectal endoscopic submucosal dissection with the patient under conscious sedation.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as one of the treatments for en bloc resection of large superficial colorectal lesions. This procedure is performed by using air insufflation, is time consuming, and is associated with severe abdominal discomfort. The safety and efficacy of carbon dioxide (CO(2)) insufflation during colonoscopy already has been assessed in some trials. OBJECTIVE: To assess the safety and efficacy of CO(2) insufflation instead of air insufflation during colorectal ESD with the patient under conscious sedation. DESIGN: A case-control series with a historical control. PATIENTS: A total of 35 consecutive patients were enrolled in this study. Another 35 consecutive patients who previously received colorectal ESDs by using air insufflation were included as a historical control. INTERVENTIONS: Arterial partial pressure of CO(2) (pCO(2)) was measured before and after each procedure with the total dose of midazolam used as an index of abdominal discomfort. MAIN OUTCOME MEASUREMENTS AND RESULTS: The mean (standard deviation [SD]) operation time was 90 +/- 57 minutes in the CO(2) group and 100 +/- 80 minutes in the control group (not significant). In the CO(2) group, the mean (SD) dose of midazolam was significantly lower than that of the control group; 5.6 +/- 4.9 mg and 9.7 +/- 5.9 mg, respectively (P = .005). Blood analysis revealed a slight pCO(2) elevation in the CO(2) group; however, only 2 patients complained of mild abdominal discomfort. LIMITATIONS: Abdominal discomfort and pCO(2) were not evaluated in the control group. CONCLUSIONS: This study strongly suggests that CO(2) insufflation is safe and effective during lengthy colonic endoscopic procedures, eg, ESD, with the patient under conscious sedation.

Role of ganglion cells in sigmoid volvulus.

The aim of this study was to clarify the role of ganglion cells in the development and recurrence of sigmoid volvulus. We analyzed 9 samples obtained from 9 patients who had undergone sigmoidectomy for sigmoid volvulus, and, for comparison, 18 samples from 18 patients who had undergone sigmoidectomy or low anterior resection for rectal cancer. Neuron-specific enolase was used for immunohistochemical staining to detect ganglion cells, and the number of ganglion cells in 20 contiguous fields was counted at 200? magnification. The average number of ganglion cells per 1000 cm(3) was corrected using the ratio of the circumference of the resected sigmoid colon to the average circumference in the control group. The raw numbers of ganglion cells in the Meissner's and Auerbach's plexuses in the volvulus group were significantly lower than those in the non-volvulus group (Meissner: p = 0.017, Auerbach: p = 0.007). The circumference of the resected sigmoid colons with volvulus was greater than that of those without volvulus (p = 0.00013). There was no significant difference in the corrected numbers of ganglion cells in the Meissner's plexus or Auerbach's plexus per 1000 cm(3) between the volvulus and non-volvulus groups (Meissner: p = 0.410, Auerbach: p = 0.890).Furthermore, there was no significant difference in the corrected numbers of ganglion cells between the revolvulus and non-revolvulus groups. These findings led us to conclude that functional disorder of bowel movement or elongation of the bowel in sigmoid volvulus or revolvulus is not related to the number of ganglion cells in Auerbach's or Meissner's plexus.