Outpatient hybrid endoscopic submucosal dissection with SOUTEN for early gastric cancer, followed by endoscopic suturing of the mucosal defect: A case report.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is becoming more common for early gastric cancer, it requires more advanced techniques and a longer treatment duration than endoscopic mucosal resection. Hybrid ESD using a multifunctional snare (SOUTEN) has been reported to be effective for colorectal lesions, as it can reduce treatment duration. Endoscopic suturing of post-ESD mucosal defects has been reported to reduce the incidence of ESD-related complications. CASE SUMMARY: This study reports outpatient hybrid ESD for early gastric cancer using SOUTEN, followed by endoscopic suturing of post-ESD mucosal defects in an 86-year-old man. On referral for ESD, a 10-mm flat, depressed lesion was found on the posterior wall of the gastric antrum, the depth of which was expected to be mucosal. Given his history of delirium, we performed outpatient endoscopic treatment. The procedure used was hybrid ESD using SOUTEN to reduce the duration of treatment and endoscopic suturing of post-ESD mucosal ESD defects to reduce complications. The procedure time was 62 min and the lesion was completely resected based on histopathological examination, with no reported postoperative complications. CONCLUSION: This safe and useful procedure may be especially important for outpatient endoscopic treatment.

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy.

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors.

Prognostic impact of clinical outcome after endoscopic gastroduodenal stent placement for malignant gastric outlet obstruction: a multicenter retrospective cohort study using a time-dependent analysis.

Background: Endoscopic gastroduodenal stent (GDS) placement is widely used as a safe and effective method to rapidly improve gastrointestinal symptoms of malignant gastric outlet obstruction (MGOO). While previous studies reported the utility of chemotherapy after GDS placement for prognosis improvement, they did not fully address the issue of immortal time bias. Objectives: To examine the association between prognosis and clinical course following endoscopic GDS placement, using a time-dependent analysis. Design: Multicenter retrospective cohort study. Methods: This study included 216 MGOO patients who underwent GDS placement between April 2010 and August 2020. Data of patient baseline characteristics, including age, gender, cancer type, performance status (PS), GDS type and length, GDS placement location, gastric outlet obstruction scoring system (GOOSS) score, and history of chemotherapy before GDS were collected. The clinical course following GDS placement was evaluated by GOOSS score, stent dysfunction, cholangitis, and chemotherapy. A Cox proportional hazards model was used to identify prognostic factors after GDS placement. Stent dysfunction, post-stent cholangitis, and post-stent chemotherapy were analyzed as time-dependent covariates. Results: Mean GOOSS scores before and after GDS were 0.7 and 2.4, respectively, with significant improvement after GDS placement (p < 0.001). The median survival time after GDS placement was 79 [95% confidence interval (CI): 68-103] days. In multivariate Cox proportional hazards model with time-dependent covariates, PS 0-1 [hazard ratio (HR): 0.55, 95% CI: 0.40-0.75; p < 0.001], ascites (HR: 1.45, 95% CI: 1.04-2.01; p = 0.028), metastasis (HR: 1.84, 95% CI: 1.31-2.58; p < 0.001), post-stent cholangitis (HR: 2.38, 95% CI: 1.37-4.15; p = 0.002), and post-stent chemotherapy (HR: 0.01, 95% CI: 0.002-0.10; p < 0.001) significantly affected prognosis after GDS placement. Conclusion: Post-stent cholangitis and tolerability to receive chemotherapy after GDS placement influenced prognosis in MGOO patients.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas.

Background and objective The isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications. Methods In this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher's exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves. Results The unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria. Conclusions These results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.

Prediction of nuclide accumulation spread based on the volume of enhancing MRI lesion in glioblastoma patients.

BACKGROUND: 11C-methionine-PET (MET) and Thallium-201 chloride-SPECT (TL) are useful for predictive proliferation ability and tumor invasion range identification in glioma patients, however they are not always possible in any hospital or country. Our study aimed to assess whether the range of MET and Tl accumulation could be predicted from the contrast-enhanced lesions in Gadolinium (Gd)-T1 weighted MR image (Gd-MRI) in glioblastoma multiforme (GBM) patients. METHODS: In 25 cases, the MET-Area, TL-Area, O-Area where MET and TL overlap, and all accumulation area (AA-Area) were measured in the same axial cross section as the Gd enhanced maximum area (Gd-Area). This tracing operation was repeated with all axial fusion slices, and each volume was also measured (Gd-V, MET-V, TL-V, O-V, AA-V). RESULTS: The maximum accumulation distance of MET and TL beyond the Gd-Area was limited to within 30 mm, 35 mm, respectively. Significant positive correlations were showed in all combinations with Gd-Area: MET-Area (r=0.851, p<0.0001), TL-Area (r=0.955, p<0.0001), O-Area (r=0.935, p<0.0001) and AA-Area (r=0.893, p<0.0001), respectively. All combinations with Gd-V showed significant positive correlation: MET-V (r=0.867, p<0.0001), TL-V (r=0.952, p<0.0001), O-V (r=0.935, p<0.0001) and AA-V (r=0.897, p<0.0001), respectively. CONCLUSIONS: Approximate tumor volume Gd-V can be calculated using the formula A * B * C / 2, where A, B, and C represent the dimensions of Gd-enhanced lesion in 3 axes perpendicular to each other. The nuclide accumulation predictive table created using the obtained linear approximation functions can be used to predict the average tumor invasion range from the Gd-V without preoperative nuclear examinations.

Self-study of the non-extension sign in an e-learning program improves diagnostic accuracy of invasion depth of early gastric cancer.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P  < 0.0001). Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Successful endoscopic closure of a refractory postoperative rectovaginal fistula.

Background and study aims A 71-year old female who received low anterior resection for rectal cancer visited Komatsu Municipal Hospital with complaints of passing feces from the vagina. Endoscopic examination revealed a postsurgical rectovaginal fistula. Medical approaches, including nonoperative management, initial endoscopic closure, transvaginal and endorectal surgery, and fecal diversion, were unsuccessful. Therefore, the patient underwent endoscopy with a pre-procedural endoscopic creation of mucosal pin holes around the fistula opening and clip insertion into the rectal wall in combination with electrocautery and clip closure. This novel approach was effective in achieving permanent closure of the fistula in a single procedure. Most rectovaginal fistulas are surgically managed, however, surgery may be more difficult, invasive, and unsatisfactory for refractory fistulas. Although endoscopic treatment with over-the-scope clips has been increasingly used as a less invasive approach for gastrointestinal fistulas with favorable results, it is not as effective for refractory rectovaginal fistulas. As a minimally invasive surgical procedure, this approach might be effective in small rectovaginal fistulas, particularly refractory ones.

Dissociation Between 11C-Methionine-Positron Emission Tomography and Gadolinium-Enhanced Magnetic Resonance Imaging in Longitudinal Features of Glioblastoma After Postoperative Radiotherapy.

The aims of the present study were to compare the longitudinal changes of glioblastoma multiforme after radiotherapy (RT) between 11C-methionine positron emission tomography (MET-PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and to clarify whether these changes were predictive of survival. We included 30 patients, who had undergone MET-PET and Gd-MRI before and every 3 months after RT. The lesion/normal brain uptake (L/N) ratio and contrast-enhancing lesion volume were examined. The L/N ratio was decreased until 9 months after RT with significance until 3 months. The contrast-enhancing lesion volume was decreased until 3 months and thereafter increased until 9 months with significance. The variation rates of the L/N ratio between pre-RT and 3 months differentiated survival of >23 months from ≤23 months. A dissociation could exist in the longitudinal changes of GBM after RT between MET-PET and Gd-MRI. The variation rate of the L/N ratio could be related to survival.

11C-methionine positron emission tomography for target delineation of recurrent glioblastoma in re-irradiation planning.

AIM: To define the optimal margin on MRI scans in the re-radiation planning of recurrent glioblastoma using methionine positron emission tomography (MET-PET). BACKGROUND: It would be very useful if the optimal margin on MRI to cover the uptake area on MET-PET is known. MATERIALS AND METHODS: CT, MRI, and MET-PET were performed separately over the course of 2 weeks. Among the MRI scans, we used the contrast-enhanced T1-weighted images (Gd-MRI) and T2-weighted images (T2-MRI). The Gd-MRI-based clinical target volume (CTV) (CTV-Gd) and the T2-MRI-based CTV (CTV-T2) were defined as the contrast-enhanced area on Gd-MRI and the high intensity area on T2-MRI, respectively. We defined CTV x mm (x = 5, 10, 15, 20) as x mm outside the CTV. MET-PET-based CTV (CTV-MPET) was defined as the area of accumulation of MET-PET. We calculated the sensitivity and specificity of CTV-Gd and CTV-T2 following comparison with CTV-MPET, which served as the gold standard in this study. RESULTS: The sensitivity of CTV-T2 5 mm (98%) was significantly higher than CTV-T2 (87%), and there was no significant difference in the sensitivity between CTV-T2 5 mm and CTV T2 10, 15, or 20 mm. The sensitivity of CTV-Gd 20 mm (97%) was lower than that of CTV-T2 5 mm (98%). CONCLUSIONS: A margin of at least 5 mm around the high intensity area on T2-MRI is necessary in the target volume delineation of recurrent glioblastoma for the coverage of MET-PET findings in re-radiation therapy planning.

Asymptomatic Pancreatic Metastasis from Renal Cell Carcinoma Diagnosed 21 Years after Nephrectomy.

This report presents our experience with a case of pancreatic metastasis of renal cell carcinoma (RCC) at a long-term follow-up after nephrectomy. A 73-year-old man underwent nephrectomy for right RCC 21 years ago; computed tomography (CT) scanning on routine follow-up revealed a solid mass in the tail of the pancreas, and magnetic resonance imaging (MRI) showed some tumors in the head and tail of the pancreas. The patient was asymptomatic and allergic to contrast medium. Therefore we could not perform contrast CT/MRI for further examination to diagnose pancreatic tumors. We undertook endoscopic ultrasonography (EUS) and detected a hypervascular and low echoic mass; tumor tissues were obtained by EUS-guided fine-needle aspiration (EUS-FNA). Pathological diagnosis revealed pancreatic metastasis of clear cell RCC; this was similar to the pathological findings of tumor tissues initially obtained by nephrectomy. EUS-FNA was extremely useful for the definitive diagnosis of a rare type of pancreatic tumor.

Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium.

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood-brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

Interobserver agreement in detection of "white globe appearance" and the ability of educational lectures to improve the diagnosis of gastric lesions.

BACKGROUND: White globe appearance (WGA) refers to a small white lesion of globular shape underneath cancerous gastric epithelium that can be clearly visualized by magnifying endoscopy with narrowband imaging (M-NBI). WGA has been reported to be a novel endoscopic marker that is highly specific in differentiating early gastric cancer (GC) from low-grade adenoma, and has a significantly higher prevalence in early GCs than in noncancerous lesions. However, interobserver agreement in detecting WGA and whether training intervention can improve diagnostic accuracy are unknown. METHODS: Twenty sets of M-NBI images were examined by 16 endoscopists. The endoscopists attended a lecture about WGA, and examined the images again after the lecture. Interobserver agreement in detecting WGA in the second examination and increases in the proportion of correct diagnoses and the degree of confidence of diagnoses of cancerous lesions were evaluated. RESULTS: The kappa value for interobserver agreement in detecting WGA in the second examination was 0.735. The proportion of correct diagnoses was significantly higher in the second examination compared with the first examination when WGA was present (95.5% vs 55.4%; P < 0.001), but not when WGA was absent (61.6% vs 52.7%; P = 0.190). The proportion of correct diagnoses with a high degree of confidence was significantly higher in the second examination, both with WGA (91.1% vs 29.5%; P < 0.001) and without WGA (36.6% vs 20.5%; P = 0.031). CONCLUSIONS: The detection of WGA by endoscopists was highly reproducible. A brief educational lecture about WGA increased the proportion of correct diagnoses and the degree of confidence of diagnoses of GC with WGA.

A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†.

BACKGROUND: Brain radiation necrosis (BRN) can be a complication of radiotherapy for primary and secondary brain tumors, as well as head and neck tumors. Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN. METHODS: Patients with surgically untreatable, symptomatic BRN refractory to conventional medical treatments (eg, corticosteroid, anticoagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilesional edema with a lesion-to-normal brain ratio ≤1.8 on 11C-methionine or ≤2.5 on 18F-boronophenylalanine PET was BRN, not tumor recurrence, and 6 cycles of biweekly bevacizumab (5 mg/kg) were administered. The primary endpoint was a ≥30% reduction from the patients' registration for perilesional edema continuing for ≥1 month. RESULTS: Of the 41 patients enrolled, 38 were fully eligible for the response assessment. The primary endpoint was achieved in 30 of the 38 (78.9%) patients at 3.0 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of their Karnofsy Performance Score. Corticosteroid use could be reduced in 29 patients (76.3%). Adverse events at grade ≥3 occurred in 10 patients (24.4%). CONCLUSIONS: Bevacizumab treatment offers certain clinical benefits for patients with surgically untreatable, symptomatic BRN. The determination of BRN using amino-acid PET, not biopsy, is adequate and less invasive for determining eligibility to receive bevacizumab.

Dynamic study of methionine positron emission tomography in patients with glioblastoma with oligodendroglial components.

Anaplastic oligoastrocytoma (AOA) with necrosis is classified as glioblastoma (GBM) with oligodendroglioma component (GBMO), according to the 2007 World Health Organization classification. The prognosis of GBMO remains controversial because definitive diagnostic criteria regarding the percentage of the oligodendroglial components (OC) in the GBM do not exist. We previously reported dynamic methionine (MET) positron emission tomography (PET) in patients with these tumors. A significant decrease in the MET signal was seen in oligodendrocytic tumors, in contrast to a significant MET increase in GBMs. In this study, we analyzed the dynamic MET PET signal in four patients with primary (n = 2) and secondary (n = 2) GBMOs. Static PET scanning was performed in three consecutive phases. Both cases of primary GBMOs and one case of secondary GBMO presented with a gradual decrease in MET PET signal over the consecutive phases. In contrast, the remaining case of secondary GBMO presented with a pattern of slight increase. It is likely that the dynamic change of MET in patients with GBMO resemble those in patients with oligodendroglial tumor, however, further studies are needed to confirm them. We discuss the mechanisms from a viewpoint of pathological findings.

Re-irradiation of recurrent glioblastoma multiforme using 11C-methionine PET/CT/MRI image fusion for hypofractionated stereotactic radiotherapy by intensity modulated radiation therapy.

BACKGROUND: This research paper presents a valid treatment strategy for recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy by intensity modulated radiation therapy (HS-IMRT) planned with 11C-methionine positron emission tomography (MET-PET)/computed tomography (CT)/magnetic resonance imaging (MRI) fusion. METHODS: Twenty-one patients with recurrent GBM received HS-IMRT planned by MET-PET/CT/MRI. The region of increased amino acid tracer uptake on MET-PET was defined as the gross tumor volume (GTV). The planning target volume encompassed the GTV by a 3-mm margin. Treatment was performed with a total dose of 25- to 35-Gy, given as 5- to 7-Gy daily for 5 days. RESULTS: With a median follow-up of 12 months, median overall survival time (OS) was 11 months from the start of HS-IMRT, with a 6-month and 1-year survival rate of 71.4% and 38.1%, respectively. Karnofsky performance status was a significant prognostic factor of OS as tested by univariate and multivariate analysis. Re-operation rate was 4.8% for radiation necrosis. No other acute or late toxicity Grade 3 or higher was observed. CONCLUSIONS: This is the first prospective study of biologic imaging optimized HS-IMRT in recurrent GBM. HS-IMRT with PET data seems to be well tolerated and resulted in a median survival time of 11 months after HS-IMRT.

Hypofractionated high-dose irradiation with positron emission tomography data for the treatment of glioblastoma multiforme.

This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT) with (11)C-methionine positron emission tomography (MET-PET) data for the treatment of glioblastoma multiforme (GBM). A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV) was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV) was the area with 5 mm margin surrounding the GTV; planning target volume (PTV) was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS) was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM.

Assessment of still and moving images in the diagnosis of gastric lesions using magnifying narrow-band imaging in a prospective multicenter trial.

OBJECTIVES: Magnifying narrow-band imaging (M-NBI) is more accurate than white-light imaging for diagnosing small gastric cancers. However, it is uncertain whether moving M-NBI images have additional effects in the diagnosis of gastric cancers compared with still images. DESIGN: A prospective multicenter cohort study. METHODS: To identify the additional benefits of moving M-NBI images by comparing the diagnostic accuracy of still images only with that of both still and moving images. Still and moving M-NBI images of 40 gastric lesions were obtained by an expert endoscopist prior to this prospective multicenter cohort study. Thirty-four endoscopists from ten different Japanese institutions participated in the prospective multicenter cohort study. Each study participant was first tested using only still M-NBI images (still image test), then tested 1 month later using both still and moving M-NBI images (moving image test). The main outcome was a difference in the diagnostic accuracy of cancerous versus noncancerous lesions between the still image test and the moving image test. RESULTS: Thirty-four endoscopists were analysed. There were no significant difference of cancerous versus noncancerous lesions between still and moving image tests in the diagnostic accuracy (59.9% versus 61.5%), sensitivity (53.4% versus 55.9%), and specificity (67.0% versus 67.6%). And there were no significant difference in the diagnostic accuracy between still and moving image tests of demarcation line (65.4% versus 65.5%), microvascular pattern (56.7% versus 56.9%), and microsurface pattern (48.1% versus 50.9%). Diagnostic accuracy showed no significant difference between the still and moving image tests in the subgroups of endoscopic findings of the lesions. CONCLUSIONS: The addition of moving M-NBI images to still M-NBI images does not improve the diagnostic accuracy for gastric lesions. It is reasonable to concentrate on taking sharp still M-NBI images during endoscopic observation and use them for diagnosis. TRIAL REGISTRATION: Umin.ac.jp UMIN-CTR000008048.

Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis.

We investigated morphological and metabolic changes of radiation necrosis (RN) of the brain following bevacizumab (BEV) treatment by using neuroimaging. Nine patients with symptomatic RN, who had already been treated with radiation therapy for malignant brain tumors (6 glioblastomas, 1 anaplastic oligodendroglioma, and 2 metastatic brain tumors), were enrolled in this prospective clinical study. RN diagnosis was neuroradiologically determined with Gd-enhanced MRI and 11C-methionine positron emission tomography (MET-PET). RN clinical and radiological changes in MRI, magnetic resonance spectroscopy (MRS) and PET were assessed following BEV therapy. Karnofsky performance status scores improved in seven patients (77.8 %). Both volumes of the Gd-enhanced area and FLAIR-high area from MRI decreased in all patients after BEV therapy and the mean size reduction rates of the lesions were 80.0 and 65.0 %, respectively. MRS, which was performed in three patients, showed a significant reduction in Cho/Cr ratio after BEV therapy. Lesion/normal tissue (L/N) ratios in MET- and 11C-choline positron emission tomography (CHO-PET) decreased in 8 (89 %) and 9 patients (100 %), respectively, and the mean L/N ratio reduction rates were 24.4 and 60.7 %, respectively. BEV-related adverse effects of grade 1 or 2 (anemia, neutropenia and lymphocytopenia) occurred in three patients. These results demonstrated that BEV therapy improved RN both clinically and radiologically. BEV therapeutic mechanisms on RN have been suggested to be related not only to the effect on vascular permeability reduction by repairing the blood-brain barrier, but also to the effect on suppression of tissue biological activity, such as immunoreactions and inflammation.

Insulin-derived amyloidosis and poor glycemic control: a case series.

OBJECTIVES: Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption. METHODS: Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients. RESULTS: When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030). CONCLUSIONS: Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.