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.

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.

Detection of pharyngeal cancer in the overall population undergoing upper GI endoscopy by using narrow-band imaging: a single-center experience, 2009-2012.

BACKGROUND: Nonmagnifying observation by using narrow-band imaging (NBI) is useful for detecting pharyngeal lesions. Magnifying observation by using NBI can distinguish between cancerous and noncancerous lesions and is therefore useful for the early detection of pharyngeal cancer. OBJECTIVE: To evaluate the usefulness of observation of the pharynx by using NBI in the overall population undergoing upper GI endoscopy. DESIGN: Retrospective study. SETTING: Single tertiary referral center. PATIENTS: A total of 11,050 upper GI endoscopies between January 2009 and December 2012. INTERVENTIONS: Observation of the pharynx by using NBI. MAIN OUTCOME MEASURES: The rate of detection of pharyngeal cancer, the rates of detection according to the reason for endoscopy, and the types of cancers detected. RESULTS: Thirty-eight cancerous lesions were detected in 29 patients (0.26%, 29/11,050). The rate of detection of pharyngeal cancer was significantly higher in patients with a history of head and neck cancer (9.7%, 3/31) or a history of esophageal cancer (3.5%, 10/282). In patients undergoing endoscopy for screening, pharyngeal discomfort, and a history of gastric cancer, the rates of detection of pharyngeal cancer were 0.11% (10/8872), 1.1% (3/265), and 0.19% (3/1600), respectively. Two patients (6.9%) were female. One had a history of esophageal cancer, and the other had pharyngeal discomfort. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Observation of the pharynx by using NBI in patients with previous head and neck cancer or esophageal cancer or who have pharyngeal discomfort is very important. Moreover, pharyngeal cancer was certainly found in the male patients undergoing screening endoscopy, although the rate was lower.

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.

Discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor.

Vascular endothelial growth factor (VEGF) plays important roles in tumor angiogenesis, and the inhibition of its signaling pathway is considered an effective therapeutic option for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of 2-acylamino-6-phenoxy-imidazo[1,2-b]pyridazine derivatives. Hybridization of two distinct imidazo[1,2-b]pyridazines 1 and 2, followed by optimization led to the discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (23a, TAK-593) as a highly potent VEGF receptor 2 kinase inhibitor with an IC50 value of 0.95 nM. The compound 23a strongly suppressed proliferation of VEGF-stimulated human umbilical vein endothelial cells with an IC50 of 0.30 nM. Kinase selectivity profiling revealed that 23a inhibited platelet-derived growth factor receptor kinases as well as VEGF receptor kinases. Oral administration of 23a at 1 mg/kg bid potently inhibited tumor growth in a mouse xenograft model using human lung adenocarcinoma A549 cells (T/C=8%).

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.

Evaluation of brain tumors using dynamic 11C-methionine-PET.

The aim of this study is to assess whether dynamic imaging of (11)C-methionine (MET) uptake on positron emission tomography (PET) is useful for the differential diagnosis of brain tumor histology. Regional MET uptake in static brain PET scans from three consecutive phases (5-15, 15-25, and 25-35 min) after intravenous injection were measured in 144 patients with brain tumors. Regions of interest (ROI) were placed in the pituitary gland, confluence, choroid plexus, coronal radiation, brainstem, frontal cortex, parietal cortex, cerebellum, and brain tumors. The standard uptake value (SUV) of the ROIs in the normal brain structures and brain tumors were measured, and the mean MET SUV region/normal frontal lobe cortex uptake ratio (R/N ratio) of the normal brain structures and the maximum MET SUV tumor/normal frontal cortex uptake ratio (T/N ratio) were evaluated semi-quantitatively. There were significant dynamic declines of the mean MET R/N ratio in the normal pituitary gland and confluence; however, there were significant dynamic increases in white matter. Significant dynamic decrease of the maximum MET T/N ratio was seen in meningiomas and oligodendrocytic tumors, whereas significant dynamic increase was seen in glioblastomas and malignant lymphomas. Dynamic changes of MET uptake vary significantly with the normal brain structures and brain tumor histology. These results suggest that MET-PET may be useful in the differential diagnosis of brain tumors.

Can magnifying endoscopy with narrow band imaging be useful for low grade adenomas in preoperative biopsy specimens?

BACKGROUND: In biopsy specimens with low grade adenomas, it is often difficult to identify the presence of high grade adenomas or early carcinomas and low grade adenomas preoperatively, and clear guidelines have not yet been defined for the applicability of endoscopic treatment to low grade adenomas identified in biopsy specimens. METHODS: We aimed to clarify the usefulness of magnifying endoscopy with narrow band imaging (NBI) compared to conventional white light endoscopy for diagnosing actual high grade adenomas or early carcinomas with low grade adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S]) classification for low grade adenomas in biopsy specimens. The study cohort consisted of 135 patients who were diagnosed with low grade adenomas in preoperative biopsy specimens and received endoscopic submucosal dissection. RESULTS: In the elevated type of lesion, magnifying endoscopy with NBI diagnosed high grade adenomas or early carcinomas at a higher sensitivity and specificity than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs. 54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light endoscopy. Although the specificity was high, at 100%, the difference when compared to conventional white light endoscopy was not significant (100 vs. 100%, P > 0.99). CONCLUSIONS: For low grade adenomas in biopsy specimens, it is vital to take sufficient consideration of endoscopic findings and not take action based only on the biopsy results. If a decision is made using the VS classification with magnifying endoscopy with NBI, actual high grade adenomas or early carcinomas can be differentiated from low grade adenomas so that endoscopic treatment can be performed more strictly.

Design and synthesis of pyrrolo[3,2-d]pyrimidine HER2/EGFR dual inhibitors: improvement of the physicochemical and pharmacokinetic profiles for potent in vivo anti-tumor efficacy.

During the course of our studies on a novel HER2/EGFR dual inhibitor (TAK-285), we found an alternative potent pyrrolo[3,2-d]pyrimidine compound (1a). To enhance the pharmacokinetic (PK) profile of this compound, we conducted chemical modifications into its N-5 side chain and conversion of the chemically modified compounds into their salts. Among them, 2cb, the tosylate salt of compound 2c, showed potent HER2/EGFR kinase inhibitory activity (IC(50): 11/11 nM) and cellular growth inhibitory activity (BT-474 cell GI(50): 56 nM) with a good drug metabolism and PK (DMPK) profile. Furthermore, 2cb exhibited significant in vivo antitumor efficacy in both mouse and rat xenograft models with transplanted 4-1ST gastric cancer cell lines (mouse, T/C=0%, 2cb po bid at 100 mg/kg; rat, T/C: -1%, 2cb po bid at 25 mg/kg).

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.

High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease.

OBJECTIVE: Although many mutations of the Wilson's disease (WD) gene (ATP7B) have been reported, few data exist regarding the occurrence of fulminant hepatic failure (FHF). We sought to determine if genotypic assignment according to type of protein-product could be related to the prevalence of FHF among patients with WD. MATERIAL AND METHODS: We performed gene analysis in Japanese patients with WD as well as genotype-phenotype analysis in 51 patients. We divided genotypes into two groups according to type of ATP7B product: truncated group [T] consisted of two truncated alleles including nonsense, insertion, deletion, or splice site mutation, and missense group [M] consisted of one or two missense alleles. We also divided phenotypes into two groups: [FHF] group and [non-FHF] group. RESULTS: We were able to determine genotype in 42 patients. Genotypically, 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [FHF] and 38 were [non-FHF]. All patients in [FHF] group belonged to [T] group. The prevalence of [FHF] in [T] group was 36.4% and was significantly higher than in [M] group (p < 0.003). CONCLUSIONS: These results demonstrated that genotypes for truncation of ATP7B are associated with high prevalence of FHF.

Double helix formation of oligoresorcinols in water: thermodynamic and kinetic aspects.

We previously reported that the oligoresorcinols formed double-stranded helices in neutral water through interstrand aromatic interactions. In the present study, we synthesized a new series of oligomers from the 2mer to the 15mer to explore the thermodynamics, kinetics, and mechanism of the double helix formation of the oligoresorcinols in water. The double helix formation was dependent on the chain length of the oligomers and significantly affected by solvent, pH, salt, and temperature. The free energy change (-DeltaG) for the double helix formation linearly increased with the chain length from the 4mer to the 11mer (DeltaDeltaG = -0.94 kcal mol(-1) unit(-1)), whereas it did not change for the oligomers longer than the 11mer. The van't Hoff analysis of the 9mer revealed that the double helix formation was an enthalpically driven process (DeltaH = -27 +/- 1.5 kcal mol(-1) and DeltaS = -70 +/- 5 cal mol(-1) K(-1)), which was consistent with the upfield shifts in the (1)H NMR spectra and the hypochromicity of the absorption spectra as a result of the interstrand aromatic interactions in water. Furthermore, the kinetic analysis of the chain exchange reaction between the double helices of the optically active and optically inactive 11mers revealed a small DeltaS(double dagger), suggesting that the chain exchange proceeds not via the dissociation-association pathway, but via the direct exchange pathway.

Double helix formation of poly(m-phenylene)s bearing achiral oligo(ethylene oxide) pendants and transformation into an excess of one-handed single helix through cholate binding in water.

A water-soluble poly(m-phenylene) bearing an achiral oligo(ethylene oxide) chain at the 5-position was synthesized by the Ni(0)-mediated homo-coupling polycondensation of a 3,5-dibromophenol monomer. The poly(m-phenylene) adopted a single helical conformation in protic media and self-assembled into a double helix in water through aromatic interaction, while it took a random-coil conformation in chloroform. Upon the addition of sodium cholate in water, the double helical poly(m-phenylene) was transformed into single strands, which bound the cholate molecules to form an excess of one-handed single helix.

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.