Surgery and postoperative definitive radiotherapy for management of canine soft tissue sarcoma: a multi-institutional retrospective study of 272 dogs (2010-2020).

OBJECTIVE: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival. METHODS: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted. Selected variables were assessed for association with local progression and overall survival. RESULTS: 272 dogs were included. Histologic grade was reported in 249 dogs: 102 were grade 1 (40.9%), 120 were grade 2 (48.2%), and 27 were grade 3 (10.8%). Local progression was suspected or confirmed in 56 dogs. Local progression rates were similar for grade 1 (24 of 89 [26.7%]), grade 2 (23 of 111 [20.7%]), and grade 3 tumors (6 of 22 [27.3%]). Previous recurrence (P = .010) and subsequent distant metastasis (P = .014) were associated with more frequent local progression; intensity-modulated radiotherapy was associated with decreased local progression (P = .025) compared to other forms of delivery. Age (P = .049), grade (P = .009), previous recurrence (P = .009), and institution type for surgery (P = .043) were associated with overall survival. CONCLUSIONS: Outcomes for most dogs were good; however, the frequency of local progression indicates an ongoing need to critically appraise local management strategies, particularly for low-grade STS. Intensity-modulated radiotherapy was associated with lower rates of local progression and may be preferred to less precise forms of delivery. CLINICAL RELEVANCE: These data may guide clinicians when making decisions regarding dRT for management of STS.

Acceptance and Preference of Computed Tomographic Colonography and Colonoscopy: Results of a Nationwide Multicenter Comparative Questionnaire Survey in Japan.

Objectives: To investigate patient acceptance and preference for computed tomographic colonography (CTC) over colonoscopy. Methods: Participants were recruited from a nationwide multicenter trial in Japan to assess the accuracy of CTC detection. They were scheduled to undergo colonoscopy after CTC with common bowel preparation on the same day. Some were administered sedative drugs during colonoscopy, depending on the referring clinician and participant's preferences. The participants were requested to complete a questionnaire to evaluate the acceptability of bowel preparation, examinations, and preference for future examinations. Results: Of the 1,257 enrolled participants, 1,180 (mean age: 60.6 years; women: 43.3%) completed the questionnaire. Sedative drugs were not administered in 687 participants (unsedated colonoscopy group) and were administered intravenously during colonoscopy in 493 participants (sedated colonoscopy group). Before propensity score matching, the mean participants' age, percentages of asymptomatic participants, insufflation of gas during colonoscopy, and number of participants with a history of abdominal/pelvic operation significantly differed between the groups. After propensity score matching, 912 participants from each group were included in the analysis. In the unsedated colonoscopy group, CTC was answered as significantly easier than colonoscopy (p<0.001). Conversely, CTC was significantly more difficult than colonoscopy in the sedated colonoscopy group (p<0.001). In the unsedated colonoscopy group, 48% preferred CTC and 22% preferred colonoscopy for future examinations, whereas in the sedated colonoscopy group, 26% preferred CTC and 38% preferred colonoscopy (p<0.001). Conclusions: CTC has superior participant acceptability compared with unsedated colonoscopy. However, our study did not observe the advantages of CTC acceptance over sedative colonoscopy.

Rectal volume is correlated with interfractional positional shifts of the prostate gland in dogs receiving radiation therapy.

Variability in prostate gland positioning during RT for prostate tumors is a recognized challenge in both human and veterinary oncology. This retrospective study investigates the interfractional variability in prostate gland positioning in relation to rectal and bladder volumes in dogs undergoing radiation therapy (RT) for prostate tumors. The study tracked 10 dogs undergoing five RT sessions from February 2016 to November 2021, delivering a total of 25 Gy each. Each dog underwent CT scans for treatment simulation, and cone-beam CT (CBCT) images were acquired before each RT. The focus was to analyze the positional shifts of the prostate gland concerning the volumes of the rectum and urinary bladder. The pelvic bones were used as the point of reference. The rectal and bladder volumes were measured before each RT, and shifts in the prostate gland position were calculated by comparing coordinates from planning CT and treatment session images. Findings revealed significant correlations between prostate positional shifts in the dorsal-ventral (repeated measures correlation coefficient of -0.58 [range 00.75-00.33]; P < .001) and cranial-caudal directions (repeated measures correlation coefficient [95%CI] 0.56 [range 0.31-0.74]; P < .001) and rectal volume, while no significant relationship was observed with bladder volume. Shifts in the lateral direction were not correlated with either organ's volume. This study highlights the importance of considering rectal volume in canine prostate tumor RT to minimize positional uncertainties. Maintaining consistent rectal volume may enhance the precision of prostate targeting, potentially influencing the safety of RT.

Impact of apitherapy on canine, equine, and chicken lymphocytes, in vitro.

Apitherapy is a form of alternative medicine that utilizes products from the western honeybee (Apis mellifera), including honey, propolis, and honeybee venom, to improve the health status of human patients by altering host immunity. An added benefit of these products is that they are nutraceuticals and relatively inexpensive to aquire. Currently, little is known about the use of honeybee products in veterinary species, as well as their impact on host immunity. In the present in vitro study, honey, propolis, and honeybee venom were co-cultured with enriched canine, equine, and chicken peripheral blood lymphocytes (PBLs) with cell proliferation, cell viability/apoptosis, and cellular morphology evaluated. Concanavalin A (Con A) and dexamethasone were used as stimulatory and suppressive controls, respectively. Honeybee products' effects on the three veterinary species varied by product and the species. Honey stimulated the PBLs proliferation in all three species but also displayed some increased cytotoxicity. Propolis stimulated proliferation in canine and equine PBLs, however, it suppressed proliferation in the chicken PBLs. Honeybee venom was the strongest PBL stimulant for all three species and in the equine, surpassed the stimulant response of Con A and yet, enhanced PBL cell viability post culture. In summary, the results of this preliminary in vitro study show that these three honeybee products do impact lymphocyte proliferation and viability in dogs, horses, and chickens, and that more research both in vitro and in vivo will be necessary to draw conclusions regarding their future use as immune stimulants or inhibitors.

Neutral Chromium Complex with a Cr≡Si Triple Bond: Synthesis and Photoinduced H-H and Benzene C-H Bond Activation.

A neutral silylyne complex with a Cr≡Si triple bond was prepared by dehydrogenation of a chromium silylene complex with Cr-H and Si-H bonds, and was isolated as monomeric crystals, unlike dimeric forms of its tungsten and molybdenum congeners. The strong Cr(δ-)-Si(δ+) bond polarity was revealed by the reaction with MeOH and DFT calculations. The chromium silylyne complex reacted with H2 under LED (365 nm) irradiation to reproduce the precursor silylene complex with a (H)Cr=Si(H) moiety, as a result of 1,2-H-H addition across the Cr≡Si triple bond. Similarly, the chromium silylyne complex reacted with benzene under irradiation to afford an 1,2-addition product with a (H)Cr=Si(Ph) moiety, via benzene C-H bond activation accompanied by Si-C bond forming.

Π-Character of Chromium Germylyne Complex in the Reactions with Enone, Butadiene, and Alkynes: Formation of Germacycles through [2+4] Cycloaddition with Conjugated Molecules.

Germylyne complex Cp*(OC)2 Cr≡Ge{C(SiMe3 )3 } (1) reacted with methyl vinyl ketone to give an η3 -allyl complex 2 with an oxagermacyclopentenyl ring. An analogous η3 -allyl complex 3 with a germacyclopentenyl ring was obtained by the reaction with butadiene, a non-polar conjugated molecule, under photoirradiation. These reactions are accompanied by cleavage of the Cr≡Ge triple bond. On the other hand, the reactions of complex 1 with alkynes under photoirradiation resulted in clean substitution of a CO ligand of 1 to afford (η2 -alkyne)germylyne complexes, where the Cr≡Ge triple bond is intact.

Synthesis and molecular structural studies of racemic chiral-at-vanadium(V) complexes using an unsymmetric achiral phenolic bidentate ligand.

Mononuclear oxovanadium(V) complexes [V(O)XL (1: X = Ot-Bu, 2: X = Cl)] [H2L: 2,2'-methylene bis(4,6-di-tert-butylphenol)(4'-tert-butyl-6'-(1-adamantyl)phenol)] directed towards asymmetric catalysis have been synthesised as racemic compounds using an unsymmetric and achiral phenolic bidentate ligand (H2L), and NMR and UV-vis absorption spectroscopies, single-crystal X-ray diffraction, and IR spectroscopy revealed their racemic chiral-at-vanadium structures in solution and in the crystal. In addition, theoretical calculations revealed that the HOMO-LUMO energy gap is smaller for unsymmetric ligands, which promotes d-orbital splitting of the metal centre.

Intravenous immunoglobulin for chronic residual peripheral neuropathy in microscopic polyangiitis: A multicentre randomised double-blind trial.

OBJECTIVES: We conducted a Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in patients with glucocorticoid-refractory neuropathy associated with microscopic polyangiitis. METHODS: Patients received immunoglobulin or placebo intravenously for 5 consecutive days at baseline and after 4 weeks. The IVIg and placebo groups received IVIg and placebo, respectively, after 8 weeks. The primary and major secondary end-points were the least squares mean of the change in the manual muscle test (MMT) sum score after 8 and 4 weeks, respectively. RESULTS: A total of 37 patients were randomised into two groups (IVIg [19] and placebo [18]). The least squares mean for the change in the MMT sum score was 9.02 for IVIg and 6.71 for placebo (difference 2.32, 95% confidence interval -2.60 to 7.23, p = .345) after 8 weeks and 6.81 and 2.83 (difference 3.99, 95% confidence interval -1.22 to 9.19, p = .129), respectively, after 4 weeks. There were no new safety concerns for IVIg. CONCLUSIONS: MMT sum scores improved with IVIg compared with placebo after 8 weeks of dosing and two courses of treatment, but the differences were not statistically significant, and the results showed no clear efficacy of IVIg in this patient population. No new safety concerns were raised.

N-Heterocyclic carbene-based C-centered Au(I)-Ag(I) clusters with intense phosphorescence and organelle-selective translocation in cells.

Photoluminescent gold clusters are functionally variable chemical modules by ligand design. Chemical modification of protective ligands and introduction of different metals into the gold clusters lead to discover unique chemical and physical properties based on their significantly perturbed electronic structures. Here we report the synthesis of carbon-centered Au(I)-Ag(I) clusters with high phosphorescence quantum yields using N-heterocyclic carbene ligands. Specifically, a heterometallic cluster [(C)(AuI-L)6AgI2]4+, where L denotes benzimidazolylidene-based carbene ligands featuring N-pyridyl substituents, shows a significantly high phosphorescence quantum yield (Φ = 0.88). Theoretical calculations suggest that the carbene ligands accelerate the radiative decay by affecting the spin-orbit coupling, and the benzimidazolylidene ligands further suppress the non-radiative pathway. Furthermore, these clusters with carbene ligands are taken up into cells, emit phosphorescence and translocate to a particular organelle. Such well-defined, highly phosphorescent C-centered Au(I)-Ag(I) clusters will enable ligand-specific, organelle-selective phosphorescence imaging and dynamic analysis of molecular distribution and translocation pathways in cells.

Asymmetric Twisting of C-Centered Octahedral Gold(I) Clusters by Chiral N-Heterocyclic Carbene Ligation.

Asymmetric induction of metal clusters by ligation of chiral ligands is intriguing in terms of the mechanism of chirality transfer and the stability of the resulting chiral structure. Here we report the asymmetric induction of C-centered hexagold(I) CAuI6 clusters into an asymmetrically twisted structure through monodentate, chiral benzimidazolylidene-based N-heterocyclic carbene (NHC) ligands. X-ray diffraction analysis revealed that the NHC-ligated CAuI6 cluster was diastereoselectively twisted with directionally selective, bond length expansion, and contraction of the Au···Au contacts and that the original cluster with high symmetry was transformed into an optically pure, asymmetric CAuI6 cluster with C1 symmetry. Moreover, the circular dichroism spectroscopy and the time-dependent density functional theory calculation confirmed that the asymmetrically twisted CAuI6 structure was maintained even in solution. Such asymmetric induction of configurationally stable metal clusters would greatly expand the molecular design possibilities of asymmetric catalysts and chiroptical materials by utilizing library chiral NHC ligands.

Bowel habits and gender correlate with colon length measured by CT colonography.

PURPOSE: CT colonography enables three-dimensional measurement of colon length. However, previous studies using CT colonography have not examined the association with gender, age, physique, a history of laparotomy and bowel habits, all possible contributory factors to colon length. The aim of this study is to investigate factors associated with colon length. MATERIALS AND METHODS: We conducted a post hoc analysis based on data obtained from a previous multi-center trial including 321 patients with positive fecal immunochemical tests who underwent CT colonography. Colon length was measured using a computer-generated center line and was divided at the iliac crest level into the distal and proximal colons. Bowel habits were classified into three groups: A-daily; B-once every 2 or 3 days; and C-less than once in 3 days. Statistical comparison was made using one-way ANOVA with Bonferroni's correction. RESULTS: A total of 295 patients were analyzed. The entire colon length (cm, mean ± standard deviation) of individual patients was 150.3 ± 18.5 cm and ranged from 109.7 to 195.9 cm. The female colon was significantly longer than the male colon (154.3 ± 18.1 cm vs. 147.1 ± 18.3 cm; p = 0.022). Colon length showed trends associated with age (p = 0.18) and a history of laparotomy (p = 0.14). According to bowel habits, the entire colon measured 147.4 ± 17.9 in group A, 154.7 ± 18.5 in group B and 158.6 ± 18.3 in group C, and significant differences were observed for "A vs. C" (p = 0.002) and "A vs. B" (p = 0.014). In subgroup analysis by colon segment, the proximal colon trended similarly to the entire colon while there were no trends for the distal colon. CONCLUSIONS: This study has clearly demonstrated that bowel habits and gender both correlate with the length of the entire colon measured by CT colonography, and in particular, the proximal colon. Using CT colonography, we measured the colon length in 295 patients. The entire colon length was 150.3 ± 18.5 cm on average. Females and constipated (less frequent defecation) patients have a significantly longer colon, and in particular, the proximal colon. Colon length showed trends associated with age and a history of laparotomy.

Intramuscular Grade 1 fibrosarcoma: Magnetic resonance imaging findings in 2 dogs.

Two adult neutered male dogs were presented for evaluation of firm, painless masses arising within muscle: an 8-year-old German wirehaired pointer dog with an accessory tricipital growth, and a 3-year-old German shepherd dog with a gracilis muscle growth. Magnetic resonance imaging (MRI) characteristics suggested malignant behavior, with a central fluid-like portion with a hyperenhancing lining, a nidus of disorganized tissue, and an extensive reactive zone, whereas histopathology was consistent with low-grade fibrosarcoma. This report describes histologically low-grade, yet biologically high-grade intramuscular fibrosarcoma, in which MRI provided detailed information on tumor behavior and assisted with biopsy and surgical planning.

Fibrosarcome intramusculaire de Grade 1 chez deux chiens : Imagerie par résonance magnétique. Ce rapport de cas décrit des fibrosarcomes intramusculaires de bas grade histologique mais au comportement biologique de haut grade ainsi que leur imagerie par résonance magnétique (IRM) chez deux chiens mâles castrés évalués pour des masses musculaires fermes et indolores : un Braque Allemand de 8 ans avec une masse originant de la branche accessoire du muscle triceps, et un Berger Allemand de 3 ans avec une masse au muscle gracile. L'IRM a révélé une zone centrale liquide bordée d'une mince couche au rehaussement marqué, adjacent à un foyer de tissu désorganisé, entourés par une zone réactive étendue. L'histopathologie des lésions révèle un fibrosarcome et malgré la présence d'anomalies histologiques de bas grade, l'infiltration des muscles adjacents est documentée par microscopie et les caractéristiques d'imagerie sont celles associées chez l'humain avec un comportement malin.(Traduit par les auteurs).

Recent trends in the prevalence and distribution of colonic diverticula in Japan evaluated using computed tomography colonography.

BACKGROUND: Computed tomography colonography (CTC) may be superior to colonoscopy and barium enema for detecting diverticula. However, few studies have used CTC to diagnose diverticula. AIM: To evaluate the current prevalence and distribution of colonic diverticula in Japan using CTC. METHODS: This study was conducted as part of the Japanese National Computed Tomographic Colonography Trial, which included 1181 participants from 14 hospitals in Japan. We analyzed the prevalence and distribution of colonic diverticula and their relationships with age and sex. The relationship between the diverticula and the length of the large intestine was also analyzed. RESULTS: Diverticulosis was present in 48.1% of the participants. The prevalence of diverticulosis was higher in the older participants (P < 0.001 for trend). The diverticula seen in younger participants were predominantly located in the right-sided colon. Older participants had a higher frequency of bilateral type (located in the right- and left-sided colon) diverticulosis (P < 0.001 for trend). The length of the large intestine with multiple diverticula in the sigmoid colon was significantly shorter in those without diverticula (P < 0.001). CONCLUSION: The prevalence of colonic diverticulosis in Japan is higher than that previously reported. The prevalence was higher, and the distribution tended to be bilateral in older participants.

McKesson® lubricating jelly and Aquasonic® ultrasound gel can be used as bolus materials for radiation therapy.

Bolus materials are commonly used for both human and veterinary radiation therapy (RT). Commercially available bolus materials often leave an air gap between the bolus and the skin which can lead to underdosing of the tumor. This prospective exploratory study evaluated the 6 MV X-ray and electron beam (6, 9, and 12 MeV) attenuating properties for two alternative bolus materials: McKesson lubricating jelly® (MLJ) and Aquasonic 100 Ultrasound gel® (AUG). The results comparing MLJ and water for 12 MeV and 9 MeV electron beams showed <3% difference, however, no other significant differences in radiation dose between water and MLJ nor AUG were seen. Findings demonstrated that both AUG and MLJ have radiation dose attenuating properties similar to water and supported use of these materials as alternative bolus materials for veterinary radiation therapy applications.

Asymmetric construction of tetrahedral chiral zinc with high configurational stability and catalytic activity.

Chiral metal complexes show promise as asymmetric catalysts and optical materials. Chiral-at-metal complexes composed of achiral ligands have expanded the versatility and applicability of chiral metal complexes, especially for octahedral and half-sandwich complexes. However, Werner-type tetrahedral complexes with a stereogenic metal centre are rarely used as chiral-at-metal complexes because they are too labile to ensure the absolute configuration of the metal centre. Here we report the asymmetric construction of a tetrahedral chiral-at-zinc complex with high configurational stability, using an unsymmetric tridentate ligand. Coordination/substitution of a chiral auxiliary ligand on zinc followed by crystallisation yields an enantiopure chiral-only-at-zinc complex (> 99% ee). The enantiomer excess remains very high at 99% ee even after heating at 70 °C in benzene for one week. With this configurationally stable zinc complex of the tridentate ligand, the remaining one labile site on the zinc can be used for a highly selective asymmetric oxa-Diels-Alder reaction (98% yield, 87% ee) without substantial racemisation.

Preference and Experience of Colonic Examination for Participants Presenting to Hospitals with a Positive Fecal Immunochemical Test Result.

PURPOSE: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination. PATIENTS AND METHODS: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience. RESULTS: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups. CONCLUSION: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more "comfortable" examination. Clinicians should therefore be aware of patients' potential preference for noninvasive colorectal examinations.

Multimodality treatment including ONCEPT for canine oral melanoma: A retrospective analysis of 131 dogs.

Canine oral melanoma (OM) is an aggressive cancer with a high rate of metastasis. Surgery and/or radiotherapy (RT) are effective local treatments, yet many dogs succumb to distant metastasis. Immunotherapy represents an attractive strategy for this potentially immunogenic tumor. The objective of this multi-institutional retrospective study was to examine the clinical outcome of dogs with OM treated with ONCEPT melanoma vaccine. Most dogs also underwent surgery and/or RT (8 Gy × four weekly fractions). Dogs with distant metastasis at diagnosis and those receiving concurrent chemotherapy were excluded. One hundred thirty-one dogs treated with ONCEPT were included: 62 had adequate local tumor control defined as complete tumor excision or irradiation of residual microscopic disease; 15 were treated in the microscopic disease setting following an incomplete excision without adjuvant RT; and 54 had gross disease. Median time to progression, median progression-free survival, and median tumor-specific overall survival were 304, 260, and 510 days, respectively. In multivariable analysis, presence of gross disease correlated negatively with all measures of clinical outcome. Other negative prognostic indicators were primary tumor ≥2 cm, higher clinical stage (stages 2 and 3), presence of lymph node metastasis at diagnosis, and caudal location in the oral cavity. Radiotherapy had a protective effect against tumor progression. To date, this is the largest reported series of dogs with OM treated with ONCEPT. Several previously reported prognostic indicators were confirmed.

Efficacy of screening using annual fecal immunochemical test alone versus combined with one-time colonoscopy in reducing colorectal cancer mortality: the Akita Japan population-based colonoscopy screening trial (Akita pop-colon trial).

PURPOSE: Screening programs using fecal occult blood testing help reduce mortality from colorectal cancer (CRC). Colonoscopy and colonoscopy combined with fecal occult blood testing are considered alternatives with higher sensitivity than fecal tests; however, to our knowledge, randomized controlled trials (RCTs) providing such evidence have not been reported. Therefore, this study aimed to compare screening using the fecal immunochemical test (FIT) combined with colonoscopy and FIT alone to evaluate the efficacy of colonoscopy screening in reducing CRC mortality. METHODS: This multicenter, prospective, randomized, controlled study included average-risk individuals for CRC living in the study areas and aged 40-74 years. The exclusion criteria were history of CRC, hereditary non-polyposis CRC, familial adenomatous polyposis, inflammatory bowel diseases, history of cancer other than CRC within the past 5 years, and not expected to survive from comorbid illness. The intervention group underwent one-time colonoscopy and annual FIT, while the control group underwent annual FIT. The primary endpoint was mortality from CRC, while the secondary endpoints were cumulative incidence of invasive CRC, advanced CRC (invasion into the muscle layer or deeper), invasive cancer and screening sensitivities and specificities of invasive CRC, whole CRC, advanced neoplasia, and prevalence of adverse events. The intervention and control groups comprised 4876 and 4875 participants, respectively. CONCLUSION: This explanatory RCT evaluated the efficacy of colonoscopy screening by valid statistical inference based on randomization. Data on adverse events from this kind of screening are necessary when considering implementation of future screening programs. TRIAL REGISTRATION: UMIN Clinical Trials Registry, number UMIN000001980.

Nanoparticles Encapsulating Nitrosylated Maytansine To Enhance Radiation Therapy.

Radiotherapy remains a major treatment modality for cancer types such as non-small cell lung carcinoma (or NSCLC). To enhance treatment efficacy at a given radiation dose, radiosensitizers are often used during radiotherapy. Herein, we report a nanoparticle agent that can selectively sensitize cancer cells to radiotherapy. Specifically, we nitrosylated maytansinoid DM1 and then loaded the resulting prodrug, DM1-NO, onto poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles. The toxicity of DM1 is suppressed by nanoparticle encapsulation and nitrosylation, allowing the drug to be delivered to tumors through the enhanced permeability and retention effect. Under irradiation to tumors, the oxidative stress is elevated, leading to the cleavage of the S-N bond and the release of DM1 and nitric oxide (NO). DM1 inhibits microtubule polymerization and enriches cells at the G2/M phase, which is more radiosensitive. NO under irradiation forms highly toxic radicals such as peroxynitrites, which also contribute to tumor suppression. The two components work synergistically to enhance radiotherapy outcomes, which was confirmed in vitro by clonogenic assays and in vivo with H1299 tumor-bearing mice. Our studies suggest the great promise of DM1-NO PLGA nanoparticles in enhancing radiotherapy against NSCLC and potentially other tumor types.

Colon Capsule Endoscopy versus CT Colonography in Patients with Large Non-Polypoid Tumours: A Multicentre Prospective Comparative Study (4CN Study).

BACKGROUND/AIMS: Non-polypoid colon lesions compared with polypoid lesions has a high malignant potential. The diagnostic performance of colon capsule endoscopy (CCE) and CT colonography (CTC) for large colorectal non-polypoid tumours, that is, laterally spreading tumours is still unclear. The aim of this study is to evaluate the performance of CCE and CTC for the diagnosis of large non-polypoid tumours. METHODS: Thirty patients referred for endoscopic submucosal dissection of non-polypoid tumours measuring ≥20 mm were enrolled. Patients first underwent CCE, then colonoscopy (without resection) and CTC on the same day. An experienced gastroenterologist in a third hospital evaluated the CCE and recorded the location, size and morphology of all lesions detected, blinded to the colonoscopic findings. An experienced radiologist read the CTC under the same conditions. Colonoscopic findings were defined as the reference. RESULTS: A total of 30 lesions (T1 cancer: 3, Tis cancer: 7, adenoma: 14, sessile serrated adenoma/polyp: 6) in 27 patients were observed for evaluation. The capsule excretion rate within 8 h was 85% (23/27), and all capsules went beyond the target lesions. Non-polypoid tumours tend to be depicted as polypoid on CCE. Per patient sensitivities were 0.89 (24/27) by CCE and 0.70 (19/27) by CTC (p = 0.0253, McNemar), and per lesion sensitivities were 0.87 (26/30) and 0.67 (20/30) respectively (p = 0.0143). Most lesions missed by both modalities were located in the proximal colon. CONCLUSION: Eighty-seven per cent of non-polypoid tumours were detected by CCE, and the sensitivity using CCE was higher than that obtained using CTC (UMIN0000014772).