A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. FUNDING: Olympus.

Evaluation of a novel infra-red endoscopy system in the assessment of early neoplasia in Barretts esophagus: pilot study from a single center.

Infrared endoscopy (IRE) has been shown to be useful in detecting submucosal (SM) invasion in early gastric cancer. Its role in the endoscopic assessment of Barrett's neoplasia has not been reported to date. We aimed in this study to evaluate the role of IRE in the detection and characterization of early neoplastic lesions within Barrett's esophagus (BE). The secondary aim was to explore its usefulness for the assessment of the presence of submucosal invasion in these early neoplastic Barrett's lesions. We included in the study patients with dysplastic BE who were referred to our institution for endoscopic therapy of a previously diagnosed early Barrett's neoplasia. An examination with white light high resolution endoscopy (HRE) and near IRE after intravenous injection of indocyanine green was performed for all patients using an infrared endoscope prototype. Staining on IRE and correlation with final histological staging by endoscopic mucosal resection/surgery or histological diagnosis on mapping biopsies was analyzed. A total of 23 patients were enrolled in our study: 17 of them with 19 visible lesions and 6 patients with flat BE and no lesions. Staining on IRE was noted in 18 cases: 17 (94%) had at least high grade dysplasia (HGD). No stain was noted in 7 cases: final histology was

Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience.

OBJECTIVE: Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. DESIGN: This study was conducted as part of the service evaluation audit. SETTING: Tertiary referral centre. PATIENTS: All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. INTERVENTIONS: All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. RESULTS: Fifty patients were analysed; median age 73 years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). CONCLUSIONS: In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high-incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise.

Animal models for endoscopic training: do we really need them?

Gastrointestinal endoscopy currently includes many therapeutic methods that are technically challenging and frequently associated with a significant risk of complications. Several issues such as the limited number of clinical cases and practice in emergency situations, and technical difficulty may limit the opportunity for training, and increased exposure in more relaxed situations would be desirable. Moreover, providing the patient with the best possible standard of care is a must. Animal models are the most easily available simulators. Training in these models has been recommended for several complex techniques, among which hemostasis, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and endoscopic submucosal dissection are reviewed here. Ex vivo models are much easier to set up and, from an ethical standpoint, they should be used for the initial step in training whenever possible before moving on to in vivo models. Although simulation with animal models has been the subject of a good number of studies, very few of them have evaluated the impact on clinical outcomes, and clearly more studies are needed. Nevertheless, available evidence does suggest that practicing on animal models has an influence on the learning curve and facilitates the acquisition of skills in the complex endoscopic techniques reviewed.

Chemical and in vitro study of the potential of 3-(aryl)-2-sulfanylpropenoic acids and their Zn(II) complexes as protective agents against cadmium toxicity.

The free H(2)xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ](2)[Zn(xspa)(2)] (HQ = diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR ((1)H, (13)C) spectroscopy. X-Ray studies of the crystal structures of [HQ](2)[Zn(pspa)(2)], [HQ](2)[Zn(Clpspa)(2)], [HQ](2)[Zn(tspa)(2)] and [HQ](2)[Zn(fspa)(2)] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO(2)S(2) environment. In the structures of [HQ](2)[Cd(pspa)(2)] and [HQ](2)[Cd(Clpspa)(2)] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn(II) and Cd(II) was studied by (113)Cd NMR spectroscopy. The in vitro protective effect of H(2)xspa and their Zn(II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn(II) was found to be relevant in the case of H(2)pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.

Ab initio and DFT studies on van der Waals trimers: the OCS.(CO2)2 complexes.

Ab initio calculations [MP2, MP4SDTQ, and QCISD(T)] using different basis sets [6-31G(d,p), cc-pVXZ (X = D, T, Q), and aug-cc-pVDZ] and density functional theory [B3LYP/6-31G(d,p)] calculations were carried out to study the OCS.(CO2)2 van der Waals trimer. The DFT has proved inappropriate to the study of this type of systems where the dispersion forces are expected to play a relevant role. Three minima isomers (two noncyclic and one cyclic) were located and characterized. The most stable isomer exhibits a noncyclic barrel-like structure whose bond lengths, angles, rotational constants, and dipole moment agree quite well with the corresponding experimental values of the only structure observed in recent microwave spectroscopic studies. The energetic proximity of the three isomers, with stabilization energies of 1442, 1371, and 1307 cm-1, respectively, at the CBS-MP2/cc-pVXZ (X = D, T, Q) level, strongly suggests that the two unobserved structures should also be detected as in the case of the (CO2)3 trimer where both noncyclic and cyclic isomers have been reported to exist. The many-body symmetry-adapted perturbation theory is employed to analyze the nature of the interactions leading to the formation of the different structures. The three-body contributions are small and stabilizing for the two most stable structures and almost negligible for the cyclic isomer.

Mechanistic aspects of the abstraction of an allylic hydrogen in the chlorine atom reaction with 2-methyl-1,3-butadiene (isoprene).

The different channels for the abstraction of an allylic hydrogen in the chlorine atom reaction with isoprene were explored using ab initio methodology. It is shown that the metathesis reaction proceeds through an association-elimination mechanism in which a weakly bound intermediate (HCl.C(5)H(7)(*)) is formed first (formal addition). Further evolution by HCl elimination leads to the final C(5)H(7)(*) radical. QCISD(T)/aug-cc-pVDZ//MP2/6-31G(d,p) calculations show that for two of the possible pathways the barrier heights involved are moderate and the formation of the intermediates are exergonic (DeltaG < 0). Therefore, the mechanism proposed is both kinetically and thermodynamically feasible. The pressure dependence experimentally observed for the Cl + isoprene reaction can be rationalized in terms of the association-elimination mechanism proposed.

Dichlorobis(3,5-dimethylpyrazole-N2)methylphenyltin(IV)

The title compound, [SnCl(2)(CH(3))(C(6)H(5))(C(5)H(8)N(2))(2)], was obtained by reaction of dichloromethylphenyltin(IV) and 3, 5-dimethylpyrazole (dmpz) in chloroform, and was recrystallized from acetone. The structure consists of octahedral all-trans [SnMePhCl(2)(dmpz)(2)] molecules, with the Sn atom coordinated to two C [Sn-C 2.127 (5) and 2.135 (4) A], two Cl [Sn-Cl 2.5753 (8) A] and two N atoms [Sn-N 2.357 (3) A]. The dmpz ligands, bound to the metal through their unprotonated N atoms, form weak intra- and intermolecular hydrogen bonds with the Cl ligands via their NH groups, giving rise to a polymeric chain along the c axis.

Synthesis, structure, spectroscopic properties and biological activity of mixed diorganotin(IV) complexes containing pyridine-2-carbaldehyde thiosemicarbazonato and diphenyldithiophosphinato ligands.

Reaction of the title ligands (HPyTSC and HS(S)PPh2, respectively) with R2SnO (R = Me, Et, Bu) in ethanol (EtOH) afforded the complexes [SnMe2(PyTSC) (S2PPh2)].EtOH (1) and [SnR2(PyTSC) (S2PPh2)] (R = Et (2), Bu (3)). The structures of 1 and 2 were determined by single-crystal X-ray diffractometry. In both these complexes the tin atom is coordinated to an N,N,S-dentate thiosemicarbazonate ligand, an anisobidentate dithiophosphinato ligand and the two R groups. The coordination polyhedrons can be described as distorted pentagonal bipyramids. A comparative study of the IR spectra of 1, 2 and 3 indicates that the butyl complex has a similar structure. Multinuclear (1H, 13C, 31P and 119Sn) NMR data suggest that the structures of 1 and 2 probably remain in CDCl3 (or DMSO-d6) solution but compound 3 partially decomposes in these media. Preliminary results on the effects of the complexes on the proliferation and differentiation of FLC, CEM, U937, K562 and TOM-1 leukaemia cells, and on the clonogenic activity of K562 cells are also described.

Diorganotin(IV) complexes of pyridoxal thiosemicarbazone: synthesis, spectroscopic properties and biological activity.

The complexes [SnR2(L)] (R = Me, Et, Bu, Ph; H2L = pyridoxal thiosemicarbazone) have been prepared and characterized. In the light of the spectral properties of the complexes in the solid state (IR, mass, Mössbauer) the bideprotonated thiosemicarbazonato anion is O(phenolic)-, N(3)-, S-bonded to the tin atom which probably has trigonal bipyramidal coordination with N(3) atom and R groups occupying equatorial positions. NMR ( 1H, 13C and 119Sn) data in CDCl3 or DMSO-d6 suggest that this coordinative picture remains in these solutions. The ethyl, butyl and phenyl derivatives suppress proliferation of Friend erithroleukaemia cells (FLC). Of the pyridoxal thiosemicarbazone complexes so far evaluated. [SnBu2(L)] and [SnPh2(L)] showed the lowest thresholds for inhibition of FLC proliferation. The effects of these compounds on DMSO-induced differentiation of FLC, DNA synthesis and reverse transcriptase were also assayed.

Synthesis, structure, and spectroscopic properties of acetato(dimethyl)(pyridine-2-carbaldehydethiosemicarbazonato)tin(IV) acetic acid solvate, [SnMe2(PyTSC)(OAc)].HOAc. Comparison of its biological activity with that of some structurally related diorganotin(IV) bis(thiosemicarbazonates).

The synthesis, X-ray structure, behavior in solution, and biological properties of the complex [SnMe2(PyTSC)(OAc)].HOAc (HPyTSC = pyridine-2-carbaldehydethiosemicarbazone) are reported. The tin atom of this complex is coordinated to an N,N,S-tridentate PyTSC- anion, to a monodentate acetate ion, and to the two methyl groups in an approximately pentagonal bipyramidal environment with a vacant equatorial position. The complex partially evolves in DMSO and in DMSO/CHxCl4-x (X = 1, 2) mixtures, giving HPyTSC and SnMe2(OAc)2. [SnMe2 (PyTSC)(OAc)].HOAc, [SnMe2(DAPTSC)], and [SnPh2(DAPTSC)].2DMF (H2DAPTSC = 2,6-diacetylpyridine bis(thiosemicarbazone)) all suppress proliferation of Friend erythroleukaemia cells (FLC). DMSO-induced differentiation of FLC is slightly suppressed by [SnMe2(DAPTSC)] and is unaffected by [SnPh2(DAPTSC)].2DMF and [SnMe2(PyTSC)(OAc)].HOAc.

Chemical and in vivo studies of interaction between cadmium and vitamin B6.

The interaction of vitamin B6 pyridoxine with cadmium acetate in ethanolic solution has been studied. The new compound Cd(PN-H)(OOCCH3) (PN-H = pyridoxinato anion) was isolated and its structure studied in the solid state by IR and 13C and 113Cd CP/MAS NMR spectroscopies. The effect of pyridoxine on survival rate among male Sprague rats injected intraperitoneally with 5 mg CdCl2.H2O/kg was also investigated. Vitamin treatment seems to increase (Protocol C) or does not affect the cadmium lethality. Although the analysis of the metal burden in some organs seems to suggest a light increase of the cadmium level in the liver, this change has no significance at a statistical level.

Effects of vitamin B12 on cadmium toxicity in rats.

The survival rate was high among male Sprague rats treated with 0.15 mg/kg vitamin B12 (cyanocobalamine) after injection of 5 mg/kg CdCl2.H2O (LD50). The cadmium content of the liver and, for some protocols, in the kidney was significantly reduced in survivors. According to UV-V and multinuclear (1H, 13C, 31P, and 113Cd) magnetic resonance spectroscopy no direct interaction seems to take place between cyanocobalamine and CdCl2 in aqueous solution at pH 4.5. An indirect mechanism is put forward to explain the antidotal activity.

Diorganotin dihalide complexes of 2,2'-biimidazole. A preliminary study of their inhibitory effects on cell division.

We report the synthesis of new complexes with the general formula (R2SnX2)y.H2BiIm, where y = 1 or 2; R = Me, Et, Bun; X = Cl or Br (for R = Et) and H2BiIm = 2,2'-Biimidazole. The complexes have been characterized by elemental analysis and Mössbauer, infra-red and 1H n.m.r. spectroscopy and tested (like the ligand, Me2SnCl2 and Et2SnCl2) against P388D1 leukemic cells.

Thallium (I) interactions in biological fluids: a potentiometric investigation of thallium(I) complex equilibria with some sulphur-containing amino acids.

Formation constants for thallium(I) complexes of L-cysteine (CysH2), DL-penicillamine (PenH2), N-acetyl-L-cysteine (AcyH2), and N-acetyl-DL-penicillamine (ApeH2) in aqueous solution have been determined in 150 mmol dm-3 NaCl medium at 37 degrees C by potentiometric titrations using a glass electrode. Glycine has been used as a model for simple amino acids. The experimental data may be explained by the formation of the complexes T1(Cys)-, T1(Cys)H, T1(Pen)-, T1(Pen)H, T1(Acy)-, and T1(Ape)- with log formation constants 3.26, 11.28, 3.60, 12.05, 2.27, and 2.45, respectively. Analysis of the results obtained and comparison of thallium(I) complexing ability with that of dimethyl-thallium(III) seem to indicate that thallium(I) toxicity does not directly stem from its interference with the metabolism of sulphur-containing compounds.

Dithiocarbamates in heavy metal poisoning: complexes of N,N-di(2-hidroxyethyl)dithiocarbamate with Zn(II), Cd(II), Hg(II), CH3Hg(II), and C6H5Hg(II).

The complexes M(DHDC)2, CH3Hg(DHDC), and C6H5Hg(DHDC) (M = Zn, Cd, Hg; DHDC = N,N-di(2-hydroxyethyl)dithiocarbamate) were prepared and investigated in solution and in the solid state by using 1H and 13C NMR, ir, and Raman spectroscopy. The dithiocarbamate group is anisobidentate and the complexes are associated in solution and the solid state via hydrogen bonding. The possible relation of these structural properties to the behavior of DHDC in the treatment of cadmium poisoning is discussed.

[Blood levels of lead and delta-aminolevulinic dehydratase activity in a Spanish population. Effect of occupational exposure and social habits]. / Niveles de plomo y actividad delta-aminolevulínico deshidratasa sanguíneos en una población española. Efecto de la exposición profesional y de los hábitos sociales.

The effect of tobacco and alcohol on the delta-amino levulinic dehydratase (ALA-D) activity and lead level in blood is studied in a population of workers with or without exposure to lead due to their work. The lead level in the blood of workers without exposure is about 15.9 +/- 1.7 micrograms/100 ml and is unaltered by sex. The ALA-D level for men and women is 289.7 +/- 15 U/100 ml and 255.9 +/- 10 U/100 ml respectively, the difference being due mainly to the smaller hematocrit for women. Without lead exposure smoking moderately does not change the ALA-D or the lead level, whereas alcoholic drink consumption increases the lead level but does not affect the ALA-D activity. When both factors concur the ALA-D activity decreases, while the lead level increases. With lead exposure, however, neither the ALA-D activity nor the lead level undergoes any change, with of without smoking and drinking, since the values have been completely altered by the exposure. A close relationship between ALA-D activity and lead level in blood has been found in each case.