Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer.

PURPOSE: Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. PATIENTS AND METHODS: Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. RESULTS: Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. CONCLUSION: Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings.

Computational study on the reaction pathway of α-bromoacetophenones with hydroxide ion: possible path bifurcation in the addition/substitution mechanism.

The reaction of an α-haloketone with a nucleophile has three reaction channels: carbonyl addition, direct substitution, and proton abstraction. DFT calculations for the reaction of PhCOCH(2)Br with OH(-) showed that there exists an addition/substitution TS on the potential energy surface, in which OH(-) interacts with both the α- and carbonyl carbons. The intrinsic reaction coordinate calculations revealed that the TS serves as the TS for direct substitution for XC(6)H(4)COCH(2)Br with an electron-donating X or a X less electron-withdrawing than m-Cl, whereas the TS serves as the TS for carbonyl addition for derivatives with a X more electron-withdrawing than m-CF(3). Trajectory calculations starting at respective TS indicated that the single TS can serve for the two mechanisms, substitution and addition, through path bifurcation after the TS for borderline substrates. The reaction is the first example of dynamic path bifurcation for fundamental reaction types of carbonyl addition and substitution.

Dynamics effects on an E2/E1cb borderline mechanism: unimolecular elimination of 2-aryl-3-chloro-2-R-propanols.

The mechanistic dichotomy between concerted E2 and stepwise E1cb of the base-promoted elimination of 2-aryl-3-chloro-2-R-propanols was examined computationally at the HF, M05-2X, and MP2 levels of theory. Optimizations of transition states (TSs) and reaction intermediates, and intrinsic reaction coordinates (IRC) calculations showed that there was a single reaction route for each substrate, and that the mechanism could be changed from E2 to E1cb by making a carbanion intermediate more stable through the introduction of electron-withdrawing substituents. Molecular dynamics simulations revealed that trajectories started at a single TS led directly to two product regions; the carbanion intermediate region in the E1cb mechanism, and the alkene product region in the E2 mechanism, through path bifurcation after the TS. The present system is a new example of bifurcation in reactions of closed-shell molecules. The overall reaction mechanism changes dynamically from E2 to E1cb by a gradual change in the ratio of E2 and E1cb trajectories, rather than a path switch in concurrent pathways.

Reaction pathways and possible path bifurcation for the Schmidt reaction.

The N(2) liberation from iminodiazonium ion (2-X) is a key step of the Schmidt rearrangement of ketones. Molecular orbital calculations showed that two concurrent reaction channels, syn-benzyl fragmentation and anti-Me rearrangement, exist for syn-2, whereas anti-2-X proceeds via a single TS. Substituent effect analyses of the reactions of syn-2-X gave concave-upward plots, typical for a concurrent reaction mechanism. On the other hand, the reactions of anti-2-X gave linear Hammett plots, indicative of a single reaction mechanism for all anti-2-X. IRC calculations, however, revealed that the TS led to either an anti-benzyl rearrangement or an anti-benzyl fragmentation product depending on the substituent. Thus, the change of the mechanism (identity of the product) could not be detected by the Hammett plots. Ab initio dynamics simulations for anti-2-X were found to follow the IRC path for X = p-NO(2), giving the rearrangement product, and almost so for X = p-MeO, giving the fragmentation products. However, in borderline cases where X is less donating than p-MeO and less withdrawing than p-NO(2), the trajectories did not follow the minimum energy path on the potential energy surface but gave both rearrangement and fragmentation products directly from the single TS. This is a novel example of path bifurcation for a closed shell anionic reaction. It was concluded that a reactivity-selectivity argument based on the traditional TS theory might not always be applicable even to a well-known textbook organic reaction.

Structural effect on the stability of acetophenone-B(OMe)2 complexes in the gas phase. The nature of the bond between the boron cation and neutral molecules.

The free energy changes (DeltaG, boron cation basicity; BCB) for the reaction [(MeO)2B]L+ = (MeO)2B+ + L (L = acetophenones) were determined in the gas phase by measuring ligand exchange equilibria using an FT-ICR mass spectrometer. On the basis of the correlation analysis by the Yukawa-Tsuno equation, DeltaG = rho(sigma degrees + r+DeltasigmaR+), the substituent effect on DeltaBCB of acetophenone was characterized by a rho value (in kJ mol(-1) sigma(-1) unit) of -43.2 and an r+ value of 0.89. Both the rho and r+ values were found to be similar to the corresponding values for protonation, indicating that the bond between (MeO)2B+ and the oxygen atom of the carbonyl group has a high covalent character similar to the H+-O=C bond. This conclusion was consistent with the geometrical features and the charge distribution calculated at DFT-B3LYP/6-311+G(d,p) level of theory. A comparison with the results for a series of Lewis cation basicity of the acetophenone system showed that the r+ value decreases in the order of H+ = (MeO)2B+ > Me3Si+ > Me3Ge+ > Cu+ > Li+. This decreasing order is related to increasing ionic (ion-dipole interaction) nature of the bonding interaction between Lewis cations and the carbonyl oxygen atom. This was also supported by the theoretical calculations.

Structural effect on the stability of (pyridine)(2)Cu(+) complexes in the gas phase: nature of the bond between copper(I) ion and neutral molecules.

Free energy changes (DeltaG degrees , copper cation basicity) for the reaction L(2)Cu(+) = Cu(+) + 2L were obtained in the gas phase for substituted pyridines based on the measurement of ligand-exchange equilibria in a Fourier transform ion cyclotron resonance (FT-ICR) spectrometer. For 3- and 4-substituted pyridines, the relative copper cation basicities (DeltaCCB[L(2)Cu(+)]) were linearly correlated with the corresponding gas-phase proton basicities (DeltaGB) with a slope of 1.01. On the basis of a linear relationship between the calculated copper cation basicities of dimeric and monomeric complexes at MP2/6-311+G(2p,2d)//B3LYP/6-311G*, DeltaCCB[L(2)Cu(+)](calcd) = 1.54DeltaCCB[LCu(+)](calcd), the substituent effect on the DeltaCCB for the first ligand was estimated to be 0.66 times smaller than the corresponding DeltaGB. A comparison with the corresponding results for other Lewis cation basicity of the pyridine system showed that the magnitude of the substituent effect decreases in the order H(+) (1.00) > Me(3)Si(+) (0.95) > Cl(+) (0.83) > Cu(+) (0.66) > Li(+) (0.47). This change was associated with the natural charges at the Lewis cation moiety and the natural atomic orbital (NAO) bond order of the M+-N bond of the complex ion, indicating the decrease in covalent character of the M(+)-N bond in this order. Furthermore, when a variety of neutral bases such as amines, carbonyl compounds, and ethers were included in a comparison between CCB[L(2)Cu(+)] and GB, it was found that there is a good linear relationship with significant deviations of small molecules and bulky tributylamine, which is attributed to their different steric environment at the binding sites from others, while there is no simple linear relationship with the lithium cation basicities (LCB). The similarity of the substituent effect between CCB[L(2)Cu(+)] and GB reflects the covalent character in the Cu(+) interaction. In conclusion, although the ionic (ion-dipole interaction) nature of the Cu(+) interaction results in a smaller substituent effect than that for the protonation, the covalent nature also plays an important role in the Cu(+) interaction with neutral molecules.

Treatment results of radical surgery and definitive chemoradiotherapy for patients with submucosal esophageal squamous cell cancinomas.

BACKGROUND: A radical esophagectomy with extensive lymph node dissection is the mainstay treatment for submucosal esophageal cancer, though definitive chemoradiotherapy (CRT) has also been applied. However, the treatment outcomes have not yet been extensively investigated. PATIENTS AND METHODS: Forty-nine patients with submucocal esophageal squamous cell carcinoma, 24 and 25 of whom had been treated by a radical esophagectomy with extensive lymph node dissection (Surgery group) and definitive CRT using 5-Fluorouracil and CDDP with concurrent radiation of 60 Gy (CRT group), respectively, formed the study cohort. RESULTS: In the Surgery group, the overall and cause-specific 5-year survival rates were 75.4% and 90.0%, respectively. No operative or hospital deaths had occurred. In the CRT group, a complete response (CR) had been achieved in 22 (88%) patients. The 3- and 5-year overall survival rates were 79.3% and 36.9%, respectively, while the cause-specific 3- and 5-year survival rates were 75.2% and 55. 7%, respectively. No treatment-related deaths had occurred. CONCLUSION: These data suggest that: (i) a radical esophagectomy with extensive lymph node dissection can be a standard treatment offering excellent survival and (ii) a definitive CRT is a reasonable alternative to surgery, especially for patients with complications.