RESUMEN
AIM: The objective was to assess the effect of three different surgical treatments for T1 rectal tumours, radical resection (RR), open local excision (open LE) and laparoscopic local excision (laparoscopic LE), on overall survival (OS). METHODS: Adults from the National Cancer Database (2008-2016) with a diagnosis of T1 rectal cancer were stratified by treatment type (LE vs RR). We assumed that laparoscopic LE equates to transanal minimally invasive surgery (TAMIS) or transanal endoscopic microsurgery. The primary outcome was 5-year OS. Subgroup analyses of the LE group stratified by time period [2008-2010 (before TAMIS) vs 2011-2016 (after TAMIS)] and approach (laparoscopic vs open) were performed. RESULTS: Among 10 053 patients, 6623 (65.88%) underwent LE (74.33% laparoscopic LE vs 25.67% open LE) and 3430 (34.12%) RR. The use of LE increased from 52.69% in 2008 to 69.47% in 2016, whereas RR decreased (P < 0.001). In unadjusted analysis, there was no significant difference in 5-year OS between the LE and RR groups (P = 0.639) and between the two LE time periods (P = 0.509), which was consistent with the adjusted analysis (LE vs RR, hazard ratio 1.05, 95% CI 0.92-1.20, P = 0.468; 2008-2010 LE vs 2011-2016 LE, hazard ratio 1.09, 95% CI 0.92-1.29, P = 0.321). Laparoscopic LE was associated with improved OS in the unadjusted analysis only (P = 0.006), compared to the open LE group (hazard ratio 0.94, 95% CI 0.78-1.12, P = 0.495). CONCLUSIONS: This study supports the use of a LE approach for T1 rectal tumours as a strategy to reduce surgical morbidity without compromising survival.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Laparoscopía , Neoplasias del Recto , Microcirugía Endoscópica Transanal , Cirugía Endoscópica Transanal , Adulto , Humanos , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
The ability to design agonists that target peptide signaling is a strategy to delineate underlying mechanisms and influence biology. A sequence that uniquely characterizes a peptide provides a distinct site to generate novel agonists. Drosophila melanogaster sulfakinin encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2). Drosulfakinin is typical of sulfakinin precursors, which are conserved throughout invertebrates. Non-sulfated DSK II is structurally related to DSK I, however, it contains a unique 5-residue N-terminal extension; drosulfakinins signal through G-protein coupled receptors, DSK-R1 and DSK-R2. Drosulfakinin II distinctly influences adult and larval gut motility and larval locomotion; yet, its structure-activity relationship was unreported. We hypothesized substitution of an N-terminal extension residue may alter nsDSK II activity. By targeting the extension we identified, not unexpectedly, analogs mimicking nsDSK II, yet, surprisingly, we also discovered novel agonists with increased (super) and opposite (protean) effects. We determined [A3] nsDSK II increased larval gut contractility rather than, like nsDSK II, decrease it. [N4] nsDSK II impacted larval locomotion, although nsDSK II was inactive. In adult gut, [A1] nsDSK II, [A2] nsDSKII, and [A3] nsDSK II mimicked nsDSK II, and [A4] nsDSK II and [A5] nsDSK II were more potent; [N3] nsDSK II and [N4] nsDSK II mimicked nsDSK II. This study reports nsDSK II signals through DSK-R2 to influence gut motility and locomotion, identifying a novel role for the N-terminal extension in sulfakinin biology and receptor activation; it also led to the discovery of nsDSK II structural analogs that act as super and protean agonists.
Asunto(s)
Proteínas de Drosophila/genética , Locomoción/genética , Péptidos/agonistas , Péptidos/genética , Receptores Acoplados a Proteínas G/genética , Secuencia de Aminoácidos/genética , Animales , Proteínas de Drosophila/química , Drosophila melanogaster/genética , Péptidos y Proteínas de Señalización Intercelular , Larva/efectos de los fármacos , Larva/genética , Locomoción/efectos de los fármacos , Neuropéptidos/química , Neuropéptidos/genética , Oligopéptidos/química , Oligopéptidos/genética , Péptidos/química , Péptidos/farmacología , Receptores de Colecistoquinina/química , Receptores de Colecistoquinina/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
We report the investigation of electronic excitations in InGaAs self-assembled quantum dots using resonant inelastic light scattering. The dots can be charged via a gate by N=1, em leader,6 electrons. We observe excitations, which are identified as transitions of electrons, predominantly from the s to the p shell (s-p transitions) of the quasiatoms. We find that the s-p transition energy decreases and the observed band broadens, when the p shell is filled with 1 to 4 electrons. By a theoretical model, which takes into account the full Coulomb interaction in the few-electron artificial atom, we can confirm the experimental results to be an effect of the Coulomb interaction in the quantum dot.