RESUMO
Survivin, an inhibitor of apoptosis, has been shown to be expressed in various malignancies. However, its role in gallbladder cancer (GBC) has not been evaluated yet. We investigated its expression in peripheral blood of patients with gallbladder diseases (gallstone disease (GSD), n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Survivin expression was correlated with clinicopathological parameters, diagnosis, and prognosis of patients with GBC. Expression of survivin messenger RNA (mRNA) in blood was evaluated by real-time PCR. Significantly higher (P < 0.0001) expression of survivin mRNA was observed in GBC (2.2-fold) and GSD (1.52-fold) as compared to control. In GBC, increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and tumor differentiation (poor and moderate vs. well differentiated; P < 0.0001). No significant correlation was observed with any of the other clinicopathological parameters (age, gender, and presence or absence of gallstones) studied. Cutoff value of survivin mRNA relative quantification (RQ) was 1.08, with a sensitivity of 98.55 % and specificity of 100 % for the diseased group (GSD or GBC). RQ value of 1.71 differentiated GBC from GSD with a sensitivity of 89.74 % and specificity of 100 %. Increased expression of survivin was associated with a shorter median overall survival (12 vs. 18 months) in GBC patients. Differential expression of survivin in GBC suggests its possible role and association with poor prognosis. Expression of survivin in peripheral blood could be useful both in the diagnosis and prognosis of GBC.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Inibidoras de Apoptose/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Feminino , Doenças da Vesícula Biliar/sangue , Doenças da Vesícula Biliar/diagnóstico , Doenças da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Survivina , Adulto JovemRESUMO
BACKGROUND: We have reported perineal antropyloric segment transposition with its pudendal innervation as a replacement for anal sphincter. Our aim herein was to neuromodulate this segment by electrical stimulation. METHODS: Eight patients with a permanent colostomy underwent perineal antropyloric segment transposition followed by neural anastomosis of its anterior vagus branch to pudendal nerve branch in the perineum. Perineal antropyloric graft was assessed for its functional integrity and electrophysiological effects. Nerve stimulation was done by surface stimulation technique, using a customized stimulation protocol for smooth muscle. Antral pressures were recorded on voluntary attempts and on nerve stimulation with simultaneous concentric needle electromyography of the perineal antropylorus. KEY RESULTS: The antral segment showed slow spontaneous contractions (2-3/min) on digital examination, endoscopy, and electrophysiology. Stimulated antropyloric electromyography showed a latency of 2-5 s with a differential rise in amplitude (mean range 58.57-998.75 µV) according to the frequency of stimulation (range 10-150 Hz). An average latency of 10 s in relation to rise in the antral pressure was observed on pudendal nerve stimulation. Triggering of the intrinsic rhythm was observed in patients where it was initially absent. Voluntary attempts at contraction also showed a rise in perineally transposed antral pressure. CONCLUSIONS & INFERENCES: Spontaneous rhythm, its generation after electrical stimulation, and response to voluntary contraction demonstrates the viability and functional reinnervation of the perineally transposed antropyloric segment. Rise in pressure on electrical stimulation shows evidence for its neuromodulation.
Assuntos
Canal Anal/fisiopatologia , Canal Anal/cirurgia , Incontinência Fecal/cirurgia , Nervo Pudendo/fisiopatologia , Piloro/fisiopatologia , Piloro/transplante , Adolescente , Adulto , Canal Anal/inervação , Anastomose Cirúrgica , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piloro/inervação , Procedimentos de Cirurgia Plástica , Adulto JovemRESUMO
PURPOSE: Perineal transposition of the antropyloric valve following an anorectal excision as a substitute for a permanent colostomy has recently been reported in humans. However, the problem of neural control still remains in these patients. Our aim herein was to study the anatomical feasibility of an anastomosis between the pudendal nerve branches (inferior rectal nerve) innervating the external anal sphincter and the anterior vagal branches of the perineally-transposed antropyloric segment in cadavers. METHODS: The antropyloric segment, along with its carefully dissected branch of the anterior vagus, was mobilized based on the left gastroepiploic pedicle in six fresh human cadavers. The antropyloric valve was then transposed in the perineum after the pudendal nerve branches had been dissected out, and an approximation of these two nerves was performed to ascertain the technical feasibility of their neural anastomosis. RESULTS: The anterior vagus innervating the antropylorus could be harvested in all cadavers below the hepatic division of the main vagus trunk. The inferior rectal nerve or its branches were found consistently around the 3 or the 9 o'clock position in the ischioanal fossa. An anatomical tension-free approximation of the anterior vagus branch (of the transposed antropyloric segment) to the inferior rectal nerve in the perineum was feasible in all the cadavers studied. CONCLUSION: An inferior rectal nerve anastomosis with the anterior vagal branch of the perineally-transposed antropyloric segment can be achieved anatomically. This preliminary step can be the basis for future animal studies and subsequent clinical application of the procedure for possible neural control of the transposed antropyloric segment in the perineum.