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1.
BMC Gastroenterol ; 23(1): 416, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017468

RESUMEN

Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.


Asunto(s)
Cavidad Abdominal , Colestasis , Neuroma , Humanos , Calidad de Vida , Neuroma/diagnóstico , Neuroma/epidemiología , Neuroma/etiología , Colestasis/etiología , Cavidad Abdominal/patología , Factores de Riesgo
2.
World J Surg Oncol ; 21(1): 276, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37658360

RESUMEN

BACKGROUND: The optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients. METHOD: We retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis. RESULT: Among 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI < 6 group. However, the overall survival (OS) (p = 0.012) and disease-free survival (DFS) (p = 0.013) of the patients in the 4≦TI < 6 group were better than those in the 6≦TI≦8 group. Subgroup analysis found that the above conclusions still apply in age ≥ 60, non-anemic patients, and patients who underwent R0 resection. OS was inversely correlated with TI in patients without preoperative jaundice. DFS was negatively correlated with TI in patients with preoperative jaundice. Multivariate analysis showed that the prolongation of TI after NAC to surgery was an independent prognostic risk factor for OS and DFS. CONCLUSIONS: Patients with SLM may be a better choice for surgery within 4-6 weeks after receiving NAC. Although patients with SLM undergoing surgery 4-6 weeks after NAC has a higher rate of postoperative complications, radical surgery is still recommended for a better survival benefit.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Terapia Neoadyuvante , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía
3.
BMC Gastroenterol ; 21(1): 329, 2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34433421

RESUMEN

BACKGROUND: Mixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions. METHODS: In all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed. RESULTS: The 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477-28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409-79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719-19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451-10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100-0.705 P = 0.008) were independent predictors of overall survival. CONCLUSIONS: Mixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.


Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias Gástricas , Adenocarcinoma/cirugía , Ampolla Hepatopancreática/cirugía , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/cirugía
4.
Surg Today ; 51(8): 1352-1360, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33651221

RESUMEN

PURPOSE: Elevated fibrinogen (Fbg) levels contribute to tumor progression and metastasis. However, little is known regarding the association of the clinicopathological characteristics and the prognosis of hilar cholangiocarcinoma (HC) with plasma fibrinogen. METHODS: Data on the plasma Fbg levels, clinicopathological characteristics, and overall survival were retrospectively collected. Plasma fibrinogen concentrations over 4.0 g/L were classified as hyperfibrinogen, elevated fibrinogen, or abnormal fibrinogen levels. We then analyzed the relationships among plasma fibrinogen level, clinicopathological features, and patient prognosis. RESULTS: A total of 171 HC patients were included. An elevated plasma fibrinogen level was associated with lymph-node metastasis (P < 0.001), the AJCC stage (P < 0.001), the surgical margin (P = 0.005), and vascular invasion (P = 0.027). Univariate analyses revealed that preoperative plasma fibrinogen (P < 0.001), operative blood loss (P = 0.044), vascular invasion (P < 0.001), CA19-9 (P = 0.003), surgical margin (P < 0.001), T stage (P < 0.001), histologic differentiation (P = 0.007), and lymph-node metastasis (P < 0.001) were associated with OS. The survival time of patients with high Fbg levels was shorter than that of patients with normal fibrinogen levels (P < 0.001). Furthermore, a multivariate analysis showed that fibrinogen was negatively and independently associated with the HC prognosis (P = 0.029). CONCLUSIONS: An elevated plasma Fbg level was associated with lymph-node metastasis, vascular invasion, the surgical margin, and the tumor stage, and the Fbg level might therefore be an independent factor associated with poor outcomes in HC patients.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Fibrinógeno , Tumor de Klatskin/diagnóstico , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Tumor de Klatskin/mortalidad , Tumor de Klatskin/patología , Tumor de Klatskin/cirugía , Metástasis Linfática , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Invasividad Neoplásica , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
5.
J Cell Mol Med ; 23(3): 2184-2193, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30648816

RESUMEN

The aim of this research was to determine the underlying mechanism of activating transcription factor 3 (ATF3) on cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT). The differentially expressed mRNAs in cholangiocarcinoma (CC) and its adjacent tissues were screened by microarray analysis, and the expression of ATF3 was detected through Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot. The expression of EMT markers and p53-related proteins was analysed by Western blot. Analyses using the Cell Counting Kit-8 and TUNEL were performed to assess the rate of apoptosis and cell proliferation. Scratch wound and transwell assays were performed to study cell migration and invasion. Activating transcription factor 3 was restrained in CC cell lines and tissues and inhibited EMT while activating the p53 signalling pathway. Knockdown of ATF3 promoted cell proliferation but reduced the rate of apoptosis by inhibiting p53 signalling. Cell migration and invasion can be strengthened by ATF3 through activating the p53 signalling pathway.


Asunto(s)
Factor de Transcripción Activador 3/genética , Neoplasias de los Conductos Biliares/genética , Colangiocarcinoma/genética , Transición Epitelial-Mesenquimal/genética , Transducción de Señal/genética , Proteína p53 Supresora de Tumor/genética , Factor de Transcripción Activador 3/metabolismo , Apoptosis/genética , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Interferencia de ARN , Proteína p53 Supresora de Tumor/metabolismo
6.
FASEB J ; : fj201800113R, 2018 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-29799789

RESUMEN

Growing evidence indicates that microRNAs are involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the functional mechanisms of miR-205 in HCC remain largely unknown. Here, we demonstrate that miR-205 expression was significantly down-regulated in HCC tissues and cell lines and was correlated with metastatic pathologic features and shorter disease-free and overall survival. Overexpression of miR-205 dramatically inhibited HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) in vitro, and tumor growth in vivo. We subsequently identified semaphorin 4C (SEMA4C) as a novel target of miR-205. Furthermore, high expression levels of SEMA4C were frequently found in HCC tissues and were associated with poor prognosis. Ectopic expression of SEMA4C restored the suppressive effect of overexpressed miR-205 on migration, invasion, and EMT. Taken together, our findings provide new insight into the critical role of miR-205 in regulating tumor growth, invasion, and EMT of HCC, suggesting miR-205 may serve as a promising therapeutic target and novel prognostic indicator for patients with HCC.-Lu, J., Lin, Y., Li, F., Ye, H., Zhou, R., Jin, Y., Li, B., Xiong, X., Cheng, N. MiR-205 suppresses tumor growth, invasion and epithelial-mesenchymal transition by targeting SEMA4C in hepatocellular carcinoma.

7.
J Surg Oncol ; 120(8): 1341-1349, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31612493

RESUMEN

BACKGROUND: The presence of mucinous component has been indicated to have a prognostic value in adenocarcinoma. However, little is known regarding the clinicopathological characteristics and prognosis of hilar cholangiocarcinoma (HC) with mucinous component (HCM). METHODS: Between January 1996 and December 2014, a total of 61 HCM patients who underwent curative-intent resection at West China Hospital were retrospectively reviewed. The clinicopathological characteristics and survival of these patients were compared with a large cohort of 217 surgically resected conventional HC patients during the same period. RESULTS: The clinicopathological characteristics of HCM were distinct from conventional HC, including higher CA19-9 levels, larger tumor sizes, less differentiation, and a high frequency of liver parenchyma invasion, portal vein invasion, and lymphovascular invasion. HCM patients showed significantly worse recurrence-free survival (13.4 vs 23.9 months; P = .011) and overall survival (18.2 vs 32.1 months; P = .019) compared with conventional HC patients. Multivariate analysis confirmed liver parenchyma invasion, N stage, surgical margin, and histological grade as independent prognostic factors influencing overall survival in HCM patients. CONCLUSION: HCM showed distinct clinicopathological features, more aggressive biological behaviors, and poor prognosis in comparison with conventional HC. Therefore, the mucinous component is an adverse prognostic factor for HC.


Asunto(s)
Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Tumor de Klatskin/mortalidad , Tumor de Klatskin/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Carbohidratos Asociados a Tumores/sangre , Neoplasias de los Conductos Biliares/terapia , Quimioterapia Adyuvante , Femenino , Humanos , Tumor de Klatskin/terapia , Neoplasias Hepáticas/secundario , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos
8.
Cochrane Database Syst Rev ; 6: CD011670, 2017 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-28574593

RESUMEN

BACKGROUND: Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms and avoid complications. The timing of appendicectomy for appendiceal phlegmon or abscess is controversial. OBJECTIVES: To assess the effects of early versus delayed appendicectomy for appendiceal phlegmon or abscess, in terms of overall morbidity and mortality. SEARCH METHODS: We searched the Cochrane Library (CENTRAL; 2016, Issue 7), MEDLINE Ovid (1950 to 23 August 2016), Embase Ovid (1974 to 23 August 2016), Science Citation Index Expanded (1900 to 23 August 2016), and the Chinese Biomedical Literature Database (CBM) (1978 to 23 August 2016). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform search portal (23 August 2016) and ClinicalTrials.gov (23 August 2016) for ongoing trials. SELECTION CRITERIA: We included all individual and cluster-randomised controlled trials, irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We included two randomised controlled trials with a total of 80 participants in this review. 1. Early versus delayed open appendicectomy for appendiceal phlegmonForty participants (paediatric and adults) with appendiceal phlegmon were randomised either to early appendicectomy (appendicectomy as soon as appendiceal mass resolved within the same admission) (n = 20), or to delayed appendicectomy (initial conservative treatment followed by interval appendicectomy six weeks later) (n = 20). The trial was at high risk of bias. There was no mortality in either group. There is insufficient evidence to determine the effect of using either early or delayed open appendicectomy onoverall morbidity (RR 13.00; 95% CI 0.78 to 216.39; very low-quality evidence), the proportion of participants who developed wound infection (RR 9.00; 95% CI 0.52 to 156.91; very low quality evidence) or faecal fistula (RR 3.00; 95% CI 0.13 to 69.52; very low quality evidence). The quality of evidence for increased length of hospital stay and time away from normal activities in the early appendicectomy group (MD 6.70 days; 95% CI 2.76 to 10.64, and MD 5.00 days; 95% CI 1.52 to 8.48, respectively) is very low quality evidence. The trial reported neither quality of life nor pain outcomes. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscessForty paediatric participants with appendiceal abscess were randomised either to early appendicectomy (emergent laparoscopic appendicectomy) (n = 20) or to delayed appendicectomy (initial conservative treatment followed by interval laparoscopic appendicectomy 10 weeks later) (n = 20). The trial was at high risk of bias. The trial did not report on overall morbidity or complications. There was no mortality in either group. We do not have sufficient evidence to determine the effects of using either early or delayed laparoscopic appendicectomy for outcomes relating to hospital stay between the groups (MD -0.20 days; 95% CI -3.54 to 3.14; very low quality of evidence). Health-related quality of life was measured with the Pediatric Quality of Life Scale-Version 4.0 questionnaire (a scale of 0 to 100 with higher values indicating a better quality of life). Health-related quality of life score measured at 12 weeks after appendicectomy was higher in the early appendicectomy group than in the delayed appendicectomy group (MD 12.40 points; 95% CI 9.78 to 15.02) but the quality of evidence was very low. This trial reported neither the pain nor the time away from normal activities. AUTHORS' CONCLUSIONS: It is unclear whether early appendicectomy prevents complications compared to delayed appendicectomy for people with appendiceal phlegmon or abscess. The evidence indicating increased length of hospital stay and time away from normal activities in people with early open appendicectomy is of very low quality. The evidence for better health-related quality of life following early laparoscopic appendicectomy compared with delayed appendicectomy is based on very low quality evidence. For both comparisons addressed in this review, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy.Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities, quality of life and the length of hospital stay.


Asunto(s)
Absceso/cirugía , Apendicectomía/métodos , Apendicitis/cirugía , Celulitis (Flemón)/cirugía , Tiempo de Tratamiento , Absceso/complicaciones , Absceso/mortalidad , Adulto , Apendicectomía/mortalidad , Apendicitis/complicaciones , Apendicitis/mortalidad , Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/mortalidad , Niño , Tratamiento Conservador , Urgencias Médicas , Humanos , Tiempo de Internación , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
J Surg Oncol ; 114(2): 202-10, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27199001

RESUMEN

INTRODUCTION: Lymphocytes are an integral part of lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI). Both LMR and PNI which reflect body's inflammatory and nutritional status can be obtained from routine blood and biochemical test conveniently. Little evidence concerning the prognostic value of LMR and PNI in hepatocellular carcinoma (HCC) patients has been published. This study aimed to investigate the prognostic value of LMR and PNI in hepatitis B virals (HBV)-associated HCC patients who underwent curative hepatectomy. METHODS: Between January 2008 and June 2013, 450 surgically treated HCC patients were retrospectively analyzed. Clinicopathological parameters, LMR and PNI were collected and compared. The multivariate analysis was performed to indentify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) rates were also compared. RESULTS: Tumor size, vascular invasion, alpha fetoprotein level, LMR and PNI were independent prognostic factors for OS. Tumor number, tumor size, vascular invasion, LMR and PNI were independent prognostic factors for RFS. Either a high LMR or PNI could predict favorable OS and RFS in surgically treated HCC patients and vice versa. CONCLUSIONS: Both LMR and PNI were significant independent predictors that can predict survival outcomes in HBV-associated HCC patients who received curative hepatectomy. J. Surg. Oncol. 2016;114:202-210. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/mortalidad , Hepatitis B/complicaciones , Neoplasias Hepáticas/cirugía , Linfocitos , Monocitos , Evaluación Nutricional , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Femenino , Estudios de Seguimiento , Predicción , Humanos , Recuento de Leucocitos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Adulto Joven
10.
Cochrane Database Syst Rev ; 2: CD009621, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26876721

RESUMEN

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched The Cochrane Library (2015, Issue 7), MEDLINE (1946 to 26 August 2015), EMBASE (1980 to 26 August 2015), Science Citation Index Expanded (1900 to 26 August 2015), and Chinese Biomedical Literature Database (CBM) (1978 to 26 August 2015). SELECTION CRITERIA: We included all randomized controlled trials that compared fibrin sealant group (fibrin glue or fibrin sealant patch) versus control group (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We included nine trials involving 1095 participants who were randomized to the fibrin sealant group (N = 550) and the control group (N = 545) after pancreatic surgery. All of the trials were at high risk of bias. There was no evidence of differences in overall postoperative pancreatic fistula (fibrin sealant 29.6%; control 31.0%; RR 0.93, 95% CI 0.71 to 1.21; P = 0.58; nine studies; low-quality evidence), postoperative mortality (3.1% versus 2.1%; Peto OR 1.29, 95% CI 0.59 to 2.82; P = 0.53; eight studies; very low-quality evidence), overall postoperative morbidity (29.6% versus 28.9%; RR 1.04, 95% CI 0.82 to 1.32; P = 0.77; five studies), reoperation rate (8.7% versus 10.7%; RR 0.80, 95% CI 0.53 to 1.21; P = 0.29; five studies), or length of hospital stay (12.9 days versus 13.1 days; MD -0.73 days, 95% CI -2.20 to 0.74; P = 0.331; six studies) between the groups. The proportion of postoperative pancreatic fistula that was clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was inadequate evidence to establish the effect of fibrin sealants on clinically significant postoperative pancreatic fistula (9.4% versus 13.4%; RR 0.72, 95% CI 0.42 to 1.21; P = 0.21; three studies). Quality of life and cost effectiveness were not reported in any of the trials. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants do not seem to prevent postoperative pancreatic fistula in people undergoing pancreatic surgery.


Asunto(s)
Adhesivo de Tejido de Fibrina/uso terapéutico , Páncreas/cirugía , Fístula Pancreática/prevención & control , Complicaciones Posoperatorias/prevención & control , Adhesivos Tisulares/uso terapéutico , Adhesivo de Tejido de Fibrina/efectos adversos , Humanos , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como Asunto , Reoperación/estadística & datos numéricos
11.
Ann Surg Oncol ; 22 Suppl 3: S1048-56, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26286198

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. METHODS: From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. RESULTS: The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p < 0.001). On multivariable analysis, macrovascular invasion, satellite nodules, and R1/R2 resection were identified as independent risk factors for shorter disease-free survival and OS. CONCLUSIONS: The presence of SC in HCC was uncommon, and was associated with much poorer prognosis than ordinary HCC. Radical resection with negative margin is essential for improving the prognosis. Future prospective studies are warranted to determine if recurrent patients can benefit from postoperative adjuvant therapies.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Sarcoma/patología , Adulto , Anciano , Carcinoma Hepatocelular/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
12.
J Surg Res ; 193(1): 196-201, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25151466

RESUMEN

BACKGROUND: Gallbladder cancer (GBC) is rare but the most common malignancy of biliary tract with a dismal prognosis. The early diagnosis and surgical treatment of GBC offers the only chance of long-term survival. Despite advances in radiological imaging, early diagnosis of GBC is still rarely achieved without histopathology. In our hospital, routine histologic examination of all resected gallbladder specimens has been standard practice. This study seeks to define whether selective histologic examination for gallbladder specimens based on preoperative imaging or intraoperative findings is justified. MATERIALS AND METHODS: From September 2008-September 2013, all histopathology reports of gallbladder specimens after elective cholecystectomy were retrospectively analyzed in a single surgical unit. Preoperative imaging, intraoperative findings, and histology notes were analyzed in all cases. RESULTS: Out of 14,369 (60% female and 40% male) patients undergoing cholecystectomy, GBC was found in only 46 cases (0.32%). More than one fifth (10/46) of GBC patients presented with acute cholecutitis (AC). All 10 AC patients coexisted with GBC harbored "significantly inflamed' gallbladders, and about 83.49% AC patients were judged with "significant inflammation." Carcinoma in situ and early GBC (T1a, T1b) accounted for 61% of all cases. Only two patients with Tis and T1a respectively did not show suspicious lesion on preoperative and intraoperative findings, but for the remaining cases (44/46), GBC was suspected either by preoperative imaging and/or intraoperative findings. CONCLUSIONS: Almost all cases of invasive GBC will show macroscopic abnormalities following examination by a simple procedure-a full dissection, inspection, and palpation of the gallbladder. Any patient with early GBCs "missed" on macroscopic examination can still receive the appropriate treatment by the cholecystectomy alone. The gallbladder should be sent for histology only if macroscopic examination raises suspicion. This selective policy is more cost-effective, and does not appear to compromise patients outcome.


Asunto(s)
Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/cirugía , Colecistectomía/mortalidad , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Procedimientos Innecesarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Vesícula Biliar/patología , Vesícula Biliar/cirugía , Humanos , Masculino , Persona de Mediana Edad , Patología Clínica/métodos , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Adulto Joven
13.
Cochrane Database Syst Rev ; (2): CD010168, 2015 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-25914903

RESUMEN

BACKGROUND: Appendectomy, the surgical removal of the appendix, is performed primarily for acute appendicitis. Patients who undergo appendectomy for complicated appendicitis, defined as gangrenous or perforated appendicitis, are more likely to suffer from postoperative complications. The routine use of abdominal drainage to reduce postoperative complications after appendectomy for complicated appendicitis is controversial. OBJECTIVES: To assess the safety and efficacy of abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis. SEARCH METHODS: We searched The Cochrane Library (Issue 1, 2014), MEDLINE (1950 to February 2014), EMBASE (1974 to February 2014), Science Citation Index Expanded (1900 to February 2014), and Chinese Biomedical Literature Database (CBM) (1978 to February 2014). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage and no drainage in patients undergoing emergency open appendectomy for complicated appendicitis. DATA COLLECTION AND ANALYSIS: Two review authors identified the trials for inclusion, collected the data, and assessed the risk of bias independently. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We included five trials involving 453 patients with complicated appendicitis who were randomised to the drainage group (n = 228) and the no drainage group (n = 225) after emergency open appendectomies. All of the trials were at a high risk of bias. There were no significant differences between the two groups in the rates of intra-peritoneal abscess or wound infection. The hospital stay was longer in the drainage group than in the no drainage group (MD 2.04 days; 95% CI 1.46 to 2.62) (34.4% increase of an 'average' hospital stay). AUTHORS' CONCLUSIONS: The quality of the current evidence is very low. It is not clear whether routine abdominal drainage has any effect on the prevention of intra-peritoneal abscess after open appendectomy for complicated appendicitis. Abdominal drainage after an emergency open appendectomy may be associated with delayed hospital discharge for patients with complicated appendicitis.


Asunto(s)
Absceso Abdominal/prevención & control , Apendicectomía/efectos adversos , Apendicitis/cirugía , Drenaje/métodos , Enfermedades Peritoneales/prevención & control , Complicaciones Posoperatorias/prevención & control , Apendicitis/complicaciones , Urgencias Médicas , Humanos , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Hepatobiliary Pancreat Dis Int ; 14(3): 300-4, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26063032

RESUMEN

BACKGROUND: Unexpected gallbladder cancer may present with acute cholecystitis-like manifestations. Some authors recommended that frozen section analysis should be performed during laparoscopic cholecystectomy for all cases of acute cholecystitis. Others advocate selective use of frozen section analysis based on gross examination of the specimen by the surgeon. The aim of the present study was to evaluate whether surgeons could effectively identify suspected gallbladder with macroscopic examination alone. If not, is routine frozen section analysis worth advocating? METHODS: A total of 1162 patients with acute cholecystitis who had undergone simple cholecystectomy in our hospital from February 2009 to February 2014 were enrolled in the study. The data of patients with acute cholecystitis especially those with concurrent gallbladder cancer in terms of clinical characteristics, operative records, frozen section diagnosis and histopathology reports were analyzed. RESULTS: Thirteen patients with acute cholecystitis were found to have concurrent gallbladder cancer, with an incidence of 1.1% in acute cholecystitis. Forty patients with acute cholecystitis were suspected to have gallbladder cancer by macroscopic examination and specimens were taken for frozen section analysis. Six patients with gallbladder cancer were correctly identified by macroscopic examination alone but 7 patients with gallbladder cancer missed, including 3 patients with advanced cancer (2 T3 and 1 T2). Meanwhile, in 6 gallbladder cancer specimens sent for frozen section analysis, 3 early gallbladder cancers (2 Tis and 1 T1a) were missed by frozen section analysis. However, the remaining 3 patients with advanced gallbladder cancers (2 T3 and 1 T2) were correctly diagnosed. CONCLUSIONS: The incidence of comorbidity of gallbladder cancer and acute cholecystitis is higher than that of non-acute cholecystitis. The accurate diagnosis of gallbladder cancer by surgeons is poor and frozen section analysis is necessary.


Asunto(s)
Adenocarcinoma/patología , Carcinoma Adenoescamoso/patología , Colecistectomía , Colecistitis Aguda/cirugía , Secciones por Congelación , Neoplasias de la Vesícula Biliar/patología , Vesícula Biliar/cirugía , Cuidados Intraoperatorios/métodos , Adenocarcinoma/epidemiología , Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/patología , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/epidemiología , China , Colecistitis Aguda/diagnóstico , Colecistitis Aguda/epidemiología , Comorbilidad , Errores Diagnósticos , Femenino , Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas
15.
HPB (Oxford) ; 17(3): 195-201, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25209740

RESUMEN

OBJECTIVE: The aim of this study was to compare the effectiveness of percutaneous needle aspiration (PNA) and percutaneous catheter drainage (PCD) in the management of liver abscess. METHODS: Electronic searches (Cochrane Library, MEDLINE, EMBASE, SCIE) were conducted to identify randomized controlled trials (RCTs) comparing PNA and PCD. A meta-analysis was subsequently performed. RESULTS: A total of five RCTs covering 306 patients were included. The meta-analysis showed that outcomes in patients treated with PCD were superior to those in patients treated with PNA in terms of success rate [relative risk (RR): 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.04], clinical improvement [standardized mean difference (SMD): -0.73, 95% CI 0.36-1.11; P = 0.0001] and days to achieve a 50% reduction in abscess cavity size (SMD: -1.08, 95% CI 0.64-1.53; P < 0.00001). No significant differences were found in duration of hospitalization (mean difference: -0.17, 95% CI -2.10 to 1.75; P = 0.86) or procedure-related complications (RR: 0.50, 95% CI 0.10-2.63; P = 0.41). Days to achieve the total or near total resolution of the abscess cavity and mortality were not calculated because data in the RCTs in the meta-analysis were insufficient. CONCLUSIONS: Both PNA and PCD are safe methods of draining liver abscesses. However, PCD is more effective than PNA because it facilitates a higher success rate, reduces the time required to achieve clinical relief and supports a 50% reduction in abscess cavity size. However, among successfully treated patients, the outcomes of PNA are comparable with those of PCD.


Asunto(s)
Cateterismo/métodos , Drenaje/métodos , Absceso Hepático/terapia , Succión/métodos , Drenaje/instrumentación , Femenino , Humanos , Absceso Hepático/diagnóstico por imagen , Absceso Hepático/mortalidad , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Ultrasonografía Intervencional
16.
Hepatobiliary Pancreat Dis Int ; 13(5): 464-73, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25308356

RESUMEN

BACKGROUND: Acute cellular rejection (ACR) after liver transplantation (LT) is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid (UDCA) reduced the incidence of ACR significantly. However, others have shown contradictory conclusion. Therefore, we performed a meta-analysis of rigorous randomized controlled trials (RCTs) to determine the efficacy of UDCA in reducing ACR after LT. DATA SOURCES: All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science (from January 1981 to March 2012). There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually. RESULTS: A total of 234 patients from four high-quality RCTs (Jadad score 4 to 5) were included in this meta-analysis. Prophylactic use of UDCA did not decrease the incidence of ACR (RR: 0.94, 95% CI: 0.77-1.16, P>0.05), steroid-resistant rejection (RR: 0.77, 95% CI: 0.47-1.27, P>0.05) and the number of patients with the multiple episodes of ACR (RR: 0.60, 95% CI: 0.28-1.30, P>0.05). Different intervention programs (high-dose vs low-dose UDCA; early vs delayed UDCA treatment) also did not alter the outcomes. CONCLUSIONS: UDCA, as an adjuvant treatment, was not able to prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.


Asunto(s)
Colagogos y Coleréticos/uso terapéutico , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Hígado , Ácido Ursodesoxicólico/uso terapéutico , Quimioterapia Adyuvante/métodos , Colagogos y Coleréticos/administración & dosificación , Humanos , Inmunidad Celular , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido Ursodesoxicólico/administración & dosificación
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(4): 628-32, 2014 Jul.
Artículo en Zh | MEDLINE | ID: mdl-25286689

RESUMEN

OBJECTIVE: To explore the risk factors of hepatolithasis-associated intrahepatic cholangiocarcinoma (HICC) and the clinical value of serum tumor-related markers for the detection of HICC. METHODS: Clinical data were collected from 58 patients pathologically diagnosed as HICC between 2005 and 2011 in West China Hospital of Sichuan University and 189 patients diagnosed as hepatolithiasis alone in the same period as matched control group. Logistic regression analysis was used to detect the independent risk factors of HICC and ROCs curve were constructed to assess the diagnostic value of CA199, CEA, GGT and ALP. RESULTS: The patients in both HICC group and control group presented similar clinical symptoms except weight loss. The results of univariate analysis suggested cholangioenterostomy (P < 0.001), early stone removal (OR = 0.001), family history of cancer (P = 0.001) were associated with the incidence of HICC. The results of Multivariate analysis suggested diabetes mellitus (OR = 3.621, 95% CI: 1.333-9.834, P = 0.012), family history of cancer (OR = 16.830, 95% CI: 1.937-146.21, P = 0.010), cholangioenterostomy (OR = 5.115, 95% CI: 1.733-15.098, P = 0.003), early removal of stone (OR = 0.315, 95% CI: 0.128-0.771, P = 0.011) and CA199 > 100 IU/mL (OR = 5.478, 95% CI: 2.539-11.820, P < 0.001) were independent risk factors for hICC. Serum CA199 and CEA level presented low diagnostic accuracy, a combined test (CA199 > 100 IU/mL or CEA > 5 ng/mL) showed better diagnostic performance with a 71.05% of sensitivity and 82.05% of specificity. CONCLUSION: Cholangioenterostomy, diabetes, early and complete stone removal were independent risk factors for hepatolithiasis-associated ICC. A combined test of CA199 and CEA could be an effective detecting tool for HICC.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Biomarcadores de Tumor/sangre , Colangiocarcinoma/diagnóstico , Neoplasias de los Conductos Biliares/sangre , Conductos Biliares Intrahepáticos , China , Colangiocarcinoma/sangre , Humanos , Factores de Riesgo , Sensibilidad y Especificidad
18.
Oncogene ; 43(14): 1050-1062, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38374407

RESUMEN

In a previous study, we discovered that the level of lnc-TSPAN12 was significantly elevated in hepatocellular carcinoma (HCC) and correlated with a low survival rate. However, the function and mechanism of lnc-TSPAN12 in modulating epithelial-mesenchymal transition (EMT) and metastasis in HCC remains poorly understood. This study demonstrates that lnc-TSPAN12 positively influences migration, invasion, and EMT of HCC cells in vitro and promotes hepatic metastasis in vivo. The modification of N6-methyladenosine, driven by METTL3, is essential for the stability of lnc-TSPAN12, which may partially contribute to the upregulation of lnc-TSPAN12. Mechanistically, lnc-TSPAN12 exhibits direct interactions with EIF3I and SENP1, acting as a scaffold to enhance the SENP1-EIF3I interaction. As a result, the SUMOylation of EIF3I is inhibited, preventing its ubiquitin-mediated degradation. Ultimately, this activates the Wnt/ß-catenin signaling pathway, stimulating EMT and metastasis in HCC. Our findings shed light on the regulatory mechanism of lnc-TSPAN12 in HCC metastasis and identify the lnc-TSPAN12-EIF3I/SENP1 axis as a novel therapeutic target for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Tetraspaninas , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Transición Epitelial-Mesenquimal , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Largo no Codificante/genética , Vía de Señalización Wnt
19.
Signal Transduct Target Ther ; 9(1): 107, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38697972

RESUMEN

Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.


Asunto(s)
Colangiocarcinoma , Exosomas , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/sangre , Colangiocarcinoma/genética , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/sangre , Colangiocarcinoma/patología , Exosomas/genética , Masculino , Femenino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/patología , Pronóstico , Colestasis/genética , Colestasis/diagnóstico , Colestasis/sangre
20.
Cochrane Database Syst Rev ; (1): CD009569, 2013 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-23440841

RESUMEN

BACKGROUND: Laparoscopic surgery is now widely performed to treat various abdominal diseases. Currently, carbon dioxide is the most frequently used gas for insufflation of the abdominal cavity (pneumoperitoneum). Many other gases have been introduced as alternatives to carbon dioxide for establishing pneumoperitoneum. OBJECTIVES: To assess the safety, benefits, and harms of different gases for establishing pneumoperitoneum in patients undergoing laparoscopic abdominal surgery. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and Chinese Biomedical Literature Database (CBM) until September 2012. SELECTION CRITERIA: We only included randomized controlled trials comparing different gases for establishing pneumoperitoneum in patients undergoing laparoscopic abdominal surgery under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors identified the trials for inclusion, collected the data, and assessed the risk of bias independently. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Carbon dioxide pneumoperitoneum versus nitrous oxide pneumoperitoneum Three trials randomized 196 participants (the majority with low anaesthetic risk) to carbon dioxide pneumoperitoneum (n =96) or nitrous oxide pneumoperitoneum (n =100). All of the trials were of high risk of bias. Two trials (n=143) showed lower pain scores in nitrous oxide pneumoperitoneum at various time points on the first post-operative day. One trial (n=53) showed no difference in the pain scores between the groups. There were no significant differences in cardiopulmonary complications, surgical morbidity, or cardiopulmonary changes between the groups. There were no serious adverse events related to either carbon dioxide or nitrous oxide pneumoperitoneum. Carbon dioxide pneumoperitoneum versus helium pneumoperitoneum Four trials randomized 144 participants (the majority with low anaesthetic risk) to carbon dioxide pneumoperitoneum (n =75) or helium pneumoperitoneum (n =69). All of the trials were of high risk of bias. Fewer cardiopulmonary changes were observed with helium pneumoperitoneum than carbon dioxide pneumoperitoneum. There were no significant differences in cardiopulmonary complications, surgical morbidity, or pain scores. There were three serious adverse events (subcutaneous emphysema) related to helium pneumoperitoneum. Carbon dioxide pneumoperitoneum versus any other gas pneumoperitoneum There were no randomized controlled trials comparing carbon dioxide pneumoperitoneum to any other gas pneumoperitoneum. AUTHORS' CONCLUSIONS: 1. Nitrous oxide pneumoperitoneum during laparoscopic abdominal surgery appears to decrease post-operative pain in patients with low anaesthetic risk.2. Helium pneumoperitoneum decreases the cardiopulmonary changes associated with laparoscopic abdominal surgery. However, this did not translate into any clinical benefit over carbon dioxide pneumoperitoneum in patients with low anaesthetic risk.3. The safety of nitrous oxide and helium pneumoperitoneum has yet to be established. More randomized controlled trials on this topic are needed. Future trials should include more patients with high anaesthetic risk. Furthermore, such trials need to use adequate methods to reduce the risk of bias.


Asunto(s)
Abdomen/cirugía , Dióxido de Carbono , Helio , Laparoscopía/métodos , Óxido Nitroso , Neumoperitoneo Artificial/métodos , Dióxido de Carbono/efectos adversos , Helio/efectos adversos , Humanos , Óxido Nitroso/efectos adversos , Neumoperitoneo Artificial/efectos adversos
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