Impact of increased utilization of neoadjuvant chemotherapy on survival in patients with advanced ovarian cancer: experience from a comprehensive cancer center / 부인종양

OBJECTIVE: The choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NAC) in advanced ovarian cancer remains controversial. We evaluated NAC use in our center before and after results from a randomized trial were published, with the aim to determine the impact of changes in the neoadjuvant strategy on survival in advanced-stage ovarian cancer. METHODS: We retrospectively investigated the clinical course of 435 patients with ovarian, tubal, or peritoneal carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV). According to the period of treatment, we stratified patients into a control group (n=216; diagnosed between 2006 and 2010; 83.8% underwent PDS) and a study group (n=219; diagnosed between 2011 and 2014; 48.9% received NAC followed by interval debulking surgery [IDS]). RESULTS: There were no between-group differences in age, body mass index, histology findings, or tumor grade. Compared to patients in the control group, those in the study group were more likely to receive NAC followed by IDS as first-line treatment (48.9% vs. 16.2%; p < 0.001), cytoreductive surgery to no-residual disease (21.5% vs. 10.2%; p < 0.001), or radical surgery (57.5% vs. 35.6%; p < 0.001). However, there was no between-group difference in postoperative morbidity. Kaplan-Meier analysis showed no between-group differences in progression-free or overall survival (p=0.449 and 0.952, respectively). CONCLUSION: NAC incorporation resulted in increased optimal cytoreduction rates although no significant differences in survival outcomes were noted. NAC is advantageous for patients with high perioperative morbidity or unresectable disease.

Delayed hemorrhage effect of local anesthesia with epinephrine in the loop electrosurgical excisional procedure

OBJECTIVE: The aim of this study was to investigate factors preventing delayed hemorrhage after the loop electrosurgical excisional procedure (LEEP). METHODS: Medical records of patients who underwent LEEP at one university affiliated hospital from October 2013 to January 2015 were reviewed. Patients with or without delayed hemorrhage were classified. LEEP was performed either in an operating room under general anesthesia or in a procedure room with local anesthesia in the outpatient clinic. Delayed hemorrhage was defined as excisional site bleeding occurring between 1 and 30 days after the LEEP requiring intervention such as electro-cauterization, gauze packing, or application of another hemostatic agent. RESULTS: During the study period, 369 patients underwent LEEP. Twenty-three (6.2%) patients with delayed hemorrhage returned to our hospital either to the outpatient clinic or to the emergency unit. A third of the population (103, 27.9%) underwent LEEP in the operating room under general anesthesia without injection of local anesthesia. The remaining patients (266, 72.1%) underwent LEEP with local anesthesia (lidocaine HCl 2% with epinephrine 1:100,000) in the office procedure room. Patients given local anesthesia including epinephrine had significantly lower delayed hemorrhage compared to patients with general anesthesia without injection of local anesthesia (P=0.001). Hemostats, such as fibrin glue or patch, were used for the majority of patients (346, 93.8%) during the procedure. However, using hemostats was not statistically associated with delayed hemorrhage (P=0.163). CONCLUSION: Local anesthesia with the powerful vasoconstrictor epinephrine is effective not only to control perioperative bleeding, but also to prevent delayed hemorrhage after LEEP.

The ON-Q pain management system in elective gynecology oncologic surgery: Management of postoperative surgical site pain compared to intravenous patient-controlled analgesia

OBJECTIVE: The goal of this study was to compare postoperative surgical site pain in gynecologic cancer patients who underwent elective extended lower midline laparotomy and managed their pain with either the ON-Q pain management system (surgical incision site pain relief system, ON-Q pump) or an intravenous patient-controlled analgesia pump (IV PCA). METHODS: Twenty gynecologic cancer patients who underwent elective extended lower midline laparotomy were divided into two groups. One group received a 72-hour continuous wound perfusion of the local anesthetic ropivacaine (0.5%, study group) into the supraperitoneal layer of the abdominal incision through the ON-Q pump. The other group received intravenous infusion pump of patient-controlled analgesia (fentanyl citrate 20 mg/mL . kg+ondansetron hydrochloride 16 mg/8 mL+normal saline). Postoperative pain was assessed immediately and at 6, 24, 48, 72, and 96 hours after surgery using the visual analogue scale. RESULTS: Postoperative surgical site pain scores at 24, 48, and 72 hours after surgery were lower in the ON-Q group than the IV PCA group. Pain scores at 24 hours and 48 hours after surgery were significantly different between the two groups (P=0.023, P<0.001). Overall painkiller administration was higher in the ON-Q group but this difference was not statistically significant (5.1 vs. 4.3, P=0.481). CONCLUSION: This study revealed that the ON-Q pain management system is a more effective approach than IV PCA for acute postoperative surgical site pain relief after extended lower midline laparotomy in gynecologic cancer patients.

Microarray Analysis of Gene Expression During Differentiation of Human Mesenchymal Stem Cells Treated with Vitamin E in vitro into Osteoblasts

OBJECTIVE: Supplementation with vitamin E is able to protect bone against free radical-induced elevation of bone-resorbing cytokines. We examined gene expression by microarray analysis during the differentiation of human mesenchymal stem cells treated with vitamin E into osteoblasts in vitro. METHODS: Human bone marrow stem cells were cultured in osteogenic differentiation medium and vitamin E was added. A colorimetric immunoassay for the quantification of cell proliferation was used to measure osteoblast differentiation. Gene expression was analyzed using a microarray technique. We also used a real time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: It was found that vitamin E enhanced cell proliferation when compared to cells cultured in media without vitamin E. We focused on 68 genes which are related to osteogenesis and osteoclastogenesis. Alkaline phosphatase, transforming growth factor-beta 1, fibroblast growth factor receptor 1, matrix metalloproteinase 2, muscle segment homeobox 2, bone morphogenetic protein 1, biglycan, vascular endothelial growth factor B, dentin sialophosphoprotein, cartilage oligomeric matrix protein, runt-related transcription factor 2, fibroblast growth factor receptor 3, and SMAD2 were upregulated > 2-fold compared to the control. Conversely, osteopetrosis-associated transmembrane protein 1, microphthalmia-associated transcription factor, and epidermal growth factor receptor were downregulated > 2-fold compared to the control. Vitamin E produced a 1.5-fold increase in the expression of runt-related transcription factor 2 and transforming growth factor-beta 1 as determined by real time RT-PCR. CONCLUSION: Vitamin E had a positive effect on the gene expressions regarding osteogenic differentiation of mesenchymal stem cells.

The Effect of Succinylcholine on the Neuromuscular Block Induced with Mivacurium in the abbits / 대한마취과학회지

BACKGROUND: There were many reports about the effect of succinylcholine on the action of nondepolarizing muscle relaxants. The results are inconsistent depend on the nondepolarizing muscles relaxants used, time when nondepolarizing blockers administered and methods of experiments etc. We investigated the effect of succinylcholine on the neuromuscular blockade induced with mivacurium, a new short acting nondepolarizing muscle relaxant, when mivacurium was administered during early and late recovery from succinylcholine block and when different dose of succinylcholine were used. METHODS: 30 rabbits were divided into 5 groups including control group. Control group was administered mivacurium only. In other 2 groups, succinylcholine (3xED95) was administered, and mivacurium was given at 5% and 100% recovery from succinylcholine. In the other two groups, succinylcholine (6xED95) was administered, and mivacurium was given at 5% and 100% recovery from succinylcholine. We investigated onset time, duration of relaxation, and recovery index of mivacurium induced neuromuscular block. RESULTS: Onset time was shortened in all groups compare to control group. Duration and recovery index were not changed significantly at 5% and 100% recovery of succinylcholine (3xED95) administered group, but prolonged significantly (p<0.05) in succinylcholine (6xED95) administered groups compare to control group. CONCLUSION: Mivacurium induced block were more prolonged at 100% recovery of succinylcholine (3xED95) induced block and these effect were more potentiated by the increasing the dose of succinlycholine (6xED95) administered group.

Regulatory role of cyclic nucleotides in non-adrenergic non-cholinergic relaxation of lower esophageal sphincter from dogs

The role of the lower esophageal sphincter (LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic (NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation (EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin (1 micrometer), but not by atropine (100 micrometer), guanethidine (100 micrometer) and indomethacin (10 micrometer). The nitric oxide synthase inhibitors, N-G-nitro-L-arginine, N-G-nitro-L-arginine methyl ester and N-G-monomethyl-L-arginine inhibited EFS-induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N-ethylmaleimide (NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.