Influence of carbon dioxide insufflation of the neck on intraocular pressure during robot-assisted endoscopic thyroidectomy: a comparison with open thyroidectomy.

BACKGROUND: Increased intraocular pressure (IOP) during surgery can result in serious ophthalmic complications. We hypothesized that carbon dioxide (CO2) insufflation of the neck during endoscopic thyroidectomy would constrict the jugular veins mechanically, causing elevated venous pressure and thus elevated IOP. We compared IOP changes at each step of open thyroidectomy (OT) versus robot-assisted endoscopic thyroidectomy (RET) METHODS: Perioperatively, IOP was measured at six time points in patients undergoing OT (n = 18) or RET with CO2 insufflation (n = 19). Anesthesia, ventilatory strategy, intravenous infusions, and surgical positioning were standardized RESULTS: In both groups, induction of anesthesia reduced IOP, but surgical positioning with the neck in extension had no effect on IOP. In the OT group, IOP remained unchanged during anesthesia. In the RET group, CO2 insufflation significantly increased IOP to an average of 3.6 ± 3.0 mmHg higher than the previous measurement (P < 0.001), and this IOP increase persisted immediately before gas deflation. These elevated IOP values during CO2 insufflation in the RET group were significantly higher than those at corresponding time points in the OT group. However, these elevated IOP values were similar to the pre-anesthetic baseline IOP CONCLUSION: CO2 insufflation of the neck at pressure of 6 mmHg increased the IOP significantly compared with open thyroidectomy. However, this increase in IOP could be balanced by an anesthetic-induced IOP-lowering effect, thereby having no clinical significance in patients with normal IOP undergoing robot-assisted endoscopic thyroidectomy.

What influence does intermittent pneumatic compression of the lower limbs intraoperatively have on core hypothermia?

BACKGROUND: Intermittent pneumatic compression (IPC) devices have been widely used for thrombosis prophylaxis in laparoscopic colorectal surgery. However, periodic compression using an IPC device may inject augmented boluses of cool blood from the lower limbs into the central circulation repetitively, thereby causing a reduction in core temperature. The authors therefore conducted a prospective, randomized, double-blind, controlled study to compare the effects of intraoperative IPC on core temperature in patients undergoing laparoscopic colorectal surgery. METHODS: For this study, 56 patients ages 18-60 years and scheduled to undergo laparoscopic resection for colorectal cancer under general anesthesia were randomly assigned to receive either no IPC (control group) or calf-thigh-length IPC in both legs using the SCD Express (IPC group). Anesthetic, thermal, and pneumoperitoneum management were standardized. Esophageal temperature, as an indicator of core temperature, was measured at 15-min intervals for 2 h after induction of anesthesia. RESULTS: A total of 47 subjects (23 control and 24 IPC subjects) were included in the analysis. The core temperature drop in the IPC group was significantly greater than in the control group, starting from 45 min after induction of anesthesia (P < 0.05). As a result, the total temperature drop during the 2-h study period was significantly greater in the IPC group (1.2 ± 0.3 °C) than in the control group (0.9 ± 0.3 °C) (P = 0.004). CONCLUSIONS: Because intraoperative application of IPC carries an increased risk of a core temperature drop, appropriate temperature monitoring and active thermal management are required for surgical patients receiving IPC.

Influence of the organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer.

To investigate whether the OATP1B1 polymorphisms affect irinotecan-pharmacokinetics and subsequent toxicity and tumor response of patients with advanced NSCLC. A total of 81 Korean NSCLC patients enrolled in a phase II study of irinotecan and cisplatin chemotherapy were genotyped for OATP1B1 -11187G>A, 388A>G and 521T>C variants. The 521TC or CC and -11187AA genotypes were associated with higher AUC(SN-38) (p=0.016 and 0.030, respectively). When haplotypes were assigned, patients with *15 haplotype showed significantly higher AUC(SN-38) than *1a or *1b haplotypes (p=0.006). Grade 4 neutropenia was associated with the 521TC or CC genotypes, whereas, grade 3 diarrhea was associated with 388GG genotype (p=0.046). Of the 81 patients enrolled, 77 were assessable for response and 36 (47%) patients achieved partial responses (PR). However, no statistical significance was observed between genotype and response. These findings suggest that OATP1B1 variants are involved in SN-38 disposition and highly predictive for severe toxicity of NSCLC patients treated with irinotecan-based chemotherapy.

Fine-scale map of encyclopedia of DNA elements regions in the Korean population.

The International HapMap Project aims to generate detailed human genome variation maps by densely genotyping single-nucleotide polymorphisms (SNPs) in CEPH, Chinese, Japanese, and Yoruba samples. This will undoubtedly become an important facility for genetic studies of diseases and complex traits in the four populations. To address how the genetic information contained in such variation maps is transferable to other populations, the Korean government, industries, and academics have launched the Korean HapMap project to genotype high-density Encyclopedia of DNA Elements (ENCODE) regions in 90 Korean individuals. Here we show that the LD pattern, block structure, haplotype diversity, and recombination rate are highly concordant between Korean and the two HapMap Asian samples, particularly Japanese. The availability of information from both Chinese and Japanese samples helps to predict more accurately the possible performance of HapMap markers in Korean disease-gene studies. Tagging SNPs selected from the two HapMap Asian maps, especially the Japanese map, were shown to be very effective for Korean samples. These results demonstrate that the HapMap variation maps are robust in related populations and will serve as an important resource for the studies of the Korean population in particular.

Is routine preoperative spirometry necessary in elderly patients undergoing laparoscopy-assisted gastrectomy?

OBJECTIVES: To identify predictors of postoperative pulmonary complications (PPCs) in patients aged ≥ 60 years who underwent laparoscopy-assisted gastrectomy (LAG), and to examine the value of preoperative spirometry to predict PPCs. METHODS: Patients with preoperative spirometric results who underwent LAG were retrospectively studied. Spirometry included four parameters: forced expiratory volume in 1 s; functional vital capacity; mean forced expiratory flow during middle of functional vital capacity; peak expiratory flow rate. RESULTS: Of 213 patients, overall incidence of PPCs was 19.2%. Abnormal spirometry findings were not identified as an independent predictor of PPCs using multivariate logistic regression analysis. Age was found to be the only independent predictor of PPCs out of all variables evaluated. Separate assessment of individual spirometric parameters using receiver-operating curve analyses indicated poor diagnostic accuracy. CONCLUSIONS: Preoperative spirometry was not reliably predictive of PPCs, either as combined or individual parameters, in patients aged ≥ 60 years who underwent LAG. These results do not support routine use of spirometry to stratify risk of PPCs in this surgical population.

Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations.

BACKGROUND: Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. METHODS: The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. RESULTS: The association previously observed on chromosome 9p21 was independently replicated (p=3.08e-07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. CONCLUSION: A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors.

HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.

OBJECTIVE: To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. METHODS: A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population. RESULTS: The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively. CONCLUSION: The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.

Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy.

PURPOSE: To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. PATIENTS AND METHODS: We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). RESULTS: The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 x 10(-5)), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). CONCLUSION: These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.

Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer.

BACKGROUND: The authors investigated whether ABCB1, ABCC2, and ABCG2 genetic polymorphisms affect pharmacokinetics (PK) of irinotecan and treatment outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Blood samples from 107 NSCLC patients treated with irinotecan and cisplatin chemotherapy were used for genotyping ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCC2 (-24C > T, 1249G > A, 3972C > T), and ABCG2 (34G > A, 421C > A) polymorphisms. Genotypes were correlated with irinotecan-PK, toxicity, tumor response, and survival. RESULTS: Among 8 polymorphisms, 3435TT and 2677TT were associated with AUC(SN-38G) and CL(SN-38G). When haplotypes are assigned, 2677TT/3435TT carriers showed significantly lower AUC(SN-38G) (P = .006), whereas 2677GG/3435CC carriers showed significantly higher AUC(SN-38) (P = .039). These findings suggest that 2677TT and 3435TT variants are associated with higher efflux activity. In toxicity, the 2677G/T or A was associated with grade 4 neutropenia. The 2677GG carriers showed significantly lower absolute neutrophil count during the 1(st) cycle (P = .012) as well as entire course of chemotherapy (P = .042). The 3435TT was associated with higher frequency of grade 3 diarrhea (P = .047). In tumor response, ABCC2 -24TT and 3972TT genotypes were associated with higher response rates (P = .031 and P = .048, [corrected] respectively) and longer progression-free survival (P = .010 and P = .019, [corrected] respectively), which was sustained in haplotype analysis. CONCLUSIONS: Specific polymorphisms of ABCB1 and ABCC2 can influence disposition and tumor response to irinotecan by regulating transporter activity. These findings may help to individualize irinotecan-based chemotherapy in patients with advanced NSCLC.

Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin.

PURPOSE: To determine whether uridine diphosphate-glucuronosyltransferase 1A1, UGT1A7, and UGT1A9 polymorphisms affect the pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Eighty-one patients with advanced NSCLC were treated with irinotecan (80 mg/m2) on day 1 and 8 and cisplatin (60 mg/m2) on day 1 intravenously of each 3-week cycle. Genomic DNA was extracted from peripheral blood and genotyped using direct sequencing. We analyzed the association of UGT1A genotypes with irinotecan PK and clinical outcomes. All statistical tests were two-sided. RESULTS: In genotype-PK association analysis, UGT1A1*6/*6 (n = 6), UGT1A7*3/*3 (n = 6), and UGT1A9-118(dT)9/9 (n = 11) were associated with significantly lower area under the time-concentration curve (AUC) SN-38G to SN-38 (AUC(SN-38G)/AUC(SN-38)) ratio (P = .002, P = .009, and P = .001, respectively). In linkage disequilibrium analysis, the UGT1A7 variants were highly linked with the UGT1A1*6 (D' = 0.85, r2 = 0.63) and UGT1A9*22 (D' = 0.95, r2 = 0.88), which was substantiated in haplotype analysis. Patients with UGT1A1*6/*6 had lower tumor response and higher incidence of severe neutropenia. UGT1A9-118(dT)9/9 also showed a trend for high incidence of severe diarrhea, but not tumor response. In survival analysis, patients with UGT1A1*6/*6 had significantly shorter progression-free survival (P = .001) and overall survival (P = .017). CONCLUSION: These findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for SN-38 glucuronidation and associate with irinotecan-related severe toxicity. Specifically, UGT1A1*6 might be useful for predicting tumor response and survival outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy.