Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial.

BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer.

PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer.

BACKGROUND: We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). PATIENTS AND METHODS: Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). RESULTS: Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37-0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. CONCLUSION: The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. CLINICAL TRIALS NUMBER: Japan Pharmaceutical Information Center: JapicCTI-111554.

Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer.

Background Elpamotide is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. Given the high expression of VEGFR-2 in biliary tract cancer, combination chemoimmunotherapy with elpamotide and gemcitabine holds promise as a new therapy. Patients and Methods Patients with unresectable advanced or recurrent biliary tract cancer were included in this single-arm phase II trial, with the primary endpoint of overall survival. Survival analysis was performed in comparison with historical control data. The patients concurrently received gemcitabine once a week for 3 weeks (the fourth week was skipped) and elpamotide once a week for 4 weeks. Results Fifty-five patients were registered, of which 54 received the regimen and were included in the full analysis set as well as the safety analysis set. Median survival was 10.1 months, which was longer than the historical control, and the 1-year survival rate was 44.4%. Of these patients, injection site reactions were observed in 64.8%, in whom median survival was significantly longer (14.8 months) compared to those with no injection site reactions (5.7 months). The response rate was 18.5%, and all who responded exhibited injection site reactions. Serious adverse reactions were observed in five patients (9%), and there were no treatment-related deaths. Conclusion Gemcitabine and elpamotide combination therapy was tolerable and had a moderate antitumor effect. For future development of therapies, it will be necessary to optimize the target population for which therapeutic effects could be expected.

Hypertension induced by erythropoietin has a correlation with truncated erythropoietin receptor mRNA in endothelial progenitor cells of hemodialysis patients.

Endothelial nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contribute to erythropoietin (EPO)-induced hypertension, a major adverse reaction associated with EPO therapy. To investigate the mechanism of EPO-induced hypertension, we examined circulating endothelial progenitor cells (EPCs) taken from 56 hemodialysis (HD) patients. Among these EPCs (which reflect the condition of the endothelium), we looked for EPO receptor (EPOR) mRNAs. A truncated form of EPOR acts as a dominant negative regulator of EPO signaling, leading to hypertension. We found that the ratio of truncated EPOR mRNA in EPCs has a correlation with EPO-induced increase in blood pressure (r = 0.36, P = 0.02). The ratio of truncated to total EPOR mRNA in EPCs had an inverse correlation with EPO-induced cGMP production in vitro (r = -0.31, P = 0.02). A similar correlation was observed in cultured human endothelial cells after transfection of the full-length or truncated forms of EPOR (r = -0.92, P < 0.001). It follows, therefore, that evaluation of EPOR isoform mRNA in EPCs can predict EPO-induced hypertension. The termination of the EPO signal by truncated EPORs may decrease NO/cGMP production after EPO exposure, thereby raising blood pressure.

Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) proliferation is a key event in the progression of arteriosclerosis. Clinical studies show that uremic toxins deteriorate the arteriosclerosis in renal failure patients. Indoxyl sulfate (IS) is a strong protein-bound uremic toxin, but the effect of IS on VSMC proliferation has not been studied. We examined the effect of IS on rat VSMC proliferation, assessed by a cell counting kit (4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] assay) and by [(3)H]thymidine incorporation in vitro. We further evaluated a contribution of mitogen-activated protein kinase (MAPK; p44/42 MAPK) to VSMC proliferation by IS. Immunohistochemical staining was performed for VSMCs using antirat organic anion transporter (OAT)3 antibody. The mRNA expressions of platelet-derived growth factor (PDGF)-A and -C chains, and PDGF-beta receptor were evaluated by real-time PCR. IS stimulated the proliferation of VSMCs in a concentration-dependent manner and activated p44/42 MAPK. Concentration of IS needed to stimulate the proliferation of rat VSMC was about 250 microM, which is compatible with that in the serum of end-stage renal failure patients. PD98059 (10 microM), a selective inhibitor of MAPK/extracellular signal-regulated kinase, inhibited the IS-induced (250 microM) VSMC proliferation and phosphorylation of MAPK. Probenecid (0.5 mM), an inhibitor and substrate of OAT, inhibited the IS-induced (250 microM) VSMC proliferation. Rat OAT3 was detected in VSMCs. The mRNA expressions of PDGF-C chain and PDGF-beta receptor were significantly increased by IS. We conclude that IS directly stimulates rat VSMC proliferation and activates MAPK in vitro. This might be one of the mechanisms underlying the progression of atherosclerotic lesions in end-stage renal disease patients.

Evaluation of epithelial cell proliferation rate in normal-appearing colonic mucosa as a high-risk marker for colorectal cancer.

To determine whether the colonic epithelial proliferation rate is useful as a marker for colorectal cancer, we measured the Ki-67 labeling index (LI) in normal-appearing mucosa from the sigmoid and ascending colon in patients with two or more tumors (early cancers, which are defined as tumors the depth of invasion of which is limited to mucosal layer or submucosal layer, adenomas, or both). The association of baseline LI with the risk of development of colon tumors 2 years after endoscopic removal was assessed by cohort analysis. The presence of two or more tumors was defined as occurrence. One hundred and six specimens from the sigmoid colon and 130 from the ascending colon from 246 subjects (203 males and 43 females) were used for analysis. The patients with higher upper-third LI in the normal-appearing mucosa in the sigmoid colon, but not in the ascending colon, had significantly more tumors at follow-up colonoscopy 2 years later (risk ratio, 3.6; 95% confidence interval, 1.2-10.6). Moreover, multivariate analysis showed that it was an independent factor. We concluded that the higher upper-third Ki-67 LI of normal-appearing mucosa in the sigmoid colon indicates a high risk for colorectal cancer.

Dynamic sonography of hepatic tumors.

OBJECTIVE: Our objectives were to propose and evaluate a dynamic sonography protocol for the characterization of hepatic tumors. SUBJECTS AND METHODS: The subjects were 107 patients with focal liver lesions that initially had been found on conventional sonograms. The final diagnoses for the lesions were hepatocellular carcinoma in 60 patients, cholangiocellular carcinoma in six, metastatic carcinoma in 24, hemangioma in 10, and focal fat-spared region in seven. The pulse inversion harmonic imaging mode and a galactose-based contrast agent (Levovist) were used. Dynamic sonography was designed to obtain vascular-phase (composed of the arterial phase and the portal phase) images of the focal lesion and liver-parenchymal-phase images of the whole liver in a series obtained after a bolus injection of the contrast agent. RESULTS: If the whole-tumor or mosaic enhancement patterns (arterial phase) and/or the reticular enhancement (parenchymal phase) are regarded as positive findings for hepatocellular carcinoma, the sensitivity, specificity, and positive predictive value of dynamic sonography in our study were 92%, 96%, and 96%, respectively. If a ring enhancement (arterial to portal phase) or a clear defect (parenchymal phase) or both are regarded as positive findings for cholangiocellular carcinoma or metastasis, the sensitivity, specificity, and positive predictive value were 90%, 95%, and 88%, respectively. If puddle enhancement (portal phase) is regarded as a positive finding for hemangioma, the figures for sensitivity, specificity, and positive predictive value were 60%, 100%, and 100%, respectively. Also, the tumors that showed no focal sign in the liver parenchymal phase were all benign lesions, such as hemangiomas or focal fat-spared regions. CONCLUSION: Dynamic sonography in a protocol combining pulse inversion harmonic imaging and an IV bolus injection of the contrast agent proved to be an effective tool in characterizing liver tumors.

Chlamydia pneumoniae infection and accelerated development of coronary artery disease in patients with chronic renal failure.

AIMS: This study examined the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and the accelerated development of coronary artery disease (CAD) in patients with chronic renal failure (CRF). METHODS: Two-hundred and fourteen patients undergoing coronary angiography, including 67 controls and 147 patients with CAD (97 without CRF and 50 with CRF), were enrolled in this study. Anti-C. pneumoniae specific IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Coronary artery disease (expressed as CAD score) was more severe in patients with than without CRF (14.9 +/- 6.0 vs. 11.3 +/- 6.0, p < 0.01). Seropositive rates of IgG and IgA antibodies against C. pneumoniae were higher in all CAD patients than in the controls (76.2% vs. 44.8%, p < 0.001 for IgG; 59.9% vs. 40.3%, p < 0.01 for IgA). In both CAD subgroups, IgG seropositive rates were similarly elevated (82.0% and 73.2% vs. 44.8% for control, p < 0.001, respectively), whereas those of IgA were significantly elevated only in CAD with CRF (68.0% vs. 55.7% for control, p < 0.01). The mean antibody index of IgG was elevated in all CAD patients compared with the controls (1.9 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.0001), but that of IgA was not (1.5 +/- 1.0 vs. 1.2 +/- 0.9). Levels of IgG were elevated in all patients with CAD compared with the control (2.4 +/- 1.1 and 1.8 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.001 and p < 0.001, respectively), whereas those of IgA were elevated only in CAD with CRF (1.8 +/- 1.1 vs. 1.2 +/- 0.9, p < 0.05). Stepwise logistic regression analysis revealed that the elevated IgG antibody index was an independent risk factor for CAD regardless of CRF (odds ratios 1.9, 1.8, and 2.3), whereas the IgA index was a risk factor only in CAD with CRF (odds ratio 1.7). CONCLUSIONS: Chlamydia pneumoniae infection may be related to the accelerated CAD in patients with CRF, which was specifically suggested by an elevated IgA level. In other words, the prevalence of active C. pneumoniae infection is higher in patients with CAD and CRF than that in those with CAD without CRF.

Evaluation of tissue harmonic imaging for the diagnosis of focal liver lesions.

This was a prospective study to evaluate tissue harmonic imaging (THI) for the diagnosis of focal liver lesions. A total of 15 reviewers read 100 randomly arranged liver images, a fundamental grey-scale image (FGI) and a THI (transmitted: 2 MHz, received: 4 MHz) of each of 50 patients (29 with liver cirrhosis, 42 with focal lesions) taken from the same section. The mean value of overall accuracy for detecting lesions (presence or absence) was significantly higher with THI (82.3%) than with FGI (79.6%) (t = 1. 96, p< 0.05). When only the 29 cirrhosis patients were analyzed, the difference was more significant (t = 2.48, p < 0.02). The correct count rate of the number of focal lesions was higher with THI (78. 0%) than with FGI (67.0%) (t = 3.61, p< 0.005) in 23 cirrhosis patients with focal lesions. The correct diagnosis of HCC was achieved at a higher rate with THI (42.5%) than with FGI (36.8%). THI was statistically effective for detecting focal lesions, particularly in cirrhotic livers.

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells.

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO4 caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO4 for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression.

Confirmation of a "safety zone" by intraoperative cholangiography during laparoscopic cholecystectomy.

BACKGROUND: Creating a "safety zone" during laparoscopic cholecystectomy is defined as dissection of the cystic duct as close as possible to the gallbladder. METHODS: In 29 out of 802 cases in which laparoscopic cholecystectomy was difficult to perform due to uncertainty about the orientation of Calot's triangle, intraoperative cholangiography was performed, using a titanium clip as a marker that designated the safety zone. The distance between the clip and the common hepatic duct or the common bile duct could be determined by evaluation of two intraoperative cholangiograms taken in different orientation. RESULTS: If the clip was located in the safety zone, and was distant from the common hepatic duct or common bile duct, the safety of preparation around the clip was ensured. No complication was encountered in these cases with this method. Eventually, no biliary tract injury was experienced, and the overall conversion rate to open cholecystectomy was only 0.4% (3 of 802 consecutive cases). CONCLUSIONS: This method of confirming the safety zone by intraoperative cholangiography is a useful procedure for avoiding inadvertent injury to the biliary tract.

Laparoscopic transcystic cholangioscopic lithotripsy for common bile duct stones during laparoscopic cholecystectomy.

BACKGROUND AND STUDY AIMS: Following the recent introduction of laparoscopic cholecystectomy (LC) for cholecystolithiasis, treatment of concomitant common bile duct (CBD) stones has been evaluated by using laparoscopic choledochotomy, a transcystic approach, or by means of endoscopic sphincterotomy (ES) before or after LC. PATIENTS AND METHODS: During laparoscopic cholecystectomy, we attempted lithotripsy of CBD stones using laparoscopic transcystic cholangioscopy with lithotripsy (LTCL), in 70 patients out of 950 laparoscopic cholecystectomies. Preparatory tests included laboratory values, ultrasound, and performance of endoscopic retrograde cholangiography (ERC) with placement of a nasobillary tube (without sphincterotomy). RESULTS: Introduction of the cholangioscope into the CBD was successful in 65 patients (92.9%) and CBD clearance was completely achieved by LTCL alone in 51 (78.5%). The overall success rate was therefore 73%. The remaining 19 cases required postoperative procedures such as extracorporeal shock-wave lithotripsy without ERC or ES (successful in all). The average hospital stay period was 9.4 days for patients in whom CBD clearance was achieved by LTCL alone. This period did not differ significantly from that of patients who underwent LC alone (8.4) days. The operation time was about 70 minutes longer for the LTCL group (total time 174 minutes on average) than for the LC group (107 minutes). We did not observe any series complications during or after LTCL (mean follow-up period: 34 months). CONCLUSION: LTCL in combination with LC allows shortening of the hospital stay and a swift return to work for patients with CBD stones. This procedure also preserves the function of the sphincter of Oddi, so that the longterm prognosis for patients is likely to be very good.

Laparoscopic cholecystectomy in the elderly: analysis of pre-operative risk factors and postoperative complications.

A retrospective study was conducted of two groups of patients over (group 1, n = 57) and under (group 2, n = 655) the age of 70 years who underwent laparoscopic cholecystectomy (LC). The pre-operative physical status and systemic complications, operation time, postoperative complications, postoperative hospital stay and other clinical features of the two groups were compared. The incidence of pre-operative complications in group 1 was significantly higher than that in group 2 (P < 0.05). Postoperatively no severe complication was found in any patient. Group 1 showed significantly prolonged operation time and postoperative hospital stay compared with group 2 (P < 0.05). The difference between the groups in the intra-operative treatment time and postoperative treatment is attributed to the greater prevalence of common bile duct stone in group 1 as there was little difference between the groups in the postoperative recovery after exclusion of these patients. No pulmonary complications, which are associated with LC, were observed; the postprocedure pain was slight and the period of bedrest was short. If complications associated with pneumoperitoneum can be prevented, this surgery is an excellent measure to improve the quality of life of even elderly patients with cholecystolithiasis.

Femoral vein stasis during laparoscopic cholecystectomy: effects of graded elastic compression leg bandages in preventing thrombus formation.

Venous stasis of the legs during laparoscopic cholecystectomy was compared between patients without graded compression leg bandages (Group 1; n = 12) and patients with such bandages (Group 2; n = 12) by measuring mean blood flow velocity and cross-sectional area of the femoral vein using a color Doppler ultrasonography. In Group 1, when velocity and area were measured in the supine position, a significant decrease in velocity (p < .05) and a significant increase in area (p < .05) occurred after abdominal insufflation to 10 mm Hg. These changes were greater during abdominal insufflation in the reverse Trendelenburg position than during abdominal insufflation in the supine position. In Group 2, flow velocity was significantly higher (p < .05) before abdominal insufflation as compared with Group 1. After abdominal insufflation to 10 mm Hg and a postural change, velocity significantly decreased (p < .05) and area significantly increased (p < .05) in Group 2, similar to the results in Group 1. During abdominal insufflation at 5 mm Hg or lower, the use of the graded compression bandage was found to be useful for preventing femoral vein stasis. During abdominal insufflation at 10 mm Hg or in the reverse Trendelenburg position, the bandage did not prevent femoral vein stasis.

Lower-extremity venous stasis during laparoscopic cholecystectomy as assessed using color Doppler ultrasound.

Lower-extremity venous stasis during laparoscopic cholecystectomy was evaluated in 16 patients by monitoring the blood velocity in the femoral vein and the femoral vein size (cross-sectional area) using color Doppler ultrasonography. The blood velocity in the femoral vein decreased significantly after the start of 10-mmHg abdominal insufflation in the supine position. When the patients were placed in a reverse Trendelenburg position during 10-mmHg insufflation, blood velocity in the femoral vein further decreased. However, velocity returned to the baseline after deflation. The cross-sectional area of the femoral vein was significantly elevated after the start of 10 mm Hg insufflation in the supine position. When patients were placed in the reverse Trendelenburg position during 10-mmHg insufflation, this parameter was further elevated, but returned to the baseline soon after deflation. These results indicate that femoral vein stasis during laparoscopic cholecystectomy can be minimized by reducing the pressure of abdominal insufflation and avoiding elevation of the patient's head as much as possible.