A graph placement methodology for fast chip design.

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates chip floorplans that are superior or comparable to those produced by humans in all key metrics, including power consumption, performance and chip area. To achieve this, we pose chip floorplanning as a reinforcement learning problem, and develop an edge-based graph convolutional neural network architecture capable of learning rich and transferable representations of the chip. As a result, our method utilizes past experience to become better and faster at solving new instances of the problem, allowing chip design to be performed by artificial agents with more experience than any human designer. Our method was used to design the next generation of Google's artificial intelligence (AI) accelerators, and has the potential to save thousands of hours of human effort for each new generation. Finally, we believe that more powerful AI-designed hardware will fuel advances in AI, creating a symbiotic relationship between the two fields.

Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

Deep learning-accelerated T2-weighted imaging versus conventional T2-weighted imaging in the female pelvic cavity: image quality and diagnostic performance.

BACKGROUND: The deep learning (DL)-based reconstruction algorithm reduces noise in magnetic resonance imaging (MRI), thereby enabling faster MRI acquisition. PURPOSE: To compare the image quality and diagnostic performance of conventional turbo spin-echo (TSE) T2-weighted (T2W) imaging with DL-accelerated sagittal T2W imaging in the female pelvic cavity. METHODS: This study evaluated 149 consecutive female pelvic MRI examinations, including conventional T2W imaging with TSE (acquisition time = 2:59) and DL-accelerated T2W imaging with breath hold (DL-BH) (1:05 [0:14 × 3 breath-holds]) in the sagittal plane. In 294 randomly ordered sagittal T2W images, two radiologists independently assessed image quality (sharpness, subjective noise, artifacts, and overall image quality), made a diagnosis for uterine leiomyomas, and scored diagnostic confidence. For the uterus and piriformis muscle, quantitative imaging analysis was also performed. Wilcoxon signed rank tests were used to compare the two sets of T2W images. RESULTS: In the qualitative analysis, DL-BH showed similar or significantly higher scores for all features than conventional T2W imaging (P <0.05). In the quantitative analysis, the noise in the uterus was lower in DL-BH, but the noise in the muscle was lower in conventional T2W imaging. In the uterus and muscle, the signal-to-noise ratio was significantly lower in DL-BH than in conventional T2W imaging (P <0.001). The diagnostic performance of the two sets of T2W images was not different for uterine leiomyoma. CONCLUSIONS: DL-accelerated sagittal T2W imaging obtained with three breath-holds demonstrated superior or comparable image quality to conventional T2W imaging with no significant difference in diagnostic performance for uterine leiomyomas.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Prevention of Petersen's hernia using jejunal mesentery fixing (Mefix).

BACKGROUND: The aim of this study was to compare the 1 year incidence of Petersen's hernia between individuals who were treated with the jejunal mesentery fixing (Mefix) method and those with the closure of Petersen's space method. MATERIAL AND METHODS: We retrospectively collected clinical data of patients who underwent gastrectomy for gastric cancers with the closure of Petersen's space defect (N = 49) and Mefix (N = 26). The Mefix method was performed by fixing the jejunal mesentery (jejunojejunostomy below 30 cm) to the transverse mesocolon using nonabsorbable barbed sutures. RESULTS: The procedure time for mesentery fixing (3.7 ± 1.1 mins) was significantly shorter than that for Petersen's space closure (7.5 ± 1.5 mins) (p < .001) although the operation times were similar between the two groups. There was no incidence of Petersen's hernias postoperatively in both groups. One case of reoperation was reported in the closure group due to small bowel obstruction by kinking of the jejunojejunostomy. CONCLUSION: We found no occurrence of Petersen's hernias postoperatively in either group. We also found that the Mefix method was faster and easier to perform than the closure method. The Mefix method is an excellent alternative method to prevent the occurrence of Petersen's hernia after B-II or Roux-en-Y reconstruction.

Outcome of No-Touch Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Multicenter Clinical Trial.

Background Recently introduced no-touch radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) has the potential to improve local tumor control. Purpose To evaluate midterm clinical outcomes of monopolar no-touch RFA in single HCCs 2.5 cm or smaller. Materials and Methods In this multicenter clinical trial (ClinicalTrials.gov: NCT03375281), participants were evaluated for eligibility from November 2017 to January 2019. Patients with single HCCs 2.5 cm or smaller planning to be treated with no-touch RFA were enrolled. The rate of successful no-touch RFA, defined as performing RFA without violation of the tumor itself, was recorded. Multivariable logistic regression analysis was used to determine associated factors for failure of no-touch RFA. Development of major complication after no-touch RFA was also recorded. Cumulative incidence of local tumor progression (LTP) and recurrence-free survival were estimated by using the Kaplan-Meier method. Results A total of 140 participants (mean age, 62 years ± 9 [standard deviation]; 106 men) were evaluated. No-touch RFA was successfully performed in 128 participants (128 of 140; 91.4%), and conversion to tumor puncture RFA was undertaken in 12 participants because of the lack of a safe access route. By using either no-touch RFA or conversion to tumor puncture RFA, all participants achieved technical success of RFA, which was defined as complete coverage of target tumor by ablation zone. Insufficient peritumoral parenchyma (<5 mm width around more than half portion of tumor; odds ratio, 74; 95% CI: 18, 309; P < .001) was the only significant predictive factor for failure of the no-touch technique. Among the 140 participants, LTP developed in two participants, and the estimated 1- and 2-year cumulative incidence of LTP was 0.7% and 1.6%, respectively. The estimated 1- and 2-year recurrence-free survival was 82.8% and 74.1%, respectively. Conclusion No-touch radiofrequency ablation was an effective and safe treatment method for small hepatocellular carcinomas (≤2.5 cm), with 1.6% of cumulative incidence of local tumor progression at 2 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Soulen and García-Mónaco in this issue.

A comparison of postoperative outcomes after open and laparoscopic reduction of Petersen's Hernia: a multicenter observational cohort study.

BACKGROUND: The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen's hernia (PH) reduction. METHOD: We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015-2018. Forty patients underwent PH reduction operations that were performed by six surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH. RESULTS: We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p > 0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p = 0.03) and length of hospital stay (12.6 vs. 8.2 days, p = 0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH. CONCLUSION: Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction in selected cases.

Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells.

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.

Safety and location analysis of transumbilical endoscopic submucosal dissection with single-basin lymph node dissection in the upper gastric body: a porcine model.

BACKGROUND: In our previous study, transumbilical endoscopic submucosal dissection (TU-ESD) was revealed to be feasible, but delayed gastric perforation was observed in 30% of ESD sites. In this study, we aimed to verify locations at which it is feasible to perform TU-ESD in the upper gastric body and to demonstrate the safety of TU-ESD in single-basin lymph node dissection (SBLND). METHODS: In vitro, TU-ESD was performed at three lesion sites (anterior wall, AW; posterior wall, PW; and lesser curvature, LC) in each porcine stomach using an EASIE-R tray (cases = 10). In vivo, TU-ESD was performed with SBLND in 9 pigs. Seven days after the operation, the pigs were sacrificed and examined. RESULTS: In the in vitro feasibility study, the TU-ESD time was significantly faster in the PW group (5.9 ± 2.0 min) than in the LC group (8.5 ± 1.5 min) (p < 0.05) in all 10 cases. In the in vivo survival study, TU-ESD with SBLND was successfully performed without any complications (N = 9). There were no cases of delayed perforation, and healing ulcers were found in all pigs 7 days after the operation. Ulcer size (5.2 ± 3.5 cm2) was approximately 36% smaller than that observed at the ESD operation site (8.1 ± 1.9 cm2) (p = 0.05). Epithelialization in the margin and healing of the gastric ulcers were confirmed by microscopy. CONCLUSIONS: TU-ESD with SBLND is a feasible and safe method. The upper posterior gastric body could be the most feasible location for performing TU-ESD, perhaps because of the difference in the subcutaneous dissection time.

Safety and efficacy of post-anastomotic intraoperative endoscopy to avoid early anastomotic complications during gastrectomy for gastric cancer.

BACKGROUND: Anastomotic complications such as leaks, bleeding, and stricture remain the most serious complications of surgery for gastric cancer. No perfect method exists for an accurate and reliable prevention of these complications. This study investigated the safety and efficacy of post-anastomotic intraoperative endoscopy (PAIOE) for avoidance of early anastomotic complications during gastrectomy in gastric cancer. METHODS: This retrospective case-control study enrolled patients from a tertiary care, academic medical center. Routine PAIOE was performed on 319 patients undergoing gastrectomy for gastric cancer between 2015 and 2016. As controls, without PAIOE 270 patients from 2013 to 2014 were used for comparison. Early anastomotic complications and outcomes after PAIOE were determined. RESULTS: Although there were no differences between the PAIOE and non-PAIOE group in terms of overall complication rates (20.1% vs 26.7%; P > 0.05), there were fewer complications related to anastomosis (3.4% vs 8.9%; P < 0.01) in the PAIOE group. The PAIOE group had rates of 2.5% for anastomotic leakage, 0.9% for intra-luminal bleeding, and 0% for anastomotic stenosis, while the non-PAIOE group exhibited rates of 5.6%, 2.6%, and 0.7%, respectively. Thirty-one abnormalities were detected in 26 PAIOE patients (9.71%) (20 venous bleeding, 7 mucosal tearing, 2 air leaks, 1 arterial bleeding, and 1 anastomotic stricture). All abnormalities were corrected by proper interventions (13 reinforced additional suture, 13 endoscopic hemostasis, and 2 re-anastomosis). There were no morbidities associated with PAIOE. CONCLUSIONS: PAIOE appears to be a safe and reliable procedure to evaluate the stability of gastrointestinal anastomosis for gastric cancer patients. Further data collection and a well-designed prospective study are needed to confirm the validity of PAIOE.

Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision markers and drivers of hepatocellular carcinoma.

An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, given that early detection of HCC markedly improves survival. We aimed to investigate the molecular markers underlying early progression of HCC that can be detected in precancerous lesions. We designed a gene selection strategy to identify potential driver genes by integrative analysis of transcriptome and clinicopathological data of human multistage HCC tissues, including precancerous lesions, low- and high-grade dysplastic nodules. The gene selection process was guided by detecting the selected molecules in both HCC and precancerous lesion. Using various computational approaches, we selected 10 gene elements as a candidate and, through immunohistochemical staining, showed that barrier to autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), and splicing factor 3b subunit 4 (SF3B4) are HCC decision markers with superior capability to diagnose early-stage HCC in a large cohort of HCC patients, as compared to the currently popular trio of HCC diagnostic markers: glypican 3, glutamine synthetase, and heat-shock protein 70. Targeted inactivation of BANF1, PLOD3, and SF3B4 inhibits in vitro and in vivo liver tumorigenesis by selectively modulating epithelial-mesenchymal transition and cell-cycle proteins. Treatment of nanoparticles containing small-interfering RNAs of the three genes suppressed liver tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. We also demonstrated that SF3B4 overexpression triggers SF3b complex to splice tumor suppressor KLF4 transcript to nonfunctional skipped exon transcripts. This contributes to malignant transformation and growth of hepatocyte through transcriptional inactivation of p27Kip1 and simultaneously activation of Slug genes. CONCLUSION: The findings suggest molecular markers of BANF1, PLOD3, and SF3B4 indicating early-stage HCC in precancerous lesion, and also suggest drivers for understanding the development of hepatocarcinogenesis. (Hepatology 2018;67:1360-1377).

Whole tumor ablation of locally recurred hepatocellular carcinoma including retained iodized oil after transarterial chemoembolization improves progression-free survival.

OBJECTIVES: To evaluate and compare clinical outcomes of two different radiofrequency ablation (RFA) methods for locally recurred hepatocellular carcinoma (LrHCC) after locoregional treatment. METHODS: Our institutional review board approved this study with a waiver of informed consent. A total of 313 patients previously treated with transarterial chemoembolization (TACE) (n = 167) and RFA (n = 146) with a single LrHCC ≤ 3 cm was included from five tertiary referral hospitals. RFA was done for LrHCCs using either viable tumor alone ablation (VTA) method (VTA: n = 61 in the TACE group and n = 127 in the RFA group) or whole tumor ablation (WTA) method which includes both viable tumor and retained iodized oil or previously ablated zone (WTA: n = 106 in the TACE group and n = 19 in the RFA group). Local tumor progression (LTP)-free survival as well as progression-free survival (PFS) were estimated using the Kaplan-Meier method, and prognostic factors were evaluated using the Cox proportional hazards regression model. RESULTS: In 167 patients with LrHCC who underwent TACE, the 5-year LTP-free survival after RFA was significantly higher with the VTA method than with the WTA method (26.9% vs. 87.8%; p < 0.001; hazard ratio (HR) = 8.53 [4.16-17.5]). The estimated 5-year PFS after RFA for LrHCC after TACE using the VTA method was 5.7%, which was significantly lower than that with the WTA method (26.4%) (p = 0.014; HR = 1.62 [1.10-2.38]). However, in 146 patients with LrHCC after initial RFA, there were no significant differences in cumulative incidence of LTP (p = 0.514) or PFS (p = 0.905) after RFA between the two ablation methods. CONCLUSIONS: For RFA of LrHCC after TACE, the WTA method including both viable tumor and retained iodized oil could significantly lower LTP and improve PFS than VTA. KEY POINTS: • Whole tumor ablation (WTA) could provide significantly better local tumor control for locally recurred HCC (LrHCC) after TACE than viable tumor alone ablation (VTA). • WTA for LrHCC after TACE could also provide significantly better progression-free survival than VTA. • Regarding LrHCC after RFA, VTA would provide a comparable clinical outcome to WTA.

Prebiopsy Biparametric MRI for Clinically Significant Prostate Cancer Detection With PI-RADS Version 2: A Multicenter Study.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) with respect to prebiopsy MRI with and without dynamic contrast enhancement in the detection of clinically significant cancer (CSC). MATERIALS AND METHODS: A total of 113 patients with prostate cancer who underwent radical prostatectomy and prebiopsy multiparametric 3-T MRI (mpMRI) that included T2-weighted imaging, DWI, and dynamic contrast-enhanced MRI (DCE-MRI) were enrolled in a retrospective study conducted at two institutions. For detecting CSC at prebiopsy mpMRI with DCE-MRI and biparametric MRI (bpMRI) without DCE-MRI, two independent radiologists using PI-RADSv2 scored suspicious lesions in all patients. RESULTS: CSC was identified in 74.3% (84/113) of patients. For CSC detection rate, no statistical differences between bpMRI and mpMRI were found for any PI-RADS score (p > 0.05). For cancer in the peripheral zone, reader 1 upgraded 22 lesions and reader 2 upgraded 13 lesions from PI-RADS score 3 at bpMRI to PI-RADS 4 (3 + 1) at mpMRI. The CSC detection rate of PI-RADS 3 + 1 lesions at mpMRI (reader 1, 63.6%; reader 2, 69.2%) was slightly greater than that of PI-RADS 3 lesions at bpMRI (reader 1, 53.8%; reader 2, 60.0%), which was not statistically different (p > 0.05). Interreader agreement on PI-RADS scoring was moderate for both bpMRI (κ = 0.540) and mpMRI (κ = 0.478). CONCLUSION: For detecting CSC, the diagnostic performance of prebiopsy bpMRI without DCE-MRI is similar to that of mpMRI with DCE-MRI.

Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer.

BACKGROUND: Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy. METHODS: We evaluated the PD-L1 expression of 72 patients with primary gastric cancer, before and after palliative first-line platinum-based chemotherapy, between January 2015 and March 2017. The PD-L1 ratio was defined as pre-chemotherapy PD-L1 expression divided by the post-chemotherapy PD-L1 expression. RESULTS: In 30 patients with PD-L1 negative pre-chemotherapy, 12 (40%) were positive post-chemotherapy; among the 42 patients with PD-L1 positive pre-chemotherapy, 24 (57.1%) were negative post-chemotherapy. The degree of PD-L1 expression decreased from 58.3% before chemotherapy to 41.7% after chemotherapy (P = 0.046). Among patients with complete response/partial response (CR/PR), the degree of PD-L1 expression decreased (P = 0.002), as well as PD-L1 positivity with statistical significance (P = 0.013) after chemotherapy, but not among patients with stable disease/progressive disease (SD/PD). Higher disease control rates (CR/PR/SD) were observed in patients with an elevated PD-L1 ratio (P = 0.043). Patients with a high PD-L1 ratio (> 1) were found to be associated with a better progression-free survival (HR 0.34, 95% CI 0.17-0.67, P = 0.002). CONCLUSIONS: PD-L1 expression can change during chemotherapy. Moreover, changes in patterns of PD-L1 expression might be associated with patient prognosis and response to chemotherapy.

Validation of the oncologic effect of hepatic resection for T2 gallbladder cancer: a retrospective study.

BACKGROUND: While extended cholecystectomy is recommended for T2 gallbladder cancer (GBC), the role of hepatic resection for T2 GBC is unclear. This study aimed to identify the necessity of hepatic resection in patients with T2 GBC. METHODS: Data of 81 patients with histopathologically proven T2 GBC who underwent surgical resection between January 1999 and December 2017 were enrolled from a retrospective database. Of these, 36 patients had peritoneal-side (T2a) tumors and 45 had hepatic-side (T2b) tumors. To identify the optimal surgical management method, T2 GBC patients were classified into the hepatic resection group (n = 44, T2a/T2b = 20/24) and non-hepatic resection group (n = 37, T2a/T2b = 16/21). The recurrence pattern and role of hepatic resection for T2 GBC were then investigated. RESULTS: Mean age of the patients was 69 (range 36-88) years, and the male-to-female ratio was 42:39 (male, 51.9%; female, 48.1%). Hepatic-side GBC had a higher rate of recurrence than peritoneal-side GBC (44.4% vs. 8.3%, p = 0.006). The most common type of recurrence in T2a GBC was para-aortic lymph node recurrence (n = 2, 5.6%); the most common types of recurrence in T2b GBC were para-aortic lymph node recurrence (n = 7, 15.6%) and intrahepatic metastasis (n = 6, 13.3%). Hepatic-side GBC patients had worse survival outcomes than peritoneal-side GBC patients (76.0% vs. 96.6%, p = 0.041). Hepatic resection had no significant treatment effect in T2 GBC patients (p = 0.272). Multivariate analysis showed that lymph node metastasis was the only significant prognostic factor (p = 0.002). CONCLUSIONS: Hepatic resection is not essential for curative treatment in T2 GBC, and more systemic treatments are needed for GBC patients, particularly for those with T2b GBC.

Effects of Yukmijihwang-tang, a Polyherb, on the Pharmacokinetics of Metformin.

Metformin is one of the most common medicines for the treatment of type 2 diabetes, however, recent studies suggest that concomitant antihyperglycemic agents should be administered for better efficacy. Yukmijihwang-tang (YMJHT) is a nephroprotective polyherb prescribed for renal disorders or diabetic mellitus in traditional Korean medicine. Therefore, the pharmacokinetics between metformin and YMJHT were examined for their coadministration. Rats were orally coadministered with metformin and YMJHT as a combination group or metformin and distilled water as the corresponding control. Then, the metformin concentration in plasma and its pharmacokinetic parameters including maximum concentration (Cmax) and area under the plasma concentration time curve (AUC) were analyzed. There were no interactions between metformin and YMJHT in the single coadministration at intervals within 5 min. However, pretreatments with YMJHT for 6 days increased the metformin concentration and its Cmax and AUC (p<0.05). The repeated coadministration for 8 days increased the Cmax of metformin (p<0.05). Conversely, when the combination was coadministered at 2h -intervals, there were no interactions between metformin and YMJHT after a single dosing or repeated dosing of coadministration for 7 days. These results of the present study will help structure proper dosing regimens for the concomitant therapy of metformin and YMJHT.

Laparoscopy-assisted versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: Results From a Randomized Phase II Multicenter Clinical Trial (COACT 1001).

OBJECTIVE: This randomized, phase II, multicenter clinical trial was conducted to evaluate the feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for the treatment of advanced gastric cancer (AGC). SUMMARY OF BACKGROUND DATA: D2 lymph node dissection has been accepted as standard treatment for AGC. Although LADG is widely performed in early gastric cancer (EGC), the feasibility of LADG in AGC has not been proven yet. METHODS: Patients with cT2-T4a and cN0-2 (AJCC 7 staging system) distal gastric cancer were randomly but not blindingly assigned to LADG or ODG groups using fixed block sizes with a 1:1 allocation ratio. The primary endpoint was the noncompliance rate of the lymph node dissection, which was used to evaluate feasibility. Secondary endpoints included 3-year disease-free survival (DFS), 5-year overall survival, complications, and surgical stress response. RESULTS: Between June 2010 and October 2011, 204 patients enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of these, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the overall noncompliance rate of lymph node dissection between LADG and ODG groups (47.0% and 43.2%, respectively; P = 0.648). In the subgroup analysis, the noncompliance rate in the LADG group was significantly higher than the ODG group for clinical stage III disease (52.0% vs 25.0%, P = 0.043). No difference was found in the 3-year DFS rate between the groups (LADG, 80.1%; ODG, 81.9%; P = 0.448). Differences in postoperative complication rates and surgical stress response were found to be insignificant between the 2 arms. CONCLUSIONS: LADG was feasible for AGC treatment based on the noncompliance rate of D2 lymph node dissection. Subgroups analysis data suggest that further studies are needed for stage III gastric cancer.

Prediction of Posthepatectomy Liver Failure: MRI With Hepatocyte-Specific Contrast Agent Versus Indocyanine Green Clearance Test.

OBJECTIVE: The objective of our study was to identify whether quantitative measurements from gadoxetic acid-enhanced MRI are useful for predicting posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) compared with and in combination with future remnant liver volume (FRLV) and an indocyanine green (ICG) clearance test. MATERIALS AND METHODS: Preoperative gadoxetic acid-enhanced MR images were retrospectively evaluated in 73 patients who underwent anatomic liver resection for HCC between 2011 and 2013. For quantitative measurement of hepatocyte function, relative liver enhancement (RLE) and remnant hepatocyte uptake index (rHUI) were measured using hepatobiliary phase MR images. FRLV was determined using measurements from preoperative CT scans. Univariate and multivariate analyses of measurements from gadoxetic acid-enhanced MRI, ICG clearance tests, and FRLV for finding predictors of PHLF were performed. To compare the diagnostic performance of predictors, ROC analyses were also performed. RESULTS: Eighteen (25%) of 73 patients met the criteria for PHLF. Univariate analysis revealed that all measurements related to MRI including RLE, rHUI, ICG clearance, and FRLV were significantly associated with PHLF. Multivariate analysis showed that RLE, FRLV, ICG-plasma disappearance rate (ICG-PDR), rHUI, and rHUI corrected for body weight (rHUI-BW) were independent predictors of PHLF (p = 0.011, p = 0.034, p = 0.003, p < 0.001, and p = 0.001, respectively). In ROC analyses, AUCs of rHUI and rHUI-BW were larger than those of other independent predictors; the differences were statistically significant (for rHUI-BW vs RLE, ICG-PDR, and FRLV, p = 0.016, 0.007, and 0.046, respectively; for rHUI vs RLE and ICG-PDR, p = 0.045 and 0.016, respectively). CONCLUSION: Measurements from gadoxetic acid-enhanced MRI predicted PHLF better than the ICG clearance test in patients with HCC who underwent hepatectomy.

Feasibility of a novel laparoscopic technique with unidirectional knotless barbed sutures for the primary closure of duodenal ulcer perforation.

BACKGROUND: Laparoscopic primary repair is one of the main procedures used for perforated gastric ulcers, and this technique requires reproducible and secure suturing. The aim of this study was to investigate the safety and efficacy of a novel continuous suture method with barbed sutures during laparoscopic repair for perforated peptic ulcers. PATIENTS AND METHODS: Clinical data from 116 consecutive patients undergoing laparoscopic repair for perforated peptic ulcers were collected between November 2009 and October 2015. Continuous suturing with 15-cm-long unidirectional absorbable barbed sutures was used for laparoscopic repair in the study group, termed group V (n = 51). Patients who underwent laparoscopic repair with conventional interrupted sutures were defined as group C (n = 65). The complication and operative data were compared between groups. RESULTS: Although there was no difference between group V and group C in the overall complication rate (15.7% vs. 24.6%; p = 0.259), the complication rate related to suturing was lower (3.9% vs. 15.4%; p = 0.04) in group V. Group V showed rates of 0% for leakage, 2% for intra-abdominal fluid collection, and 2% for stricture; the corresponding rates in group C were 3.1, 7.7, and 4.6%, respectively. Regarding operative data, the total operation time (V vs. C, 87.7 min vs. 131.2 min), total suture time (7.1 min vs. 25.3 min), and suture time per stitch (1.2 min vs. 6.2 min) were significantly shorter in group V than in group C (p < 0.001). CONCLUSION: The use of a continuous suture technique with unidirectional barbed sutures is as safe as the conventional suture technique and allows easier and faster suturing in the repair of perforated peptic ulcers.