Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

TMS motor thresholds correlate with TDCS electric field strengths in hand motor area

Transcranial direct current stimulation (TDCS) modulates cortical activity and influences motor and cognitive functions in both healthy and clinical populations. However, there is large inter-individual variability in the responses to TDCS. Computational studies have suggested that inter-individual differences in cranial and brain anatomy may contribute to this variability via creating varying electric fields in the brain. This implies that the electric fields or their strength and orientation should be considered and incorporated when selecting the TDCS dose. Unfortunately, electric field modeling is difficult to perform; thus, a more-robust and practical method of estimating the strength of TDCS electric fields for experimental use is required. As recent studies have revealed a relationship between the sensitivity to TMS and motor cortical TDCS after-effects, the aim of the present study was to investigate whether the resting motor threshold (RMT), a simple measure of transcranial magnetic stimulation (TMS)sensitivity, would be useful for estimating TDCS electric field strengths in the hand area of primary motor cortex (M1). To achieve this, we measured the RMT in 28 subjects. We also obtained magnetic resonance images from each subject to build individual three-dimensional anatomic models, which were used in solving the TDCS and TMS electric fields using the finite element method (FEM). Then, we calculated the correlation between the measured RMT and the modeled TDCS electric fields. We found that the RMT correlated with the TDCS electric fields in hand M1 (R2 = 0.58), but no obvious correlations were identified in regions outside M1. The found correlation was mainly due to a correlation between the TDCS and TMS electric fields, both of which were affected by individual's anatomic features. In conclusion, the RMT could provide a useful tool for estimating cortical electric fields for motor cortical TDCS.Peer reviewe

Benefits and limitations of middle bile duct segmental resection for extrahepatic cholangiocarcinoma

Background: Pancreaticoduodenectomy (PD) is a standardized strategy for patients with middle and distal bile duct cancers. The aim of this study was to compare clinicopathological features of bile duct segmental resection (BDR) with PD in patients with extrahepatic cholangiocarcinoma. Methods: Consecutive cases with extrahepatic cholangiocarcinoma who underwent BDR (n = 21) or PD (n = 84) with achievement of R0 or R1 resection in Kobe University Hospital between January 2000 and December 2016 were enrolled in the present study. Results: Patients who underwent PD were significantly younger than those receiving BDR. The frequency of preoperative jaundice, biliary drainage and cholangitis was not significantly different between the two groups. The duration of surgery was longer and there was more intraoperative bleeding in the PD than in the BDR group (553 vs. 421 min, and 770 vs. 402 mL; both PClavien-Dindo IIIa) were observed in the PD group (46% vs. 10%, P<0.01). Postoperative hospital stay was also longer in that group (30 vs. 19 days, P = 0.02). Pathological assessment revealed that tumors were less advanced in the BDR group but the rate of lymph node metastasis was similar in both groups (33% in BDR and 48% in PD, P = 0.24). The rate of R0 resection was significantly higher in the PD group (80% vs. 38%, P<0.01). Adjuvant chemotherapy was more frequently administered to patients in the BDR group (62% vs. 38%, P = 0.04). Although 5-year overall survival rates were similar in both groups (44% for BDR and 51% for PD, P = 0.72), in patients with T1 and T2, the BDR group tended to have poorer prognosis (44% vs. 68% at 5-year, P = 0.09). Conclusions: BDR was comparable in prognosis to PD in middle bile duct cancer. Less invasiveness and lower morbidity of BDR justified this technique for selected patients in a poor general condition

Lymphadenectomy Combined with Locoregional Treatment for Multiple Advanced Hepatocellular Carcinoma with Lymph Node Metastases

Lymphadenectomy of lymph node metastasis (LNM) from hepatocellular carcinoma (HCC) may potentially improve survival of patients with intrahepatic tumors controllable by means of locolegional treatment. However, the treatment strategy has not gained wide clinical acceptance, especially in patients with multiple advanced HCC. Thus, the purpose of this study is to evaluate the role of lymphadenectomy combined with locoregional treatment for the management of multiple advanced HCC with LNM.Between January 1998 and August 2012, 15 patients underwent a selective lymphadenectomy either concurrently or sequentially after hepatectomy. Seven of 15 patients underwent reductive hepatectomy while the remaining 8 patients had hepatectomy at curative intent. In patients with reductive hepatectomy, lymphadenectomy was concurrently performed and the residual intrahepatic tumors were treated thereafter with additional locoregional treatments consisting of transcatheter arterial chemoembolization, radiofrequency ablation, and percutaneous isolated hepatic perfusion.Only 4 patients (26.6%) of 15 patients developed lymph node recurrence. However, intrahepateic recurrence was encountered in 13 of 15 patients. The median survival time after lymphadenectomy was 25.2 months with the overall survival rates at 1, 2, and 3 years being 76.9%, 52.7%, and 26.4%, respectively. Selective lymphadenectomy and multimodal locoregional treatment in patients with multiple residual tumors exhibited a similar overall survival to complete resection of LNM and intrahepatic tumors (P=0.78).Lymphadenectomy combined with an additional aggressive locoregional treatments may be justified in selected patients with multiple advanced HCC with LN

The Predictive Power of Serum α-Fetoprotein and Des-γ-Carboxy Prothrombin for Survival Varies by Tumor Size in Hepatocellular Carcinoma

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP.181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy.The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors >5 cm.The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved