Search

Background/objective: Robotic pancreaticoduodenectomy in ampullary cancer has never been studied. This study aimed to clarify the feasibility and justification of robotic pancreaticoduodenectomy in ampullary cancer in terms of surgical risks, and oncologic and survival outcomes. Methods: A propensity score-matching comparison of robotic and open pancreaticoduodenectomy based on seven factors commonly used to predict the survival outcomes in ampullary cancer patients. Results: A total of 147 patients were enrolled, of which 101 and 46 underwent robotic and open pancreaticoduodenectomies, respectively. After propensity score-matching with a 2:1 ratio, 88 and 44 patients in the robotic and open pancreaticoduodenectomy groups were included. The operation time was of no significant difference after matching. The median intraoperative blood loss was much less in those who underwent robotic pancreaticoduodenectomy, both before (median, 120 vs. 320 c.c. P

Abstract The study of robotic pancreaticouodenectomy (RPD) focusing on delayed gastric emptying (DGE) is seldom reported. This study explored the incidence of DGE in RPD with extracorporeal hand-sewn gastrojejunostomy involving downward positioning of the stomach. Patients with periampullary lesions undergoing RPD or open pancreaticouodenectomy (OPD) were included for comparison. A variety of clinical factors were evaluated for the risk of developing DGE. There were 409 (68.2%) RPD and 191 (31.8%) OPD in this study. DGE occurred in 7.7% of patients after pancreaticoduodenectomy, with 4.4% in RPD and 14.7% in OPD, p 200 c.c. was the other factor related to DGE (11.2% vs. 4.4% in those with blood loss ≤ 200 c.c.). None of the postoperative complications was significantly associated with DGE. Hospital stay was significantly longer in the group with DGE (median, 37 vs. 20 days in the group without DGE). After multivariate analysis by binary logistic regression, compared with OPD, RPD was the only independent factor associated with a lower incidence of DGE. RPD with extracorporeal hand-sewn antecolic, antiperistaltic, and inframesocolic gastrojejunostomy via a small umbilical wound involving careful downward positioning of the stomach was associated with a low incidence of DGE and presented as the most powerful independent predictor of this condition.

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by right–left reversal of visceral organs and dextrocardia; the use of robotic pancreaticoduodenectomy (RPD) may be challenging in these patients. A male patient presented with jaundice; imaging studies revealed a bile duct tumor and SIT with variant celiacomesenteric trunk and multiple vascular anomalies. RPD was carried out cautiously and successfully. The trocar port design mirrored that of a normal patient. Pathological examination revealed extrahepatic bile duct adenocarcinoma, classified as pT3N1M0, stage IIB. The patient recovered uneventfully. Although difficult, RPD is technically feasible in an SIT patient with cholangiocarcinoma.

Summary: Background/objective: This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia. Methods: Patients undergoing pancreas transplant with enteric drainage were included. Clinical data and outcomes were evaluated and compared between each subgroup. Results: There were 165 cases of pancreas transplant, including 38 (23 %) simultaneous pancreas-kidney transplant (SPK), 24 (15 %) pancreas after kidney transplant (PAK), 75 (46 %) pancreas transplant alone (PTA), and 28 (17 %) pancreas before kidney transplant (PBK). The overall surgical complication rate was 46.1 %, with highest (62.5 %) in PAK and lowest (32.0 %) in PTA, P = 0.008. The late complications included 32.7 % infection and 3.6 % malignancy. Overall rejection of pancreas graft was 24.8 % including 18.2 % acute and 9.7 % chronic rejection. Rejection was highest in PTA group (36.0 %) and lowest in PBK (3.6 %). There were 56 cases (33.9 %) with graft loss in total, with highest graft loss rate in PTA (38.7 %). The 1-year, 5-year and 10-year pancreas graft survivals for total patients were 98.0 %, 87.7 % and 70.9 % respectively. Conclusions: Enteric drainage in pancreas transplant could be applied safely not only in SPK but also in other subgroups. Enteric drainage itself would not compromise the immunological and graft survival outcomes.

Abstract Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.

Abstract Pancreaticoduodenectomy, so‐called “Whipple operation,” is a time‐consuming and technically demanding complex operation. Traditionally, this procedure has been performed most usually by open approach, which results in a large and painful wound. With the introduction of laparoscopic and robotic surgery, minimally invasive surgery (MIS) has emerged as a worldwide trend to improve wound cosmesis and to minimize wound pain. Although MIS for pancreaticoduodenectomy has also been attempted at some centers, the role of MIS, either robotic or laparoscopic approach, has not been well‐established for complex pancreaticoduodenectomy. Given that laparoscopic pancreaticoduodenectomy has been limited by its technical complexity and the high level of advanced laparoscopic skills required for pancreatic reconstruction, a robotic surgical system is introduced to overcome several limitations related to the laparoscopic approach. Providing high‐quality three‐dimensional (3‐D) vision, high optical magnification, articulation of robotic instruments, greater precision with suture targeting, and elimination of surgeon tremor, robotic surgical systems innovatively perform more delicate and complex procedures involving extensive dissection and suturing techniques such as pancreaticoduodenectomy. Although associated with longer operative time, robotic pancreaticoduodenectomy (RPD) has been claimed to have the benefits of less delayed gastric emptying, less blood loss, shorter length of postoperative stay, and lower wound infection rate, as compared with the traditional open pancreaticoduodenectomy (OPD). Moreover, RPD seems to be not only technically feasible but also justified without compromising the survival outcomes for pancreatic head and ampullary adenocarcinomas. Therefore, RPD could be recommended not only to surgeons but also to patients in terms of surgical feasibility, surgical outcomes, and patient satisfaction.

Abstract Background and Aims There is no consensus on the superiority of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP). Methods Data of patients undergoing RDP and LDP were prospectively collected and compared. Results There were 65 RDP and 112 LDP. RDP took a shorter operation time than LDP. Overall, DP with splenectomy took a longer operation time than that with spleen preservation. This difference was only significant in LDP group. In both RDP and LDP groups, splenectomy was associated with increased blood loss, as compared with spleen preservation. No significant differences were observed in surgical morbidity between RDP and LDP. The hospital cost in RDP was almost double that of LDP, with a median of 13,404 versus 7765 USD. Conclusion LDP is comparable to RDP in regard to surgical outcomes. LDP with spleen preservation is highly recommended whenever possible and feasible for benign or low malignant lesions in terms of lower costs and less blood loss.

Abstract Residual intra-peritoneal gas may be associated with post-laparoscopic shoulder pain (PLSP), which is a frequently and disturbance compliant after surgery. Herein, we aimed to examine whether expiring residual gas via a surgical drain reduces the frequency and intensity of PLSP in the first day after laparoscopic cholecystectomy. 448 participants were enrolled in this prospective cohort study. The incidence and severity of PLSP after surgery were recorded. Of these, the cumulative incidence of PLSP in the drain group was lower particularly at the 12th postoperative hour (18.3% vs. 27.6%; P = 0.022), 24th postoperative hour (28.8% vs. 38.1%; P = 0.039), and throughout the first postoperative day (P = 0.035). The drain group had less severe PLSP (crude Odds ratio, 0.66; P = .036). After adjustment using inverse probability of treatment weighting, the drain group also had a significant lower PLSP incidence (adjusted hazard ratio = 0.61, P

Summary: Background/Objective: There are no reports available on patient satisfaction and quality-of-life after robotic pancreaticoduodenectomy (RPD). This study aimed to evaluate not only surgical outcomes but also patient satisfaction after RPD. Methods: Prospectively collected data for RPD were analyzed for surgical outcomes. Questionnaires were sent to patients to assess patient satisfaction regarding RPD. Results: The study included 105 patients who underwent RPD, with 44 (41.9%) patients presenting with associated surgical complications. There were no significant differences between the without and with complication groups in median console time (390 min. Vs. 373 min.), blood loss (100 mL vs. 100 mL), and harvested lymph node number (14 vs. 15). There was no surgical mortality in this study. Major complications ≥ Clavien–Dindo III occurred in 7.6% of the total 105 RPD patients. The most common complication was chyle leakage (18.1%), followed by postoperative pancreatic fistula (5.7%), intra-abdominal abscess (4.8%), delayed gastric emptying (3.8%), and post pancreatectomy hemorrhage (3.8%). Almost all of the patients responded to this RPD-related survey with “fair” to “excellent” grades for all items, except 1 (

BackgroundTo date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC).MethodsIn total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients.ResultsAmong the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC.ConclusionsCardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.

Circulating cell-free DNA (cfDNA) in ampullary cancer patients was measured to clarify the correlation between cfDNA and clinicopathological factors and the impact of cfDNA on survival outcomes. Patients with ampullary cancer undergoing pancreaticoduodenectomy were included. Correlations between cfDNA and clinicopathological and prognostic factors were determined. The cfDNA levels in patients ranged from 1282 to 21,674 copies/mL, with a median of 6687 copies/mL. The cfDNA level was significantly higher in patients with lymph node involvement, lymphovascular invasion, abnormal serum carcinoembryonic antigen (CEA) level, and stage II and III cancer. Poor prognostic factors for ampullary cancer included high cfDNA > 6687 copies/mL, lymph node involvement, abnormal serum CEA > 5 ng/mL, and advanced stage II and III cancer. The 1- and 5-year survival rates were 92.0% and 66.5%, respectively, for patients with low cfDNA < 6687 copies/mL and 84.0% and 49.9%, respectively, for patients with high cfDNA > 6687 copies/mL (p < 0.001). After multivariate analysis, only the cfDNA level and stage were independent prognostic factors of ampullary cancer. Thus, the cfDNA level could act as a surrogate marker of both disease extent and biological aggressiveness of ampullary cancer. Moreover, cfDNA plays a significant role in the prognosis of resectable ampullary cancer.

Abstract Background Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. Methods Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and real-time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on cancer cell/endothelial cell interactions was assessed using co-culture and ELISA. Results In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells. Conclusion We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast cancer patients.

Abstract Background As life expectancy continues to increase around the world, the use of minimally invasive surgery (MIS) could be beneficial for octogenarian and older gastric cancer patients. Methods A total of 359 gastric cancer patients who underwent curative surgery between March 2011 and March 2015 were enrolled; 80 of these patients (22.2%) were octogenarians and older. Surgical approaches included MIS (50 laparoscopic and 65 robotic) and open surgery (n = 244). Surgical outcomes of MIS and open surgery in octogenarian and older patients were compared with younger patients. Results Among octogenarian and older patients, relative to open surgery (n = 53), MIS (n = 27) was associated with less operative blood loss, a shorter postoperative hospital stay and similar rates of surgical complications and mortality. For MIS (n = 115), octogenarian and older patients exhibited similar postoperative outcomes to those of younger patients. For open surgery (n = 244), relative to younger patients, octogenarian and older patients experienced longer postoperative hospital stays, a higher rate of wound infection and a higher incidence of pneumonia. Conclusions MIS for gastric cancer is beneficial and can be performed safely in octogenarian and older patients.

Abstract Background/aim Evidence shows that Luminal A breast cancer is likely to undergo bone metastasis, but the mechanisms involved remain unknown. This study’s aim was to demonstrate a correlation between estrogen receptor (ER) positivity and bone metastasis as the clinically preferred site of metastasis, as well as investigating the role of ERα-Src signaling in MCF-7 cells using Snail over-expression as an in vivo bone metastasis model. Methods Clinically, the records of breast cancer with distant metastasis were retrospectively reviewed to correlate breast cancer subtypes and preferential metastatic sites. An in vivo bone metastasis model was created by injection of MCF-7 cells with/without Snail over-expression into the tibia of nude mice. The human MCF-7 cells that over-expressed (o/e) Snail were examined and the expression of epithelial–mesenchymal transitions (EMT) markers, ER-Src signaling proteins and p190 RhoGAP analyzed by Western blotting and real-time PCR. The role of ERα was elucidated using ESR1 silence by transfecting shRNA (∆ESR1) into MCF-7 o/e Snail cells in vitro and in vivo. Results The clinical results showed that ER ≥1% breast cancers showed a positive correlation with bone metastasis, which was found to be the preferred site of metastasis. An in vivo bone metastasis was successfully established using injection of MCF-7 o/e Snail cells into the tibia of nude mice, but no such metastasis was found using control MCF-7 cells. The proteins expressed in MCF-7 o/e Snail cells showed an EMT pattern, while those of the MCF-7 o/e Snail metastatic tissue showed a mesenchymal–epithelial pattern. There was an increase in cytosolic Src, p190 RhoGAP and nuclear ERα proteins, but not in Snail, in MCF-7 o/e Snail tissue compared to the same cell line in vitro. ESR1 knock down decreased Src and p190 RhoGAP expression in vitro and also decreased the incidence of bone metastasis in vivo. Conclusion We conclude that ER-Src signaling plays an important role in ER (+) breast cancer, which shows a high potential for bone metastasis.

Abstract Background Gallbladder metastasis from renal cell carcinoma (RCC) is extremely rare. The purpose of this study is to clarify the characteristics of metastatic RCC to gallbladder. Methods The pooled data for analysis were collected from the case of metastatic RCC to gallbladder encountered by our institution along with sporadic cases reported in literature from 1991 to 2015. Results A total of 50 cases of metastatic RCC to gallbladder were recruited for study. Fifty-seven percentage of the primary RCC was from the right kidney and 43% from the left. The median interval between diagnoses of primary and metastatic RCC to gallbladder was 36 months, with the longest duration up to 324 months. Most (70%) were asymptomatic. The size of metastatic RCC to gallbladder ranged from 0.8 cm to 9 cm, with median of 2.6 cm. Majority (91%) of the metastatic RCCs presented as a polypoid mass with narrow stalk, and 82% were hypervascular lesion. The overall 1 year, 3 year and 5 year survival rate was 91.5%, 76.2% and 59.3% respectively, with a median of 26.5 months. Number of the metastatic site, timing of gallbladder metastasis, symptom, tumor size and operation type of cholecystectomy seemed to have no impact on survival. Conclusions Metastatic RCC to the gallbladder should be taken into account for a gallbladder polypoid mass with narrow hypervascular stalk during the diagnosis and/or follow-up of primary RCC. Gallbladder metastasis from RCC is not necessarily to be an advanced stage with poor outcome, and cholecystectomy is recommended whenever possible.

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.

Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) is one of four major gastric cancer types and is traditionally considered to be related to lymphoepithelioma-like GC. Few studies have investigated the clinical significance of EBV infection in intestinal/solid type, diffuse (poorly cohesive) type, and lymphoepithelioma-like GC. Methods: A total of 460 GC patients receiving curative surgery were enrolled. The clinicopathological features, genetic alterations and prognoses were compared between patients with and without EBV infection. Results: EBV-positive GC patients (n = 43) had more tumors located in the upper and middle stomach, more common in lymphoepithelioma-like carcinoma, more lymphoid stroma, fewer Helicobacter pylori infections, and higher programmed death-ligand 1 (PD-L1) expression than EBV-negative GC patients. For intestinal/solid type GC, EBV-positive tumors were more likely to be located in the upper and middle stomach, have more lymphoid stroma, fewer Helicobacter pylori infections, higher PD-L1 expression, and more liver metastases than EBV-negative tumors. For diffuse (poorly cohesive) type GC, EBV-positive tumors were more likely to be located in the upper stomach, and have more lymphoid stroma than EBV-negative tumors. For lymphoepithelioma-like GC, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors. Conclusions: Intestinal/solid type GC patients with EBV-positive tumors were associated with higher PD-L1 expression and more liver metastases, while lymphoepithelioma-like GC patients with EBV-positive tumors had more PI3K/AKT pathway mutations. Immunotherapy and targeted therapy may be beneficial for these groups of patients. Routine EBV survey is recommended in GC.

Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST− tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST− tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST− tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.

We detected a significant elevation of serum HSP90α levels in pancreatitis patients and even more in pancreatic ductal adenocarcinoma (PDAC) patients. However, there was no significant difference in the serum HSP90α levels between patients with early-stage and late-stage PDAC. To study whether elevation of serum HSP90α levels occurred early during PDAC development, we used LSL-KrasG12D/Pdx1-Cre transgenic mice as a studying model. Elevated serum HSP90α levels were detected before PDAC formation and an extracellular HSP90α (eHSP90α) inhibitor effectively prevented PDAC development. Both serum HSP90α level and pancreatic lesion were suppressed when the mice were administered a CD11b-antagonizing antibody, suggesting that CD11b+-myeloid cells were associated with eHSP90α levels and pancreatic carcinogenesis. Consistently, in CD11b-DTR-EGFP transgenic mouse model with CD11b+-myeloid cells depletion, serum HSP90α levels were suppressed and Panc-02 cell grafts failed to develop tumors. Macrophages and granulocytes are two common tissue-infiltrating CD11b+-myeloid cells. Duplex in situ hybridization assays suggested that macrophages were predominant HSP90α-expressing CD11b+-myeloid cells during PDAC development. Immunohistochemical and immunohistofluorescent staining results revealed that HSP90α-expressing cells included not only macrophages but also pancreatic ductal epithelial (PDE) cells. Cell culture studies also indicated that eHSP90α could be produced by macrophages and macrophage-stimulated PDE cells. Macrophages not only secreted significant amount of HSP90α, but also secreted interleukin-6 and interleukin-8 to induce a JAK2−STAT3 signaling axis in PDE cells, stimulating them to express and secrete HSP90α. eHSP90α further promoted cellular epithelial-mesenchymal transition, migration, and invasion in PDE cells. Besides myeloid cells, eHSP90α can be potentially taken as a target to suppress PDAC pathogenesis.

Objectives: Robotic gastrectomy has become increasingly popular in the treatment of gastric cancer, especially in Asian countries. The use of indocyanine green fluorescence has been reported in lymphatic mapping for gastric cancer in laparoscopic gastrectomy; however, there have been few reports regarding the use of indocyanine green in robotic gastrectomy. Methods: From January 2011 to March 2016, a total of 79 patients underwent robotic gastrectomy for gastric cancer. Among them, intraoperative subserosal injection (n = 9) or preoperative submucosal injection (n = 5) of indocyanine green with near-infrared imaging was performed in 14 patients, and the other 65 patients underwent robotic gastrectomy without the use of indocyanine green. Results: There was no significant difference in the operative time, total number of retrieved lymph nodes, operative blood loss, and postoperative hospital stay between the patients who underwent robotic gastrectomy with or without indocyanine green fluorescence. For each lymph node station, there was significantly more number of retrieved lymph nodes in the indocyanine green group than in the no-indocyanine green group at the greater curvature side of the low body (#4d) to the infrapyloric region (#6) of the stomach. Five of the 14 patients who received an indocyanine green injection for lymphatic mapping had lymph node metastasis, and metastatic lymph nodes were located in the lymph node stations as detected by indocyanine green fluorescence during surgery. Conclusion: Indocyanine green fluorescence with near-infrared imaging is feasible and is a promising method of lymphatic mapping in robotic gastrectomy for gastric cancer. In future studies, larger patient numbers and long-term follow-up are required.

The classification of pathological tumor-node-metastasis (pTNM) staging of gastric cancer was revised in the 8th American Joint Committee on Cancer (AJCC) edition. The major revision was the separation of pN3a and pN3b in the pTNM staging. The current study evaluated the prognostic impact of this change.A total of 1,517 patients who underwent curative surgery for gastric cancer with a retrieved lymph node number ≥15 at our institution from January 1995 to December 2011 were enrolled. Survival was compared for the disease classified according to both the 7th and 8th editions.After separation of pN3a and pN3b in the pTNM stage definition, the 8th edition still provides significant survival differences between each stage. The multivariate analysis demonstrated that the pTNM stage in both the 7th and 8th editions was an independent prognostic factors of overall survival and disease-free survival. The 8th edition has a better homogeneity than the 7th edition with a significantly higher likelihood ratio chi-square test. Regarding the OS and DFS, the time-dependent receiver operating characteristic (ROC) curves of the two staging systems are almost overlapping, indicating that the prognostic performance is comparable between the two staging systems.Both the 7th and 8th edition-based stages are independent prognostic factors for gastric cancer. The 8th edition has a better homogeneity than the 7th edition; the 8th edition provides discriminant survival differences among each pTNM stage that are comparable to those in the 7th edition.

There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells.We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples.The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS.Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in triple negative breast cancer cell. In addition, BDNF can function in either an autocrine or a paracrine manner to increase the migration ability of both MDA-MB-231 cells and HUVEC cells. Finally, overexpression of TrkB, but not of BDNF, is significantly associated with a poor survival outcome for TNBC patients.

Abstract.: This study investigated the herb–drug interaction of xanthorrhizol and tamoxifen in human breast cancer cells. Using MCF-7 cell line as an in vitro model, the herb–drug interaction between xanthorrhizol and tamoxifen was measured by MTT assay, luciferase reporter assay, and cell cycle analysis. The effects of xanthorrhizol on growth/autophagy related signaling were determined by immunostaining, western blotting, and real time RT-PCR. Additionally, the in vivo effect of xanthorrhizol and tamoxifen on athymic nude mice implanted with MCF-7 cells was evaluated. When MCF-7 cells were co-treated with tamoxifen and xanthorrhizol, there were no significant changes in terms of cell number, luciferase activity, percentage S-phase cells and LC3-II expression. However, using the MCF-7 implanted nude mice model, it was possible to detect significantly increased tumor volumes, a larger tumor size, and increased protein expression of P38 and P27(Kip1) in the xanthorrhizol + tamoxifen group compared to the tamoxifen-alone group. It can be concluded that while there is no significant herb–drug interaction between xanthorrhizol and tamoxifen in vitro, there is such an interaction in tumor-bearing mice, which provides important information that affects breast cancer treatment translational research. Keywords:: breast cancer, tamoxifen, interaction, xanthorrhizol

Pancreatic leakage is a leading cause of morbidity and mortality after pancreaticoduodenectomy (PD). Pancreaticogastrostomy (PG) has been reported to be associated with a lower pancreatic leakage rate and morbidity rate than pancreaticojejunostomy (PJ). This study compared the preoperative characteristics, surgical risk factors, intraoperative parameters, and postoperative outcome between PJ and PG. Methods: From March 1992 to March 2005, a comparative study between PJ and PG for patients with periampullary lesions undergoing PD was conducted. A total of 377 consecutive patients underwent PD. Among them, 188 patients underwent PJ and 189 underwent PG. Results: The overall mortality, morbidity and pancreatic leakage following PD were 5%, 45.1% and 10.6%, respectively. The mortality, morbidity and pancreatic leakage were 8.9%, 56.4% and 17.6% in the PJ group, and 2.1%, 33.9% and 3.7% in the PG group (p< 0.001). Mean operative time was 9.3 hours versus 6.7 hours (p < 0.001), mean blood loss was 1032 mL versus 891 mL (p = 0.064) and mean hospital stay was 34.8 days versus 26.1 days (p 65 years) were identified as risk factors for pancreatic leakage, while PJ, soft pancreas, pancreatic duct stenting and low surgical volume (< 20) were four significant risk factors for surgical morbidity. Further, PJ, pancreatic leakage, low surgical volume ( 65 years) were identified to be surgical risk factors for mortality. Conclusion: PG is a safer method than PJ following PD as a significantly lower rate of pancreatic leakage, surgical morbidity and mortality, shorter operation time, and shorter postoperative hospital stay are reported.