Impact of hepatic artery variation on surgical and oncological outcomes in robotic pancreaticoduodenectomy.

BACKGROUND: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. METHODS: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV ( +) and (-) patients were compared. RESULTS: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV ( +) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV ( +) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (-) patients. There was no significant difference between the HAV ( +) and (-) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV ( +) and (-) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV ( +) group. CONCLUSIONS: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV ( +). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively.

Propensity score-matched comparison of the oncological feasibility and survival outcomes for pancreatic adenocarcinoma with robotic and open pancreatoduodenectomy.

BACKGROUND: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. METHODS: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. RESULTS: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). CONCLUSION: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results.

Surgical, survival, and oncological outcomes after vascular resection in robotic and open pancreaticoduodenectomy.

BACKGROUND: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD). METHODS: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group). RESULTS: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group. CONCLUSIONS: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection.

Printing a Three-Dimensional Patient-Specific Safety Device for Reducing the Potential Risk of Mental Nerve Injury During Transoral Thyroidectomy.

BACKGROUND: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. METHODS: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. RESULTS: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. CONCLUSIONS: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive.

Comparison of the Clinicopathological Characteristics and Genetic Alterations Between Patients with Gastric Cancer with or Without Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC). MATERIALS AND METHODS: Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein-Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single-nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared. RESULTS: Among the 356 patients, 185 (52.0%) had HP infection. For intestinal-type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse-type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability-high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5-year overall survival (87.7% vs. 73.9%, p = .012) and disease-free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal-type GC. For EBV-negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5-year overall survival and disease-free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease-free survival. CONCLUSION: Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV-negative and intestinal-type GC. IMPLICATIONS FOR PRACTICE: Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein-Barr virus (EBV)-negative and intestinal-type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease-free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.

Clinicopathological differences in signet ring cell adenocarcinoma between early and advanced gastric cancer.

BACKGROUND: Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate. METHODS: From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients. RESULTS: The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017). CONCLUSION: The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection.

A comparison of the molecular subtypes of triple-negative breast cancer among non-Asian and Taiwanese women.

BACKGROUND: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women. METHODS: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes. RESULTS: The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification. CONCLUSION: Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.

Role of estrogen receptors and Src signaling in mechanisms of bone metastasis by estrogen receptor positive breast cancers.

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.

Metastatic polyp of the gallbladder from renal cell carcinoma.

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.

Polypoid lesions of the gallbladder: analysis of 1204 patients with long-term follow-up.

BACKGROUND: Polypoid lesions of the gallbladder (PLG) are common, and most are benign. Few lesions are found to be malignant, but are not preoperatively distinguished as such using common imaging modalities. Therefore, we compared characteristics of benign and malignant PLGs in depth. METHODS: We enrolled 1204 consecutive patients diagnosed with PLG at Taipei Veterans General Hospital between January 2004 and December 2013. Patients underwent either surgery or regular follow-up with various imaging modalities for at least 24 months. The mean follow-up duration was 72 ± 32 months. RESULTS: Of 1204 patients, 194 underwent surgical treatment and 1010, regular follow-up. In addition, 73 % patients were asymptomatic. The mean PLG size was 6.9 ± 7.7 (range 0.8-129) mm; the PLGs of 337 patients (28 %) grew during their follow-up periods. The majority of PLGs (90.4 %) were single lesions, and 10.5 % of patients had associated gallstones. The PLGs of 20.1 % of surgical patients were malignant. Malignant PLGs were found in 32.4 % of patients ≥50 years old and in 4.7 % of those <50 years old (p < 0.001). Right quadrant abdominal pain, epigastric pain, and body weight loss were the three most common symptoms associated with malignancy. Malignant PLGs were significantly larger than benign lesions (means: 27.5 ± 18.4 mm vs. 12.3 ± 12.3 mm, respectively, p < 0.001). Notably, the size of 5 % of malignant PLGs was 3-5 mm, and that of 8 % was 5-10 mm. The negative predictive value for gallbladder malignancy was 92.8 % based on a size ≥10 mm and 100 % based on a size ≥3 mm. CONCLUSIONS: Our study reassesses the PLG size that warrants more aggressive intervention. Cholecystectomy remains mandatory for PLGs > 10 mm, but should also be considered a definitive diagnostic and treatment modality for PLGs with diameters of 3-10 mm.

Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs.

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.

Comparison of the surgical outcomes of minimally invasive and open surgery for octogenarian and older compared to younger gastric cancer patients: a retrospective cohort study.

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.

Clinical significance of circulating plasma DNA in gastric cancer.

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.

Prognostic factors of primary resected retroperitoneal soft tissue sarcoma: Analysis from a single asian tertiary center and external validation of gronchi's nomogram.

BACKGROUND: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. METHODS: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July 30th, 2011. The prognostic influence of clinicopathological characteristics as well as treatments on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were examined by univariate and multivariate analyses. A histology-specific nomogram developed by Gronchi et al was used for validation. RESULTS: Liposarcoma, leiomyosarcoma, and malignant peripheral sheath tumor (MPNST) were the most common histologies (70%). Multivariate analysis revealed FNCLCC tumor grade was the most significant prognostic factor for OS (P = 0.001) and DMFS (P < 0.001) and complete resection was the only significant prognostic factor for LRFS (P = 0.043). Incomplete resection of grade 3 tumor was significantly associated with a worse OS. Despite some differences in characteristics between our patients and Gronchi's cohort, external validation of Gronchi's nomogram demonstrated excellent concordance in predicting survival. CONCLUSIONS: Our study demonstrated tumor grade and surgical margins had significant prognostic influence and the Gronchi's nomogram has an excellent applicability in predicting survival of STS patients. J. Surg. Oncol. 2016;113:355-360. © 2016 Wiley Periodicals, Inc.

Comparison of Modified Blumgart pancreaticojejunostomy and pancreaticogastrostomy after pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to compare perioperative outcomes after Blumgart pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) for pancreatic-enteric reconstruction following pancreaticoduodenectomy. METHODS: Data of patients undergoing Blumgart PJ and PG were retrieved from prospectively-collected database. Matched patients in each surgical groups were included based on the Callery risk scoring system for clinically relevant postoperative pancreatic fistula (CR-POPF) (grades B and C). Surgical parameters and risks were compared between these two groups. RESULTS: A total of 206 patients undergoing PD were included. Blumgart PJ was associated with shorter postoperative hospital stay (median (range) 25 (10-99) vs. 27 (10-97) days, P = 0.022). There was no surgical mortality in the Blumgart PJ group, but a 4.9% perioperative mortality in the PG, P = 0.030. The CR-POPF by Blumgrt PG is significantly lower than that by PG for overall patients (7% vs. 20%, P = 0.007), especially for those in intermediate fistula risk zone (6% vs. 21%, P =0.048) and high fistula risk zone (14% vs. 47%, P=0.038). CONCLUSIONS: Blumgart PJ is superior to PG in terms of pancreatic leakage and surgical mortality. Blumgart PJ can be recommended for pancreatic reconstruction after PD for all pancreatic remnant subtypes.

The Correlation Between RhoA Expression and Clinicopathological Characteristics in Gastric Cancer Patients After Curative Surgery.

BACKGROUND: The expression of RhoA, a member of the ras homologue family, is reported to be involved in tumorigenesis in some cancers; however, its prognostic value in gastric cancer is controversial. METHODS: Between April 1988 and January 2005, a total of 206 gastric cancer patients receiving curative surgery were enrolled in this study. Immunohistochemical staining of the RhoA protein was performed, and the clinicopathological characteristics and initial recurrence patterns were compared between low RhoA expression (n = 55) and high RhoA expression (n = 151) gastric cancer patients. RESULTS: For intestinal-type (n = 134) gastric cancer, there is no significant difference between the clinicopathological characteristics and RhoA expression. However, for diffuse-type (n = 82) gastric cancer, high RhoA expression was associated with more advanced pathological N category compared to low RhoA expression. A multivariate analysis revealed that age, pathological T and N categories, and RhoA expression were independent prognostic factors for overall survival after curative surgery. For all patients, the five-year overall survival rates and disease-free survival rates were higher in patients with low RhoA expression compared to those with high RhoA expression, which was observed in diffuse-type gastric cancer, not in intestinal-type gastric cancer. With regard to the initial recurrence pattern, patients with high RhoA expression had more distant metastasis compared to those with low RhoA expression, especially more liver metastasis. CONCLUSIONS: RhoA expression is an independent prognostic factor for gastric cancer, especially for diffuse-type. We should be aware of liver metastasis during the follow-up of gastric cancer with high RhoA expression.

The role of lymph nodes in predicting the prognosis of ampullary carcinoma after curative resection.

BACKGROUND: Lymph node involvement is one of the well-demonstrated prognostic factors in ampullary carcinoma. The aim of this study is to clarify the role of lymph nodes in predicting the survival outcome of ampullary carcinoma. METHODS: A cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma from 1999 to 2014 was retrospectively analyzed. The effect of node-associated variables, including lymph node status, positive lymph node number, total harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using univariate and multivariate analyses for survival outcome prediction. RESULTS: In 194 evaluable patients, univariate analysis demonstrated that stage, cell differentiation, perineural invasion, and nodal status were significant conventional prognostic factors. Concerning the node-associated variables, positive nodal status, positive lymph node number≥2, THLN number<14, and LNR≥0.15 were significantly associated with poorer survival outcomes, with a 5-year survival rate of 20.3, 38.9, 25.4, and 18%, respectively. By multivariate analysis, nodal status and THLN number were two independent predictors of survival. The most favorable 5-year survival rate was 84.4% in patients with negative nodal involvement and THLN number≥14, compared with the poorest 5-year survival rate of 16.1% in those with positive nodal status and THLN number<14. CONCLUSIONS: Tumor biology reflected by lymph node status is the most important independent prognostic factor; nevertheless, surgical radicality based on THLN number also plays a significant role in the survival outcome for patients with ampullary carcinoma after curative pancreaticoduodenectomy.

Hepatoid carcinoma of the pancreas.

BACKGROUND: Hepatoid carcinoma of the pancreas is extremely rare. This article tries to summarize the clinical features and outcomes of pancreatic hepatoid carcinoma. METHODS: The data pool for analysis includes the case we encountered with hepatoid carcinoma of the pancreas and the reported cases in the literature. RESULTS: Twenty-three cases of hepatoid carcinoma of the pancreas were analyzed. This tumor occurred more frequently in male than in female patients (69.6 vs. 30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic head, nausea/vomiting (62.5 %) is more common, followed by jaundice and epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in 60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form or mixed form with other malignancy (40.9 %), with the most common coexisted pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4 % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8 % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1 % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and lymph node metastases are associated with negative impact on survival outcome. CONCLUSIONS: Elevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma. This tumor could be mixed form with other malignancy. Surgical resection should be the treatment of choice whenever possible.

Herb-induced autoimmune-like hepatitis in C57BL/6J mice.

BACKGROUND & AIMS: Animal model suitable for studying herb-induced experimental autoimmune hepatitis (AIH) remains a challenging problem. A medicinal herb containing Scutellaria baicalensis Georgi (Sb) and Bupleurum chinense DC (Bc) has been sporadically reported to be related to liver fibrosis. The aim of this study was to investigate the effects of Sb and Bc on experimental AIH in mice. METHODS: C57BL/6J mice received intraperitoneal injection of Sb and/or Bc herbal extracts (1 mg/kg) for 4 or 8 weeks. Serum samples were collected to analyse serum transferase (AST, ALT), creatinine, markers for AIH and hepatic cytokine levels such as IFN-γ, IL10 and TGF-ß1. Peripheral mononuclear cell (PBMC) gene expression profiles were analysed to show their effects on immune system. RESULTS: Our results showed that Sb or Bc treatment increased serum AST, ALT, IgG and ANA levels. Prominent necroinflammatory changes were demonstrated in the livers of Sb- or Bc-treated mice while the decrease in IFN-γ and elevation of IL10 and TGF-ß1 levels in liver tissues. Furthermore, the PMBC gene expression profile suggested that Sb or Bc treatment could modulate immune responses. CONCLUSION: We conclude that the presence of AIH in Sb- or Bc-treated mice and C57BL/6J strain mice is a reliable animal model for studying herb-induced AIH-like hepatitis.

In vitro and in vivo effects of xanthorrhizol on human breast cancer MCF-7 cells treated with tamoxifen.

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.