Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer.

Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been identified in the blood circulation of patients with cancer metastasis, and metastatic cancer cells can recruit circulating CAFs. However, primary carcinoma sites usually regulate the behavior of metastatic cancer cells through exosomes. Here, we hypothesized that cancer-derived exosomes could enhance CAF recruitment. Exosomes secreted by pancreatic cancer cells (PANC-1 and MIA PaCa-2) were isolated and characterized. The ability of pancreatic cancer to recruit pancreatic stellate cells (PSCs) was assessed with Transwell assays in vitro and bioluminescent imaging in a mouse model in vivo, and the underlying molecular mechanism was also investigated. The results showed that pancreatic cancer cell-derived exosomes (Exo-Pan and Exo-Mia) promoted the pancreatic cancer recruitment of PSCs. This effect was mediated partially by the transfer of the exosomal protein Lin28B to the recipient cells to activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway. These results suggested that exosomes derived from local cancer could promote the formation of distant metastases through transferring the exosomal protein Lin28B to the metastatic cancer cells.

Radiofrequency ablation versus hepatic resection for breast cancer liver metastasis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for breast cancer liver metastases (BCLMs). METHODS: Studies that had examined the outcomes for both RFA and HR for BCLM were identified by searching the electronic databases PubMed, EMBASE, and the Cochrane Library. Pooled analyzes of the overall survival (OS), disease-free survival (DFS), and short-term outcomes of BCLM were performed. RESULTS: Patients with BCLM gained many more survival benefits from HR than from RFA with regard to the 3-year OS rate (combined odds ratio (OR) 0.41, 95% confidence interval (CI) 0.29-0.59, P<0.001), 5-year OS rate (combined OR 0.38, 95% CI 0.32-0.46, P<0.001), 3-year DFS (combined OR 0.36, 95% CI 0.27-0.49, P<0.001), and 5-year DFS (combined OR 0.51, 95% CI 0.40-0.66, P<0.001). RFA had fewer postoperative complications (combined OR 0.30, 95% CI 0.20-0.44, P<0.001) and shorter hospital stays (combined OR -9.01, 95% CI -13.49-4.54, P<0.001) than HR. CONCLUSIONS: HR takes precedence over RFA in the treatment of patients with BCLM, considering the better survival rate. RFA gives rise to fewer complications and can be carried out with a shorter hospital stay, compared to HR. RFA should be reserved for patients who are not optimum candidates for resection.

Predictive Factors for Differentiating Pancreatic Cancer-Associated Diabetes Mellitus from Common Type 2 Diabetes Mellitus for the Early Detection of Pancreatic Cancer.

BACKGROUND: The purpose of this study was to find the factors that may be helpful for differentiating pancreatic cancer-associated diabetes mellitus (PC + DM) from common type 2 diabetes for the early diagnosis of pancreatic cancer. METHODS: From January 2008 to August 2013, 171 patients with pancreatic cancer and new-onset diabetes were recruited for the study; 242 age- and gender-matched patients with common type 2 diabetes were also identified as control during the same period. The patient's characteristics and laboratory parameters were compared between the 2 groups. RESULTS: By multivariate logistic regression analysis, we found that body mass index (BMI), the age of onset of diabetes, hepatitis B virus (HBV) infection, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine (Cr), apolipoprotein-A1 (APO-A1), and white blood cell (WBC) were independent predictive factors for differentiating PC + DM from common type 2 diabetes; the areas under receiver operating characteristic curves were up to 0.815 for the combination of these 8 markers. CONCLUSIONS: These results suggest that BMI, the age of onset of diabetes, HBV infection, TBIL, ALT, Cr, APO-A1, and WBC are factors that could differentiate PC + DM from common type 2 -diabetes and may be used for early diagnosis of pancreatic cancer.

Effects of targeted CD97 immune epitopes small interference RNA on cellular biological behaviors in MDA-MB231 malignant breast cancer cell line.

Two CD97 immune epitopes, CD97EGF (epidermal growth factor domain) and CD97Stalk (stalk domain), have different distribution patterns in malignant epidermal tumors. However, little is known about the effect of CD97EGF and CD97Stalk immune epitopes in breast cancer metastasis. To explore the effects on cell proliferation, infiltration, apoptosis, and the cell cycle, we used small interfering RNA (siRNA) against CD97EGF and CD97Stalk immune epitopes to knock down CD97 in MDA-MB231 breast cancer cells. Compared with controls, CD97 knockdown caused decreased cell growth, proliferation, migration, infiltration, and altered distribution of the percentage of cells in G0/G1 and S phase. We suggest that the potential mechanism of CD97EGF and CD97Stalk immune epitopes on the biological behaviors of MDA-MB231 breast cancer cells may be related to the altered number of N-terminal glycosylation sites, which influence the stability and signaling intensity of CD97 heterodimers.

Enucleation of non-invasive tumors in the proximal pancreas: indications and outcomes compared with standard resections.

OBJECTIVE: The aim of this study was to evaluate the safety and efficiency of enucleation (EU) for proximal pancreatic non-invasive neoplasms. METHODS: Patients with solitary non-invasive neoplasms in the proximal pancreas from January 1998 to April 2014 at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China were included. Different operations and outcomes were analyzed. RESULTS: A total of 123 patients were enrolled. Forty patients (32.5%) underwent EU including 18 patients who had tumors close to the main pancreatic duct (MPD). Sixty-one patients (49.6%) had pancreaticoduodenectomy (PD) performed and 22 (17.9%) underwent central pancreatectomy (CP). Pathological outcomes included neuroendocrine tumors, cystic lesions, and solid pseudopapillary tumors. Operation time, intra-operative blood loss, and duration of hospital stay were significantly reduced in the EU group. PD was associated with the greatest complication rate (55.7%), followed by EU (50%) and CP (40.9%), though the pancreatic fistula rate after EU was the highest (50%), especially in patients with tumors larger than 3 cm and tumors close to the MPD. EU had advantages in the preservation of pancreatic parenchyma and endocrine and exocrine function. CONCLUSIONS: EU can be carried out safely and effectively for tumors in the proximal pancreas with improved outcomes compared with standard resections, even if the tumor is larger than 3 cm and close to the MPD.

3D Printout Models vs. 3D-Rendered Images: Which Is Better for Preoperative Planning?

INTRODUCTION: Correct interpretation of a patient's anatomy and changes that occurs secondary to a disease process are crucial in the preoperative process to ensure optimal surgical treatment. In this study, we presented 3 different pancreatic cancer cases to surgical residents in the form of 3D-rendered images and 3D-printed models to investigate which modality resulted in the most appropriate preoperative plan. METHODS: We selected 3 cases that would require significantly different preoperative plans based on key features identifiable in the preoperative computed tomography imaging. 3D volume rendering and 3D printing were performed respectively to create 2 different training ways. A total of 30, year 1 surgical residents were randomly divided into 2 groups. Besides traditional 2D computed tomography images, residents in group A (n = 15) reviewed 3D computer models, whereas in group B, residents (n = 15) reviewed 3D-printed models. Both groups subsequently completed an examination, designed in-house, to assess the appropriateness of their preoperative plan and provide a numerical score of the quality of the surgical plan. RESULTS: Residents in group B showed significantly higher quality of the surgical plan scores compared with residents in group A (76.4 ± 10.5 vs. 66.5 ± 11.2, p = 0.018). This difference was due in large part to a significant difference in knowledge of key surgical steps (22.1 ± 2.9 vs. 17.4 ± 4.2, p = 0.004) between each group. All participants reported a high level of satisfaction with the exercise. CONCLUSION: Results from this study support our hypothesis that 3D-printed models improve the quality of surgical trainee's preoperative plans.

CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway.

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high (SGC/wt) or low (SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal miRNAs were subsequently isolated from the two samples and their miRNA profiles were compared via microarray assay analysis. Reverse transcription-quantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed microRNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis. RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomes also significantly elevated the invasiveness of both SGC/wt (129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd (114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 miRNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes. CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosome-mediated MAPK signaling pathway, and exosomal miRNAs are probably involved in activation of the CD97-associated pathway.

Prophylactic hepatic artery infusion chemotherapy improved survival after curative resection in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: To explore the effect of prophylactic hepatic artery infusion chemotherapy (HAIC) on survival probability after curative resection in patients with hepatocellular carcinoma (HCC). METHODOLOGY: 85 patients with HCC were randomly assigned to HAIC group (42 cases) and control group (43 patients), all the database of two groups had no significant difference. Patients in HAIC groups underwent hepatic artery infusion chemotherapy (5-FU 1000 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1 and Gemcitabine 1000 mg/m2 on day 1 and 8) starting 3 weeks after operation with intervals of 4 weeks. All patients were followed up for 3 years and intrahepatic recurrence-free survival, disease-free survival rate and overall survival rate were recorded. RESULTS: Intrahepatic recurrence rate of HAIC group and the control group was respectively 19.05% and 39.53%, P < 0.05. Disease-free survival rate was respectively 57.14% and 44.19%, P < 0.05. Overall survival rate was 66.67% and 46.51%, P < 0.05. All patients in HAIC group tolerated the therapy. No adverse effect above grade 3 was reported in HAIC group. CONCLUSION: HAIC effectively and safely prevents intrahepatic recurrence and improves the prognosis of patients with HCC after curative resection.

[Three different strategies of urine drainage following hypospadias surgery: clinical nursing and observation].

OBJECTIVE: To study 3 different strategies of urine drainage following hypospadias urethroplasty, the clinical nursing in their application, and their effects. METHODS: We retrospectively analyzed the clinical data of 595 cases of hypospadias treated by urethroplasty. After surgery, 133 of the patients underwent urine drainage by suprapubic cystostomy (group A), 202 by urethral stent- tube indwelling (group B), and 260 by early initiative micturition with the urethral stent-tube (group C). All the patients received routine postoperative nursing care required for hypospadias repair. RESULTS: Operations were successfully completed in all the cases. Group C showed a remarkably shorter hospital stay and lower incidence rates of urinary fistula and urethral stricture than groups A and B (P<0.05), but there were no significant differences in the three indexes between A and B (P<0.05). CONCLUSION: For urine drainage following hypospadias repair, early initiative micturition with the urethral stent-tube can significantly reduce postoperative complications, decrease difficulties and workload of nursing care, and shorten the hospital stay of the patient.

Detection of pancreatic cancer with normal carbohydrate antigen 19-9 using protein chip technology.

AIM: To develop a method to differentiate pancreatic cancer patients from healthy or benign individuals when carbohydrate antigen (CA) 19-9 is normal. METHODS: Forty-one serum samples from patients with pancreatic lesions and blood samples from 20 healthy individuals were collected at the first stage of the experiment according to the enrolment criteria. General characteristics and some clinical features were carefully compared to ensure that the results were reasonable. All the blood samples were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) combined with CM10 chips and a related bioinformatics analysis program to generate diagnostic models with different proteins. Forty-seven consecutive samples were tested at the next stage to verify the veracity and efficiency of the models. RESULTS: The sex, age, and serum CA19-9 levels among the three groups (malignant, benign, and healthy) were statistically matched (P values were 0.957, 0.145, and 0.382, respectively). Two patterns were generated. Pattern 1 with four proteins theoretically had a specificity and sensitivity of 100% in distinguishing pancreatic cancer from healthy individuals, while it was 86.7% and 86.4%, respectively, in the subsequent practical verification. The positive predictive value (PPV) of the model was 86.4%. One of the four proteins was expressed highly in pancreatic cancer while the other three were expressed weakly. Pattern 2 consisted of six proteins that showed a specificity of 70.0% and sensitivity of 77.3% for differentiating malignancy from benign tumors. Its PPV reached 85.0%. Only one of these six proteins showed high expression in the malignant group. CONCLUSION: SELDI-TOF-MS may facilitate diagnosis or differential diagnosis of pancreatic cancer when CA19-9 is normal. Pattern 1 may serve as a useful screening tool.

[Clinical study of liver resection with bipolar radiofrequency device: Habib 4X].

OBJECTIVE: To assess the application value of a new radiofrequency device Habib 4X in liver resection. METHODS: A retrospective study was performed during March 2010 to July 2011.Forty-four patients underwent liver resection with radiofrequency device Habib 4X and another 54 patients traditional liver resection.Intraoperative blood loss, blood transfusion, Pringle's maneuver requirement, liver parenchyma transaction time, liver function recovery, complications, mortality and recurrence were recorded. RESULTS: The mean resection time was (67 ± 22) min for Habib 4X group versus (93 ± 23) min for traditional group (P = 0.000). Pringle's maneuver was required in 10 patients (22.7%) for Habib 4X group and 31 (57.4%) for traditional group (P = 0.001). The mean blocking time was (7 ± 2) vs (18 ± 6) min (P = 0.001), mean blood loss volume (243 ± 132) vs (500 ± 421) ml (P = 0.002). Postoperative recovery of liver function was better in Habib 4X group than traditional group. None developed mortality in Habib 4X group. And no resection margin recurred during a 18-month follow-up. CONCLUSIONS: Bipolar radiofrequency device Habib 4X is recommended for pre-coagulation in hepatectomy. And the advantages of minimized blood loss and reduced resection time result in its lower rates of morbidity and mortality.

Preoperative intestinal stent decompression with primary laparoscopic surgery to treat left-sided colorectal cancer with obstruction: a report of 21 cases.

OBJECTIVE: This work aimed to study the safety and efficacy of preoperative intestinal stent decompression combined with laparoscopic surgery to treat left-sided colorectal cancer with obstruction (LCCO). METHODS: Retrospective analysis was conducted on data obtained from 21 LCCO patients admitted to The First Affiliated Hospital of Zhejiang Chinese Medicine University during March 2008 and December 2011. To remove the intestinal obstruction, preoperative intestinal stent placement under colonoscopic guidance was performed. Approximately 7 to 10 days after the operation, laparoscopic radical surgery of colorectal cancer was conducted. RESULTS: Among the 21 cases studied, laparoscopic surgery was successful in 20 patients. Emergent laparotomy was conducted in one patient because of tumor invasion in the ureter. The duration of the operation ranged from 180 to 320 min, and the average time was 220 min. The recovery time for bowel function ranged from 2 to 5 days with an average time of 3 days. Postoperative infection of the incision occurred in one case. No anastomotic leakage was observed in any of the cases. CONCLUSION: Preoperative intestinal stent decompression, combined with primary stage laparoscopic surgery, is a safe and effective method for the treatment of LCCO.

MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance.

It has been suggested that the newly identified metastasis-associated in colon cancer-1 (MACC1) oncogene is involved in the progression and metastasis of cancer. Several studies have indicated that MACC1 has potential as a novel biomarker. In this study, we aimed to investigate the functions and serum expression levels of MACC1 in pancreatic cancer patients. Blood serum samples from 60 cancer patients and 49 controls were analyzed for serum MACC1 by ELISA. The results revealed that high expression levels of MACC1 were correlated with lymph node metastasis, distant metastasis and a later TNM stage. Inhibition of MACC1 by siRNAs significantly suppressed pancreatic cancer cell proliferation and migration. Furthermore, it was found that the downregulation of MACC1 sensitized pancreatic cancer cells to gemcitabine treatment through the inhibition of the Ras/ERK signaling pathway. Our findings suggest that MACC1 may aid in the diagnosis of pancreatic cancer and serve as a potential therapeutic target.

Adenosquamous carcinoma of the uncinate process of the pancreas with synchronous gastrointestinal stromal tumor of the stomach: Case report and review of the literature.

Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.

Impact of nodular size on the predictive values of gray-scale, color-Doppler ultrasound, and sonoelastography for assessment of thyroid nodules.

OBJECTIVE: To define the roles of gray-scale, color-Doppler ultrasound, and sonoelastography for the assessment of thyroid nodule to determine whether nodule size affects the differential diagnosis of benign and malignant. METHODS: A total of 243 consecutive subjects (214 women, 29 men) with 329 thyroid nodules were examined by gray-scale, color-Doppler ultrasound, and sonoelastography in this prospective study. All patients underwent surgery and the final diagnosis was obtained from histopathological examination. RESULTS: Three hundred and twenty-nine nodules (208 benign, 121 malignant) were divided into small (SNs, 5-10 mm, n=137) and large (LNs, >10 mm, n=192) nodules. Microcalcifications were more frequent in malignant LNs than in malignant SNs, but showed no significant difference between benign LNs and SNs. Poorly-circumscribed margins were not significantly different between malignant SNs and LNs, but were less frequent in benign LNs than in benign SNs. Among all nodules, marked intranodular vascularity was more frequent in LNs than in SNs. By comparison, shape ratio of anteroposterior to transverse dimensions (A/T) ≥ 1 was less frequent in LNs than in SNs. Otherwise, among all nodules, marked hypoechogenicity and elasticity score of 4-6 showed no significant difference between LNs and SNs. CONCLUSIONS: The predictive values of microcalcifications, nodular margins, A/T ratio, and marked intranodular vascularity depend on nodule size, but the predictive values of echogenicity and elastography do not.

Incarcerated internal hernia within a huge irreducible parastomal hernia with intestinal obstruction: a rare case report of "hernia within hernia".

We report an incarcerated internal hernia in a huge irreducible parastomal hernia-"hernia within hernia." A 70-year-old obese woman with diabetes who underwent an abdomino-perineal resection 20 years ago was admitted to our hospital with 20 years history of a huge irreducible bulge, 25 cm in diameter. An internal hernia due to an adhesive band extending from the sac wall to proximal colon was found in the parastomal hernia sac during an emergency laparotomy. We cut off the distal colon and relocated the colostomy stoma. The patient was discharged uneventfully 2 weeks after the surgery and was readmitted to have a further laparoscopic hernia repair 8 months later. Unfortunately, an unrecognized enterotomy occurred during the secondary surgery that led to an additional laparotomy during which the mesh was not contaminated by the bowel contents and was kept in place. At 22-month follow-up, there were no evidences of recurrence.

Gastric duplication cyst lined by pseudostratified columnar ciliated epithelium: a case report and literature review.

Gastric duplication cyst (GDC) lined by pseudostratified columnar ciliated epithelium (PCCE) is an uncommon lesion stemming from a foregut developmental malformation. Its clinical and radiological presentation is usually nonspecific. In this study, we reported a 76-year-old man who presented with an incidentally found perigastric mass. An exploratory laparotomy revealed a non-communicating cyst below the gastroesophageal junction, measuring 4 cm×4 cm in size. Microscopically, the gastric cyst was lined merely by PCCE. Although rare, GDC lined by PCCE should be included in the differential diagnosis of gastric wall masses. Surgical intervention is warranted in patients who have clinical symptoms, or who are aged more than 50 years.

Analysis of pancreatic fistula according to the International Study Group on Pancreatic Fistula classification scheme for 294 patients who underwent pancreaticoduodenectomy in a single center.

OBJECTIVES: The purposes of this study were to validate the value of the International Study Group on Pancreatic Fistula (ISGPF) classification scheme for pancreatic fistula (PF) and to identify predictive factors for clinically significant PF. METHODS: From January 2000 to December 2007, 294 consecutive patients underwent pancreaticoduodenectomy in a single medical center. Pancreatic fistula was evaluated by the ISGPF criteria and Johns Hopkins Hospital's definition (JHH). Then, logistic regression analysis was performed to identify predictive factors for PF development. Our own management strategies with PF were also discussed. RESULTS: The overall incidence of PF was 19.4% (57/294) according to the ISGPF criteria, and 8.8% (26/294) using the JHH definition. Thirty-one patients with PF classified by the ISGPF were missed by the JHH definition. By logistic regression analysis, we found that besides the lack of cardiovascular disease and malignant diseases, our single-layer continuous circular invaginated pancreaticojejunostomy was another independent factor for the lowered incidence of PF. CONCLUSIONS: The ISGPF classification scheme was accurate for evaluating PF. Single-layer continuous circular invaginated pancreaticojejunostomy may be a promising method that may have been responsible for the lower incidence of PF in this study.