LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis.

BACKGROUND: Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer. AIM: To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism. METHODS: We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed. RESULTS: C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis. CONCLUSION: C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.

Huge peripheral primitive neuroectodermal tumor of the small bowel mesentery at nonage: A case report and review of the literature.

Extraskeletal Ewing's sarcoma/peripheral primitive neuroectodermal tumor (E-EWS/pPNET) is a rare aggressive malignant small round cell tumor. In this report, we present the case of a 15-year-old boy who suffered from acute abdominal pain accompanied by hematemesis and melena, and was eventually diagnosed with E-EWS/pPNET. To date, there have been only five reported cases of E-EWS/pPNET of the small bowel including the patient in this report. To the best of our knowledge, this is the first documentation of a pPNET of the small bowel mesentery at nonage. All these have made this report rare and significant.

Conjugated bile acids in gallbladder bile and serum as potential biomarkers for cholesterol polyps and adenomatous polyps.

PURPOSE: To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). METHODS: Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. RESULTS: These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 µg/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (≤12 µg/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. CONCLUSIONS: The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs.

Loss of heterozygosity at the calcium regulation gene locus on chromosome 10q in human pancreatic cancer.

BACKGROUND: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. MATERIALS AND METHODS: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). RESULTS: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial Ca2+ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. CONCLUSIONS: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

[Indications, technique and efficacy of organ preserving pancreatectomy].

OBJECTIVE: To discuss the proper surgical management of pancreatic benign and low-grade malignant potential neoplasm. METHODS: The experience of 72 cases who accepted organ preserving pancreatectomy from January 1990 to May 2010 was analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68 years with mean age of 46 years. There were 9 cases underwent duodenum-preserving resection of the head of the pancreas, 29 cases underwent spleen-preserving distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23 cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head and body. RESULTS: Pancreatic fistula and biliary fistula in 1 case respectively were cured among who accepted duodenum-preserving resection of the head of the pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12, 16 months after surgery respectively. CONCLUSIONS: Organ preserving pancreatectomy can obviously reduce operative injury to patients, its therapeutic effect is similar to that of classical operation, it is the first option of benign and low-grade malignant potential neoplasm.

Thrombosis of gallbladder vein presenting as acute peritonitis.

BACKGROUND: Thrombosis of the gallbladder vein occurs rarely, and few clinical features have been reported. We report here with a case of gallbladder vein thrombosis presenting as acute peritonitis in a 75-year-old man. METHODS: The old man with sudden continuous abdominal pain resorted to the emergency room and treated for peritonitis associated with acute cholecystitis. The treatment failed to slow the progress of the disease, and massive ascites appeared with thickening of the gallbladder wall. Laparotomic investigation was conducted later. RESULT: Pathologically, thrombosis of the gallbladder vein was diagnosed. CONCLUSIONS: The thrombosis of the gallbladder vein is characterized by thickening of the gallbladder wall, ascites, and sudden continuous abdominal pain. The causes of deep vein thrombosis at this unusual site vary.

[Establishment of serum protein pattern model for screening pancreatic cancers by SELDI-TOF-MS technique].

OBJECTIVE: To detect the serum specific proteins in pancreatic cancer patients and establish diagnostic model by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique. METHODS: Twenty-nine serum samples from patients of pancreatic cancer were collected before surgery and an additional 57 serum samples from age and sex matched individuals without cancer were used as controls, SELDI-TOF-MS technique and WCX magnetic beads were used to detect the protein fingerprint expression of all the serum samples and the resulting profiles between pancreatic cancer patients and controls were analyzed with biomarker wizard system, established the model using biomarker patterns system software. A double-blind test was used to determine the sensitivity and specificity of the classification model. RESULTS: A panel of four biomarkers (relative molecular weight are 5705, 4935, 5318 and 3243 Da) were selected to set up a decision trees as the classification model for screening pancreatic cancer effectively. The result yielded a sensitivity of 100%, specificity of 97.4%. The double-blind test challenged the model with a sensitivity of 88.9% and a specificity of 89.5%. CONCLUSIONS: SELDI-TOF-MS offers a unique platform for the proteomic detection of serum in pancreatic cancer patients. It also offers a noninvasive method to further study the proteomic changes in the development and progression of pancreatic cancer.

[The contribution for the diagnosis of the tumor-like polypoid lesions of the gallbladder by SELDI-TOF-MS].

OBJECTIVE: To detect the serum specific proteins in tumor-like polypoid lesions of the gallbladder patients and establish diagnostic model. METHODS: Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique and WCX Magnetic Beads were used to detect the serum proteomic patterns of 23 patients with tumor-like PLG, 21 patients with non tumor-like PLG and 26 normal persons. Biomarker Wizard and Biomarker Patterns Software were used in combination to analyze the data. RESULTS: Preliminary screening out 22 representative specific proteins for the diagnosis of the tumor-like PLG. Analysis system under the conditions set selected 3 specific proteins to establish diagnostic model for the tumor-like PLG. The sensitivity and specificity of the model for the diagnosis of the tumor-like PLG were 100% and 89.4%, respectively. CONCLUSION: SELDI-TOF-MS technique can select specific protein of the tumor-like PLG, and establish diagnostic model of the tumor-like PLG.

Application of retrograde distal pancreatectomy.

BACKGROUND: Since conventional methods are difficult to deal with pancreatic tumors close to the portal veins, we investigated the feasibility and norms for retrograde distal pancreatectomy by cutting the neck of the pancreas first. METHOD: The clinical data and surgical procedures of retrograde distal pancreatectomy given to 11 patients from July 2001 to June 2007 were analyzed. RESULTS: All 11 operations were completed successfully. The mean time of the operation was 143+/-71 minutes. The mean volume of hemorrhage was 239 ml. The mean time of hospitalization was 12+/-4.2 days. No blood transfusion was needed during the operation, and all patients had a good postoperative recovery. No neopathy of diabetes mellitus, pancreatic fistula or other complications occurred after the operation. The follow-up of all patients (4-60 months) showed that 3 patients survived for 14, 16 and 33 months, respectively, and the other patients are still alive. CONCLUSIONS: Retrograde distal pancreatectomy is useful for exposing the portal and superior mesenteric veins while avoiding operative injury. Interception of the blood supply of the spleen helps to reduce the volume of hemorrhage, while making the operation easier and the operative time short. It is advantageous for tumor resection of the body of the pancreas near the portal veins.

[Diagnosis and surgical treatment of 98 cases with adult primary retroperitoneal malignant tumor].

OBJECTIVE: To investigate the diagnosis and surgical treatment of adult primary retroperitoneal malignant tumor (APRMT). METHODS: The clinical data of 98 cases with APRMT underwent resection from January 1990 to April 2003 were analyzed retrospectively. RESULTS: Among the 98 cases, complete excision were performed in 79 cases (80.6%), palliative excision in 16 cases (16.3%), tumor biopsy only in 3 cases (3.1%). Resection of involved adjacent organs were carried out in 25 cases (25.5%) and the re-operation rate for recurrence was 28.6% (28 cases). The 1, 3, 5 year survival rates for 79 cases with complete resection were 93.7%, 73.4% and 34.2%, respectively. The 1, 3, 5 year survival rate for 16 cases with palliative resection were 75.0%, 6.3% and 6.3%, respectively. CONCLUSIONS: Certain imaging examinations are crucial to the diagnosis and preoperative evaluation of APRMT. Resection of the involved organs could improve resection rate and prognosis. For the recurrent cases, earlier reoperation is strongly recommended.

Surgical management of 143 patients with adult primary retroperitoneal tumor.

AIM: To analyze the surgical management of adult primary retroperitoneal tumors (APRT) and the factors influencing the outcome after operation. METHODS: Data of 143 cases of APRT from 1990 to 2003 in the First Affiliated Hospital of China Medical University were evaluated retrospectively. RESULTS: A total of 143 cases of APRT were treated surgically. Among them, 122 (85.3%) underwent complete resection, 16 (11.2%) incomplete resection, and 3 (3%) surgical biopsies. Twenty-nine (20.2%) underwent tumor resection plus multiple organ resections. Ninety-five malignant cases were followed up for 1 mo to 5 years. The 1-year, 3-year, and 5-year survival rates of the patients subject to complete resection was 94.9%, 76.6% and 34.3% and that of patients with incomplete resection was 80.4%, 6.7%, and 0%, respectively (P < 0.001). The Cox multi-various regression analysis showed the completeness of tumor, sex and histological type were associated closely with local recurrence. CONCLUSION: Sufficient preoperative preparation and complete tumor resection play important roles in reducing recurrence and improving survival.

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis.

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n=21) received no treatment after the SAP model was established; group B (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r= -0.748, -0.827, -0.723; P<0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P<0.01, P<0.05), but the expression of MCP was not influenced (P>0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P<0.05), but the expression of CD59 and MCP did not change (P>0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.