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1.  Detection of pancreatic cancer with normal carbohydrate antigen 19-9 using protein chip technology 
World Journal of Gastroenterology : WJG  2014;20(40):14958-14964.
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.
PMCID: PMC4209560  PMID: 25356057
Carbohydrate antigen 19-9; Diagnosis; Pancreatic cancer; Screening; Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
2.  Conservative resection for benign tumors of the proximal pancreas 
AIM: To evaluate the safety and long-term prognosis of conservative resection (CR) for benign or borderline tumor of the proximal pancreas.
METHODS: We retrospectively analyzed 20 patients who underwent CR at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2000 and October 2008. For pancreaticojejunostomy, a modified invagination method, continuous circular invaginated pancreaticojejunostomy (CCI-PJ) was used. Modified continuous closed lavage (MCCL) was performed for patients with pancreatic fistula.
RESULTS: The indications were: serous cystadenomas in eight patients, insulinomas in six, non-functional islet cell tumors in three and solid pseudopapillary tumors in three. Perioperative mortality was zero and morbidity was 25%. Overall, pancreatic fistula was present in 25% of patients. At a mean follow up of 42.7 mo, all patients were alive with no recurrence and no new-onset diabetes mellitus or exocrine dysfunction.
CONCLUSION: CR is a safe and effective procedure for patients with benign tumors in the proximal pancreas, with careful CCI-PJ and postoperative MCCL.
PMCID: PMC2731956  PMID: 19705501
Adenoma; Islet cell; Conservative resection; Cystadenoma; Enucleation; Insulinoma; Pancreatectomy; Pancreatic fistula; Pancreatic neoplasms
3.  Resection of non-cystic adenocarcinoma in pancreatic body and tail 
AIM: To report the outcome of Chinese patents with non-cystic adenocarcinoma in pancreatic body and tail (NCAPBT) after resection and to discuss its surgical strategy.
METHODS: Resection of NCAPBT was performed in eight Chinese patients with complete clinical-pathological data in our hospital from January 2000 to May 2004. The surgical strategy was explored by analyzing the results of these patients.
RESULTS: The resection rate of NCAPBT in patients without back pain was higher than that in patients with back pain (66.67% vs 20%, 2/3 vs 1/5). The prognosis in the group receiving palliative resection was poorer than that in the group receiving curative resection. The median survival time was 12 mo in the curative resection group and 6 mo in the palliative resection group, respectively.
CONCLUSION: The overall survival time of the Chinese patients with NCAPBT is dismal. The Chinese patients after curative resection of NCAPBT have a longer survival time. The Chinese NCAPBT patients with back pain trend to have a lower curative resection rate, but back pain should not be considered a contraindication for curative resection.
PMCID: PMC4088178  PMID: 17007030
Pancreas; Adenocarcinoma; Pancreatectomy; Survival; Back bain
4.  Preoperative intestinal stent decompression with primary laparoscopic surgery to treat left-sided colorectal cancer with obstruction: a report of 21 cases 
Cancer Biology & Medicine  2013;10(2):99-102.
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).
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.
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.
Preoperative intestinal stent decompression, combined with primary stage laparoscopic surgery, is a safe and effective method for the treatment of LCCO.
PMCID: PMC3719190  PMID: 23882425
Colorectal cancer; intestinal obstruction; intestinal stent; laparoscope
5.  MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance 
Oncology Letters  2012;4(4):783-791.
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.
PMCID: PMC3506703  PMID: 23205101
metastasis-associated in colon cancer-1; metastasis; epithelial-mesenchymal transition; chemoresistance
6.  Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration after partial hepatectomy 
AIM: To study the expression of tumor necrosis factor-alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo.
METHODS: Male SD rats underwent 70% partial hepatectomy. The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy. TACE expression was investigated by Western blotting, immunohistochemistry, and serial section immunostaining.
RESULTS: Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration, reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h. TACE protein was localized to mononuclear cells (MNC), which infiltrated the liver from the spleen after hepatectomy. The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α (TGFα). In addition, TACE-staining MNC partially overlapped with CD3+ T lymphocytes.
CONCLUSION: TACE may be involved in liver regeneration by pathway mediated with TGFα-EGFR in the cell-cycle progressive phase in vivo. TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.
PMCID: PMC2693681  PMID: 18322947
Tumor necrosis factor-alpha converting enzyme; Liver regeneration; Partial hepatectomy
7.  Inhibitory effect of adeno-associated virus-mediated gene transfer of human endostatin on hepatocellular carcinoma 
AIM: To investigate the effect of adeno-associated virus-mediated gene transfer of human endostatin on the growth of hepatocellular carcinoma (HCC).
METHODS: HCC cell line Hep3B was infected with recombinant adeno-associated virus containing human endostatin gene (rAAV2-hEndo). The results of transfection were detected by RT-PCR and SDS-PAGE assay. MTT assay was used to observe the effects of supernatant of transfected cells on ECV304 cell proliferation. An animal model of HCC was established by injecting Hep3B cells subcutaneously into the back of nude mice. Intratumoral injection of rAAV2-hEndo, empty virus and phosphate-buffered saline were given sequentially. Serum endostatin was determined by ELISA, the inhibitory effect of endostatin on the growth of xenograft was assessed in 3 wk.
RESULTS: The results of RT-PCR and SDS-PAGE assay confirmed that rAAV2-hEndo successfully transfected Hep3B cells, and endostatin was secreted from Hep3B cells to medium. The supernatant of transfected cells markedly inhibited the proliferation of ECV304 cells (P<0.01). Intratumoral injection of rAAV2-hEndo (2×1010 v.g.) led to a sustained serum endostatin level of approximately (86.71±5.19) ng/mL. The tumor volume and microvessel density were less in rAAV2-hEndo group than in control groups (P<0.01).
CONCLUSION: Human endostatin can be stably expressed by adeno-associated virus-mediated gene transfer and effectively inhibit the growth of HCC.
PMCID: PMC4315983  PMID: 15948234
Endostatin; Gene; Adeno-associated virus; Hepatocellular carcinoma
8.  Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma 
AIM: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC.
METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1 protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up.
RESULTS: The positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%, 16/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P<0.01). HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%, P<0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P<0.01). The poorly differentiated tumor and tumor of TNM stages III-IV had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages I-II (66.7% vs 33.3%, P<0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P<0.05). nm23-H1 expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P>0.05). The positive rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during the follow-up were obviously higher than those in the group with low tendency to metastasis and recurrence (P = 0.018) and in the patients without metastasis and recurrence (P = 0.024); but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rate of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 was 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9), respectively.
CONCLUSION: Expression of HPA and/or nm23-H1 is related with metastasis and recurrence of HCC. Detection of the expression rate of HPA and nm23-H1 may help increase the accuracy in predicting post-operative metastasis and recurrence of HCC.
PMCID: PMC4250689  PMID: 15761980
Heparanase; nm23-H1; Hepatocellular carcinoma
9.  Acute pancreatitis associated left-sided portal hypertension with severe gastrointestinal bleeding treated by transcatheter splenic artery embolization: a case report and literature review*  
Left-sided portal hypertension (LSPH) followed by acute pancreatitis is a rare condition with most patients being asymptomatic. In cases where gastrointestinal (GI) bleeding is present, however, the condition is more complicated and the mortality is very high because of the difficulty in diagnosing and selecting optimal treatment. A successfully treated case with severe GI bleeding by transcatheter splenic artery embolization is reported in this article. The patient exhibited severe uncontrollable GI bleeding and was confirmed as gastric varices secondary to LSPH by enhanced computed tomography (CT) scan and CT-angiography. After embolization, the bleeding stopped and stabilized for the entire follow-up period without any severe complications. In conclusion, embolization of the splenic artery is a simple, safe, and effective method of controlling gastric variceal bleeding caused by LSPH in acute pancreatitis.
PMCID: PMC3682172  PMID: 23733433
Left-sided portal hypertension (LSPH); Gastric varices; Acute pancreatitis; Gastrointestinal bleeding; Splenic artery embolization (SAE)
10.  Cyanidin-3-Glucoside-Rich Extract from Chinese Bayberry Fruit Protects Pancreatic β Cells and Ameliorates Hyperglycemia in Streptozotocin-Induced Diabetic Mice 
Journal of Medicinal Food  2012;15(3):288-298.
Chinese bayberry fruit is a rich source of anthocyanins, especially cyanidin-3-glucoside (C3G). The present study investigated the protective effects of C3G-rich bayberry fruit extract (CRBFE) against pancreatic β cells against oxidative stress–induced injury as well as its hypoglycemic effect in diabetic mice. Bayberry extract from “Biqi” was used for both in vitro and in vivo testing because of its high C3G content and high antioxidant capacity. Pretreatment of β cells with CRBFE (containing 0.5 μmol/L C3G) prevented cell death, increased cellular viability, and decreased mitochondrial reactive oxygen species production and cell necrosis induced by 800 or 1,200 μmol/L H2O2. CRBFE dose-dependently up-regulated pancreatic duodenal homeobox 1 gene expression, contributing to increased insulin-like growth factor II gene transcript levels and insulin protein in INS-1 cells. In addition, administration of CRBFE (150 μg of C3G/10 g of body weight twice per day) significantly reduced blood glucose in streptozotocin-induced diabetic ICR mice and increased the glucose tolerance in an oral glucose tolerance test (P<.05). Such results indicated that CRBFE might be useful in prevention and control of diabetes mellitus and diabetes-associated complications.
PMCID: PMC3282469  PMID: 22181073
anthocyanins; antioxidants; diabetes; fruit extract; oxidative stress
11.  Adenosquamous carcinoma of the uncinate process of the pancreas with synchronous gastrointestinal stromal tumor of the stomach: Case report and review of the literature 
Oncology Letters  2012;4(6):1191-1194.
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.
PMCID: PMC3506715  PMID: 23197997
adenosquamous carcinoma; gastrointestinal stromal tumor; synchronous cancer; uncinate process of the pancreas
12.  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.
PMCID: PMC3437368  PMID: 22949361
Ultrasound; Thyroid nodules; Sonoelastography; Nodule size
13.  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.
PMCID: PMC3433556  PMID: 22977766
Ventral hernia; Incarceration; Intestinal obstruction; Herniorrhaphy
14.  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.
PMCID: PMC3017413  PMID: 21194183
Gastric duplication cyst (GDC); Foregut; Pseudostratified columnar ciliated epithelium (PCCE); Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)
15.  Pancreatic somatostatinoma with obscure inhibitory syndrome and mixed pathological pattern*  
Somatostatinoma is a very rare neuroendocrine tumor that originates from D cells and accounts for less than 1% of all gastrointestinal endocrine tumors. The duodenum is the most frequent site for this tumor, followed by the pancreas. We here describe a 46-year-old Chinese woman who developed pancreatic somatostatinoma presenting with the characteristic “inhibitory” syndrome, but the symptoms were obscure and seemingly uncorrelated. This case is also unique for its large tumor size and mixed pathological pattern. Distal pancreatectomy was performed, and the patient has remained well since operation. As the syndromes of somatostatinoma may be obscure and atypical, clinicians should review all clinical findings to obtain an accurate diagnosis. Aggressive surgery is preferred to improve the survival.
PMCID: PMC2801086  PMID: 20043348
Neuroendocrine tumor; Somatostatinoma; Somatostatinoma syndrome; Pancreatic hormone-producing tumor; Pancreatectomy

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