Current status and hotspot of minimally invasive surgery for pancreatic head carcinoma / 中华外科杂志

With the improvement of laparoscopic equipment and surgical technology,pancreatic surgery has entered the "minimally invasive era".However,the use of minimally invasive pancreaticoduodenectomy in patients with pancreatic head cancer remains controversial.In recent years,China's pancreatic surgeons have been at the forefront of the world in terms of surgical technology,however,surgical philosophy, selection of indication,and perioperative management should be further stregthened. Additionally, the development of medical standards in various regions of China is seriously uneven,and minimally invasive pancreaticoduodenectomy still needs to be further standardized and popularized.Through this article,the author discusses the development status of minimally invasive surgery for pancreatic head cancer and related hot topics with fellow surgeons,in order to further improve the standard diagnosis and treatment of pancreatic cancer in China.

Effect of Hematopoietic Pre-B-cell Leukemia Transcription Factor Interacting Protein Knockdown on Proliferation,Cell Cycle and Apoptosis in Pancreatic Cancer Cells / 中国医学科学院学报

To unravel the role of hematopoietic pre-B-cell leukemia transcription factor interacting protein(HPIP)in the proliferation,cell cycle,and apoptosis of pancreatic ductal adenocarcinoma(PDAC)cells. The HPIP expression in PDAC tissue was determined by immunohistochemical staining.Knockdown of HPIP was accomplished in MIA PaCa-2 and BxPC-3 cell lines by transient transfection of HPIP siRNA and validated by Western blotting.Cell proliferation was assessed using the cell counting kit-8 assay and colony formation assay.Cell cycle and apoptosis were detected by flow cytometry.Western blotting was performed to detect the expression levels of cyclin D1,caspase 7,and cleaved caspase 7. HPIP was overexpressed in PDAC tissue compared with matched adjacent pancreatic tissue(=-2.060,=0.039).Knockdown of HPIP inhibited the proliferation of MIA PaCa-2 and BxPC-3 cells(all <0.05).Knockdown of HPIP significantly reduced the positive colonies formed by MIA PaCa-2 and BxPC-3 cells(=4.706,=0.009;=9.514,=0.000).Knockdown of HPIP decreased the proportion of S phase cells(=7.642,=0.001;=2.714,=0.051)and increased the proportion of G/G phase cells(=3.244,=0.031;=6.095,=0.003)in MIA PaCa-2 and BxPC-3 cells.Meanwhile,knockdown of HPIP increased the proportions of late-phase MIA PaCa-2 and BxPC-3 cells(=24.58,=0.000;=36.45,=0.000)and the overall apoptosis rate(=29.43,=0.000;=43.52,=0.000).In MIA PaCa-2 and BxPC-3 cells,knockdown of HPIP decreased the expression level of cyclin D1(=6.705,=0.002;=6.238,=0.003)and increased the expression level of cleaved caspase 7(=3.991,=0.016;=6.536,=0.002). HPIP is overexpressed in PDAC tissue.Knockdown of HPIP inhibits the proliferation and G/G to S transition of PDAC cells.Meanwhile,knockdown of HPIP promotes the apoptosis of PDAC cells.Thus,HPIP may act as an oncogene in PDAC.

Localized diagnosis and surgical management of insulinoma / 中国实用外科杂志

Insulinoma is a type of functional pancreatic neuroendocrine neoplasms(p NENs).As symptoms of hypoglycemia due to hyperinsulinemia are varied and nonspecific,diagnosis of insulinoma tends to be quite difficult.Both of localization diagnosis and surgical management are key points to deal with insulinoma.As for localization,while traditional imaging methods like CT and MRI improve quite fast,new molecular imaging technologies also develop rapidly.In terms of surgical treatment,main concerns of physicians often focus on the evaluation of operative procedures and experience of operating points.

Comprehensive treatment of liver metastasis of pancreatic neuroendocrine neoplasms / 中国实用外科杂志

Pancreatic neuroendocrine neoplasms(p NENs)are noted for its great variety and wide heterogeneity.The incidence is increasing gradually.Liver metastasis is not the contraindication of surgery of p NENs.Surgery is consider as a significant role in the multi-disciplinary team about treating p NENs.Although p NENs liver metastasis is relatively rare,its overall prognosis is significantly better than that of patients with pancreatic cancer liver metastasis.It is of great significance to grasp the indications and principles of surgical treatment for improving the survival of patients.Despite the relevant guidelines for diagnosis and treatment,the choice of surgical treatment options and the grasp of surgical indications for p NENs liver metastasis are still controversial.All pancreatic centers should give full play to the advantages of MDT and formulate individualized treatment plans for patients.Meanwhile,hospitals at all levels should strengthen cooperation to reduce missed diagnosis,misdiagnosis and mistreatment,and further standardize the surgical diagnosis and treatment of p NENs liver metastasis in China.

Diagnosis,treatment and etiology of hepatic infarction and abscess after pancreaticoduodenal surgery / 中国实用外科杂志

OBJECTIVE: To explore the causes and treatment of hepatic infarction and abscessafter pancreaticoduodenal surgery.METHODS: The clinical data of 11 cases of hepatic infarction or abscess after pancreaticoduodenal surgery in Peking Union Medical College Hospital between January 2012 and December 2018 were analyzed retrospectively.RESULTS: A total of 11 patients were diagnosed of hepatic infarction or abscess after PD.The overall mortality rate was27.3%(3 of 11 patients).54.5%(6/11)had biliary fistula.Of the 11 patients,7 had proper hepatic artery and right accessory hepatic artery occlusion or stenosis,1 had abdominal trunk root stenosis before operation,and 3 had PV stenosis.Enterococcus and Klebsiella were the organisms most frequently cultured,and fungi were also the common pathogens.Antibiotics and selective percutaneous drainage were the main means of treatment.CONCLUSION: Ischemia of hepatic artery and portal vein after PD is the main cause of liver infarction and liver abscess.Biliary fistula and multiple pathogenic bacteria are often associated with high mortality.

Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma / 中华医学杂志(英文版)

Background@#Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue.@*Methods@#PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses.@*Results@#Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = -2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = -2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499-4.367, P = 0.001).@*Conclusion@#These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.

FXR expression is associated with the prognosis and pathological staging of patients with pancreatic cancer / 基础医学与临床

Objective To explore the correlation among farnesoid X receptor (FXR), clinical stage and survival time of patients with pancreatic cancer. Methods The total protein and mRNA were extracted from cultured 8 pan-creatic cancer cell lines,and the expression level of FXR in pancreatic cancer cells was detected by Western bolt and real-time PCR. We collected 5 cases of normal pancreatic tissue and 50 cases of pancreatic cancer tissues,and used immunohistochemistry method to detect FRX expression in normal pancreatic tissue and pancreatic cancer. Ac-cording to the different expression level of FXR,these 50 patients were divided into low expression group and high expression group, the correlation of clinical data and FRX expression level was analyzed. Furthermore, Kaplan-Meier and log-rank analysis of prognostic factors was assessed in a multivariable analysis using a Cox proportional hazards model. Results FXR was differently expressed in 8 pancreatic cancer cell lines and pancreatic cancer tis-sues. FXR was closely related to the pathological G stage of pancreatic cancer(P＜0.05). FXR and pathological G stage were significantly correlated with the patients' survival time. The survival time of the patients with high FXR expression was significantly longer than that of patients with low FXR expression (P＜0.05). Conclusions The expression of FXR is closely related to the pathological G stage in patients with pancreatic cancer. Both FXR expression and pathological G stage are independent prognostic factors in patients with pancreatic cancer.

Prognostic Impact of Cell Division Cycle Associated 2 Expression on Pancreatic Ductal Adenocarcinoma / 中国医学科学杂志(英文版)

<strong>Objective</strong> To examine the expression of cell division cycle associated 2 (CDCA 2) in pancreatic ductal adenocarcinoma (PDAC) and investigate its role in prognosis of PDAC patients. <strong>Methods</strong> This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up. Clinicopathologic data were collected through clinical database. Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues. Clinicopathological characteristics between high and low CDCA2 expression were compared. Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis. <strong>Results</strong> Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues (U=4056.5, P<0.001). Univariate analysis showed that CDCA2 expression [hazard ratio (HR)=1.574, 95% confidence interval (CI)=1.014-2.443, P=0.043] and node metastasis (HR=1.704, 95%CI=1.183-2.454, P=0.004) were significantly associated with prognosis. Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor (HR=1.418, 95%CI=0.897-2.242, P=0.135) for PDCA patients. Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients (HR=2.554, 95%CI=1.446-4.511, P=0.003) or in non-perineural invasion patients (HR=2.290, 95%CI=1.146-4.577, P=0.012). <strong>Conclusions</strong> CDCA2 is highly expressed in PDAC tumor tissue. Although CDCA2 is not an independent prognostic risk factor for PDAC patients, it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.

Prognostic Impact of Cell Division Cycle Associated 2 Expression on Pancreatic Ductal Adenocarcinoma / 中国医学科学杂志(英文版)

Objective To examine the expression of cell division cycle associated 2 (CDCA 2) in pancreatic ductal adenocarcinoma (PDAC) and investigate its role in prognosis of PDAC patients. Methods This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up. Clinicopathologic data were collected through clinical database. Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues. Clinicopathological characteristics between high and low CDCA2 expression were compared. Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis. Results Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues (U=4056.5, P<0.001). Univariate analysis showed that CDCA2 expression [hazard ratio (HR)=1.574, 95% confidence interval (CI)=1.014-2.443, P=0.043] and node metastasis (HR=1.704, 95%CI=1.183-2.454, P=0.004) were significantly associated with prognosis. Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor (HR=1.418, 95%CI=0.897-2.242, P=0.135) for PDCA patients. Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients (HR=2.554, 95%CI=1.446-4.511, P=0.003) or in non-perineural invasion patients (HR=2.290, 95%CI=1.146-4.577, P=0.012). Conclusions CDCA2 is highly expressed in PDAC tumor tissue. Although CDCA2 is not an independent prognostic risk factor for PDAC patients, it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.

Changes in the Expression of Glucose-regulated Protein 78 in the Occurrence and Progression of Pancreatic Cancer in Mouse Models / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the changes in the expression of glucose-regulated protein 78 (GRP78) in the occurrence and progression of pancreatic cancer in mouse models.</p><p><b>METHODS</b>The mouse models of chronic pancreatitis,pancreatic intraepithelial neoplasia (PanIN), and pancreatic cancer were successfully established by dimethyl benzene and anthracene (DMBA) embedding in situ. GRP78 expression was detected in various stages by immunohistochemistry.</p><p><b>RESULTS</b>Of these 60 mouse models, 18 mice (30%) died during the observation period. Two months after the embedding,the survived mice were sacrificed,and HE staining and IHC staining were performed. Among these mice, 9 (15%) developed chronic pancreatitis; 18 (30%) had PanIN [PanIN1,5 (8.3%);P anIN2,9 (15%); and PanIN 3,4 (6.7%)];15 (25%) developed pancreatic cancer. Immunohistochemistry showed that the expression of GRP78 in pancreatic cancer tissue was significantly higher than that in adjacent noncancerous duct cells (χ(2)=13.39,P =0.000). Also, GRP78 expression in pancreatic cancer tissue and high grade PanIN was significantly higher than that in low grade PanIN and chronic pancreatitis (χ(2)=17.84,P=0.000).</p><p><b>CONCLUSION</b>The expression of GRP78 remarkably differs in different stages of pancreatic cancer and therefore is associated with the occurrence and progression of this disease.</p>

The role of perioperative enteral and parenteral nutrition treatment in pancreatic cancer: a multicenter, prospective randomized controlled trial / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the two different nutritional supports, enteral nutrition and parenteral nutrition in the aspects of nutritional conditions, immune status, the incidence of perioperative complications and quality of life impacts in pancreatic cancer.</p><p><b>METHODS</b>For the pancreatic cancer patients which pancreaticoduodenectomy were performed from January 2007 to December 2008 in five high-volume medical centres, prospective, randomized controlled study was carried out. The enrolled patients were randomly divided into enteral nutritional group (EN group) and parenteral nutritional group (PN group). Related indicators, such as nutritional conditions, immune status, incidence of complications, general status and quality of life were assessed.</p><p><b>RESULTS</b>The 200 patients were enrolled, while 178 cases which 90 patients in EN group and 88 patients in PN group were qualified to evaluate. The 22 cases were dropped out. For the mean hospital stay ((23 ± 13) days and (27 ± 24) days respcectively), Karnofsky score and the life quality scoring, there are no statistical differences between the two groups. In post-operation day 7 and day 10, the prealbumin was (69 ± 16) mg/L and (80 ± 22) mg/L in EN group and it was (67 ± 19) mg/L and (70 ± 11) mg/L in PN group, which are all significantly decreased than preoperational levels ((186 ± 38) mg/L for enteral group and (179 ± 37) mg/L for parenteral group, t = -2.24, -2.13, -2.23, -2.20, all P < 0.05), but there was no statistically significant between the 2 groups (P > 0.05). Other general indicators such as the albumin, hemoglobin, total bilirubin, blood urea nitrogen, serum creatinine, serum potassium and serum sodium, revealed no statistical differences in the 2 groups (P > 0.05); The total lymphocytes, CD(+)3CD(+)4 and CD(+)3CD(+)8 lymphocytes in PN group was (0.687 ± 0.065)×10(9)/L, (0.363 ± 0.029)×10(9)/L, and (0.183 ± 0.018)×10(9)/L respectively in post-operation day 10, which they are significantly decreased than in preoperational levels of PN group and the respective counterpart of EN group in post-operation day10 (t = -2.04-2.83, P < 0.05). The 35 patients were suffered from different complications in the 2 groups, but there was no statistical differences among them (P > 0.05).</p><p><b>CONCLUSIONS</b>Enteral nutritional support could not decrease the incidence of perioperative complications in pancreatic cancer patient, but it can improve the immunonutrition status in comparison with parenteral nutrition.</p>

Unsuspected gallbladder cancer during or after laparoscopic cholecystectomy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To summarize the clinical features and outcomes of unsupected gallbladder carcinoma ( UGC) detected during or after laparoscopic cholecystectomy.</p><p><b>METHODS</b>Medical records of 8005 patients, who underwent laparoscopic cholecystectomy in Peking Union Medical College Hospital between June 1993 and June 2011, were reviewed. Patients that pathologically diagnosed as UGC were retrospectively studied in terms of clinical features, preoperative and postoperative diagnosis, surviving period, and complications.</p><p><b>RESULTS</b>In the 8005 patients who received laparoscopic cholecystectomy, 36 (0.45%) were diagnosed as UGC during (25 patients) or after (11 patients) laparoscopic cholecystectomy. The gallbladder cancer was staged as T1 in 16 patients, T2 in 11 patients, and T3 in 9 patients. The 1-, 3-, and 5-year survival rates of all the patients were 88.9% (32/36), 63.9% (23/36), and 58.3% (21/36). The 5-year survival rates in T1 stage, T2 stage, and T3 stage patients were 100%, 75.0%, and 0.0%, respectively.</p><p><b>CONCLUSIONS</b>The survival rate of UGC is associated with tumor stage, not with operation approaches. Laparoscopic cholecystectomy is appropriate for T1 patients.</p>

Pancreatic acinar cell carcinoma: diagnostic and surgical treatment strategy / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, diagnostic and therapeutic strategy of pancreatic acinar cell carcinoma.</p><p><b>METHODS</b>The data of pancreatic acinar cell carcinoma patients who underwent surgical operations from January 2002 to January 2012 were retrospectively reviewed.</p><p><b>RESULTS</b>Six cases of pancreatic acinar cell carcinoma, identified with pathology were collected, including 3 males and 3 females with the average of 47.8 yeas old. Upper abdominal pain was present in 5 cases, weight loss was present in 4 cases with the average of 12.5 kg. Other symptoms included nausea/vomiting, back pain and obstructive jaundice. The serum CA19-9 and CA24-2 level were significantly elevated in 2 cases. CT scan, MRI and DSA were the main imaging methods to diagnose this disease. However, no case was diagnosed as pancreatic acinar cell carcinoma before operation. All cases were confirmed by the pathological examination. Relatively high rates of surgical resection, long operative time, more blood loss and combined multi-organ resection were the characteristics of this disease's operative surgical procedures. The average period of postoperative follow-up process was 60 months, and the mean survival time was (32 ± 8) months.</p><p><b>CONCLUSIONS</b>The clinical features and biological behavior of pancreatic acinar cell carcinoma are different from those of ductal adenocarcinoma, while the relatively specific clinical manifestations and imaging changes will be helpful for qualitative diagnosis before operation. As it has high rate of resection and better prognosis, more radical surgical strategies should be carried out for patients of this disease.</p>

Vitamin D status and the risk of pancreatic cancer: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vitamin D status in relation to pancreatic cancer risks is still inconsistent. This study was performed to evaluate the association between vitamin D status and risk of pancreatic cancer using a meta-analysis approach.</p><p><b>METHODS</b>A systemic review of all relevant literature in English was performed by searching Pubmed, Web of Science and Embase to identify eligible studies from the earliest available date to April 1, 2012. The search terms "vitamin D", "25-hydroxyvitamin D", "pancreatic cancer" or "pancreatic neoplasms" were used to retrieve relevant papers. Inclusion criteria were: (1) the exposure of interest was intake of vitamin D or blood levels of vitamin D; (2) the outcome of interest was pancreatic cancer; (3) data on high and low intake or blood vitamin D in cases and controls were available; (4) odds ratio (OR) estimates with 95% confidence interval (CI) were provided; (5) primary epidemiological data were provided reporting pancreatic cancer incidence. The combined OR values and their 95% CIs were calculated via a meta-analysis. The potential presence of publication bias was estimated using Egger's regression asymmetry test.</p><p><b>RESULTS</b>Nine studies with a total of 1 206 011 participants met the inclusion criteria. The test for heterogeneity showed there were significant differences among the included studies (I(2)=70.9%, P=0.001), so a randomized-effects model was used in the meta-analysis. The pooled OR of pancreatic cancer for the highest versus the lowest categories of vitamin D level was 1.14 (95% CI 0.896-1.451), and the Z-score for the overall effect was 1.06 (P=0.288), showing that there was no significant association between vitamin D levels and the risk of pancreatic cancer. Egger's test indicated there was a low possibility of publication bias in this study (P=0.348).</p><p><b>CONCLUSION</b>Dietary vitamin D or circulating concentrations of 25-hydroxyvitamin D are not associated with the risk of pancreatic cancer based on evidence from currently published studies.</p>

Expression of eukaryotic translation initiation factor 5A2 in pancreatic adenocarcinoma and its correlation with the prognosis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To detect the expression of eukaryotic translation initiation factor 5A2(EIF5A2) in pancreatic adenocarcinoma and its correlation with the clinicopathological characteristics and prognosis.</p><p><b>METHODS</b>A total of 73 patients who were treated in our hospital from March 2007 to December 2008 were enrolled in this study. The expression of EIF5A2 in the surgical samples was detected using immunohistochemical staining. Complete clinicopathological data were obtained from all the patients. The potential correlation between EIF5A2 expression and the clinicopathological features, particularly its role in prognosis, were analyzed.</p><p><b>RESULTS</b>Of these 73 patients, 43 had a high EIF5A2 expression. EIF5A2 expression was significantly correlated with the pathological T stage(P<0.001), N stage(P=0.004), M stage(P=0.039), and TNM stage(P=0.005). Kaplan-Meier method demonstrated that the survival was significantly longer in the low EIF5A2 expression group than in the high EIF5A2 expression group(P=0.003). Cox's hazard model showed EIF5A2 was a significant predictor of overall survival in patients with pancreatic adenocarcinoma.</p><p><b>CONCLUSION</b>EIF5A2 may be a potential predictor of the poor prognosis in patients with pancreatic adenocarcinoma.</p>

Expression of mitogen activated protein kinase phosphatase-1 in pancreatic cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the expression of mitogen activated protein kinase phosphatase-1(MKP-1)in pancreatic cancer.</p><p><b>METHODS</b>Totally 60 cases of normal pancreas, chronic pancreatitis(CP), and pancreatic cancer tissues were collected by operation in our hospital. Pancreatic tissues were analyzed by Northern blot analysis and Western blot analysis. Meanwhile, MKP-1 expression was detected in 6 pancreatic cancer cell lines by Western blot analysis.</p><p><b>RESULTS</b>Northern blot analysis of total RNA revealed relatively low MKP-1 mRNA expression in 7 of 20(35%)normal pancreatic samples. In the remaining 13 samples, the MKP-1 mRNA was absent to faint detectable. In 7 of the 20 CP samples, MKP-1 was demonstrated moderate to high expression. In contrast, 12 of 20(60%)pancreatic cancer samples MKP-1 mRNA was expressed at high levels, whereas in the remaining 8 cancer tissues this mRNA moiety was present at low to moderate levels. Densitometric analysis with normalization to 7S revealed that the median level of MKP-1 mRNA in CP and cancerous tissues was increased by 6.2 folds(P=0.035)and 8.1 folds(P=0.016)in comparison with the median level in the normal pancreatic samples, respectively. Overexpression of MKP-1 was also found in 6 pancreatic cancer cell lines, in which the expression of MKP-1 was slightly lower in one pancreatic cancer cell line but high in the remaining 5 cell lines.</p><p><b>CONCLUSIONS</b>MKP-1 is over-expressed in pancreatic cancer, CP tissues, and pancreatic cell lines. It is speculated that MKP-1 may play an important role in tumorigenesis of pancreatic cancer.</p>

Validation of candidate immunogenic membrane antigens of human pancreatic cancer screened by proteomics / 中华外科杂志

<p><b>OBJECTIVE</b>To validate those obtained immunogenic membrane antigens candidate of human pancreatic cancer in the performed research.</p><p><b>METHODS</b>In the pre-studies, serum IgG purified from clinically collected sera of pancreatic cancer patients underwent immunoblot with human pancreatic cancer cell line SW1990 membrane protein, totally obtained 9 positive protein spots. Number 5 and 6 positive dots of immunoblot were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and peptide mass fingerprinting matching. The candidate membrane antigens were further validated in cell lines by RT-PCR and real-time PCR. RNA of human normal pancreatic tissue and pancreatic cancer tissue was extracted respectively, different gene expression level of prohibitin 2 was studied by real-time PCR.</p><p><b>RESULTS</b>Number 5 and 6 positive dots were identified as prohibitin 2 and prohibitin. RT-PCR and real-time PCR all showed that gene of prohibitin 2 and prohibitin were expressed in the human pancreatic cancer cell line SW1990, AsPc and P3 respectively, especially in P3 cell with highest expression (t = 7.442, P < 0.01). In addition, gene expression level of prohibitin 2 was significant higher in human pancreatic cancer than that of normal pancreatic tissue (t = 0.893, P < 0.01).</p><p><b>CONCLUSIONS</b>Prohibitin 2 and prohibitin are both differently expressed in the pancreatic cancer cell line SW1990, AsPc and P3. Prohibitin 2 is obvious highly expressed in human pancreatic cancer tissue. Prohibitin 2 and prohibitin might be the candidate immunogenic membrane antigens of human pancreatic cancer.</p>

Clinical characteristics of hereditary and sporadic medullary thyroid carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the clinical characteristics and outcomes of the hereditary medullary thyroid carcinoma (HMTC) and the sporadic medullary thyroid carcinoma (SMTC).</p><p><b>METHODS</b>The clinical data of 78 patients with medullary thyroid carcinoma who underwent surgery in our hospital between July 1980 and May 2011 were retrospectively analyzed.</p><p><b>RESULTS</b>Of these 78 patients, there were 23 HMTC cases and 55 SMTC cases. The HMTC group was significantly younger age of onset [(36.4±13.5) years vs. (46.6±11.2) years, P<0.01] and a lower pre/post-operative serum calcitonin levels [(850.4±110.20) ng/L vs. (1450.4±118.3) ng/L, P<0.01 and (410.8±133.2) ng/L vs. (1585.4±129.5) ng/L, P<0.01] than the SMTC group. In addition, the mean tumor diameter was also significantly smaller in the HMTC group (14.3 mm vs. 21.0 mm in SMTC group, P<0.05). Tumor multifocality was seen in a significantly higher proportion of HMTC cases compared with the SMTC cases (56.6% vs. 29.1%, P<0.05). The overall 10-year survival was 100% in HMTC group and 80.2% in SMTC group (P<0.05).</p><p><b>CONCLUSION</b>HMTC has a better prognosis than SMTC.</p>

Relationship between single nucleotide polymorphisms in the deoxycytidine kinase gene and chemosensitivity of gemcitabine in six pancreatic cancer cell lines / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Single nucleotide polymorphisms (SNPs) in the deoxycytidine kinase (dCK) gene are associated with chemosensitivity to nucleoside analogs. 2',2'-Difluoro 2'-deoxycytidine (gemcitabine) is a first-line nucleoside analog drug in the treatment of pancreatic cancer. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines.</p><p><b>METHODS</b>Seven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. The chemosensitivity of these six cell lines to gemcitabine were evaluated in vitro with a Cell Counting Kit-8 (CCK-8) test. Inhibition rates were used to express the chemosensitivity of pancreatic cancer cell lines to gemcitabine.</p><p><b>RESULTS</b>The genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. The cell lines BxPC-3 and T3M4 carried the A9846G SNP genotype AG, whereas cell lines AsPC-1, Mia PaCa2, SW1990 and SU86.86 carried the GG genotype. Cell lines with the AG genotype (BxPC-3 and T3M4) were more sensitive to gemcitabine compared with cell lines with the GG genotype (AsPC-1, Mia PaCa2, SW1990 and SU86.86) and significantly different inhibition rates were observed between cell lines carrying the AG and GG genotypes (P < 0.01).</p><p><b>CONCLUSIONS</b>Variants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer.</p>

Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis. TS activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs, and its expression may be affected by gene polymorphisms. In this study, we investigated the associations between polymorphisms of the TS gene and its protein expression, and the implications on the efficacy of 5-fluorouracil (5-FU) in pancreatic cancer cells.</p><p><b>METHODS</b>Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products. A single nucleotide polymorphism (SNP) at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide sequencing. The chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 (CCK-8). TS protein expression was analyzed by Western blotting.</p><p><b>RESULTS</b>Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat, as follows: homozygous 2R/2R (T3M4 and BxPC-3 cells), heterozygous 2R/3R (AsPC-1, Capan-1, and SU86.86), and homozygous 3R/3R (PANC-1 and COLO357). The optical density ratio of genotypes 3R/3R, 2R/2R and 2R/3R was 1.393 ± 0.374, 0.568 ± 0.032 and 0.561 ± 0.056, respectively. Cells with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele, yielding heterozygous 2R/3Rc (AsPC-1, Capan-1, and SU86.86), homozygous 3Rg/3Rg (COLO357) and homozygous 3Rc/3Rc (PANC-1). The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723 ± 0.062 and 1.063 ± 0.134, respectively, and this difference was statistically significant (P < 0.05). Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R cells.</p><p><b>CONCLUSIONS</b>Polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell lines. Cells with the 3R/3R genotype had higher TS protein expression than the 2R/2R or 2R/3R genotypes. Cells of the 3R/3R genotype with high TS protein expression were shown lower 5-FU sensitivity than cells with the 2R/2R or 2R/3R genotypes. These data warrant large-scale clinical studies to assess the role of polymorphisms in the TS gene on its protein expression and chemosensitivity to 5-FU in pancreatic cancer.</p>