Recent advances in targeted therapy for pancreatic adenocarcinoma

Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-dependent kinase inhibitor 2A(90%),and tumor suppressor 53(75%–90%)being the most common.Mothers against decapentaplegic homolog 4 represents 50%.In addition,the selfpreserving cancer stem cells,dense tumor microenvironment(fibrous accounting for 90%of the tumor volume),and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC.Molecular targeted therapy is widely utilized and effective in several solid tumors.In PDAC,targeted therapy has been extensively evaluated;however,survival improvement of this aggressive disease using a targeted strategy has been minimal.There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC–erlotinib,but the absolute benefit of erlotinib in combination with gemcitabine is also minimal(2 wk).In this review,we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process,analyze possible reasons for the lack of positive results in clinical trials,and suggest ways to improve them.We also discuss emerging trends in targeted therapies for PDAC:combining targeted inhibitors of multiple pathways.The PubMed database and National Center for Biotechnology Information clinical trial website(www.clinicaltrials.gov)were queried to identify completed and published(PubMed)and ongoing(clinicaltrials.gov)clinical trials(from 2003-2022)using the keywords pancreatic cancer and targeted therapy.The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.

Advancements of molecular imaging and radiomics in pancreatic carcinoma

Despite the recent progress of medical technology in the diagnosis and treatment of tumors,pancreatic carcinoma remains one of the most malignant tumors,with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation.This paper focuses on the research progress of magnetic resonance imaging,nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma.We also briefly described the achievements of our team in this field,to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Rare ROS1-CENPW gene in pancreatic acinar cell carcinoma and the effect of crizotinib plus AG chemotherapy:A case report

BACKGROUND This is the first report of an ROS1-CENPW fusion gene in pancreatic malignancies.CASE SUMMARY A 77-year-old woman with a pancreatic tumor and multiple liver metastases was admitted to our hospital.Genetic testing revealed the presence of the ROS1-CENPW fusion gene,a rare fusion gene that has not been previously reported in the field of pancreatic cancer.The patient received crizotinib plus AG(albumin paclitaxel plus gemcitabine)chemotherapy.After treatment,the patient’s condition stabilized,and her prognosis was good.CONCLUSION The ROS1-CENPW gene treatment regimen used in this case is an excellent treatment option that provides new hope for patients with advanced pancreatic cancer and similar genetic mutations.To date,owing to the rarity of the ROS1-CENPW fusion gene,our team has encountered only a single case.Therefore,the efficacy of crizotinib plus AG chemotherapy in patients with pancreatic acinar cell carcinoma harboring the ROS1-CENPW fusion gene requires further validation.

Meiotic nuclear divisions 1 suppresses the proliferation and invasion of pancreatic cancer cells via regulating H2A.X variant histone

Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.

Pancreatic head carcinoma:clinical analysis of 189 cases

BACKGROUND: Pancreatic cancer is a lethal disease with an increasing incidence. We retrospectively reviewed the clinical data on diagnosis and treatment of pancreatic head carcinoma, and analyzed the factors affecting prognosis of the disease. METHODS: The data of 189 patients with pancreatic head carcinoma treated from September 1, 1995 to August 31, 2005 were reviewed retrospectively. Ninety-four patients treated from September 1, 2000 to August 31, 2005 were followed up in April 2008. The median survival time (MST) and 1- to 5-year cumulative survival rates of the patients were calculated by the life table method and the Kaplan-Meier method. Cox regression was used to screen out significant risk factors. RESULTS: 96.9% of the patients were more than 40 years old, and the male/female ratio was 1.63. The detection rate of transabdominal ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), and serum tumor marker CA19-9 were 82.0%, 93.1%, 94.7% and 79.8%, respectively. The MST of patients with pancreatic head carcinoma was 360 +/- 60 days. The 1- to 5-year cumulative survival rates were 50.0%, 19.2%, 12.1%, 9.4% and 4.7%, respectively. However, patients with unresectable tumor survived for a shorter time (183 +/- 18 days). Their 1- to 2-year cumulative survival rates were 28.3% and 0.0%. Cox regression analysis showed that in pancreatic head carcinoma, the independent predictors for prognosis included tumor size, invasion of the superior mesenteric vessel, and radical resection. The MST of patients with pancreatic head carcinoma after radical resection was 510 days, significantly longer than that of patients undergoing non-specific treatment and palliative therapy (225 days). In addition, patients with slight jaundice survived for the longest time (533 +/- 51 days), compared with patients with severe jaundice (236 +/- 43 days) and without jaundice (392 +/- 109 days). CONCLUSIONS: Pancreatic head carcinoma is easily misdiagnosed, and is usually found to be advanced when tumor size is too large (above 4 cm in diameter) with local spread or metastatic disease. In these cases, surgical resection is usually not feasible, and its prognosis is usually very poor. Therefore, careful attention should be paid to these high-risk patients, especially, males, more than 40 years old, and presenting slight jaundice. Then imaging examination (US, CT and EUS) and serum tumor marker examination (CA19-9) are used to detect this disease earlier, and perform curative resection earlier. In this way, it is possible to cure the patients with a longer survival time and better quality of life.

Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors

Background: Pancreaticoduodenectomy(PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival( ≥ 5 years) after PD. Methods: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group(I) patients who survived less than 5 years and group(II) patients who survived ≥ 5 years. Results: There were 47(20.6%) long-term survivors( ≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31(66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR(95% CI) = 1.712(1.24 8–2.34 8), P = 0.001], smaller tumor size [OR(95% CI) = 1.335(1.032–1.726), P = 0.028] and R0 resection [OR(95% CI) = 3.098(2.095–4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. Conclusions: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.

Analysis of gene expression profiles in pancreatic carcinoma by using cDNA microarray

OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarray and detect target genes for further study. METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases of moderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of 18 000 genes. RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively. We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and 353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0% genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normal samples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes, transcription factor genes were identified. CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate gene expression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism would play an important role in the pathogenesis of pancreatic carcinoma.

Recombinant adenovirus-p53(Gendicine) sensitizes a pancreatic carcinoma cell line to radiation

Objective： In this study, we examine the effects of recombinant adenovirus-p53 （rAd-p53） on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. Methods： Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions （SF） were calculated. Dose survival cttrves were constructed and modeled for comparison. Results： Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation （Do for the experimental and control groups was 2.199 and 2.462, respectively）. Conclusions： Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial.

Inhibition of Metastatic Progression of SSTR2 Gene Transfection Mediated by Adenovirus in Human Pancreatic Carcinoma Cells

The inhibition of metastatic progression of Somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanisms involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells （P〈0. 01）. Moreover, the expression of MMP-2 mRNA was significantly reduced in the SSTR2-expressing cells and converse- ly the expression of TIMP-2 mRNA was significantly increased in the SSTR2-expressing cells when compared with the Adv-GFP control and mock control （P〈0. 01）. The expression of reintroduced human SSTR2 gene in BXPC-3 cells by Adv-GFP-SSTR2 had the anti-migratory and anti-invasive effects, and the mechanisms involved in this effect may be due to the down-regulated expression of MMP-2 and up-regulated expression of TIMP-2.

Diagnostic accuracy of K-ras mutation for pancreatic carcinoma:a meta-analysis

BACKGROUND:The conventional tests for the diagnosis of early stage pancreatic carcinoma are not acceptable.This metaanalysis is to evaluate the accuracy of K-ras mutation for the diagnosis of pancreatic carcinoma.DATA SOURCES:A systemic search of all relevant literature was performed in Web of Science,EMBASE,Cochrane Database,and MEDLINE(PubMed as the search engine) prior to June 1,2011.Thirty-four studies fulfilled the inclusion criteria and data were pooled for analysis.RESULTS:The pooled estimates for K-ras mutation in diagnosis of pancreatic carcinoma were as follows:sensitivity 0.68(95% CI:0.66-0.71),specificity 0.87(95% CI:0.85-0.88),positive likelihood ratio 4.54(95% CI:3.47-5.94),negative likelihood ratio 0.37(95% CI:0.30-0.44) and diagnostic odds ratio 14.90(95% CI:10.02-22.15).Summary receiver operating characteristic analysis demonstrated that the maximum joint sensitivity and specificity was 0.79,and the overall area under the curve was 0.86.CONCLUSIONS:Diagnostic accuracy of K-ras mutation was not superior to that of conventional tests.Therefore,K-ras mutation analysis alone is not recommended for the diagnosis of pancreatic carcinoma.

Celecoxib Inhibits Proliferation and Induces Apoptosis via Cyclooxygenase-2 Pathway in Human Pancreatic Carcinoma Cells

In order to evaluate the effects and mechanisms of celecoxib in inhibiting proliferation and inducing apoptosis on human pancreatic carcinoma cells, the anti-proliferative effect was measured by using methabenzthiazuron (MTT) assay. Cell cycle and apoptosis were analyzed by using flow cytometry (FCM), and the PGE 2 levels in the supernatant of cultured pancreatic carcinoma cells were quantitated by enzyme-linked immunoabsordent assay (ELISA). Our results showed that celecoxib suppressed the production of PGE 2 and inhibited the growth of JF-305 cells, and the anti-proliferative effect of celecoxib could be abolished by addition of PGE 2. FCM revealed that celecoxib could inhibit proliferation and induce apoptosis by G 1-S cell cycle arrest. It was concluded that cyclooxygenase-2 specific inhibitor celecoxib could inhibit proliferation and induced apoptosis of human pancreatic carcinoma cells via suppression of PGE 2 production in vitro.

Bacteriolytic therapy of experimental pancreatic carcinoma

AIM:To investigate the effectiveness of Clostridium novyi(C.novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic,immunocompetent Panc02/C57Bl/6 model. METHODS:C.novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes.Systemic immune responses in peripheral blood and spleen were examined by flow cytometry.Supplementary,cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed. RESULTS:Application of spores identified,that(1) small tumors(<150 mm 3 )were completely unaffected (n=10);(2)very large tumors(>450 mm3)responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n=6);and(3)an optimal treatment window exists for tumors of approximately 250 mm 3 (n=21).In this latter group,all tumor-bearing animals had complete tu-mor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed(tumor volume at day 28:197.8±87.3 mm 3 vs 500.1±50.9 mm3,P<0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system. CONCLUSION:The observed complete tumor regression is encouraging and shows that immunotherapy with C.novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.

Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma

Objective：To assess the safety and efficacy of the combination of recombinant adenovirus-p53 （rAd-p53） with radiochemotherapy for treating unresectable pancreatic carcinoma.Methods：The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy.Intratumoral injection of rAd-p53 was guided by B ultrasound.Radiochemotherapy consisted of intensity-modulated radiotherapy （IMRT） at two dose levels and intravenous gemcitabine （Gem）.For radiotherapy,gross target volume （GTV） and clinical target volume （CTV） were 55-60 Gy and 45-55 Gy in 25-30 fractions,respectively.Concurrent intravenous gemcitabine was administered at 350 mg/m2,weekly,for 6 weeks.The primary end points included toxicity,clinical benefit response （CBR） and disease control rate （DCR）.The secondary end points included progression-free survival （PFS） and overall survival （OS）.Results：Fifteen eligible patients were enrolled.Eight patients （53.3%） were evaluated as CBR and 12 （80%） achieved DCR.The median PFS and OS were 6.7 and 13.8 months,respectively.One-year PFS and OS were 40.0% and 51.1%,respectively.There were 8 （53.3%） patients reported grade 3 toxicities including neutropenia （6 patients,40%）,fever （1 patient,6.7%） and fatigue （1 patient,6.7%）.There was no grade 4 toxicity reported.Conclusion：Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated.Long-term follow-up is needed to confirm the improvement of PFS and OS.

Enhancement parameters of contrast-enhanced computed tomography for pancreatic ductal adenocarcinoma: Correlation with pathologic grading

BACKGROUND Pancreatic ductal adenocarcinoma(PDA)is a malignancy with a high mortality rate and short survival time.The conventional computed tomography(CT)has been worldwide used as a modality for diagnosis of PDA,as CT enhancement pattern has been thought to be related to tumor angiogenesis and pathologic grade of PDA.AIM To evaluate the relationship between the pathologic grade of pancreatic ductal adenocarcinoma and the enhancement parameters of contrast-enhanced CT.METHODS In this retrospective study,42 patients(Age,mean±SD:62.43±11.42 years)with PDA who underwent surgery after preoperative CT were selected.Two radiologists evaluated the CT images and calculated the value of attenuation at the aorta in the arterial phase and the pancreatic phase(VAarterial and VApancreatic)and of the tumor(VTarterial and VTpancreatic)by finding out four regions of interest.Ratio between the tumor and the aorta enhancement on the arterial phase and the pancreatic phase(TARarterial and TARpancreatic)was figured out through dividing VT arterial by VAarterial and VTpancreatic by VApancreatic.Tumor-to-aortic enhancement fraction(TAF)was expressed as the ratio of the difference between attenuation of the tumor on arterial and parenchymal images to that between attenuation of the aorta on arterial and pancreatic images.The Kruskal-Wallis analysis of variance and Mann-Whitney U test for statistical analysis were used.RESULTS Forty-two PDAs(23 men and 19 women)were divided into three groups:Welldifferentiated(n=13),moderately differentiated(n=21),and poorly differentiated(n=8).TAF differed significantly between the three groups(P=0.034)but TARarterial(P=0.164)and TARpancreatic(P=0.339)did not.The median value of TAF for poorly differentiated PDAs(0.1011;95%CI:0.01100-0.1796)was significantly higher than that for well-differentiated PDAs(0.1941;95%CI:0.1463-0.3194).CONCLUSION Calculation of TAF might be useful in predicting the pathologic grade of PDA.

The relationship between loss expression of DPC4/Smad4 gene and carcinogenesis of pancreatobiliary carcinoma

Objective: To clarify the relationship between loss of DPCA gene expression and pathogenesis of pancreato- biliary carcinoma. Methods: 75 slides of normal duct (20), hyperplasia (15), dysplasia (15), invasive carcinoma (25) from patients with pancreatic diseases including pancreatic carcinoma (25 patients), chronic pancreatitis (6), pancreas injury (2) and 71 slides of common bile duct (CBD) carcinoma (38), gallbladder carcinoma (18), hilar bile duct (HBD) carcinoma (15) from patients with primary biliary tract carcinoma were analyzed for the expression of DPC4 protein by im- munohistochemical staining. Results: All specimens from 20 cases of normal duct and 15 cases of hyperplasia showed marked expres- sion of DPC4 protein. The frequency of loss expres- sion of the DPC4 gene was 33 % in dysplasia, and 48% in invasive carcinoma. There was a significant statistical difference between byperplasia and dyspla- sia (P<0.01) and in dysplasia vs invasive carcinoma (P<0.05). The frequency of loss expression of the DPC4 gene was 47.3% in CBD carcinoma, 11% in gallbladder carcinoma, and 13% in HBD carcinoma. The frequency of loss expression of the DPCA gene was significantly different in CBD carcinoma vs gall- bladder carcinoma and HBD carcinoma (P<0.01). Conclusions: Inactivation of the DPC4 gene occurs late in the neoplastic progression of pancreatic carci- noma. The frequency of DPC4 gene alternation was different in various locations of biliary tract carcino- ma. In CBD carcinoma, this frequency is similar to that in pancreatic carcinoma, indicating their similar molecular alternations.

MR dynamic Gadolinium-enhanced fast multiplanar spoiled gradient-echo and spin-echo T1-weighted fat-suppressed techniques in diagnosis of pancreatic carcinoma

Objective: To evaluate the value of MR dynamic Gadolinium-enhanced fast multiplanar spoiled gradi- ent-echo (FMPSPGR) and spin-echo (SE) T1- weighted fat-suppressed techniques in the diagnosis of pancreatic carcinoma. Methods: Eighteen cases of pancreatic carcinoma veri- fied by surgical and pathologic results were examined by MR, and the MR sequences included SE T1WI, FSE T2WI, SE T1-weighted fat-suppressed and dy- namic Gadolinium-enhanced FMPSPGR. Results: Of 18 pancreatic carcinomas, 10, 6, and 2 tumors showed respectively hypo-intensity, iso-inten- sity and hyper-intensity on SE T1WI, meanwhile, 8, 6, and 4 tumors displayed hyper-intensity, iso-inten- sity and hypo-intensity on FSE T2WI in comparison with the normal pancreatic tissue. All of the tumors showed hypo-intensity on SE T1-weighted fat-sup- pressed and also obvious non-enhancement or slight enhancement on MR dynamic Gadolinium-enhanced FMPSPGR images during the arterial dominant phase scanning. Conclusion: SE T1-weighted fat-suppressed and MR dynamic Gadolinium-enhanced FMPSPGR sequences could evidently improve the sensitivity and specificity in the diagnosis of pancreatic carcinoma.

Spiral multi-phase CT in evaluating resectability of pancreatic carcinoma

Objectives: To evaluate the specific manifestations of pancreatic carcinoma on spiral multi-phase CT and its resectability before operation. Methods: Ninety-seven patients were confirmed oper- atively and pathologically. Enhanced CT scan was performed with intravenous injection bolus of ap- proximately 75-120 ml (1-1.5 ml/kg body weight) contrast medium at a rate of 2.5-3 ml/s. In 68 pa- tients receiving dual-phase scan, the delayed scan time of arterial and venous phases was 18-20 s and 60-70 s, respectively, and in 29 patients receiving three-phase scan, the delayed scan time of arterial, pancreatic and portal venous phases was 18 s, 40 s and 75 s, respectively, with a slice of 3-5 mm thick- ness, a pitch of 1-1.5, and a reconstruction interval of 2.5-4.8 mm. Results: Positive and negative predictive values of un- resectable tumors were 97.65% and 75.86%, respec- tively. The sensitivity and accuracy were 90.67% and 90. 72%, respectively. Positive predictive values of dual-phase and three-phase were 95.83% and 100%, respectively; negative predictive values were 75% and 77.78%, respectively. Conclusions: Spiral multi-phase CT is superior in re- vealing the involvement of peripancreatic vessels, the invasion of the neighboring organs, the size, shape and range of carcinoma, and the metastasis of liver and lymph node. The predictability of resection is obviously increased for patients with pancreatic car- cinoma.

Clinical significance of SQSTM1/P62 and nuclear factor-κB expression in pancreatic carcinoma

BACKGROUND Overexpression of SQSTM1(sequestosome 1,P62)and nuclear factor-κB(NF-κB)plays an important role in the invasion and metastasis of a variety of malignant tumors.AIM To explore the expression of P62 and NF-κB in pancreatic cancer and their relationship with clinicopathological features.METHODS The expression levels of P62 and NF-κB were analyzed by immunohistochemistry with a tissue chip containing 40 cases of human pancreatic carcinoma.Then we analyzed the correlation among P62 expression,phospho-P65 expression,and clinicopathological features of pancreatic carcinoma samples.RESULTS P62 expression was mainly observed in the cytoplasm of pancreatic carcinoma cells.Phosphorylated P65(phospho-P65)was mainly expressed in the nucleus and cytoplasm of pancreatic carcinoma cells.There was a significant difference in P62 expression among T stages.And a significant difference in phosphor-P65 expression among pathology types was noted.In the cases with strongly positive P62 expression,significant differences were found in age.And there were significant differences in T stage and tumor-node-metastasis stage in the cases with strongly positive phosphor-P65 expression.CONCLUSION In pancreatic carcinoma,P62 expression is significantly correlated with T stage.It may be a valuable malignant indicator for human pancreatic carcinoma.

Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma

BACKGROUND:The association between gastric and pancreatic carcinoma is a relatively rare condition.In gastric carcinoma patients,the prevalence of second tumors varies 2.8% to 6.8% according to the reported statistics.Gastric cancer associated with pancreatic cancer is uncommon.METHODS:We report a case of a 73-year-old patient hospitalized for vomiting and weight loss.Esophagogastroduodenoscopy demonstrated an ulcerative lesion of the gastric antrum.Computed tomography and magnetic resonance showed a gastric thickening in the antral and pyloric portion and a nodular mass (3×1.7 cm) in the uncinate portion of the pancreas.RESULTS:The patient underwent pancreaticoduoden-ectomy according to Whipple regional type Ⅰ Fortner.Histological examination of the specimen demonstrated a moderately differentiated adenocarcinoma of the stomach and a poorly differentiated ductal adenocarcinoma of the pancreas.CONCLUSIONS:Long survival is rare in patients with associated gastric and pancreatic cancer.Surgical resection remains the only potentially curative treatment.

Analysis of the efficacy of transcatheter arterial infusion chemotherapy in the treatment of pancreatic carcinoma

Objective:To evaluate the clinical efficacy of infusion of gemcitabine(GEM) and fluorouracil(5-FU)through the celiac artery and superior mesenteric artery in the treatment of pancreatic carcinoma(PC).Methods:We analyzed 20 patients diagnosed clinically or pathologically with PC,without metastases,who had an estimated survival duration of>3 months in our department from May 2009 to December 2014.Nine patients were treated directly without surgical resection of the tumor,while the other 11 patients were treated after surgery.In all patients,the femoral artery was punctured using the Seldinger technique,and a catheter was placed in the opening of the celiac artery or the superior mesenteric artery.We administered 500 mg/m2 GEM and 500 mg/m2 5-FU.Observational data included data on clinical efficacy and survival rates during the follow-up period of 3-72 months.Results:Twenty patients were treated 85 times with transcatheter arterial infusion chemotherapy(TAI).The survival rates were 80%,40%,35%,20%,10%,and 5% at 3,6,12,24,and 72 months,respectively.Conclusion: TAI chemotherapy with GEM and 5-FU may be a therapeutic option for the treatment of PC.