Cases Of Ductal Adenocarcinoma Research Articles

Intratumoral Heterogeneity in Breast Cancer: A Case Report and Molecular Discussion

The emerging era of personalized medicine makes it increasingly important to consider intratumoral heterogeneity, which has been found in some breast cancer cases. However, its identification criteria, form of reporting, and subsequent effects on the clinical course of this disease remain controversial and not fully defined. Here, we report and discuss a case of breast invasive ductal adenocarcinoma with substantial intratumoral heterogeneity, discrepancy between Her2/neu immunostaining and in situ hybridization, and disparity between estrogen receptor status before and after neoadjuvant therapy.

Clinical significance and EZH2, ERG and SPINK1 protein expression in pure and mixed ductal adenocarcinoma of the prostate.

Although ERG and SPINK1 molecular alterations have been studied in acinar and ductal adenocarcinoma of the prostate, EZH2 expression has not been previously evaluated in ductal adenocarcinoma. We collected cases of pure and mixed ductal adenocarcinoma of the prostate and evaluated clinical significance and EZH2, ERG, and SPINK1 protein expression. We investigated 61 ductal adenocarcinomas, 22 pure and 39 mixed ductal/acinar. Except for tumor growth pattern, none of the clinical parameters studied significantly differed between pure and mixed tumors. Thirty-five percent of ductal adenocarcinomas were organ confined, 15% displayed seminal vesicle invasion. Lymph node and distal metastasis occurred in 13% and 24% of cases, respectively; 34% of patients experienced biochemical failure, 7% died of disease. Ninety-eight percent of tumors expressed EZH2; in 80% of cases >50% of tumor cells were positive. ERG and SPINK1 were expressed in 20% and 36% of cases, respectively. There was no difference in protein expression between pure and mixed ductal adenocarcinomas. ERG expression tended to be lower, and SPINK1 higher than reported for acinar tumors. Biochemical failure, metastasis and death did not differ between EZH2, ERG, and SPINK1 positive and negative patients, nor between <50% versus >50% expression of SPINK1 and EZH2, respectively. Pure and mixed ductal adenocarcinomas have similar clinical behavior and molecular alterations. Higher EZH2 and SPINK1 protein expression, compared to acinar prostatic adenocarcinoma, might account for the more aggressive clinical course of ductal adenocarcinoma.

A Correlation Study of Mismatch Repair (MMR) Immunohistochemical Protein Expression of Pancreatic Solid Tumors in Cytology Cell Blocks and Matching Surgical Specimens

Introduction Only 15%-20% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) cases are surgically operable. Cytology samples may be the only source for guiding clinical management. Current research indicates that mismatch repair (MMR) status could be valuable for implementing novel treatment modalities. In this study, immunohistochemical (IHC) MMR protein expression on cytology cell blocks was compared with that of the correlating surgical resection specimens. Materials and methods A retrospective review of 120 pancreatic solid tumor needle biopsies from 2016 to 2019 was performed, and 15 experimental cases were selected comprising of cellular (>100 tumor cells and >100 benign positive control cells that include benign ductal cells and/or lymphocytes) alcohol-prefixed formalin-fixed cytology cell blocks (CB), and corresponding subsequent surgical resections (Surg). The cases include 13 PDACs (87%), 1 (6.5%) low grade neuroendocrine tumor (PNET), and 1 (6.5%) acinar cell carcinoma (ACC). A routine four-panel (MLH1, MSH2, MSH6, and PMS2) MMR IHC testing was performed. The percentage of protein expression was evaluated and compared between individual CB-Surg pairs. Results About 8 of the 15 (53.3%) cytology cases showed matching protein expressivity with the surgical specimens for all four MMR markers (Table 1). The remaining 7 pairs (46.7%) appeared to have a partial concordance, including 6 values for which a surgical marker showed less expression, and 13 values for which a cytological marker showed less expression. [Table: see text] CONCLUSION: Cytology CB MMR protein panel testing could be a useful consideration for inoperable patients who would benefit from medical therapy such as immune checkpoint inhibition. However, the cellularity and overall quality of the CB is expected to be paramount in obtaining satisfactory IHC MMR results. The MMR results could be more confidently trusted when the staining is intact, but when not retained, they should be interpreted with caution in a low cellularity sample to avoid mistakenly identifying MMR-deficient tumors.

A retrospective histological comparison of EUS-guided fine-needle biopsy using a novel franseen needle and a conventional end-cut type needle.

Background and Objectives:Recently, a 22G Franseen needle for EUS-guided fine-needle biopsy (EUS-FNB) with three novel symmetric heels has been developed to adequately obtain a core tissue.Methods:All 38 consecutive patients with pancreatic masses who underwent EUS-FNB using a Franseen needle were investigated retrospectively to assess the efficacy and safety of EUS-FNB using the Franseen needle. Then, the EUS-FNB outcomes and histological assessments of the tissue obtained by EUS-FNB using the Franseen needle and EUS-FNA using the conventional end-cut type needle for each of the 30 pancreatic ductal adenocarcinoma cases were compared.Results:An accurate histological diagnosis of the Franseen needle was achieved with a mean of 2 passes in 97.4% of patients. Although the accurate histological diagnosis rate of pancreatic ductal adenocarcinoma was not significantly different (96.7% vs. 93.3%, P = 0.55), the mean number of passes in the Franseen needle was significantly less than that in the conventional needle (2.1 ± 0.4 vs. 3.2 ± 0.8, P < 0.001). The presence of desmoplastic fibrosis with neoplastic cellular elements and venous invasion were significantly higher (96.7% vs. 40.0%, P < 0.001 and 23.3% vs. 0%, P < 0.01, respectively) and the amount of obtained tissue was significantly larger with the Franseen needle (2.13 mm2 vs. 0.45 mm2, P < 0.001).Conclusions:EUS-FNB using the Franseen needle enables the acquisition of a larger amount of tissue sample and achieves an accurate histological diagnosis with a smaller number of passes than the conventional end-cut type needle.

A case of prostate ductal adenocarcinoma in the bladder washing fluid specimen

A case of prostate ductal adenocarcinoma in the bladder washing fluid specimen

Loss of ARID1A Expression Correlates With Tumor Differentiation and Tumor Progression Stage in Pancreatic Ductal Adenocarcinoma.

Mutations in the AT-rich interactive domain 1A gene, which encodes a subunit of the Switch/Sucrose nonfermentable chromatin remodeling complex, can result in loss of protein expression and are associated with different cancers. Here, we used immunohistochemistry to investigate the significance of AT-rich interactive domain 1A loss in 73 pancreatic ductal adenocarcinoma cases with paired paracancerous normal pancreatic tissues. The relationship between levels of the AT-rich interactive domain 1A protein product, BAF250a, and clinicopathological parameters in the 73 pancreatic cancer specimens was also analyzed. We found that the expression of AT-rich interactive domain 1A in normal pancreatic tissue was higher than that in tumor tissue. Loss of AT-rich interactive domain 1A expression in pancreatic tumors was associated with tumor differentiation (P = .002) and tumor stage (P = .048). Meanwhile, BAF250a protein levels were not related to lymph node metastasis, distant metastasis, sex, or age and were not associated with survival. Transfection of the pancreatic cancer cell lines AsPC-1 and PANC-1 with small-interfering RNA specific for AT-rich interactive domain 1A resulted in elevated messenger RNA and protein expression levels of B-cell lymphoma-2 (Bcl-2), CyclinD1, and Kirsten rat sarcoma viral oncogene (KRAS). The AT-rich interactive domain 1A expression level in the cells was increased following microRNA-31 (miR-31) inhibitor transfection. Our data provide additional evidence that AT-rich interactive domain 1A might function as a tumor suppressor gene in pancreatic carcinogenesis.

Increased Bcl-xL Expression in Pancreatic Neoplasia Promotes Carcinogenesis by Inhibiting Senescence and Apoptosis.

Background & AimsBcl-xL, an anti-apoptotic Bcl-2 family protein, is overexpressed in 90% of pancreatic ductal adenocarcinoma (PDAC) cases. However, Bcl-xL expression in pancreatic intraepithelial neoplasias (PanINs) and its significance in PDAC carcinogenesis remain unclear. The aim of this study was to elucidate the significance of Bcl-xL expression in PanINs.MethodsWe investigated the expression levels of Bcl-xL in pancreas-specific KrasG12D (P-KrasG12D) mice and human PanINs and PDAC. We examined the impact of Bcl-xL expression on Kras-mutated pancreatic neoplasia using Bcl-xL–overexpressing P-KrasG12D mice and Bcl-xL–knockout P-KrasG12D mice.ResultsIn P-KrasG12D mice, the number of PanINs increased and their grades progressed with age. In total, 55.6% of these mice developed PDAC at 12–14 months. According to the immunohistochemistry of mouse pancreas and human resected specimens, Bcl-xL expression was increased significantly in PanIN-1 compared with that in normal pancreatic ducts, and augmented further with the progression of pancreatic neoplasia in PanIN-2/3 and PDAC. Oncogene-induced senescence was observed frequently in PanIN-1, but rarely was detected in PanIN-2/3 and PDAC. Bcl-xL overexpression significantly accelerated the progression to high-grade PanINs and PDAC and reduced the survival of P-KrasG12D mice. Bcl-xL overexpression in P-KrasG12D mice suppressed oncogene-induced senescence in PanIN-1 and inhibited apoptosis in PanIN-3. Bcl-xL deficiency in P-KrasG12D mice induced cellular senescence in PanIN-2/3.ConclusionsBcl-xL expression increases with the progression from PanIN-1 to PDAC, whereas oncogene-induced senescence decreases. Bcl-xL overexpression increases PDAC incidence rates by inhibiting oncogene-induced senescence and apoptosis in PanINs. Conversely, Bcl-xL deficiency induced senescence in PanINs. Anti–Bcl-xL treatments may have the potency to suppress the progression from PanINs to PDAC.

The Novel KLF4/MSI2 Signaling Pathway Regulates Growth and Metastasis of Pancreatic Cancer

Musashi 2 (MSI2) is reported to be a potential oncoprotein in cases of leukemia and several solid tumors. However, its expression, function, and regulation in pancreatic ductal adenocarcinoma (PDAC) cases have yet to be demonstrated. Therefore, in the current study, we investigated the clinical significance and biologic effects of MSI2 expression in PDAC cases and sought to delineate the clinical significance of the newly identified Krüppel-like factor 4 (KLF4)/MSI2 regulatory pathway. MSI2 expression and its association with multiple clinicopathologic characteristics in human PDAC specimens were analyzed immunohistochemically. The biological functions of MSI2 regarding PDAC cell growth, migration, invasion, and metastasis were studied using gain- and loss-of-function assays both in vitro and in vivo Regulation of MSI2 expression by KLF4 was examined in several cancer cell lines, and the underlying mechanisms were studied using molecular biologic methods. MSI2 expression was markedly increased in both PDAC cell lines and human PDAC specimens, and high MSI2 expression was associated with poor prognosis for PDAC. Forced MSI2 expression promoted PDAC proliferation, migration, and invasion in vitro and growth and metastasis in vivo, whereas knockdown of MSI2 expression did the opposite. Transcriptional inhibition of MSI2 expression by KLF4 occurred in multiple PDAC cell lines as well as mouse models of PDAC. Lost expression of KLF4, a transcriptional repressor of MSI2 results in overexpression of MSI2 in PDACs, which may be a biomarker for accurate prognosis. A dysregulated KLF4/MSI2 signaling pathway promotes PDAC progression and metastasis. Clin Cancer Res; 23(3); 687-96. ©2016 AACR.

Do the Well Known Prognostic Parameters in Pancreatic Ductal Adenocarcinoma Really Reflect Survival?

Pancreatic ductal adenocarcinoma is an aggressive tumor with short survival. In this study we aimed to investigate the effect of well-known prognostic parameters on survival in these tumors. A total of 56 pancreatic ductal adenocarcinoma cases diagnosed between 2005 and 2014 were included in the study. Survival data were obtained and histopathological parameters were re-evaluated in each patient. Tumor size (p=0.029), mitotic count (p=0.030), lymph node metastasis (p=0.003), metastatic lymph node ratio (p < 0.001) and ampullary invasion (p=0.044) had a statistically significant relationship with survival. However, there was no relationship between survival and tumor grade, lymphovascular and perineural invasion, and peripancreatic soft tissue invasion. Our results showed that existent 2010 WHO pancreatic ductal adenocarcinoma grading parameters excluding mitotic count are subjective and not applicable. Considering that almost all of the tumors in our series were larger than 2 cm, we think that the 2 cm cut-off in tumor size is insufficient to make the tumor stage pT2. Peripancreatic soft tissue invasion, which is a common finding in pancreatic ductal adenocarcinoma, should also not be assessed like adjacent tissue invasion and make the tumor reach pT3 stage independent of tumor size. It is clear that the existent WHO tumor grading and pT staging parameters need to be revised and the mitotic count, which correlates with survival, should be presented in pathology reports.

Prognostic Evaluation of Vimentin Expression in Correlation with Ki67 and CD44 in Surgically Resected Pancreatic Ductal Adenocarcinoma.

Purpose. Radical surgical resection with adjuvant chemotherapy or chemo-radiotherapy is the most effective treatment for pancreatic ductal adenocarcinoma (PDAC). However, relatively few studies investigate the prognostic significance of biological markers in PDAC. This study aims to look into the expressions of vimentin, Ki67, and CD44 in PDAC surgical specimens and their potential prognostic implications in survival. Method. The study was designed as retrospective, and vimentin, Ki67, and CD44 expressions were evaluated by immunohistochemistry in 53 pancreatic ductal adenocarcinoma cases. Overall survival was assessed by the Kaplan–Meier method. Results. Patients' median age was 68 years. The median survival was 18 months. The tumors were T3-4 in 40/53 (75.5%), and metastases in lymph nodes were found in 42 out of 53 (79.2%) cases. On multivariate analysis, the size of primary tumor (p < 0.001), the surgical resection margin status (p = 0.042), and vimentin expression (p = 0.011) were independently correlated with overall survival. Conclusions. Long-term survival after resection of PDAC is still about 15%. Vimentin expression is a potential independent adverse prognostic molecular marker and should be included in histopathological reports. Also, CD44 expression correlates with high Ki67, vimentin positivity, and N stage and may represent a potential target of novel therapeutic modalities in pancreatic adenocarcinoma patients.

Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer.

Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances.

Abstract 4577: Fibroblast growth factor receptor-4 (FGFR-4) as a novel therapeutic target for pancreatic cancer

Abstract The fibroblast growth factor receptor (FGFR) family plays crucial roles in development, tissue repair, and malignant tumors. FGFR-1, -2, and -3 each exist in two isoforms, IIIb and IIIc, due to alternative splicing of the extracellular domain, whereas FGFR-4 does not have these isoforms. FGFR-4 is reportedly over-expressed in various cancers such as breast, prostate, hepatocellular, ovarian, gastric, colorectal, and pancreatic cancers, wherein it contributes to tumor progression. Recent studies have shown that a decrease in FGFR-4 levels suppresses the aggressiveness of gastric, colorectal, and ovarian cancers. We found that pancreatic cancer cell lines expressed similar levels of the IIIb and IIIc isoforms of FGFR-1 to -3, but showed different FGFR-4 levels. These findings suggest that the cancer cells surviving after treatment with recently developed anti-FGFR drugs, which target FGFR-1 to -3, tend to express high levels of FGFR-4. Moreover, a single-nucleotide polymorphism (SNP) in exon 9 of the gene encoding FGFR-4 that results in the substitution of glycine with arginine at codon 388 (388 Gly/Arg) in the transmembrane domain is associated with poor outcomes of high-grade soft tissue sarcoma, prostate, lung, head and neck carcinoma, and advanced and treatment-resistant breast cancer. It has been reported that 40-50% of Caucasians carry at least one copy of the 388 Gly/Arg SNP of FGFR-4. In the present study, we examined the expression and roles of the 388 Gly/Arg SNP in pancreatic cancer and tried to clarify whether FGFR-4 may be a novel therapeutic target for cancer treatment. In human pancreatic tissues, FGFR-4 was weakly localized in the normal exocrine and endocrine pancreas, and was strongly expressed in 67 of 136 pancreatic ductal adenocarcinoma cases (49%). FGFR-4 expression positively correlated with larger primary tumors and more advanced stages of pancreatic cancer. FGFR-4 mRNA was expressed in 5 pancreatic cancer cell lines at various levels, and the mutation in codon 388 was detected in 3 of the cell lines, including PK-1 cells. A short hairpin RNA expression vector targeting FGFR-4 was stably transfected to these mutant-expressing PK-1 cells (388 Gly/Arg), which then showed lower growth rates and cell migration and invasion abilities compared to sham vector-transfected cells. DNA microarray analysis showed that decreased expression of FGFR-4 in PK-1 cells altered the expression levels of molecules related to cellular movement, cellular development, and cell-to-cell signaling and interactions. FGF-19—one of the major ligands for FGFR-4—was expressed in all 5 of the pancreatic cancer cell lines tested. These findings suggest that inhibition of the expression of FGFR-4 harboring the 388 Gly/Arg SNP may be a novel therapeutic strategy for pancreatic cancer, especially after treatment with the newly developed anti-FGFR-1 to -3-targeted drugs. Citation Format: Toshiyuki Ishiwata, Hisashi Yoshimura, Yoko Matsuda, Shunji Ishiwata. Fibroblast growth factor receptor-4 (FGFR-4) as a novel therapeutic target for pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4577.

Intratumor Heterogeneity of KRAS Mutation Status in Pancreatic Ductal Adenocarcinoma Is Associated With Smaller Lesions.

Recent studies have demonstrated intratumor heterogeneity (ITH) for genetic mutations in various tumors and suggest that ITH might have significant clinical impact. Because KRAS is the most commonly mutated oncogene in pancreatic ductal adenocarcinoma and has an important role in pancreatic carcinogenesis, the purpose of this study was to evaluate ITH for KRAS gene mutation and its clinical significance. Deep sequencing of 47 pancreatic ductal adenocarcinoma cases was used to determine the fraction of KRAS mutant alleles. In addition, computerized morphometry was used to calculate the fraction of tumor cells. After analysis of both results, cases were classified as ITH or as having amplification of mutant KRAS. The presence of ITH was correlated with clinical and pathological factors. KRAS mutation was found in 38 (81%) cases, of which 12 (32%) showed ITH and 9 (23%) were found to have KRAS mutant allele amplification. The presence of ITH was associated with smaller tumors, whereas amplification was associated with higher tumor diameter. In pancreatic ductal adenocarcinoma, ITH for KRAS gene mutation was associated with smaller tumors. It is possible that, as the tumor progresses, more cells carry this mutation, which leads to more aggressive tumor features.

A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection.

Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed.

Identification of FRA-1 as a novel player in pancreatic cancer in cooperation with a MUC1: ERK signaling axis.

The MUC1 glycoprotein is overexpressed and aberrantly glycosylated in >90% of pancreatic ductal adenocarcinoma cases and impacts tumor progression by initiating downstream signaling through phosphorylation of its cytoplasmic tail. Previous studies have demonstrated that MUC1 alters expression of known targets of activator protein 1 (AP-1); however, no studies have evaluated the precise impact of MUC1 signaling on the activity and formation of AP-1. Given the known role of these proteins in modulating migration, invasion, and tumor progression, we explored the effects of MUC1 on AP-1 dimer formation and function. We determined that MUC1 increased the protein levels of c-Jun, the major component of AP-1, and promoted dimerization of c-Jun with the Fos-protein FRA-1. We demonstrate that FRA-1 acts as a potent mediator of migration and invasion in a manner that is modulated by signals through MUC1, which acts as a dominant regulator of specific AP-1 and FRA-1 target genes. Our results provide the first in vivo evidence of a FRA-1 mediated expression profile that impacts pancreatic tumor growth properties. In summary, we show that MUC1 enhancement of ERK activation influences FRA-1 activity to modulate tumor migration, invasion and metastasis in a subset of pancreatic cancer cases.

IL1 Receptor Antagonist Inhibits Pancreatic Cancer Growth by Abrogating NF-κB Activation

Constitutive NF-κB activation is identified in about 70% of pancreatic ductal adenocarcinoma (PDAC) cases and is required for oncogenic KRAS-induced PDAC development in mouse models. We sought to determine whether targeting IL-1α pathway would inhibit NF-κB activity and thus suppress PDAC cell growth. We determined whether anakinra, a human IL-1 receptor (rhIL-1R) antagonist, inhibited NF-κB activation. Assays for cell proliferation, migration, and invasion were performed with rhIL-1R antagonist using the human PDAC cell lines AsPc1, Colo357, MiaPaCa-2, and HPNE/K-ras(G12V)/p16sh. In vivo NF-κB activation-dependent tumorigenesis was assayed using an orthotopic nude mouse model (n = 20, 5 per group) treated with a combination of gemcitabine and rhIL-1RA. rhIL-1R antagonist treatment led to a significant decrease in NF-κB activity. PDAC cells treated with rhIL-1R antagonist plus gemcitabine reduced proliferation, migration, and invasion as compared with single gemcitabine treatment. In nude mice, rhIL-1R antagonist plus gemcitabine significantly reduced the tumor burden (gemcitabine plus rhIL-1RA vs. control, P = 0.014). We found that anakinra, an FDA-approved drug that inhibits IL-1 receptor (IL-1R), when given with or without gemcitabine, can reduce tumor growth by inhibiting IL1α-induced NF-κB activity; this result suggests that it is a useful therapeutic approach for PDAC.

Genetic polymorphisms of interleukin 1β gene and sporadic pancreatic neuroendocrine tumors susceptibility.

To evaluate the association between the interleukin 1β (IL-1β) polymorphisms and the pancreatic neuroendocrine tumor (pNET) development. A case-control study was conducted analyzing IL-1β polymorphisms using germline DNA collected in a population-based case-control study of pancreatic cancer (51 pNET cases, 85 pancreatic ductal adenocarcinoma cases, 19 intraductal papillary mucinous neoplasm and 98 healthy controls). The distribution of genotypes for the -511 C/T polymorphism in the pNET patient groups showed significant difference compared to the control group. It is known that the carriers of the IL-1β -511T allele have increased concentrations of IL-1β. The -511 CT and TT high-expression genotypes were over-represented in pNET patients. The findings of this study suggested a possible role of IL-1β -511 C/T genotypes in the pathogenesis of pNETs since the presence of the IL-1β -511 CT and TT genotypes and the T allele was associated with an increased risk of pNET only.

Application value of end-to-side closed in situ pancreaticojejunostomy in pancreaticoduodenectomy

Objective To explore the application value of end-to-side closed in situ pancreaticojejunostomy in pancreaticoduodenectomy. Methods The clinical data of 22 patients with obstructive jaundice who were admitted to the Second Affiliated Hospital of Harbin Medical University from January to March 2014 were retrospectively analyzed. All the patients were explored whether tumors invaded inferior vena cava, superior mesenteric vein and portal vein after gallbladder decompression under general anesthesia by tracheal intubation. The standard or extended pancreaticoduodenectomy was applied according to the intraoperative results. The method of pancreaticojejunostomy was end-to-side closed in situ anastomosis of pancreatic duct and jejunal seromuscular layer. The operation time, intraoperative blood loss, postoperative gastrointestinal function recovery time, amylase concentration of drainage at postoperative day 1, 3, 5, postoperative complication, pathological classification and duration of hospital stay were observed. Patients were followed up by outpatient examination and telephone interview till May 2014. The out-patient follow-up included color Doppler ultrasound examination of effusion near the pancreatic stump, and the telephone interview included whether there were diarrhea of exocrine pancreatic insufficiency. Measurement data with normal distribution were presented as ±s (range), and measurement data with skewed distribution as M(range). Results All the 22 patients underwent successfully the operation, including 17 undergoing standard pancreaticoduodenectomy and 5 undergoing extended pancreaticoduodenectomy, with end-to-side closed in situ anastomosis of pancreatic duct and jejuna seromuscular layer. The operation time of pancreaticoduodenectomy and end-to-side closed in situ pancreaticojejunostomy were (313±37)minutes (range, 228-360 minutes) and(13±4)minutes (7-22 minutes), respectively. The intraoperative blood loss was (400±207)mL (range, 100-800 mL). The mean tumor size was 3.69 cm2 (range, 0.72-1.68 cm2). The recovery time of gastrointestinal function was (5±2)days (range, 4-7 days). The serum amylase at postoperative day 1, 3, 5 in the 21 patients was (145±30)U/L (range, 116-180 U/L), (136±40)U/L (range, 105-176 U/L), (147±38)U/L (range, 110-175 U/L), and the drainage amylase was (220±56)U/L (range, 172-289 U/L), (240±54)U/L (range, 192-300 U/L), (245±52)U/L (range, 190-298 U/L), respectively. The serum amylase at postoperative day 1, 3, 5 in the patient with pancreatic fistula was 156 U/L, 178 U/L and 177 U/L, and the drainage fluid amylase was 500 U/L, 620 U/L and 605 U/L, respectively. There was 1 patient in the 22 patients with pancreatic duct stent and without death. Among the 4 patients with postoperative complications, 1 patient with grade A postoperative pancreatic fistula recovered after continuous external drainage, the other 3 including 1 case of infection, 1 case of pneumonia and 1 of stress ulcer bleeding also recovered after symptomatic and supportive treatment. Postoperative pathological examinations of the 22 patients showed 12 cases of ductal adenocarcinoma, 2 of neuroendocine tumors, 1 of simple cyst, 1 of cystadenocarcinoma, 1 of squamous carcinoma, 1 of adenocarcinoma, 1 of ampullary carcinoma, 1 of tubular adenoma, 1 of leiomyoma and 1 of atypical intraductal hyperplasia. The average length of hospital stay was (11±3)days (range, 2-15 days). There were no effusion near the pancreatic stump showed in color Doppler ultrasound examination and diarrhea of exocrine pancreatic insufficiency. Conclusion End-to-side closed in situ pancreaticojejunostomy is safe and feasible, and can be applied to any pancreatic duct size and texture. Key words: Obstructive jaundice; Pancreaticoduodenectomy; Closed pancreaticojejunostomy; Pancreatic fistula

Ductal and Acinar Adenocarcinoma of Prostate: Morphological and Immunohistochemical Characterization.

We sought to characterize the ductal and acinar subtype of prostate adenocarcinoma using hematoxylin and eosin (H&E) staining and an immunohistochemical antibody cocktail. We also investigated the clinical features, prostate-specific antigen (PSA) levels, and biological aggressiveness of these tumors. We utilized tumor bearing prostate biopsies, obtained between 2010 and 2014 from Dow Diagnostic Research and Reference Laboratory, to identify cases of prostatic ductal and acinar adenocarcinoma using routine H&E and immunohistochemical staining. The immunohistochemical antibody cocktail 34βE12/p63/AMACR was used for staining. The association of clinicopathological variables including patient's age at diagnosis, Gleason score, and PSA levels before surgery was retrospectively analyzed. A total of 10 ductal and 140 non-ductal cases were identified. Ductal cases were predominantly high grade with advanced histopathological features (90%; p=0.030). Marked elevation in PSA level was also reported in most cases. No other significant statistical difference was observed. Pathological and immunohistochemical examination could be used to characterize ductal and acinar adenocarcinoma of the prostate. Ductal adenocarcinoma of the prostate is a rare subtype of prostate carcinoma and is be more likely to present with advanced grade cancer suggesting that timely detection of the disease is vital.

Urinary prostaglandin E2 metabolite and pancreatic cancer risk: case-control study in urban Shanghai.

Pancreatic cancer has been increasing in importance in Shanghai over the last four decades. The etiology of the disease is still unclear. Evidence suggests that the COX-2 pathway, an important component of inflammation, may be involved in the disease. We aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) level and risk of pancreatic cancer. From a recent population-based case-control study in Shanghai, 200 pancreatic ductal adenocarcinoma cases and 200 gender- and age- frequency matched controls were selected for the present analysis. Urinary PGE-M was measured with a liquid chromatography/mass spectrometric assay. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A positive association was observed between PGE-M leve and pancreatic cancer risk: OR = 1.63 (95% CI 1.01–2.63) for the third tertile compared to the first. Though the interactions were not statistically significant, the associations tended to be stronger among subjects with diabetes history (OR = 3.32; 95% CI 1.20–9.19) and higher meat intake (OR = 2.12; 95% CI 1.10–4.06). The result suggests that higher urinary PGE-M level may be associated with increased risk of pancreatic ductal adenocarcinoma.