Pancreatic Ductal Cell Adenocarcinoma Research Articles

Most total pancreatectomies for ductal adenocarcinoma potentially can Be replaced by whipple over the splenic artery: a before and after study.

Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA) which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for a complete resection. Spiked by Warshaw's procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), we developed a new procedure "Whipple over the splenic artery (WOTSA)" to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique "Whipple over the splenic artery (WOTSA)" as a treatment for PDAC which traditionally requires total pancreatectomy (TP) for a complete excision. The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019. None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. DM medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and number of harvested positive lymph nodes, but higher rate of adjuvant chemotherapy completion and a trend toward better median disease free survival (14 vs. 7.5mo, P=0.023). Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.

Persistent ER stress causes GPI anchor deficit to convert a GPI-anchored prion protein into pro-PrP via the ATF6–miR449c-5p–PIGV axis

Endoplasmic reticulum (ER) stress and unfolded protein response are cells' survival strategies to thwart disruption of proteostasis. Tumor cells are continuously being challenged by ER stress. The prion protein, PrP, normally a glycosylphosphatidylinositol (GPI)-anchored protein exists as a pro-PrP retaining its GPI-peptide signal sequence in human pancreatic ductal cell adenocarcinoma (PDAC). Higher abundance of pro-PrP indicates poorer prognosis in PDAC patients. The reason why PDAC cells express pro-PrP is unknown. Here, we report that persistent ER stress causes conversion of GPI-anchored PrP to pro-PrP via a conserved ATF6-miRNA449c-5p-PIGV axis. Mouse neurons and AsPC-1, a PDAC cell line, express GPI-anchored PrP. However, continuous culture of these cells with the ER stress inducers thapsigargin or brefeldin A results in the conversion of a GPI-anchored PrP to pro-PrP. Such a conversion is reversible; removal of the inducers allows the cells to re-express a GPI-anchored PrP. Mechanistically, persistent ER stress increases the abundance of an active ATF6, which increases the level of miRNA449c-5p (miR449c-5p). By binding the mRNA of PIGV at its 3'-UTRs, miR449c-5p suppresses the level of PIGV, a mannosyltransferase pivotal in the synthesis of the GPI anchor. Reduction of PIGV leads to disruption of the GPI anchor assembly, causing pro-PrP accumulation and enhancing cancer cell migration and invasion. The importance of ATF6-miR449c-5p-PIGV axis is recapitulated in PDAC biopsies as the higher levels of ATF6 and miR449c-5p and lower levels of PIGV are markers of poorer outcome for patients with PDAC. Drugs targeting this axis may prevent PDAC progression.

Evaluating adherence to NCCN guideline-directed genetic screening for patients with pancreatic ductal cell adenocarcinoma in rural northeast Georgia.

e16311 Background: Patients with mutations in BRCA 1/2 genes are at increased risk for pancreatic ductal cell adenocarcinoma (PDAC) in addition to breast and ovarian cancer. In 2019, the NCCN updated its guidelines recommending gene testing for all patients with PDAC to include associated genes: ATM, BRCA1, BRCA2, CDKN2A, MSH2, MLH1, MSH6, EPCAM, PALB2, STK11, TP53. This retrospective, observational study reports on adherence to genetic screening recommendations among patients with newly diagnosed PDAC who received oncologic care in rural Northeast Georgia (NEGA). Methods: Chart abstraction was performed utilizing the EPIC database from hospital electronic medical records of patients who were diagnosed with PDAC between 1/1/20-12/31/21 and received oncologic care in rural NE GA. This abstraction was completed to include information on gene testing recommendations, testing completion, and time from diagnosis to testing. The deidentified dataset was then analyzed using appropriate descriptive and associative statistical testing. Results: Of the cohort of 109 patients diagnosed with PDAC over these two years, only 32 (29.4%) received recommendations and completed genetic screening. Among this segment of patients, 16 (14.7%) were screened within 10 days of diagnosis, 8 (7.3%) within 11-30 days, and 6 (5.5%) were screened over 30 days after being diagnosed with PDAC. Among the 77 (70.6%) patients who did not receive screening, 45 of them (41.3%) did not receive any discussion regarding screening despite planning for other standard of care treatment. The remaining 32 patients (29.4% of the no screening cohort) did not receive screening due to desire to pursue palliative care/hospice/or due to terminal illness that prevented further workup. Of the 45 patients who did not receive screening despite PDAC treatment intent, majority (43; 95.5%) did not receive recommendations regarding the importance of genetic screening. Gene testing of the 32 patients who had screening completed showed that 4 (12.5%) had a pathogenic mutation (3 with CFTR; 1 ATM) and 16 (50%) had variants of unknown significance (VUS). Conclusions: This study highlights a gap in adherence to guideline-directed genetic testing in PDAC patients. Notable findings include increased likelihood to complete the test when recommendations and discussions of genetic screening occurred early in the course after initial diagnosis of PDAC. Moreover, 12.5% of those screened were found to have pathogenic mutation and half were found to have at least one VUS suggesting that genetic screening may potentially identify causative mutations. The findings also highlight the consideration for gene testing recommendation for the large proportion of patients who are terminally ill at diagnosis, as genetic screening would potentially benefit the family members and inform that they receive genetic screening as well.

Metastatic Transition of Pancreatic Ductal Cell Adenocarcinoma Is Accompanied by the Emergence of Pro-Invasive Cancer-Associated Fibroblasts.

Simple SummaryHow stromal cells control tumor progression is an active area of investigation. Cancer associated fibroblasts (CAFs) have been suggested to both limit, or promote cancer dissemination in various contexts, but a systemic understanding of stromal influence in determining cancer metastasis is lacking. This study takes a closer look at the diversity of fibroblasts that emerge in different metastatic stages of PDAC (Pancreatic Ductal Cell Adenocarcinoma), a cancer type with high stromal infiltration. Specifically, we found that the CAFs respond to the growing (but yet not metastasized) tumor by transition to a myofibroblast like stage, potentially resisting cancer invasion. As the cancer disseminates, these fibroblasts are nearly entirely replaced by highly diverse set of subpopulations with distinct functions. We have previously advanced a framework, termed Evolved Levels of Invasability (ELI), explaining the vast differences in cancer metastasis and placental invasion among mammals. We found that PDAC’s metastatic transition and stromal trespass is accompanied by the downregulation of pro-resistive and the upregulation of pro-invasability ELI signatures in CAF subpopulations. Cancer-associated fibroblasts (CAFs) are now appreciated as key regulators of cancer metastasis, particularly in cancers with high stromal content, e.g., pancreatic ductal cell carcinoma (PDAC). However, it is not yet well understood if fibroblasts are always primed to be cooperative in PDAC transition to metastasis, if they undergo transformation which ensures their cooperativity, and if such transformations are cancer-driven or intrinsic to fibroblasts. We performed a fibroblast-centric analysis of PDAC cancer, as it transitioned from the primary site to trespass stromal compartment reaching the lymph node using published single-cell RNA sequencing data by Peng et al. We have characterized the change in fibroblast response to cancer from a normal wound healing response in the initial stages to the emergence of subclasses with myofibroblast and inflammatory fibroblasts such as signatures. We have previously posited “Evolved Levels of Invasibility (ELI)”, a framework describing the evolution of stromal invasability as a selected phenotype, which explains the large and correlated reduction in stromal invasion by placental trophoblasts and cancer cells in certain mammals. Within PDAC samples, we found large changes in fibroblast subclasses at succeeding stages of PDAC progression, with the emergence of specific subclasses when cancer trespasses stroma to metastasize to proximal lymph nodes (stage IIA to IIB). Surprisingly, we found that the initial metastatic transition is accompanied by downregulation of ELI-predicted pro-resistive genes, and the emergence of a subclass of fibroblasts with ELI-predicted increased invasibility. Interestingly, this trend was also observed in stellate cells. Using a larger cohort of bulk RNAseq data from The Cancer Genome Atlas for PDAC cancers, we confirmed that genes describing this emergent fibroblast subclass are also correlated with lymph node metastasis of cancer cells. Experimental testing of selected genes characterizing pro-resistive and pro-invasive fibroblast clusters confirmed their contribution in regulating stromal invasability as a phenotype. Our data confirm that the complexity of stromal response to cancer is really a function of stage-wise emergence of distinct fibroblast clusters, characterized by distinct gene sets which confer initially a predominantly pro-resistive and then a pro-invasive property to the stroma. Stromal response therefore transitions from being tumor-limiting to a pro-metastatic state, facilitating stromal trespass and the onset of metastasis.

Prion protein is required for tumor necrosis factor α (TNFα)-triggered nuclear factor κB (NF-κB) signaling and cytokine production

The expression of normal cellular prion protein (PrP) is required for the pathogenesis of prion diseases. However, the physiological functions of PrP remain ambiguous. Here, we identified PrP as being critical for tumor necrosis factor (TNF) α-triggered signaling in a human melanoma cell line, M2, and a pancreatic ductal cell adenocarcinoma cell line, BxPC-3. In M2 cells, TNFα up-regulates the expression of p-IκB-kinase α/β (p-IKKα/β), p-p65, and p-JNK, but down-regulates the IκBα protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade. When PRNP is deleted in M2 cells, the effects of TNFα are no longer detectable. More importantly, p-p65 and p-JNK responses are restored when PRNP is reintroduced into the PRNP null cells. TNFα also activates NF-κB and increases TNFα production in wild-type M2 cells, but not in PrP-null M2 cells. Similar results are obtained in the BxPC-3 cells. Moreover, TNFα activation of NF-κB requires ubiquitination of receptor-interacting serine/threonine kinase 1 (RIP1) and TNF receptor–associated factor 2 (TRAF2). TNFα treatment increases the binding between PrP and the deubiquitinase tumor suppressor cylindromatosis (CYLD), in these treated cells, binding of CYLD to RIP1 and TRAF2 is reduced. We conclude that PrP traps CYLD, preventing it from binding and deubiquitinating RIP1 and TRAF2. Our findings reveal that PrP enhances the responses to TNFα, promoting proinflammatory cytokine production, which may contribute to inflammation and tumorigenesis.

Prognostic Implications of Expression Profiling for Gemcitabine-Related Genes (hENT1, dCK, RRM1, RRM2) in Patients With Resectable Pancreatic Adenocarcinoma Receiving Adjuvant Chemotherapy.

The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles. Significantly better median survival times were found for high/moderate expression levels of hENT1 (27.9 vs 12.4 months, P = 0.001) and dCK (19.7 vs 10.5 months, P = 0.003), as well as low expression of RRM1 (23.4 vs 11.4 months, P = 0.027). A Cox proportional hazards model identified low expression of hENT1 (hazard ratio [HR], 3.38; 95% confidence intervals [CI], 2.28-10.50) and dCK (HR, 2.24; 95% CI, 1.63-3.39), and high/moderate levels of RRM1 (HR, 1.65; 95% CI, 1.23-2.45) as negative prognostic factors. Expression of hENT, RRM1, and dCK genes provides important prognostic information for PDAC patients treated with adjuvant gemcitabine.

Acinar cell carcinoma: a report of 19 cases with a brief review of the literature

BackgroundAcinar cell carcinoma (ACC) is a relatively rare pancreatic neoplasm with poorly defined prognosis. This study aimed to investigate this rare pancreatic neoplasm through comparing patients with ACC to pancreatic ductal cell adenocarcinoma (DCA).MethodsTianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 1995 to 2015, and 19 patients with pathologically confirmed ACC were enrolled while 19 conventional DCA patients assigned randomly as control. Retrospective review and follow-up were performed for each patient. Regression methods were used to identify differences between ACC and DCA.ResultsIn our study, most patients suffered from abdominal or back pain, and no lipase hypersecretion syndrome was observed. For ACC, resected cases had better survival than those without resection, and earlier staging was related to longer survival. Resection with postoperative adjuvant therapy had a better outcome than surgery alone. Twelve cases developed recurrence. Compared to DCA, ACC had earlier staging and better survival. The overall 1-, 2-, and 5-year survival rates for patients with ACC were 73.7, 26.3, and 5 %, respectively.ConclusionsACC carries a better prognosis than DCA and a similarly high recurrence rate, while surgical resection proved the best first-line approach for it. A well-planned neoadjuvant or adjuvant chemoradiotherapy indeed benefit the patients with ACC.

Semiquantitative immunohistochemistry for mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) profiling of pancreatic ductal cell adenocarcinoma improves diagnostic and prognostic performance.

Mucin (MUC) glycoproteins are involved in various steps of the carcinogenesis and progression of human malignancies. The aim of this study was to verify whether semiquantitative evaluation of MUC staining by immunohistochemistry may help to differentiate pancreatic ductal cell adenocarcinoma (PDAC) from chronic pancreatitis and normal pancreas. Mucin expression was examined by immunohistochemistry in surgical specimens resected from 101 patients with PDAC and 33 with chronic pancreatitis, and in 40 normal pancreatic tissue specimens. A quickscore (QS, range 0-300) was calculated by multiplying staining intensity by the percentage of positive cells. A diagnostic model was developed for MUC QS (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6), based on a receiver operating characteristic (ROC) curve and logistic regression analysis. Median QS values for MUC1 and MUC5AC were significantly higher for PDAC, whereas patients with non-malignant tissues had higher values for MUC3 and MUC6. The area under the curve for the ROC curve derived from the diagnostic model including MUC3, MUC5AC and MUC6 was 0.96 [95% confidence interval (CI) 0.91-0.98], with 85% sensitivity and 94% specificity. Median QS values for MUC2 were significantly higher in patients with less advanced tumours, whereas venous invasion was associated with a lower QS for MUC6. Moreover, multivariate survival analysis revealed that low MUC6 expression was a negative prognostic factor, with a hazard ratio of 1.73 (95% CI 1.07-2.81). The three-MUC diagnostic model (MUC3, MUC5AC, and MUC6) showed an excellent ability to discriminate pancreatic cancer from non-malignant tissues, and yielded information that may prove useful for the development of clinical applications.

Heparanase regulates in vitro VEGF-C expression and its clinical significance to pancreatic ductal cell adenocarcinoma.

Heparanase (HPSE) and vascular endothelial growth factor C (VEGF-C) are important cytokines that promote metastasis and angiogenesis in numerous malignant neoplasms, however, their association remains unclear in pancreatic ductal cell adenocarcinoma (PDAC). The present study aimed to investigate whether HPSE has a positive correlation with VEGF-C expression and to uncover the role it plays in the in vitro invasion of BxPC-3 cells (a pancreatic carcinoma cell line), and to analyze the value of joint detection of HPSE and VEGF-C for PDAC patients. A recombinant plasmid, GV230/HPSE was constructed and BxPC-3 cells were transiently transfected with GV230/HPSE or siRNA against HPSE. The expression levels of HPSE and VEGF-C were compared using reverse transcription quantitative PCR (RT-qPCR) and immunoblotting. The metastatic potential of treated BxPC-3 cells was evaluated using a Transwell® invasion assay. The relative mRNA levels of HPSE and VEGF-C in 34 PDAC specimens were assessed by RT-qPCR. The results of the RT-qPCR demonstrated a 10.7- and 3.24-fold elevation (P<0.01) of HPSE mRNA and VEGF-C mRNA, respectively, in GV230/HPSE group, whereas the HPSE siRNA group were downregulated for these mRNAs (−2.45-fold, P<0.01; −1.84-fold, P<0.01). The same pattern for protein expression was detected using immunoblot assays. In Transwell® invasion assays 138±5 cells in GV230/HPSE group and 53±4 cells in siRNA group migrated through the Matrigel®. A negative correlation between the mRNA levels of HPSE and VEGF-C in PDAC specimens and the prognosis factors of the postoperative patients was identified. Spearman rank correlation analysis indicated a positive correlation between HPSE and VEGF-C in PDAC (r=0.812, P<0.01). HPSE regulates the expression of VEGF-C and facilitates invasion of BxPC-3 in vitro. Joint detection of HPSE and VEGF-C may therefore be clinically useful in determining the prognosis of pancreatic cancer patients.

Resolution of New-Onset Diabetes After Radical Pancreatic Resection Predicts Long-term Survival in Patients with Pancreatic Ductal Cell Adenocarcinoma

To demonstrate the effect of diabetes mellitus (DM) (stratified by long-term/new-onset presurgical diabetes, resolved/unresolved postsurgical diabetes) on prognosis for pancreatic ductal cell adenocarcinoma (PDAC) after radical resection. One hundred ninety-nine patients who underwent radical resection for PDAC between 2007 and 2011 at Ruijin Hospital (Shanghai, China) were retrospectively analyzed. Clinical and pathologic characteristics, surgical and adjuvant chemotherapy related outcomes, disease-free survival (DFS), and postoperative survival were compared among patients with long-term (≥2 years)/new-onset (<2 years) presurgical diabetes and resolved/unresolved postsurgical diabetes. Univariate and multivariable analysis was performed to determine factors associated with DFS and overall survival (OS). Of 199 patients, 90 (44.7%) had DM, 64 of which were new onset and 26 of which were long-standing. Resolution of DM after radical pancreatic resection was observed in 65% (42 of 64) in the new-onset group, but in none of the long-standing group. Resolved new-onset DM patients had larger, well-differentiated tumors compared to patients with unresolved new-onset DM. Patients with long-standing DM had shorter postoperative DFS and OS than nondiabetic/new-onset DM, whereas postoperative resolved new-onset DM is associated with longer DFS and OS than unresolved DM. Morbidity was higher and postoperative hospital stay was longer in patients with new-onset DM compared with patients with long-standing DM and patients without DM. There was no difference in the adjuvant chemotherapy toxicity rate among patients with long-standing or new-onset DM and those without DM. Different status of DM has different effects on outcome after resection for PDAC. Long-standing DM is related to progression of disease, whereas postsurgical resolved new-onset DM is a favorable prognostic factor.

Resolution of Diabetes After Pancreaticoduodenectomy in Patients with and without Pancreatic Ductal Cell Adenocarcinoma

New-onset diabetes mellitus (DM) is associated with pancreatic ductal cell adenocarcinoma (PDCA) and can resolve after pancreaticoduodenectomy (PD). Whether DM also resolves after PD in patients operated for disease other than PDCA remains to be determined. We compared glycemic status before and after PD between patients with and without PDCA by review of a prospectively maintained database including all patients receiving PD from 2005 to 2011. New-onset DM was defined as diagnosis of DM less than 24 months before PD, and cases with DM diagnosis≥24 months preceding PD were described as long-standing DM. Of 458 patients receiving PD, there were 146 (31.9%) PDCA and 312 (68.1%) non-PDCA, including 160 benign diseases, 113 ampulla cancer, 29 distal common bile duct cancer, and 10 duodenal cancer. Overall prevalence of DM was higher in PDCA group than non-PDCA group (37.7 vs. 25.6%; P=0.011). Resolution of new-onset DM after PD was observed in 9 (41%) of 22 patients with PDCA and in 12 (63%) of 19 patients without PDCA. Resolution of long-standing DM after PD was also observed in 3 (9.1%) of 33 patients with PDCA and in 6 (9.8%) of 61 patients without PDCA. DM resolved after PD in some patients both with and without PDCA. These findings suggest that PD-associated anatomic change may play a role in resolution of DM after PD.

Binding of pro-prion to filamin A: by design or an unfortunate blunder

Over the last decades, cancer research has focused on tumor suppressor genes and oncogenes. Genes in other cellular pathways has received less attention. Between 0.5% to 1% of the mammalian genome encodes for proteins that are tethered on the cell membrane via a glycosylphosphatidylinositol (GPI)-anchor. The GPI modification pathway is complex and not completely understood. Prion (PrP), a GPI-anchored protein, is infamous for being the only normal protein that when misfolded can cause and transmit a deadly disease. Though widely expressed and highly conserved, little is known about the functions of PrP. Pancreatic cancer and melanoma cell lines express PrP. However, in these cell lines the PrP exists as a pro-PrP as defined by retaining its GPI anchor peptide signal sequence (GPI-PSS). Unexpectedly, the GPI-PSS of PrP has a filamin A (FLNA) binding motif and binds FLNA. FLNA is a cytolinker protein, and an integrator of cell mechanics and signaling. Binding of pro-PrP to FLNA disrupts the normal FLNA functions. Although normal pancreatic ductal cells lack PrP, about 40% of patients with pancreatic ductal cell adenocarcinoma express PrP in their cancers. These patients have significantly shorter survival time compared with patients whose cancers lack PrP. Pro-PrP is also detected in melanoma in situ but is undetectable in normal melanocyte, and invasive melanoma expresses more pro-PrP. In this review, we will discuss the underlying mechanisms by which binding of pro-PrP to FLNA disrupts normal cellular physiology and contributes to tumorigenesis, and the potential mechanisms that cause the accumulation of pro-PrP in cancer cells.

Acinar Cell Carcinoma of the Pancreas in the United States: Prognostic Factors and Comparison to Ductal Adenocarcinoma

IntroductionPancreatic acinar cell carcinoma (ACC) is a rare tumor with poorly defined prognosis. ObjectiveOur objective was to compare a large population of patients with ACC to pancreatic ductal cell adenocarcinoma (DCC) in order to determine distinguishing characteristics and to assess survival. MethodsPatients were identified from the National Cancer Database. Regression methods were used to identify differences between ACC and DCC and to identify predictors of survival for resected ACC. Eight hundred sixty-five patients with ACC were identified. ResultsMedian tumor size was 6.9 cm (vs. 4.6 cm DCC); 32.1% had nodal metastases (vs. 48.0% DCC); and 47% had high-grade tumors (vs. 37.3% DCC). Resection margins were R0 77.3%, R1 13.7%, and R2 9.0%. Patients with ACC were more likely to be male, white, and have larger tumor size, no nodal involvement, or pancreatic tail tumors. Stage-specific 5-year survival was significantly better for resected ACC vs. DCC Stage I: 52.4% vs. 28.4%, II: 40.2% vs. 9.8%, III: 22.8% vs. 6.8%, and IV: 17.2% vs. 2.8%. On multivariable analysis, age < 65, well-differentiated tumors, and negative resection margins were independent prognostic factors for ACC. DiscussionACC carries a better prognosis than DCC. Aggressive surgical resection with negative margins is associated with long-term survival in these more favorable pancreatic cancers.

T1739 Pancreatic Acinar Cell Carcinoma: A Multi-Institutional Study

Introduction The presentation and outcome of patients with acinar cell carcinoma (ACC) of the pancreas compared to the more common ductal cell adenocarcinoma (DCA) may be distinct. This study combines the experience with ACC from multiple academic institutions to better understand its natural history and outcomes. Methods This study is a multi-institutional retrospective review of patients with ACC. Results Between 1988 and 2008, 17 patients were identified with pathologically confirmed ACC. Median age at presentation was 59 years. Common presenting symptoms were abdominal pain (60%), back pain (50%), and weight loss (45%). Fifteen patients underwent 16 operations: pancreaticoduodenectomy (nine), distal pancreatectomy (four), and exploratory laparotomy (three). Mean tumor size was 5.3 cm. American Joint Commission on Cancer tumor stages were stage I (two), stage II (eight), stage III (four), and stage IV (three). Overall, 1- and 5-year survival rates were 88% and 50%, respectively. In resected cases (13), 1- and 5-year survival rates were 92% and 53%, respectively. Median survival in resected cases was 61 months. This is in contrast to 1,608 patients with ductal cell adenocarcinoma who underwent resection identified from recent literature reports where the average median survival was only 24 months. There was no discernable difference in the outcomes of patients with ACC between United States and Germany patients. Conclusion Acinar cell carcinoma of the pancreas is rare and appears to have a presentation and outcome distinct from the more common pancreatic DCA. Based upon these data, the outcome of patients with ACC is superior to that of DCA.

Laminin γ2-chain fragment circulating level increases in patients with metastatic pancreatic ductal cell adenocarcinomas

Laminin-5 (LN5) is expressed solely by epithelial cells and considered to enhance cell migration after being cleaved by proteases, leading to the shedding of the N-terminal fragment of the LN5 γ2-chain (G2F). We estimated circulating G2F level in 181 patients with various digestive diseases and 15 healthy subjects. The G2F level in pancreatic ductal cell adenocarcinoma patients with liver metastases was markedly elevated, but that in patients without liver metastases was not significantly elevated. The G2F levels in patients with benign pancreatic tumours (pancreatic cysts and intraductal papillary mucinous tumours) were similar to that in healthy volunteers. On the other hand, the level of the γ1-chain is a common constituent of several laminin heterotrimers. The N-terminal fragment of γ1-chain (G1F) in the circulation of these patients was also determined, and a slight increase in G1F levels was observed only in hepatocellular carcinoma patients. Interestingly, a significant increase in circulating G2F/G1F ratio was observed in patients with bile duct and gallbladder carcinoma, as well as in those with metastatic pancreatic ductal cell adenocarcinoma. The increase in the circulating G2F level, particularly compared with circulating G1F level, should correlated with LN5 overexpression in invasive carcinomas, independently of basement membrane metabolism in the entire body.