Factor In Pancreatic Cancer Patients Research Articles

Sarcopenia represents a negative prognostic factor in pancreatic cancer patients undergoing EUS celiac plexus neurolysis.

Background and Objectives:Increasing evidence suggests a prognostic role of sarcopenia in pancreatic cancer patients. The aim of this study was to assess the influence of sarcopenia on treatment outcomes after EUS-guided celiac plexus neurolysis (CPN).Materials and Methods:Data regarding 215 patients treated with EUS CPN between 2004 and 2019 were reviewed. Determination of body composition was conducted on contrast-enhanced CT scan, and pain response was considered as the primary outcome. Univariate and multivariate logistic regression was performed to identify the independent predictors of pain response.Results:Treatment was successful in 187 patients (86.9%). The median age was 62 (range 39–84) years, and most patients were male (61.8%). Of the whole study population, 139 patients (64.6%) were defined as sarcopenic, of which 116 (83.4%) responded to the treatment and 5 (3.5%) experienced a complete response. Among 76 nonsarcopenic participants, 71 (93.4%) responded to the treatment and 22 (28.9%) obtained a complete response (P = 0.03 and <0.001, respectively). The median duration of pain relief was 8 (2–10) and 15 (8–16) weeks in sarcopenic and nonsarcopenic patients, respectively (P = 0.01). The median overall survival after neurolysis was 4 months (3–5) in sarcopenic participants and 7 months (6–8) in nonsarcopenic participants (P = 0.05). Tumoral stage, interval from the diagnosis to treatment, and sarcopenia resulted as significant prognostic factors for treatment response both in univariate and multivariate regression analyses. No severe treatment-related adverse events were reported in the whole study population, with no difference between the two groups.Conclusions:Sarcopenia represents a predictor of poorer response to EUS CPN.

Retrospective analysis on resectability, survival and disease free survival prognostic factors in patients with pancreatic adenocarcinoma

Background: Pancreatic cancer is the fourth leading cause of cancer death, and its prognosis remains poor despite recent advances in treatment. Our goal was to determine prognostic factors associated with pancreatic cancer outcome by retrospective analysis of the clinical characteristics and follow-up data of patients who received palliative or curative surgical treatment. Methods: In this retrospective study, we analyzed the medical records and follow-up information of 344 pancreatic cancer patients who received curative or palliative surgical treatment at a tertiary care referral center in Greece from January 2004 to December 2015. The overall survival (OS) and disease free survival (DFS) rates were determined by the Kaplan- Meier method and univariate analysis was conducted to identify potential prognostic factors. Multivariate analysis, using the Cox proportional hazards model, was conducted to define independent prognostic factors. Results: Among the 344 patients with resectable tumors in the study cohort, 226 and 118 patients, respectively, underwent curative and palliative surgical resection. The median survival after curative resection was statistically higher compared to palliative resection (23.129 vs. 5.025months, p<0.05). The estimated 1-, 3-, and 5-year OS rates after curative resection were 35.84%, 15.48%, and 6.19% respectively. Univariate and multivariate analyses identified the following independent prognostic factors for OS: microvacular invasion, neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS) and lymph node ratio (LNR). Additionally, microvascular invasion, NLR >5 and PLR >160 were independent prognostic factors for DFS. Conclusion: Surgery remains the only curative therapy in pancreatic cancer treatment. Inflammation markers and LNR should be thoroughly assessed as independent prognostic factors in pancreatic cancer patients

The age-adjusted Charlson comorbidity index is an independent prognostic factor in pancreatic cancer patients who receive curative resection followed by adjuvant chemotherapy.

We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on the pancreatic cancer survival and recurrence after curative surgery followed by adjuvant chemotherapy. This study included 155 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. An ACCI of 8 was regarded as the optimum critical point of classification considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 25.7% and 19.0% in the ACCI-low group, respectively, and 7.6% and 0% in the ACCI-high group, which amounted to a statistically significant difference (P = 0.019). The RFS rates at 3 and 5 years after surgery were 17.3% and 13.8% in the ACCI-low group, respectively, and 7.1% and 0% in the ACCI-high group, which amounted to a marginally statistically significant difference (P = 0.104). A multivariate analysis showed that the ACCI was a significant independent risk factor for both the OS and RFS. The ACCI was a risk factor for the OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. An effective plan is needed for determining the optimum surgical strategy according to the ACCI.

Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival?

Pancreatic cancer (PC) is one of the most aggressive malignancies with no effective treatment if diagnosed in advanced stage. Systemic inflammation is a recognized characteristic of cancer progression, and we believe that the understanding of the influence of inflammatory parameters may contribute to therapeutic improvement in PC. Here, we validated the Eosinophil/Lymphocyte Ratio (ELR) together with the Neutrophil/Lymphocyte Ratio (NLR) and their components, as prognostic factors in PC patients treated with chemoradiation. A total of 66 consecutive patients (p) diagnosed with PC stage I-III and treated with External Beam Radiotherapy + chemotherapy ± surgery (28p) in our institution from 2007 to 2018 were retrospectively evaluated. The impact of pre-treatment ELR ≥ 0.04, NLR ≥ 1.9, neutrophilia (≥ 7.0 × 10(9)/l), eosinophilia (≥ 0.5 × 10(9)/l) and lymphopenia (< 1.0 × 10(9)/l) on Overall Survival (OS) and Time-to-Progression (TTP) was evaluated both in the entire cohort and separately according to surgical status. Higher ELR was associated with longer OS and TTP, both in surgically treated and not operable patients. On univariate analysis, elevated ELR was associated with better OS (HR = 0.3, 95% IC 0.13-0.65, p = 0.003), contrarily to neutrophilia (HR = 2.7, 95% IC 1.2-6.5, p = 0.026) and age > 50years (HR = 2.6, 95% IC 1.03-6.6, p = 0.044), while NLR, lymphopenia and Ca-19.9 were not significant. On multivariate regression, independent prognosticators for OS were: ELR, age and neutrophilia; while for TTP: ELR, neutrophilia, eosinophilia and lymphopenia. The host's immune response influences survival outcomes of PC patients and may be of interest for future research.

The Lymph Node Ratio Is an Independent Prognostic Factor in Pancreatic Cancer Patients Who Receive Curative Resection Followed by Adjuvant Chemotherapy.

The present study investigated the impact of the lymph node ratio (LNR) on survival and recurrence in patients with pancreatic cancer after curative surgery followed by adjuvant chemotherapy. This study included 189 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. A lymph node ratio of 0.1 was considered to be the optimal cut-off point for classification based on the 3-year and 5-year survival rates. The OS rates at three and five years after surgery were 34.4% and 28.2% in the LNR <0.1 group, respectively, and 23.1% and 5.8% in the LNR ≥0.1 group, which amounted to a statistically significant difference (p=0.003). The RFS rates at one and three years after surgery were 26.6% and 20.5% in the LNR <0.1 group, respectively, and 8.0% and 0% in the LNR ≥0.1 group, which was a significant difference (p=0.001). A multivariate analysis demonstrated that the LNR was a significant independent risk factor for both the OS and RFS. The LNR was a risk factor for overall survival in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. It is necessary to develop strategies to effectively utilize the lymph node metastasis status.

Prognostic Factors for Pancreatic Cancer Patients Treated with Immune-cell Therapy.

The past 17 years, immune-cell therapy has been administered to 990 patients with advanced or recurrent pancreatic adenocarcinoma and 50 patients with curatively resected pancreatic adenocarcinoma. The correlation between overall survival (OS) and various factors including sex, age, performance status (PS), distant metastasis, chemotherapy, radiotherapy, and type of immune-cell therapy were evaluated by univariate and multivariate analyses. The median OS of advanced or recurrent pancreatic cancer was 5.8 months, and the prognosis was improved in pancreatic cancer patients who received immune-cell therapy with PS scores of 0-1 [hazard risk (HR)=0.56; 95% confidence interval (CI)=0.46-0.68; p<0.0001], chemotherapy (HR=0.68; 95%CI=0.54-0.87; p=0.002), or radiotherapy (HR=0.76; 95%CI=0.63-0.93; p=0.006). Multivariate analysis demonstrated that distant metastasis indicated a poor prognosis for pancreatic cancer patients that were administered immune-cell therapy (HR=1.62; 95%CI=1.37-1.93; p<0.0001). Additionally, the combined immune-cell therapy with αβ T cell and dendritic cell (DC) vaccine provided a survival benefit in advanced or recurrent pancreatic cancer patients (HR=0.69; 95%CI=0.57-0.83; p<0.0001). A survival benefit could be potentially obtained with better PS by the combination of αβ T cell therapy, DC vaccine therapy, and chemotherapy at an early stage in pancreatic cancer.

PHGDH is an independent prognosis marker and contributes cell proliferation, migration and invasion in human pancreatic cancer

PurposeTo investigate the expression, clinical significance, biological function, and the potential mechanism of PHGDH in pancreatic cancer. MethodsThe expression of PHGDH in human pancreatic cancer tissues and corresponding adjacent normal tissues were analyzed through immunohistochemistry staining. Simultaneously, the association between the PHGDH expression and the clinicopathological parameters and OS and DFS was evaluated. Human pancreatic cancer cell line BxPC-3 and SW1990 were selected to investigate the effect of PHGDH knockdown on cell proliferation, migration, and invasion. In addition, we performed western blot to assess the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9 protein. ResultsOur results suggested that the expression of PHGDH is increased in pancreatic cancer compared with adjacent normal tissues and the increased expression of PHGDH is associated with tumor size, lymph node metastasis, and TNM state of pancreatic cancer patients. Moreover, the expression of PHGDH is an independent prognostic indicator for pancreatic cancer patients. In addition, we found that knockdown of PHGDH in pancreatic cancer cells inhibits the cell proliferation, migration, and invasion abilities by down-regulating the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9. ConclusionsOur data indicated that the expression of PHGDH is increased in pancreatic cancer and is an independent molecular prognostic factor for pancreatic cancer patients. In addition, PHGDH controls cell proliferation, migration and invasion abilities. Therefore, PHGDH could serve as an important prognostic indicator and therapeutic target for pancreatic cancer.

Abstract 1927: The significance of calreticulin in pancreatic cancer: a molecule highly expressed in pancreatic cancer stem-like cells

Abstract Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by two-dimensional electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis demonstrated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in CRThigh/CD44v9low population is much higher than that in CRTlow/CD44v9high population. CRT expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients’ clinicopathological features and disease outcomes in the Cox’s proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and post-operative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be useful for detecting P-CSLCs independently, which had been detectable by multiple surface markers like CD24, CD44 and ESA. We will present CSLCs properties of CRThigh population in P-CSLCs. Citation Format: Satoshi Matsukuma, Kiyoshi Yoshimura, Atsunori Oga, Moeko Inoue, Takuya Fujimtoto, Atsuo Kuramasu, Masanori Fuse, Ryouichi Tsunedomi, Hidetoshi Eguchi, Hiroto Matsui, Shinsuke Kanekiyo, Yukio Tokumitsu, Shinobu Tomochika, Michihisa Iida, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Nobuaki Suzuki, Tomoko Furuya-Kondo, Hiroshi Itoh, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Shoichi Hazama, Tomio Ueno, Hiroaki Nagano. The significance of calreticulin in pancreatic cancer: a molecule highly expressed in pancreatic cancer stem-like cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1927. doi:10.1158/1538-7445.AM2017-1927

Pathological tumor size is an independent prognostic factor in pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy with S-1

Pathological tumor size is an independent prognostic factor in pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy with S-1

Calreticulin is highly expressed in pancreatic cancer stem-like cells.

Cancer stem‐like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P‐CSLCs). A P‐CSLC‐enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2‐D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P‐CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P‐CSLCs and did not correlate with the levels of CD44v9, another P‐CSLC biomarker. Furthermore, the side population in the CRThigh/CD44v9low population was much higher than that in the CRTlow/CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P‐CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.

Prognostic significance of K-ras mutations in pancreatic cancer: a meta-analysis.

BackgroundK-ras gene mutations are common in patients with pancreatic cancer (PC); however, their prognostic value for PC remains inconclusive. This meta-analysis was performed to quantitatively evaluate the association between K-ras mutations and survival in patients with pancreatic cancer.MethodsWe performed a comprehensive search of electronic sources including MEDLINE (via PubMed), Web of Science, and the Cochrane Library. The search covered a publication period from inception to November 2015.ResultsSeventeen studies with a total of 2249 patients with pancreatic cancer were included in the tissue detection of this study. The meta-analysis indicated a significant association between mutant K-ras genes and overall survival (OS) (HR = 1.51, 95 % CI 1.32–1.72, P < 0.001). Moreover, further subgroup analyses by ethnicity, publication year, therapy method, cancer resectability, and gene detection method all revealed that pancreatic cancer patients with the K-ras mutation had significantly poorer OS (P < 0.05). And results from four studies with 225 patients focused on plasma K-ras mutations enhanced such association (HR = 2.23, 95 % CI 1.69–2.95, P < 0.001).ConclusionsAs a prediction of poor prognosis, the detection of K-ras mutations may be a useful prognostic factor for pancreatic cancer patients.

Lymphatic invasion as an independent prognostic factor in pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy with gemcitabine or S-1.

290 Background: The objective of this retrospective study was to clarify prognostic factors in pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy with gemcitabine or S-1. Methods: Both overall survival (OS) and recurrence-free survival (RFS) were examined in 122 pancreatic cancer patients who underwent curative surgery and received adjuvant gemcitabine or S-1 after surgery between 2005 and 2014. Results: When the length of OS was evaluated according to the log-rank test, significant differences were observed in lymphatic invasion and the T status. Univariate and multivariate Cox’s proportional hazard analyses demonstrated that lymphatic invasion was the only significant independent prognostic factor for both OS and RFS. The 5-year OS was 30.1% in the lymphatic invasion-negative group and 12.1% in the lymphatic invasion-positive group (p &lt; 0.001). Moreover, the 5-year RFS was 20.5% in the lymphatic invasionnegative group and 10.4% in the lymphatic invasionpositive group (p = 0.006). Conclusions: Lymphatic invasion is the most important prognostic factor for OS and RFS in patients with pancreatic cancer who undergo curative resection followed by adjuvant chemotherapy. The present results suggest that adjuvant chemotherapy is not sufficient, especially in patients with risk factors. Such patients should be evaluated as a target group for clinical trials of novel treatments.

Cyclin G2: A novel independent prognostic marker in pancreatic cancer.

Unlike other cyclins that positively regulate the cell cycle, cyclin G2 (CCNG2) regulates cell proliferation as a tumor suppressor gene. A decreased CCNG2 expression serves as a marker for poor prognosis in several types of cancer. The aim of the present study was to clarify the correlation of CCNG2 expression with overall survival and histopathological factors in pancreatic cancer patients. This retrospective analysis included data from 36 consecutive patients who underwent complete surgical resection for pancreatic cancer and did not undergo any preoperative therapies. The association between prognoses and the expression of CCNG2 was assessed using immunohistochemical staining. Multivariate analysis identified that the expression of CCNG2 is an independent prognostic factor. In addition, the Kaplan-Meier curve for overall survival revealed that decreased expression of CCNG2 was a consistent indicator of poor prognosis in pancreatic cancer patients (P=0.0198). A decreased CCNG2 expression significantly correlated with venous invasion in tumor specimens and the tumor invasion depth. In conclusion, CCNG2 expression inversely reflected cancer progression and may be a novel, independent prognostic marker in pancreatic cancer.

Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma—An Infrequent Event: Elucidation of Risk Factors and Management Implications

BackgroundGemcitabine-related pneumonitis (GRP) has been reported relatively frequently for pancreas cancer in the literature; however, underlying risk factors and optimal management remain to be defined. We studied a cohort of patients with GRP and investigated potential predisposing factors in pancreatic cancer patients. Patients and MethodsA total 2440 patients at Memorial Sloan Kettering Cancer Center were identified between January 1, 2000, and December 31, 2012, and were screened for grade 2 or higher GRP in an institutional tumor registry and using an ICD billing code database. Demographic and clinical information was extracted by electronic chart review. ResultsA total of 28 patients (1.1%) with GRP were identified. Incidence of grade 2, 3, and 4 reactions were 7 (25%), 18 (64%), and 3 (11%), respectively. No GRP-related mortality was observed. Twenty-one patients (75%) reported a history of cigarette smoking. Seventeen patients (61%) were alcohol users. Six patients (21%) were either regular or heavy drinkers. Most patients (93%) had either locally advanced or metastatic disease. Three patients (11%) underwent a diagnostic bronchoscopy, and in 1 patient a diagnosis of organizing pneumonia was established. Morbidity was significant; 3 patients (11%) required treatment in the intensive care unit. All hospitalized patients received steroid treatment. ConclusionGRP is relatively uncommon but incurs significant morbidity. Potential risk factors include advanced-stage disease, along with smoking and alcohol consumption and possibly underlying lung disease. We recommend a high level of clinical alertness regarding the diagnosis, early pulmonary referral, and cessation of gemcitabine on suspicion of GRP.

Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer.

Long non-coding RNAs (lncRNAs) have been proved to serve as a critical role in cancer development and progression. However, little is known about the pathological role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer patients. The aims of this study are to measure the expression of lncRNA MALAT1 in pancreatic cancer patients and to explore the clinical significance of the lncRNA MALAT1. Using qRT-PCR, the expression of lncRNA MALAT1 was measured in 126 pancreatic cancer tissues and 15 adjacent non-cancerous tissues. In the present study, our results indicated that lncRNA MALAT1 was highly expressed in pancreatic cancer compared with adjacent non-cancerous tissues (P < 0.001), and positively correlated with clinical stage (early stages vs. advanced stages, P < 0.001), tumor size (<2 vs. ≥2cm, P = 0.004), lymph node metastasis (negative vs. positive, P < 0.001), and distant metastasis (absent vs. present, P = 0.001) in pancreatic cancer patients. Furthermore, we also found that lncRNA MALAT1 overexpression was an unfavorable prognostic factor in pancreatic cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, increased lncRNA MALAT1 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis (P = 0.018). In conclusion, overexpression of lncRNA MALAT1 serves as an unfavorable prognostic biomarker in pancreatic cancer patients.

The lymphocyte to monocyte ratio in peripheral blood represents a novel prognostic marker in patients with pancreatic cancer.

Intra-tumoral macrophages have been involved as important players in the pathogenesis and progression of cancer. Recently, inflammatory parameters of the systemic inflammatory response have also been proposed as usefully prognostic biomarkers. One of these, the lymphocyte to monocyte ratio (LMR) in peripheral blood has been shown as a prognostic factor in hematologic and some solid tumors. In this study we analyzed for the first time the prognostic value of LMR in a large middle European cohort of pancreatic cancer (PC) patients. Data from 474 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. To further evaluate the prognostic significance of the LMR, univariate and multivariate Cox regression models were calculated. Increased LMR at diagnosis was significantly associated with well-established prognostic factors, including high tumor stage and tumor grade (p<0.05). In univariate analysis, we observed that an increased LMR was a significant factor for better CSS in PC patients (HR 0.70; 95% CI 0.57-0.85; p<0.001). In multivariate analysis including age, Karnofsky Index, tumor grade, tumor stage, administration of chemotherapy, LMR and surgical resection, we confirmed increased LMR as an independent prognostic factor for CSS (HR 0.81; 95% CI 0.66-0.99; p=0.04). In conclusion, we identified LMR as an independent prognostic factor in PC patients. Our results indicate that the LMR might represent a novel and useful marker for patient stratification in PC management.

Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients.

BackgroundRecently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC.Patients and MethodsData from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated.ResultsNone of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077–1.751; p = 0.011).ConclusionIn conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.

Abstract C33: Prognostic value of C-myc overexpression in patients with resectable pancreatic cancer.

Abstract Purpose: Pancreatic cancer is one of the leading causes of cancer-related mortality and it is well known for extremely aggressive tumor growth rate, high incidence of metastasis and high metabolic rate. The aim of this study is to determine the value of metabolic gene expression as prognostic markers in patients with resectable pancreatic cancer. We also investigate the possible association among clinical parameters, 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) and metabolic markers. Materials and Methods: We retrospectively reviewed the medical records of 49 pancreatic cancer patients who underwent curative resection. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemistry (IHC) was done for GLUT1, hexokinase (HK), p53, IDH, pmTOR, PKM2, CMYC, and AMPK. Kaplan meier analysis and Cox-regression was used for univariate and multivariate analysis to examine the prognostic impact of each marker on survival. Also, Fisher's exact test was performed to examine correlation between metabolic makers and FDG uptake. Results: Median overall survival (OS) of all patients was 27.3 months (95% CI, 15.9 - 38.6). In univariate analysis, longer overall survival was seen in patients with c-myc overexpression, higher FDG uptake, and poorly differentiated histology. Multivariate analysis revealed that c-myc overexpression was an independent poor prognostic factor after adjustment of higher FDG uptake and tumor differentiation. No association was found between clinical parameters, FGD uptake, and metabolic markers. However, higher FDG uptake was correlated with low AMPK expression (P=0.017). Conclusions: Our study demonstrated that the c-myc overexpression identified by IHC is an independent prognostic factor in pancreatic cancer patients who underwent curative resection. Future studies are required to explore the underlying mechanism how c-myc overexpression contributes to the progression of pancreatic cancer in consideration with cancer metabolism. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C33. Citation Format: Seungtaek Lim, Hye Jin Choi, Jae-hoon Lee, Soohyeon Lee. Prognostic value of C-myc overexpression in patients with resectable pancreatic cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C33.

The status of HBV infection influences metastatic pattern and survival in Chinese patients with pancreatic cancer

BackgroundIt has been proved that hepatitis B virus (HBV) infection alters the metastatic pattern and affects survival in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), while the influence of HBV infection on metastatic pattern and survival in patients with pancreatic cancer (PC) has not been investigated yet.MethodsWe conducted an investigation to evaluate the impact of HBV infection on metastatic pattern and overall survival in PC. We collected the data of 460 PC patients treated in our hospital from 1999 to 2010. Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact of HBV infection on metastatic pattern and overall survival was analyzed.ResultsWe found that the incidence of synchronous liver metastasis was significantly higher in patients with HBsAg positive than those with HBsAg negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB) group than both non HBV infection and resolved HBV infection group (61.1% vs 33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What’s more, Kaplan-Meier analysis showed that CHB, resolved HBV infection and non HBV infection group had significant longer overall survival (OS) compared with inactive HBsAg carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the multivariate analysis, only the CHB and non HBV infection group had significant better overall survival compared with IC group (P=0.010 and P=0.018 respectively).ConclusionsOur study found that HBV infection increased synchronous liver metastasis rate, and HBV infection status was an independent prognostic factor in PC patients.

APKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms.