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Cancer of the Pancreas

Pancreatic cancer is a disease in which the cells of the pancreas become malignant. The pancreas has two main functions; (i) it makes juices that help digest food and (ii) produces hormones (including insulin) that conrol how food is used and stored in the body. The vast majority of pancreatic cancers are associated with the part of the pancreas that makes digestive juices - these are known as "exocrine" pancreatic cancers. Only about 1/20 pancreatic cancers start in the hormone producing part of the pancreas ; these are known as "endocrine" pancreatic cancer or "islet cell cancer". There are several types of exocrine pancreatic cancers (based on how the cells appear under the microsope), most are classed as "ductal adenocarcinomas". Pancreatic cancer is rare before the age of 40 years, incidence increases sharply with increasing age.

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Pancreatic Neuroendocrine Tumours (Islet Cell Tumours)
Familial Pancreatic Cancer

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    MeSH term: Pancreatic Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Melo SA, Luecke LB, Kahlert C, et al.
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
Nature. 2015; 523(7559):177-82 [PubMed] Related Publications
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1(+) crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1(+) crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1(+) crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.

Sun Y, Duan Q, Wang S, et al.
Diagnosis of pancreatic cancer using ¹⁸F-FDG PET/CT and CA19-9 with SUVmax association to clinical characteristics.
J BUON. 2015 Mar-Apr; 20(2):452-9 [PubMed] Related Publications
PURPOSE: To assess the ability of 18F-FDG PET/CT alone or combined with CA19-9 to diagnose pancreatic cancer and to analyze the correlation between maximal standardized uptake value (SUVmax) and clinical characteristics.
METHODS: Ninety-one patients diagnosed with pancreatic cancer using 18F-FDG PET/CT before treatment were analyzed. Definite diagnosis was by histology or cytology. The SUVmax of the primary tumor was used for the statistical analysis and, using the best cutoff value, the patients were divided into 2 groups: a high SUVmax group (SUV- max-5.49) and a low SUVmax group (SUVmax≤5.49). Logistic regression analysis and receiver operating characteristic (ROC) analysis were applied to analyze the effects of SUVmax and/or CA19-9 on the diagnosis of pancreatic cancer.
RESULTS: Of 91 patients, 80 had pancreatic cancer and 11 had benign conditions. The ROC curve analysis of the SUVmax yielded a best cutoff value of 5.49. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹⁸F-FDG PET/CT alone in the diagnosis of pancreatic cancer were 67.5, 72.73, 94.74, 23.53, and 68.13%, respectively, while these indices for ¹⁸F-FDG PET/CT combined with CA19-9 increased to 96.25, 63.64, 95.06, 70, and 92.31%, respectively. The area under the curve (AUC) of the SUVmax combined with CA19-9 was 0.94, which was significantly higher than that of the SUVmax or CA19-9 alone (p<0.05). The SUVmax value and CA19-9 levels in pancreatic cancer patients were significantly higher than those with benign conditions (p<0.05). Only the SUVmax in the pancreatic cancer patient group was associated with tumor size (p<0.05).
CONCLUSIONS: 18F-FDG PET/CT is a common examination for diagnosing pancreatic cancer, and the SUVmax combined with the CA19-9 level can significantly improve the sensitivity and accuracy in the diagnosis of pancreatic cancer. SUVmax is merely indicative of the volume of pancreatic cancer.

Khare V, Alam N, Saneja A, et al.
Targeted drug delivery systems for pancreatic cancer.
J Biomed Nanotechnol. 2014; 10(12):3462-82 [PubMed] Related Publications
Pancreatic cancer is usually diagnosed at the advanced stages, responds poorly to the available chemotherapeutics and constitutes the major factor for high mortality rate. Selective delivery of therapeutics to their cellular targets, without side effects is the foremost objective of the current investigations for effective treatment of pancreatic cancer. The development of the drugs which can selectively target pancreatic cancer along with carriers that can deliver drugs specifically to the rapidly dividing cells is considered as magic bullet for the efficient treatment of this fatal disease. This review describes various factors hampering the efficacy of drug targeting to pancreatic cancer including stromal fortress, hypocascularity, hyaluronan and interstitial fluid pressure, and exploration of various cellular targets for the site specific drug delivery. An account of burgeoning applications of novel drug delivery systems including nanoparticles, liposomes, quantum dots, micelles and drug conjugates in the management of pancreatic cancer is also provided. Additionally, potential of target based therapeutic agents and nanomedicines in clinical trials for the pancreatic cancer therapy are highlighted.

Chang YT, Tien YW, Jeng YM, et al.
Overweight increases the risk of malignancy in patients with pancreatic mucinous cystic neoplasms.
Medicine (Baltimore). 2015; 94(20):e797 [PubMed] Related Publications
Distinguishing between benign and malignant pancreatic cysts remains a clinical challenge. The aim of this study was to investigate the influence of body mass index (BMI) and preoperative clinical and cyst features, as described by the International Consensus Guidelines, on malignancy in patients with pancreatic mucinous cystic neoplasms (PMCNs).A retrospective cohort study was performed on patients with PMCNs who underwent surgical resection between January 1994 and June 2014. Preoperative BMI, clinical demographic data, cystic features, tumor markers, and surgical pathology results were analyzed. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression.One hundred sixty-four cases of PMCNs, including 106 intraductal papillary mucinous neoplasms (IPMNs) and 58 mucinous cystic neoplasms (MCNs), were analyzed. On univariate analysis, older age (P = 0.008), male sex (P = 0.007), high-risk stigmata (P = 0.007), diabetes mellitus (DM; P = 0.008), and BMI >25 (P < 0.001) were associated with malignancy. Multivariate analysis found that BMI >25 (odds ratio, 3.99; 95% confidence interval: 1.60-10) was an independent predictor of malignancy. In subgroup analysis, BMI >25 was an independent predictor of malignancy in IPMNs but not in MCNs.Overweight patients with IPMNs have a higher risk of malignancy and should be followed closely or undergo resection. The operative strategy for PMCNs should consider cyst-related and patient-related risk factors.

de Mestier L, Hentic O, Cros J, et al.
Metachronous hormonal syndromes in patients with pancreatic neuroendocrine tumors: a case-series study.
Ann Intern Med. 2015; 162(10):682-9 [PubMed] Related Publications
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described.
OBJECTIVE: To describe MHSs in patients with sporadic PNETs.
DESIGN: Retrospective, multicenter study.
SETTING: 4 French referral centers.
PATIENTS: Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014.
MEASUREMENTS: Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling.
RESULTS: Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs.
LIMITATION: Retrospective data collection and heterogeneity of pathologic specimen size and origin.
CONCLUSION: Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates.

Hiraoka N, Ino Y, Yamazaki-Itoh R, et al.
Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer.
Br J Cancer. 2015; 112(11):1782-90 [PubMed] Related Publications
BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs.
METHODS: We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics.
RESULTS: There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes.
CONCLUSIONS: Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained.

Progress in the treatment of metastatic pancreatic cancer and the search for next opportunities.
J Clin Oncol. 2015; 33(16):1779-86 [PubMed] Related Publications
A growing number of therapeutic options are now available for patients with metastatic pancreatic cancer, informed by positive results from recently completed phase III clinical trials. These have led to modest, if not necessarily transformative, improvements in clinical outcomes. Although the standard of care for metastatic disease remains cytotoxic therapy, a variety of novel therapeutic approaches are currently under active investigation, several of which have already demonstrated encouraging results in phase I/II studies. The following three broad categories (with significant overlap among them) are highlighted here: stromal-depleting agents, immunotherapies, and signal transduction inhibitors. The mechanistic rationale, limitations, and promise of each of these strategies specific to pancreatic cancer are discussed, as are the aspects of this disease and this patient population that pose ongoing challenges in terms of both therapeutic management and biomarker-driven trial design.

Heestand GM, Murphy JD, Lowy AM
Approach to patients with pancreatic cancer without detectable metastases.
J Clin Oncol. 2015; 33(16):1770-8 [PubMed] Related Publications
The poors outcomes associated with pancreatic cancer clearly reflect the advanced stage of disease at diagnosis for most patients. Through this lens, it is easy to lose sight of the fact that roughly 50% of patients with pancreatic cancer have no clinically detectable metastases at presentation. Herein, we discuss how patients with localized pancreatic cancer are currently managed. The primary goal of care for patients with resectable and borderline-resectable tumors is cure, facilitated by achieving margin-negative resection of the primary disease and delivering effective adjuvant and/or neoadjuvant therapy. For patients with locally advanced disease, the focus is on limiting local progression and outgrowth of metastatic disease and maintaining quality of life. Although it was once a centerpiece of therapy for localized pancreatic cancer, the value and place of radiation therapy in the treatment algorithm is now under increased scrutiny. In contrast, given its value as demonstrated in multiple prospective trials, chemotherapy is an established part of the treatment paradigm for all patients. With the demonstration that cytotoxic combinations such as fluorouracil, leucovorin, irinotecan, and oxaliplatin as well as gemcitabine/nab-paclitaxel are active in the metastatic setting, these agents are now being studied in patients with localized disease. The neoadjuvant setting provides a particularly favorable setting for evaluating new systemic strategies. Given the array of new targets, including immunomodulatory approaches, there is reason for optimism that we can markedly improve survival for all patients with pancreatic cancer and enter an era in which surgery with curative intent actually fulfills this goal on a much more regular basis.

Bauden M, Tassidis H, Ansari D
In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment.
Toxicol Lett. 2015; 236(1):8-15 [PubMed] Related Publications
Apicidin is a potent histone deacetylase inhibitor (HDACI) that selectively binds to histone deacetylases (HDACs) class I and interferes with the deacetylation process, which results in modification of acetylation level of cellular proteins. The aim of the study was to investigate the potential time and dose dependent cytotoxicity of the test compound, Apicidin, in pancreatic cancer cells Capan-1 and Panc-1 as well as estimate maximal tolerable dose (MTD) of the test agent and determine EC50 using four complementary colorimetric cytotoxicity or viability assays. The cells were treated with increasing concentrations of Apicidin (0-5000nM) for 2, 4 and 6h (short term exposure) or 24, 48 and 72h (long term exposure) before conducting cytotoxic analyses with lactate dehydrogenase assay or viability analyses with sulforhodamine B (SRB), methyl tetrazolium (MTT) and crystal violet (CV) assays. In order to investigate whether Apicidin irreversibly affects the cells already during the short term exposure, the medium containing Apicidin was removed and replaced with fresh culturing medium after 6h of treatment. The cells were then incubated for additional 24, 48 or 72h before carrying out the analysis. The results obtained from cytotoxicity and viability assays indicated, that Apicidin was well tolerated by both cell lines at concentrations below 100nM at any given time point and at all applied concentrations during the short term (6h or less) treatment. Continuous prolonged term exposures (48h or greater) of the cells to Apicidin with concentration exceeding 100nM resulted in significantly increasing cytotoxicity and sustained significant loss of cell viability. Moreover, long term exposure of pancreatic cancer cells Capan-1 and Panc-1 to Apicidin concentrations exceeding 100nM showed an initial anti-proliferative effect before cytotoxicity onset. In summary, MTD was exposure time dependent and estimated to 100nM for long term treatment and to at least 5000nM for treatment not greater than 6h. EC50 concentration of Apicidin was established after long term treatment, however with some variation when comparing the different assays and cell lines. Results from this study may encourage reinvestigating the capacity of potent HDACI Apicidin as an attractive agent for interfering with the deacetylation process catalyzed by HDACs for potential pancreatic cancer intervention.

Mathur A, Luberice K, Paul H, et al.
Increasing body mass index portends abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.
Am J Surg. 2015; 209(6):969-73 [PubMed] Related Publications
BACKGROUND: Body mass index (BMI), a common surrogate marker for grading obesity, does not differentiate between metabolically active visceral fat and the relatively inert subcutaneous fat. We aim to determine the utility of BMI as a prognostic marker for the impact of obesity on outcomes and survival following pancreatoduodenectomy for pancreatic adenocarcinoma.
METHODS: From a database of over 1,000 patients who had undergone pancreatoduodenectomy, 228 patients with a diagnosis of pancreatic adenocarcinoma were identified. Demographic data including BMI and perioperative parameters-operative time, estimated blood loss, length of stay, survival, nodal status, and American Joint Committee on Cancer stage-were obtained. Data are presented as median.
RESULTS: One hundred ninety-two patients had a BMI less than or equal to 29 and 36 patients had a BMI greater than or equal to 30 (24 vs. 34, P < .001). Median age was 70 and the majority of the patients (52%) were male and the 2 groups of patients did not differ in this regard. A significantly greater number of obese patients had positive nodes (69% vs. 62%, P < .05) and this was associated with a worse survival (14 vs. 18 months, P < .05).
CONCLUSIONS: For patients with pancreatic adenocarcinoma undergoing pancreatoduodenectomy, obesity does not impact operative complexity or length of stay but results in a shortened survival. Therefore, we conclude that BMI is an important prognostic marker that portends an abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.

Kurihara T, Kogo M, Ishii M, et al.
Practical prognostic index for survival in patients with unresectable pancreatic cancer treated with gemcitabine or S-1.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):478-84 [PubMed] Related Publications
BACKGROUND/AIMS: We performed this retrospective cohort study to identify prognostic factors for unresectable pancreatic cancer treated with current standard therapy using gemcitabine (GEM) or S-1 and to stratify patients prior to treatment using a prognostic index (PI).
METHODOLOGY: We analyzed 182 patients with unresectable pancreatic cancer, who had received GEM or S-1 as first-line chemotherapy. Factors that contributed to the prognosis were identified by univariate and multivariate analysis using a Cox proportional hazards model. The PI was constructed using the factors identified in the multivariate analysis.
RESULTS: By multivariate analysis, performance status (PS), stage, and absolute neutrophil count (ANC) were identified as factors that independently contributed to the prognosis of unresectable pancreatic cancer (P < 0.05). The hazard ratios were 1.69, 3.33, and 1.18, respectively. In addition, PI was calculated using these three factors. Patients were classified into three groups according to the PI values. A significant difference was observed among the survival curves of these three groups (P < 0.05).
CONCLUSIONS: We identified three prognostic factors in the population after the introduction of S-1, and have created a simple and useful PI. This index demonstrates the ability to accurately classify advanced pancreatic cancer patients before the start of treatment.

Aoyama T, Murakawa M, Katayama Y, et al.
Lymphatic invasion is an independent prognostic factor in pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy with gemcitabine or S-1.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):472-7 [PubMed] Related Publications
BACKGROUND/AIMS: 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.
METHODOLOGY: 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 < 0.001). Moreover, the 5-year RFS was 20.5% in the lymphatic invasion-negative group and 10.4% in the lymphatic invasion- positive 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.

Tomizawa M, Shinozaki F, Motoyoshi Y, et al.
Diffusion-weighted whole body imaging with background body signal suppression/T2 image fusion is negative for patients with intraductal papillary mucinous neoplasm.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):463-5 [PubMed] Related Publications
BACKGROUND/AIMS: One major problem with Intraductal papillary mucinous neoplasm (IPMN) is the appearance of pancreatic duct adenocarcinoma. Diffusion-weighted whole body imaging with background body signal suppression (DWIBS) provides hyperintense signals in cases of cancer. DWIBS and T2 image fusion (DWIBS/T2) provides functional information in anatomical settings, and is useful for the detection of cancer with strong contrast against surrounding tissues. DWIBS/T2 signals were analyzed in patients with IPMN to investigate positive or negative results.
METHODOLOGY: Patient records were analyzed retrospectively regarding IPMN. None showed high-risk stigmata or worrisome features. To rule out T2 shine-through or differentiate malignant lesions from non-malignant causes of restricted diffusion, positive ADC maps were produced from the recorded ADC values.
RESULTS: None of the patients with IPMN had features of malignant progression. No mural nodules were detected by endoscopic ultrasonography. IPMN was hyperintense with DWIBS/T2 and the ADC map. This finding suggested that the hyperintense values of IPMN were T2 shine-through. These results showed that none of the IPMNs were positive with DWIBS/T2.
CONCLUSION: DWIBS/T2 was negative for patients with IPMN. DWIBS/T2 might be useful for the evaluation of malignant progression, in addition to observation.

Tsuchikawa T, Hirano S, Nakamura T, et al.
Detailed analysis of extra-pancreatic nerve plexus invasion in pancreatic body carcinoma analyzed by 50 consecutive series of distal pancreatectomy with en-bloc celiac axis resection.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):455-8 [PubMed] Related Publications
BACKGROUND/AIMS: Advanced pancreatic body carcinoma frequently accompany extra-pancreatic nerve plexus (PL) invasion, one of the poor indicator of patient prognosis. The present study aimed to reveal the progress of the PL invasion from cancer of the pancreas body toward the root of the celiac artery (CA) and superior mesenteric artery (SMA) followed by investigation of the relevance of diagnostic accuracy.
METHODOLOGY: Resected specimens from 50 consecutive patients who underwent distal pancreatectomy with en bloc celiac axis resection (DP-CAR) were pathologically analyzed for the direction of PL invasion. Diagnostic accuracy on CT imaging were also investigated.
RESULTS: Thirty seven of the 50 patients (74%) were positive for PL invasion around the CHA, SPA, CA and SMA. In terms of the diagnostic accuracy, positive predictive values for the PL invasion were 35%, 36%, 43% and 81% for the SPA, CHA, CA and SMA, respectively. Among 21 patients and 23 patients with PL invasion around CHA and SPA, 13 and 6 patients also accompanied PL invasion around CA, respectively.
CONCLUSIONS: Carcinoma of the pancreatic body is found to frequently accompany PL invasion around CA. Under the limitation of low diagnostic accuracy, DP-CAR might be feasible operation that increases the possibility of R0 resection.

Utsumi M, Umeda Y, Takagi K, et al.
Correlation of computed tomography imaging features and pathological features of 41 patients with pancreatic neuroendocrine tumors.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):441-6 [PubMed] Related Publications
BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (PNET) are relatively rare. Here, we present clinical and pathological characteristics of PNETs to show a relationship between computed tomography (CT) imaging and the 2010 World Health Organization (WHO) classification.
METHODOLOGY: We retrospectively reviewed the records of 41 PNET patients who were treated between 2002 and 2012. All tumors were classified as neuroendocrine tumor (NET) grade 1 (G1), NET grade 2 (G2), or neuroendocrine carcinoma (NEC) grade 3 (G3) on the basis of the 2010 WHO classification system.
RESULTS: Twenty-five tumors were classified as G1, 11 as G2, and five as G3. Mean sizes of the G1, G2 and G3 tumors were 1.84 ± 0.54, 4.90 ± 0.84, and 5.62 ± 1.18 cm, respectively, (P < 0.01). A PNET is typically hypervascular and exhibits contrast enhancement on enhanced CT. Higher percentage of G1 tumors demonstrated typical imaging and showed a significantly greater distinct mass compared with G2 and G3 tumors.
CONCLUSIONS: Although PNET has many imaging features that appear on CT, G2 and G3 tumors often show atypical imaging features, particularly with large sizes and/or ill-defined features, when compared with G1 tumors. If a PNET has atypical imaging features, possibility of malignancy should be considered.

Cao J, Xia C, Cui T, et al.
Correlations between serum trypsinogen-2 and pancreatic cancer.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):435-40 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate associations be- tween serum trypsinogen-2, pancreatitis and pancreatic cancer (PC) and determine cutoff values for PC diagnosis.
METHODOLOGY: We recruited 88 patients from Internal Medicine/Surgical Departments of General Military Hospital of Beijing PLA between 12/2009 and 6/2010. Serum samples were collected preoperatively from 23 PC patients, 30 pancreatitis patients and 35 healthy controls. Enzyme-linked immunosorbent assay was used to detect trypsinogen-2 semiquantitatively.
RESULTS: Serum trypsinogen-2 levels of PC and pancreatitis patients were significantly higher than those of controls (51.2 ± 80.3, 107.7 ± 98.1 vs. 1.0 ± 0.5, p = 0.03, p < 0.001) and significantly higher in pancreatitis vs. PC patients (107.7 ± 98.1 vs. 51.2 ± 80.3, p = 0.01). Higher Balthazar CT grades correlated with higher trypsinogen-2 in pancreatitis group. ROC curves for trypsinogen-2 revealed optimal cutoff value 1.8 as lower PC detection limit with 95.7% sensitivity and 91.4% specificity, and optimal cutoff value 19.9 for upper PC detection limit with 87.0% sensitivity and 97.1% specificity. Trypsinogen-2 levels correlated with pancreatic injury level. An AUC of 0.73 (95% Cl: 0.59-0.84, p = 0.002) distinguished PC from pancreatitis.
CONCLUSION: Serum trypsinogen-2 is associated with PC and pancreatitis. Levels between 1.8 μg/L and 19.9 μg/L strongly suggest PC. Detection of serum trypsinogen-2 may provide simple, sensitive, specific non-invasive initial screening for early PC diagnosis.

Kim JC, Kim KT, Park JT, et al.
Expression of vasohibin-2 in pancreatic ductal adenocarcinoma promotes tumor progression and is associated with a poor clinical outcome.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):251-6 [PubMed] Related Publications
This study aimed to assess the expression of vasohibin-2 (VASH2) in pancreatic ductal adenocarcinoma (PDAC) as a marker of tumor aggressiveness and its impact on tumor angiogenesis, proliferation, and clinical outcome. We examined the expression of the VASH2 gene in human pancreatic cell lines PANC-1 and MiaPaCa-2 by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry. Fifty samples from patients with PDAC were immunostained with VASH2, CD34, and Ki-67 antibodies. Further, the immunoreactivity of VASH2 correlated with the pathological features, including microvessel density (MVD), tumor cell proliferation (Ki-67 labeling index), and survival. Forty-seven of the 50 samples from PDAC patients showed immunoreactivity for VASH2 along the tumor cell cytoplasm. Among the VASH2-positive samples, 22 were categorized as high VASH2 expression group, and this group had statistical significance with pN stage (p = 0.006), UICC stage (p = 0.033), tumor proliferation (p < 0.001), and MVD (p = 0.017). Moreover, patients with high VASH2 expression showed worse prognosis compared to those showing low VASH2 expression (overall logrank p = 0.003). Thus, our results suggested that overexpression of VASH2 accelerated the pace of tumor development toward a more serious malignant phenotype and was associated with a poor clinical outcome. VASH2 may be an important novel target for the management of PDAC after surgery.

Aoyama T, Katayama Y, Murakawa M, et al.
Clinical implication of peritoneal cytology in the pancreatic cancer patients who underwent curative resection followed by adjuvant gemcitabine or S-1 chemotherapy.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):200-6 [PubMed] Related Publications
BACKGROUND/AIMS: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established.
METHODOLOGY: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated.
RESULTS: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed. The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p=0.001). The OS rates at 3 and 5 years after surgery were 17.1% and 8.6% in CY+ patients, respectively, and were 26.1% and 16.1% in CY- patients, respectively, which were trend to worse in the CY+ patients (p=0.254).
CONCLUSION: The patients with CY+ are likely to experience recurrence, even after they received curative resection and adjuvant Gemcitabine or S-1 adjuvant chemotherapy.

Ishii M, Kimura Y, Imamura M, et al.
Remnant pancreas reconstruction with duct-to-duct anastomosis after middle pancreatectomy: a report of two cases.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):190-4 [PubMed] Related Publications
Reconstruction of a remnant pancreas after middle pancreatectomy has generally been performed with a pancreaticoenterostomy. We report here two cases in which physiological reconstructive procedures were performed. The reconstructive procedures included pancreatic duct-to-duct anastomosis and parenchymal sutures with absorbable monofilament interrupted stitches. A pancreatic tube was inserted for decompression at the anastomotic site in both cases. The patients comprised one with pancreatic metastasis from renal cell carcinoma and another with a non-malignant insulinoma. The tumors were located in the pancreatic body. Although an International Study Group on Pancreatic Fistula classification grade B-pancreatic fistula was observed in each patient, they both resolved with conservative therapy. The pancreatic duct at the anastomosis site was patent in both cases, and no atrophic changes developed in the remnant pancreas in either patient. These outcomes confirmed that, in selected cases, this reconstructive procedure is safe and feasible for physiological reconstruction without involvement of the digestive tract.

Hu HK, Ke NW, Li A, et al.
Clinical characteristics and prognostic factors of gastroenteropancreatic neuroendocrine tumors: a single center experience in China.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):178-83 [PubMed] Related Publications
BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited.
METHODOLOGY: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012.
RESULTS: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05).
CONCLUSION: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Shinkawa H, Uenishi T, Takemura S, et al.
Adjuvant S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):169-74 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was determine the effectiveness of adjuvant S-1 chemotherapy for patients with resected pancreatic cancer.
METHODOLOGY: Patients with pancreatic carcinoma who underwent pancreatic resection without adjuvant S-1 chemotherapy (n = 11) or with adjuvant S-1 chemotherapy (n = 10) were included. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 consecutive days followed by a 14-day pause. The cycle was repeated 4 times. Overall and disease-free survival curves were generated using the Kaplan-Meier method, and statistical differences between groups were analyzed using the log-rank test.
RESULTS: The disease-free survival and overall survival were longer among recipients of adjuvant S-1 chemotherapy than among those who received surgery alone (P < 0.05; 5-year disease-free survival rate, 30% versus 0%; 5-year overall survival rate, 65% vs 0%). Although dose reduction was needed in 2 patients because of grade 2 anorexia, only 1 patient with grade 2 hypoalbuminemia discontinued adjuvant chemotherapy because of long-term hospitalization.
CONCLUSIONS: S-1 administered as a single agent showed promise as an adjuvant chemotherapy for resected pancreatic cancer.

Chirindel A, Alluri KC, Chaudhry MA, et al.
Prognostic Value of FDG PET/CT-Derived Parameters in Pancreatic Adenocarcinoma at Initial PET/CT Staging.
AJR Am J Roentgenol. 2015; 204(5):1093-9 [PubMed] Related Publications
OBJECTIVE: The purpose of this study is to evaluate the performance of PET-derived parameters as prognostic markers for overall survival (OS) and progression-free survival (PFS) outcome in patients with pancreatic adenocarcinoma.
MATERIALS AND METHODS: We conducted a retrospective study of 106 patients (62 men and 44 women) with histologically proven pancreatic adenocarcinoma who underwent initial staging FDG PET/CT before treatment. Peak standardized uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume, and tumor glycolytic activity of the primary pancreatic tumor were measured. Two segmentation methods were performed to obtain the metabolic tumor volume and tumor glycolytic activity for all tumors: a gradient-based segmentation model (metabolic tumor volume and tumor glycolytic activity by gradient edge detection) and a fixed-threshold model with a threshold of 50% of the lesion's SUVmax and peak SUV. Univariate and multivariate Cox regression models were developed including clinical and imaging parameters for OS and PFS.
RESULTS: Multivariate Cox regression analysis showed a statistically significant association between PFS and age, SUVmax, peak SUV, and tumor glycolytic activity by gradient edge detection. There was a statistically significant difference in PFS for patients with values above and below the median cutoff points for SUVmax (hazard ratio [HR], 1.12; p < 0.01), peak SUV (HR, 1.25; p < 0.02), and tumor glycolytic activity measured by gradient edge detection (HR, 1.00; p < 0.02) of the primary tumor. However, multivariate Cox regression analysis showed a statistically significant association only between tumor glycolytic activity by gradient edge detection and OS (p = 0.04), and there was a statistically significant difference in OS between patients with values above and below the median cutoff point for the tumor glycolytic activity by gradient edge detection of the primary tumor (HR, 1.42; p = 0.05).
CONCLUSION: Age, SUVmax, peak SUV, and total lesion glycolysis (i.e., tumor glycolytic activity) of the primary tumor are associated with PFS, and tumor glycolytic activity is associated with OS in patients with pancreatic adenocarcinoma.

Frank TS, Sun X, Zhang Y, et al.
Genomic profiling guides the choice of molecular targeted therapy of pancreatic cancer.
Cancer Lett. 2015; 363(1):1-6 [PubMed] Article available free on PMC after 10/07/2016 Related Publications
Pancreatic cancer has the worst five-year survival rate of all malignancies due to its aggressive progression and resistance to therapy. Current therapies are limited to gemcitabine-based chemotherapeutics, surgery, and radiation. The current trend toward "personalized genomic medicine" has the potential to improve the treatment options for pancreatic cancer. Gene identification and genetic alterations like single nucleotide polymorphisms and mutations will allow physicians to predict the efficacy and toxicity of drugs, which could help diagnose pancreatic cancer, guide neoadjuvant or adjuvant treatment, and evaluate patients' prognosis. This article reviews the multifaceted roles of genomics and pharmacogenomics in pancreatic cancer.

Russolillo N, Vigano' L, Razzore P, et al.
Survival prognostic factors of gastro-enteric-pancreatic neuroendocrine tumors after primary tumor resection in a single tertiary center: Comparison of gastro-enteric and pancreatic locations.
Eur J Surg Oncol. 2015; 41(6):751-7 [PubMed] Related Publications
AIM: This study aimed to evaluated prognostic factors of patients with GEP-NETs after primary tumor resection comparing pancreatic and gastro-enteric locations.
METHODS: Patients undergone surgery for primary GEP-NETs between 01/2000 and 03/2012 were considered. All specimens were reclassified according to the WHO 2010 scheme.
RESULTS: A total of 83 patients were considered: 37 pancreatic NETs (pNET) and 46 gastroenteric NETs (GE-NET). The two groups were similar in terms of age, sex and tumors size. A higher rate of patients with pNETs had Ki67 score ≥3 (64.8% vs. 39%, p = 0.027) while the rates of Mitotic Index ≥2x10HPF (62% pNET vs. 50% GE-NET, p = 0.374) and diagnosis of neuroendocrine carcinoma NEC (16.2% pNET vs. 17.3% GE-NET, p = 0.100) were similar. The rates of distant metastases (GE-NETs 30.4% vs. p-NETs 29.7%, p = 0.944) and liver metastases (19.5% GE-NET vs. 27% pNET, p = 0.421) were comparable. Radical resection was achieved in a similar proportion in both groups [33 patients (89.1%) pNET vs. 36 (78.2%) GE-NET, p = 0.393]. After a median follow-up of 47.1 months overall 3, 5 and 10-years survival rates of whole patients were 88.1%, 81.2% and 76.7%. There was not difference on 5-years overall survival between pNET (81.4%) and GE-NET (81%, p = 0.901). At multivariate analysis age ≥70 [OR 4.177 (CI 95% 1.26-13.8), p = 0.019] and NEC [OR 5.932 (CI 95% 1.81-19.40), p < 0.001] were negative prognostic factors of survival.
CONCLUSION: Overall survival of GEP-NET after resection of primary tumors seems to be correlated to patient's age and WHO 2010 staging system but not to primary tumor site.

Ohkawa S, Okusaka T, Isayama H, et al.
Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer.
Br J Cancer. 2015; 112(9):1428-34 [PubMed] Article available free on PMC after 10/07/2016 Related Publications
BACKGROUND: This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.
METHODS: Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS.
RESULTS: Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).
CONCLUSIONS: Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Murakami Y, Satoi S, Motoi F, et al.
Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma.
Br J Surg. 2015; 102(7):837-46 [PubMed] Related Publications
BACKGROUND: The aim of this study was to determine the added value of portal or superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy for pancreatic head carcinoma.
METHODS: A multicentre observational study was conducted in patients with pancreatic head carcinoma who underwent pancreatoduodenectomy in seven Japanese hospitals between 2001 and 2012. Clinicopathological factors were compared between patients who did and did not undergo PV/SMV resection. Those with an impact on survival were identified by univariable and multivariable analysis.
RESULTS: Of the 937 patients who underwent pancreatoduodenectomy, 435 (46·4 per cent) had PV/SMV resection, whereas the remaining 502 (53·6 per cent) did not. Some 71·5 and 63·9 per cent of patients with and without PV/SMV resection respectively had lymph node-positive disease. Patients who underwent PV/SMV resection had more advanced tumours. Perioperative mortality and morbidity rates did not differ between the two groups. Multivariable analysis revealed that PV/SMV resection was not an independent prognostic factor for overall survival (P = 0·268). Among the 435 patients in whom the PV/SMV was resected, borderline resectable tumours with arterial abutment (P = 0·021) and absence of adjuvant chemotherapy (P < 0·001) were independent predictors of poor survival in multivariable analysis. Patients with resectable or borderline resectable tumours with PV/SMV involvement had a median survival time with additional adjuvant chemotherapy of 43·7 and 29·7 months respectively. Median survival time in patients with borderline resectable tumours with arterial abutment was 18·6 months despite adjuvant chemotherapy.
CONCLUSION: Pancreatoduodenectomy with PV/SMV resection and adjuvant chemotherapy in patients with pancreatic head carcinoma may provide good survival without increased mortality and morbidity.

Choi CH, Chung JY, Park HS, et al.
Pancreatic adenocarcinoma up-regulated factor expression is associated with disease-specific survival in cervical cancer patients.
Hum Pathol. 2015; 46(6):884-93 [PubMed] Related Publications
Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel soluble protein involved in tumor development and metastases. This study was to investigate the PAUF expression and its prognostic value in cervical cancer patients. The expression of PAUF was immunohistochemically determined in 345 formalin-fixed, paraffin-embedded cervical cancer tissues and 107 normal cervical epitheliums. Subsequently, its associations with clinicopathological characteristics and patient survival were assessed. PAUF protein was expressed both in cytoplasm and nucleus, and cytoplasmic expression was more frequent in cancers than normal tissues (32% versus 17%, P = .002), and the difference was prominent in glandular cells. Notably, the expression was more frequent in adenocarcinoma than in squamous cell carcinoma (57% versus 25%, respectively; P < .001), and the differential expression was also seen at the messenger RNA level (P = .014). Cox regression analysis showed that the cytoplasmic expression of PAUF protein was independently associated with poor disease-free (hazard ratio = 2.3; 95% confidence interval, 1.2-4.3; P = .008) and overall survival (hazard ratio = 2.9; 95% confidence interval, 1.2-7.5; P = .020). Detection of PAUF expression may aid current evaluation of prognosis in cervical adenocarcinoma.

Hoffman RL, Gates JL, Kochman ML, et al.
Analysis of cyst size and tumor markers in the management of pancreatic cysts: support for the original Sendai criteria.
J Am Coll Surg. 2015; 220(6):1087-95 [PubMed] Related Publications
BACKGROUND: In 2006, the Sendai Consensus Guidelines identified size >3.0 cm as the only independent predictor of malignancy in incidentally discovered pancreatic cysts. The 2012 updated guidelines increased emphasis on radiographic features over size. Earlier studies included patients with preoperatively diagnosed carcinoma or with a corresponding mass. In this report, we characterize the use of size and serum tumor markers in the initial evaluation of pancreatic cystic neoplasms without preoperatively diagnosed adenocarcinoma and correlate them with clinical and pathologic outcomes.
STUDY DESIGN: A retrospective cohort study was undertaken of 112 patients with a resected pancreatic cystic neoplasm. Patient demographics, cyst characteristics, preoperative serum tumor markers, morbidity, and mortality were captured. Statistical analysis included nonparametric tests of comparison, multivariate logistic regression, and receiver operating characteristic curve analyses.
RESULTS: One hundred and twelve pancreatic cystic neoplasms were resected; there was one perioperative death. Mucinous cysts were common (78%), followed by serous cysts (13%). In total, 17% of cysts harbored malignancy. On multivariate analysis, the risk of malignancy in cysts≥3 cm was more than 4 times that of smaller cysts (relative risk (RR)=4.32; 95% CI, 1.55-12.07). There was no significant difference in serum CEA, cancer antigen 19-9, or cyst-fluid CEA levels between the benign and malignant groups. At a median follow-up of 30 months, the incidence of diabetes was 15%.
CONCLUSIONS: Surgical resection of pancreatic cysts can be performed with low perioperative mortality and acceptable long-term morbidity. Use of cyst size as a rationale for resection of cystic lesion, as per the Sendai criteria, is justified.

Zhu Z, Xu Y, Zhao J, et al.
miR-367 promotes epithelial-to-mesenchymal transition and invasion of pancreatic ductal adenocarcinoma cells by targeting the Smad7-TGF-β signalling pathway.
Br J Cancer. 2015; 112(8):1367-75 [PubMed] Article available free on PMC after 14/04/2016 Related Publications
BACKGROUND: Aberrant Smad7 expression contributes to the invasion and metastasis of pancreatic cancer cells. However, the potential mechanism underlying aberrant Smad7 expression in human pancreatic ductal adenocarcinoma (PDAC) remains largely unknown.
METHODS: Bioinformatic prediction programmes and luciferase reporter assay were used to identify microRNAs regulating Smad7. The association between miR-367 expression and the overall survival of PDAC patients was evaluated by Kaplan-Meier analysis. The effects of miR-367 and Smad7 on the invasion and metastasis of pancreatic cancer cells were investigated both in vitro and in vivo.
RESULTS: We found that miR-367 downregulated Smad7 expression by directly targeting its 3'-UTR in human pancreatic cancer cells. High level of miR-367 expression correlated with poor prognosis of PDAC patients. Functional studies showed that miR-367 promoted pancreatic cancer invasion in vitro and metastasis in vivo through downregulating Smad7. In addition, we showed that miR-367 promoted epithelial-to-mesenchymal transition by increasing transforming growth factor-β (TGF-β)-induced transcriptional activity.
CONCLUSIONS: The present study identified and characterised a signalling pathway, the miR-367/Smad7-TGF-β pathway, which is involved in the invasion and metastasis of pancreatic cancer cells. Our results suggest that miR-367 may be a promising therapeutic target for the treatment of human pancreatic cancer.

Spolverato G, Maqsood H, Kim Y, et al.
Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies.
J Surg Oncol. 2015; 111(7):868-74 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: We sought to determine whether Neutrophil-lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR) were associated with outcomes of patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy.
METHOD: Between 2000 and 2013, 452 patients who underwent an HPB procedure for a malignant indication were identified. Clinicopathological characteristics, NLR, and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR were classified using a cut-off value of 5 and 190, respectively, based on ROC curve analysis.
RESULTS: Patients with low versus high NLR and PLR had similar baseline characteristics with regard to performance status and tumor stage (all P > 0.05). Elevated PLR (HR = 1.40) tends to be association with shorter recurrence-free survival (RFS) (P = 0.05), whereas NLR was not a predictor of shorter RFS. Differently, both elevated NLR (HR = 1.94) and PLR (HR = 1.79) were associated with worse overall survival (OS) (both P < 0.05). Patients with NLR ≥5 and those with PLR ≥190 had a significantly shorter OS compared to patients with NLR <5 and PLR <190, respectively (log-rank test, both P < 0.05). Moreover, patients who had both NLR and PLR elevated had worse OS compared to patients with either one or none inflammatory markers elevated (log-rank P = 0.02).
CONCLUSION: Elevated NLR and PLR were predictors of worse long-term outcome among patients with HPB malignancy undergoing resection.

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