Efficacy of nab­paclitaxel vs. Gemcitabine in combination with S­1 for advanced pancreatic cancer: A multicenter phase II randomized trial.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

Label-Free Histology and Evaluation of Human Pancreatic Cancer with Coherent Nonlinear Optical Microscopy.

Surgeries achieving maximal tumor resection remain the major effective treatment of pancreatic cancer. Rapid and precise intraoperative diagnosis of pancreatic tissues is critical for optimum surgical outcomes but is challenging for the current staining-based histological methods. We demonstrated that label-free coherent nonlinear optical microscopy with combined stimulated Raman scattering (SRS) and second harmonic generation (SHG) could reveal key diagnostic features of both normal and cancerous human pancreatic tissues. Adjacent pairs of tissue sections from resection margins of 37 patients were imaged by SRS and hematoxylin and eosin staining for direct comparison, demonstrating high diagnostic concordance (Cohen's kappa, κ > 0.97) between them. Fresh unprocessed tissues showed well-preserved histoarchitectures including pancreatic ducts, islets, acini, and nerves. Moreover, the area ratios of collagen fibers were analyzed and found to correlate with the drainage pancreatic amylase level (odds ratio = 28.0, p = 0.0017). Our results indicated that SRS/SHG histology provides potential for rapid intraoperative diagnosis of pancreatic cancer as well as a predictive value of postoperative pancreatic fistula.

Evaluating perioperative glycemic status after different types of pancreatic surgeries via continuous glucose monitoring system: a pilot study.

BACKGROUND: Perioperative glycemic status after pancreatic surgery has never been described. However, it's essential for optimal perioperative glucose management and understanding the pathogenesis of new-onset diabetes mellitus (NODM) after pancreatectomy. Continuous glucose monitoring (CGM) system provides us a helpful tool for closely monitoring and studying perioperative glucose change. This study tried to describe and compare perioperative glucose level and glycemic variability between different types of pancreatic surgeries via CGM device. METHODS: This study was designed as a prospective observational study. Eighteen patients were enrolled and were grouped by different types of surgery received: control group (CTRL), pancreaticoduodenectomy (PD), distal pancreatectomy (DP), and total pancreatectomy (TP). CGM devices were implanted and initiated right after the surgery. Mean glucose value (MGV), coefficient of variation (CV), mean of daily difference (MODD), continuous overall net glycemic action (CONGA), and time above range (TAR)/time below range (TBR) was compared between groups to assess glucose level and glycemic variability. RESULTS: TP showed the highest MGV and CV among all groups (P<0.001), while CTRL showed the lowest (P<0.001). PD and DP had similar MGV and CV lower than TP but higher than CTRL (P<0.001). TP had the highest MODD and CONGA, CTRL had the lowest, but no significant differences were found between groups. TP had the highest TAR (24.29%) and the lowest TBR (1.28%), while the control group showed the opposite. The differences in TAR/TBR between groups were all significant (P<0.05). CONCLUSIONS: TP had the highest mean glucose level and the greatest glycemic variability. PD and DP had similar results: a higher mean glucose level than control but lower than TP. For glycemic variability, PD and DP seemed to have a near-normal result resembling the control group. CGM is useful for glucose monitoring in the perioperative management of pancreatic surgery.

WD repeat-containing protein 1 maintains ß-Catenin activity to promote pancreatic cancer aggressiveness.

BACKGROUND: The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. METHODS: Eight-plex isobaric tags coupled with two-dimensional liquid chromatography-tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation. RESULTS: A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/ß-Catenin pathway; ectopic expression of a stabilised form of ß-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of ß-Catenin. CONCLUSION: Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.

Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment.

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

LyP-1-fMWNTs enhanced targeted delivery of MBD1siRNA to pancreatic cancer cells.

Functionalized multi-walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP-1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP-1-conjugated functionalized multi-walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP-1-conjugated functionalized multi-walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi-walled carbon nanotubes, cellular uptake of LyP-1-functionalized multi-walled carbon nanotubes was shown to be increased. Compound of LyP-1-functionalized multi-walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP-1-fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.

Partial pancreatic tail preserving subtotal pancreatectomy for pancreatic cancer: Improving glycemic control and quality of life without compromising oncological outcomes.

BACKGROUND: Total pancreatectomy (TP) is usually considered a therapeutic option for pancreatic cancer in which Whipple surgery and distal pancreatectomy are undesirable, but brittle diabetes and poor quality of life (QoL) remain major concerns. A subset of patients who underwent TP even died due to severe hypoglycemia. For pancreatic cancer involving the pancreatic head and proximal body but without invasion to the pancreatic tail, we performed partial pancreatic tail preserving subtotal pancreatectomy (PPTP-SP) in selected patients, in order to improve postoperative glycemic control and QoL without compromising oncological outcomes. AIM: To evaluate the efficacy of PPTP-SP for patients with pancreatic cancer. METHODS: We retrospectively reviewed 56 patients with pancreatic ductal adenocarcinoma who underwent PPTP-SP (n = 18) or TP (n = 38) at our institution from May 2014 to January 2019. Clinical outcomes were compared between the two groups, with an emphasis on oncological outcomes, postoperative glycemic control, and QoL. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and EORTC PAN26). All patients were followed until May 2019 or until death. RESULTS: A total of 56 consecutive patients were enrolled in this study. Perioperative outcomes, recurrence-free survival, and overall survival were comparable between the two groups. No patients in the PPTP-SP group developed cancer recurrence in the pancreatic tail stump or splenic hilum, or a clinical pancreatic fistula. Patients who underwent PPTP-SP had significantly better glycemic control, based on their higher rate of insulin-independence (P = 0.014), lower hemoglobin A1c (HbA1c) level (P = 0.046), lower daily insulin dosage (P < 0.001), and less frequent hypoglycemic episodes (P < 0.001). Global health was similar in the two groups, but patients who underwent PPTP-SP had better functional status (P = 0.036), milder symptoms (P = 0.013), less severe diet restriction (P = 0.011), and higher confidence regarding future life (P = 0.035). CONCLUSION: For pancreatic cancer involving the pancreatic head and proximal body, PPTP-SP achieves perioperative and oncological outcomes comparable to TP in selected patients while significantly improving long-term glycemic control and QoL.

Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy.

Maximal resection of tumor while preserving the adjacent healthy tissue is particularly important for larynx surgery, hence precise and rapid intraoperative histology of laryngeal tissue is crucial for providing optimal surgical outcomes. We hypothesized that deep-learning based stimulated Raman scattering (SRS) microscopy could provide automated and accurate diagnosis of laryngeal squamous cell carcinoma on fresh, unprocessed surgical specimens without fixation, sectioning or staining. Methods: We first compared 80 pairs of adjacent frozen sections imaged with SRS and standard hematoxylin and eosin histology to evaluate their concordance. We then applied SRS imaging on fresh surgical tissues from 45 patients to reveal key diagnostic features, based on which we have constructed a deep learning based model to generate automated histologic results. 18,750 SRS fields of views were used to train and cross-validate our 34-layered residual convolutional neural network, which was used to classify 33 untrained fresh larynx surgical samples into normal and neoplasia. Furthermore, we simulated intraoperative evaluation of resection margins on totally removed larynxes. Results: We demonstrated near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) between SRS and standard histology as evaluated by three pathologists. And deep-learning based SRS correctly classified 33 independent surgical specimens with 100% accuracy. We also demonstrated that our method could identify tissue neoplasia at the simulated resection margins that appear grossly normal with naked eyes. Conclusion: Our results indicated that SRS histology integrated with deep learning algorithm provides potential for delivering rapid intraoperative diagnosis that could aid the surgical management of laryngeal cancer.

High cytoplasm HABP1 expression as a predictor of poor survival and late tumor stage in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Hyaluronan-binding protein 1 (HABP1) overexpression has been confirmed in different malignancies and found to be strongly associated with tumor development and progression. The aim of the present study was to explore the impact of HABP1 in pancreatic ductal adenocarcinoma (PDAC) patients. METHOD: HABP1 expression was evaluated in 89 PDAC specimens. RESULTS: The expression of HABP1 was significantly higher in tumor tissues than that in adjacent normal tissues. High nucleus HABP1 expression and high cytoplasm HABP1 expression were both detected in PDAC tissues. Overall survival analysis by optical density showed that the mean survival was similar between patients with low and high optical density values of HABP1 expression (P = 0.312). The similar result was also found between patients with low-moderate or high nucleus HABP1 expression (P = 0.275). However, the mean survival was significantly poorer in patients with cytoplasm HABP1 overexpression (P < 0.001). High cytoplasm HABP1 expression was strongly correlated with late tumor stages, arterial involvement, lymph node metastasis and carbohydrate antigen 19-9 levels. CONCLUSION: High cytoplasm HABP1 expression may prove to be a predictor of poor survival and late tumor stage in PDAC patients. HABP1 could serve as a promising biomarker to identify subsets of PDAC patients with high malignant clinical behavior.

Antitumor effect of gemcitabine-loaded albumin nanoparticle on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression.

PURPOSE: Gemcitabine is currently the standard first-line chemotherapeutic drug for treating pancreatic cancer. However, many factors can contribute to gemcitabine resistance. One of the most important reasons is the low hENT1 expression. In this study, we tested the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression. MATERIALS AND METHODS: S-(4-nitrobenzyl)-6-thioinosine was utilized to inhibit the activity of hENT1 and simulate low hENT1 expression. Growth inhibition assays and cell cycle and apoptosis analyses were performed on human pancreatic cancer cell lines such as BxPC-3 and SW1990. The in vivo antitumor effect was studied by using patient-derived xenograft (PDX) models. The in vivo toxicity assessment was performed on healthy Kunming mice. RESULTS: In in vitro studies, GEM-HSA-NP showed its ability to inhibit cell proliferation, arrest cell cycle and induce apoptosis when tumor cells were resistant to gemcitabine. In in vivo studies, GEM-HSA-NP was more effective than gemcitabine on inhibiting tumor growth whether the expression levels of hENT1 were high or low in PDX models. The in vivo toxicity assessment showed that the biotoxicity of GEM-HSA-NP did not increase compared with gemcitabine. CONCLUSION: GEM-HSA-NP can overcome gemcitabine resistance induced by low hENT1 expression, which suggests its potential role for the clinical application.

Tumor-Infiltrating Platelets Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Platelets are believed to promote tumor growth and metastasis in several tumor types. The prognostic role of blood platelets in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the prognostic value of tumor-infiltrating platelets (TIPs) remains unknown. METHODS: A total of 303 patients who underwent curative pancreatectomy for PDAC were enrolled from two independent centers in China and divided into three cohorts. Paired preoperative blood samples and surgical specimens from all patients were analyzed. The correlations between patient outcomes and preoperative blood platelet counts and the presence of TIPs, respectively, were analyzed. TIPs were identified by immunohistochemical staining of CD42b. Prognostic accuracy was estimated by concordance index (C-index) and Akaike information criterion (AIC). RESULTS: TIPs, but not preoperative blood platelet counts, were associated with overall survival (OS; all P < 0.001) and recurrence-free survival (RFS; all P < 0.001) in the training, testing, and validation sets. Positive CD42b expression predicted poor postsurgical survival. Incorporation of TIPs improved the predictive accuracy of the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for OS in each of the three cohorts (C-index: 0.7164, 0.7569, and 0.7050, respectively; AIC: 472, 386, and 1019, respectively). The new predictor system was validated by incorporating TIPs with the 7th edition AJCC TNM staging system (C-index: 0.7052, 0.7623, and 0.7157; AIC: 476, 386, and 1015). CONCLUSION: TIPs were an independent prognostic factor that could be incorporated into the AJCC TNM staging system to refine risk stratification and predict surgical outcomes of patients with PDAC.

Dynamic quantitative detection of ABC transporter family promoter methylation by MS-HRM for predicting MDR in pancreatic cancer.

The main focus of the present study was to evaluate whether ABC transporter family promoter methylation predicted multidrug resistance in gemcitabine-resistant cancer cell lines (BxPC-3/Gem and PANC-1/Gem). Using low concentrations of gemcitabine, the cell lines acquired drug resistance with different initial gemcitabine concentrations. A novel technology, methylation-sensitive high-resolution melting, was used to monitor the dynamic changes of ABC transporter family promoter methylation, including ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C (ABCC) and ATP binding cassette subfamily G member 2 (ABCG2) mRNA expression. It was revealed that, with elevation of initial gemcitabine concentration, expression of ABCB1, ABCC and ABCG2 mRNA and corresponding downstream proteins was increased while promoter methylation was decreased. These discoveries indicate that promoter methylation of ABCB1, ABCC and ABCG2 may be a valuable indicator of drug-resistance characteristics in BxPC-3/Gem and PANC-1/Gem cells via quantitative and simultaneous detection. These results also implied that MDR in pancreatic cancer not only arises from gene mutation, but also originates from promoter methylation.

The roles of ID-1 in human pancreatic ductal adenocarcinoma and the therapeutic effects of 2-methoxyestradiol.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rate. Inhibitor of differentiation-1 (ID-1) overexpression has already been reported to be associated with low survival, but the detailed roles of ID-1 in PDAC are unclear. As an ID-1 inhibitor, 2-methoxyestradiol (2-ME) has been shown effective in the antitumor therapies, but its effect on PDAC is unknown. In this study, ID-1 overexpression and knockdown stable SW1990 cells were used to examine proliferation, migration and invasion abilities. Effectiveness of 2-ME was estimated in vivo, as well as in vitro by survival analysis, magnetic resonance imaging and tissue analysis. PDAC patients were retrospectively reviewed to assess the ID-1 expression and prognosis. We found that ID-1 was closely associated with in vitro SW1990 cells proliferation, migration and invasion abilities, as well as the expression of HIF-1α, VEGF and MMP-9. 2-ME was shown to be effective on tumor suppression both in vivo and in vitro, perhaps mainly by ID-1 regulation. Moreover, the relevance between high ID-1 expression and poor prognosis was validated in PDAC patients. Our data collectively reveals the roles of ID-1 in PDAC malignancy, and suggests 2-ME treatment may be a potential alternative chemotherapeutic agent for PDAC patients.

Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA (lncRNA) in Human Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Long noncoding RNAs have been shown to play crucial roles in cancer biology, while the long noncoding RNA landscapes of pancreatic ductal adenocarcinoma have not been completely characterized. We aimed to determine whether long noncoding RNA could serve as early diagnostic biomarkers for pancreatic ductal adenocarcinoma. METHOD: We conducted a genome-wide microarray analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous tissues from 8 Chinese patients. RESULTS: A total of 3352 significantly differentially expressed long noncoding RNAs were detected. Of total, 1249 long noncoding RNAs were upregulated and 2103 were downregulated (fold change ≥2, P < 0.05, FDR <0.05). These differentially expressed long noncoding RNAs were not evenly distributed among chromosomes in human genome. Hierarchical clustering of these differentially expressed long noncoding RNAs revealed large variabilities in long noncoding RNA expression among individual patient, indicating that certain long noncoding RNAs could play a unique role or be used as a biomarker for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-γ-mediated signaling pathway, mitotic cell cycle and proliferation, extracellular matrix receptor interaction, focal adhesion, and regulation of actin cytoskeleton. The co-expression network analysis detected 393 potential interactions between 80 differentially expressed long noncoding RNAs and 105 messenger RNAs. We experimentally verified 7 most markedly dysregulated long noncoding RNAs from the network. CONCLUSION: Our study provided a genome-wide survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA co-regulation networks in pancreatic ductal adenocarcinoma tissue. These dysregulated long noncoding RNA/messenger RNA networks could be used as biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its subtype, predict prognosis, and evaluate treatment efficacy.

Central pancreatectomy with external drainage of monolayer pancreaticojejunostomy for prevention of postoperative pancreatic fistula: A retrospective cohort study.

OBJECTIVE: Postoperative pancreatic fistula (POPF) remains a common problem and leading cause of morbidity and mortality after central pancreatectomy (CP). The aim of this study was to present a technique of external drainage of monolayer pancreaticojejunostomy for prevention of POPF. METHODS: Patients received elective CP with external drainage of monolayer pancreaticojejunostomy between January 2010 and December 2016 were retrospectively analyzed. The occurrence and severity of POPF, overall complications, reoperation rate, in-hospital mortality, and length of postoperative hospital stay were measured. The 2016 updated definition and classification system of the International Study Group of Pancreatic Surgery (ISGPS) was used for POPF. In addition, a matched-pairs comparison with internal drainage of pancreaticojejunostomy was made. RESULTS: 33 consecutive patients underwent CP with external drainage of monolayer pancreaticojejunostomy during this period. 4 (12.1%) cases developed grade B POPF, among which one patient was classified as having Clavien-Dindo classification IIIa complication. None of the patients developed grade C POPF, delayed gastric emptying, or postpancreatectomy hemorrhage. There was no reoperation or in-hospital mortality occurred. Matched-pairs comparison revealed that patients with external drainage of pancreaticojejunostomy had significantly lower incidence of POPF. CONCLUSION: External drainage of monolayer pancreaticojejunostomy seems effective in prevention of POPF after CP.

Portal vein resection and reconstruction with artificial blood vessels is safe and feasible for pancreatic ductal adenocarcinoma patients with portal vein involvement: Chinese center experience.

Evidence shows that portal vein resection (PVR) increase the resectability but does little benefit to overall survival in all pancreatic ductal adenocarcinoma (PDAC) patients. But for patients with portal vein involvement, PVR is the only radical choice. But whether the PDAC patients with portal vein involvement would benefit from radical pancreaticoduodenectomy with PVR or not is controversial. All 204 PDAC patients with portal vein involvement were enrolled in this study [PVR group, n=106; surgical bypass (SB) group, n=52; chemotherapy group, n=46]. Overall survival and prognostic factors were analyzed among three groups. Moreover, a literature review of 13 studies were also conducted. Among 3 groups, patients in PVR group achieved a significant longer survival (median survival: PVR group, 22.83 months; SB group, 7.26 months; chemotherapy group, 10.64 months). Therapy choice [hazard ratio (HR) =1.593, 95% confidence interval (CI) 1.323 to 1.918, P<0.001], body mass index (HR=0.772, 95% CI 0.559 to 0.994, P=0.044) and carbohydrateantigen 19-9 (HR=1.325, 95% CI 1.064 to 1.651, P=0.012) were independent prognostic factors which significantly affected overall survival. Pancreaticoduodenectomy combined with PVR and reconstruct with artificial blood vessels is a safe and an appropriate therapy choice for resectable PDAC patients with portal vein involvement.

Novel and supplementary management of pancreatic fluid collections: Endoscopic ultrasound-guided drainage.

AIM: To compare efficacy and safety of endoscopic ultrasound (EUS)-guided and surgical drainage in pancreatic fluid collection management. METHODS: Data were obtained retrospectively from January 2012 to December 2016. Patients with pancreatic fluid collection were performed EUS-guided or surgical procedure. Main outcome measures including clinical efficiency, complication, duration of procedures, hospital stay and cost were analyzed. RESULTS: Thirty-six patients were enrolled into the study, including 14 in endoscopic group while 22 in the surgical group. Twelve (86%) patients were treated successfully by endoscopic approach while 21 (95%) patients benefited through surgical procedure. Endoscopic treatment had higher recurrence and complication rates than surgery, resulting in more re-interventions. Meanwhile, duration of procedure, hospital stay and cost were significantly lower in endoscopic group. CONCLUSION: Both approaches were effective and safe. EUS-guided approach should be the first-line treatment in mild and simple cases, while surgical approach should be considered as priority in severe and complex cases.

Radical resection and enucleation in Chinese adolescents with pancreatic tumors: A 15-year case series.

Pancreatic tumors rarely occur in adolescents, and the appropriateness of radical resection for these patients remains controversial.Medical records were retrospectively reviewed for patients younger than 19 years who underwent radical resection or limited resection (enucleation) between 2000 and 2015. Patient demographics, clinical characteristics, operative details, growth, and survival were analyzed.During the study period, 11 adolescents (mean age, 16.18 years; standard deviation, 1.99; interquartile range, 15.0-18.0) underwent radical resection (n = 7) or enucleation (n = 4) to treat solid pseudopapillary tumors (n = 5), pancreatic neuroendocrine tumors (n = 5), or pancreatic ductal adenocarcinoma (n = 1). None of the 7 patients who underwent radical resection experienced recurrence or serious complications, while 3 of 4 patients who underwent enucleation experienced recurrence (P = 0.02). Recurrence-free survival was slightly longer in patients who underwent radical resection, and this procedure did not appear to affect adolescent growth and development.Radical resection might be safe and effective for adolescents with pancreatic tumors.

Circulating tumor cells in pancreatic cancer patients: efficacy in diagnosis and value in prognosis.

Detection of circulating tumor cells (CTCs) has become widely used as a liquid biopsy for many patients. In pancreatic cancer patients, there have been a number of published reports on the efficacy of CTCs in the diagnosis and prognosis of pancreatic cancer, and in the evaluation of response to treatment. We systematically reviewed the diagnosis efficiency and prognostic value of CTCs reported in the literature. We found that the frequency of CTCs is rare, limited to a certain degree by the current enrichment and detection methodologies. The sensitivity of CTCs for diagnosis is variable likely due to the different stages of the disease at the time of diagnosis (varied from 25.0% to 100.0%) but specificity remained relatively high (varied from 99.7% to 100.0%). However, pooled results from meta-analyses (patients with CTC positivity had worse overall survival than patients with CTC negativity) demonstrated that CTCs could be used as an effective tool in the prognosis prediction in pancreatic cancer patients.

Application of Deuteporfin in the Metastatic Lymph Node Mapping of Pancreatic Cancer: An in vivo Study.

For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P < 0.05). Our research confirmed this targeting property of deuteporfin using in vivo fluorescent imaging. Consistent with observations from in vivo imaging experiments, frozen sections of metastatic lymph nodes intuitively displayed significantly higher and wider distributions of deuteporfin than normal sections.