The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies.

PURPOSE: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach. METHODS: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs). RESULTS: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity. CONCLUSION: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

Chemotherapy-induced early transient increase and surge of CA 19-9 level in patients with pancreatic Adenocarcinoma✰.

This study aimed to characterize chemotherapy-induced transient increase and surge of CA 19-9 level to treatment response in patients with advanced pancreatic ductal adenocarcinoma (PDAC). A retrospective case series was performed of advanced PDAC patients treated with first-line chemotherapy at City of Hope Comprehensive Cancer Center from Jan 2017 to May 2020. CA 19-9 surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CA 19-9 levels compared to baseline. Out of 106 advanced PDAC patients, 38 were evaluable for CA 19-9 surge. Fourteen (51.9%) patients treated with FOLFIRINOX and 3 (27.3%) patients treated with nab-P + Gem chemotherapy demonstrated an early transient rise in CA 19-9 level. A CA 19-9 surge was documented in 9 (23.7%) patients, all with duration of surge lasting < 16 weeks. Five out of 9 (55.6%) patients (4: FOLFIRINOX, 1: nab-P + Gem) with CA 19-9 surge demonstrated partial objective response rate on surveillance cross-sectional imaging. One patient (FOLFIRINOX) had stable disease, and 2 patients (1: FOLFIRINOX, 1: nab-P + Gem) were found to have disease progression after treatment interruption. The initial early rise of CA 19-9 levels during chemotherapy in patients with advanced PDAC may not indicate tumor progression. Rather, it may represent a chemotherapy-induced transient increase or surge phenomenon of the tumor marker in patients responding to treatment.

Tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding neuropeptides via Lgr3/8 in the brain.

In patients with advanced-stage cancer, cancer-associated anorexia affects treatment success and patient survival. However, the underlying mechanism is poorly understood. Here, we show that Dilp8, a Drosophila homologue of mammalian insulin-like 3 peptide (INSL3), is secreted from tumour tissues and induces anorexia through the Lgr3 receptor in the brain. Activated Dilp8-Lgr3 signalling upregulated anorexigenic nucleobinding 1 (NUCB1) and downregulated orexigenic short neuropeptide F (sNPF) and NPF expression in the brain. In the cancer condition, the protein expression of Lgr3 and NUCB1 was significantly upregulated in neurons expressing sNPF and NPF. INSL3 levels were increased in tumour-implanted mice and INSL3-treated mouse hypothalamic cells showed Nucb2 upregulation and Npy downregulation. Food consumption was significantly reduced in intracerebrospinal INSL3-injected mice. In patients with pancreatic cancer, higher serum INSL3 levels increased anorexia. These results indicate that tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding hormones through the Lgr3/Lgr8 receptor in Drosophila and mammals.

Pre-treatment serum vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancer.

BACKGROUND: Vitamin D deficiency and inflammation are associated with increased mortality. We investigated the relationship between pre-treatment serum vitamin D levels, inflammatory biomarkers (IL-6, YKL-40 and CRP) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Pre-treatment serum vitamin D, IL-6, YKL-40 and CRP levels were determined in 1,267 patients with PDAC enrolled from July 2008 to September 2018 in the prospective BIOPAC study (NCT03311776). The patients were grouped according to vitamin D levels: sufficient >50 nmol/L, insufficient 25-50 nmol/L and deficient <25 nmol/L. RESULTS: Across all tumour stages, vitamin D-deficient patients had the highest median levels of IL-6 (8.3 pg/mL, range 0.7-91), YKL-40 (177 ng/ml, range 25-5279) and CRP (15.5 mg/L, range 0.8-384). The resected stage I and II patients with vitamin D deficiencies had a shorter median OS, 18.3 months (95% CI, 12.1-31.5 months) than those with sufficient levels, 29.7 months (95% CI, 22.3-36.1 months), and the hazard ratio for death was 1.55 (95% CI, 1.04-2.31; p = 0.03). In advanced PDAC, there was no significant difference in OS between the vitamin D groups. CONCLUSIONS: Vitamin D deficiency was associated with increased inflammatory biomarkers in all PDAC stages. The resected stage I and II patients with sufficient vitamin D levels had a higher OS than those with a vitamin D deficiency. However, there was no correlation between vitamin D levels and survival in advanced PDAC. Future studies need to investigate vitamin D supplementation effects on survival in PDAC.

Neutrophil-lymphocyte ratio (NLR) was associated with prognosis and immunomodulatory in patients with pancreatic ductal adenocarcinoma (PDAC).

Although the oncological outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) have markedly improved over the past decade, the survival prediction is still challenging. The aim of this study was to investigate the prognostic value of neutrophil-lymphocyte ratio (NLR) and analyze the relationship of between the NLR and immune cells phenotypes in patients with PDAC. Sixty-seven consecutive patients with PDAC were recruited in this study. Life-table estimates of survival time were calculated according to the Kaplan and Meier methodology. The phenotypic T cells subclasses were evaluated by flow cytometry. All the 67 patients in this study were treated with surgical resection and among them, 46 patients received adjuvant chemotherapy. Receiver operating characteristic (ROC) curves analysis was performed to compare prognostic value of NLR with CA199. We found that the Harrell's area under ROC (AUROC) for the NLR to predict overall survival (OS) (0.840; 95% CI, 0.766-0.898) was significantly higher than that of the CA199 levels. After that we stratified all patients into NLR > 2.5 (n = 42) and NLR ≤ 2.5 (n = 25) groups according to the OS of patients with PDAC. Survival analysis showed that patients with NLR ≤ 2.5 had significantly favorable OS and progressive free survival (PFS) compared with patients with NLR > 2.5. The CD3+ and CD8+/CD28+ T cell subsets were significantly increased in patients with NLR ≤ 2.5 (P<0.05), while the CD8+/CD28- and CD4+/CD25+ cell subsets were significantly decreased in patients with NLR ≤ 2.5 (P<0.05). In conclusion, a high NLR value independently predicts poor survival in patients with PDAC after surgical resection. The NLR was closely related with immune cells phenotypes The NLR may help oncologists evaluate outcomes of patients received surgical resection and chemotherapy to choose alternative therapies for patients with high NLR value.

Prolonged time to treatment initiation in advanced pancreatic cancer patients has no major effect on treatment outcome: a retrospective cohort study controlled for lead time bias and waiting time paradox.

PURPOSE: A prolonged time to treatment initiation (TTI) correlates with an adverse prognosis in different cancer types including resectable pancreatic cancer (PC). Only limited evidence on the correlation between TTI and prognosis in advanced PC exists. METHODS: Consecutive PC patients (n = 368) who were diagnosed or treated at our high-volume comprehensive cancer center were included in a prospectively maintained database. We retrospectively analyzed time from first imaging showing advanced PC to initiation of palliative first-line chemotherapy. Lead time bias and waiting time paradox were addressed by landmark analysis and correlation of tumor burden with TTI. RESULTS: Two hundred and ninety-seven patients met the pre-specified in- and exclusion criteria of our study. Median TTI was 29 days (range: 1-124 days). Most common reasons for prolonged TTI (> 21 days) were referral from an external treatment center (39%) and a second biopsy (31%). A TTI above the median-, 75th or 90th percentile (43 or 60 days, respectively) had no impact on overall survival. Furthermore, no correlation between levels of carbohydrate antigen 19-9 (CA 19-9) at time of treatment initiation and TTI was observed. CONCLUSION: While a timely work-up of advanced PC patients remains important, delays in treatment initiation due to repeated biopsies, inclusion in a clinical study or transfer to a specialized cancer center appear to be justified in light of the absence of a strong adverse effect of prolonged TTI on prognosis in advanced PC patients.

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients.

We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites.

Serum selenium and pancreatic cancer: a prospective study in the Prostate, Lung, Colorectal and Ovarian Cancer Trial cohort.

PURPOSE: Pancreatic cancer(PCa) is one of the most lethal cancers with few known consistent nutrition-related risk factors. Epidemiologic associations between the trace element selenium and PCa are inconsistent. This study examined the association of pre-diagnostic serum selenium with incident PCa. METHODS: We conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Study (PLCO) cohort of men and women 55-70 years old at baseline (1993-2001). In total, 303 PCa cases developed during the 17-year follow-up period (1993-2009). We selected two controls (n = 606) for each case who were alive at the time the case was diagnosed who were matched on age, sex, race, and date of blood draw. We used conditional logistic regression analysis to calculate the odds ratio (OR) and 95% confidence intervals (CI) adjusting for smoking status and diabetes mellitus. RESULTS: Mean serum selenium concentrations were slightly lower in cases (mean, 95% CI: 139.0 ng/ml, 135.6-138.9) compared to controls (142.5 ng/ml, 140.4-142.4, p = 0.08). Overall, serum selenium was not associated with PCa risk (continuous OR: 0.66; 0.32-1.37). There was no significant interaction by sex, smoking, diabetes, or follow-up time (p > 0.05). CONCLUSION: Our results do not support the hypothesis that serum selenium is associated with PCa risk.

Selecting chemotherapy for pancreatic cancer: Far away or so close?

Pancreatic cancer is a lethal disease with a very poor prognosis. In contrast to treatments for many other tumor types, cytotoxic agents are still the first-line drugs for pancreatic cancer in both the palliative and adjuvant settings. Some progress has been made in recent years, but most large phase 3 studies have not shown significant improvements in survival. Because the available drugs and regimens are limited in both type and effect, the selection of chemotherapy based on clinicopathologic characteristics may be consequential for pancreatic cancer. In the present report, we focused on 7 landmark clinical trials for pancreatic cancer. We observed that FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) and NG (nab-paclitaxel and gemcitabine), 2 first-line regimens, exerted opposite effects on metastatic pancreatic cancer patients with different baseline carbohydrate antigen 19-9 (CA19-9) levels. This suggested that not only the performance status but possibly also CA19-9 levels should be considered when making a therapeutic choice for patients with advanced pancreatic cancer. Moreover, we found that patients with a diagnosis of pancreatic cancer who have undergone a surgical resection with a negative margin (R0) may benefit more from fluorouracil and/or oral prodrugs of fluorouracil-based adjuvant therapy than from gemcitabine. Conversely, gemcitabine or gemcitabine-based regimens may be more effective for patients with a positive resection margin (R1). Based on these findings, we propose flowcharts for selecting chemotherapy for both advanced and resected pancreatic cancer. Furthermore, we present possible mechanisms and interpretations underlying the selection of chemotherapy for pancreatic cancer and propose the tumor burden as a key variable in this process. Regardless of the possible bias and exact treatment selection process, this study offers an opportunity to improve patient outcomes by using agents currently used in the therapy of pancreatic cancer. Although these conclusions are based on indirect evidence, we provide insights and possibilities to drive the selection of chemotherapy for pancreatic cancer.

New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that "CA19-9 will be undetectable in Lewis antigen-negative individuals". However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status. METHODS: Patients with pancreatic cancer (1482 cases) were retrieved from a prospectively maintained database. Patients with benign pancreatic disease (210 cases) and normal subjects (315 cases) were used as controls. Lewis genotypes were examined by fucosyltransferase 3 (FUT3) sequencing. RESULTS: In patients with pancreatic cancer, 8.4% of subjects were Lewis (-), but only 41.9% of Lewis (-) subjects had CA19-9 values ≤ 2 U/mL. CA19-9 was even elevated (>37 U/mL) in 27.4% of Lewis (-) patients. The area under the receiver operating characteristic (ROC) curve for CA19-9 as a diagnostic biomarker was 0.842 in Lewis (-) patients with pancreatic cancer, which is closing to that of CA19-9 applied in all of patients with pancreatic cancer (0.898). Lewis (-) status was an independent prognostic factor for shorter survival in a multivariable analysis (hazard ratio (HR), 1.30, 95% confidence interval (CI), 1.03-1.64; P = 0.028). CONCLUSIONS: Not all Lewis (-) patients with pancreatic cancer are non-secretors of CA19-9. Contrary to general understanding, CA19-9 can retain its utility as a biomarker in these patients in spite of Lewis (-) genotype.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Treatment of pancreatic cancer with intravenous vitamin C: a case report.

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is often discovered at an advanced stage with few therapeutic options. Current conventional regimens for PDA are associated with significant morbidity, decreased quality of life, and a considerable financial burden. As a result, some patients turn to integrative medicine therapies as an alternate option after a diagnosis of PDA. Intravenous pharmacologic ascorbic acid (PAA) is one such treatment. The use of PAA has been passionately debated for many years, but more recent rigorous scientific research has shown that there are significant blood concentration differences when ascorbic acid is given parenterally when compared to oral dosing. This pharmacologic difference appears to be critical for its role in oncology. Here, we report the use of PAA in a patient with poorly differentiated stage IV PDA as an exclusive chemotherapeutic regimen. The patient survived nearly 4 years after diagnosis, with PAA as his sole treatment, and he achieved objective regression of his disease. He died from sepsis and organ failure from a bowel perforation event. This case illustrates the possibility of PAA to effectively control tumor progression and serve as an adjunct to standard of care PDA chemotherapy regimens. Our patient's experience with PAA should be taken into consideration, along with previous research in cell, animal, and clinical experiments to design future treatment trials.

Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic cancer.

To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure-sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.

Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.

Novel TREM-1 Inhibitors Attenuate Tumor Growth and Prolong Survival in Experimental Pancreatic Cancer.

Pancreatic cancer (PC) is a highly lethal cancer with an urgent need to expand the limited treatment options for patients. Tumor-associated macrophages (TAMs) promote tumor aggressiveness and metastasis. High expression of triggering receptor expressed on myeloid cells 1 (TREM-1) on TAMs directly correlates with poor survival in patients with non-small cell lung cancer (NSCLC). We have previously hypothesized that blockade of TREM-1 could be a promising therapeutic strategy to treat cancer and shown that the novel, ligand-independent TREM-1 inhibitory peptides rationally designed using the signaling chain homooligomerization (SCHOOL) strategy suppress NSCLC growth in vivo. Here, we evaluated the therapeutic potential of these inhibitors in three human PC xenograft mouse models. Administration of SCHOOL peptides resulted in a strong antitumor effect achieving an optimal treatment/control (T/C) value of 19% depending on the xenograft and formulation used and persisting even after treatment was halted. The effect correlated significantly with increased survival and suppressed TAM infiltration. The peptides were well-tolerated when deployed either in free form or formulated into lipopeptide complexes for peptide half-life extension and targeted delivery. Finally, blockade of TREM-1 significantly reduced serum levels of interleukin (IL)-1α, IL-6, and macrophage colony-stimulating factor (M-CSF), but not vascular endothelial growth factor, suggesting M-CSF-dependent antitumor mechanisms. Collectively, these promising data suggest that SCHOOL TREM-1-specific peptide inhibitors have a cancer type independent, therapeutically beneficial antitumor activity and can be potentially used as a stand-alone therapy or as a component of combinational therapy for PC, NSCLC, and other solid tumors.

Necessity for autologous blood storage and transfusion in patients undergoing pancreatoduodenectomy.

PURPOSE: To establish which patients undergoing pancreaticoduodenectomy (PD) need autologous blood storage and transfusion. METHODS: Autologous blood was collected and stored for 69 patients scheduled to undergo PD, and not used in 50 patients. Based on the use of the deposited autologous blood and the estimated postoperative hemoglobin (Hb) level when blood was not deposited, we divided the patients into a "transfusion necessary" group and a "transfusion unnecessary" group. By comparing the two groups, we proposed a method of scoring to predict the necessity for storing autologous blood. RESULTS: The "transfusion necessary" group comprised 6 patients (2 who received homologous blood transfusion and 4 with an estimated postoperative Hb of <8.0 g/dL) and the "transfusion unnecessary" group comprised 63 patients (24 whose autologous blood was discarded and 39 with an estimated Hb ≥8.0 g/dL). By analyzing the differences between the groups, including the preoperative hemoglobin level and the need for portal vein resection, we devised a scoring system to predict the necessity of collecting autologous blood. The scoring significantly correlated with the proportion of patients who did not require autologous blood storage and transfusion. CONCLUSIONS: Not all patients benefited from autologous blood storage and transfusion. Our scoring system proved useful for identifying which patients required autologous blood storage and transfusion during PD.

Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9.

PURPOSE: The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body. METHODS: The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea. RESULTS: About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19-9 in all individuals was ranged 69-105 U/ml. CONCLUSIONS: Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined.

Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer.

BACKGROUND: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. METHODS: The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. RESULTS: Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity. CONCLUSIONS: Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.

CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer.

BACKGROUND: Compared to the widely adopted 2-4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival. METHODS: Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992-2014 were reviewed. RESULTS: After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P = 0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P = 0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P = 0.930). CONCLUSIONS: Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.