Induction chemotherapy in pancreatic cancer: CA 19-9 may predict resectability and survival

BackgroundPreoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, ∼40% of patients cannot be resected after NT and reliable preoperative response evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival.MethodsWe screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed.ResultsOf 318 patients 165 (51.9%) were resected and 153 (48.1%) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 U/ml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692–0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 U/ml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients.DiscussionCA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.     

Specific increase in serum core-fucosylated haptoglobin in patients with chronic pancreatitis

Background/ObjectivesPancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancreatic exocrine cell atrophy. We recently found that inflammation and fibrosis are independent characteristic histological changes in noncancerous lesions in PDAC patients despite the absence of a past history of clinical CP. Subclinical CP is an important background for PDAC occurrence. Therefore, there is an urgent need to develop a noninvasive and reliable biomarker for CP diagnosis.MethodsFifty-nine healthy volunteers (HV), 159 patients with CP, and 83 patients with PDAC were enrolled in this study. We measured serum total fucosylated haptoglobin (Fuc-Hpt) and core-Fuc-Hpt levels using lectin-antibody enzyme-linked immunosorbent assay kits that we developed. In these kits, total Fuc-Hpt and core-Fuc-Hpt were measured using Aleuria aurantia lectin and Pholiota squarrosa lectin, respectively.ResultsSerum Fuc-Hpt levels were significantly increased in CP patients compared to HV (P < 0.0001) and were further increased in PDAC patients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Multivariate analyses demonstrated that total serum core-Fuc-Hpt was an independent determinant for CP diagnosis, but Fuc-Hpt was not.ConclusionsA dramatic change in oligosaccharides was observed in serum haptoglobin between CP and PDAC. Serum core-Fuc-Hpt may be a novel and useful biomarker for CP diagnosis.     

Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma

BackgroundWisteria floribunda agglutinin-positive mac-2 binding protein (WFA⁺-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA⁺-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis.MethodsIn this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA⁺-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA⁺-M2BP, we investigated the presence of WFA⁺-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray.ResultsWe found that the serum WFA⁺-M2BP level could distinguish the 2 groups. The median serum COI of WFA⁺-M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA⁺-M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA⁺-M2BP negative PDACs (91.6% vs. 41.7%, P = 0.009). The MDA-PATC53 cells alone produced WFA⁺-M2BP. However, we found that MDA-PATC53 supernatant containing WFA⁺-M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1.ConclusionsSerum WFA⁺-M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro-oncologic glycosylation enzymes.     

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study

BackgroundThe aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.MethodsData were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.ResultsCompared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069–1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032–1.736; p = 0.0277). High carbohydrate antigen 19–9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261–2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199–1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).ConclusionsOur large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.     

Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: A retrospective cohort study

BackgroundCarbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC.MethodsA total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL.ResultsMedian RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p < 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p < 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was >1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value.ConclusionsThe present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.     

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis

BackgroundChronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP.MethodsA pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I–III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method.ResultsThe cytokines CTACK, GRO-α, and β-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738–0.880), compared with 0.791 (95% CI 0.728–0.854) for CA19-9 alone (not significant).ConclusionsWe found that inflammatory cytokines CTACK, GRO-α, and β-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.     

Survival impact of occult liver metastasis and peritoneal dissemination compared with radiologically defined distant organ metastasis in pancreatic ductal adenocarcinoma

BackgroundCharacteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported.ObjectiveWe aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM.MethodsThis single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images.ResultsOM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19–9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590).ConclusionThe prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.     

Cell-free DNA promoter hypermethylation as a diagnostic marker for pancreatic ductal adenocarcinoma – An external validation study

BackgroundWe recently identified a diagnostic prediction model based on promoter hypermethylation of eight selected genes in plasma cell-free (cf) DNA, which showed promising results as a diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to validate this biomarker profile in an external patient cohort and examine any additional effect of serum CA 19-9.MethodsPatients with PDAC (n = 346, stage I-IV) and chronic pancreatitis (n = 25) were included. Methylation-specific PCR of a 28-gene panel was performed on serum cfDNA samples. The previously developed diagnostic prediction model (age>65 years, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) was validated alone and in combination with serum CA 19-9 in this external patient cohort.ResultsPatients with PDAC had a higher number of hypermethylated genes (mean 8.11, 95% CI 7.70–8.52) than patients with chronic pancreatitis (mean 5.60, 95% CI 4.42–6.78, p = 0.011). Validation of the diagnostic prediction model yielded an AUC of 0.77 (95% CI 0.69–0.84). The combination of serum CA 19-9 and our test had an AUC of 0.93 (95% CI 0.89–0.96) in the primary study and 0.85 (95% CI 0.79–0.91) in the validation study.ConclusionIn this validation study, PDAC was associated with a higher number of hypermethylated genes in serum cfDNA than chronic pancreatitis. Our diagnostic test was superior to the predictive value of serum CA 19-9 alone in both the primary and the validation study. The combination of our test with CA 19-9 may serve as a clinically useful diagnostic biomarker for PDAC.     

Comparison of platelet-lymphocyte ratio and CA 19-9 in differentiating benign from malignant head masses in patients with chronic pancreatitis

Introduction

Pancreatic head ductal adenocarcinoma (PDAC) and inflammatory head masses (IHM) related to chronic pancreatitis are often difficult to differentiate. PDAC produces significant inflammatory response with resultant lymphopenia and thrombocytosis. The prognostic role of platelet-lymphocyte ratio (PLR) as a tumor marker has been defined. We aimed to find the role of PLR as a diagnostic marker for PDAC in differentiating benign head mass comparing with carbohydrate antigen 19-9 (CA 19-9).

Methods

A prospective study of patients with biopsy-proven PDAC and benign IHM with underlying chronic pancreatitis from 1st November 2014 to 30th June 2016 was performed. Total blood count including platelet count and CA 19-9 were recorded and statistically analyzed.

Results

There was no significant difference in total leukocyte counts (7789±2027 vs. 7568±1289 cells/mm³) between PDAC (n = 34) and IHM (n = 27). However, the mean lymphocyte (2235±837 vs. 2701±631 cells/mm³) and platelet counts in mm³ (3.36±0.789) × 10⁵ vs. (2.45±0.598) × 10⁵ showed difference. The median PLR was 161.9 (IQR = 117.5–205.6) in PDAC and 91 (IQR = 77.2–106.6) in IHM. The median CA 19-9 (U/mL) in PDAC and IHM was 69.3 (IQR = 22.7–427.7) and 13.9 (IQR = 7.2–23.6), respectively. On plotting the receiver operator characteristic curve (ROC curve), area under the curve was maximum for PLR (88.7%) compared to CA 19-9 (77.8%) in diagnosing PDAC (p<0.0001). Using coordinates of ROC, PLR cutoff value was 113.5 (sensitivity—79.4%, specificity—92.6%, positive predictive value (PPV)—91.5%, negative predictive value (NPV)—99.7%) while CA 19-9 cutoff value was 25.3 U/mL (sensitivity—73.5%, specificity—77.8%, PPV—78.5%, NPV—74.6%).

Conclusion

PLR may be useful to differentiate PDAC from benign IHM in patients with chronic pancreatitis.

     

Prognostic impact of the ratio of preoperative CA19-9 to liver enzyme levels in pancreatic cancer patients with jaundice (predictability of combined CA19-9/AST and CA19-9/γ-GGT for jaundiced PDAC patients)

BackgroundCarbohydrate antigen 19–9 (CA19-9) has been reported as the most significant survival predictor of patients with pancreatic ductal adenocarcinoma (PDAC). However, the elevation of CA19-9 could interfere with obstructive jaundice and the predictive value of CA19-9 in PDAC patients with jaundice remains to be analyzed and elucidated to find possible adjustments.ObjectiveTo evaluate the predictability of preoperative CA19-9 and its adjustments for the overall survival (OS) of PDAC patients by analyzing the relationship between preoperative serum CA19-9 and total bilirubin (TBIL).MethodsA total of 563 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma in our center between January 2015 and September 2018 were retrospectively reviewed. Clinicopathologic information was collected and preoperative parameters such as CA19-9, CEA, TBIL, γ-GGT, AST, ALT, and ALP were recorded as well as overall survival rates, which began from the date of operation to that of death or the last follow-up. Kaplan-Meier survival curves with log-rank test and Cox regression models were applied using SPSS and the survival and survminer packages in R software.ResultsUsing 39/390/1000 as the cut-off values for preoperative serum CA19-9, significant capability of OS stratification was found in the total cohort (p < 0.001, MST = 29.7/19.1/15.2/12.1 months) and patients with TBIL <102.6 μmol/L (p < 0.001, MST = 32.2/19.6/15.0/11.2 months). However, in the subgroup of TBIL≥102.6 μmol/L, this classification method was replaced by the combined scoring of CA19-9/AST and CA19-9/γ-GGT.ConclusionsAs an independent predictor of overall survival of PDAC patients, preoperative serum CA19-9 is defective in survival stratification when TBIL≥102.6 μmol/L but a positive survival prognosis could be achieved with the application of combined preoperative CA19-9/AST and CA19-9/γ-GGT.     

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma

Background/Objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).MethodsNinety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.ResultsThe low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19–9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.ConclusionsLow mitochondrial OGG1 expression might aggravate the PDAC prognosis.     

Shear-wave versus strain elastography in endoscopic ultrasound for the diagnosis of chronic pancreatitis

Background/Objectives: Endoscopic ultrasound (EUS) elastography is a non-invasive diagnostic method for evaluating tissue elasticity. The aims of this study were to compare shear-wave elastography (SWE) and conventional strain elastography (SE) in determination of the diagnosis and degree of chronic pancreatitis (CP).MethodsForty-nine patients who underwent computed tomography (CT), EUS-SWE, EUS-SE, and pancreatic exocrine function testing between January 2019 and January 2022 were prospectively evaluated. CP was diagnosed according to Japan Pancreatic Society criteria (JPSC) 2019, Rosemont criteria (RC), CT findings, and pancreatic exocrine dysfunction. The cut-off values, sensitivity, and specificity for CP diagnosed according to the four criteria were calculated for EUS-SWE and EUS-SE. Relationships between values measured by either of the EUS elastography methods and the number of EUS features were also assessed.ResultsEUS-SWE values were positively correlated with the severity grades of RC and JPSC, but EUS-SE values were not. EUS-SWE was significantly better than EUS-SE for diagnosing CP defined according to CT findings (area under the receiver operating characteristics curve [AUROC]: 0.77 vs. 0.61, P < 0.001), RC (AUROC: 0.85 vs. 0.56, P < 0.001), JPSC 2019 (AUROC: 0.83 vs. 0.53, P < 0.001), and exocrine dysfunction (AUROC: 0.78 vs. 0.61, P < 0.001). EUS-SWE values were positively correlated with the number of EUS features, but EUS-SE values were not.ConclusionsEUS-SWE provides objective assessment for diagnosing and assessing the degree of CP defined according to the criteria of CT findings, RC, JPSC, or exocrine dysfunction, and it can be considered a non-invasive diagnostic tool for CP and exocrine dysfunction.     

Invasive IPMN relapse later and more often in lungs in comparison to pancreatic ductal adenocarcinoma

BackgroundThe different oncological outcomes of invasive intraductal papillary mucinous neoplasm (I-IPMN) and pancreatic ductal adenocarcinoma (PDAC) are debated. This study aimed to compare disease recurrence patterns and histopathological characteristics in patients with resected I-IPMN and PDAC.MethodsConsecutive patients undergoing surgical resection for stage I-III I-IPMN or PDAC between 2010 and 2016 were retrospectively analyzed. Patients treated with neoadjuvant therapy or resected for Tis neoplasia were excluded. All surgical specimens were re-staged according to AJCC-8th-edition.ResultsA total of 330 patients were included, of whom 43 had I-IPMN and 287 had PDAC. Median follow-up time was 26.7 (1.3–92.3) months and estimated median disease-free survival (DFS) was 60.3 months (47.2–73.4) for I-IPMN and 23.8 (19.3–28.2) months for PDAC (p < 0.001). During follow-up, 32.6% of I-IPMN and 67.9% of PDAC patients experienced recurrence (p < 0.001). The sites of first recurrence were the lungs (38.5% vs 13.1%, p = 0.027), liver (28.6% vs 45.0%, p = 0.180) and local (15.4% vs 36.6%, p = 0.101) for I-IPMN and PDAC, respectively. At multivariate analysis, I-IPMN histology remained an independent predictive factor for longer DFS (OR 0.528, CI 95% 0.278–1.000, p = 0.050), regardless of stage or adjuvant chemotherapy. I-IPMN and PDAC differed in rates of neuroinvasion (51.2% vs 97.2%) and positive lymph node status (N+) (46.5% vs 82.7%), especially in patients with lower T status.ConclusionI-IPMN showed a different recurrence pattern compared to PDAC, with a higher lung tropism, and longer DFS. This different biological behavior is associated with lower rates of neuroinvasion and nodal involvement, especially in early-stage disease.     

Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.

BackgroundAcute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection.AimWe performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak.Material and MethodsSystematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I² statistic.ResultsWe analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9–21.3%, I²=95.0%, p<0.0001) and 23.4% (95% CI:16.7–31.8%, I2=88.7%, p<0.0001), respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35.3% of patients with COVID-19 infection across six studies.ConclusionsThe in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients compared to those hospitalized in general wards. CTPA was rarely used suggesting a potential underestimation of PE cases.     

Close Association of Matrix Metalloproteinase-9 Levels With the Presence of Thin-Cap Fibroatheroma in Acute Coronary Syndrome Patients: Assessment by Optical Coherence Tomography and Intravascular Ultrasonography

BackgroundThin-cap fibroatheroma (TCFA) has been suggested as a precursor lesion of coronary plaque rupture. As elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been documented in patients with acute coronary syndrome (ACS), we sought to determine whether the presence of TCFA is linked to MMP-9 levels in these patients.MethodsWe evaluated 51 ACS patients with de novo culprit lesions who were examined via optical coherence tomography and intravascular ultrasound. Blood samples were obtained from the peripheral vein (PV) and the ostium and culprit lesion of the infarct-related coronary artery (CA) in the acute phase of ACS and from the PV in the chronic phase (8 months after ACS).ResultsThe plasma MMP-9 level in the acute phase was significantly higher than that in the chronic phase. Plasma MMP-9 levels at the culprit lesion of the infarct-related CA were significantly higher than, but positively correlated with those in the PV (10.9 (5.9–16.1) ng/mL and 8.9 (5.6–13.0) ng/mL, p < 0.0001, respectively; Spearman ρ = 0.84, p < 0.0001). Significantly higher PV plasma MMP-9 levels were observed in patients with TCFA than in patients without TCFA (12.1 (7.0–13.5) and 5.7 (4.0–8.2) ng/ml, p<0.0001, respectively). Further, plasma MMP-9 levels in the PV were positively correlated with the remodeling index (Spearman ρ = 0.29, p = 0.039) and negatively correlated with fibrous cap thickness (Spearman ρ = −0.42, p = 0.0021). Receiver operating characteristic curve analysis showed that the plasma MMP-9 levels in the PV could predict the presence of TCFA at a cut-off value of 9.9 ng/mL.ConclusionsPlasma MMP-9 levels were closely associated with MMP-9 levels in the CA and were further linked with TCFA in patients with ACS.     

CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts

BackgroundAlthough carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring.MethodsThis was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort.ResultsA total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14–0.44).ConclusionsA CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.     

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma

BackgroundThis study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy.MethodsIncluded were patients who underwent PDAC resection (2014–2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection.Results836 patients with a median follow-up of 37 (interquartile range [IQR] 30–48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3–6 months and 226 patients (27%) within 6–12 months. LogCA 19–9 (OR 1.25 [95% CI 1.10–1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01–0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19–9 (OR 1.23 [95% CI 1.10–1.38]; P < 0.001) and 0–90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60–5.37]; P < 0.001) were associated with recurrence within 3–6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09–2.16]; P = 0.02) and logCA 19–9 (OR 1.24 [95% CI 1.14–1.35]; P < 0.001) were related to recurrence within 6–12 months.ConclusionThis study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.     

The sixth nationwide epidemiological survey of chronic pancreatitis in Japan

ObjectivesA nationwide survey was conducted to clarify the epidemiological features of patients with chronic pancreatitis (CP) in Japan.MethodsTwo sequential surveys were conducted. In the first survey, both the prevalence and incidence of CP in Japan in 2007 were estimated by a questionnaire, which was mailed to 3027 randomly chosen Japanese facilities. In the second survey, the second questionnaire was then mailed to 1110 facilities selected by the first survey to clarify the clinicoepidemiological features of the patients.ResultsThe estimated annual prevalence of CP was 36.9 per 100,000; 53.2 in males and 21.2 in females. The estimated annual incidence was 11.9 per 100,000. The prevalence and the incidence of CP gradually increased in Japan as compared to former surveys. The sex ratio (male/female) of definitive and probable CP patients was 4.5, with a mean age of 59.4 years; 59.2 years in males and 60.2 years in females. Alcoholic (69.7%) was most the common and idiopathic (21.0%) was the second most common cause of CP. The proportion of alcoholic CP increased as compared to the 55.5% found in 1994. The clinical features of overall Japanese patients with CP were: abdominal pain (60.6%), malabsorbtion (12.2%), diabetes mellitus (39.7%) and pancreatolithiasis (75.7%). Alcoholic patients were characterized by high morbidity as compared to nonalcoholic patients: abdominal pain (alcoholic 65.0% vs nonalcoholic 53.0%, p < 0.0001), diabetes mellitus (44.8% vs 31.4%, p < 0.0001) and pancreatolithiasis (84.0% vs 60.8%, p < 0.0001).ConclusionThe prevalence and the incidence of CP, especially alcoholic CP, have been increasing in Japan.     

Influence of potassium levels on one-year outcomes in elderly patients with acute heart failure

BackgroundAbnormal serum potassium levels (K⁺) in patients with heart failure (HF) relate to worse prognosis. We evaluated whether admission K⁺ levels predict 1-year outcomes in elderly patients admitted for acute HF.MethodsWe evaluated 2865 patients aged >74 years from the RICA Spanish Heart Failure Registry, classified according to admission serum K⁺ levels: hyperkalemia (>5.5 mmol/L), normokalemia (3.5–5.5 mmol/L) and hypokalemia (<3.5 mmol/L). We explored whether K⁺ levels were significantly associated with one-year all-cause mortality or hospital readmission and their combination.ResultsMean admission K⁺ value was 4.3 ± 0.6 mmol/L; 97 patients (3.38%) presented with hyperkalemia and 174 (6.06%) with hypokalemia. Overall, 43% of the patients died or were readmitted for HF during the follow-up period; the risk was higher for those with hyperkalemia (59% vs 41% in hypokalemic patients). The HR for one-year mortality was 1.43 (p = .073) and 1.67 for readmissions (p = .007) when K⁺ was >5.5 mmol/L and 1.08 (p = .618) and 0.90 (p = .533) respectively for K⁺ < 3.5 mmol/L. The HR for the combined outcome was 1.59 (1.19–2.13); p = .002 in hyperkalemic patients and 0.96 (0.75–1.23); p = .751in hypokalemic patients. Multivariate analysis showed a significant association of admission K⁺ values >5.5 mmol/L with the combined outcome of mortality and readmission (HR 1.15 [95% CI 1.04–1.27], p = .008).ConclusionIn patients hospitalized for decompensated HF, admission hyperkalemia predicts a higher mid-term risk for HF readmission and mortality, probably related to the significant higher risk of readmission.     

Lipoprotein lipase gene HindIII polymorphism and risk of myocardial infarction in South Indian population

IntroductionStudies have reported an association between lipoprotein lipase (LPL) gene and myocardial infarction in some populations. Therefore, the present study aimed to investigate the association of the HindIII polymorphism of the (LPL) gene with myocardial infarction and to explore its potential role in susceptibility in a South Indian population.Subjects and methodsWe included a total of 412 subjects (202 myocardial infarction patients and 210 age- and sex-matched controls). Demographic and clinical characteristics were collected. Lipid profiles were estimated. DNA was isolated and the LPL gene HindIII polymorphism was determined by polymerase chain reaction.ResultsComparison of the lipid profiles between patients and controls showed that patients had statistically high significant values (p = 0.0001). The H⁺ H⁺ genotype of the LPL gene is associated with myocardial infarction. H⁺ H⁺ vs. H^? H^? was χ2 = 19.4, OR 3.1, CI 95% 1.8–5.2, p < 0.0001.ConclusionOur study strongly suggests that the LPL gene HindIII Hþ Hþ genotype is an independent risk factor for first MI.