Background FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.
Human low density lipoprotein (LDL) with a molecular mass of 2.5 million contains on average 1300 molecules of polyunsaturated fatty acids (PUFAs) bound in the different lipid classes. The predominant antioxidant in LDL is alpha-tocopherol, with an average of 6 molecules in each LDL particle. The other substances with potential antioxidant activity are: gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, cryptoxanthin, cantaxanthin, phytofluene and ubiquinol-10. Each is present in amounts of only 1/20th to 1/300th of that of alpha-tocopherol. If LDL is exposed to oxidative conditions (Cu++ ions, macrophages) a lag phase precedes the oxidation of PUFAs. During the lag phase the antioxidants disappear with alpha-tocopherol the first to go and beta-carotene the last. The lag phase, which can readily be determined, is an index of the oxidation resistance of LDL. If LDL is loaded with vitamin E in vitro its oxidation resistance increases linearly with its alpha-tocopherol content according to the equation, y = kx+a. The same relationship is applicable if the alpha-tocopherol content of LDL is increased by taking oral vitamin E. Daily doses of 150, 225, 800 and 1200 IU RRR-alpha-tocopherol increased the LDL alpha-tocopherol on average to 138%, 158%, 144% and 215% of the initial value, the oxidation resistance being increased to 118%, 156%, 135% and 175%, respectively. The efficiency of vitamin E-dependent (= k) and the vitamin independent (= a) oxidation resistance seem to be subject specific with strong individual variation.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE. The purposeof our studywas to assessthe potentialof thin-sectionmul tiphasichelicalCT in diagnosisandstagingof hilar cholangiocarcinomas. SUBJECTS AND METHODS. IdenticallycollimatedhelicalCT studieswereperformedbefore and during the hepatic artery dominant phase and during the portal vein dominant phase of contrastenhancementin 29 consecutivepatientswith proven hilar cholangiocarcinomas.Dif ferencesin attenuation betweenthetumorandtheliverwerecalculatedin eachcaseby subtract ing the average attenuation of the tumor from that of the liver. A four-point scale termed a â€oe¿ lesion conspicuityscore― was usedto determineratesof tumordetection.CT findingswere correlated with surgically assessed extent of tumor, histologic findings, or both in all cases. RESULTS. Ten (34%) of the 29 hilar cholangiocarcinomas were detectedon unenhanced images.All hilar cholangiocarcinomas (100%) were seenon hepaticartery dominantphase scans,and 25 (86%) of 29 hilar cholangiocarcinomas were seen on portal vein dominant phase scans, regardless of the morphologic appearance. An infiltrating stenotic lesion was found in 17 (59%) of 29 patients, an exophytic hilar lesion was found in 11 patients (38%), and one patient (3%) had an intraluminal polypoid lesion. Mean differences in enhancement between infiltrating stenotic lesions and the liver were significantly greater on hepatic artery dominant phase scans (28 ±10 H) than on portal vein dominant phase scans (10 ±8 H), whereas the mean difference in enhancement between the exophytic lesions and the liver was statisticallygreaterduringtheportalveindominantphase(p < .01). Two of the hilar cholang iocarcinomas were resectableat surgery, and I 8 were not.The overallaccuracyof helicalCT for assessing resectability was 60%. In 10 (56%) of 18 patients, unresectable disease was cor rectlydiagnosedwith helicalCT (sensitivity, 56%). Eight (44%) of I 8 patientsconsideredto have resectable tumors with helical CT had unresectable tumors at surgery. A resectable Ut mor was correctly diagnosed in two patients with helical CT. CONCLUSION.MultiphasichelicalCT canbe usedto detectandclassifyhilar cholang iocarcinomas. However,theexactproximaltumorextentalongbile ductstendsto be underes timated with helical CT; therefore, helical CT is inaccurate for determining resectability.H ilar cholangiocarcinomas are typi cally small, slow-growing, locally invasive tumors that have a dismal prognosis ifleft untreated, witha meansurvival of approximately 3 months after initial presen tation [1â€"7]. The anatomic location of hilar cholangiocarcinoma makesresectiondifficult [7]. Surgical exploration of these patients should be undertaken only when preoperative examination has shown a potential for curative resection because the risks of palliative surgery for malignant obstructive jaundice are high, with surgical mortality rates of 20â€"30% [8,9]. Accordingly, preoperative assessment of resec tability of hilar cholangiocarcinoma has in creased in importance in recent years because percutaneous and endoscopic p...
Reactive oxygen species (ROS), important mediators of cell and tissue injury during inflammation, are produced by several types of inflammatory cells. The formation of ROS can be monitored by detection of lipid peroxidation products. The extremely broad spectrum of biological effects of aldehydic lipid peroxidation products has necessitated the development of a technique that enables the sensitive routine quantitation of aldehydes formed in biological materials. MalondiaJdehyde (MDA) is a by-product of enzymatic eicosanoid formation and an endproduct of nonenzymatic peroxidation of polyunsaturated fatty acids with three or more bisallylic double bonds, The determination of the thiobarbituric acid derivative of MDA (TBA-MDA) is a widely used method for estimating overall lipid peroxidation. We describe a rapid, isocratic, simple, and sensitive high-performance liquid chromatographic (HPLC) method with spectrafluorimetric detection for measurement oF MDA-TBA in human biological samples such as plasma, urine, wound secretions, amniotic fluid, sputum and tissue samples. By use of this method, picomole quantities of MDA can be readily and specifically detected in different biological materials. Coefficients of variation of repeated MDA-TBA assays were 4.4% within run and 6.9% from run to run. Reference values are given for a variety of human body fluids and for rat tissues.
Experience with 46 patients diagnosed with liver abscesses over a 13-year period was reviewed to ascertain the impact of percutaneous versus surgical drainage. In most of the cases the abscesses were diagnosed by sonography or computed tomography. The most common pathogenetic mechanism was ascending biliary tract infection. Of the 46 total patients, 27 were primarily treated surgically, whereas 19 underwent percutaneous drainage. In the surgical group five (18.5%) patients required reoperation. Percutaneous drainage failed in four patients (21.1%). Multivariate stepwise logistic regression analysis revealed that a high APACHE II score, low hemoglobin level, and high serum bilirubin level were significant predictors of a complicated clinical course. Death was related more closely to the overall condition of the patient, as expressed by a high APACHE II score, and the underlying disease (malignancy) than to the mode of therapy.
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