Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS.
Methods
Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS).
Results
The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4–51.2 months], and the median DFS was 13.6 months (95% CI, 12.3–14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4–24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS.
Conclusion
For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.
The stroke volume (SV) during exercise is an important index of the heart's functional capacity. A new method has been developed for the non-invasive estimation of exercise SV (SVex). It requires the determination of the slope for the oxygen uptake versus heart rate relationship in the steady state of graded exercise testing (GXT). The product of the slope and a constant (reciprocal of an assumed value of the arterial oxygen content) equals an estimated value for SVex. It was validated in a previous study using invasive measurements while subjects were performing steady-state GXT. However, currently the most commonly used GXT protocols are non-steady state, e.g. protocols with 1-min increment durations. We tested the hypothesis that SVex is the same for steady-state and non-steady-state GXT. A total of 30 subjects (15 males and 15 females) served as subjects for the study. Each subject performed two GXTs on different days with different increment durations - 1 and 4 min. Ventilation and gas exchange were measured with the Vacumed metabolic cart. For the male subjects, the mean (SD) SVex values for the 1- and 4-min GXTs were 155.4 (39.5) and 134.6 (27.5) ml, respectively. The corresponding values for the female subjects were 151.6 (37.6) and 134.3 (36.4) ml. Paired t-test analysis demonstrated that for both genders the mean SVex for the 1-min GXT was significantly larger than the 4-min GXT mean value (P<0.05). Hence, the commonly used 1-min GXT does not yield the same values for SVex as the steady-state GXT. 相似文献
The hepatic plasma membrane fatty acid-binding protein (h-FABPPM) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate with a Ka approximately 1.2-1.4 x 10(7) M-1. Sinusoidally enriched liver plasma membranes and purified h-FABPPM have GOT enzymatic activity; the relative specific activities (units/mg) of the membranes and purified protein suggest that h-FABPPM constitutes 1-2% of plasma membrane protein in the rat hepatocyte. Monospecific rabbit antiserum against h-FABPPM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [3H]oleate but not that of [35S]sulfobromophthalein or [14C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABPPM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABPPM and mGOT are closely related. 相似文献
1. Following intravenous administration of morphine.HCl a reduction in mean arterial blood pressure (MABP) was produced, quaternary morphine analogue was ineffective. 2. Theophylline and 8-phenyltheophylline administration reduced morphine-induced hypotension. 3. A2 adenosine receptor agonist caused an hypotension while A1 adenosine receptor agonist was ineffective. 4. L-NG-Mono-methylarginine administration reduced the hypotensive effect of exogenous A2 agonist while it was ineffective on morphine-induced hypotension. 5. Morphine-induced hypotension was increased by pretreatment with dipyridamole, whereas tetrabenazine abolished it. 6. The present study is consistent with previous reports on the central hypotensive action of morphine and propose a role for adenosine release in morphine-induced hypotension. 相似文献
Digestive Diseases and Sciences - Crohn’s disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal... 相似文献
PURPOSE: To estimate which combination of restorative materials resulted in the most homogeneous stress and strain distributions in post-and-core treated teeth. MATERIALS AND METHODS: Eight experimental finite element models with different material configurations were simulated; both indirect and direct restorations were considered. An arbitrary load of 50 N was applied on the palatal surface of the crown at a 60-degree angle to the tooth's longitudinal axis to simulate tearing function. RESULTS: In all the models, the values of both strain and stress recorded in the middle third of the buccal aspect of the root surface were off the scale. In contrast, the minimum values were noticed at the level of both the apical portion of the post and the root apex. CONCLUSION: The mechanical properties of the crown and core materials influenced both the position of concentration areas and the level of stress and strain along the dentin/cement/post interfaces. 相似文献