Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

Identification and characterization of an endogenous chemotactic ligand specific for FPRL2

Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein-coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases through the G(i) class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.     

Evaluation of indicators of cobalamin deficiency defined as cobalamin-induced reduction in increased serum methylmalonic acid

BACKGROUND: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. METHODS: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17-87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 micromol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used. RESULTS: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0. 810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information. CONCLUSIONS: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.     

Trimethoprim resistance of Escherichia coli in outpatients in Finland after ten years' use of plain trimethoprim

Development of trimethoprim resistance among Escherichia coli collected from urine samples in three areas in Finland was studied in 1978-1984. Three different trends of development of resistance were found: in the Turku area resistance has increased evenly during 1978-1982 from 5.4% to 10.1%, but thereafter a plateau seems to have been reached; in the Helsinki area resistance increased rapidly from 2.9% in 1980 to 11.1% in 1984, possibly due to the spread of a trimethoprim resistance transposon Tn7, which occurred significantly more often among E. coli strains in this area than in the Turku area; in the Rovaniemi area resistance has been at a plateau level, between 3.1 and 5.7%, during the whole study. No clear correlation between the consumption of trimethoprim and the level of resistance was found. The frequency of trimethoprim resistance in E. coli isolated from patients less than 65 years was 5.2% and in those isolated from patients greater than or equal to 65 years 14.7%.     

Reproducibility of two coronary calcium quantification algorithms in patients with different degrees of calcification

Purpose: To evaluate the reproducibility of coronary calcium quantification algorithms by electron beam CT (EBT) in patients with different amounts of calcified plaque using the conventional (Agatston) score and an area score and to demonstrate a potential application of these results for evaluation of follow-up scans. Methods: In 50 consecutive patients, the conventional calcium score (CCS = Agatston score) and the area score (AS) were summed for each artery and patient. Data were analyzed in four groups according to degrees of calcification: 0 (absent–minimal): CCS 0–9, I (mild): CCS 10–99, II (moderate): CCS 100–399, III (severe): CCS 400. We determined and compared the reproducibility for each algorithm within and among groups. Results: Median percent reproducibility improved with increasing amounts of calcified plaque for the CCS and the AS (p = 0.002 and p = 0.004, respectively). We demonstrate how these reproducibility values can be used to evaluate long-term follow-up studies. The reduction of median reproducibility per patient using the AS vs. the CCS was 32% (13 vs. 19%, respectively). On a vessel-by-vessel basis, the reduction of median reproducibility was 7% (24.3 vs. 22.6%, CCS vs. AS, p < 0.02), which was attributable to a 45% reduction in reproducibility in arteries with mild scores (46.1 vs. 25.5%, CCS vs. AS, p < 0.005). Conclusion: The AS has an improved reproducibility compared with the CCS, especially in patients with small amounts of coronary calcifications which may prove clinically useful. Different reproducibility values in different degrees of calcification can be used for an individual assessment of changes in amounts of coronary calcification.     

Computer-assisted patient data management: from department-specific individual solutions to Vienna-wide network comprehensive solution]

Up to now the daily routine work and statistics have been facilitated by using some self-developed microcomputer based data collection systems. No network has been established. Currently we implemented in out hospital "Krankenanstalt Rudolfstitung" a country-wide patient oriented data collection net system. In future it will be possible to compare all patients datas, methods and success of treatment of all Viennese hospitals.