Chance of Cure Following Liver Resection for Initially Unresectable Colorectal Metastases: Analysis of Actual 5-Year Survival

Background

Survival with long-term follow-up following liver resection for unresectable colorectal liver metastases (CRLM) downsized by chemotherapy has rarely been reported. The aim of this study was to determine the chance of cure following liver resection for initially unresectable CRLM.

Methods

Between January 2000 and December 2009, 61 patients underwent hepatectomy for unresectable liver-only CRLM downsized after chemotherapy. Cure was defined as a recurrence-free interval of at least 5 years after primary hepatectomy.

Results

Resectability of CRLM was achieved after a mean number of 11 courses, and 42.6 % of patients underwent liver resection after ≥10 courses. Postoperative mortality was nil, and morbidity rate was 19.7 %. The 5- and 10-year actuarial overall survival rates were 42.6 and 16.0 %. Of 30 patients with a follow-up ≥5 years, 11 were alive, yielding a 5-year actual overall survival rate of 36.7 %, and 7 (23.3 %) were considered cured because they are alive without recurrence. On multivariate analysis, response to chemotherapy was the only independent predictor of both overall and disease-free survival.

Conclusions

Cure can be achieved in about 23 % of patients resected for initially unresectable CRLM downsized by chemotherapy. Liver resection can be safely performed in selected patients even after multiple courses of chemotherapy.     

Clinical efficacy of minimally invasive surgical (MIS) and non-surgical (MINST) treatments of periodontal intra-bony defect. A systematic review and network meta-analysis of RCT’s

Clinical Oral Investigations - The aim of this systematic review was to explore the efficacy of different minimal invasive surgical (MIS) and non-surgical (MINST) approaches for the treatment of...     

Possible Identification of Cervicogenic Headache Among Patients With Migraine: An Analysis of 374 Headaches

According to Sjaastad, the pain in cervicogenic headache, a form not recognized by the IHS, is long lasting and always side-locked unilateral. The frequency of side-locked unilateral pain (defined here as no change in side from onset) and other characteristics of cervicogenic headache were investigated in 300 outpatients using information collected on standard forms in structured interviews. Three hundred seventy-four headaches diagnosed according to IHS criteria were identified. Three hundred forty-eight of these headaches were long-lasting (duration of more than 4 hours); migraine (65%) followed by tension-type headache (25%) were the commonest forms. Side-locked unilaterality was present in 29% (101 of 348), and occurred most frequently in migrainous disorders not fulfilling the criteria (25 of 56, 44.6%). This group differed significantly from the other migraine conditions for longer pain duration ( P <0.02) and less frequent nausea, vomiting, photophobia, phonophobia ( P <0.0001), and aggravation by physical activity ( P <0.02). With these characteristics, this group resembled cervicogenic headache. However, in none of these patients was pain triggered by head or neck movements, and the frequency of head or neck trauma did not differ from other headaches. A more precise definition of clinical criteria for cervicogenic headache vs migraine is, therefore, required.     

Predictors of malignancy and recommended follow-up for patients with negative endoscopic ultrasound-guided fine-needle aspiration of suspected pancreatic lesions

BACKGROUND:

Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) can characterize and diagnose pancreatic lesions as malignant, but cannot definitively rule out the presence of malignancy. Outcome data regarding the length of follow-up in patients with negative or nondiagnostic EUS-FNA of pancreatic lesions are not well-established.

OBJECTIVE:

To determine the long-term outcome and provide follow-up guidance for patients with negative EUS-FNA diagnosis of suspected pancreatic lesions based on imaging predictors.

METHODS:

A retrospective review of patients undergoing EUS-FNA for suspected pancreatic lesions, but with negative or nondiagnostic FNA results was conducted at a tertiary care referral medical centre. Patient demographics, EUS imaging characteristics and follow-up data were examined.

RESULTS:

Seventeen of 55 patients (30.9%) with negative/nondiagnostic FNA were subsequently diagnosed with pancreatic malignancy. The risk of cancer was significantly higher for patients who had associated lymph nodes on EUS (P<0.001) and vascular involvement on EUS (P=0.001). The mean time to diagnosis in the group with false-negative EUS-FNA diagnosis was 66 days. The true-negative EUS-FNA patients were followed for a mean of 403 days after negative EUS-FNA results without the development of malignancy.

CONCLUSION:

For patients undergoing EUS-FNA for a suspected pancreatic lesion, a negative or nondiagnostic FNA does not provide conclusive evidence for the absence of cancer. Patients for whom vascular invasion and lymphadenopathy are detected on EUS are more likely to have a true malignant lesion and should be followed closely. When a patient has been monitored for six months or more with no cancer being diagnosed, there appears to be much less chance that a pancreatic malignancy is present.     

Analyzing Mycobacterium tuberculosis proteomes for candidate vaccine epitopes

Secreted antigens of Mycobacterium tuberculosis (Mtb) induce strong T cell responses and interferon-gamma (IFN-gamma) secretion, both of which are integral in the defense against Mtb. We used web-based tools (SignaIP and Prosite) to identify putative secreted proteins from Mtb genomes CDC 1551 and H37Rv. We then used EpiMatrix, a proprietary pattern-matching algorithm, to do a preliminary analysis of these proteins for regions that contained a high number of class II MHC binding motif matches. The use of bioinformatics tools reduced the number of potential epitopes to be screened to 5% of the 1.3 million overlapping peptides. Peripheral blood mononuclear cells (PBMC) were obtained from healthy, asymptomatic tuberculin skin test-positive donors. Of the 17 highest-ranking peptide candidates that could be synthesized for this preliminary in vitro evaluation, 15 (88%) stimulated IFN-gamma response, and eight (47%) stimulated lymphocyte proliferation in vitro. IFN-gamma ELISpot assays were therefore a more sensitive test for T cell response to these peptides than were proliferation assays. One highly promiscuous epitope (MT2281-26-J, WRRRPLSSALLSFGLLLGGLPL) induced IFN-gamma secretion in PBMC from 11 of 25 Mtb immune subjects (44%). Overall, 15 epitopes, and MT2281-26-J in particular, are candidates for inclusion in a multi-epitope TB vaccine. These findings support the systematic application of bioinformatics tools to whole genomes when used in combination with in vitro methods for screening and confirming epitopes.     

Behavior of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Colon Cancer Patients Undergoing Surgery

CD4+CD25+Foxp3+ regulatory T cells (Treg) specialize in suppressing immune responses. In this study, 47 consecutive colon cancer patients were subjected to circulating Treg frequency assessment by flow cytometry before and after cancer resection. Thirty-two healthy subjects served as controls. Circulating Treg frequencies were significantly higher in colon cancer patients with respect to healthy controls. When patients were subgrouped according to Dukes stages, a linear relationship was observed between Dukes stages and Treg frequencies. In radically resected patients, Treg frequencies were shown to have significantly dropped down. Patients with advanced colon cancer were more likely to have significantly higher proportions of circulating Treg frequencies than Dukes A and B patients when compared to healthy subjects. Of note, nonradically resected patients were found to display reductions in—but not normalization of—Treg frequencies. These results suggest that cancer itself may be able to drive Treg recruitment as a strategy of immunoevasion.     

Hepatocellular Hyperplasia, Plasmacytoma Formation, and Extramedullary Hematopoiesis in Interleukin (IL)-6/Soluble IL-6 Receptor Double-Transgenic Mice

Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6-induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.