Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

Objective

To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer.

Materials and methods

The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method.

Results

The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group.

Conclusion

Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.     

Ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve: involvement and clinical relevance of smooth muscle cell apoptosis and expression of cell death-initiating proteins.

OBJECTIVE: There is relationship between a dilated ascending aorta and a bicuspid aortic valve. Controversy exists concerning techniques available for surgical restoration of the functional and anatomical integrity of the aortic root. The present study was undertaken to define the histopathologic and molecular biologic condition of ascending aortic aneurysms associated with bicuspid (BAV) or tricuspid aortic valve (TAV) and the relationship to valve sparing or pulmonary autograft procedures. METHODS: Aortic aneurysm wall specimens from 20 patients (10 BAV; 10 TAV) undergoing elective repair and normal aortic tissues from organ donors (n=5) were analysed for patterns of smooth muscle cells (SMCs) and infiltrating leukocytes (immunohistochemistry), apoptosis (in situ end-labelling of DNA-fragments (TUNEL)), and expression of the death-promoting proteins perforin, Fas, and FasLigand (Immunoblotting). RESULTS: Segments from aneurysms exhibited a distinct pattern of medial destruction, elastic fragmentation, and disorientation with rarefication of SMCs. BAV wall segments contained more cells bearing markers of apoptosis than TAV specimens whereas normal aorta displayed only few apoptotic cells (P<0.05). TUNEL showed higher levels of DNA fragmentation in BAV than in TAV, and double immunostaining identified SMCs as the principal cell type displaying fragmented DNA. Immunohistochemistry confirmed expression of death-promoting mediators by infiltrating lymphocytes, and Western blotting documented their presence in BAV and TAV aneurysmal tissue, with the greatest increases seen in specimens from aneurysms associated with BAV. CONCLUSIONS: There is evidence for a molecular link between SMC apoptosis initiated by infiltration and local signal expression of immune cells and weakening of the aortic wall being more prevalent in patients with BAV. Our findings may suggest a mechanism responsible for aneurysm formation of the aorta and aortic dilatation after autograft root or sinus remodelling procedures.     

Transpulmonary chemoembolization (TPCE) as a treatment for unresectable lung metastases

To evaluate tumor response after treating unresectable lung metastases with transpulmonary chemoembolization (TPCE) in palliative intention. From 2001 to 2005, 52 patients (mean: 59.8 years; 32 males/20 females) suffering from 106 unresectable lung metastases (mean:6 metastases/patient; range,1–21) were treated with 2–10 TPCE-sessions (mean: 3.3 sessions/patient). Metastases originated from primaries, including colorectal carcinoma (n = 20), breast cancer (n = 6), renal cellular carcinoma (n = 5), thyroid cancer (n = 4), cholangiocellular carcinoma (n = 2), leiomyosarcoma (n = 2), and others (n = 13). Tumor-feeding pulmonary arteries were selectively probed after puncturing the femoral vein, and administering 10 ml lipiodol, mitomycin C, and microspheres (Spherex) each via balloon catheter over pulmonary approach. During therapy, follow-up was accomplished at 4-week intervals using unenhanced and contrast-enhanced CT. After sequential therapy, follow-up was performed every 3 months for a period of 6 months up to 2.25 years. All patients tolerated the treatments well without major side effects or complications. In 24% (n = 13) moderate to high lipiodol uptake was found, while 75% (n = 39) of the tumors showed a low uptake. According to the RECIST criteria, “partial response” was achieved in 16 cases, “stable disease” in 11 cases, and “progressive disease” in 25 cases [mean survival: 17 months/median: 21.1 months (Kaplan-Meyer)]. According to these findings, TPCE is a well-tolerated procedure for palliative treatment of unresectable lung metastases.     

RETRACTED ARTICLE: Volume replacement with HES 130/0.4 may reduce the inflammatory response in patients undergoing major abdominal surgery

PURPOSE: To investigate the effects of intravascular volume replacement therapy on the inflammatory response during major surgery. METHODS: Thirty-six patients scheduled for elective abdominal surgery were randomized to receive either 6% hydroxyethylstarch (130,000 Dalton mean molecular weight, degree of substitution 0.4; n = 18, HES-group) or lactated Ringer's solution (RL-group; n = 18) for intravascular volume replacement. Fluid therapy was given perioperatively and continued for 48 hr in the intensive care unit. Volume replacement was guided by physiological parameters. Serum concentrations of interleukin (IL)-6, IL-8 and IL-10 and soluble adhesion molecules (sELAM-1 and sICAM-1) were measured after induction of anesthesia, four hours after the end of surgery, as well as 24 hr and 48 hr postoperatively. RESULTS: Biometric and perioperative data, hemodynamics and oxygenation were similar between groups. On average, 4470 +/- 340 mL of HES 130/0.4 per patient were administered in the HES-group compared to 14310 +/- 750 mL of RL in the RL-group during the study period. Release of pro-inflammatory cytokines IL-6 and IL-8 was significantly lower in the HES-group [(peak values) 47.8 +/- 12.1 pg*dL(-1) of IL-6 and 35.8 +/- 11.2 pg*mL(-1) of IL-8 (HES-group) vs 61.2 +/- 11.2 pg*dL(-1) of IL-6 and 57.9 +/- 9.7 pg*mL(-1) of IL-8 (RL-group); P < 0.05]. Serum concentrations of sICAM-1 were significantly higher in the RL-group [(peak values) 1007 +/- 152 ng*mL(-1) (RL-group) vs 687 +/- 122 ng*mL(-1), (HES group); P < 0.05)]. Values of sELAM-1 were similar in both groups. CONCLUSION: Intravascular volume replacement with HES 130/0.4 may reduce the inflammatory response in patients undergoing major surgery compared to a crystalloid-based volume therapy. We hypothesize that this is most likely due to an improved microcirculation with reduced endothelial activation and less endothelial damage.     

Traditional cardiac risk factors in individuals with chronic kidney disease

Individuals with chronic kidney disease (CKD) are at increased risk for the development and progression of cardiovascular disease (CVD). The increased risk is due to a higher prevalence of both traditional risk factors as well as nontraditional risk factors. In this review we focus on individuals at all stages of CKD and discuss modifiable traditional risk factors, namely hypertension, dyslipidemia, diabetes mellitus and poor glycemic control, smoking, and physical inactivity. The prevalence of each risk factor and its relationship with CVD is described. Treatment recommendations are provided using evidence available from populations with CKD or evidence extrapolated from the general population when there are insufficient data on individuals with CKD.     

Ca sensitizer superior to catecholamine during myocardial stunning?

BACKGROUND: After open-chest cardiac surgery, ventricular function remains depressed (myocardial stunning). Catecholamines (epinephrine) improve ventricular function by increasing the intracellular Ca(2+) concentration. In parallel, the oxygen consumption is increased, so that the hitherto intact myocardium can be jeopardized. In the very insufficient ventricle, epinephrine can even become ineffective. Since Ca(2+) sensitizers provide another therapeutic avenue, the effects of epinephrine and levosimendan on postischemic hemodynamics were investigated. METHODS: After hemodynamic steady state, isolated, blood (erythrocyte-enriched Krebs-Henseleit solution)-perfused rabbit hearts were subjected to 25 min normothermic, no-flow ischemia and 20 min reperfusion. Heart rate (HR), cardiac output (CO), left ventricular pressure (LVP), coronary blood flow (CBF), and arterio-venous oxygen difference (AVDO(2)) were recorded during reperfusion and after administration of either epinephrine (n=16; 0.03 micromol), or levosimendan (n=11; 0.75 micromol) or epinephrine plus levosimendan (n=5). RESULTS: Epinephrine increased HR (19%, p=0.01) and improved hemodynamics in terms of CO (62%, p=0.0006), stroke volume SV (46%, p=0.02), stroke work W (158%, p=0.01), LVP(max) (58%, p=0.0001), maximal pressure increase dP/dt(max)(140%, p=0.0004), minimal pressure increase dP/dt(min) (104%, p=0.0002), LVP(ed) (-26%, p=0.02), and increased coronary resistance CR (31%, p=0.05). Epinephrine impaired hemodynamics in terms of AVDO(2) (+63%, p=0.003), myocardial oxygen consumption MVO(2) (+67%, p=0.0003) and MVO(2)/beat (+36%, p=0.01). External efficiency eta was increased by 92% (p=0.02). Levosimendan in postischemic hearts increased HR (32%, p=0.009) and improved hemodynamics in terms of CO (85%, p=0.01), SV (44%, p=0.03), W (115%, p=0.04), LVP(max) (95%, p=0.04), dP/dt(max) (133%, p=0.009), dP/dt(min) (121%, p=0.007), LVP(ed) (-63%, p=0.0006), and CR (-17%; n.s., p=0.1). It altered hemodynamics in terms of AVDO(2) (+7.0%; n.s., p=0.3) and MVO(2) (+32%, p=0.007) and MVO(2)/beat (+2.3%; n.s., p=0.4). External efficiency was increased by 307% (p=0.04). In five additional extremely dysfunctional rabbit hearts, epinephrine was ineffective. Additional levosimendan increased hemodynamics in terms of HR (56%; n.s., p=0.1), CO (159%, p=0.04), SV (89%, p=0.03), W (588%, p=0.02), LVP(max) (168%, p=0.03), dP/dt(max) (102%, p=0.005), dP/dt(min) (78%, p=0.006), LVP(ed) (-98%, p=0.0006), and CR (-50%, p=0.02). It altered hemodynamics in terms of AVDO(2) (-11%; n.s., p=0.05), MVO(2) (+131%, p=0.04) and MVO(2)/beat (+171%, p=0.03). External efficiency was increased by 212% (p=0.04). CONCLUSION: In contrast to epinephrine, levosimendan improves ventricular function without increasing oxygen demand, thereby considerably improving external efficiency. Even during epinephrine resistance in extremely dysfunctional hearts, levosimendan successfully improves ventricular function.     

Comparative early and midterm results of open juxtarenal and infrarenal aneurysm repair

Background and aims Since the introduction of endovascular aortic aneurysm repair (EVAR) for aortic aneurysms, the number of juxtarenal aortic aneurysms (JRA) has been growing steadily due to selection bias (neck morphology for EVAR). This case-match study compares the perioperative outcome and midterm results of suprarenally clamped JRA with infrarenal aortic aneurysms (AAA). Methods From 1997 to 2004, patients who received open surgery with suprarenal clamping for JRA were included in the study and compared to matched patients with infrarenal clamping (AAA). Measurements analyzed were the in-hospital mortality and morbidity. Midterm results were obtained through clinical investigation and magnetic resonance angiography imaging. Results Thirty-five patients (mean age, 68.4 years; 30 male and 5 female) received suprarenal cross-clamping for JRA. The overall in-hospital mortality for JRA and for the controls (AAA) with elective aortic repair was 4.5% (6.1% JRA; 3% AAA, p = 0.058). The morbidity of JRA was elevated according to the rate of pulmonary complications (p = 0.021) and the need for re-operation (p = 0.019). The mean follow-up time was 2.3 years (range, 8–96 months). At follow-up, 28 patients (80%) from the JRA group and 29 patients from the AAA group (82.9%) were alive. Conclusion Open aortic surgery for JRA with the need for suprarenal cross-clamping shows a slightly elevated in-hospital mortality rate without statistical significance and equal midterm mortality results in comparison with infrarenally clamped aortic aneurysms.     

Hemispheric asymmetry for auditory processing in the human auditory brain stem, thalamus, and cortex

We report evidence for a context- and not stimulus-dependent functional asymmetry in the left and right human auditory midbrain, thalamus, and cortex in response to monaural sounds. Neural activity elicited by left- and right-ear stimulation was measured simultaneously in the cochlear nuclei, inferior colliculi (ICs), medial geniculate bodies (MGBs), and auditory cortices (ACs) in 2 functional magnetic resonance imaging experiments. In experiment 1, pulsed noise was presented monaurally to either ear, or binaurally, simulating a moving sound source. In experiment 2, only monaural sounds were presented. The results show a modulation of the neural responses to monaural sounds by the presence of binaural sounds at a time scale of tens of seconds: In the absence of binaural stimulation, the left and right ICs, MGBs, and ACs responded stronger to stimulation of the contralateral ear. When blocks of binaural stimuli were interspersed in the sound sequence, the contralateral preference vanished in those structures in the right hemisphere. The resulting hemispheric asymmetry was similar to the asymmetry demonstrated for spatial sound processing. Taken together, the data demonstrate that functional asymmetries in auditory processing are modulated by context. The observed long time constant suggests that this effect results from a "top-down" mechanism.     

Benefit of phosphodiesterase 4 inhibitors as supplemental therapy after lung transplantation concerning their antiproliferative effects: an experimental study using a heterotopic rodent model

BACKGROUND: Recent advances in the understanding of immunomodulatory properties of phosphodiesterase 4 (PDE4) inhibitors recommend these drugs for immunosuppressive therapy after lung transplantation. The potency of three PDE4 inhibitors was tested using an established model of heterotopic tracheal transplantation in rats. METHODS: Five allogenic groups were investigated and treated with the PDE4 inhibitors: rolipram, cilomilast (Ariflo, SB-207499, SmithKline Beecham, Munich, Germany), roflumilast (Altana Pharmacia, Bad Homburg, Germany) or cyclosporine A (CsA), or left without immunosuppression. The grafts were quantitatively analyzed for epithelial integrity, monocyte/macrophage content, cell proliferation, and tracheal obliteration by histology/immunohistochemistry (days 1, 5, 7, 21, 28; n=4-7). RESULTS: In animals treated with the PDE4 inhibitors, the epithelium was completely lost until day 21. The epithelium was partially preserved in the rats receiving CsA until day 28. In the acute phase (days 5 and 7) the infiltration of monocytes and macrophages was significantly inhibited similarly (cilomilast) or less effective (rolipram, roflumilast) as in CsA-treated rats. In the chronic phase (day 28) the significant increase of monocytes and macrophages after CsA-treatment was not found in PDE4 inhibitor-treated rats. The PDE4 inhibitors showed lower (rolipram) or higher (cilomilast, roflumilast) potency as CsA to inhibit the cell proliferation. Only treatment with PDE4 inhibitor (Ariflo) significantly inhibited the obliteration, but to a lesser degree as CsA. CONCLUSION: The PDE4 inhibitors tested in our study are not suitable on their own for immunosuppressive therapy after lung transplantation because of the limited protection against the epithelial disturbance, infiltration of immune cells, and luminal obliteration. The strong anti-proliferative effect of the second-generation PDE4 inhibitors, cilomilast and roflumilast, suggest a benefit for the effective inhibition of immune cell and fibroblast proliferation contributing to the development of obliterative bronchiolitis.     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.