First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI)

The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile

Combined transarterial chemoembolization and arterial administration of Bletilla striata in treatment of liver tumor in rats

AIM: To evaluate and compare the effect of combined transarterial chemoembolization (TACE) and arterial administration of Bletilla striata (a Chinese traditional medicine against liver tumor) versus TACE alone for the treatment of hepatocellular carcinoma (HCC) in ACI rats. METHODS: Subcapsular implantation of a solid Morris hepatoma 3 924A (2 mm3) in the liver was carried out in 30 male ACI rats. Tumor volume (V1) was measured by magnetic resonance imaging (MRI) on day 13 after implantation. The following different agents of interventional treatment were injected after retrograde catheterization via gastroduodenal artery (on day 14), namely, (A) TACE (0.1 mg mitomycin + 0.1 ml Lipiodol) + Bletilla striata (1.0 mg) (n=10); (B) TACE + Bletilla striata (1.0 mg) + ligation of hepatic artery (n=10), (C) TACE alone (control group, n=10). Tumor volume (V2) was assessed by MRI (on day 13 after treatment) and the tumor growth ratio (V2/V1) was calculated. RESULTS: The mean tumor volume before (V1) and after (V2) treatment was 0.0355 cm3 and 0.2248 cm3 in group A, 0.0374 cm3 and 0.0573 cm3 in group B, 0.0380 cm3 and 0.3674 cm3 in group C, respectively. The mean ratio (V2/V1) was 6.2791 in group A, 1.5324 in group B and 9.1382 in group C. Compared with the control group (group C), group B showed significant inhibition of tumor growth (P0.05). None of the animals died during implantation or in the postoperative period. CONCLUSION: Combination of TACE and arterial administration of Bletilla striata plus ligation of hepatic artery is more effective than TACE alone in the treatment of HCC in rats

Pancreatic pseudocyst eroding into the splenoportal venous confluence and mimicking an arterial aneurysm

We report the case of a 62-year-old man with chronic pancreatitis who presented with increasing abdominal pain. Sonography, magnetic resonance imaging, contrast-enhanced computed tomography, and ultimately catheter angiography demonstrated a pancreatic pseudocyst that had eroded into the splenoportal venous confluence, mimicking an arterial aneurysm. The diagnostic was confirmed at the time of surgical treatment. This case demonstrates the use of imaging to diagnose complications of pancreatitis, and the difficulty of distinguishing an eroding pseudocyst from an arterial aneurysm

Portal vein thrombosis and arterioportal shunts : effects on tumor response after chemoembolization of hepatocellular carcinoma

AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS

Analysis of and function predictions for previously conserved hypothetical or putative proteins in Blochmannia floridanus

BACKGROUND: There is an increasing interest to better understand endosymbiont capabilities in insects both from an ecological point of view and for pest control. Blochmannia floridanus provides important nutrients for its host, the ant Camponotus, while the bacterium in return is provided with a niche to proliferate. Blochmannia floridanus proteins and metabolites are difficult to study due to its endosymbiontic life style; however, its complete genome sequence became recently available. RESULTS: Improved sequence analysis algorithms, databanks and gene and pathway context methods allowed us to reveal new information on various enzyme and pathways from the Blochmannia floridanus genome sequence [EMBL-ID BX248583]. Furthermore, these predictions are supported and linked to experimental data for instance from structural genomics projects (e.g. Bfl341, Bfl 499) or available biochemical data on proteins from other species which we show here to be related. We were able to assign a confirmed or at least a putative molecular function for 21 from 27 previously conserved hypothetical proteins. For 48 proteins of 66 with a previous putative assignment the function was further clarified. Several of these proteins occur in many proteobacteria and are found to be conserved even in the compact genome of this endosymbiont. To extend and re-test predictions and links to experimentally verified protein functions, functional clusters and interactions were assembled. These included septum initiation and cell division (Bfl165, Bfl303, Bfl248 et al.); translation; transport; the ubiquinone (Bfl547 et al.), the inositol and nitrogen pathways. CONCLUSION: Taken together, our data allow a better and more complete description of the pathway capabilities and life style of this typical endosymbiont

Transarterielle Chemoembolisation als Selektionsmarker für Patienten mit HCC vor LTX unter retrospektiver Zuhilfenahme histologischer Ergebnisse [meeting abstract]

Einleitung: Für die meisten Patienten mit HCC ist die LTX die einzige kurative Behandlungsoption. Bei diesen Patienten scheint eine Kontrolle der Erkrankung durch lokale Verfahren im Intervall bis zur LTX zu erreichen zu sein. Als das beste Verfahren gilt die transarterielle Chemoembolisation (TACE). Die Effektivität ist jedoch umstritten. Möglicherweise kann sie aber Patienten startifizieren, die ein hohes Rezidivrisiko haben. Material und Methoden: Im Zeitraum zwischen 1995 und 2005 wurden n=27 Patienten mit HCC im Alter zwischen 22 und 69 Jahren transplantiert. Hiervon erhielten n=15 Patienten eine Vorbehandlung in Form einer alleinigen TACE oder kombiniert mit PEI [n=1] bzw. LITT [n=1]. Retrospektiv wurde das Gesamtüberleben sowie das „Event-free-survival“ (Rezidiv, Reinfektion und Tod) analysiert. Ergebnisse: Die mittlere Wartezeit betrug bei Patienten in der TACE-Gruppe 214 Tage, bei Patienten ohne Vorbehandlung 133 Tage. Bei einem mittleren Nachbeobachtungszeitraum von 1097 ± 1193 Tagen für TACE-Patienten und 1674 ± 966 Tagen für non-TACE-Patienten betrug das Überleben für Patienten, die mit TACE vorbehandelt wurden 83,3%, für Patienten, die keine TACE erhielten 86.7% (p=0,5693). Gleiches fand sich für das Event-free-survival (p=0,8823). Das Gesamtüberleben der Patienten, die auf der Warteliste einen Tumorprogress hatten lag bei 77%, während Patienten mit stabiler Tumorgröße oder Regredienz der Tumore ein Überleben von 93% aufwiesen (p=0,0153). Unter TACE-Behandlung zeigten 5/15 Patienten eine zunehmende Anzahl an Herden im histologischen Präparat verglichen mit der Ausgangsbildgebung. Nur bei einem Patienten zeigte sich der Progress der Erkrankung bereits in der präoperativen Bildgebung. Patienten mit einem Progress der Erkrankung hatten ein Gesamtüberleben von 60%, während Patienten mit „stable disease“ oder Rückgang der Herde ein Gesamtüberleben von 100% hatten (p=0,0180). Schlussfolgerung: Unseren Ergebnisse zufolge ist der Effekt der TACE als Bridgingverfahren auf das Überleben der Patienten fraglich. Allerdings scheint die TACE zur Riskostratifizierung geeignet zu sein. In unserem Patientenkollektiv hatten Patienten, die eine Progredienz der Erkrankung auf der Warteliste zeigten ein signifikant schlechteres Gesamtüberleben. Dies gilt auch bei ausschließlicher Betrachtung der Patienten mit TACE

Sarcoidosis of the hypothalamus and pituitary stalk

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up

Early-Time Ultraviolet and Optical Hubble Space Telescope Spectroscopy of the Type II Supernova 2022wsp

We report early-time ultraviolet (UV) and optical spectroscopy of the young, nearby Type II supernova (SN) 2022wsp obtained by the Hubble Space Telescope (HST)/STIS at about 10 and 20 days after the explosion. The SN 2022wsp UV spectra are compared to those of other well-observed Type II/IIP SNe, including the recently studied Type IIP SN 2021yja. Both SNe exhibit rapid cooling and similar evolution during early phases, indicating a common behavior among SNe II. Radiative-transfer modeling of the spectra of SN 2022wsp with the TARDIS code indicates a steep radial density profile in the outer layer of the ejecta, a supersolar metallicity, and a relatively high total extinction of E(B-V) = 0.35 mag. The early-time evolution of the photospheric velocity and temperature derived from the modeling agree with the behavior observed from other previously studied cases. The strong suppression of hydrogen Balmer lines in the spectra suggests interaction with a pre-existing circumstellar environment could be occurring at early times. In the SN 2022wsp spectra, the absorption component of the Mg II P Cygni profile displays a double-trough feature on day +10 that disappears by day +20. The shape is well reproduced by the model without fine-tuning the parameters, suggesting that the secondary blueward dip is a metal transition that originates in the SN ejecta.Comment: Submitted to ApJ Letters on 4/11/202

In vivo and ex vivo measurements: noninvasive assessment of alcoholic fatty liver using 1H-MR spectroscopy

PURPOSEWe aimed to evaluate the ability of 1H-magnetic resonance spectroscopy (1H-MRS) to detect and quantify hepatic fat content in vivo and ex vivo in an experimental rat model of alcoholic fatty liver using histopathology, biochemistry, and laboratory analyses as reference.METHODSAlcoholic fatty liver was induced within 48 hours in 20 Lewis rats; 10 rats served as control. Intrahepatic fat content determined by 1H-MRS was expressed as the percent ratio of the lipid and water peaks and was correlated with intrahepatic fat content determined histologically and biochemically. Liver enzymes were measured in serum.RESULTSFatty liver could be detected in vivo as well as ex vivo using 1H-MRS, in all 20 animals. Histologic analysis showed a fatty liver in 16 of 20 animals. Histology and 1H-MRS results were highly correlated (in vivo, r=0.93, P = 0.0005; ex vivo, r=0.92, P = 0.0006). Also a strong correlation was noted between in vivo 1H-MRS measurements and the fat content determined biochemically (r=0.96, P = 0.0003). Ex vivo results showed a similarly strong correlation between 1H-MRS and biochemistry (r=0.89, P = 0.0011).CONCLUSION1H-MRS can be carried out in ex vivo models, as well as in vivo, to detect and quantify intrahepatic fat content in the acute fatty liver