Abstract Objective To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in ...diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods Twenty preoperative tri-phasic MDCT (4–64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1–60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference ( p < .001), particularly for the detection of small lesions (≤1 cm; p < .004). There was no significant difference between the two modalities in the detection of lesions > 1 cm. Conclusion For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.
Background
18F‐2‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography/computed tomography (FDG‐PET/CT) imaging provides important information about the size and metabolic activity of ...lesions caused by Echinococcus multilocularis and is therefore recommended for the initial assessment and follow‐up of human alveolar echinococcosis (AE). The introduction of positron emission tomography/magnetic resonance imaging (PET/MRI) into clinical practice in affluent health care systems provides an alternative dual imaging modality, which has not yet been evaluated for AE.
Objective
Here, we describe the initial clinical experience with comparative PET/CT and PET/MR imaging in four human AE patients at an Austrian reference centre.
Results
PET/MR imaging showed comparable diagnostic capacity for liver lesions attributable to E. multilocularis infection, with a discrepancy only in the assessment of calcifications in one patient. Effective doses of radiation were 30.4–31 mSV for PET/CT, which were reduced in PET/MRI to the exposure of 18F‐FDG only (4.9–5.5 mSv).
Conclusions
PET/MRI provides comparable diagnostic information for AE management. The reduction in radiation exposure compared to PET/CT may be of particular importance for children and young patients not amenable for curative surgery requiring repeated long‐term follow‐up with dual imaging modalities. Further studies are warranted to prospectively evaluate the potential of PET/MRI in the management of AE.
Données de base
L'imagerie par la tomographie par émission de positrons au 18F‐2‐fluoro‐2‐désoxy‐D‐glucose (18F‐FDG)/tomodensitométrie (TEP/TDM) fournit des informations importantes sur la taille et l'activité métabolique des lésions causées par Echinococcus multilocularis et est donc recommandée pour l’évaluation initiale et le suivi de l’échinococcose alvéolaire (EA) humaine. L'introduction de la tomographie par émission de positons/imagerie par résonance magnétique (TEP/IRM) dans la pratique clinique des systèmes de soins de santé aisés offre une alternative de modalité d'imagerie double, qui n'a pas encore été évaluée pour l’EA.
Objectif
Nous décrivons ici l'expérience clinique initiale comparant les imageries TEP/TDM et TEP/IRM chez quatre patients humains atteints d’EA dans un centre de référence autrichien.
Résultats
L'imagerie TEP/IRM a montré une capacité de diagnostic comparable pour les lésions hépatiques imputables à une infection à E. multilocularis, avec une divergence uniquement lors de l’évaluation des calcifications chez un patient. Les doses efficaces de rayonnement étaient de 30,4 à 31 mSV pour la TEP/TDM, qui ont été réduites dans la TEP/IRM à une exposition au 18F‐FDG uniquement (4,9 à 5,5 mSv).
Conclusions
La TEP/IRM fournit des informations de diagnostic comparables pour la prise en charge de l’EA. La réduction de l'exposition aux rayonnements comparée à la TEP/TDM pourrait avoir une importance particulière pour les enfants et les jeunes patients ne pouvant pas subir de chirurgie curative nécessitant un suivi répété à long terme avec des modalités de double imagerie. Des études supplémentaires sont nécessaires pour évaluer de manière prospective le potentiel de la TEP/IRM dans la prise en charge de l’EA.
Purpose
Total parathyroidectomy (tPTX) in patients with renal hyperparathyroidism (RHPT) aims at the complete removal of all hyperfunctioning parathyroid tissue. Whenever parathyroidectomy is termed ...“total,” undetectable postoperative parathyroid hormone (PTH) levels within the first postoperative week are expected. The aim of this study was to evaluate if tPTX is technically possible using a radical surgical procedure.
Methods
In 109 consecutive patients with RHPT (on hemodialysis:
n
= 50; after kidney grafting
n
= 59), removal of all visible parathyroid tissue, bilateral thymectomy, bilateral central neck dissection (level VI), and immediate autotransplantation (AT) was performed. Intact PTH (iPTH) levels were measured in the first postoperative week. PTX was classified “total” when iPTH dropped below 10 pg/ml, “subtotal” between 10 and 65 pg/ml, and “insufficient” where levels stayed above 65 pg/ml.
Results
According to the postoperative PTH value, tPTX was achieved in 80 of 109 (73.4%) patients (hemodialysis
n
= 27, normal kidney function:
n
= 43, restricted:
n
= 10). PTX was “subtotal” in 25 patients (22.9%), 19 on hemodialysis, 2 had normal, and 4 had restricted kidney graft function. PTX turned out to be insufficient in four patients (3.7%); all of them were on hemodialysis. Insufficient PTX was not observed in kidney-grafted patients. Postoperative temporary laryngeal nerve morbidity was 1.8% (no permanent paresis).
Conclusions
Although applying a very radical concept in patients with RHPT, PTX was “total” in only 73.4%. Persistence of disease was avoided in 91.7%, and low morbidity was documented. In conclusion, it seems difficult to remove all parathyroid tissue from the neck which has to be considered when choosing the surgical procedure.
This trial investigates the addition of panitumumab to chemotherapy with fluorouracil/folinic acid and oxaliplatin (FOLFOX) in a 2:1 randomised, controlled, open-label, phase II trial in RAS ...wild-type colorectal cancer patients with R0/1-resected liver metastases.
The primary endpoint was progression-free survival (PFS) two years after randomisation. The experimental arm (12 weeks of biweekly mFOLFOX6 plus panitumumab followed by 12 weeks of panitumumab alone) was considered active if the two-year PFS rate was ≥65%. Based on historical data, a two-year PFS rate of 50% was estimated in the control arm (12 weeks of biweekly FOLFOX). The trial was performed with a power of 80% and an alpha of 0.05. Secondary endpoints included overall survival (OS) and toxicity. The trial is registered with ClinicalTrials.gov, NCT01384994.
The full analysis set consists of 70 patients (pts) in the experimental arm and 36 pts in the control arm. The primary endpoint was missed with a two-year PFS of 35.7% with FOLFOX plus panitumumab and 30.6% in the control arm. In comparative analyses, trends towards improved PFS (HR 0.83; 95%CI, 0.52–1.33; P = 0.44) and OS (HR 0.70; 95% CI, 0.34–1.46; P = 0.34) were observed in favour of the panitumumab-based study arm. No new or unexpected safety signals were observed with FOLFOX plus panitumumab following liver resection.
The PARLIM trial failed to demonstrate a two-year PFS rate of 65% after resection of colorectal liver metastases. The positive trends in survival endpoints may support future trials evaluating treatment with anti-EGFR agents after resection of liver metastases.
•FOLFOX plus panitumumab after the resection of liver metastases is safe and feasible.•The free-of-disease endpoint was missed with panitumumab and FOLFOX.•Survival trends may suggest panitumumab efficacy after the resection of metastases.
Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex
Echinococcus granulosus
. Albendazole (ABZ)—the first-line anthelminthic drug for medical treatment of CE—is ...metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = −0.03,
p
= 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L;
p
= 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L;
p
= 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4;
p
= 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L;
p
= 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (
β
= −17.2 μg/L/cm; 95th CI, −35.9 to 1.6;
p
= 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.
The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was ...retrospectively investigated in this study.
Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively.
One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0–80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases.
Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.
The aim of this study was to investigate the impact of portal hypertension (PH) on gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) and assess diagnostic and prognostic implications in ...comparison to established imaging features of PH.
Institutional review board-approved retrospective study of 178 patients (142 men; median age, 59.4 years) with chronic liver disease undergoing MRI and hepatic venous pressure gradient (HVPG) measurement between January 2008 and April 2015. Magnetic resonance imaging was assessed for established features of PH (splenic and portal vein diameters, portosystemic collaterals, ascites) and for features on 20 minutes delayed T1-weighted gadoxetic acid-enhanced MRI, that is, relative liver enhancement (RLE), biliary contrast excretion, or portal vein hyperintensity or isointensity (ie, portal vein hyperintensity sign, PVHS). Statistics encompassed linear regression, logistic regression, and survival analysis.
There was an inverse correlation between HVPG and RLE (r = 0.18, P < 0.0001). On univariate analysis, clinically significant PH (ie, HVPG ≥ 10 mm Hg, n = 109) and severe PH (ie, HVPG ≥ 12 mm Hg, n = 99) were associated with delayed biliary contrast excretion (n = 33) and the PVHS (n = 74) (P < 0.01 for all). Multivariate analysis demonstrated significant associations between the PVHS and severe PH (odds ratio OR, 3.33; P = 0.008), independently of spleen size (OR, 1.26; P = 0.002), portosystemic collaterals (n = 81; OR, 5.46; P = 0.0001), and ascites (n = 88; OR, 3.24; P = 0.006). Lower RLE and the PVHS were associated with lower 3-year, transplantation-free survival (hazards ratios, 0.98 and 3.99, respectively, P = 0.002 for all), independently of the Child-Pugh and Model for End-Stage Liver Disease scores.
The presence of the PVHS on gadoxetic acid-enhanced MRI is an independent indicator of severe PH and may enable more accurate diagnosis. This feature and decreased hepatic contrast uptake may also comprise prognostic information.
This study was conducted to analyze if the combination of Bevacizumab with standard chemotherapy increases postoperative morbidity and mortality after resection of colorectal liver metastases as ...compared with resection after chemotherapy alone. Parameters contributing to an increased morbidity were evaluated.
Most patients referred for colorectal liver metastases are treated with neoadjuvant chemotherapy before hepatic surgery. Targeted agents like the vascular endothelial growth factor-antagonist Bevacizumab are increasingly added to standard therapy to prolong survival; however, little is known about the consequences of this policy in the perioperative period.
One hundred-two patients treated between 2005 and 2009, who received neoadjuvant chemotherapy combined with Bevacizumab (CHT + B) were identified. A cohort of 112 patients treated without chemotherapy alone before resection served as the control group (CHT). Complications were graded within an established staging system and the therapeutic consequences were laid down. Uni- and multivariate analysis of factors contributing to postoperative complications in the CHT + B group was performed using a logistic regression model.
Postoperative complications occurred in 45 (44%, CHT + B) and 38 (34%, CHT) patients, respectively (P = 0.216). The incidence of severe complications requiring surgical or radiologic intervention or leading to organ failure was 10.8% in the CHT + B group and 7.1% in the CHT group (P = 0.350). Increased age, low serum albumin, resection of more than 3 liver segments and synchronous bowel procedures requiring an anastomosis were associated with an increased morbidity rate in the multivariate regression analysis. No patient died in either group.
The addition of Bevacizumab to standard chemotherapy before resection of colorectal liver metastases does not seem to increase postoperative morbidity. Caution should be given to extended resections >3 liver segments and synchronous bowel anastomoses.
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