This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and ...irinotecan-based systemic chemotherapy regimens.
Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).
Of 50 eligible patients, 38 (76%) had received > or =4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%.
Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.
Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal ...cord compartment segmentation (SCORE) in patients with MS.
The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer.
The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all
< .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (
< .05), and total anterior horn areas (
< .01 respectively), as measured with SCORE.
We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.
There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).
To determine how serum glial fibrillary acidic protein (sGFAP) ...and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression.
Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022. The SMSC is a prospective, multicenter study performed in 8 centers in Switzerland. For this nested study, participants had to meet the following inclusion criteria: cohort 1, patients with MS and either stable or worsening disability and similar baseline Expanded Disability Status Scale scores with no relapses during the entire follow-up; and cohort 2, all SMSC study patients who had initiated and continued B-cell-depleting treatment (ie, ocrelizumab or rituximab).
Patients received standard immunotherapies or were untreated.
In cohort 1, sGFAP and sNfL levels were measured longitudinally using Simoa assays. Healthy control samples served as the reference. In cohort 2, sGFAP and sNfL levels were determined cross-sectionally.
This study included a total of 355 patients (103 29.0% in cohort 1: median IQR age, 42.1 33.2-47.6 years; 73 female patients 70.9%; and 252 71.0% in cohort 2: median IQR age, 44.3 33.3-54.7 years; 156 female patients 61.9%) and 259 healthy controls with a median IQR age of 44.3 36.3-52.3 years and 177 female individuals (68.3%). sGFAP levels in controls increased as a function of age (1.5% per year; P < .001), were inversely correlated with BMI (-1.1% per BMI unit; P = .01), and were 14.9% higher in women than in men (P = .004). In cohort 1, patients with worsening progressive MS showed 50.9% higher sGFAP levels compared with those with stable MS after additional sNfL adjustment, whereas the 25% increase of sNfL disappeared after additional sGFAP adjustment. Higher sGFAP at baseline was associated with accelerated gray matter brain volume loss (per doubling: 0.24% per year; P < .001) but not white matter loss. sGFAP levels remained unchanged during disease exacerbations vs remission phases. In cohort 2, median (IQR) sGFAP z scores were higher in patients developing future confirmed disability worsening compared with those with stable disability (1.94 0.36-2.23 vs 0.71 -0.13 to 1.73; P = .002); this was not significant for sNfL. However, the combined elevation of z scores of both biomarkers resulted in a 4- to 5-fold increased risk of confirmed disability worsening (hazard ratio HR, 4.09; 95% CI, 2.04-8.18; P < .001) and PIRA (HR, 4.71; 95% CI, 2.05-9.77; P < .001).
Results of this cohort study suggest that sGFAP is a prognostic biomarker for future PIRA and revealed its complementary potential next to sNfL. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.
The choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is ...not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, the aim of this study was to compare the choroid plexus volume in MS and NMOSD.
In this retrospective, cross-sectional study, patients were included by convenience sampling from 4 international MS centers. The choroid plexus of the lateral ventricles was segmented fully automatically on T1-weighted MRI sequences using a deep learning algorithm (Multi-Dimensional Gated Recurrent Units). Uni- and multivariable linear models were applied to investigate associations between the choroid plexus volume, clinically meaningful disease characteristics, and MRI parameters.
We studied 180 patients with MS and 98 patients with NMOSD. In total, 94 healthy individuals and 47 patients with migraine served as controls. The choroid plexus volume was larger in MS (median 1,690 µL, interquartile range IQR 648 µL) than in NMOSD (median 1,403 µL, IQR 510 µL), healthy individuals (median 1,533 µL, IQR 570 µL), and patients with migraine (median 1,404 µL, IQR 524 µL; all
< 0.001), whereas there was no difference between NMOSD, migraine, and healthy controls. This was also true when adjusted for age, sex, and the intracranial volume. In contrast to NMOSD, the choroid plexus volume in MS was associated with the number of T2-weighted lesions in a linear model adjusted for age, sex, total intracranial volume, disease duration, relapses in the year before MRI, disease course, Expanded Disability Status Scale score, disease-modifying treatment, and treatment duration (beta 4.4; 95% CI 0.78-8.1;
= 0.018).
This study supports an involvement of the choroid plexus in MS in contrast to NMOSD and provides clues to better understand the respective pathogenesis.
Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice.
To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other ...conditions showing brain lesions on magnetic resonance imaging (MRI).
This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 64.4% female; mean SD age, 41.5 12.3 years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 66.8% female; mean SD age, 49.2 14.5 years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2).
MS/CIS vs non-MS conditions.
Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model.
The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 95% CI, 0.86-0.91) was superior to that of CLs (AUC, 0.77 95% CI, 0.75-0.80; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 95% CI, 0.90-0.94; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis.
The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.
A great number of locoregional treatments are currently carried out to treat a variety of locoregional neoplastic diseases. Indications are the treatment of primary and metastatic liver tumors, ...peritoneal mesotheliomas, peritoneal spread of ovarian carcinomas, peritoneal recurrences of gastrointestinal cancers, peritoneal spread of retroperitoneal sarcomas, melanomas and sarcomas of the limbs, some primary tumors of the brain, breast, kidney, lung, bladder. But to deal with locoregional therapy demands to clarify some features of these malignancies. At this regard, the knowing of their natural history can be crucial to guide the choice of the correct locoregional treatment. For instance peritoneal carcinomatosis is considered as a main step of disease progression for ovarian cancer and often for gastrointestinal tumors as well. However when the tumors are confined on the surface of the peritoneum, basing on their own natural history, they can be considered as localized diseases. Selected patients with peritoneal neoplastic seeding, previously considered in a preterminal condition, can be considered as candidates for curative treatment, using cytoreductive surgical tecniques (16) and hyperthermic intraperitoneal chemotherapy (19). The same can be thought about others primary or metastatatic tumors when the neoplastic deposits are confined within a definite site or region of the body. In this paper the main aspects of liver metastases and peritoneal carcinomatosis natural history, two of the most frequently recognized indications for locoregional therapy, are presented.
Circular staplers have reduced the incidence of anastomotic leaks in esophagovisceral anastomosis. However, the prevalence of stenosis is greater with staplers than with manual suturing. The aim of ...this study was to analyze potential risk factors for the onset of anastomotic stenoses and to evaluate their treatment and final outcome.
Between 1990 and 1995, 187 patients underwent esophagectomy and esophagogastrostomy with anastomosis performed inside the chest using a circular stapler.
Twenty-three patients (12.3%) developed an anastomotic stenosis. The incidence of strictures was inversely related to the diameter of the stapler. Concomitant cardiovascular diseases; morphofunctional disorders of the tubulized stomach, such as those related to duodenogastric reflux; and neoadjuvant chemotherapy were also recognized as significant risk factors. Endoscopic dilatations proved safe and were effective in the treatment of most anastomotic stenoses.
To reduce the risk of anastomotic stenosis after stapled intrathoracic esophagogastrostomy, adequate vascularization of the viscera being anastomized should be maintained, and it is mandatory to use the largest circular stapler suitable. Furthermore, it is essential to reduce the negative inflammation-inducing effects of duodenogastroesophageal reflux to a minimum. Endoscopic dilatations are safe and effective in curing the great majority of anastomotic stenoses.
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