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Objective: Slit ventricle syndrome (SVS) is an iatrogenic disease occurring in patients with ventriculoperitoneal shunt. This article reports the management modalities and results in a case series from a single center., Methods: We reviewed a series 48 hospitalized patients with severe SVS whom we managed in a 10-year period. Thirty-seven patients harboring programmable valves (P-valves) first underwent attempts at valve reprogramming. This treatment produced no effect in 21 patients, who therefore required surgical treatment. Surgery was also required by 11 patients without P-valve. Accordingly, 32 patients had to be operatively treated by shunt externalization followed by valve replacement or endoscopic third ventriculostomy basing on intracranial pressure and ventricular size. The new valve was either ProGav Mietke (Aesculap) or Medos Codman (Integra), each equipped with its own antisiphon system. In selected cases, a programmable antisiphon system (ProSa Mietke) was used., Results: Surgical mortality was 3% and major morbidity accounted for 6%. Complete resolution was obtained in 55% of cases, improvement in 32%, and no effect or worsening in 13%. Only 1 patient became shunt free after endoscopic third ventriculostomy. Medos and ProGrav provided comparable outcomes, whereas ProSa was determinant in selected cases. Pediatric age, uncomplicated shunt courses, and short SVS histories were significantly favorable indicators., Conclusions: SVS management remains problematic. However, this study individuated factors that may improve the outcome, such as wider use of P-valves to treat hydrocephalus, timely diagnosis of overdrainage, and earlier and more aggressive indications to manage SVS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Endoscopic third ventriculostomy (ETV) is now widely used to manage ventriculoperitoneal shunt (VPS) malfunctions, but outcome predictors are still debated. Different opinions exist about the prognostic factors, but shunt duration is generally considered unimportant although its influence remains poorly investigated., Methods: A total of 139 patients undergoing ETV for VPS malfunction were reviewed. Successful ETV was defined as shunt independence. There were 56 children and 83 adults; hydrocephalus had different causes. The mean VPS-ETV interval was 8.1 years., Results: Ninety patients (64.7%) became shunt free. Children and adults achieved comparable success rates (64.3% and 65.1%, respectively). Age, gender, and cause of shunt malfunction were scarcely significant. The success rates were 86.8% (33/38 patients) in obstructive hydrocephalus (OH), 55.2% (36/67) in communicating hydrocephalus, and 58.8% (21/34) in myelomeningocele-related hydrocephalus, which was significant (P = 0.02). History of multiple revisions was a negative predictor (P < 0.001): success rate, 39% (16/48) versus 81.3% (74/91). Any individual time step increase reduced the odds of ETV success by 34% (P = 0.014). In OH, the results were good regardless of any other factor, including shunt duration. In communicating hydrocephalus, short VPS-ETV intervals correlated with better outcome (P = 0.021), although they were irrelevant in perinatal posthemorrhagic hydrocephalus. In myelomeningocele-related hydrocephalus, shunt duration had intermediate effects., Conclusions: ETV is the first option for shunt malfunctions in OH and perinatal posthemorrhagic hydrocephalus, regardless of other factors. Conversely, in other types of hydrocephalus, the chances of shunt independence are lower and shunt duration and history of multiple shunt revisions are significant., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection., Materials and Methods: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis., Results: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001)., Conclusion: KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To refine the surgical indications of surgery for life-threatening cerebral hematomas caused by aneurysm rupture, through the analysis of possible outcome predictors., Methods: Forty-nine consecutive patients requiring prompt clot evacuation were retrospectively reviewed. In all cases, the hematoma was equal to or greater than 60 mL. The bleeding aneurysm was located on the middle cerebral artery in 26 cases, on the internal carotid artery in 10 cases, and on the anterior cerebral artery in 13 cases; four aneurysms were giant. Six patients underwent aneurysm coiling followed by clot removal, whereas 43 patients were managed by concomitant clot evacuation and aneurysm clipping. The main clinical and radiologic features, the management paths and the treatment modalities were correlated with the outcomes. A statistical analysis was conducted., Results: Overall mortality was 32.6%, severe morbidity was 22.4% and 22 patients (44.8%) achieved favorable results. The short-term results were more significantly influenced by the radiological parameters than by the initial clinical conditions. The prognostic weight of the radiologic findings was partially lost for six-month results, whereby management factors gained in importance., Conclusions: The bleeding severity was strongly determinant for early mortality. However, if patients can survive the initial crucial phase, their chances of a favorable outcome are not negligible. Further improvement may be possible through better patient selection and the identification of nonsalvageable subjects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To identify prioritization based on hemorrhagic risk and indications for treatment of arterial and venous aneurysms associated with arteriovenous malformation (AVM)., Methods: From a global series of 400 consecutively treated AVMs, 34 patients (8.5%) with 45 arterial or venous aneurysms were extrapolated. These 45 lesions were classified as unrelated aneurysms (n = 5 cases; 11.%), flow-related aneurysms (n = 18 cases; 40%), and intranidal and postnidal venous aneurysms (n = 22; 49.%). The 18 flow-related aneurysms were further divided into remote (n = 6 cases) and adjacent (n = 12 cases) types. Of 45 aneurysms associated with AVMs, 15 were unruptured with a 5-year mean follow-up. Various possible risk indicators were considered and measured by univariate and multivariate analyses., Results: During the follow-up period, 1 of 15 unruptured aneurysms bled, and the patient died. A significantly different bleeding incidence was found between unrelated aneurysm and flow-related aneurysm types (P = 0.002). Bleeding was significantly less probable in flow-related remote aneurysm type than in venous and flow-related adjacent aneurysm types (P = 0.007). The location of the aneurysm was the only true risk factor for bleeding; the other parameters had no influence on bleeding., Conclusions: In this series, different subtypes of aneurysms associated with AVMs had different clinical behaviors. The bleeding risk of the unrelated aneurysm and the flow-related remote aneurysm types should be considered almost the same as any other unruptured aneurysm. In other words, bleeding risk should be considered taking into account the parameters established by the International Study of Unruptured Intracranial Aneurysms (location, size, and morphology). Conversely, flow-related adjacent aneurysm and venous aneurysm types have significantly higher bleeding potentials., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: This study aims to identify the angiographic parameters that could help predict the risks of hyperemic complications (HCs) in the treatment of cerebral arteriovenous malformations (AVMs)., Methods: The charts and the pre- and post-treatment angiographies of 400 consecutively treated patients with cerebral AVMs were retrospectively reviewed. Several parameters were analyzed: grade, size, drainage depth, number of the "recruited veins" (veins coming from the brain and joining the main AVM drainage), and "venous times" (the times of visualization of the nidus and the main drainage, of the "recruited veins," and finally of the normal cerebral veins). On this basis, two groups were identified: group 1, consisting of 309 patients (77.3%) with normal/subnormal venous times, and group 2, consisting of 91 patients (22.7%) with altered venous times and venous engorgement. Finally, the weight of the various parameters was measured by univariate and multivariate analyses., Results: An overall number of 245 patients (61.2%) achieved favorable outcomes. HCs occurred in a total of 28 patients (7%): No patient belonged to group 1, so that these adverse effects were reported in 30.7% of group 2 patients. The presence of deep drainage and the number of recruited veins resulted in statistically significantly different impacts on the risk of the different grades., Conclusions: The statistical analysis allowed the identification of three different risk scores, which were named Nig-scores (Niguarda scores). Nig-score 0 means no risk of HCs and concerns patients without altered venous times; Nig-score 1 represents patients with intermediate risk, that is, with moderately altered venous times and few recruited veins; Nig-score 2 indicates high risk of HCs and refers to patients with markedly altered venous times., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The clinical course of patients with B-cell CLL is often complicated by autoimmune phenomena. The DAT might be positive at some time during the course of the disease in up to 35% of cases. The aim of this retrospective study was to investigate the relationship between the occurrence of a positive DAT and biological features of CLL patients., Patients and Methods: In our institution, 146 untreated patients with CLL were studied using the DAT., Results: According to the statistical analysis, a high level of β2-microglobulin and unmutated IgHV emerged as factors significantly related to the presence of DAT positivity. Time to first TFS was significantly shorter in DAT-positive patients. The adverse effect of a DAT positive result was maintained in terms of TFS when patients with mutated IgHV status were excluded from statistical analysis., Conclusion: These results suggest that the DAT might provide additional prognostic information regarding patients with IgHV unmutated status., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: We show that detection, by week-2 magnetic resonance imaging, of tumor shrinkage >10% in response to therapy with cetuximab or panitumumab for metastatic colorectal carcinoma represents an early indicator of clinical outcome because it is predictive of the prolongation of progression-free survival and overall survival., Purpose: The early identification of patients with metastatic colorectal carcinoma who are likely to benefit from treatment with panitumumab or cetuximab remains of paramount importance. We evaluated whether the early tumor shrinkage assessed by magnetic resonance imaging (MRI) is predictive of long-term outcome to these epidermal growth factor receptor-targeted therapies., Patients and Methods: Thirty-nine patients with chemorefractory metastatic colorectal carcinoma were treated with cetuximab or panitumumab. The patients were evaluated by unenhanced MRI at baseline, week 2, and week 8 after the beginning of the treatment and by contrast-enhanced computed tomography within 3 months. Early response was defined as a tumor shrinkage ≥ 10% at week-2 MRI, whereas response by contrast-enhanced computed tomography was defined according to standard Response Evaluation Criteria in Solid Tumors 1.1., Results: At week-2 MRI, 15 (38.5%) of 39 patients had an early response. Eleven (73.3%) of these 15 early responders then presented a partial response by contrast-enhanced computed tomography, whereas none of the 24 early nonresponders obtained a partial response (P < .0005, Fisher exact test). Median progression-free survival (PFS) was 29.7 and 8 weeks in patients with or without early response, respectively (hazard ratio [HR] 0.156 [95% CI, 0.069-0.355]; P < .0001)]. The median overall survival (OS) was 80 weeks in patients with early response and 23.3 weeks in those without early response, respectively (HR 0.154 [95% CI, 0.057-0.420]; P < .00005])., Conclusions: Early detection of tumor response by week-2 MRI without contrast medium is associated with a prediction of clinical outcome in patients with metastatic colorectal carcinoma treated with cetuximab or panitumumab., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM MG) into symptomatic lymphoproliferative disease in 287 patients all analyzed for bone marrow histopathology and immunophenotyping. This series included 201 patients with IgM MG of undetermined significance (IgM MGUS) and 86 with smoldering Waldenström's macroglobulinemia (sWM). After a median of 50 months (range, 12-322 months), 32 cases of aIgM-MG (11.1%) evolved into symptomatic malignant lymphoproliferative disease, as follows: symptomatic WM (n=26), non-Hodgkin lymphoma (n=6). The cumulative transformation percentage at 5 and 10 years was 8% and 19.5%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, serum MC, serum IgM size, and serum IgA size. Among patients with aIgM-MG, those at high risk of evolution were patients with sWM, a distinct entity with serum IgM monoclonal protein≥3 g/dL and/or ≥10% bone marrow lymphoplasmacytic infiltration.

Advanced age is one of the variables more frequently considered to be associated with an adverse prognosis in Waldenström's macroglobulinemia (WM). In a series of 238 symptomatic and asymptomatic WM patients, we retrospectively identified an age cut-off distinguishing two groups of patients with different outcome in terms of overall survival (OS), disease-specific survival (DSS) and treatment-free survival (TFS). Although for the OS the best cut-off was identified at 65 years with shorter OS for elderly patients, no difference was detected in terms of DSS between the two groups. Furthermore, patients over 65 years showed a longer TFS compared with patients under 65 years. Clinical and laboratory disease characteristics did not significantly differ between the two groups of patients except for β2M level. Therefore, the poorer survival of patients over 65 years at diagnosis should probably be attributed to the higher number of no disease-related deaths and is independent from WM.

Core-binding factor leukemia (CBFL) is a subgroup of acute myeloid leukemia (AML) characterized by genetic mutations involving the subunits of the core-binding factor (CBF). The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for leukemia development. One of the most common mutations associated with CBF mutations involves the KIT receptor. A high expression of KIT is a hallmark of a high proportion of CBFL. Previous studies indicate that microRNA (MIR) 222/221 targets the 3' untranslated region of the KIT messenger RNA and our observation that AML1 can bind the MIR-222/221 promoter, we hypothesized that MIR-222/221 represents the link between CBF and KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid differentiation of normal bone marrow AC133(+) stem progenitor cells. CBFL blasts with either t(8;21) or inv(16) CBF rearrangements with high expression levels of KIT (CD117) display a significantly lower level of MIR-222/221 expression than non-CBFL blasts. Consistently, we found that the t(8;21) AML1-MTG8 fusion protein binds the MIR-222/221 promoter and induces transcriptional repression of a MIR-222/221-LUC reporter. Because of the highly conserved sequence homology, we demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the 32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study provides the first hint that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining the concomitant occurrence of CBF genetic rearrangements and overexpression of wild type or mutant KIT in AML.

Background: Patients with a recently implanted coronary drug-eluting stent (DES) who need urgent surgery are at increased risk of surgical bleeding unless clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been associated with a high rate of adverse events due to stent thrombosis. This pilot study tested the hypothesis that the i.v. perioperative administration of the short-acting antiplatelet agent tirofiban allows the safe withdrawal of clopidogrel without increasing the rate of surgical bleeding., Methods: Phase II study with a Simon two-stage design., Results: Thirty patients with a recently implanted DES [median (range) 4 (1-12) months] and high-risk characteristics for stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was to be withdrawn 5 days before surgery, and tirofiban started 24 h later, continued until 4 h before surgery, and resumed 2 h after surgery until oral clopidogrel was resumed. The use of aspirin was decided by the surgeon. There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0-11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding., Conclusions: In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a 'bridging strategy' using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding.

Distinct forms of tyrosine kinase domain (TKD), juxtamembrane domain, exon 8, and internal tandem duplication (ITD) mutations of c-KIT, were observed in about 46% of core binding factor leukemia (CBFL) patients. To evaluate their prognostic significance, 67 adult patients with CBFL were analyzed to ascertain the c-KIT mutation status. In acute myeloid leukemia (AML) with t(8;21), the presence of c-KIT TKD mutation at codon 816 (TKD(816)) was associated with a high white blood cell count at diagnosis (median, 29.60 x 10(9)/L) and a higher incidence (33%) of extramedullary leukemia (EML) during the course of the disease. Data also showed that the TKD(816) mutated patients (n = 12) had a significantly higher incidence of relapse and a lower overall survival (OS) at 24 months, compared with the 17 c-KIT unmutated (c-KIT(-)) patients (90% vs 35.3%, P = .002; 25% vs 76.5%, P = .006, respectively). No difference in relapse incidence (P = .126) and OS (P = .474) was observed between the c-KIT mutated other than TKD(816) (n = 7) and the c-KIT(-) patients. These findings indicate that c-KIT TKD(816) mutation has a negative impact on the outcome of AML with t(8;21).

Background: VWF:RCo assay is the standard and widely used laboratory test for von Willebrand disease (VWD) diagnosis. It is hampered by high intra- and inter-assay imprecision and is time consuming. Automation may improve the assay performance and allow its routine application., Objective: Automation of VWF:RCo on the ACL 7000 coagulometer (Instrumentation Laboratory, Milan, Italy) and its evaluation in VWD diagnosis., Methods and Materials: Method performance determination: precision, detection limit (DL), interferences, dose-response curve. Method comparison: analysis of 105 plasma samples from normal subjects (50), VWD type 1 (24), VWD type 2 (24) and VWD type 3 (7) with ACL VWF:RCo and comparison with the reference aggregometric (AGM) method., Results: ACL VWF:RCo: CVs around 10% vs. 19% of AGM method; DL: 0.08 U mL(-1); potential interferences from bilirubin, triglycerides and hemoglobin, avoided by suitable plasma dilution; high correlation with AGM VWF:RCo (Deming regression Y =-0.0277 + 1.0519X) either in normal or VWD plasmas. In VWD types 1 and 2, the VWF:RCo/VWF:Ag ratios are >0.6 or <0.6, respectively, when calculated with both AGM and ACL VWF:RCo values., Conclusions: The automated VWF:RCo on the ACL 7000 coagulometer shows precision improvement and high correlation with the reference AGM method. The test allows the diagnosis of both quantitative (VWD types 1 and 3) and qualitative (VWD type 2) forms of the disease. These results and the assay feasibility make it a suitable and reliable test for the routine diagnosis of VWD.