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BACKGROUND AND AIMS: Adequate bowel cleansing is essential for colonoscopy quality. A novel 1 L polyethylene glycol plus ascorbate (1 L PEG+ASC) solution has been recently introduced. Nevertheless, the efficacy of 1 L PEG+ASC as compared to that of high-volume bowel preparation in both inpatients and outpatients is still unclear. PATIENTS AND METHODS: This single-blinded, non-inferiority study randomized patients undergoing colonoscopy to receive split-dose 1 L PEG+ASC or 4 L PEG. The primary endpoint was the overall cleansing success. Secondary endpoints were excellent cleansing and high-quality cleansing of the right colon, as well as lesions detection rate, patient compliance, tolerability and safety. RESULTS: Overall, 478 patients were randomized to 1 L PEG+ASC (N = 236) or 4 L PEG (N = 242). The 1 L PEG+ASC showed higher cleansing success rate (91.8% vs 83.6%; P=0.01) and a high-quality cleansing of the right colon (52.3% and 38.5%; P=0.004) compared to 4 L PEG. Moreover, 1 L PEG+ASC achieved a higher cleansing success in out-patients (96.3%% vs 88.6%; P=0.018), and a similar success rate in the in-patients (84.7% vs 76.7%; P=0.18). Adenoma detection rate, tolerability and incidence of adverse events were comparable between preparations. CONCLUSIONS: The 1 L PEG+ASC showed higher efficacy in achieving adequate colon cleansing compared with 4 L PEG, particularly in the right colon. No differences in the tolerability and safety were detected.
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Catárticos , Polietilenoglicóis , Humanos , Polietilenoglicóis/efeitos adversos , Catárticos/efeitos adversos , Colonoscopia , Laxantes , Colo , Ácido Ascórbico/efeitos adversosRESUMO
The approved combination of Tixagevimab/Cilgavimab has been shown to decrease the rate of symptomatic SARS-CoV-2 infection in patients at increased risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematological malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. We performed a real-life prospective cohort study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab in anti-spike seronegative patients compared to a cohort of seropositive patients who were observed or received a fourth vaccine dose. We recruited 103 patients with a mean age of 67 years: 35 (34%) received Tixagevimab/Cilgavimab and were followed from March 17, 2022, until November 15, 2022. After a median follow-up of 4.24 months, the 3-month cumulative incidence of infection was 20% versus 12% in the Tixagevimab/Cilgavimab and observation/vaccine groups respectively (HR 1.57; 95% CI: 0.65-3.56; p = 0.34). In this study, we report our experience with Tixagevimab/Cilgavimab and a tailored approach to SARS-CoV-2 infection prevention in patients with hematological malignancies during the SARS-CoV-2 omicron surge.
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Occurrence of venous thromboembolism in cancer patients (patients) undergoing chemotherapy is a remarkable concern for the oncologist. In addition, careful attention has to be paid to the possible major bleeding when patients carrying gastrointestinal cancer need antithrombotic therapies. To date some Cancer Associated Thrombosis (CAT) risk scores as Khorana and PROTECHT score have been developed to identify the cancer population at high-risk for venous thromboembolism (VTE). Consensus guidelines recommend to consider also low molecular weight heparin (LMWH) for primary thromboprophylaxis in high-risk patients. This is a report on a retrospective case series of 15 intra-luminal not surgically treated gastrointestinal cancer patients deemed high risk for VTE. The patients had a Khorana or PROTECHT score of 2 points or more (at least ≥ 2 points). They were undergoing first line chemotherapy in the absence of endoscopic signs of cancer spontaneous bleeding. A prophylactic dose of LMWH was administered just before starting the chemotherapy session and until 48 hours after its completion. The authors mainly aimed to report occurrence of clinically perceptible gastrointestinal bleeding events. Fifteen patients were administered LMWH - median age: 59 (range: 42-79); gender: male 12 (80%); tumor type: stomach - 13 patients (86%); gastro-esophageal junction: 2 patients (14%). Duration of heparin treatment: the total treatment duration was 228 days; mean 15.2 days (range: 5-45); nadroparin: mean 14.7 days (range: 5-45); enoxaparin: mean 10.1 days (range: 5-20); parnaparin: a total of 5 days. None of the patients experienced perceptible gastrointestinal bleeding. Short-term LMWH thromboprophylaxis appeared to be safe for this series of patients.
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Accessory spleens (AcS) may play a relevant role in immune thrombocytopenia (ITP) and possibly contribute to ITP relapse following splenectomy. Little is known about the immune microenvironment of AcS in ITP. To address this issue, we compared the histological features of eight matched AcS and main spleen (MS) samples, obtained from adult patients with primary ITP. AcS and MS had overlapping immune architectural features and lymphoid composition, suggesting that similar immunologic events occur in AcS and MS of ITP. These findings may have implications for the potential mechanisms of AcS-mediated ITP relapse. Further studies are needed to confirm these results and to dissect spleen immunity in ITP.
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Púrpura Trombocitopênica Idiopática , Esplenopatias , Trombocitopenia , Adulto , Humanos , Esplenectomia/métodos , RecidivaRESUMO
We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.
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Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib , Proteínas de Fusão bcr-abl/genética , Inibidores de Proteínas Quinases/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Indução de RemissãoRESUMO
BACKGROUND: In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multicenter retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of digital-single operator cholangioscopy (D-SOC) to treat difficult biliary stones in cases with a previous failure of conventional endoscopic methods. METHODS: Only patients with a previous failure of endoscopic standard treatment and a D-SOC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient. RESULTS: Out of 1258 ERCP performed at our centers, 31 cholangioscopes in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs. 77.7%, P>0.05). Furthermore, the success rate of digital D-SOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon. CONCLUSIONS: Our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.
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Cálculos Biliares , Litotripsia , Humanos , Estados Unidos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Biliares/cirurgia , Cálculos Biliares/etiologia , Litotripsia/efeitos adversos , Litotripsia/métodosRESUMO
Thrombopoietin receptor agonists (TPO-RA) are a valid therapy for immune thrombocytopenia (ITP), due to megakaryocyte stimulation and (poorly characterised) immune-modulatory effects. The spleen is pivotal in the pathogenesis of ITP, yet little is known on its immune microenvironment and on effects of TPO-RA on this organ. To address these topics, we analysed 35 spleens removed for primary refractory ITP. Pre-splenectomy TPO-RA administration correlated with increased splenic regulatory T cells (Tregs), type 2 T-helper cells and histiocyte density and with reduced red pulp sinusoids. Surgical outcome was not associated with TPO-RA administration, other pre-splenectomy therapies and/or Treg density. In conclusion, TPO-RA affect the splenic microenvironment, but this has no impact on splenectomy outcome.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/etiologia , Receptores Fc , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão , Baço/patologia , Linfócitos T Reguladores/patologia , Trombocitopenia/complicações , Trombopoetina/farmacologia , Trombopoetina/uso terapêuticoRESUMO
BACKGROUND: Direct bile ducts visualization through cholangioscopy has gained popularity due to its better diagnostic accuracy than a standard ERCP in indeterminate biliary stricture. AIM: We aimed to review our catheter-based cholangioscopy interventions in patients with indeterminate biliary stenosis, using the SpyGlass Direct Visualization System (SDVS) and summarize our experience in terms of procedures and results. RESULTS: we collected 25 consecutive patients with indeterminate biliary stricture over 3 years. The overall procedural success in our cohort amounted to 96% (24/25). If we focus on the diagnostic procedures, the ability to merely visualize the region of interest/lesion and perform biopsy of the lesion was possible in 96 % (24/25) In our cohort localization in the common bile duct (P = 0.03; 95 % CI 0.27-0.96) was found as positive determining factor for diagnosis. Sensitivity, specificity and accuracy for visual diagnosis by SDVS in our cohort were 100, 83.3 and 96 %, respectively. The use of biopsy or obtaining a histological diagnosis to assist in identifying patients with malignant stenosis, to exclude malignancy and to correctly classify diagnosed patients resulted in a sensitivity of 100 %, a specificity of 73% % with an overall accuracy of 94.4 %. Only a mild adverse event (cholangitis, treated conservatively) occurred. CONCLUSIONS: Today, the SDVS should be considered essential in diagnosing indeterminate biliary strictures, since the procedure is associated with high procedural success in terms of diagnostic accuracy, alters clinical outcome in over 80 % of considered insolvable cases, with an acceptable safety profile.
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Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22-4·60, P = 0·01] and thrombocytosis> 400 × 109 /l at RUX start (HR:1·98, 95%CI: 1·10-4·60, P = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24-7·92, P = 0·02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3·20, 95%CI: 1·17-8·75, P = 0·02 and HR: 2·93, 95%CI: 1·39-6·17, P = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11-5·25, P = 0·03), platelet > 400 × 109 /l (HR: 3·30, 95%CI: 1·67-6·50, P = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48-8·14, P = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.
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Inibidores de Janus Quinases/efeitos adversos , Segunda Neoplasia Primária/induzido quimicamente , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Incidência , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/toxicidade , Linfoma/diagnóstico , Linfoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Nitrilas , Mielofibrose Primária/patologia , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Pirazóis/toxicidade , Pirimidinas , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Trombocitose/induzido quimicamente , Trombocitose/diagnóstico , Trombose/induzido quimicamente , Trombose/diagnósticoRESUMO
OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.
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Púrpura Trombocitopênica Idiopática/diagnóstico , Baço/patologia , Adolescente , Adulto , Idoso , Autoimunidade , Biópsia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/mortalidade , Púrpura Trombocitopênica Idiopática/terapia , Estudos Retrospectivos , Esplenectomia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
: Thrombopoietin receptor agonists (TPO-RA) are currently approved to treat chronic immune thrombocytopenia (ITP) but there is increasing interest in considering these drugs earlier during the course of the disease. We present six patients with primary ITP resistant to corticosteroids and intravenous immunoglobulins, who received TPO-RA in the persistent phase and then underwent splenectomy in the chronic phase. Eltrombopag was administered as a second-line therapy in four patients, whereas two patients received romiplostim. Five out of six patients rapidly reached response or complete response (four and one, respectively) and steroid suspension. In one case, remission was obtained with steroid and TPO-RA. No significant side effects were reported. After splenectomy, complete response and response was reached in four and two patients, respectively. One relapse was recorded, rescued by steroid and eltrombopag. Postsplenectomy complication was registered in one patient (grade 4 intra-abdominal bleeding). TPO-RA could be a valuable choice in ITP patients in persistent phase candidates to splenectomy.
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Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Corticosteroides/farmacologia , Doença Crônica , Resistência a Medicamentos , Feminino , Humanos , Imunoglobulinas Intravenosas/farmacologia , Masculino , Púrpura Trombocitopênica Idiopática/cirurgia , EsplenectomiaRESUMO
The use of generic drugs after patent expiration of their originators is a relative novelty in the treatment of chronic cancer patients in Western countries. In this observational study we analyzed a cohort of 294 Italian chronic phase chronic myeloid leukemia patients treated frontline with branded imatinib (Glivec®) for at least 6 months and then uniformly switched to generic imatinib upon requirement of health authorities in early 2017. Median age at diagnosis was 57 years (range 19-87). Sokal risk was low/intermediate/high in 55%, 32% and 8% of cases, respectively. Median duration of branded imatinib treatment was 7.4 years (range 0.5-16.7). At a median follow-up of 7.5 months after switch to generic imatinib, 17% of patients reported new or worsening side effects, but grade 3-4 non-hematological adverse events were rare. Six patients switched back to branded imatinib, with improvement in the side effect profile, and 4 pts moved to bosutinib or nilotinib for resistance/intolerance. The majority of patients were in major (26%) or deep molecular response (66%) at the time of switch. Molecular responses remained stable, improved or worsened in 61%, 25% and 14% of patients, respectively. We conclude that switch to generic imatinib for patients who have been receiving branded imatinib appears to be effective and safe. Molecular responses may continue to improve over time. Some patients experienced new or worsened side effects but less than 5% of the whole cohort needed to switch back to branded imatinib or move to other treatments. Savings were around 3 million Euros.
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Medicamentos Genéricos/administração & dosagem , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos Genéricos/efeitos adversos , Feminino , Seguimentos , Humanos , Mesilato de Imatinib/efeitos adversos , Itália/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Self-expandable metal stents are a non-surgical option for the treatment of symptomatic malignant colorectal obstruction as palliative treatment or as a bridge to surgery. AIMS: To report data from a regional study on self-expandable metal stent (SEMS) placement for malignant colorectal obstruction. METHODS: Two hundred and four patients (male 54.9%, mean age of 69.5 ± 14.2) were retrospectively evaluated and data on technical and clinical success, and complications, were analyzed. RESULTS: Technical and clinical success rates were 99% and 94.6% respectively, with 36.7% treated on an emergency basis and 63.3% electively. Palliative treatment was administered to 70.1%, and as a bridge to surgery for 29.9%. Complications were 17 neoplastic ingrowths, 10 stent migrations, and 4 perforations. Palliative treatment was associated with a higher risk of stent ingrowth (p=0.003), and chemotherapy with a lower risk of stent ingrowth (p=0.009). CONCLUSION: This regional study, although it has certain limitations, confirms the positive role of self-expandable metal stents in the treatment of symptomatic malignant colorectal obstruction, and that chemotherapy decreases the risk of ingrowth.