Retroperitoneal paraduodenal unicentric Castleman disease: case report and review of the literature.

Castleman disease is a rare and benign disorder, characterized by enlarged lymph nodes and angiofollicular lymphoid hyperplasia. We report a case of a 57-year-old male, who was admitted to our surgical department because of a retroperitoneal nodular mass measuring about 4 cm in maximum diameter, incidentally discovered on a radiologic exam performed for the onset of vague abdominal pain with posterior irradiation. The patient was subdue to laparoscopic removal of the mass and no intra- and post-operative complications were recorded. Histologic diagnosis of hyaline-vascular variant of the Castleman disease was confirmed. Only two cases have been found in the literature reporting the paraduodenal unicentric Castleman disease localization like our case. Although rare, the Castleman disease must be considered in the differential diagnosis among all the lymph nodes diseases, for avoiding improper therapies.

Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular manifestations?

In this article, we reviewed the possible mechanisms linking the clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). CHIP is characterized by the presence of clonal mutations with an allelic frequency >2% in the peripheral blood without dysplasia, overt hematological neoplasms, or abnormalities in blood cell count. The prevalence may reach 20% of elderly healthy individuals and is considered a risk factor for myelodysplastic neoplasms and acute leukemia. In MPNs, CHIP is often associated with mutations such as JAK2V617F or DNMT3A, TET2, or ASXL1, which exhibit a 12.1- and 1.7-2-fold increase in CADs. Specifically, JAK2-mutated cells produce excessive cytokines and reactive oxygen species, leading to proinflammatory modifications in the bone marrow microenvironment. Consequently, the likelihood of experiencing thrombosis is influenced by the variant allele frequency (VAF) of the JAK2V617F mutation, which also appears to be correlated with anti-endothelial cell antibodies that sustain thrombosis. However, DNMT3A mutations induce pro-inflammatory T-cell polarization and activate the inflammasome complex, while TET2 downregulation leads to endothelial cell autophagy and inflammatory factor upregulation. As a result, in patients with TET2 and DNMT3A-related CHIP, the inflammasome hyperactivation represents a potential cause of CADs. CHIP also occurs in patients with large and small vessel vasculitis, while ADs are more frequently associated with MPNs. In these diseases, monocytes and neutrophils play a key role in the formation of neutrophil extracellular trap (NET) as well as anti-endothelial cell antibodies, resulting in a final procoagulant effect. ADs, such as systemic lupus erythematosus, psoriasis, and arthritis, are also characterized by an overexpression of the Rho-associated coiled-coil containing protein kinase 2 (ROCK2), a serine/threonine kinase that can hyperactivate the JAK-STAT pathway. Interestingly, hyperactivation of ROCK2 has also been observed in myeloid malignancies, where it promotes the growth and survival of leukemic cells. In summary, the presence of CHIP, with or without neoplasia, can be associated with autoimmune manifestations and thrombosis. In the presence of these manifestations, it is necessary to consider a "disease-modifying therapy" that may either reduce the clonal burden or inhibit the clonally activated JAK pathway.

Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 µg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met. RESULTS: In total, 127 patients were enrolled (ropeg: n=64; standard group: n=63). The primary end point was met in 81% and 51% in the ropeg and standard groups, respectively. Responders continued the assigned treatment until month 24 and maintained response in 83% and 59%, respectively (P=0.02). Ropeg responders less frequently experienced moderate/severe symptoms (33% vs. 67% in the standard group) and palpable splenomegaly (14% vs. 37%) and showed normalization of ferritin levels and blood counts. Nonresponders at 12 months crossed over to the standard (n=9) or ropeg (n=23) group; in patients switched to ropeg only, 7 of 23 met the response criteria in 12 months, and phlebotomy need was high (4.7 per patient per year). Discontinuation because of adverse events occurred in seven patients treated with ropeg. CONCLUSIONS: In this 24-month trial, ropeg was superior to phlebotomy alone in maintaining hematocrit on target. No dose-limiting side effects or toxicities were noted; 9.2% of patients on ropeg and no patients on standard treatment developed neutropenia. (Funded by AOP Health and others; ClinicalTrials.gov number, NCT03003325.)

Label-Free Enrichment of Circulating Tumor Plasma Cells: Future Potential Applications of Dielectrophoresis in Multiple Myeloma.

In multiple myeloma (MM), circulating tumor plasma cells (CTPCs) are an emerging prognostic factor, offering a promising and minimally invasive means for longitudinal patient monitoring. Recent advances highlight the complex biology of plasma cell trafficking, highlighting the phenotypic and genetic signatures of intra- and extra-medullary MM onset, making CTPC enumeration and characterization a new frontier of precision medicine for MM patients, requiring novel technological platforms for their standardized and harmonized detection. Dielectrophoresis (DEP) is an emerging label-free cell manipulation technique to separate cancer cells from healthy cells in peripheral blood samples, based on phenotype and membrane capacitance that could be successfully tested to enumerate and isolate CTPCs. Herein, we summarize preclinical data on DEP development for CTPC detection, as well as their clinical and research potential.

Impact of Different Cell Counting Methods in Molecular Monitoring of Chronic Myeloid Leukemia Patients.

BACKGROUND: Detection of BCR-ABL1 transcript level via real-time quantitative-polymerase-chain reaction (Q-PCR) is a clinical routine for disease monitoring, assessing Tyrosine Kinase Inhibitor therapy efficacy and predicting long-term response in chronic myeloid leukemia (CML) patients. For valid Q-PCR results, each stage of the laboratory procedures need be optimized, including the cell-counting method that represents a critical step in obtaining g an appropriate amount of RNA and reliable Q-PCR results. Traditionally, manual or automated methods are used for the detection and enumeration of white blood cells (WBCs). Here, we compared the performance of the manual counting measurement to the flow cytometry (FC)-based automatic counting assay employing CytoFLEX platform. METHODS: We tested five different types of measurements: one manual hemocytometer-based count and four FC-based automatic cell-counting methods, including absolute, based on beads, based on 7-amino actinomycin D, combining and associating beads and 7AAD. The recovery efficiency for each counting method was established considering the quality and quantity of total RNA isolated and the Q-PCR results in matched samples from 90 adults with CML. RESULTS: Our analyses showed no consistent bias between the different types of measurements, with comparable number of WBCs counted for each type of measurement. Similarly, we observed a 100% concordance in the amount of RNA extracted and in the Q-PCR cycle threshold values for both BCR-ABL1 and ABL1 gene transcripts in matched counted specimens from all the investigated groups. Overall, we show that FC-based automatic absolute cell counting has comparable performance to manual measurements and allows accurate cell counts without the use of expensive beads or the addition of the time-consuming intercalator 7AAD. CONCLUSIONS: This automatic method can replace the more laborious manual workflow, especially when high-throughput isolations from blood of CML patients are needed.

Impact of Anti-Endothelial Cell Antibodies (AECAs) in Patients with Polycythemia Vera and Thrombosis.

Polycythemia vera (PV) causes thrombosis. Erythrocytosis and cell adhesiveness are responsible for thrombosis. JAK2V617F causes inflammation and autoimmunity; however, whether or not autoimmunity or inflammation causes thrombosis has yet to be proven. In 60 PV patients, we analyzed JAK2V671F and its allele burden, autoimmune Th17 cells, interleukin-17 (IL-17), anti-endothelial cell antibodies (AECAs), endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor antigen (VWF: Ag). Fifty blood donors were used as the controls. All patients were on phlebotomy-maintaining hematocrit <45% and aspirin. Of the 60 patients, 40 had thrombosis. Those patients with thrombosis had a higher JAK2V617F allele burden than those without thrombosis, andTh17 cells and IL-17 were also higher in patients with thrombosis. Interestingly, we observed a high AECA IgG ELISA ratio (ER) in patients with thrombosis, which was normal in patients without thrombosis. We found high ELAM-1 and ICAM-1 as well as high VWF:Ag in patients with thrombosis compared to patients without thrombosis. AECA-positive sera from patients with thrombosis showed enhanced binding to cytokine-treated HUVEC and a positive antibody-dependent cellular cytotoxicity, suggesting that AECA may contribute to vascular injury. A positive correlation between AECAs, allele burden, and thrombosis was found. These results suggest that autoimmunity may be an additional mechanism in PV thrombogenesis.

Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy.

INTRODUCTION: Coronavirus 2 (CoV-2) infection or coronavirus disease 2019 (COVID-19) is frequently associated with microvascular thrombosis.The microthrombosis in COVID-19 is the result of the interplay between inflammation and endotheliopathy. Elevated interleukin-6 (IL-6) characterizes COVID-19 inflammation resulting in endotheliopathy and coagulopathy marked by elevated D-dimer (DD). Aim of this study is to identify and to describe the coagulation changes in 100 moderate COVID-19 patients having lung involvement and to determine the association of coagulopathy with the severity and prognosis. METHODS: Inflammation, endothelial and coagulation molecules were measured in moderate and mild disease. RESULTS: IL-6 and tumor necrosis factor-α (TNF-α) and tissue factor (TF), von Willebrand factor (VWF), and tissue factor pathway inhibitor (TFPI) significantly increased in moderate disease as well as D-dimer, thrombin antithrombin complex (TAT), Fibrinogen (Fib), platelet factor-4 (PF4), ß-thromboglobulin (ß-TG), P-selectin, and platelet adhesion. Shortened clotting time (CT) and clot formation time (CFT), high maximum clot firmness (MCF) and low LY at 30 min were present in 100% of moderate COVID-19 patients compared with mild COVID-19 patients. CONCLUSIONS: These findings demonstrate that moderate COVID-19 has a profound inflammation associated with severee ndotheliopathy and intense coagulation activation uncontrolled by TFPI. Attention should be paid to coagulopathy in COVID-19. Closely monitoring of coagulation and application of appropriate anticoagulation may improve the prognosis of moderate COVID-19 and to prevent the progression to severe COVID-19 disease.

Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial.

BACKGROUND: There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone. METHODS: In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18-60 years, with a diagnosis of polycythaemia vera according to 2008-16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 µg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov, NCT03003325. FINDINGS: Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0-12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7-41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred. INTERPRETATION: Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera. FUNDING: AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro.

Hemocoagulative post-operative changes after laparoscopic surgery compared to open surgery: the role of lupus anticoagulant.

Although still debated, post-operative modification of hemostasis seems to be less pronounced after laparoscopy compared to open surgery. Antiphospholipid antibodies might play a role in the post-operative thromboembolic risk, although their evaluation in surgical patients has never been performed. Post-operative modification of antiphospholipid antibodies could be related to the surgical approach (laparoscopic or open). In this prospective study, the authors statistically compared the pre-operative values and post-operative modification of antiphospholipid antibodies in two homogeneous groups of patients operated on by laparoscopic and open surgery. No statistical differences within each group and between the two groups were shown comparing mean values of pre-operative and post-operative antiphospholipid antibodies. In the open group, there was a significant difference between pre-operative and post-operative LAC means (P < 0.01). In the laparoscopic group, on the contrary, no significant change in LAC values between pre- and post-operative tests (P = 0.55) was observed. Since LAC could be related to coagulation disorders, this study seems to support that laparoscopic surgery might induce a less risk of post-operative thromboembolic disease.

Idiopathic intramural hematoma of the right colon. A case report and review of the literature.

INTRODUCTION: Intestinal hematoma is usually observed after an abdominal trauma or in patients treated with anticoagulant therapy. Conversely, idiopathic bowel hematoma is very rare, being colon involvement sporadic with few reports in the Literature. PRESENTATION OF CASE: The Authors report a case of idiopathic spontaneous large bowel hematoma. A 48-year-old man was admitted for a thoraco-abdominal pain and signs of acute abdomen and fever. After ruling out heart diseases, a CT scan revealed a marked thickening of the ascending colon wall, obstructing the bowel lumen. Leukocytosis was observed. In an emergency setting, an explorative laparotomy was performed. Hemoperitoneum and a large hematoma involving the caecum and the ascending colon were detected, together with intramesenteric and retroperitoneal blood effusion. A right hemicolectomy was accomplished. Histopathology confirmed the diagnosis of large bowel hematoma. Post-operative molecular diagnostic testing for coagulative disorders failed to demonstrate any genetic variation associate with hemorrhagic predisposition. In the post-operative course, the patient experienced a left basal bronco-pneumonia with increased unilateral pleural effusion, successfully treated by a thoracic drain and antibiotic therapy. DISCUSSION: The reported case and Literature data show that diagnosis of idiopathic colon intramural hematoma is challenging, especially in the emergency setting. Although conservative therapy is the first line treatment, surgery still has an important role when the diagnosis is uncertain, medical treatment fails or a complication, such untreatable bleeding, perforation or occlusion occur. CONCLUSION: The Authors report a very rare case of spontaneous intramural hematoma of the right colon. Surgery still has a role in selected cases.

Preoperative Predictive Factors of Conversions in Laparoscopic Splenectomies.

PURPOSE: Presently, laparoscopic splenectomy (LS) is being performed for several indications in clinical practice. However, conversion to open surgery is occasionally required in some patients. We analyzed the intraoperative indications and potential preoperative predictors associated with conversion to open surgery in those presenting for LS. METHODS: We reviewed 107 patients who underwent LS. We analyzed the surgical indications, spleen size, surgical procedure performed, operative time, rate of and indications for conversions, as well as postoperative complications. RESULTS: Among the 15 patients (14.0%) who underwent conversion, the conversion was related to the occurrence of a splenic lymphoma in 10, severe bleeding in 3, a lack of anatomic definition in 1, and splenic candidiasis in 1 patient. A comparison between the results obtained in the initial 30 patients (LS performed during the learning curve) and those obtained in the remaining 77 patients, showed that conversions appeared to be related to the experience/expertise of the surgical team excluding patients with splenic malignancies. Conversion was not associated with a higher morbidity-mortality rate, but only a longer length of hospitalization. CONCLUSIONS: LS is a gold standard procedure when performed by experienced and competent surgeons. However, careful patient selection is recommended before using the laparoscopic approach in those presenting with splenic malignancies.

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms.

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.

Surgical management of hereditary spherocytosis Current strategies.

BACKGROUND: Hereditary spherocytosis is a benign hematologic disease, which needs surgical treatment when medical therapy fails. Currently, the surgical strategies consist mainly in total or partial splenectomy, which can be performed either in open or in laparoscopic fashion. In this study, we analyzed our series of splenectomies for hereditary spherocytosis and we discuss about the surgical management, reviewing the Literature. MATERIAL AND METHODS: Twenty-seven patients (mean age 16.5 years, range 8 - 30 years) affected by hereditary spherocytosis were retrospectively evaluated. Indication to surgery was based on hemolysis severity. Thirteen patients were submitted to laparoscopic splenectomy and 14 to open splenectomy, after preventive specific vaccinations. Cholecystectomy for associated cholelithiasis was performed during the same operation in 4 laparoscopic patients and in 6 open patients. RESULTS: Main reasons for performing splenectomy were anemia unresponsive to iron supplementation in 7 patients (42%), splenomegaly in 6 patients (37%), and jaundice in 4 cases (21%). All the patients had a severe disease with hemoglobin level below 80 g/L, median reticulocytes count 6,5%, median value of indirect bilirubin concentration 2,0 mg/dL. Indications to splenectomy were increased need for red cell transfusions in 11 patients (66%) and symptoms related to cholelithiasis in 6 patients (34%). A post-operative early complication was observed after open splenectomy, consisting in a pancreatic fistula, which was treated conservatively. No post-operative complications were observed after laparoscopic splenectomy. Neither intra-operative complications nor conversions to open surgery were recorded during the laparoscopic approach. In a long-term follow- up, no infective complications were recorded. CONCLUSIONS: According to our results, total splenectomy is associated with good results and few complications. In our opinion, it remains the best therapeutic option in selected adult patients non-responder to the medical treatment. KEY WORDS: Hereditary spherocytosis, Laparoscopic splenectomy, Partial splenectomy.

The use of surgical drains in laparoscopic splenectomies Consideration on a large series of 117 consecutive cases.

BACKGROUND DATA: The use of surgical drains after traditional splenectomy has been largely debated and several Authors have been unfavorable to their use. With the advent of laparoscopic splenectomy, their role has been re-discussed. The increased risk of undetectable pancreatic, gastric or colon injury in challenging laparoscopic removal of the spleen have induced some surgeons to reconsider the advantages related to their use. METHODS: One hundred seventeen consecutive cases of laparoscopic splenectomy with routine use of surgical drains have been reviewed. Indications for surgery, length of operations, post-operative day of drain removal, post-operative complications were retrospectively analyzed. RESULTS: Laparoscopic splenectomy was performed for idiopathic thrombocytopenic purpura in 77 patients (65,8%), splenic lymphoma in 11 (9,4%), hereditary spherocytosis in 12 (10,2%), ß-thalassemia in 6 (5.1%), other diseases in 11 (9,4%) cases. Conversion to open surgery was necessary in 11,1% of cases. Drains were removed 2-3 days after surgery in 95,8%, within 10 days in 3.4%, within 2 months in 0,8% of cases. In 2 cases a post-operative bleeding, detected through the drainage, required re-operation. One patient with myelofibrosis and massive splenomegaly developed a late post-operative subphrenic abscess, successfully treated by a percutaneous drainage. CONCLUSIONS: In Authors' experience, the use of drains after laparoscopic splenectomy helped detect early post-operative bleeding. Surgical drains could reduce the incidence of fluid intra-abdominal collections and infections. Their use should be recommended in the laparoscopic approach, especially in technically demanding surgical procedures. KEY WORDS: Laparoscopy, Surgical drainage, Splenectomy.

Late results after splenectomy in adult idiopathic thrombocytopenic purpura.

BACKGROUND: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count. MATERIALS AND METHODS: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ≤30,000/µL (study group: 22 patients) and >30,000/µL (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ≥100,000/µL or in patients with a postoperative platelet count ≥30,000/µL and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test. RESULTS: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = -0.41; P = .089), whereas a significant negative correlation (r = -0.68; P = .0004) was found in the study group. CONCLUSIONS: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count.

Cerebral vein thrombosis in patients with Philadelphia-negative myeloproliferative neoplasms. An European Leukemia Net study.

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN-CVT) to 87 with MPN and other venous thrombosis (group MPN-VT) and 178 with MPN and no thrombosis (group MPN-NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN-CVT and MPN-VT than in MPN-NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN-VT, MPN-CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow-up period (6.1 vs. 10.3 years, P = 0.019), a higher long-term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN-CVT than in MPN-VT group (8.8% and 4.2% patient-years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05-3.72 and 2.09, 1.09-4.00, respectively).

Laparoscopic splenectomy coupled with laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the results of laparoscopic surgery performed for coexisting spleen and gallbladder surgical diseases. METHODS: Between May 2004 and October 2012, 12 patients underwent concomitant laparoscopic splenectomy and cholecystectomy. Indications for surgery included idiopathic thrombocytopenic purpura in 5 patients, hereditary spherocytosis in 4 patients, and thalassemia intermedia in 3 patients. RESULTS: The mean operative time was 100 minutes (range, 80 -160 minutes), and the blood loss ranged from 0 to 150 mL (mean, 50 mL). The mean longitudinal diameter of the spleen was 14 cm. One patient required conversion to open procedure. An accessory spleen was detected and removed in one case. The mean length of hospital stay was 5 days. No deaths or other major intraoperative and/or postoperative complications occurred. CONCLUSION: Provided that the technique is performed by an experienced surgical team, concomitant laparoscopic splenectomy and cholecystectomy is a safe and feasible procedure and may be considered for coexisting spleen and gallbladder diseases.