Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120 mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile

Right ventricular morpho-functional remodelling in never treated hypertensives: role of aortic pressure and bi-ventricular parameters

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Efficacy of Percutaneous Transarterial Embolization in Patients with Spontaneous Abdominal Wall Hematoma and Comparison between Blind and Targeted Embolization Approaches

Background: Endovascular treatment of abdominal wall hematomas (AWHs) has been increasingly used when conservative treatments were not sufficiently effective, and it is often preferred to surgical interventions. The aim of our study was to evaluate the safety and technical and clinical success of percutaneous transarterial treatment of AWH and to evaluate the efficacy of blind embolization compared to targeted embolization. Materials and Methods: We retrospectively enrolled 43 patients (23 men and 20 females) with spontaneous AWH who underwent digital subtraction angiography (DSA) and embolization, focusing on the presence of signs of bleeding at pre-procedural CT-Angiography (CTA) and at DSA. Furthermore, we divided patients into two groups depending on blind or targeted embolization approaches. Results: The mean age of the study population was 71 \ub1 12 years. CTA revealed signs of active bleeding in 31 patients (72%). DSA showed signs of active bleeding in 34 patients (79%). In nine patients (21%), blind embolization was performed. The overall technical success rate was 100%. Clinical success was achieved in 33 patients (77%), while 10 patients (23%) rebled within 96 h, and all of them were re-treated. No major peri-procedural complication was reported. The comparison between blind and targeted embolization showed no statistically significant differences for characteristics of groups and for clinical success rates (78% and 77%, respectively, 12p = 0.71). The technical success was 100% in both groups. Conclusions: Our study confirms that transarterial embolization is a safe and effective option for the treatment of spontaneous AWHs, and it suggests that the efficacy and safety of blind embolization is comparable to non-blind

Technical pitfalls and proposed modifications of instructions for use for endovascular aortic aneurysm repair using the Gore Excluder conformable device in angulated and short landing zones

We describe a case of an abdominal aortic aneurysm (AAA) and angulated proximal neck treated with a Gore Excluder conformable endoprosthesis and show relevant technical pitfalls in the deployment of the graft main body. An 82-year-old man presented with a 71-mm asymptomatic AAA with an angulated infrarenal proximal neck (75°) and was referred to our unit. The patient was treated with a 26-mm Gore Excluder conformable device, which was deployed slightly above the renal arteries after precatheterization of the lowest renal artery. The graft was then repositioned with support of the introducer sheath and a stiff guide wire. The proximal sealing zone was ballooned before the endograft delivery system was retrieved to avoid distal migration. Technical success was achieved. The patient was discharged with no complications. No type Ia endoleak was present on the 6-month computed tomography scan. Endovascular treatment of an AAA with a severe angulated proximal neck can be effective with a conformable stent graft if technical measures are used during deployment of the main body to optimize the seal.</p

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3&nbsp;years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6&nbsp;months (median). The median age was 72&nbsp;years, and the baseline median prostate-specific antigen level was 15.0&nbsp;ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7&nbsp;months (95% confidence interval [CI], 28.6-32.2&nbsp;months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7&nbsp;months (95% CI, 39.4-46.2&nbsp;months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

Spontaneous Abdominal Wall Hematoma Treated with Percutaneous Transarterial Embolization: Diagnostic Findings, Procedural Outcome, and Efficacy—A Multicenter Study

Endovascular management of abdominal wall hematomas (AWHs) is now the primary treatment option in hemodynamically stable patients, and it is often preferred to surgical interventions. The purpose of this multicentric study was to assess the safety, technical, and clinical success of percutaneous transarterial embolization (PTAE) of spontaneous AWHs to evaluate the efficacy of blind or empiric embolization compared to targeted embolization and to compare the outcome of the endovascular treatment approach in patients affected by COVID-19 and non-COVID-19 patients. We retrospectively enrolled 112 patients with spontaneous AWHs who underwent PTAE, focusing on signs of bleeding at pre-procedural CTA and DSA. Patients were separated into two groups depending on whether a blind or targeted embolization approach was used. We also divided patients into COVID-19 and non-COVID-19 groups. The mean age of the study population was 68.6 ± 15.8 years. CTA and DSA revealed signs of active bleeding in 99 and 88 patients, respectively. In 21 patients, blind embolization was performed. The overall technical success rate was 99%. Clinical success was obtained in 96 patients (86%), while 16 (14%) re-bled within 96 h. One patient reported a major peri-procedural complication. The comparison between blind and targeted embolization approaches showed no statistically significant differences in the characteristics of groups and technical and clinical success rates. No significant differences were found in the procedural outcome between COVID-19 and non-COVID-19 groups. Our study confirmed that PTAE is effective for treating spontaneous AWHs, even in COVID-19 patients. It suggests that the efficacy and safety of blind embolization are comparable to targeted embolization

Biomechanical properties and histomorphometric features of aortic tissue in patients with or without bicuspid aortic valve

Background: We sought to investigate and compare biomechanical properties and histomorphometric findings of thoracic ascending aorta aneurysm (TAA) tissue from patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in order to clarify mechanisms underlying differences in the clinical course. Methods: Circumferential sections of TAA tissue in patients with BAV (BAV-TAA) and TAV (TAV-TAA) were obtained during surgery and used for biomechanical tests and histomorphometrical analysis. Results: In BAV-TAA, we observed biomechanical higher peak stress and lower Young modulus values compared with TAV-TAA wall. The right lateral longitudinal region seemed to be the most fragile zone of the TAA wall. Mechanical stress-induced rupture of BAV-TAA tissue was sudden and uniform in all aortic wall layers, whereas a gradual and progressive aortic wall breakage was described in TAV-TAA. Histomorphometric analysis revealed higher amount of collagen but not elastin in BAV-TAA tunica media. Conclusions: The higher deformability of BAV-TAA tissue supports the hypothesis that increased wall shear stress doesn't explain the increased risk of sudden onset of rupture and dissection; other mechanisms, likely related to alteration of specific genetic pathways and epigenetic signals, could be investigated to explain differences in aortic dissection and rupture in BAV patients

Spontaneous retroperitoneal hematoma treated with transarterial embolization: a systematic review and metanalysis

Purpose: The purpose of this systematic review and meta-analysis was to evaluate the safety, technical, and clinical effectiveness of percutaneous Transarterial Embolization (TAE) in treating spontaneous retroperitoneal hematomas as well as assess treatment outcomes in patients who underwent target or empirical embolization. Materials and methods: Through the PubMed, Embase, and Google Scholar databases, an extensive search was performed in the fields of spontaneous retroperitoneal hematomas treated with transcatheter arterial embolization. We collected pooled data on 141 patients from 6 separate articles selected according to the inclusion and&nbsp;exclusion criteria. Results: Technical success rate was 100% in all six studies, for both targeted and empirical embolization. The clinical success rate varied from 56.3 to 89.5%. The total number of complications related to the embolization procedure was 10 events out of 116 procedures analyzed. Empirical or empirical embolization was performed in three studies, where the source of active bleeding was not evident during DSA. A meta-analysis compared the rebleeding rates between targeted and empirical embolization groups. The odds ratio from pooled data from the three assessed studies (72 patients) showed no significant difference in rebleeding rates after empirical TAE compared with targeted TAE. Conclusions: TAE is a safe, effective, and potentially life-saving procedure for the treatment of life-threatening spontaneous retroperitoneal hematomas. Empirical and targeted TAE procedures demonstrate a relatively low risk of complications, compared to the high technical and relatively high clinical success rates

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms

Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs). Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality. Results: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach. Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population