Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population. METHODS: Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS). RESULTS: One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients' response and survival outcomes. CONCLUSIONS: Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.

Psoriasis induced by first­line pembrolizumab in metastatic non­small cell lung cancer: A case report.

Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response.

Methotrexate in the therapeutic pathway of patients with psoriasis. Analysis of clinical practice data and comparison with guidelines.

Psoriasis is an inflammatory skin disease with a chronic-relapsing course. It is estimated that the prevalence in Italy is 3%. An adequate model of taking care of the patient with psoriasis allows the patient to benefit from the most suitable treatment option for his health needs. In this position statement the observations, criticalities and proposals for improvement of the Pso-Path Working Group, composed by health economists, clinicians and patients, on the diagnostic-therapeutic pathway of the patient with psoriasis have been collected. In particular, the deviation of clinical practice from the current Guidelines for the management of patients with psoriasis, which recommend the use of biologic drugs in case of non-response, intolerance or contraindication to Methotrexate or Cyclosporine, was evaluated. A Working Group was convened whose participants were asked to express their thoughts on the diagnostic and therapeutic pathway of the patient with psoriasis, bringing out critical elements and proposals for improvement, based on their experiences. This position statement summarizes the experiences and consensus between clinicians and patients on actions to optimize the management of patients with psoriasis undergoing biological treatment. Compared to the epidemiological data currently available, it is believed that only a small percentage of patients with psoriasis are treated with systemic drugs. The perception of clinicians, according to their experience, confirms the data emerging from the National Report "National Observatory on the Use of Medicines" (Osmed) compiled by AIFA in 2015, according to which more than 77% of patients with psoriasis are started to treatment with biological drugs without a previous use of Methotrexate or Cyclosporine for at least 3 months. The Pso-Path Working Group concluded that it would be desirable to incentivize, through the formalization of regional guidelines, the creation of a network system that promotes not only a greater awareness, at the territorial level, of the importance and impact of the disease and the possible paths, but also the collaboration and connection between all the actors involved in the overall care of the patient.

Stunning Response with Low-Dose Enzalutamide after Abiraterone Acetate Failure in a Patient Diagnosed with Metastatic Castration-Resistant Prostate Cancer: A Case Report.

We report a case of an elderly patient with metastatic castration-resistant prostate cancer, initially treated with abiraterone acetate (1,000 mg/day) combined with LH-RH antagonist, prednisone (10 mg/day), and zoledronic acid to manage bone metastases. In consideration of his poor performance status, radiological and biochemical progression of the disease, we decided to switch abiraterone to enzalutamide (160 mg/day). Due to adverse events, we reduced enzalutamide to a dose of 80 mg/day. Currently, the disease is under control despite the use of a low dose of enzalutamide.

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review.

INTRODUCTION: Gemcitabine is a nucleoside analog and pyrimidine antimetabolite that inhibits RNA synthesis, currently approved for use to treat a variety of cancers, among which ovarian cancers. Gemcitabine is considered relatively safe and it is generally well tolerated, with rarely reported cardiac side effects. CASE REPORT: We report a case of gemcitabine induced dilated cardiomyopathy in a 41-year-old woman receiving gemcitabine as second line treatment for platinum-resistant ovarian cancer without pre-existing hypertension or significant cardiac history.Management and Outcome: The patient presented with clinical symptoms and laboratory and imaging results suggestive of congestive cardiac failure, with a left ventricular ejection fraction of 15%. Gemcitabine administration was stopped and Furosemide with ACE-inhibitors and Beta-blocker agents were initiated. At that point the clinical situation improved: symptoms and findings disappeared with gemcitabine cessation. DISCUSSION: Our case demonstrated for the first time objective evidence for dilated cardiomyopathy induced by gemcitabine in a young patient with platinum-resistant ovarian cancer without pre-existing significant cardiac history. Although rare, gemcitabine-induced cardiotoxicity should be promptly recognized in order to take appropriate measures to manage it.

How to manage catheter-related right atrial thrombosis: Our conservative approach.

BACKGROUND: Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death. CASE SERIES: We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported. CONCLUSION: The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

Bullous pemphigoid in elderly woman affected by non-small cell lung cancer treated with pembrolizumab: A case report and review of literature.

INTRODUCTION: Immunotherapy has changed the management of patients with various types of malignancies (melanoma, renal, lung, and bladder cancers) but immune checkpoint inhibitors may be associated with several adverse events. Up to 20% of patients treated with immune checkpoint inhibitors may develop dermatological immune-related adverse events, mostly rashes and pruritus but rarely even bullous pemphigoid. CASE REPORT: We report a case of an elderly patient with advanced non-small cell lung cancer in therapy with pembrolizumab, 200 mg/body every three weeks. After 26 cycles of therapy, the patient developed widespread itching and then after 28 cycles she developed strained blisters filled with serous fluids on predominantly erythematous skin with suspicious of bullous pemphigoid.Management and outcome: Skin biopsy confirms bullous pemphigoid, so we decided to permanently discontinue therapy with pembrolizumab and the patient is currently on therapy with doxycycline, nicotinamide, and clobetasol propionate with good regression of symptoms and cutaneous lesions. DISCUSSION: In the literature, the first case of bullous pemphigoid induced by pembrolizumab has been described in 2015. On Pubmed, from 2015 to date, we have found 19 cases of bullous pemphigoid during pembrolizumab therapy but only three of them are related to non-small cell lung cancer, adding our patient we reach a total of 20 cases. It could be interesting to investigate if there is a specific relationship between the appearance of itching and the development of bullous pemphigoid.

[Target therapies in translocated ALK lung cancer: treatment management in oncology center of Lazio.] / Target therapies nel tumore al polmone ALK-positivo: gestione del trattamento nei centri di oncologia del LazioIncontro di approfondimento e confronto sulla gestione dei pazienti e sulla strategia terapeutica nei carcinomi polmonari positivi al riarrangiamento di ALK.

Lung cancer is a disease extremely heterogeneous in the molecular aspect and knowing the mutational profile of patients is essential in order to initiate the most appropriate treatment. In 2018, alectinib was approved in Italy for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), becoming a new therapeutic option for this patient group which constitutes approximately 3-7% of patients with NSCLC. On October 26th a virtual meeting was held in which 10 clinicians from various oncology centers in Lazio took part on the management of therapy of patients with Alk translocation, directed by Dr. Maria Rita Migliorino. The aim of the meeting was to share their clinical experience and to provide a series of practical that can help clinicians during treatment with target therapies in ALK-positive NSCLC.

Colorectal cancer metastatic to the breast: A case report.

BACKGROUND: Breast metastases from colorectal cancer (CRC) are very uncommon. There is no unanimous consensus regarding the best treatment for this rare condition, and management is, especially in elderly patients, limited to diagnosis and palliative care. Capecitabine, an oral fluoropyrimidine derivative, might be helpful in controlling the disease and may be a treatment option for patients unable to receive more aggressive chemotherapy. CASE SUMMARY: We report a case of synchronous massive breast metastasis from CRC in an 85 year old patient who came to the hospital presenting a huge mass originating from the axillary extension of the right breast. A whole body computed tomography also showed a mass in the right colon. The patient underwent a simple right mastectomy along with right hemicolectomy. The resected breast showed massive metastasis from CRC with intense and homogeneous nuclear CDX2 staining, while the colon specimen revealed poorly differentiated adenocarcinoma stage pT4a pN0 pM1 (breast) (Tumor Node Metastasis 2017). Three months later she developed a subcutaneous mass at the site of the previous mastectomy. An ultrasound guided biopsy was carried out again and revealed a metastasis from CRC. The patient then started treatment with capecitabine plus bevacizumab, obtaining stable disease (RECIST criteria) and a clinical benefit after 3 mo of therapy. CONCLUSION: In our experience, capecitabine and bevacizumab may be a useful treatment option for breast metastases from primary CRC in elderly patients.

Alectinib in the treatment of ocular metastases of ALK rearranged non small cell lung cancer: Description of 2 case reports.

RATIONALE: Choroidal metastasis is a rare metastatic location although the most common intraocular neoplasm. In general, choroidal metastases respond favorably to systemic therapy targeted toward the primary neoplasm. In patients with choroidal metastasis of ALK rearranged non small cell lung cancer (NSCLC), targeted therapy using Alk inhibitors gradually replaced radiotherapy as the best treatment. Alectinib is a second-generation ALK inhibitors. Here we describe 2 clinical cases of patients with choroidal metastasis of ALK rearranged NSCLC who received Alectinib as first-line therapy achieving disease control and quality of life improvement. PATIENTS CONCERNS: In case report 1, 62-year-old man presented with scintillated scotomas at the level of the right eye; in case report 2, 69-year-old man presented with respiratory distress, persistent cough resistant to medical therapy, pain, and blurred vision. DIAGNOSES: In case report 1, fundus and ultrasonographic examination showed circumscribed choroid thickening with dome-like appearance compatible with repetitive lesion. Computed tomographic/y (CT) showed multiple bilateral pulmonary nodular formations and adenocarcinoma of the lung was diagnosed by a transbronchial biopsy.In case report 2, CT showed a primary lesion of 36 × 27 mm in the middle lobe with bilateral lung metastases and lymphadenopathies. Multiple hepatic metastases and minor suspicious bone repetitions. A liver biopsy made a diagnosis of adenocarcinoma compatible with pulmonary primitiveness. An ocular fluoroangiography evidenced a left choroidal metastasis. INTERVENTIONS: Case report 1, 2, medical treatment with Alectinib 1200 mg/day was initiated. OUTCOMES: In case report 1, a few days after beginning the treatment, both systemic symptoms like respiratory distress and low vision were palliated. Reassessment by CT confirmed treatment response. In case report 2, clinically, visus disorders had already improved 2 weeks after beginning treatment. CT showed pulmonary, nodal, and hepatic response. Stability of bone metastases occurred after 2 months. In addition, ocular ultrasonography documented the regression of previously reported lesions confirmed treatment response. LESSONS: Alectinib works very well in intracranial metastases and is assumed to be so on the ocular ones as well, with benefit for the patient in quality of life.

Synchronous and Metachronous Metastatic Breast Cancer, with Different Histology and Opposite Immunophenotype, Treated with Combination of Chemotherapy, Anti-Her2, and Endocrine Therapy: A Case Report.

In the case of our patient, the synergic action of endocrine therapy and chemotherapy plus dual anti-HER2 combination allowed a complete disease control. Therapy should be scheduled by considering the two cancers as individual entities. The approach to breast cancer is changing from being considered a singular disease to a multiform one, according to current research focused on biological markers such as HER2, ERs, and PRs, with important implications in clinical, prognostic, and therapeutic features.

Green nephrology and eco-dialysis: a position statement by the Italian Society of Nephrology.

High-technology medicine saves lives and produces waste; this is the case of dialysis. The increasing amounts of waste products can be biologically dangerous in different ways: some represent a direct infectious or toxic danger for other living creatures (potentially contaminated or hazardous waste), while others are harmful for the planet (plastic and non-recycled waste). With the aim of increasing awareness, proposing joint actions and coordinating industrial and social interactions, the Italian Society of Nephrology is presenting this position statement on ways in which the environmental impact of caring for patients with kidney diseases can be reduced. Due to the particular relevance in waste management of dialysis, which produces up to 2 kg of potentially contaminated waste per session and about the same weight of potentially recyclable materials, together with technological waste (dialysis machines), and involves high water and electricity consumption, the position statement mainly focuses on dialysis management, identifying ten first affordable actions: (1) reducing the burden of dialysis (whenever possible adopting an intent to delay strategy, with wide use of incremental schedules); (2) limiting drugs and favouring "natural" medicine focussing on lifestyle and diet; (3) encouraging the reuse of "household" hospital material; (4) recycling paper and glass; (5) recycling non-contaminated plastic; (6) reducing water consumption; (7) reducing energy consumption; (8) introducing environmental-impact criteria in checklists for evaluating dialysis machines and supplies; (9) encouraging well-planned triage of contaminated and non-contaminated materials; (10) demanding planet-friendly approaches in the building of new facilities.

Herpes zoster granulomatous dermatitis in metastatic lung cancer treated with nivolumab: A case report.

Granulomatous dermatitis (GD) is the most common among a variety of skin reactions that may occur in the varicella-zoster virus (VZV) reactivation area. It is thought that the formation of granulomas may be the result of a delayed hypersensitivity reaction to viral envelope glycoproteins. Immune checkpoint inhibitors (ICIs), such as nivolumab stimulate T cells and promote hypersensitivity reactions, leading to the formation of granulomas in VZV wrapping proteins, thus triggering VZV-GD. Few cases of the use of ICIs in patients diagnosed with VZV-GD have been reported in the literature. Here, we report the clinical case of a patient with metastatic lung cancer which was treated with nivolumab who subsequently developed VZV-GD. Accurate clinical diagnosis and prompt treatment with antiviral agents have resulted in a complete resolution of the clinical picture. KEY POINTS: Significant findings Treatment with ICIs may result in VZV reactivation. Accurate differential diagnosis and early treatment led to the resolution of VZV-GD. WHAT THIS STUDY ADDS: Few cases of ICI and VZV reactivation have been reported in the literature. Full and timely resolution of VZV-GD allowed the continuation of ICI treatment.

Metachronous and Synchronous Cancers in Patients with Neuroendocrine Tumors.

INTRODUCTION: Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with various clinical presentations and growth rates. NET incidence has been estimated to 2.5-5 per 100,000 people per year, and NET prevalence is 35 per 100,000. They are frequently associated with synchronous or metachronous second primary malignancies (SPM). METHODS: We retrospectively reviewed our institutional database on NET patients. We report on 30 patients with NETs and SPMs from a series of 262 patients with NETs: 10 patients with synchronous NETs (33.3%) and 20 with metachronous SPMs (66.6%). RESULTS: The median patient age was 67 years. Of the 10 synchronous lesions, 50% were observed in the GI tract. The most common locations of these lesions were the colon (15%) and pancreas (25%). In 2 patients, there was an association of prostate neoplasia with a subsequent NET of the pancreas. CONCLUSIONS: Only few studies have examined the association between NETs and SPMs. Our study showed that the risk of second cancer following NETs is increased. In this single-institution retrospective review, our incidence of additional malignancies in patients with NET was 11.4%.

What volume to choose to assess online Kt/V?

INTRODUCTION: Urea distribution volume (V) can be assessed in different ways, among them the anthropometric Watson Volume (VW). However, many studies have shown that VW does not coincide with V and that the latter can be more accurately estimated with other methods. The present multicentre study was designed to answer the question: what V to choose to assess online Kt/V? MATERIALS AND METHODS: Pre- and postdialysis blood urea nitrogen concentrations and the usual input data set for urea kinetic modelling were obtained for a single dialysis session in 201 Caucasian patients treated in 9 Italian dialysis units. Only dialysis machines measuring ionic dialysance (ID) were utilized. ID reflects very accurately the mean effective dialyser urea clearance (Kd). Six different V values were obtained: the first one was VW; the second one was computed from the equation established by the HEMO Study to predict the single pool-adjusted modelled V from VW (VH) (Daugirdas JT et al. KI 64: 1108, 2003); the others were estimated kinetically as: 1. V_ID, in which ID is direct input in the in the double pool variable volume (dpVV) calculation by means of the Solute-solver software; 2. V_Kd, in which the estimated Kd is direct input in the dpVV calculation by means of the Solute-solver software; 3. V_KTV, in which V is calculated by means of the second generation Daugirdas equation; 4. V_SPEEDY, in which ID is direct input in the dpVV calculation by means of the SPEEDY software able to provide results quite similar to those provided by Solute-solver. RESULTS: Mean± SD of the main data are reported: measured ID was 190.6 ± 29.6 mL/min, estimated Kd was 211.6 ± 29.0 mL/min. The relationship between paired data was poor (R2 = 0.34) and their difference at the Bland-Altman plot was large (21 ± 27 mL/min). VW was 35.3 ± 6.3 L, VH 29.5 ± 5.5, V_ID 28.99 ± 7.6 L, V_SPEEDY 29.4 ± 7.6 L, V_KTV 29.7 ± 7.0 L. The mean ratio VW/V_ID was 1.22, (i.e. VW overestimated V_ID by about 22%). The mean ratio VH/V_ID was 1.02 (i.e. VH overestimated V_ID by only 2%). The relationship between paired data of V_ID and VW was poor (R2 = 0.48) and their mean difference at the Bland-Altman plot was very large (- 6.39 ± 5.59 L). The relationship between paired data of V_ID and VH was poor (R2 = 47) and their mean difference was small but with a large SD (- 0.59 ± 5.53 L). The relationship between paired data of V_ID and V_SPEEDY was excellent (R2 = 0.993) and their mean difference at the Bland-Altman plot was very small (- 0.54 ± 0.64 L). The relationship between paired data of V_ID and V_KTV was excellent (R2 = 0.985) and their mean difference at the Bland-Altman plot was small (- 0.85 ± 1.06 L). CONCLUSIONS: V_ID can be considered the reference method to estimate the modelled V and then the first choice to assess Kt/V. V_SPEEDY is a valuable alternative to V_ID. V_KTV can be utilized in the daily practice, taking also into account its simple way of calculation. VW is not advisable because it leads to underestimation of Kt/V by about 20%.

Expression of ER, PgR, HER-2, and Ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among breast cancer subtypes. METHODS: The aim of our study is to evaluate the effect of this treatment on the expression of estrogen and progesterone receptors, human epidermal growth hormone receptor 2 and Ki67 in breast cancer. We identified 125 patients. RESULTS: The estrogen receptor modified its expression from positive to negative in 8% patients and from negative to positive in 22%; progesterone in 21% and in 37% cases. Median Ki-67 value was 20.9% at biopsy and 18% after, HER-2 status did not show a remarkable change before or after neoadjuvant chemotherapy (NACT). We have identified a significant reduction in Ki-67 expression levels after chemotherapy in patients with a pathologic response. Detection of pretreatment Ki-67 could identify patients most likely to benefit from NACT. CONCLUSIONS: NACT can change the status of ER, PgR, and Ki-67 expression in patients with breast adenocarcinoma, but it did not exert a significant effect on HER-2 status; HER-2 amplification appears to be more stable. We have identified a prognostic role for a decreased expression of PgR and Ki-67 after preoperative chemotherapy in breast cancer patients.

[Nephrologists' role in a changing climate].

Human-induced climate changes represent an increasing concern in recent years. Among the medical specialties, Nephrology is the most interested in the negative effects of climate changes on human health. Kidneys in fact play a crucial role in blood volume regulation as well as in the extra- and intracellular osmolality that allow normal metabolism. Furthermore, urinary concentration minimizes fluid losses, while also insuring the excretion of nitrogenous wastes. The harmful effects of heat can lead to both acute and chronic kidney diseases, electrolyte abnormalities, kidney stone formation and urinary tract infections. As global warming increases, major efforts are required worldwide to assure adequate hydration and prevent overheating in vulnerable populations. While our activities make us responsible agents, there are also several opportunities to change the game, both individually and as a scientific society. This call to action intends to raise awareness on environmentally sustainable practices and encourage the nephrology community in Italy to participate in this important discussion.

[Bevacizumab e altri farmaci. Attività e sicurezza degli agenti anti-VEGF nel carcinoma ovarico.] / Bevacizumab and others. Activity and safety of anti-VEGF agents in ovarian cancer.

Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in quelli maligni. Negli ultimi anni questo fenomeno è stato ampiamente studiato in oncologia sperimentale e clinica perché ci sono evidenze che sia coinvolto nella diffusione e nella diffusione metastatica del carcinoma ovarico. Il fattore di crescita dell'endotelio vascolare (vascular endothelial growth factor - VEGF) è l'attore principale nel meccanismo di angiogenesi e svolge un ruolo strategico nella proliferazione e migrazione delle cellule neoplastiche, con un impatto significativo sulla sopravvivenza e sull'outcome clinico. Secondo quanto emerge da molti studi sperimentali e clinici, le nostre conoscenze sulla biologia dell'angiogenesi e del VEGF sono aumentate portando allo sviluppo farmacologico di specifici agenti in grado di targeting VEGF. Questo nuovo campo di indagine offre agli scienziati l'opportunità di testare nuove possibilità terapeutiche nei pazienti con carcinoma ovarico con nuovi agenti mirati. Il bevacizumab, un anticorpo monoclonale anti-VEGF umanizzato, è stato il primo farmaco anti-VEGF scoperto ed è usato oggi per il trattamento di diversi tumori solidi. Negli ultimi anni questo agente è stato ampiamente testato nei pazienti con carcinoma ovarico, mostrando un'attività clinica interessante e un profilo di tossicità tollerabile sia nelle pazienti giovani sia in quelle anziane. Il bevacizumab, combinato con carboplatino e paclitaxel e successivamente utilizzato come agente singolo, è indicato per il trattamento del carcinoma epiteliale dell'ovaio di stadio III o IV, tuba di Falloppio o carcinoma peritoneale primario dopo iniziale resezione chirurgica. Il bevacizumab è anche usato per il trattamento di pazienti con carcinoma ovarico epiteliale ricorrente e resistente al platino, delle tube di Falloppio o dal tumore peritoneale primario che hanno ricevuto non più di 2 regimi precedenti di chemioterapia. Inoltre, il bevacizumab, combinato con carboplatino e paclitaxel o con carboplatino e gemcitabina (e usato come agente singolo), è indicato per il trattamento di pazienti con carcinoma epiteliale dell'ovario sensibile al platino, tuba di Falloppio o tumore peritoneale primario. Le linee guida più accreditate suggeriscono quando bevacizumab deve essere usato nel trattamento del carcinoma ovarico avanzato e ricorrente. Altri agenti anti-VEGF, come gli inibitori della tirosin-chinasi del recettore VEGF (VEGFR), sono stati ampiamente testati nel carcinoma ovarico e molti altri sono in corso di studi al fine di testare la loro attività e sicurezza rispetto a bevacizumab. Gli agenti anti-VEGF e gli inibitori di PARP svolgono oggi un ruolo strategico nel trattamento del cancro ovarico con agenti mirati in associazione con la chemioterapia e la chirurgia in un'ottica multidisciplinare e personalizzata.

[Membranoproliferative glomerulonephritis with relapsing episodes of acute kidney injury in the Schnitzler syndrome].

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years the SS has evolved from an elusive, little-known disorder to the paradigm of a late-onset auto-inflammatory acquired syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin 1 (IL-1) receptor antagonist anakinra. Here we describe the case of a 56-year-old male Caucasian patient affected by SS and hospitalized several times in our unit because of relapsing episodes of acute kidney injury. He underwent an ultrasound-guided percutaneous kidney biopsy in September 2012, which showed the histologic picture of type I membranoproliferative glomerulonephritis. He has undergone conventional therapies, including nonsteroidal anti-inflammatory drugs, steroids and immunosuppressive drugs; more recently, the IL-1 receptor antagonist anakinra has been prescribed, with striking clinical improvement. Although the literature regarding kidney involvement in the SS is lacking, it can however be so severe, as in the case reported here, to lead us to recommend the systematic search of nephropathy markers in the SS.

Is the removal of a central venous catheter always necessary in the context of catheter-related right atrial thrombosis?

Catheter-related right atrial thrombosis is a severe and life-threatening complication of central venous catheters in both adult and young patients. Catheter-related right atrial thrombosis can occur with any type of central venous catheters, utilized either for hemodialysis or infusion. Up to 30% of patients with central venous catheter are estimated to be affected by catheter-related right atrial thrombosis; however, neither precise epidemiological data nor guidelines regarding medical or surgical treatment are available. This complication seems to be closely associated with positioning of the catheter tip in the atrium, whereas it is unlikely with a tip located within superior vena cava. Herein, we report the case of a patient affected by catheter-related right atrial thrombosis, who showed a quick resolution of thrombosis with a new therapeutic scheme combining loco-regional thrombolytic therapy (urokinase as a locking solution) and systemic anticoagulation therapy (vitamin K antagonists), thus avoiding catheter removal. Neither complications of the combination therapy were reported, nor recurrence of catheter-related right atrial thrombosis occurred. In conclusion, the combination therapy here described was safe, quick and effective, achieving the goal of not removing the catheter.