ABSTRACT
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; Pâ =â .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.
Subject(s)
Breast Neoplasms , Camptothecin/analogs & derivatives , Immunoconjugates , Neutropenia , Male , Humans , Aged , Breast Neoplasms/drug therapy , Retrospective Studies , Trastuzumab/adverse effects , Nausea , Receptor, ErbB-2/geneticsABSTRACT
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.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunotherapy/adverse effects , Lung Neoplasms/drug therapy , Pemphigoid, Bullous/chemically induced , Aged , Carcinoma, Non-Small-Cell Lung/immunology , Female , Humans , Lung Neoplasms/immunology , Pemphigoid, Bullous/diagnosisABSTRACT
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.
Subject(s)
Cardiomyopathy, Dilated , Ovarian Neoplasms , Adult , Cardiomyopathy, Dilated/chemically induced , Cardiomyopathy, Dilated/drug therapy , Deoxycytidine/analogs & derivatives , Female , Humans , Ovarian Neoplasms/drug therapy , Stroke Volume , Ventricular Function, Left , GemcitabineABSTRACT
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%.
Subject(s)
Neoplasms, Multiple Primary/epidemiology , Neoplasms, Second Primary/epidemiology , Neuroendocrine Tumors/epidemiology , Adult , Aged , Aged, 80 and over , Female , Humans , Italy/epidemiology , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Second Primary/diagnosis , Neuroendocrine Tumors/diagnosis , Retrospective StudiesABSTRACT
Acid-base equilibrium is a complex and vital system whose regulation is impaired in chronic kidney disease (CKD). Metabolic acidosis is a common complication of CKD. It is typically due to the accumulation of sulfate, phosphorus, and organic anions. Metabolic acidosis is correlated with several adverse outcomes, such as morbidity, hospitalization and mortality. In patients undergoing hemodialysis, acid-base homeostasis depends on many factors: net acid production, amount of alkali given by the dialysate bath, duration of interdialytic period, as well as residual diuresis, if any. Recent literature data suggest that the development of postdialysis metabolic alkalosis may contribute to adverse clinical outcomes. Unfortunately, no randomized studies exist about the effect of different dialysate bicarbonate concentrations on hard outcomes, such as mortality. Like everything else in dialysis, the quest for the "ideal" dialysate bicarbonate concentration is far from over. The Latin aphorism "ne quid nimis" ie "nothing in excess" (excess of neither acid nor base) probably best summarizes our current state of knowledge in this field. For the present, the clinician should understand that target values for predialysis serum bicarbonate concentrations have been established primarily based on observational studies and expert opinion. On the basis of this information, we should keep predialysis serum bicarbonate concentrations at least at 22 mEq/L. Furthermore, a specific focus should be addressed to the clinical and nutritional status of the major outliers on both the acid and alkaline sides of the curve.
Subject(s)
Acidosis/etiology , Bicarbonates/metabolism , Hemodialysis Solutions/chemistry , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Acid-Base Equilibrium/physiology , Acidosis/mortality , Bicarbonates/blood , Hemodialysis Solutions/adverse effects , Humans , Kidney Failure, Chronic/complications , Renal Dialysis/mortality , Risk Factors , Survival RateABSTRACT
Metabolic acidosis is a common complication of chronic kidney disease; it is typically caused by the accumulation of sulfate, phosphorus, and organic anions. Metabolic acidosis is correlated with several adverse outcomes, such as morbidity, hospitalization, and mortality. Thus, correction of metabolic acidosis is fundamental for the adequate management of many systemic complications of chronic kidney disease. In patients undergoing hemodialysis, acid-base homeostasis depends on many factors including the following: net acid production, amount of alkali given by the dialysate bath, duration of the interdialytic period, and residual diuresis, if any. Recent literature data suggest that the development of metabolic alkalosis after dialysis may contribute to adverse clinical outcomes. Our review is focused on the potential effects of different dialysate bicarbonate concentrations on hard outcomes such as mortality. Unfortunately, no randomized studies exist about this issue. Acid-base equilibrium is a complex and vital system whose regulation is impaired in chronic kidney disease. We await further studies to assess the extent to which acid-base status is a major determinant of overall survival in patients undergoing hemodialysis. For the present, the clinician should understand that target values for predialysis serum bicarbonate concentration have been established primarily based on observational studies and expert opinion. Based on this, we should keep the predialysis serum bicarbonate level at least at 22 mmol/l. Furthermore, a specific focus should be addressed by the attending nephrologist to the clinical and nutritional status of the major outliers on both the acid and alkaline sides of the curve.
Subject(s)
Acid-Base Equilibrium/drug effects , Acidosis/prevention & control , Bicarbonates/administration & dosage , Hemodialysis Solutions/administration & dosage , Renal Dialysis/methods , Renal Insufficiency, Chronic/therapy , Acidosis/etiology , Acidosis/mortality , Acidosis/physiopathology , Bicarbonates/adverse effects , Bicarbonates/standards , Hemodialysis Solutions/adverse effects , Hemodialysis Solutions/standards , Humans , Hydrogen-Ion Concentration , Male , Models, Biological , Practice Guidelines as Topic , Renal Dialysis/adverse effects , Renal Dialysis/mortality , Renal Dialysis/standards , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/physiopathology , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: It is the object of debate whether a low or high dialysate sodium concentration (DNa(+)) should be advocated in chronic haemodialysis patients. In this paper, we aimed at evaluating benefits and harms of different DNa(+) prescriptions through a systematic review of the available literature. METHODS: MEDLINE and CENTRAL databases were searched for studies comparing low or high DNa(+) prescriptions. Outcomes of interest were mortality, blood pressure (BP), interdialytic weight gain (IDWG), plasma sodium, hospitalizations, use of anti-hypertensive agents and intradialytic complications. RESULTS: Twenty-three studies (76 635 subjects) were reviewed. There was high heterogeneity in the number of patients analysed, overall study quality, duration of follow-up, DNa(+) and even in the definition of 'high' or 'low' DNa(+). The only three studies looking at mortality were observational. The risk of death was related to the plasma-DNa(+) gradient, but was also shown to be confounded by indication from the dialysate sodium prescription itself. BP was not markedly affected by high or low DNa(+). Patients treated with higher DNa(+) had overall higher IDWG when compared with those with lower DNa(+). Three studies reported a significant increase in intra-dialytic hypotensive episodes in patients receiving low DNa(+). Data on hospitalizations and use of anti-hypertensive agents were sparse and inconclusive. CONCLUSIONS: There is currently no definite evidence proving the superiority of a low or high uniform DNa(+) on hard or surrogate endpoints in maintenance haemodialysis patients. Future trials adequately powered to evaluate the impact of different DNa(+) on mortality or other patient-centred outcomes are needed.
Subject(s)
Dialysis Solutions/metabolism , Outcome Assessment, Health Care , Renal Dialysis , Sodium/blood , Blood Pressure , Chronic Disease , Diet, Sodium-Restricted , Hospitalization , Humans , Weight GainABSTRACT
OBJECT: the aim of this study is to present a preliminary analysis of efficacy and effectiveness of a model of chronically ill care (Chronic Care Model, CCM). METHODS: the analysis took into account 106 territorial modules, 1016 General Practitioners and 1,228,595 patients. The diagnostic and therapeutic pathways activated (PDTA), involved four chronic conditions, selected according to the prevalence and incidence, in Tuscany Region: Diabetes Mellitus (DM), Heart Failure (SC), Chronic Obstructive Pulmonary Disease (COPD) and stroke. Six epidemiological indicators of process and output were selected, in order to measure the model of care performed, before and after its application: adherence to specific follow-up for each pathology (use of clinical and laboratory indicators), annual average of expenditure per/capita/euro for diagnostic tests, in laboratory and instrumental, average expenditure per/capita/year for specialist visits; hospitalization rate for diseases related to the main pathology, hospitalization rate for long-term complications and rate of access to the emergency department (ED). Data were collected through the database; the differences before and after the intervention and between exposed and unexposed, were analyzed by method "Before-After (Controlled and Uncontrolled) Studies". The impact of the intervention was calculated as DD (difference of the differences). RESULTS: DM management showed an increased adhesion to follow-up (DD: +8.1%), and the use of laboratory diagnostics (DD: +4,9 /year/pc), less hospitalization for long-term complications and for endocrine related diseases (DD respectively: 5.8/1000 and DD: +1.2/1000), finally a smaller increase of access to PS (DD: -1.6/1000), despite a slight increase of specialistic visits (DD: +0,38 /year/pc). The management of SC initially showed a rising adherence to follow-up (DD: +2.3%), a decrease of specialist visits (DD:E 1.03 /year/pc), hospitalization and access to PS for exacerbations (DD: -4.4/1000 and DD: -6.1/100, respectively), compared with a slight increase of diagnostic tests (DD: +2.10 /year/pc). Stroke showed the following outcomes: increased consumption of instrumental diagnostics and imaging (DD: +1.65 /year/pc) and growing hospitalizations for related conditions (DD 6.1/1,000). The care of patients with COPD, finally, has produced an increase in overall expenditure on medicines (DD: +39.71/year/pc) associated with the decrease of hospitalization for related conditions (DD: -2.7/1,000). CONCLUSION: the Tuscany CCM has proven a promising model of integrated management and taking care for chronic patients, can have a positive impact on the quality of life and on the total health expenditure. Additional monitoring studies are desirable in perspective of expanding the model on all over the national territory.
Subject(s)
Chronic Disease/economics , Chronic Disease/therapy , Health Expenditures , Length of Stay , Primary Health Care , Chronic Disease/epidemiology , Diabetes Mellitus/economics , Diabetes Mellitus/therapy , Follow-Up Studies , Heart Failure/economics , Heart Failure/therapy , Humans , Incidence , Italy/epidemiology , Models, Theoretical , Patient Compliance/statistics & numerical data , Prevalence , Pulmonary Disease, Chronic Obstructive/economics , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Retrospective Studies , Stroke/economics , Stroke/therapyABSTRACT
Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Epigenesis, Genetic/genetics , Pathology, Molecular , Biomarkers, Tumor/genetics , Cell Transformation, Neoplastic/genetics , Chromosomal Instability/genetics , Colorectal Neoplasms/diagnosis , CpG Islands/genetics , DNA Methylation/genetics , Humans , MicroRNAs/geneticsABSTRACT
The relationship between fertility, reproductive hormones, and risk of malignant melanoma has acquired much interest in recent years. Melanocytes are hormonally responsive cells, and some in vitro studies demonstrated that estrogen hormones stimulate the growth of melanocytes. Moreover, estrogen receptors have been identified in melanoma cells, as well as in melanocytic nevi and in normal skin. Some evidences suggest a possible link between fertility treatments and the increased risk of malignant melanoma. This article addresses this association through a scrupulous search of the literature published thus far. The aim of this review is to determine the incidence of malignant melanoma in women treated with fertility drugs and to examine if the exposure to fertility treatments really increases the risk of malignant melanoma. In particular, our analysis focused on the different types of drugs and different treatment schedules used. Finally, this study provides additional insights regarding the long-term relationships between fertility drugs and the risk of malignant melanoma.
Subject(s)
Fertility Agents, Female/adverse effects , Melanoma/epidemiology , Skin Neoplasms/epidemiology , Female , Humans , Incidence , Melanoma/chemically induced , Risk Assessment , Risk Factors , Skin Neoplasms/chemically inducedABSTRACT
Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.
Subject(s)
Adenocarcinoma/pathology , Adenoma, Pleomorphic/pathology , Parotid Neoplasms/pathology , Splenic Neoplasms/secondary , Adenocarcinoma/surgery , Adenoma, Pleomorphic/surgery , Aged , Humans , Male , Parotid Neoplasms/surgery , Prognosis , Splenic Neoplasms/surgeryABSTRACT
Plerixafor, a CXCR4 antagonist, induces the rapid release of hematopoietic progenitor stem cells from the bone marrow into peripheral blood; it is approved for autologous hematopoietic progenitor stem cell mobilization in multiple myeloma and non-Hodgkin's lymphoma patients. We report the case of a 34-year-old patient with metastatic testicular embryonal carcinoma who was extensively and in vain pretreated with chemotherapy and failed to mobilize an adequate number of hematopoietic progenitor stem cells following high-dose chemotherapy, with the support of granulocyte colony-stimulating factors. After a cycle of high-dose cyclophosphamide associated with granulocyte colony-stimulating factors, plerixafor was administered to the patient, with the clinical evidence of an increase in hematopoietic progenitor stem cells in the peripheral blood. The patient achieved a complete engraftment following two cycles of high-dose chemotherapy (paclitaxel, ifosfamide, carboplatin, etoposide), with the support of hematopoietic progenitor stem cells; the patient showed discrete tolerability to the treatment. At biochemical control, the ß-human chorionic gonadotropin value decreased from 86 to less than 1.2 mUI/ml and total body PET-CT scan showed a complete response to chemotherapy. According to this experience, we believe that in patients with advanced germ cell cancer, it is essential to explore the possibility of the use of high-dose chemotherapy to induce a stable and permanent response; in this context, plerixafor, with the support of granulocyte colony-stimulating factors, may be an innovative option for satisfactory mobilization during high-dose chemotherapy protocols.
Subject(s)
Heterocyclic Compounds/therapeutic use , Neoplasms, Germ Cell and Embryonal/therapy , Receptors, CXCR4/antagonists & inhibitors , Stem Cell Transplantation/methods , Testicular Neoplasms/therapy , Adult , Antineoplastic Agents/administration & dosage , Benzylamines , Cyclams , Cyclophosphamide/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cells/drug effects , Heterocyclic Compounds/administration & dosage , Humans , Immunosuppressive Agents/therapeutic use , MaleABSTRACT
AIM: To assess the remission rate of gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma after an eradication therapy in Helicobacter pylori-negative patients. METHODS: We performed a systematic review with pooled analysis of published studies. Data were analyzed according to: (1) number of H. pylori-negative patients treated with only eradication therapy; (2) number of patients in whom the complete lymphoma remission was achieved; and (3) the method used to exclude H. pylori infection. RESULTS: Overall, 11 studies with 110 patients met the inclusion criteria for this pooled analysis. H. pylori infection was excluded in all studies with at least 3 different diagnostic tests. Eradication therapy achieved a complete lymphoma regression in 17 (15.5%; 95% confidence interval, 8.7-22.2) patients. CONCLUSIONS: Eradication therapy is successful in a small but distinct subgroup of H. pylori-negative patients with low-grade mucosa-associated lymphoid tissue lymphoma. On the basis of the generally indolent behavior of this neoplasia, before resorting to aggressive, costly, and potentially more toxic oncologic therapies, it would seem reasonable to attempt eradication therapy in all patients, irrespective of their H. pylori status.
Subject(s)
Helicobacter Infections/drug therapy , Lymphoma, B-Cell, Marginal Zone/drug therapy , Stomach Neoplasms/drug therapy , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Humans , Lymphoma, B-Cell, Marginal Zone/microbiology , Lymphoma, B-Cell, Marginal Zone/pathology , Remission Induction , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Breast adenomyoepithelioma is an unusual tumor characterized by a biphasic proliferation of epithelial and myoepithelial cells. Most breast adenomyoepitheliomas are considered to be benign or to have a low-grade malignant potential, characterized by propensity for local recurrence. Malignant changes arising in this lesion are extremely rare and may involve one or both cellular components. CASE REPORT: We discuss a case of a 60 year-old woman who began to experience pain in her right breast in January 2009. Breast ultrasound and mammography were performed showing a rounded, hypoechoic solid lesion with ill-defined margins in the right inner-inferior quadrant, suspicious of malignancy. Quadrantectomy of the inner-inferior quadrant of the right breast with sampling of ipsilateral axillary lymph nodes was performed. The histological analysis confirmed the diagnosis of adenomyoepithelioma with focal malignant change of the epithelial component, associated with high-grade malignant myoepithelial change. The patient was treated with adjuvant radiotherapy and her right breast received a dose of Gy 50 with a boost of Gy 10 to the tumor bed. At present, the patient shows no sign of tumor recurrence. CONCLUSION: Breast malignant adenomyoepithelioma is a rare tumor which should be considered in the differential diagnosis of other solid breast lesions. Only few cases have been reported in the literature. Diagnosis, optimal therapy and predicting the outcome are problematic issues due to the rarity of this disease which appears to have hematogenous rather than lymphatic spread and usually occurs in primary tumors ≥ 1.6 cm in size.
Subject(s)
Adenomyoepithelioma/pathology , Breast Neoplasms/pathology , Cell Proliferation , Epithelial Cells/pathology , Adenomyoepithelioma/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Epithelial Cells/metabolism , Female , Humans , Middle Aged , PrognosisABSTRACT
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.
ABSTRACT
AIM: The effect of KRAS status on response to bevacizumab plus chemotherapy in metastatic colorectal cancer is still unclear. We aimed to evaluate the overall clinical response to such a therapy in clinical practice and assess the role of KRAS status on therapy response. PATIENTS & METHODS: This was a retrospective study enrolling 108 metastatic colorectal cancer patients. KRAS mutation analysis was performed by PCR. RESULTS: Overall, 41.7% of patients had stable disease, 39.8% a partial response, 3.7% a complete response and 14.8% disease progression. Both clinical benefit and objective response rate tended to be higher in patients with only hepatic metastases than those with extrahepatic or multiple metastases. Response to therapy would appear to be independent of KRAS status, but larger studies are needed. CONCLUSION: Bevacizumab plus chemotherapy provides clinical benefit and objective response rate in patients with metastatic colorectal cancer independently of KRAS expression, especially in those patients with only liver metastases.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Survival Analysis , Treatment Outcome , ras Proteins/geneticsABSTRACT
In 40% of patients with chronic hepatitis C, standard therapy is unable to eradicate the virus. Since the response to pharmacological treatment depends on the initial viral load, there is a rationale for reducing this load by means of apheretic depletion of the C virus. The aim of this work was to administer cascade filtration (CF) to non responder patients affected by hepatitis C (pts) before resuming the pharmacological treatment. 10 pts underwent 12 sessions of CF, 3 per week (treated plasma volume/session: 3000 mL). After the first week, therapy with PEG-IFN (1.5 ug/Kg/week) plus Ribavirin (1200 mg/day) was added. The viral load was determined before and after each CF session, and at the 1st, 3rd and 6th month. The mean pre-apheresis viral load dropped from 2176275+/-3109997 U/mL at the first session to 1486726+/-2091975 U/mL by the fourth (p<0.001), and 347500+/-637428 U/mL before the last (p<0.001). The mean percentage reduction of the viral load went from a minimum of 29.5% to a maximum of 42%. Early viral response (EVR) was obtained in 70% of these patients as compared with only 10% in an age- and sex-matched control group consisting of 10 patients. Unfortunately, we did not get the same good results in terms of sustained viral response (SVR: 10% in apheretic patients vs 0% in the control group). Efficacious removal of HCV was obtained with CF. However, the successful reduction in the viral load achieved with apheresis in terms of EVR was not confirmed when we considered the SVR.
Subject(s)
Antiviral Agents/therapeutic use , Filtration , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Plasmapheresis/methods , Ribavirin/therapeutic use , Viral Load/drug effects , Drug Therapy, Combination , Filtration/methods , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Recombinant Proteins/therapeutic use , Treatment Failure , Treatment OutcomeABSTRACT
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.
ABSTRACT
OBJECTIVES: To investigate the independent association between the homeostasis model assessment of the insulin resistance (HOMA-IR) score and rapid virological response (RVR) and sustained virological response (SVR) in chronic hepatitis C (CHC). METHODS: Observational prospective cohort study of 412 CHC patients [59% males; mean age 45 years; genotype 1 (44%), 2 (32%), 3 (19%) and 4 (5%)] treated with pegylated interferon α plus ribavirin. RESULTS: A HOMA-IR ≥2.0 was present in 49% and a metabolic syndrome in 4% of patients. By multivariate analysis, independent predictors of SVR were the lack of advanced fibrosis (≥F3) in genotype 1 and a lower body mass index in genotype 3 patients. In the subgroup of patients in whom HCV-RNA was evaluated at week 4 (n = 281), independent predictors of RVR were HCV-RNA <700,000 IU/ml, age <40 years and lower aspartate aminotransferase:alanine aminotransferase ratio in genotype 1 and baseline HOMA-IR ≤2 in genotype 3 patients. No predictive factor of RVR was identified among genotype 2 patients. RVR was the strongest predictor of SVR among genotype 1 or 3 patients. CONCLUSIONS: In this series of treatment-naïve, Caucasian CHC patients at a low risk for the metabolic syndrome, HOMA-IR is not a predictor of SVR, irrespective of the HCV genotype, although it may predict RVR in genotype 3 infection.
Subject(s)
Antiviral Agents/therapeutic use , Health Status Indicators , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Insulin Resistance , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , Chi-Square Distribution , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/ethnology , Hepatitis C, Chronic/physiopathology , Humans , Interferon alpha-2 , Italy , Logistic Models , Male , Middle Aged , Models, Biological , Predictive Value of Tests , Prospective Studies , RNA, Viral/blood , Recombinant Proteins , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Viral Load , White PeopleABSTRACT
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.