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Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease. In addition to pathology, molecular analysis is pivotal in differential diagnosis, especially with malignant melanoma. A key aspect in identifying clear cell sarcoma is specific genetic alterations, notably the translocation of t(12;22) (q13;q13), a diagnostic hallmark of this sarcoma subtype, which is absent in malignant melanoma. Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.
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BACKGROUND/AIM: Surgical resection with a minimally invasive approach is the standard for diagnosing and treating solitary pulmonary nodules. A computed tomography (CT)-guided technetium99m-macroaggregated albumin (99mTc-MAA) injection-based procedure has been employed for small and non-palpable lung nodule radio-guided preoperative localization (ROLL). This procedure is usually followed by video-assisted thoracoscopic surgery (VATS). This study retrospectively evaluated the feasibility, clinicopathologic outcomes, and complications of this localization radio-guided procedure followed by uniportal VATS. PATIENTS AND METHODS: This retrospective study included 63 patients with suspicious lung nodules who underwent 99mTc-MAA CT-guided localization before uniportal VATS. The analysis examined the imaging and procedure characteristics, procedural risks, successful intra-operative localization, wedge resection, conversion from VATS to open thoracotomy, the reason, and histological diagnosis for each nodule. Also, it was evaluated how nodule and procedure features affected successful intra-operative localization. RESULTS: All patients were diagnosed using a CT scan, and 90.4% had a PET scan at basal staging. A round-glass morphology was present in 9.6% of cases, whereas most had a solid appearance. The mean nodule size was 9.78 mm (maximal tumoral diameter) with a 1-23 mm range. The mean distance from the pleural surface was 15.6 mm (range=1-117 mm). The detection rate of the 99mTc-MAA CT-guided localization procedure was 100%. Surgical procedures were uniportal VATS and transpleural thoracoscopy in 52 (82.5%) and 11 (17.5%) patients, respectively. The intraoperative localization rate was 98.4%. Pneumothorax represented the most frequent complication (6.3%), with one case clinically significant and three only with minimal radiological evidence. Pathology confirmed radical excision in all cases. CONCLUSION: Lung nodule localization with CT-guided 99mTc-MAA followed by uniportal VATS is feasible with a high success rate and low complication rate.
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Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Cirugía Torácica Asistida por Video , Tomografía Computarizada por Rayos X , Humanos , Cirugía Torácica Asistida por Video/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Nódulo Pulmonar Solitario/cirugía , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Tomografía Computarizada por Rayos X/métodos , Adulto , Radiofármacos/administración & dosificación , Anciano de 80 o más AñosRESUMEN
Ileal (I) and pancreatic (Pan) neuroendocrine tumors (NETs) are among the most common digestive neuroendocrine neoplasms (NENs). Coexisting NETs at both sites are rare, and establishing the primary or metastatic nature of the two lesions may be crucial for the appropriate treatment. We reviewed all the clinical reports of patients with INETs or PanNETs, diagnosed and treated in our ENETS Center of Excellence between 2012 and 2022. We selected patients with a history of synchronous or metachronous neuroendocrine (NE) lesions at the ileum and pancreas. For those with available histological samples from both sites, an immunohistochemistry (IHC) analysis for CDX2, Islet1, and serotonin has been performed. We found seven patients with NET in both the ileum and pancreas. F to M ratio was 4:3, and the median age at first diagnosis was 54 years (42-79). Five cases had synchronous lesions; in 2 cases, PanNETs were diagnosed respectively 8 and 56 months, after INETs. In four patients, with available histological samples from both the sites, a pathologic review and the IHC analysis have been performed, identifying three different scenarios: (i) primary INET metastatic to the pancreas, (ii) primary PanNET metastatic to the ileum, and (iii) synchronous primary PanNET and INET. In our experience, coexisting ileal and pancreatic NENs are rare occurrences. A multidisciplinary evaluation case-by-case and, whenever feasible, a comprehensive histopathological examination are needed to distinguish between metastatic and primary disease, in order to properly treat the patient.
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INTRODUCTION: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants?Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected. METHODS: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers.Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes. CONCLUSIONS: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization.
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Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Italia/epidemiología , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/tratamiento farmacológico , Estudios Retrospectivos , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Femenino , Masculino , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Persona de Mediana Edad , AncianoRESUMEN
PURPOSE: The aim of this study is to describe the clinical management of an Italian series of patients with advanced gastro-entero-pancreatic (GEP) MiNENs treated in clinical practice. METHODS: Clinical records of patients from four Italian referral Centers were retrospectively analyzed to correlate clinical/biological data with clinical outcomes. All the surgical specimens were centrally reviewed. RESULTS: Clinical data and surgical samples of 51 patients during 1995-2015 were analyzed. Sites of origin were: 32 colorectal, 14 gastro-esophageal, and 5 pancreatobiliary. Twenty-one out of fifty-one (42.2%) developed metachronous distant metastases. Only 5/51 (9.8%) patients received peri-operative therapy, and 23/51 (45.1%) first-line chemotherapy, mostly fluoropyrimidines/oxaliplatin. The NEN component was poorly differentiated in the whole population. Patients with Ki67 index < 55% in the NEC component had a significantly longer median overall survival (OS) (35.3 months; 95% CI 27.1-41.0) than those with Ki67 ≥ 55% (11.9 months; 95% CI 9.1-14.0) P = 0.0005. The median OS was 14 months (95% CI 10.1-19.1) in the whole cohort, with 11.4 months (95% CI 6.2-20.2) in patients who received a first-line therapy. CONCLUSION: This study confirms that GEP-MiNENs represent a complex disease and that over the past years the clinical management has been predominantly guided by the subjective judgment of the clinicians. Although, in this series, the NEC component appeared mostly responsible for the systemic spread and prognosis on the whole neoplasm, the lack of strong prognostic and predictive factors universally recognized seems to condition their management so far. Future prospective clinical and biomolecular studies could help clinicians to improve clinical management of GEP-MiNENs.
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We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5-66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs (miR-378e, miR-1233, miR-99b-5p, miR-1260b, miR-448, -miR-1252-5p, miR-324-3p, miR-1233-3p) showed a statistically significant negative association with PFS. When we considered PFS < 6 months, miR-378e, miR-99b-5p, miR-877-5p, miR-1297, miR-455-5p, and miR-4536-5p were statistically associated with a poor outcome. In the multivariate analysis, the first three miRNAs confirmed a significant and independent impact on PFS. The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.
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Neoplasias de la Mama , MicroARNs , Piridinas , Humanos , Femenino , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Piperazinas/farmacología , Piperazinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Receptor ErbB-2/metabolismo , Quinasa 4 Dependiente de la Ciclina/genéticaRESUMEN
BACKGROUND/AIM: Chronic inflammation and cytokine storm can cause uncontrolled events in cancer. Pro-inflammatory molecules released by malignant cells send signals to the brain, liver, and neuroendocrine cells, interfering with appetite and promoting anorexia. Malnutrition in cancer patients is associated with increased treatment toxicity, reduced physical efficiency, and decreased survival. Therefore, early recognition of malnutrition could improve quality of life, treatment compliance, and survival. The aim of the study was to explore the relationship between inflammatory parameters with disease stage and nutritional status in patients with solid cancers. PATIENTS AND METHODS: We screened 77 consecutive patients from 3 clinical Institutions in Sicily, Italy, with solid tumors who were either in follow-up after curative treatment or being treated for metastatic disease using the Mini Nutritional Assessment (MNA) questionnaire. Inflammatory parameters, including interleukin 6 (IL6), C-reactive protein (CRP), ß2-microglobulin, ferritin, and transferrin were evaluated. RESULTS: A statistically significant difference was found in mean values of IL6, CRP, ß2-microglobulin, ferritin, and transferrin between patients without evidence of disease and metastatic patients. Among the metastatic group, there was a significant difference in mean values of these inflammatory parameters between patients with malnutrition and those with normal nutritional status. The difference in average IL6, CRP, ß2-microglobulin, and ferritin between patients at risk of malnutrition and those with normal nutritional status was also significant. However, the difference between patients at risk of malnutrition and those with malnutrition was not significant. CONCLUSION: IL6, CRP, transferrin, ferritin, and ß2-microglobulin are functional inflammatory parameters that indicate risk of malnutrition and support the MNA screening test to identify patients with solid tumors who require nutritional support.
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Desnutrición , Neoplasias , Humanos , Estado Nutricional , Calidad de Vida , Interleucina-6/metabolismo , Desnutrición/etiología , Evaluación Nutricional , Proteína C-Reactiva/metabolismo , Transferrina/metabolismo , Ferritinas , Neoplasias/complicacionesRESUMEN
Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH. Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4-8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL. Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold. Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin.
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BACKGROUND: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus. METHODS: Patients with advanced, low- or intermediate-grade pancreatic, gastrointestinal, or lung neuroendocrine tumors received either oral everolimus at 10 mg/d or a placebo in the RAD001 in Advanced Neuroendocrine Tumors 3 (RADIANT-3) and RAD001 in Advanced Neuroendocrine Tumors 4 (RADIANT-4) trials. A landmark progression-free survival (PFS) analysis by central review was performed for patients treated for at least 16 weeks (n = 308) and according to the occurrence of any-grade adverse events (AEs) within this treatment period. RESULTS: The overall PFS with everolimus from the pooled analysis was 11.4 months (95% confidence interval, 11.01-13.93 months), which was consistent with the findings of RADIANT-3 and RADIANT-4. Overall, 19.1% and 9.8% of patients in RADIANT-3 and 11.9% and 6.4% of patients in RADIANT-4 developed any-grade hyperglycemia and hypercholesterolemia, respectively (regardless of the study drug). The duration of everolimus exposure was longer in patients who developed these AEs versus patients without these AEs. Overall, 308 patients were exposed to treatment for at least 16 weeks (hyperglycemia, 39 of 269 patients; hypercholesterolemia, 20 of 288 patients). No association was observed between the development of these AEs and PFS (18.8 and 14.1 months with and without hyperglycemia, respectively, and 14.1 and 14.8 months with and without hypercholesterolemia, respectively). CONCLUSIONS: Although limitations apply because of the small number of AEs observed, there was no significant impact of these AEs on PFS; this suggests similar efficacy in the presence or absence of these events.
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Antineoplásicos , Everolimus , Tumores Neuroendocrinos , Antineoplásicos/toxicidad , Ensayos Clínicos Fase III como Asunto , Everolimus/toxicidad , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP. METHODS: Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion. RESULTS: Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]). CONCLUSIONS: Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.
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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Carcinoma de Células de Merkel/tratamiento farmacológico , Humanos , Italia , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of the study was to assess the impact of systemic markers of inflammation on the outcomes in patients with neuroendocrine tumors (NETs) treated with everolimus or placebo (as measured by baseline neutrophil-to-lymphocyte ratio [NLR] and lymphocyte-to-monocyte ratio [LMR]). METHODS: Patient data (gastrointestinal, pancreatic, and lung NETs) from 2 large phase 3 studies, RADIANT-3 (n = 410) and RADIANT-4 (n = 302), were pooled and analyzed. The primary end point was centrally assessed progression-free survival (PFS) as estimated by the Kaplan-Meier method. RESULTS: In the pooled population, elevated LMR (median PFS, 11.1 months; 95% confidence interval, 9.3-13.7; hazard ratio, 0.69; P < 0.001) and reduced NLR (median PFS, 10.8 months; 95% confidence interval, 9.2-11.7; hazard ratio, 0.75; P = 0.0060) correlated with longer PFS among all patients. These markers were also found to be prognostic in the everolimus- and placebo-treated subgroups. CONCLUSIONS: Data from this study suggest that LMR and NLR are robust prognostic markers for NETs and could potentially be used to identify patients who may receive or are receiving the most benefit from targeted therapies. As both are derived from a complete blood count, they can be routinely used in clinical practice, providing valuable information to clinicians and patients alike.
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Neoplasias Gastrointestinales/sangre , Inflamación/sangre , Neoplasias Pulmonares/sangre , Linfocitos , Monocitos , Tumores Neuroendocrinos/sangre , Neutrófilos , Antineoplásicos/uso terapéutico , Toma de Decisiones Clínicas , Ensayos Clínicos Fase III como Asunto , Everolimus/uso terapéutico , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/mortalidad , Humanos , Inflamación/diagnóstico , Inflamación/tratamiento farmacológico , Inflamación/mortalidad , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Recuento de Linfocitos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/mortalidad , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present.
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Neoplasias del Colon , Oncología Médica , Humanos , Incidencia , Italia , Estadificación de NeoplasiasRESUMEN
There is scant evidence about optimal management of poorly differentiated neuroendocrine carcinoma of the bladder (BNEC). We performed a multicenter retrospective study on BNEC patients from 13 Italian neuroendocrine-dedicated centers to analyze strategies associated with better outcomes. Mixed adeno-neuroendocrine carcinomas (MANEC) were included. We analyzed overall survival (OS) in the overall cohort, relapse-free survival (RFS) in radically operated patients and progression-free survival (PFS) in patients who received chemotherapy for metastatic disease. Fifty-one BNEC patients were included (male: 46, median age: 70 years). Overall, median OS was 16.0 months, radical tumor resection was performed in 37 patients (72.5%) and 11 of these (29.7%) also received peri-operative platinum-etoposide chemotherapy. Median OS was longer in patients with better performance status (PS) and in those with stage I-III disease at diagnosis compared to stage IV. Among patients who underwent radical tumor resection (N = 37), RFS was longer in patients with better PS and showed a trend towards a longer RFS in those treated with peri-operative chemotherapy than with surgery alone (11 vs. 6 months; p = 0.078). Among 28 patients receiving chemotherapy for metastatic disease, PFS was 5.0 months and there was a trend towards improved PFS in patients receiving carboplatin-etoposide chemotherapy compared to other regimens. A multivariate model unmasked a significant association between carboplatin-etoposide chemotherapy and risk for disease progression or death (HR: 0.39 (95%CI: 0.16-0.96) p = 0.040). Performance status might be associated with improved RFS in radically operated patients, while type of chemotherapy might affect PFS in patients receiving chemotherapy for metastatic BNEC.
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BACKGROUND: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting. METHODS: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical-pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed. RESULTS: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate. CONCLUSIONS: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.
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BACKGROUND: The role of adjuvant chemotherapy (ACT) for resected biliary tract cancer (BTC) is still unclear and there is no specific recommendation by international guidelines. AIM: To perform a meta-analysis of randomized clinical trials (RCTs) to better define the clinical benefit and risks of ACT or observation in resected BTC. METHOD: A systematic literature search of Pubmed, Embase, and the Cochrane Library was performed up to April 2019. A meta-analysis was carried out using the random effects model. RESULTS: ACT provided a mild improvement in recurrence free survival (RFS) (HR:0.83, 95%CI 0.69-0.99) and no effect on overall survival (OS) (HR:0.91, 95%CI 0.75-1.09). Similarly, ACT showed no effect on OS in lymph-node positive subgroup (HR:0.84, 95% CI 0.65-1.08) and surgical margin positive subgroup (HR:0.95, 95%CI 0.69-1.31). Moreover, ACT led to a substantial increase of chemotherapy-associated adverse events (RR:3.03, 95%CI 2.22-4.15). CONCLUSION: ACT for resected BTC patients modestly improved RFS with no effect on OS and a substantial increase in chemotherapy associated AEs.
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Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. OBJECTIVES: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. METHODS: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. RESULTS: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. CONCLUSION: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Organización Mundial de la Salud , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/diagnóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: The well-being and quality of life (QoL) of long-term cancer survivors may be affected, both positively and negatively, by psychosocial factors related to the experience of being a cancer patient. We investigated whether, in long-term cancer survivors, the psychosocial impacts of cancer associate with socio-demographic-clinical variables; whether, within the positive and negative dimensions taken separately, some impacts are more intense than others; and whether these impacts explain QoL. METHODS: Italian long-term cancer survivors (n = 500) completed the Impact of Cancer (IOC-V2) and Short Form 36 Health Survey (SF-36) questionnaires. RESULTS: The IOC-V2 negative impact score associated with gender, education, occupational status and health issues, whereas no association was found between the positive impact score and socio-demographic-clinical variables. Of the positive impacts, Altruism/Empathy was the highest (p < 0.001); Positive self-evaluation was higher than Health awareness (p = 0.001); and Meaning of cancer was the lowest (p < 0.001). Among the negative impacts, Worry was the highest (p < 0.001), whereas Body changes concerns was higher than both Appearance concerns (p < 0.001) and Life Interferences (p < 0.001). The assessed impacts explained more than 25% of the variance of both physical and mental functioning scores. CONCLUSIONS: The provided data document psychosocial factors affecting QoL in Italian long-term cancer survivors.
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Supervivientes de Cáncer/psicología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Altruismo , Imagen Corporal , Costo de Enfermedad , Escolaridad , Empatía , Empleo , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Italia , Masculino , Persona de Mediana Edad , Rendimiento Físico Funcional , Autoevaluación (Psicología) , Factores SexualesRESUMEN
BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.
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Antineoplásicos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Everolimus/uso terapéutico , Metformina/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Somatostatina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Diabetes Mellitus Tipo 2/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Not all patients with resectable colorectal liver metastases (CLM) benefit from liver resection (LR); only patients with disease progression during chemotherapy are excluded from surgery. OBJECTIVE: This study was performed to determine whether tumor behavior (stable disease/progression) from the end of chemotherapy to LR impacts prognosis. METHODS: Patients undergoing LR after tumor response or stabilization during chemotherapy were considered. Overall, 128 patients who underwent examination by two imaging modalities (computed tomography/magnetic resonance imaging) after chemotherapy with a > 3-week interval between the two imaging modalities were analyzed. Any variation in CLM size was registered. Tumor progression was defined according to the response evaluation criteria in solid tumors (RECIST) criteria. RESULTS: Among 128 patients with stable disease or partial response to preoperative chemotherapy, 32 (25%) developed disease progression in the chemotherapy to LR interval, with a disease progression rate of 17% when this interval was < 8 weeks. Survival was lower among patients with progression than those with stable disease [3-year overall survival (OS) 23.0 vs. 52.4%, and recurrence-free survival (RFS) 6.3% vs. 21.6%; p < 0.001]. Survival was extremely poor in patients with early progression (< 8 weeks) (0.0% 2-year OS, 12.5% 6-month RFS). Disease progression in the chemotherapy to LR interval was an independent negative prognostic factor for OS and RFS [hazard ratio 3.144 and 2.350, respectively; p < 0.001]. CONCLUSIONS: Early disease progression in the chemotherapy to LR interval occurred in approximately 15% of patients and was associated with extremely poor survival. Even if these data require validation, the risk for early disease progression after chemotherapy should be considered, and, if progression is evident, the indication for surgery should be cautiously evaluated.