Impact of Signet-Ring Cell Histology in the Management of Patients with Non-Metastatic Gastric Cancer: Results from a Retrospective Multicenter Analysis Comparing FLOT Perioperative Chemotherapy vs. Surgery Followed by Adjuvant Chemotherapy

Simple Summary FLOT-based perioperative chemotherapy is the mainstay of treatment for patients with non-metastatic gastric cancer in Western countries. Although signet-ring cell histology has been proven to be associated with a lack of response to chemotherapy, there is a lack of data concerning whether FLOT-based chemotherapy might be less effective in patients with signet-ring histology. The aim of this retrospective study is to assess whether patients whose gastric cancer is signet-ring cell positive might benefit less compared to others when treated with perioperative FLOT. Background: FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. Methods: We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Results: Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56-6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55-6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50-7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18-12-68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Conclusions: Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients

Prospective multicenter evaluation of real time PCR Kit prototype for early diagnosis of congenital Chagas disease

Background: Current algorithm for Congenital Chagas Disease (cCD) diagnosis is unsatisfactory due to low sensitivity of the parasitological methods. Moreover, loss to follow-up precludes final serodiagnosis after nine months of life in many cases. A duplex TaqMan qPCR kit for Trypanosoma cruzi DNA amplification was prospectively evaluated in umbilical cord (UCB) and peripheral venous blood (PVB) of infants born to CD mothers at endemic and non-endemic sites of Argentina. Methods: We enrolled and followed-up 370 infants; qPCR was compared to gold-standard cCD diagnosis following studies of diagnostic accuracy guidelines. Findings: Fourteen infants (3·78%) had cCD. The qPCR sensitivity and specificity were higher in PVB (72·73%, 99·15% respectively) than in UCB (66·67%, 96·3%). Positive and negative predictive values were 80 and 98·73% and 50 and 98·11% for PVB and UCB, respectively. The Areas under the Curve (AUC) of ROC analysis for qPCR and micromethod (MM) were 0·81 and 0·67 in UCB and 0·86 and 0·68 in PVB, respectively. Parasitic loads ranged from 37·5 to 23,709 parasite equivalents/mL. Discrete typing Unit Tc V was identified in five cCD patients and in six other cCD cases no distinction among Tc II, Tc V or Tc VI was achieved. Interpretation: This first prospective field study demonstrated that qPCR was more sensitive than MM for early cCD detection and more accurate in PVB than in UCB. Its use, as an auxiliary diagnostic tool to MM will provide more accurate records on cCD incidence. Funding: FITS SALUD 001-CHAGAS (FONARSEC, MINCyT, Argentina) to the Public-Private Consortium (INGEBI-CONICET, INP-ANLIS MALBRAN and Wiener Laboratories); ERANET-LAC-HD 328 to AGS and PICT 2015-0074 (FONCYT, MinCyT) to AGS and FA.Fil: Benatar, Alejandro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Danesi, Emmaría. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Besuschio, Susana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bortolotti, Santiago. Wiener Laboratorios SAIC; ArgentinaFil: Cafferata, María Luisa. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lopez Albizu, Maria Constanza. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaFil: Scollo, Karenina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaFil: Baleani, María. Wiener Laboratorios SAIC; ArgentinaFil: Lara, Laura. Instituto de Maternidad y Ginecología ''Nuestra Señora de las Mercedes''; ArgentinaFil: Agolti, Gustavo. Gobierno de la Provincia de Chaco. Hospital Julio César Perrando; ArgentinaFil: Seu, Sandra. Gobierno de la Provincia de Santiago del Estero. Hospital Regional Dr. Ramón Carrillo; ArgentinaFil: Adamo, Elsa. Provincia de Santiago del Estero. Centro Integral de Salud La Banda; ArgentinaFil: Lucero, Raul Horacio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; ArgentinaFil: Irazu, Lucía. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Rodriguez, Marcelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Poeylaut Palena, Andrés Alberto. Wiener Laboratorios SAIC; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaFil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rojkin, Federico. Wiener Laboratorios SAIC; ArgentinaFil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sosa-Estani, Sergio Alejandro. Instituto de Efectividad Clínica y Sanitaria; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Congenital Chagas Disease Study Group. No especifíca

Multicentre observational study on multisystem inflammatory syndrome related to COVID-19 in Argentina

Background: The impact of the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in low- and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina. Methods: This observational, prospective, and retrospective multicenter study enrolled patients younger than 18 years-old manifesting PIMS-TS, Kawasaki disease (KD) or Kawasaki shock syndrome (KSS) between March 2020 and May 2021. Patients were followed-up until hospital discharge or death (one case). The primary outcome was pediatric intensive care unit (PICU) admission. Multiple logistic regression was used to identify variables predicting PICU admission. Results: Eighty-one percent, 82%, and 14% of the 176 enrolled patients fulfilled the suspect case criteria for PIMS-TS, KD, and KSS, respectively. Temporal association with SARS-CoV-2 was confirmed in 85% of the patients and 38% were admitted to the PICU. The more common clinical manifestations were fever, abdominal pain, rash, and conjunctival injection. Lymphopenia was more common among PICU-admitted patients (87% vs. 51%, p < 0.0001), who also showed a lower platelet count and higher plasmatic levels of inflammatory and cardiac markers. Mitral valve insufficiency, left ventricular wall motion alterations, pericardial effusion, and coronary artery alterations were observed in 30%, 30%, 19.8%, and 18.6% of the patients, respectively. Days to initiation of treatment, rash, lymphopenia, and low platelet count were significant independent contributions to PICU admission. Conclusion: Rates of severe outcomes of PIMS-TS in the present study agreed with those observed in high-income countries. Together with other published studies, this work helps clinicians to better understand this novel clinical entity.Fil: Vainstein, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Baleani, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Urrutia, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Affranchino, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ackerman, Judith. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Cazalas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Goldsman, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Sardella, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Tolin, Ana Laura. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Goldaracena, Pablo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fabi, Mariana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Cosentino, Mariana. Hospital Británico de Buenos Aires; ArgentinaFil: Magliola, Ricardo. Hospital Británico de Buenos Aires; ArgentinaFil: Roggiero, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Manso, Paula. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Triguy, Jésica. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Ballester, Celeste. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Cervetto, Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Vaccarello, María. Sanatorio de la Trinidad; ArgentinaFil: De Carli, Domingo Norberto. Clínica del Niño de Quilmes; ArgentinaFil: De Carli, Maria Estela. Clínica del Niño de Quilmes; ArgentinaFil: Ciotti, Ana Laura. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Sicurello, María Irene. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rios Leiva, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Villalba, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Hortas, María. Sanatorio de la Trinidad; ArgentinaFil: Peña, Sonia. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: González, Gabriela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Grippo, M.. No especifíca;Fil: Vázquez, H.. No especifíca;Fil: Morós, C.. No especifíca;Fil: Di Santo, M.. No especifíca;Fil: Villa, A.. No especifíca;Fil: Lazota, P.. No especifíca;Fil: Foti, M.. No especifíca;Fil: Napoli, N.. No especifíca;Fil: Katsikas, M. M.. No especifíca;Fil: Tonello, L.. No especifíca;Fil: Peña, J.. No especifíca;Fil: Etcheverry, M.. No especifíca;Fil: Iglesias, D.. No especifíca;Fil: Alcalde, A. L.. No especifíca;Fil: Bruera, M.J.. No especifíca;Fil: Bruzzo, V.. No especifíca;Fil: Giordano, P.. No especifíca;Fil: Pena Acero, F.. No especifíca;Fil: Netri Pelandi, G.. No especifíca;Fil: Pastaro, D.. No especifíca;Fil: Bleiz, J.. No especifíca;Fil: Rodríguez, M. F.. No especifíca;Fil: Laghezza, L.. No especifíca;Fil: Molina, M. B.. No especifíca;Fil: Patynok, N.. No especifíca;Fil: Chatelain, M. S.. No especifíca;Fil: Aguilar, M. J.. No especifíca;Fil: Gamboa, J.. No especifíca;Fil: Cervan, M.. No especifíca;Fil: Ruggeri, A.. No especifíca;Fil: Marinelli, I.. No especifíca;Fil: Checcacci, E.. No especifíca;Fil: Meregalli, C.. No especifíca;Fil: Damksy Barbosa, J.. No especifíca;Fil: Fernie, L.. No especifíca;Fil: Fernández, M. J.. No especifíca;Fil: Saenz Tejeira, M.M.. No especifíca;Fil: Cereigido, C.. No especifíca;Fil: Nunell, A.. No especifíca;Fil: Villar, D.. No especifíca;Fil: Mansilla, A. D.. No especifíca;Fil: Darduin, M. D.. No especifíca

Managing hyponatremia in lung cancer: latest evidence and clinical implications

Hyponatremia is the most common electrolyte disorder in lung cancer patients. This condition may be related to many causes including incidental medications, concurrent diseases and side effects of antineoplastic treatments or the disease itself. Although not frequently life-threatening, it is usually associated with prolonged hospitalization, delays in scheduled chemotherapy, worsening of patient performance status and quality of life and may also negatively affect treatment response and survival. Most of the available data focus on thoracic tumors, especially small-cell lung cancer (SCLC), where hyponatremia is frequently related to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Few studies specifically focus on non-small cell lung cancer (NSCLC) patients. Hyponatremia treatment needs to be personalized based on severity and duration of sodium serum reduction, extracellular fluid volume and etiology. However, literature data highlight the importance of early correction of the serum concentration levels. To achieve this the main options are fluid restriction, hypertonic saline, loop diuretics, isotonic saline, tolvaptan and urea. The aim of this review is to analyze the role of hyponatremia in lung cancer patients, evaluating causes, diagnosis, management and clinical implications

Alarming Drop in Early Stage Colorectal Cancer Diagnoses After COVID-19 Outbreak: A Real-World Analysis from the Italian COVID-DELAY Study

Background: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter Italian study aimed to evaluate whether COVID-19 has impacted access to diagnosis, staging, and treatment for patients newly diagnosed with colorectal cancer (CRC), compared with pre-pandemic time. Methods: All consecutive new CRC patients referred to 8 Italian oncology institutions between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset, radiological and cytohistological diagnosis, treatment start and first radiological evaluation were analyzed and compared with the same months of 2019. Results: A reduction (29%) in newly diagnosed CRC cases was seen when compared with 2019 (360 vs 506). New CRC patients in 2020 were less likely to be diagnosed with early stage (stages I-II-III) CRC (63% vs 78%, P < .01). Gender and sidedness were similar regardless of the year. The percentage of tumors with any mutation among BRAF, NRAS, and KRAS genes were significantly different between the 2 years (61% in 2020 vs 50% in 2019, P = .04). Timing of access to cancer diagnosis, staging, and treatment for patients with CRC has not been negatively affected by the pandemic. Significantly shorter temporal intervals were observed between symptom onset and first oncological appointment (69 vs 79 days, P = .01) and between histological diagnosis and first oncological appointment (34 vs 42 days, P < .01) during 2020 compared with 2019. Fewer CRC cases were discussed in multidisciplinary meetings during 2020 (38% vs 50%, P = .01). Conclusions: Our data highlight a significant drop in CRC diagnosis after COVID-19, especially for early stage disease. The study also reveals a remarkable setback in the multidisciplinary management of patients with CRC. Despite this, Italian oncologists were able to ensure diagnostic-therapeutic pathways proper operation after March 2020