Malignant Gastrointestinal Neuroectodermal Tumor of Small Intestine Showing DOG1 Expression: A Case Report and Review of Literature.

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like tumor of the GI tract is a rare mesenchymal tumor of the gastrointestinal tract. It has to be distinguished from various mimickers including gastrointestinal stromal tumor (GIST) due to its aggressive course and different natural history and therapeutic approach. Here we report a case of GNET arising in the small intestine with aberrant DOG1 expression posing a diagnostic challenge. In this context, the combination of clinical, histomorphological, immunohistochemical, and molecular features helped to establish a proper diagnosis.

Hypertensive Crisis in a Patient With a Functioning Mesenteric Paraganglioma: Dramatic Response to Octreotide Treatment.

Background/Objective: To report a dramatic and immediate clinical and biochemical response during treatment with octreotide in a patient with a functioning mesenteric paraganglioma (PGL). Case Report: A 44-year-old woman was admitted with a severe hypertensive crisis and a blood pressure reaching 260/150 mm Hg. She was 2 months postpartum and had been previously diagnosed with pre-eclampsia. Secondary hypertension was suspected. This was confirmed by finding a 6 × 5-cm2 retroperitoneal mass located using 68-Gallium DOTA-octreotate positron emission tomography/computed tomography and a grossly elevated plasma catecholamine level of 93 000 pmol/L (normal reference range: 650-2433 pmol/L). Treatment was immediately started with high doses of long- and short-acting octreotide. After 6 weeks and before surgery, the patient was normotensive, with a blood pressure of 120/70 mm Hg and a norepinephrine level of 6000 pmol/L. The tumor resection was uneventful, and histology confirmed the diagnosis. Following the surgery, the patient remained normotensive without any medications. Discussion: PGLs and pheochromocytomas are neuroendocrine tumors, and most have receptors for octreotide. This case and another patient previously reported responded dramatically to treatment with a high dose of octreotide. Earlier reports of patients failing to respond are likely to have been the result of using a smaller octreotide dose. Conclusion: We conclude that high doses of short- and long-acting octreotide are valuable in severely hypertensive patients. Our experience suggests that octreotide is of value in other patients with PGLs and pheochromocytomas. The response is rapid, sustained, effective, and with minimal reported side effects. To the best of our knowledge, this is the first report of a hypertensive crisis in a functional mesenteric PGL.

Comparación de la mortalidad en pacientes en quimioterapia o inmunoterapia durante y antes de la pandemia de COVID-19. Estudio multicéntrico de cohortes emparejadas en Argentina / Comparison of mortality in patients on chemotherapy or immunotherapy during and before COVID-19 pandemic. Multicenter matched cohort study in Argentina

RESUMEN Objetivos. Comparar la mortalidad por todas las causas de pacientes oncológicos no vacunados que recibieron quimioterapia o inmunoterapia durante la pandemia, con aquellos tratados antes de la pandemia. Materiales y métodos. Realizamos un estudio de cohortes en cuatro hospitales terciarios en Argentina. Pacientes ambulatorios con una neoplasia sólida de cualquier estadio en tratamiento citotóxico o inmune intravenoso fueron elegibles. La cohorte pandémica se enroló durante la fase inicial del brote y se comparó con una cohorte de un período anterior a la pandemia utilizando emparejamiento por puntuación de propensión (PSM, por sus siglas en inglés). Los sujetos se emparejaron por edad, sexo, seguro de salud, factores de riesgo para complicaciones graves por COVID-19, estado funcional, tipo de cáncer y tratamiento, línea de tratamiento e índice de masa corporal. La mortalidad por todas las causas se estimó en ambas cohortes después de seis meses de seguimiento. Resultados. 169 pacientes fueron reclutados entre abril y agosto de 2020 para la cohorte pandémica y 377 para la cohorte prepandémica en el mismo período de 2019, 168 pacientes fueron emparejados. Luego de la PSM, la mortalidad por todas las causas fue del 17,9% en la cohorte pandémica y del 18,5% en la cohorte prepandémica, Riesgo Relativo: 0,97 (intervalo de confianza al 95 %: 0,61-1,52; p=0,888). En la cohorte pandémica, 30/168 pacientes fallecieron, ninguno por infección por COVID-19. Conclusiones. No hemos observado un aumento de mortalidad en pacientes ambulatorios no vacunados en tratamiento oncológico endovenoso activo durante la pandemia por COVID-19.

ABSTRACT Objectives. To compare all-cause mortality of unvaccinated oncology patients who received chemotherapy or immunotherapy during the pandemic with those treated before the pandemic. Materials and methods. We conducted a cohort study in four tertiary hospitals in Argentina. Outpatients with a solid neoplasm of any stage under-going cytotoxic or intravenous immunotherapy were eligible. The pandemic cohort was enrolled during the initial phase of the outbreak and compared with a pre-pandemic cohort using propensity score matching (PSM). Subjects were matched for age, sex, health insurance, risk factors for severe COVID-19 complications, performance status, cancer type and treatment, line of treatment, and body mass index. All-cause mortality was estimated for both cohorts after 6 months of follow-up. Results. A total of 169 patients were recruited between April and August 2020 for the pandemic cohort and 377 for the pre-pandemic cohort in the same months of 2019; 168 patients were matched. After PSM, all-cause mortality was 17.9% in the pandemic cohort and 18.5% in the pre-pandemic cohort; the Relative Risk was 0.97 (95 % confidence interval: 0.61-1.52; p=0.888). In the pandemic cohort, 30/168 patients died, but none from COVID-19. Conclusions. Our findings show that the mortality rate of unvaccinated ambulatory patients on active intravenous oncology treatment during the COVID-19 pandemic did not increase.

Comparison of mortality in patients on chemotherapy or immunotherapy during and before COVID-19 pandemic. Multicenter matched cohort study in Argentina. / Comparación de la mortalidad en pacientes en quimioterapia o inmunoterapia durante y antes de la pandemia de COVID-19. Estudio multicéntrico de cohortes emparejadas en Argentina.

OBJECTIVES.: Motivation for the study. The impact of the COVID-19 pandemic on the risk of death in cancer patients on chemotherapy and immunotherapy is controversial. Published studies mainly compared patients on anti-cancer therapy to those off treatment or COVID-19 positive cancer patients to COVID-19 negative ones. Few studies were conducted in developing countries. Main findings. Mortality didn't increase in unvaccinated outpatients on active intravenous oncology treatment during the COVID-19 pandemic. Implications. This is the first propensity score-matched cohort study evaluating the impact of the COVID-19 pandemic on the population of unvaccinated oncology patients receiving intravenous anticancer therapy. . To compare all-cause mortality of unvaccinated oncology patients who received chemotherapy or immunotherapy during the pandemic with those treated before the pandemic. MATERIALS AND METHODS.: We conducted a cohort study in four tertiary hospitals in Argentina. Outpatients with a solid neoplasm of any stage under-going cytotoxic or intravenous immunotherapy were eligible. The pandemic cohort was enrolled during the initial phase of the outbreak and compared with a pre-pandemic cohort using propensity score matching (PSM). Subjects were matched for age, sex, health insurance, risk factors for severe COVID-19 complications, performance status, cancer type and treatment, line of treatment, and body mass index. All-cause mortality was estimated for both cohorts after 6 months of follow-up. RESULTS.: A total of 169 patients were recruited between April and August 2020 for the pandemic cohort and 377 for the pre-pandemic cohort in the same months of 2019; 168 patients were matched. After PSM, all-cause mortality was 17.9% in the pandemic cohort and 18.5% in the pre-pandemic cohort; the Relative Risk was 0.97 (95 % confidence interval: 0.61-1.52; p=0.888). In the pandemic cohort, 30/168 patients died, but none from COVID-19. CONCLUSIONS.: Our findings show that the mortality rate of unvaccinated ambulatory patients on active intravenous oncology treatment during the COVID-19 pandemic did not increase.

OBJETIVOS.: Comparar la mortalidad por todas las causas de pacientes oncológicos no vacunados que recibieron quimioterapia o inmunoterapia durante la pandemia, con aquellos tratados antes de la pandemia. MATERIALES Y MÉTODOS.: Realizamos un estudio de cohortes en cuatro hospitales terciarios en Argentina. Pacientes ambulatorios con una neoplasia sólida de cualquier estadio en tratamiento citotóxico o inmune intravenoso fueron elegibles. La cohorte pandémica se enroló durante la fase inicial del brote y se comparó con una cohorte de un período anterior a la pandemia utilizando emparejamiento por puntuación de propensión (PSM, por sus siglas en inglés). Los sujetos se emparejaron por edad, sexo, seguro de salud, factores de riesgo para complicaciones graves por COVID-19, estado funcional, tipo de cáncer y tratamiento, línea de tratamiento e índice de masa corporal. La mortalidad por todas las causas se estimó en ambas cohortes después de seis meses de seguimiento. RESULTADOS.: 169 pacientes fueron reclutados entre abril y agosto de 2020 para la cohorte pandémica y 377 para la cohorte prepandémica en el mismo período de 2019, 168 pacientes fueron emparejados. Luego de la PSM, la mortalidad por todas las causas fue del 17,9% en la cohorte pandémica y del 18,5% en la cohorte prepandémica, Riesgo Relativo: 0,97 (intervalo de confianza al 95 %: 0,61-1,52; p=0,888). En la cohorte pandémica, 30/168 pacientes fallecieron, ninguno por infección por COVID-19. CONCLUSIONES.: No hemos observado un aumento de mortalidad en pacientes ambulatorios no vacunados en tratamiento oncológico endovenoso activo durante la pandemia por COVID-19.

Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis.

The reported rates of HER2 positivity in cervical cancer (CC) range from 0% to 87%. The importance of HER2 as an actionable target in CC would depend on HER2 positivity prevalence. Our aim was to provide precise estimates of HER2 overexpression and amplification in CC, globally and by relevant subgroups. We conducted a PRISMA compliant meta-analytic systematic review. We searched Medline, EMBASE, Cochrane database, and grey literature for articles reporting the proportion of HER2 positivity in CC. Studies assessing HER2 status by immunohistochemistry or in situ hybridization in invasive disease were eligible. We performed descriptive analyses of all 65 included studies. Out of these, we selected 26 studies that used standardized American Society of Clinical Oncology / College of American Pathologists (ASCO/CAP) Guidelines compliant methodology. We conducted several meta-analyses of proportions to estimate the pooled prevalence of HER2 positivity and subgroup analyses using geographic region, histology, tumor stage, primary antibody brand, study size, and publication year as moderators. The estimated pooled prevalence of HER2 overexpression was 5.7% (CI 95%: 1.5% to 11.7%) I2 = 87% in ASCO/CAP compliant studies and 27.0%, (CI 95%: 19.9% to 34.8%) I2 = 96% in ASCO/CAP non-compliant ones, p < 0.001. The estimated pooled prevalence of HER2 amplification was 1.2% (CI 95%: 0.0% to 5.8%) I2 = 0% and 24.9% (CI 95%: 12.6% to 39.6%) I2 = 86%, respectively, p = 0.004. No other factor was significantly associated with HER2 positivity rates. Our results suggest that a small, but still meaningful proportion of CC is expected to be HER2-positive. High heterogeneity was the main limitation of the study. Variations in previously reported HER2 positivity rates are mainly related to methodological issues.

New Treatments in Renal Cancer: The AhR Ligands.

Kidney cancer rapidly acquires resistance to antiangiogenic agents, such as sunitinib, developing an aggressive migratory phenotype (facilitated by c-Metsignal transduction). The Aryl hydrocarbon receptor (AhR) has recently been postulated as a molecular target for cancer treatment. Currently, there are two antitumor agent AhR ligands, with activity against renal cancer, that have been tested clinically: aminoflavone (AFP 464, NSC710464) and the benzothiazole (5F 203) prodrug Phortress. Our studies investigated the action of AFP 464, the aminoflavone pro-drug currently used in clinical trials, and 5F 203 on renal cancer cells, specifically examining their effects on cell cycle progression, apoptosis and cell migration. Both compounds caused cell cycle arrest and apoptosis but only 5F 203 potently inhibited the migration of TK-10, Caki-1 and SN12C cells as well as the migration signal transduction cascade, involving c-Met signaling, in TK-10 cells. Current investigations are focused on the development of nano-delivery vehicles, apoferritin-encapsulated benzothiazoles 5F 203 and GW610, for the treatment of renal cancer. These compounds have shown improved antitumor effects against TK-10 cells in vitro at lower concentrations compared with a naked agent.

Prognosis of metastatic giant cell tumor of bone in the pre-denosumab era. A systematic review and a meta-analysis.

BACKGROUND: Data on long-term prognosis of metastatic GCT (mGCT) is scant. The frequency of spontaneous regressions (SRs) is unknown. We aimed to estimate the prognosis of mGCT. METHODS: We searched electronic scientific literature databases and generic Internet from January 1980 to August 2017. After identifying eligible studies we performed descriptive analyses and meta-analyses to estimate overall survival (OS), disease specific survival (DSS) and frequency of SRs in the years before the widespread use of denosumab. We performed pre-specified subgroup analyses of studies published before and after 2000 and of those with more and less than 10 years of follow-up. RESULTS: After retrieving and combining data from 26 relevant retrospective case-series totaling 242 patients with a median follow-up of 6.9 years, the estimated pooled OS was 86.9% (95% CI 78.0-94.2). Pooled DSS was 88.0% (95% CI 79.7-94.7). SRs were observed in 4.5% of patients. In the subgroup of studies published after 2000 mGCT was the only cause of death of affected subjects. In case-series with a follow-up longer than 10 years pooled DSS was 69.7% (95% CI 25.5-99.8). CONCLUSIONS: To our knowledge this is the first study to derive estimated pooled OS and DSS of mGCT based on a large dataset. SRs were not exceptional phenomena. In a long run the disease could impact in a significant way on the life expectancy of affected subjects.

Respuesta completa y prolongada al tratameinto con pamidronato en metástasis pulmonares de un tumor de células gigantes óseo / Complete and prolonged response to treatment with pamidronate in lung metastases from a giant cell tumor of the bone

A pesar de ser considerado benigno, el tumor de células gigantes (TCG) de hueso con baja frecuencia puede presentar metástasis (MTS) a distancia, mayormente pulmonares. El curso clínico de las MTS, aunque habitualmente indolente, es muy variable. Se comunicaron tanto muertes por progresión de MTS, como su regresión sin mediar tratamiento alguno. Los marcadores pronósticos moleculares están aún en desarrollo. El manejo terapéutico de las MTS pulmonares es controversial. Las principales modalidades de tratamiento fueron tradicionalmente la cirugía, la quimioterapia y observación. En la última década los bifosfonatos (BF) y el denosumab, fueron empleados con éxito en el tratamiento adyuvante y neoadyuvante, pero la efectividad de estos fármacos, especialmente los BF, en pacientes con MTS está estudiada en menor medida. Presentamos un caso de MTS pulmonares múltiples histológicamente verificadas de TCG con respuesta completa al tratamiento con pamidronato que continúa a los 7 años de seguimiento (AU)

Although it is considered benign, on rare occasions giant cell tumor (GCT) of bone may present systemic dissemination, predominantly to the lung. The clinical course of metastasis (MTS), while usually indolent, is unpredictable. Both, deaths from progressive lung MTS and regressions without any treatment were reported. Molecular prognostic biomarkers are under development yet. The management of GCT is controversial. Surgical removal, chemotherapy and observation were traditionally the treatment modalities of choice. In the last decade biphosphonates and denosumab were successfully used in the adjuvant and neoadjuvant/unresectable setting. Nonetheless, the effectiveness of these drugs in metastatic disease is less studied. We submit a case report of complete response of multiple histopathologically confirmed unresectable lung MTS of TCG to the treatment with pamidronate with total follow-up length of 7 years (AU)

Aryl hydrocarbon receptor activation by aminoflavone: new molecular target for renal cancer treatment.

Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials.