[Primary hepatic sarcomatoid carcinoma, an unusual case]. / Carcinoma sarcomatoide hepático primario metastásico, una neoplasia infrecuente.

Primary hepatic sarcomatoid carcinoma is a very aggressive tumor, representing 0.4-0.7% of all primary hepatic neoplasms. The disease is associated with liver disease due to hepatotropic viruses and is more prevalent in Asians. Histology shows sarcomatous and carcinoma components. It does not have pathognomonic clinical or imaging characteristics and its diagnosis is based on the pathological and immunohistochemistry findings. Surgery could prolong survival in localized stages. We report the case of a 72-year-old Korean patient with a history of chronic liver disease due to B virus, who was diagnosed with primary hepatic sarcomatoid carcinoma with bone and lymph node metastases.

El carcinoma sarcomatoide primario hepático es un tumor agresivo que representa el 0.4-0.7% de todas las neoplasias primarias hepáticas. Se asocia a hepatopatía por virus hepatotropos, es más prevalente en la población asiática y en su histología se evidencian componentes de carcinoma y sarcoma. No posee características clínicas ni imagenológicas patognomónicas y su diagnóstico se realiza en base a los hallazgos de la anatomía patológica e inmunohistoquímica. La cirugía en estadio localizado representa la única modalidad terapéutica con impacto en la sobrevida. Reportamos el caso de una paciente de 72 años, coreana, con antecedentes de hepatopatía crónica por virus B, a quien se le diagnosticó un carcinoma sarcomatoide hepático primario con metástasis ósea y ganglionares.

Efficacy and Safety of Nivolumab in Previously Treated Patients With Non-Small-cell Lung Cancer: Real World Experience in Argentina.

BACKGROUND: Nivolumab was the first anti-programmed cell death 1 drug approved in Argentina for non-small-cell lung cancer treatment in the second-line setting. MATERIALS AND METHODS: The present study was a multicenter, observational, retrospective study of patients with progression to stage IV NSCLC during platinum-based chemotherapy who had received nivolumab monotherapy in a drug-expanded access program in Argentina. RESULTS: The data from 109 patients were assessed retrospectively for safety and clinical outcomes. The follow-up period was 8.83 months (interquartile range, 3.4-12.67); 57.8% were men, 29.4% were current smokers, and 78.0% had a diagnosis of nonsquamous cell cancer. The median number of chemotherapy lines before nivolumab was 2 (range, 1-4). Also, 59.6% had received radiotherapy and 89% had received platinum-based chemotherapy. The drug-related toxicity rate was 78.9%, the grade 2-3 toxicity rate was 28.4%, and 33.9% of patients had required corticosteroids. The treatment response was evaluated in 104 patients. The best response was a complete response in 2 (2%), partial response in 28 (27%), stable disease in 33 (32%), and progressive disease in 41 (39%). Univariate analysis revealed that the absence of corticosteroid use (P = .034), toxicity grade 1-3 (P = .0025), and performance status of ≤ 1 (P = .049) were associated with longer disease-free survival, performance status of ≤ 1 (P < .001), and toxicity grade 1-3 (P = .001) were associated with longer overall survival. On multivariate Cox regression analysis, toxicity grade 1-3 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; P = .008) and age ≤ 50 years (HR, 0.28; 95% CI, 0.13-0.61; P = .001) were associated with longer progression-free survival and corticosteroid use was associated with shorter progression-free survival (HR, 2.06; 95% CI, 1.22-3.48; P = .007). CONCLUSIONS: The use of nivolumab in the real world setting in patients with heavily pretreated NSCLC was well tolerated and showed promising clinical efficacy. The performance status, use of corticosteroids, and immune-mediated toxicity seem to be the conditions that can affect the clinical outcomes.

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non-small cell lung cancer (NSCLC) compared with chemotherapy (Quijote-CLICaP).

BACKGROUND: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second- or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. METHODS: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third- or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. RESULTS: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%, [95% CI 14.5-25.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. CONCLUSIONS: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice.

BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. IN CONCLUSION: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.

Spinal cord compression secondary to metastasis of malignant chondroid syringoma: case report.

The authors describe a case of spinal cord compression due to an epidural metastasis of malignant chondroid syringoma. Chondroid syringoma is a rare mixed tumor of the skin composed of both epithelial and mesenchymal elements. Although most are benign, malignant forms have been reported. Malignant chondroid syringoma may progress very slowly and the metastatic spread occurs late, appearing years after the original diagnosis. There is only one other report of spinal cord compression secondary to metastasis of malignant chondroid syringoma, which was finally diagnosed by microscopic examination of an autopsy specimen. This 63-year-old woman presented with a 4-week history of progressive paraparesis. Admission MRI of the thoracic spine showed an extradural mass arising from the posterior elements and left pedicle of T-9, which caused posterior compression of the spinal cord. Surgical decompression resulted in resolution of the neurological impairments. The histological results were consistent with metastasis of malignant chondroid syringoma. The patient underwent adjuvant radiotherapy and a favorable outcome was noted at the 2-year follow-up visit. This represents the first reported case of spinal cord compression from a metastasis of a malignant chondroid syringoma histologically confirmed in vivo. The authors' experience in this case suggests that resection followed by radiotherapy might be an acceptable means for achieving short-term, progression-free survival.

Acalculous cholecystitis in a patient with metastatic renal cell carcinoma treated with sunitinib.

A 62-year-old woman was treated with sunitinib as a second-line therapy for metastatic clear-cell renal carcinoma. She was given oral sunitinib 50 mg once daily, 4 weeks on followed by 2 week off. During the fourth week of her first cycle, the patient was admitted to our hospital because of an acute-onset, right upper quadrant pain associated with nausea and vomiting. She was diagnosed with acute acalculous cholecystitis, which was treated with broad-spectrum antibiotics, and sunitinib therapy was discontinued. A follow-up computed tomography scan of the abdomen revealed a complete resolution of gallbladder changes. Our patient did not have major risk factors for developing an acalculous cholecystitis except for a relative immunosuppressed state secondary to her advanced renal cancer. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 5, indicating a probable association of the event with sunitinib. Because the use of sunitinib is expanding in clinical practice, we want to alert the oncology community about this uncommon and life-threatening complication in patients receiving sunitinib or another agent with antiangiogenic activity.

Irinotecan, oxaliplatin plus bolus 5-fluorouracil and low dose folinic acid every 2 weeks: a feasibility study in metastatic colorectal cancer patients.

OBJECTIVES: Irinotecan or oxaliplatin combined with 5-fluorouracil (5-FU) +/- folinic acid (FA) has changed the treatment standards for metastatic colorectal cancer (CRC). The oxaliplatin and irinotecan combination has reported consistent activity. The purpose of this phase II study was to assess the efficacy and safety of the simultaneous administration of a triple chemotherapy combination of oxaliplatin, irinotecan, 5-FU bolus, and FA. MATERIALS AND METHODS: Eligible patients had metastatic CRC with no prior oxaliplatin or irinotecan-based chemotherapy. Treatment consisted of oxaliplatin 85 mg/m2 followed by irinotecan 150 mg/m2, repeated every 15 days, with 5-FU 500 mg/m2 bolus and FA 20 mg/m2 on days 1, 8, and 15. An early amendment suppressed the day 8 5-FU/FA. RESULTS: Twenty-six eligible treated patients receiving 253 doses were assessed for toxicity. Myelosuppression was the most frequent toxicity; grade 3 to 4 neutropenia and febrile neutropenia occurred in 50% and 15% of patients, respectively. The treatment schedule modification, omitting the 5-FU dosing on day 8, considerably improved treatment compliance, reducing the incidence of febrile neutropenia, diarrhea, and asthenia. Among the 25 patients evaluable for efficacy, 10 had objective responses including 1 complete response (CR) (4%) and 9 partial responses (PR) (36%), giving an overall response rate of 40%. Median time to progression was 6.20 months [95% confidence interval (CI), 5.44-6.96]. Median overall survival was 12.95 months. CONCLUSIONS: The administration of a triple combination produced promising objective responses with acceptable toxicity but does not seem to produce an evident benefit in time-related parameters.

Frecuencia de diferentes patógenos como causa de vaginitis en México. Estudio multicéntrico / Frecuency of different pathogens as cause vaginitis in Mexico. Multicentry study

Dada la escasa información en nuestro medio acerca de los patógenos que causan vaginitis y a la aparición de nuevos patógenos causales de esta enfermedad, se decició llevar a cabo este estudio prospectivo para conocer la frecuencia relativa de los patógenos que causan vaginitis. También se investigó la respuesta al tratamiento con fármacos considerados como específicos para esos patógenos. Se incluyeron 318 mujeres que asistían a las consultas de ginecología o control de la natalidad en cuatro centros del país, Hospital General de Occidente/Guadalajara, Hospital Miguel Silva/Morelia, Hospital Gea González/México, D.F., y Hospital Regional/Huejotzingo, para investigar la presencia de: Ureaplasma urealytcum, Chlamidia trachomatis, Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis y Neisseria gonorrhoeae. La freuencia relativa fue como sigue: Ureaplasma urealyticum, 37% (solo detectada en ciudad de México); Chlamydia trachomatis, 17 a 44%; Gardmerella vaginalis, 13 a 35%; Candida albicans, 11 a 26% y Trichomona vaginalis, 4 a 11%. No hubo ningún caso de N. gonorrhoeae. En 65 pacientes (20.4%) no se encontró ningún patógeno y se aislaron gérmenes no considerados como patógenos específicos en 58 mujeres (18.2%). La respuesta al tratamiento se evaló en 274 mujeres, obteniéndose la curación en 89.9% de las pacientes con G. vaginalis y 100% de las pacientes con T. vagnais tratadas con tinidazol oral; 81% (U. urealyticum) y 92% (C. trachomatis) de las pacientes tratadas con doxiciclina. Se concluye que la etiología de la vaginitis ha cambiado radicalmente lo que deberá tener en cuenta el médico para escoger el medicamento específico.

Tratamiento de la vaginitis causada por Trichomoas vaginalis, Candida albicans, Gardnerella vagilalis, solas o combinadas con la asociación de tinidazol/tioconazol / Treatment of vaginitis caused by Trichomonas vaginalis, Candida albicans, Gardnerella vaginallis, individually or combined, with a Tinidazole/Thioconazole association

Con el objeto de comprobar la eficacia y la tolerancia de la combinación de tinidazol con tioconazol, ambos fármacos derivdos del imidazol, en dosis de 150 y 100 mg respectivamente, para el tratamiento de las vaginitis causadas por Trichomonas vaginalis, Candida albicans y Gardnerella vaginalis ya sea como germen patógeno único o asocaidos entre sí, fueron estudiadas de manera avierta no comparativa, 27 pacientes adultas con leucorea, con diagnóstico clínico y bacteriológico de vaginitis por Trichomonas, Candida o Gardnella solas o en combinación. Descartadas las enfermas embarazadas, lactantes, alérgicas a los derivados imidazólicos y con otras enfermedades venéreas, entre otros excluyentes se revisaron clínica y bacteriológicamente al principio del estudio y una segunda vez en el 6o. y 15o. día después de haber aplicado por vía vaginal una tableta de tinidazol cada 12 hrs., durante tres días consecutivos. Se consideraron clínicamente duradas el 74% de las enfermas y mejoradas 26% sin falla alguna; y desde el punto de vista bacteriológico se consiguió 93% de curación en candidiasis, 100% en tricomoniasis y 50% de curación cuando el fermen fue Gardnerella, aún cuando se considera que el número de casos de este agente no permite una valoración correcta. Por otra parte, la tolerancia puede considerarse como una buena dada a la casi total ausencia de síntomas y signos adversos durante la aplicación del medicamento

Tioconazol óvulos de 300mg. administrados endósis única para el tratamiento de candidiasis vaginal / Thioconazole administration in 300 mg. ovulos single dose for the treatment of vaginal candidiasis

Tioconazol es un nuevo derivado imidazólico que tiene una concentración fungicida mínima in vitro para C. albicans, mucho menor que clotrimazol, ketoconazol y econazol. Diversos estudios clínicos han demostrado su gran eficacia y excelente tolerancia cuando se administra en dosis única para el tratamiento de candidiasis vaginal. En este trabajo se valora la eficacia y tolerancia del óvulo de tioconazol en dosis única de 300 mg. Se estudiaron 30 pacientes con candidiasis vaginal. Se observó curación y micológica en 93.3% (28/30%) y mejoría clínica con cura micológica en 3.3% (1/30) de las pacientes, entre el quinto y el noveno día posterior al tratamiento. En 18 pacientes que acudieron a ser valoradas cuatro a seis semanas despúes de la terapéutica, el 100% permanecían curadas. No se registratron reacciones adversas con el tratamiento. Con base en este trabajo se concluye que la dosis única de 300 mg de tioconazol en óvulos es eficaz y tiene una tolerancia excelente en el tratamiento de candidiasis vaginal. La mínima absorción de tioconazol, cuando se aplica por vía vaginal, y la gran eficacia terapéutica en su dosificación única de 300 mg son grandes ventajas en el tratamiento actual de vaginitis por C. albicans