Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer.

BACKGROUND: The antiangiogenic tyrosine kinase inhibitor regorafenib provides a survival benefit in patients with previously treated metastatic colorectal cancer (CRC). Antiangiogenic therapy causes hypoxic stress within tumor cells, which activates autophagy as a survival mechanism. The histone deacetylase inhibitor (HDAC) entinostat increases dependence on autophagy through epigenetic mechanisms. Hydroxychloroquine (HCQ) blocks autophagy by blunting lysosomal acidification. We hypothesized that HCQ and entinostat would be tolerable with regorafenib and potentiate the antitumor response. METHODS: This was a 3+3 phase I trial of HCQ and entinostat with regorafenib in patients with metastatic CRC. The primary objective was safety, and the secondary objective was clinical efficacy. RESULTS: Twenty patients received study therapy. Six evaluable patients were enrolled at each of the three planned dose levels, one patient at an intermediate dose level, and one additional patient withdrew consent after 4 days to receive treatment closer to home. One dose-limiting toxicity was noted in the study at dose level 2 (grade 3 fatigue). Seven patients discontinued therapy due to related toxicities; rapid weight loss was near universal, with a median weight loss of 4.4 kg (range 1.5-12.2 kg) in the first 2 weeks of treatment. No objective responses were observed. CONCLUSION: The combination of regorafenib, HCQ, and entinostat was poorly tolerated without evident activity in metastatic CRC. CLINICALTRIALS.GOV IDENTIFIER: NCT03215264.

Pancreas-Kidney Transplantation: Do We Know the Frequency of Clinical Complications?

BACKGROUND: The objective of this study was to describe the most common medical complications in simultaneous pancreas-kidney recipients in our center. METHODS: Retrospective and descriptive study of complications observed in a series of 73 simultaneous pancreas-kidney transplant recipients, which included 54 men and 19 women with an average age of 40.6 years, between February 2009 and April 2019. The study assessed the incidence of cytopenia, viral infections, tumors, and graft rejection. Frequency tables were created for each complication in the analysis. RESULTS: Cytopenia was the most common complication, either by itself or associated with a different complication, and it was found in 23.3% of all patients. The most common infection was cytomegalovirus, which was in 55.6% of all 9 patients who presented infections in spite of universal prophylaxis with valganciclovir, followed by herpes virus (11.1%), papillomavirus (11.1%), and polyoma BK virus (22.2%). Regarding tumors, the number of patients who presented this complication was low; 2 gynecologic tumors were detected (cervical intracellular neoplasia and one ovarian tumor), and 1 case of skin tumor was also observed. There were 3 cases of acute rejection, which represents 4.1% of all patients. Rejection was cellular and steroid-sensitive except for 1 case that was humoral, with good response to treatment. CONCLUSIONS: In spite of the doses of immunosuppressive drugs received by these patients, the incidence of infections was low, and cytomegalovirus was the most common infection. As a consequence of the drugs administered, virtually all patients developed cytopenia. The number of tumors observed in this series was low in spite of the immunosuppressive treatment.

A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma.

TGFß is a pleiotropic cytokine with immunosuppressive activity. In preclinical models, blockade of TGFß enhances the activity of radiation and invokes T-cell antitumor immunity. Here, we combined galunisertib, an oral TGFß inhibitor, with stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC) and assessed safety, efficacy, and immunologic correlatives. Patients (n = 15) with advanced HCC who progressed on, were intolerant of, or refused sorafenib were treated with galunisertib (150 mg orally twice a day) on days 1 to 14 of each 28-day cycle. A single dose of SBRT (18-Gy) was delivered between days 15 to 28 of cycle 1. Site of index lesions treated with SBRT included liver (9 patients), lymph node (4 patients), and lung (2 patients). Blood for high-dimensional single cell profiling was collected. The most common treatment-related adverse events were fatigue (53%), abdominal pain (46.6%), nausea (40%), and increased alkaline phosphatase (40%). There were two instances of grade 2 alkaline phosphatase increase and two instances of grade 2 bilirubin increase. One patient developed grade 3 achalasia, possibly related to treatment. Two patients achieved a partial response. Treatment with galunisertib was associated with a decrease in the frequency of activated T regulatory cells in the blood. Distinct peripheral blood leukocyte populations detected at baseline distinguished progressors from nonprogressors. Nonprogressors also had increased CD8+PD-1+TIGIT+ T cells in the blood after treatment. We found galunisertib combined with SBRT to be well tolerated and associated with antitumor activity in patients with HCC. Pre- and posttreatment immune profiling of the blood was able to distinguish patients with progression versus nonprogression.

Hepatectomía central combinada con ligadura de la vena porta derecha en un niño con hepatoblastoma bilobar: reporte de un caso / Central hepatectomy combined with ligation of the right portal vein in a child with bilobar hepatobastoma: a case report

Resumen El hepatoblastoma es un tumor maligno, la resección quirúrgica es la meta del tratamiento. Paciente de 7 meses de edad con masa hepática en los segmentos IV A y B, V y VIII, clasificada como PRETEXT III, se realizó hepatectomía central conservando segmentos VI, VII, II, III y doble derivación biliodigestiva. La vena porta derecha involucrada, se ligó para producir hiperplasia compensadora izquierda, conservando el derecho como auxiliar. Hígado izquierdo en 14 días aumentó 48.1 %. Como alternativa al trasplante, en un tiempo quirúrgico se combinó hepatectomía central con ligadura de la vena porta derecha.

Abstract Hepatoblastoma is a malignant tumor. Surgical resection is the goal of treatment. A 7-month-old female patient with a hepatic mass in segments IV A and B, V, and VIII, classified as PRETEXT III. A central hepatectomy preserving segments VI, VII, II, and III, and a double biliodigestive derivation were performed. The right portal vein involved was ligated to produce a compensatory hyperplasia of the left liver, retaining the right one as an auxiliary. At 14 days, the left liver had increased by 48.1%. As an alternative to transplantation, central hepatectomy was combined with ligation of the right portal vein in a single surgical time.

Anemia inducida por linezolid / Anemia induced by linezolid

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Pleuropulmonary blastoma type III extended into the left atrium in a 16-month old boy.

Pleuropulmonary blastoma is an uncommon paediatric neoplasm. Approximately 300 cases have been reported. In seven tumours, extension involved the left heart. Type III occurs typically at ages 3 or 4 years. We report this very unusual case of extensive disease in a 16-month old male patient. Chest computerized tomography revealed a mass extending into the right hemithorax from the posterior mediastinum and propagating inside the left atrium through the right pulmonary veins. Echocardiography showed a huge flexible mass occupying almost all of the left atrium cavity and intermittently prolapsing through the mitral valve. Two preoperative chemotherapy courses of ifosfamide, vincristine, actinomycin D and doxorubicin were administered at 3-week intervals. The patient was placed on cardiopulmonary bypass, cardiac arrest and the left atrium was opened. The tumour and orifice of the inferior right pulmonary vein were resected and the normal free borders reconstructed. A large mass occupying the right pleural space was removed. Seven additional courses of chemotherapy were given. In a 'second-look' surgery 6 months later, through a right thoracotomy, the residual mass at the posterior mediastinum was resected. The child received four additional courses of chemotherapy. After 12 months of the initial resection, there is no evidence of recurrence.

Interrupted left aortic arch and isolated right subclavian artery from the right pulmonary artery.

We report a 10-day-old newborn, weighing 2.9 kg with an interrupted left aortic arch type B, a large subarterial ventricular septal defect and a right ductus connecting the right pulmonary artery to an isolated right subclavian artery. The patient underwent successful total surgical repair and the isolated right subclavian artery was ligated. He was discharged from hospital without complication and maintains excellent perfusion to the right arm via collaterals.

Pesquería y parámetros biométricos de los cangrejos del género Calappa (Brachyura: Calappidae) en el oriente de Venezuela / Fishery and biometrics of genus Calappa crabs (Brachyura: Calappidae) in northeastern Venezuela

The box crabs, genus Calappa, are important crab species landed by the industrial trawl fleet in Venezuela. These crabs have a wide distribution in the country, from the Gulf of Venezuela to the Orinoco River, but major landings take place in such gulf, near Margarita Island and northern Sucre State. Average annual landing in the eastern region was 69 t during 1970-2001, with a maximum of 221 t. For this study a sample of 2 398 box crabs was collected by observers on board of industrial trawl vessels, which operated in eastern Venezuela from 1994 to 2000. Three species were found in the landings, Calappa sulcata and C. flammea, each represented 47% of the sample, and C. nítida, which accounted for 5% of the sample. Sex ratio was strongly biased towards males in C. sulcata (2.8:1) and in C. flammea (1.9:1), while it was only slightly biased in C. nitida (1.4:1). Due to its large size, C. sulcata is of great commercial interest, with average weight 290 g and a maximum weight of 720 g; C. flammea showed an average weight of 140 g and a maximum weight of 418 g, while C. nitida is the smallest species, with average weight 46 g and maximum weight not beyond 113 g. Box crabs were captured by day and night in similar proportions, and were found in a wide depth range, from a few meters to 126 m deep; however, the largest captures were obtained in the interval 38 - 54 m. Regressions between weight of chelae and total weight were linear, and significantly different between sexes. The relation between total weight and carapace width was allometric, with a power exponent ca. three in C. sulcata, and less than three in C. flamea and C. nítida. Females of C. sulcata and C. nitida showed power exponents significantly smaller than males. Since claws are removed from the animal to be commercialized, while the rest of the...

Los cangrejos moros, del género Calappa, constituyen las principales especies de cangrejos desembarcados por la flota arrastrera industrial en Venezuela. Su distribución es amplia en el país, desde el Golfo de Venezuela hasta el delta del Río Orinoco, pero las mayores capturas provienen de dicho golfo, los alrededores de la Isla de Margarita y norte del estado Sucre. Las capturas en la región oriental alcanzaron 221 t por año, con un promedio de 69 t en el período 1970-2001. Para este estudio se procesó una muestra de 2 398 cangrejos moros recolectada por observadores científicos a bordo de las embarcaciones de arrastre industrial que operaron en el oriente del país entre 1994 y 2000. Tres especies componen las capturas, Calappa sulcata y C. flammea, ambas en proporción de 47%, y C. nítida, que representó 5% de la muestra. La proporción de sexos estuvo fuertemente sesgada hacia los machos en C. sulcata (2,8:1) y en C. flammea (1,9:1), y ligeramente sesgada en C. nitida (1,4:1). Calappa sulcata es la especie con mayor interés comercial para la flota, alcanzando un peso promedio de 290 g y máximo de 720 g; C. flammea alcanzó un peso promedio de 140 g y máximo de 418 g, mientras que el peso promedio de C. nitida fue 46 g y su peso máximo no superó los 113 g. Los cangrejos moros son capturados de noche y de día en similar proporción en la región oriental. Aunque la distribución batimétrica de estas especies es amplia, desde pocos metros a 126 m de profundidad, las mayores capturas tuvieron lugar entre 38 y 54 m. Las relaciones entre el peso de las quelas y el peso total fueron lineales y difirieron significativamente entre sexos. La relación entre el peso total y el ancho del caparazón fue alométrica, con exponente ca. 3 en C. sulcata, y menor que 3 en C. flamea y C. nítida. Las hembras de C. sulcata y C. nitida presentaron exponentes significativamente menores que los machos. Motivado a que las quelas son separadas a bordo para ser...

[Fishery and biometrics of genus Calappa crabs (Brachyura: Calappidae) in northeastern Venezuela]. / Pesqueria y parámetros biométricos de los cangrejos del género Calappa (Brachyura: calappidae) en el oriente de Venezuela.

The box crabs, genus Calappa, are important crab species landed by the industrial trawl fleet in Venezuela. These crabs have a wide distribution in the country, from the Gulf of Venezuela to the Orinoco River, but major landings take place in such gulf, near Margarita Island and northern Sucre State. Average annual landing in the eastern region was 69 t during 1970-2001, with a maximum of 221 t. For this study a sample of 2 398 box crabs was collected by observers on board of industrial trawl vessels, which operated in eastern Venezuela from 1994 to 2000. Three species were found in the landings, Calappa sulcata and C. flammea. each represented 47% of the sample, and C. nitida, which accounted for 5% of the sample. Sex ratio was strongly biased towards males in C. sulcata (2.8:1) and in C. flammnea (1.9:1). while it was only slightly biased in C. nitida (1.4:1). Due to its large size, C. sulcuta is of great commercial interest, with average weight 290 g and a maximum weight of 720 g: C. flammea showed an average weight of 140 g and a maximum weight of 418 g, while C. nitida is the smallest species, with average weight 46 g and maximum weight not beyond 113 g. Box crabs were captured by day and night in similar proportions, and were found in a wide depth range, from a few meters to 126 m deep; however, the largest captures were obtained in the interval 38 - 54 m. Regressions between weight of chelae and total weight were linear, and significantly different between sexes. The relation between total weight and carapace width was allometric, with a power exponent ca. three in C. sulcata, and less than three in C. flamea and C. nitida. Females of C. sulcata and C. nitida showed power exponents significantly smaller than males. Since claws are removed from the animal to be commercialized, while the rest of the animal is returned alive to the sea, for practical purposes a common equation among species and sexes to convert claws weight into total body weight is: total weight - 3 x claws weight. The relationship between catch per unit of effort (CPUE) and effort did not show a significantly decreasing trend, but landings follow the effort trend, with a decreasing tendency in recent years. No mature females were found in any of the three species, thus there could be reproductive migrations towards deeper waters from October to January, when abundance of crabs is lower in the study area. It is recommended that the practice of exploiting only one claw, returning the rest of the animal alive to the sea, should be promoted among fishers, while the removal of claws from female crabs should be avoided.