Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.

BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.

Association between hepatoblastoma and very low birth weight: a trend or a chance?

Hepatoblastoma, a malignant hepatic tumor in children, is thought to be an embryonal tumor resulting from developmental disturbances during organogenesis. Although factors that might be involved in the tumorigenesis have been suggested, an association between hepatoblastoma and the patient's birth weight has not been reported. We have accessed the data in the Japan Children's Cancer Registry and have analyzed patients' diagnoses and birth weights. During the 9 years from 1985 to 1993, 38 (0.38%) patients with tumors who weighted less than 1500 gm at birth were identified among 9923 registered patients. Hepatoblastoma was diagnosed in 9 patients of very low birth weight, representing 3.9% of the 231 patients with hepatoblastoma registered. A significant linear trend toward an increase in the percentage of patients with a birth weight of less than 1500 gm was observed specifically in hepatoblastoma (p = 0.0047). The percentage rose from 0.7% (1/138) in the 5-year period of 1985 to 1989 to 8.6% (8/93) in the next 4-year period (1990 to 1993). This increase was attributed to the significant increase in the percentage of patients who weighed less than 1000 gm at birth (p = 0.0028). A separate peak in the number of patients in the birth weight range of less than 1000 gm suggests that the cause of hepatoblastoma related to very low birth weight may be different from that of other patients. Full analysis of the patients' data is an urgent matter.

Variation in courtship sounds among three geographical strains of Drosophila mercatorum.

Sound recordings of courtship in Drosophila mercatorum were analyzed with an oscilloscope. Sounds in this species consist of two kinds of pulses, referred to as the A and B sounds, respectively. These differ from each other in their oscilloscope pattern and in the behavior accompanying them. A comparative study of three strains from widely separated geographical regions (New York, El Salvador, and Hawaii) revealed significant differences among strains in the interpulse interval (ipi) of the A sound. The ipi of the B sound increased as it proceeded for New York and Hawaii males but not for males from El Salvador. These characteristics may influence mating success in interstrain crosses. The present results suggest that the first steps toward divergence in the nature of the sound are quantitative; this may affect the response threshold of the female. Genetic systems responsible for female receptivity may have been independently developed in the two sexes.

[Transhepatic biliary drainage as a method in the diagnosis and treatment of obstructive jaundice]. / Drenaje biliar transparietohepático como método de diagnóstico y tratamiento en las ictericias obstructivas.

Percutaneous transhepatic biliary drainage was performed on eleven jaundiced patients, who had obstruction of the bile duct, in order to determine the exact site and nature of the obstruction and to alleviate the jaundice. In the present series, six patients were treated with external biliary drainage. Four of them received this treatment prior to radical surgery. In the remaining two cases the external drainage was a palliative procedure. In five patients, the drainage catheter was internalized through the obstructed bile duct (internal biliary drainage). One of these patients was subsequently treated with radical surgery. In two cases, the internal biliary drainage was palliative. In the two remaining cases, intraluminal selective irradiation was introduced via Iridium 192 flexible wires. Severe hemobilia occurred in one patient, who was successfully treated by lithotomy and "T" tube drainage. We conclude that the simplicity and low cost of these drainage procedures recommend them as extremely useful for the diagnosis and treatment of obstructive jaundiced patients.

Drenaje biliar transparietohepático como método de diagnóstico y tratamiento en las ictericias obstructivas / [Transhepatic biliary drainage as a method in the diagnosis and treatment of obstructive jaundice]

Percutaneous transhepatic biliary drainage was performed on eleven jaundiced patients, who had obstruction of the bile duct, in order to determine the exact site and nature of the obstruction and to alleviate the jaundice. In the present series, six patients were treated with external biliary drainage. Four of them received this treatment prior to radical surgery. In the remaining two cases the external drainage was a palliative procedure. In five patients, the drainage catheter was internalized through the obstructed bile duct (internal biliary drainage). One of these patients was subsequently treated with radical surgery. In two cases, the internal biliary drainage was palliative. In the two remaining cases, intraluminal selective irradiation was introduced via Iridium 192 flexible wires. Severe hemobilia occurred in one patient, who was successfully treated by lithotomy and [quot ]T[quot ] tube drainage. We conclude that the simplicity and low cost of these drainage procedures recommend them as extremely useful for the diagnosis and treatment of obstructive jaundiced patients.

Drenaje biliar transparietohepático como método de diagnóstico y tratamiento en las ictericias obstructivas. / [Transhepatic biliary drainage as a method in the diagnosis and treatment of obstructive jaundice]

Percutaneous transhepatic biliary drainage was performed on eleven jaundiced patients, who had obstruction of the bile duct, in order to determine the exact site and nature of the obstruction and to alleviate the jaundice. In the present series, six patients were treated with external biliary drainage. Four of them received this treatment prior to radical surgery. In the remaining two cases the external drainage was a palliative procedure. In five patients, the drainage catheter was internalized through the obstructed bile duct (internal biliary drainage). One of these patients was subsequently treated with radical surgery. In two cases, the internal biliary drainage was palliative. In the two remaining cases, intraluminal selective irradiation was introduced via Iridium 192 flexible wires. Severe hemobilia occurred in one patient, who was successfully treated by lithotomy and [quot ]T[quot ] tube drainage. We conclude that the simplicity and low cost of these drainage procedures recommend them as extremely useful for the diagnosis and treatment of obstructive jaundiced patients.

Unusual chorioretinal degeneration in sickle cell disease. Possible sequelae of posterior ciliary vessel occlusion

The vascular occlusive process characteristic of sickle cell disease may affect the retinal circulation and the resulting pathological changes, from peripheral vessel obstructions to a proliferative retinpathy, are well recognized. In the present report, three cases of sickle cell disease are described with an unusual chorioretinopathy. It is suggested that these change may have resulted from the vascular occlusive process affecting the posterior ciliary vessels. (Summary)