ABSTRACT
Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets. PRL3-zumab, a first-in-class humanized antibody, was administered in a dose escalation schedule in a first-in-child clinical trial to study toxicity, pharmacokinetics, and clinical outcomes. Among 64 pediatric tumors, PRL3 was most frequently expressed in neuroblastoma (100%), rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcomas (71%), and renal sarcomas (60%) but absent in paired normal tissues. PRL3 was expressed in 75% of relapsed tumors and associated with shorter median event-free survival. Microarray profiling of PRL3-positive tumors showed elevation of angiogenin, TIMP1 and TIMP2, and GPCR-MAPK signaling proteins that commonly interacted with PRL3. The first use of PRL3-zumab in a pediatric patient saw no adverse events. A 28.6% reduction in maximum target lesion diameter was achieved when PRL3-zumab was administered concurrently with hypofractionated radiation. These findings support wider exploration of PRL3 expression in embryonal and mesenchymal tumors and further clinical application of PRL3-zumab in pediatric patients.
ABSTRACT
Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker widely accepted as the most useful blood test in diagnosing and monitoring pancreatic cancer. However, CA 19-9 may also be raised in other conditions such as colorectal, hepatic, lung, and ovarian carcinoma as well as benign conditions such as hepatobiliary and pulmonary diseases. CA 19-9 is rarely elevated above 200 U/ml in benign conditions with values exceeding 1000 U/ml being highly suggestive of malignancy. The mechanism of secretion in both malignant and benign conditions remains unclear. Desmoplastic fibroblastoma (DF) is a benign soft tissue tumor. CA 19-9 has not been reported in association with DF previously. We present a case of raised serum CA 19-9 in a 71-year-old male attributed solely to DF in his left cubital fossa. The patient's CA 19-9 level rose from 56 U/ml at the time of presentation to 3763.8 U/ml over a period of 9 months. Post-DF excision, the CA 19-9 level decreased to 1464 U/ml at 1 month, 162.3 U/ml at 2.5 months, and 24U/ml, within normal range, at 7 months post-surgery. CA 19-9 levels continued to remain at 24 U/ml 1.5 years post-tumor excision. The CA 19-9 level in this patient was highly elevated which is unusual in association with a benign tumor. The rate of decrease in CA 19-9 level post-excision was in keeping with that reported after pancreatic cancer resections. This is the first case of DF in association with raised CA 19-9.
ABSTRACT
BACKGROUND: The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction. METHODS: Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients. RESULTS: All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap. CONCLUSION: The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure.
