Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

Investigation of surgical managements of olfactory neuroblastoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of transnasal endoscopic resection and craniofacial resection through an external approach for olfactory neuroblastoma (ONB).</p><p><b>METHODS</b>Thirty two patients with ONB treated between 1987 and 2006 were retrospectively reviewed.</p><p><b>RESULTS</b>The patients were followed up for 8-135 months, the median follow-up time was 20 months. The longest follow-up time of patients treated by endoscope was 79 months, and patients treated by combined endoscope and transcranial surgery was 87 months. At Kadish stage B the 3-year survival rate of patients with transnasal endoscopic resection was 78.8% and at Kadish stage C it was 50.0%. At Kadish stage B the 3-year survival rate of patients with craniofacial resection through an external approach was 60.0% and at Kadish stage C it was 44.4%. The bleeding amounts in above two approaches were 140 ml and 450 ml. The average length of stay in hospital in transnasal endoscopic resection approach was markedly reduced (P < 0. 01).</p><p><b>CONCLUSIONS</b>Olfactory neuroblastoma can be safely and effectively excised and reconstructed endoscopically with comparable degrees of tissue removal as with external approaches. The time of stay in hospital can be reduced and the surgical trauma can be diminished.</p>

Intra-nasal scanning of tumors in nasal cavity and paranasal sinus with endoscopic ultrasonography / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate endoscopic ultrasonography for masses in nasal cavity and paranasal sinus.</p><p><b>METHODS</b>Under the guidance of nasal endoscope, sonographic scan of 18 masses within nasal cavity and paranasal sinus was performed by using 10 MHz catheter transducer with diameter of 3.3 mm under local anesthesia. Twelve of them were benign tumors and 6 of them were malignant ones, which were confirmed by pathological examination of resected specimens.</p><p><b>RESULTS</b>Under the guidance of nasal endoscope, masses could be observed accurately with catheter transducer. On gray scale ultrasound, most masses were heterogeneous hypoechoic, tumors with rich blood vessels were lower hypoechoic, and some showed irregular anechoic area due to dilated vascular net. Neurofibroma was with well-defined and regular border and entire capsule; chordoma was without distinct edge and capsule. A giant pituitary tumor eroding bone of sphenoid sinus and intruding into nasal cavity. The relationship between mass and internal carotid artery could be demonstrated using color Doppler flow imaging (CDFI). Blood flowing signals in masses could be detected by CDFI, and spectral Doppler could discriminate arterial or venous blood flowing signals and measure its velocity. The rich blood supply was observed in fibroangioma, the rich flow signals and high velocity could be detected in malignant tumors.</p><p><b>CONCLUSIONS</b>Nasal endoscope-guided sonography for soft tissue masses in nasal cavity is of exact location, clear image and high resolution, which can reveal blood flow signals sensitively, differentiate arterial and venous blood signals and measure the velocity of them. It provides a new imaging modality for masses within nasal cavity, sinuses and skull base.</p>