[Osseointegrated implant supported prostheses in the rehabilitation of severe orbital deformity in 6 cases].

Objective: To assess the effectiveness of osseointegrated implant supported prostheses in the rehabilitation of severe orbital deformity. Methods: Retrospective case series. The study collected 6 patients (6 eyes) with severe orbital deformity, who were treated with osseointegrated implant supported prostheses between 2010 and 2016 in Beijing Tongren Eye Center, Beijing Tongren Hospital. Data included demographic characteristics, causes of the deformity, the history of radiotherapy, the site, number and survival of implants, and the ability to wear prostheses. Results: Among the 6 patients, 4 were males, and 2 were females, with a mean age of 27 (16-44) years. The deformity resulted from evisceration or enucleation and radiotherapy for malignancies in 4 patients, from evisceration because of inflammatory pseudotumor in 1 patient, and from enucleation and debridement because of explosion injury and secondary infection in 1 patient. Each patient received 3 implants at the first operation. A total of 18 implants were installed, including 9 placed into the lateral aspect of the supraorbital rim, 6 into the lateral aspect of the infraorbital rim, 1 into the medial aspect of the supraorbital rim, and 2 into the medial aspect of the infraorbital rim. One superior lateral implant failed half a year after implantation, and an additional implant was implanted into the medial aspect of the inferior medial orbital rim for prostheses retention. All the patients were followed up for more than 2 years. No other failures were observed. The soft tissue reaction was acceptable in all patients. All of them were able to wear prostheses with satisfying appearance. Conclusions: Osseointegrated implants provid excellent retention for orbital prostheses. This technique could be used in patients with severe orbital deformity to improve their life quality. (Chin J Ophthalmol, 2019, 55: 665-669).

125I seed implant brachytherapy-assisted surgery with preservation of the facial nerve for treatment of malignant parotid gland tumors.

The surgical treatment of malignant parotid gland tumors combined with (125)I seed implant brachytherapy and preservation of the facial nerve is described. Tumor and parotid gland resection with preservation of the facial nerve was carried out in 12 patients with malignant parotid gland tumors. (125)I seeds were implanted into the target area intra- or postoperatively. The extent of regional control of the tumor was followed up, and facial nerve function was evaluated. None of the patients had tumor recurrence during the follow-up period of 50-74 months (median follow-up period, 66 months). Facial nerve function had recovered to normal by 6 months postoperatively in all patients. A limited surgical resection combined with (125)I seed implant brachytherapy is therefore considered to be an alternative treatment for local control of malignant parotid gland tumors with preservation of the facial nerve.

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma.

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.