Phase II study of Disulfiram and Cisplatin in Refractory Germ Cell Tumors. The GCT-SK-006 phase II trial.

BACKGROUND: Multiple relapsed/refractory germ cell tumor (GCT) patients have extremely poor prognosis. Cisplatin resistant testicular GCTs overexpress aldehyde-dehydrogenase (ALDH) isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity in vitro as well as in animal model. This study aimed to determine the efficacy and toxicity of ALDH inhibitor disulfiram in combination with cisplatin in patients with multiple relapsed/refractory GCTs. METHODS: Disulfiram was administered at a dose of 400 mg daily until progression or unacceptable toxicity, cisplatin was administered at dose 50 mg/m2 day 1 and 2, every 3 weeks. Twelve evaluable patients had to be enrolled into the first cohort, and if 0 of 12 patients had treatment response, the study was to be terminated. The results of the first stage of the trial are presented in this report. RESULTS: Twelve patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from May 2019 to September 2021. Median number of treatment cycles was 2 (range 1-6). None of patients achieved objective response to treatment, therefore the study was terminated in first stage. Median progression-free survival was 1.4 months, 95% CI (0.7-1.5 months), and median overall survival was 2.9 months 95% CI (1.5-4.7 months). Disease stabilization for at least 3 months was observed in 2 (16.7%) patients. Treatment was well tolerated, however, 5 (41.7%) of patients experienced grade 3/4 fatigue, 4 (33.3%) thrombocytopenia, 3 (25.0%) anemia, while 2 (16.7%) experienced neutropenia, nausea and infection. CONCLUSIONS: This study failed to achieve its primary endpoint and our data suggest limited efficacy of disulfiram in restoring sensitivity to cisplatin in multiple relapsed/refractory GCTs.

Importance of PET/CT examination in patients with malignant uveal melanoma.

INTRODUCTION: Diagnostic and therapeutic management of the patient with malignant uveal melanoma (MMU) is subject to ongoing efforts to innovate. PET/CT (Positron Emission Tomography / Computed Tomography) examination is important in both diagnosis and metastases. MATERIAL AND METHODS: Evaluation of the importance of PET/CT examination in the group of patients diagnosed with MMU in the period 12.1.2016 to 6.12.2018. All patients with a diagnosis of secondary retinal detachment, suspected uveal melanoma, underwent standard examinations to detect possible metastases (liver ultrasound, chest X-ray). Patients for whom a stereotactic radiosurgery solution was planned due to the stage of the disease this examination was to exclude metastasis in the liver or lungs. PET/CT examination is part of the protocol within the exclusion criteria for treatment with stereotactic radiosurgery in one day session surgery. RESULTS: In the group of 84 patients, 47 women (56 %) and 37 men (44 %) were aged between 26 and 90 years. Their average age was 61.4 years. The median group was 64 years, modus 65 years. Of 84 patients, 79 (94 % of cases) had a diagnosis of C69.3 (choroidal melanoma) and 5 patients (6 % of cases) had a diagnosis of C69.4 (ciliary body melanoma). Subsequent PET/CT examination in many patients did not reveal hypermetabolic manifestations that could involve various pathological processes, in others the radiopharmaceutical was captured in the primary tumor area of the uveal tract. Hypermetabolism in eye globe was only found in melanomas with a volume of more than 0.5 cm3. PET/CT examinations were 85, with one patient undergoing examination twice. However, in 25 patients (26 examinations), the radiopharmaceutical was taken up in places that subsequently required closer attention. The initial aim of the examination was to locate possible metastases of MMU. In the others, 3 incidents have been reported: increased metabolism in the lung and liver, thyroid and mediastinal lymph nodes. Of the 85 examinations, 26 (30.6 %) resulted in a hypermetabolic manifestation of accumulation, which was not located in the eye tract, resp. right in the eye. Two malignancies (prostatic carcinoma and rectosigmal carcinoma) have occurred in two patients. Very important was the discovery of MMU metastasis in the liver, which confirmed the important role of PET/CT examination in the management of MMU patients. The metastasis was discovered after repeated PET/CT examination. CONCLUSION: PET/CT examination is a technically demanding examination and is one of the possibilities of imaging intraocular melanoma in tumors with volume more than 0.5 cm3. It is important in determining the grading and staging of the disease before radiosurgical treatment and also in detecting possible metastases after MMU treatment in cases where ultrasound or MRI examinations do not give a definite result. However, our study confirmed the significance of this examination for randomly detected 2 duplex malignancies (2.4%) and 3 incidentalomas (3.6%) in patients whose ophthalmologist diagnosed uveal melanoma and sent patients for full-body PET/CT examination.

Variation of the arthroscopic Mumford procedure for resecting the distal clavicle.

Fifty-seven patients had arthroscopic Mumford procedures for acromioclavicular (AC) pain unresponsive to conservative treatment. Thirty-nine of these patients had concomitant rotator cuff repairs. All had significant improvement of distal clavicular pain. Neither the amount nor the completeness of the distal clavicle resection affected the results. One patient with a significant retained lateral clavicular spike required additional surgery for excision. Arthroscopic distal clavicle resection is a safe and effective method of alleviating AC pain.

Arthroscopic Mumford procedure variation of technique.

Fifty-seven patients had arthroscopic Mumford procedures for acromioclavicular pain non-responsive to conservative treatment. Thirty-nine of these patients had concomitant rotator cuff repairs. All had significant improvement of their distal clavicular pain. Neither the amount nor the completeness of distal clavicle resection affected the results. Arthroscopic distal clavicle resection is a safe and effective method of alleviating acromioclavicular pain.

Talonavicular dislocations and midfoot arthropathy in neuropathic diabetic feet. Natural course and principles of treatment.

Talonavicular dislocations, sometimes associated with other midtarsal arthropathy, occasionally occur in patients with diabetic neuropathy. The natural course and rationale of treating this diabetic arthropathy is presented, based on the literature and the authors' experience with eight cases. Appropriate management depends on the acuteness of the injury, the degree of deformity, and the degree of bone fragmentation. If the injury is acute and alignment is acceptable, immobilization and protective weight bearing may prevent progression of the neuropathic joint destruction. If dislocation is acute with marked deformity but there is little fragmentation and the foot has intact circulation, reduction and surgical arthrodesis may be indicated. If dislocation is chronic, with bone fragmentation and severe deformity, proper management consists of wearing custom-molded shoes with stiff rocker-bottom soles. Patellar tendon weight-bearing braces may be added if needed. For patients in this last category, surgical treatment is recommended as a last resort only if soft-tissue breakdown cannot be prevented by appropriate footwear and bracing alone.

Irreducible Salter-Harris type II fracture of the distal radial epiphysis.

A Salter-Harris Type II fracture of the distal radius in a skeletally immature adolescent was irreducible by closed means. At open reduction, an invaginated periosteal flap was found to be responsible for the incomplete reduction. Removal of the flap resulted in an anatomic reduction.