Melanocortin 1 Receptor-Targeted α-Particle Therapy for Metastatic Uveal Melanoma.

New effective therapies are greatly needed for metastatic uveal melanoma, which has a very poor prognosis with a median survival of less than 1 y. The melanocortin 1 receptor (MC1R) is expressed in 94% of uveal melanoma metastases, and a MC1R-specific ligand (MC1RL) with high affinity and selectivity for MC1R was previously developed. Methods: The 225Ac-DOTA-MC1RL conjugate was synthesized in high radiochemical yield and purity and was tested in vitro for biostability and for MC1R-specific cytotoxicity in uveal melanoma cells, and the lanthanum-DOTA-MC1RL analog was tested for binding affinity. Non-tumor-bearing BALB/c mice were tested for maximum tolerated dose and biodistribution. Severe combined immunodeficient mice bearing uveal melanoma tumors or engineered MC1R-positive and -negative tumors were studied for biodistribution and efficacy. Radiation dosimetry was calculated using mouse biodistribution data and blood clearance kinetics from Sprague-Dawley rat data. Results: High biostability, MC1R-specific cytotoxicity, and high binding affinity were observed. Limiting toxicities were not observed at even the highest administered activities. Pharmacokinetics and biodistribution studies revealed rapid blood clearance (<15 min), renal and hepatobillary excretion, MC1R-specific tumor uptake, and minimal retention in other normal tissues. Radiation dosimetry calculations determined pharmacokinetics parameters and absorbed α-emission dosages from 225Ac and its daughters. Efficacy studies demonstrated significantly prolonged survival and decreased metastasis burden after a single administration of 225Ac-DOTA-MC1RL in treated mice relative to controls. Conclusion: These results suggest significant potential for the clinical translation of 225Ac-DOTA-MC1RL as a novel therapy for metastatic uveal melanoma.

[The surgical approach to non-neoplastic abdominal pathology in the geriatric patient]. / L'approccio chirurgico alla patologia addominale non neoplastica nel paziente geriatrico.

BACKGROUND: The authors evaluate the most suitable approach to be used in elderly patients suffering from non-neoplastic abdominal pathology. METHODS: A retrospective evaluation was made of cases observed over the past two years. Follow-up continued for at least three months after treatment. SETTING: General Surgery 1, Department of Surgical and Anatomic Disciplines, Policlinico, University of Palermo. PATIENTS: A total of 92 patients were treated aged between 65 and 94 years old (mean age 79.5). The most frequently observed pathologies were cholelithiasis and hernia, treated both electively and in emergency. OPERATIONS: 76 patients were treated electively and 16 underwent emergency surgery. Parameters examined: The authors evaluated postoperative progress, morbidity and mortality. RESULTS: Morbidity was equal to 6.5%. Death occurred in three patients, one of whom had been operated a month earlier. CONCLUSIONS: Surgery is considered appropriate in the elderly patient provided an adequate pre-, intra- and postoperative approach is used. The preoperative phase should include a multidisciplinary evaluation to assess surgical risk (ASA and APACHE). During surgery, the most beneficial solution should be found which takes account of the patient's life expectancy; whenever possible, is it advantageous to resort to video-laparoscopy owing to the diagnostic accuracy of this method, as well as the capacity to adjust subsequent surgery whether it is performed using video-assisted laparoscopy or targeted mini-laparotomy. This causes less surgical aggression and therefore a more comfortable postoperative recovery. During the latter phase, vital and biohumoral parameters should be accurately monitored to ensure the prompt recognition of organic collapse and/or metabolic disorders consequent to surgical stress.

[Video laparoscopy in abdominal emergencies]. / La videolaparoscopia nelle urgenze addominali.

BACKGROUND: Personal experience about the use of video laparoscopy (VL) in abdominal emergencies is reported. DESIGN: retrospective evaluation of patients observed in the last years. SETTING: General Surgery I. Policlinico, University of Palermo. SUBJECTS: 61 VL have been performed: 30 acute appendicitis, 21 acute cholecystitis, 4 perforated peptic ulcer, 1 haemoperitoneum by haemorrhaged luteal corpus, 2 pelvic inflammatory disease (PID), 1 terminal ileitis, 1 choledochal perforation after ERCP and 1 bleeding after CVL. INTERVENTIONS: the following interventions have been performed: 22 VL appendectomy, 8 VL-assisted appendectomy, 21 VL cholecystectomy, 1 VL duodenal suture, 3 minilaparotomic duodenal suture, 2 prophylactic VL-assisted appendectomy, in 1 patient with terminal ileitis and in 1 PID, 1 VL partial ovarian resection. In the case with choledochal perforation during ERCP a traditional cholecystectomy was performed with an outer biliary drainage. In the patient with bleeding after CVL the spontaneous haemostasis seen during VL was confirmed by laparotomy performed to exclude baro-haemostasis and to prevent from legal motivation. The procedure was only diagnostic in 1 patient with PID. MAIN OUTCOME MEASURES: the diagnostic and therapeutic value, versus traditional surgery have been valued. RESULTS: VL is useful both for a correct diagnosis and to lead a laparotomy if necessary, allowing an adequate peritoneal exploration and toilet without large incisions; the operation is therefore, in any case, less invasive. CONCLUSIONS: In our experience the usefulness of VL is clear in the suspect of acute appendicitis, acute cholecystitis, perforated peptic ulcer, haemoperitoneum and when diagnosis is not sure and in all other situations in which correct preoperative diagnosis is impossible. So this procedure is useful to make easy a correct diagnosis and to surgical treatment.

[Video laparoscopic appendectomy. Our experience]. / Appendicectomia videolaparoscopica. Nostra esperienza.

OBJECTIVE: Personal experience with the use of VL in the treatment of acute appendicitis (AA) is reported. The main advantage of this method is its high diagnostic reliability. SETTING: Chirurgia Generale I. Dipartimento di Discipline Chirurgiche e Anatomiche. Policlinico Università Palermo. SUBJECTS: The VL method has been used in 36 patients with diagnosis of suspect acute appendicitis. INTERVENTIONS: In the cases in which the diagnosis has been confirmed, a VL appendectomy with endoabdominal technique according to Semm has been performed in 23 cases, and an assisted VL appendectomy, trough a minimal and guided laparotomy, in 8 cases. In order to avoid vascular and visceral injuries, an "open" laparoscopy technique is always used. RESULTS: The diagnosis has been confirmed in 31 cases, 21 women and 10 men. The diagnosis has not been confirmed in 5 cases, a man of 74 years with sigmoidal diverticulitis and 4 women with terminal ileitis in a case, torsion of right ovarian cyst in another and, finally, pelvic inflammatory disease in 2. CONCLUSIONS: From this brief experience it is evident the diagnostic advantage of VL particularly in the female and in elderly patients. Other advantages of this method are the excellent aesthetic result, light postoperative pain, the rapid functional resumption, the small impact of adherences, wound infection, and incisional hernia, and the lower cost, when staplers are not used. The disadvantages are the extension of the operative time, using the "open" laparoscopy technique, and the difficulty to find Meckel diverticulum.

[Long-term central venous access. Our experience]. / Accesso venoso centrale a lungo termine. Nostra esperienza.

Prolonged venous access devices (PVAD) represent a useful tool for many patients with chronic diseases. In the last 3 years 50 PVAD have been placed. Polyurethane catheters with a subcutaneous tunnel > 6 cm, have been used. There were no complications related to catheter insertion. The average life of PVAD was 95 days (range 7-425).

Carrageenan from Eucheuma striatum (Schmitz) in Media for Fungal and Yeast Cultures.

Fungi and yeasts were cultivated on media prepared from Eucheuma carrageenan. The cultures were found to compare well with those grown on agar media.

Carrageenan from Eucheuma striatum (Schmitz) in Bacteriological Media.

The use of carrageenan from the red alga Eucheuma striatum as a possible substitute for bacteriological agar was investigated. The carrageenan medium was compared with several commercially available media in terms of both their physical properties and the colony characteristics of 16 microorganisms grown on the media.