Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients Euro-Net (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought
Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of change. A total of 6 of 28 (21.4%) ceftriaxone-treated patients and 1 of 8 (12.5%) patients who received the placebo demonstrated abnormal gallbladder sonograms on day 14 (P = 0.491). Four of the six ceftriaxone-treated patients demonstrating abnormal sonograms were clinically asymptomatic, while two patients reported vomiting. The abnormal sonograms of gallbladders of patients treated with ceftriaxone returned to normal between 9 and 26 days posttherapy. These data suggest an association between ceftriaxone treatment and the development of gallbladder abnormalities on ultrasound examination which resolve spontaneously on discontinuation of ceftriaxone therapy.
We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility which causes pulmonary gas embolism. Healthy adult sheep (n=3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n=7), the priming solution was preheated (42–46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hrs of 42 °C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35–44 mm Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiological range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy to use vv-PISH system for cancer treatment.
Objective Since hyperthermia selectively kills lung cancer cells, we developed a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced lung cancer therapy. Our objective was to test the safety/accuracy of our vv-PISH system in five day sheep survival studies, following Good Laboratory Practice standards. Methods The vv-PISH system, which included a double lumen cannula (DLC, AvalonElite™); a centrifugal pump (Bio-Pump 560®); a heat exchanger (BIOtherm™); and a heater/cooler (modified Blanketrol III™), was tested in healthy adult sheep (n=5). The perfusion circuit was primed with pre-warmed Plasma-Lyte®A and de-aired. Calibrated temperature probes were placed in right/left nasopharynx, bladder, and blood in/out of animal. The DLC was inserted in jugular vein into the superior vena cava, with the tip in the inferior vena cava. Results Therapeutic core temperature (42-42.5°C), calculated from right/left nasopharnx and bladder temperatures, was achieved in all sheep. Heating time was 21±5 minutes. Therapeutic core temperature was maintained for 120 minutes followed by a cooling phase (35±6 min) to reach baseline temperature. All sheep recovered from anesthesia with spontaneous breathing within 4 hours. Arterial, pulmonary, and central venous pressures were stable. Transient increases in heart rate, cardiac output, and blood glucose occurred during hyperthermia but returned to normal range after vv-PISH termination. Electrolytes, complete blood counts, and metabolism enzymes were within normal to near normal range throughout the study. No significant vv-PISH-related hemolysis was observed. Neurological assessment showed normal brain function all 5 days. Conclusion Our vv-PISH system safely delivered the hyperthermia dose with no significant hyperthermia-related complications.
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