The PhaSeal® system: impact of its use on workplace contamination and duration of chemotherapy preparation.

PURPOSE: The primary objective of this study was to compare the levels of environmental contamination before and after the introduction of PhaSeal® (closed-system drug transfer device) in two hospital pharmacies. Our secondary objective was to assess the impact of the device on the duration of drug preparation compared to procedures involving the use of needles and syringes. METHODS: The study involved two French hospitals, which prepared antineoplastic chemotherapy using a biological safety cabinet and an isolator. Five skilled pharmacy technicians at each hospital prepared a total of 100 chemotherapy preparations using the standard procedure and 100 using the PhaSeal® system. To control for possible contamination occurring in the course of the procedure, we used fluorescein which becomes fluorescent when exposed to UV light. To reply the second objective, we timed the duration of the different steps of the manipulation. RESULTS: Our findings showed a major reduction in the contamination of the work environment when using the PhaSeal® system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used. On the duration of preparation, our results indicate that this duration would be approximately 1 h longer for the preparation of 100 samples. CONCLUSION: In conclusion, this study clearly establishes the benefit of using PhaSeal® for protecting the staff members who work with hazardous agents. It also indicates that the duration of drug preparation is not impacted by the use of the system.

Adenosine triphosphate attenuates renal sympathetic nerve activity through left ventricular chemosensitive receptors.

We previously reported that ATP, but not adenosine, administered i.v. attenuates the baroreflex-mediated increase in sympathetic nerve activity in response to arterial hypotension by a vagal afferent mechanism. It was not elucidated in that study which vagal afferent endings are involved. Mongrel dogs were anesthetized with alpha-chloralose, thoracotomy was performed and a 27-gauge hypodermic needle was inserted into the left circumflex coronary artery. The left renal sympathetic nerves were isolated and placed on a bipolar silver electrode for measurement of renal sympathetic nerve activity (RSNA). Dose-response effects of intracoronary or i.v. infusion of ATP (100, 200 or 400 microg/kg/min) on RSNA and mean arterial pressure were studied in neuraxis-intact and cervically vagotomized dogs. RSNA was increased dose-dependently with decreasing mean arterial pressure during the i.v. ATP infusion. Elevation of RSNA was attenuated by higher intracoronary ATP infusion rates, despite the fact that mean arterial pressure was decreased dose-dependently. Left ventricular end-diastolic pressure, however, remained unchanged. This suppression of RSNA by the intracoronary ATP infusion was completely abolished by bilateral cervical vagotomy. Our data suggest that ATP attenuates reflex increases in sympathetic nerve activity by possibly stimulating ventricular chemoreceptors with cardiac vagal afferents.

[Lung metastases--can resection also be justified in synchronous liver metastasis?]. / Lungenmetastasen--Kann eine Resektion auch bei synchroner Lebermetastasierung gerechtfertigt sein?

There is general agreement on the preconditions necessary for the resection of lung metastases: the primary tumor has to be resected completely, a local tumor recurrence as well as metastases in other organs have to be excluded. 5-year survival rate of patients operated under these criteria is said to be about 20 to 40% (number of own patients: 72; 5-year survival rate: 30.2%. Only in a few cases, however, lack of metastases in other organs is given. Often there are synchronic liver metastases. Local intraarterial chemotherapy doesn't put much burden on the patient, induces a decrease of liver metastases in 30% and a complete remission in a few cases, respectively. Between 1981 and 1987 we performed local chemotherapy of the liver in 575 patients. 110 patients showed lung metastases in the course of the treatment or during the aftercare period. In 8 patients we resected lung metastases occurring after remission of liver metastases. 7 patients died 11 to 28 months after the operation, 1 patient is still alive 16 months postoperatively.

[Cold struma nodule--enucleation or resection]. / Kalter Strumaknoten--Enucleation oder Resektion.

During 1969-1984 2,408 patients underwent thyroid surgery at the Dept. of General Surgery, Giessen University. In 72.5% cold nodules have been diagnosed. However, a cold nodule has been in less than 50% of all cases with cold nodules the causal indication for operation. Inspecting closely the whole thyroid gland, the operating surgeon removes the nodule with a segmental resection if there are no further regressions or suspicion of malignancy. This technique facilitates the histological detection of a possible highly differentiated carcinoma because of its invasion into the capsule.

Perfluorocarbone (FDA 20) and extracorporeal circuit of isolated extremity perfusion.

The applicability of Fluosol DA 20 as a perfusion fluid was investigated in the isolated limb perfusion of 14 mongrel dogs and its performance compared with that of diluted blood. Control of perfusion parameters permitted a direct comparison of the two perfusion liquids. Muscle tissue, blood and perfusate were analyzed for pH, pO2, pCO2, O2 content, lactate, pyruvate, ATP and creatine phosphate. Due to given experimental conditions, the pH values of the perfusion liquid and muscle tissue were in a slightly acidic range. The oxygen uptake of the perfusion liquids and the oxygenation of tissue was satisfactory, the metabolism of the muscle tissue was not disrupted.

[Stroma-free hemoglobin solution and perfusion of isolated extremities]. / Stromafreie Hämoglobinlösung und isolierte Extremitätenperfusion.

Pyridoxylated stroma-free hemoglobin solution was compared to hemodiluted blood in extremity perfusion of mongrel dogs. pH-values in tissue and in perfusate as well as oxygen tension showed no significant difference, and oxygen supply to the periphery was sufficient. Measurement of lactate, pyruvate, ATP and CP demonstrated domination of aerobic metabolism. We proved that stroma-free hemoglobin solution ( SFHb -PLP) can substitute hemodiluted blood (Hk 18) in isolated extremity perfusion. Metabolic results were confirmed by histological examination where no tissue alterations could be found in the perfused extremity or the whole body system.

Isolated extremity perfusion with DTIC. An experimental and clinical study.

Dacarbazine (DTIC) was used for isolated perfusion of extremities in dogs and man. In the animal experiment perfusions with DTIC at dosages up to 100 mg per kg of extremity weight were well tolerated. The concentration of DTIC in the perfusate ranged from 70 to 400 micrograms/ml without evidence for formation of metabolites. Electron microscopy, performed 14 days later, revealed a decrease of glycogen in striated muscle cells. Vascular damage was not observed. Five patients with advanced malignant melanoma or soft tissue sarcoma of the extremities were treated by isolation perfusion with 75 to 133 mg DTIC per kg of extremity at 40 degrees C for 60 minutes. A tumor regression of at least 30% was observed.

Regional perfusion with cis-platinum and dacarbazine.

In 22 patients isolated extremity perfusion with cis-platinum for treatment of malignant melanoma was performed; 18 had local metastastic disease (M. D. Anderson stages II and III A, B, AB) and four were stage I. A further five patients were submitted to isolated DTIC perfusion. DTIC-perfused tumors showed regression rates of 30%-80%, followed by recurrences within 4 months. After cis-platinum perfusion stage-III AB cases tended to show tumor recurrence within 4 months, while to date stage-III A and stage-II cases have reached disease-free survival times of 17 and 20 months respectively. While in DTIC perfusion the tissue temperature may range between 40 degrees and 41 degrees C, in cis-platinum perfusions 40 degrees C should not be exceeded; otherwise neural damage will occur.

Fluorescence-histochemical and electron-microscopical investigations in melanoma patients after isolated cytostatic perfusion.

The effect of isolated cytostatic perfusion was determined in in-transit metastases from malignant melanomas at various times after therapy. Fluorescence-microscopically positive tumor cells (formalin-induced fluorescence) were regarded as viable and possibly capable of dividing. Most of the metastases examined showed fluorescent cells even after perfusion, and these were often found at characteristic sites within the metastases. Under the electron microscope, the cell damage was seen mainly in the nucleus, but also in the organelles of the cytoplasm. The source of cell damage might be multifactorial, and the cytostatic effect could not be clearly separated from the effect of hyperthermia or hypoxia.

[The delayed split-skin coverage--use and advantages]. / Die verzögerte Spalthautdeckung--Anwendung und Vorteile.

In 119 patients a "delayed skin flap transplantation" was carried out after excision of malignant melanomas. The skin graft can be stored in a refrigerator at 4 degrees C up to two weeks without damage to the transplant. The transplantation may be accomplished at any time, but is usually due 3 to 4 days postoperatively. Advantages of this method are decreased risk of local infection, early mobilisation of the patient and generally good cosmetic results.

[Somatostatin in the medical treatment of fistula of the pancreas and the small intestine]. / La somatostatine dans le traitement médical des fistules du pancréas et de l'intestin grêle.

Somatostatin is a peptide hormone which inhibits the secretion of the growth hormone and certain gastrointestinal hormones. Its main effect is to reduce the gastric acid output and inhibit the exocrine function of the pancreas. It was therefore used as an adjuvant therapy in the conservative treatment of ten patients presenting with fistulas of the small intestine or pancreas. The treatment was successful in eight cases. The short halflife of the hormone makes continuous application of the somatostatin as important as the carrying on of the conservative treatment itself.

[New modifications in isolated extremity perfusion ]. / Neue Entwicklungen in der isolierten Extremitäten-perfusion.

Hyperthermic isolated extremity perfusion has been undertaken in 117 patients with advanced melanoma of the extremities from october 1979 to may 1981. Perfusion is indicated in cases above level III and tumor thickness above 1,5 mm. Among the cytostatic agents used were melphalane, melphalane and dactinomycin, nitrogen mustard/dactinomycin, as well as DTIC, cis-platinum and the combination of cis-platinum and dactinomycin. All cytostatics lead to tumor regression, as observed on tumors left in situ. Longterm results have yet to be awaited. While melphalane may be perfused at 42 degrees C, the cisplatinum perfused extremity should not be heated to above 40 degrees C because permanent neurological damage may be induced. For this reason maximal hyperthermia is reached before the cytostatic agent is introduced and has to be lowered when the drug is added.

Levels of Cis-Platinum in hyperthermic isolated perfusion.

The Cis-platinum levels in isolated extremity perfusion were measured in dogs and man. We found that prolonged presence of Cis-platinum in the tissue is attributed to its strong and rapid binding to serum and tissue proteins. Protein binding follows the concentration gradient. Subsequent re-diffusion into the blood followed by urinary excretion was also noted.

[Malignant sacrococcygeal teratoma in an adult]. / Maligne entartetes Steissbeinteratom beim Erwachsenen.

Malignant sacrococcygeal teratoma is rare in adults. diagnosis is difficult when the tumour is presacral located. A 42-year-old female patient underwent rectum extirpation with resection of a malignant sacrococcygeal teratoma. Histological biopsy and clinical staging did not show whether the teratomas were malignant or not. These tumours have to be resected totally, when necessary together organs of the pelvic region.

[Complications following thoracic surgery (author's transl)]. / Komplikationen nach thoraxchirurgischen Eingriffen.

From 1968--1977 a total of 2,670 patients with thoracic injury or disease were treated in the Department of General and Thoracic Surgery at the University of Giessen. Of these, 1,185 patients were operated on: 701 lung resections, 371 thoracotomies, and 113 operations on the diaphragm and thoracic wall. Postoperative complications were observed in 16% and 8% died. Frequency and severity of the complications were dependent on the type of surgery and the underlying disease.