Preoperative Hyperoxyradiotherapy of Colorectal Carcinoma

Aim: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. Patients and Methods: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplan-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A. four patients, B: 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was peformed extending from the perineum to the vertebral L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). Results: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6ndash;105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of approximately 61.5% and a local relapse-free survival rate of approximately 84.2% can be expected. Treatment failures were predominantly systemic. Conclusion: We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncancerous tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma. Zusammenfassung Zielsetzung: Analyse von frühen und späten Nebenwirkungen und Komplikationen bei präoperativer lokoregionärer akzelerierter Hypoxyradiotherapie kolorektaler Karzinome. Patienten und Methoden: Zwischen April 1991 und Februar 1997 wurden 50 Patienten (36 Männer und 14 Frauen) mit kolorektalen Karzinomen präoperativ durch lokoregionäre akzelerierte hypofraktionierte Hypoxieradiotherapie behandelt. Die Beurteilung des Erkrankungsausmaßes erfolgte nach Dukes-Kriterien (A: vier Patienten, B: 28 Patienten, C: 18 Patienten). Ein 20-MeV-Linearbeschleuniger mit zwei opponierenden Feldern auf zwei Ebenen wurde verwendet. Die akute Hypoxie wurde während der Bestrahlung durch Atmen eines hypoxischen Gasgemischs von 7,8-8,0% Sauerstoff induziert. Gesamtdosen von 24 Gy/8 tage, 28 Gy/9 Tage bzw. 32 Gy/10 Tage wurden bei fünf, 20 bzw. 25 Patienten verabreicht. Eine anteriore Resektion oder abdominoperineale Amputation des Rektums wurde 1 Tag nach Abschluss der präoperativen Hypoxieradiotherapie durchgeführt. Die Bewertung der frühen Reaktionen nach Bestrahlung erfolgte nach den "Common Toxicity Criteria of the National Cancer Institute" (CTC-NCI). Ergebnisse: Nach Irradiation wurden bei drei Patienten eine frühe Proktitis und bei zwei Patienten eine frühe bestrahlungsbedingte Zystitis festgestellt. Weder akute noch späte strahlenbedingte Komplikationen wurden beobachtet. Auf der Grundlage der Kaplan-Meier-Analyse (median 48 Monate) könne eine 5-Jahres-Gesamtüberlebensrate von ca. 61,5% und eine lokal rezidivfreie Überlebensrate von ca. 84,2% erwartet werden. Schlussfolgerung: Die akute Hypoxie übt während akzelerierter Hypoxieradiotherapie kolorektaler Karzinome eine radioprotektive Wirkung auf Normalgewebe aus. Die Hypoxieradiotherapie erlaubt eine sichere Verabreichung von Dosen, die die Toleranzgrenze von gesunden Organen überschreiten.     

Renal pelvic carcinoma with unusual appearance simulating amyloidosis (myeloma kidney): a report of five cases

We describe 5 cases of urothelial carcinoma (UC) of the renal pelvis, which grew in a distinctive gross and microscopical pattern into the renal parenchyma. Five patients (2 men and 3 women, mean age 67.4 years) underwent nephrectomy for vague clinical findings. The cut surface of the tumor was white to light gray and the consistency was elastic. The corticomedullary border was indistinct, resulting in an appearance that suggested amyloidosis or myeloma. The renal pelvis showed normal mucosa with areas of dysplastic changes. The tumors spread from the renal pelvis in a diffuse and irregular, infiltrative pattern and surrounded intact glomeruli. Detailed sampling of invasive tumor component showed foci of UC with transitions to clear squamous cells. The predominant clear squamous neoplastic cells had foci of granular eosinophilic cytoplasm and resembled conventional renal cell carcinoma. Four patients were alive and without signs of the disease for 5 months to 4 years after nephrectomy; 1 died of generalized tumor 7 months after nephrectomy. The unusual gross and microscopic features result in varied problems in differential diagnosis, which are discussed herein.     

Prevalence rates of Borrelia burgdorferi sensu lato in host-seeking Ixodes ricinus ticks in Europe

Borrelia burgdorferi sensu lato spirochetes have been found in all examined Ixodes ricinus (L.) populations in Europe. The overall mean proportions of unfed I. ricinus infected with B. burgdorferi s.l. were 1.9% (range 0–11%), 10.8% (2–43%) and 17.4% (3–58%) for larvae (n = 5699), nymphs (n = 48 804) and adults (n = 41 666), respectively. However, the results varied according to the method used. Cultivation in BSK medium is the least sensitive technique (an average of 11% adult ticks found infected), whereas polymerase chain reaction detecting spirochetal DNA is probably the most sensitive method (29% adults found infected). Microscopic methods (dark field, phase contrast, direct or indirect fluorescence) are generally comparable to each other (17–20% adults found infected) and should be regarded as standard procedures because they also make possible a quantitative estimation of spirochetes in the vector. Some technical problems of these methods are discussed. Received: 18 August 1997 / Accepted: 12 September 1997     

Health risk of occupational exposure in welding processes II. Immunological effects

Many of epidemiological studies have certified the relationship between welding and various forms of health damages. In our study we performed an immunological research within a group of twenty men, working in the risky environment of manufacturing of stainless steel constructions (11 welders and 9 grinders, average age was 31 years, 55% of smokers, average time period in welding occupational exposure was 8 years). The exposed group of men was compared with a group of healthy blood donors, marked as the control group (people with various types of employment, living in same locality as a people from exposed group). People within the control group were not occupationally exposed to harmful chemical compounds (from 30 to 100 men were chosen for the individual immune parameters, average age of the whole group was 38 years, 40% of smokers). When compared with the control group, the exposed group of welders and grinders showed higher level of C3 complement (p < 0.001), orosomucoid (p < 0.05), beta-2-microglobulin (p < 0.001), neopterin (p < 0.001) and all fagocytic cells (p < 0.001). On the contrary, in the group of exposed people decreased values of IgA (p < 0.001), IgG (p < 0.001), IgM (p < 0.001), transferin (p < 0.001), alpha-1-antitrypsin (p < 0.001), alpha-2-macroglobulin (p < 0.001), haptoglobulin (p < 0.001) and ceruloplasmin (p < 0.05) were found. Some of these changes were characteristic for the exposed group. They could be considered as precursors of biological markers of effect for given type of exposure.     

Chemical binding of folic acid and methotrexate to bovine fibrinogen

The binding of folic acid as a model compound and methotrexate as a representative of antifolates to bovine fibrinogen with the aid of 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide was investigated in order to study the possibility of using fibrinogen as a drug carrier. Soluble modified fibrinogen derivatives containing 0.03-0.1 mg of folic acid or methotrexate per mg of protein were obtained under optimal conditions. These derivatives retained the ability to form fibrin clot by the action of thrombin and to copolymerize with native fibrinogen to the three dimensional fibrin network. At higher concentrations of water soluble carbodiimide, higher temperature and low pH highly crosslinked derivatives of fibrinogen and folic acid (or methotrexate) were formed which were insoluble in water and salt solutions (pseudofibrin). The modified fibrin was extensively proteolytically cleaved by plasmin, pepsin, trypsin and cathepsin D, whereas the proteolysis of insoluble pseudofibrin was very slow.     

Quantitative Bestimmung der Aktivität von pankreatischen Proteasen

Ohne Zusammenfassung     

Isotope lymphography of the retrosternal region

The authors have examined 150 patients with Hodgkin's lymphomas and cancer of the breast and lung.They consider indirect lymphography as a screening method necessary to be completed with available clinical examinations.In normal scintigram it is possible eliminate the pathological process. Even when some part of lymphatic region is not scanned it is possible to say that the suspicion of a pathological process is highly probable. It is necessary to consider the anatomical variability of lymphatic vessels. Therefore, the scintigram must be evaluated together with other clinical findings.The examination of axillar and cervical area of lymphatic system and the determination of eventual collateral circulation is recommended simultaneously with retrosternal lymphography.     

Die toxische Wirkung von Tri-n-butylzinn-Verbindungen auf weiße Mäuse

Zusammenfassung Es wurde die toxische Wirkung reiner Tri-n-butylzinn-Acetat,-Benzoat, -Chlorid, -Laurat, -Oleat-Präparate an weißen Mäusen mit einem durchschnittlichen Körpergewicht von 25 g verfolgt. Diese Verbindungen wurden in Oleum helianthi gelöst und den nüchternen Mäusen mittels einer Magensonde in einer Menge von 500 mg/kg Lebendgewicht einmalig verabfolgt.In jeder Versuchsgruppe, 10 Mäuse zählend, wurde eine der obengenannten Verbindungen appliziert. In den drei Kontrollgruppen wurde Oleum helianthi, Oleum helianthi + Alkohol, Wasser, appliziert.Die Tiere wurden 8 Std beobachtet, dann getötet, seziert und die Organe histologisch verarbeitet. Die Präparate wurden mit Hämatoxylin-Eosin und die Gefrierschnitte mit Oil red gefärbt.Im klinischen Bild entwickelten sich schon 4 Std nach der Applikation bei den Tieren der Gruppe-Acetat,-Benzoat,-Chlorid und-Oleat typische Anzeichen einer akuten Intoxikation, während der Zustand der Tiere aus der Gruppe Laurat, nur gering verändert war. 8 Std nach der Applikation hatte sich der Zustand aller Experimentaltiere verschlechtert, sie waren im präfinalen Stadium.Im makroskopischen Befund überwogen bei allen Gruppen Zeichen der Schädigung des Verdauungstraktes, der Leber und der Milz.Im histologischen Bild wurden bei den Tieren aller Gruppen eine Steatose der Leberzellen, aber unterschiedlicher Schwere, Spuren von Lipiden in den Zellen der Nierentubuli (in der Gruppen Laurat und Oleat) und zahlreiche Hämorrhagien im Verdauungstrakt und in den Nieren gefunden.Bei allen Tieren der Kontrollgruppen wurden keine Veränderungen, weder im klinischen, noch im morphologischen Befund (Bild) nachgewiesen.