COMPARISON OF DIFFERENT TECHNIQUES FOR EVALUATION OF DOSE DISTRIBUTIONS IN RADIOTHERAPY USING RADIOCHROMIC EBT3 FILMS.

In radiotherapy, radiochromic films can be used for verification of delivery of dose distributions calculated by treatment planning systems. The main objective of this work was to compare three different techniques for evaluation of dose distributions for prostate cancer treatment plans using radiochromic EBT3 films. These techniques are: red channel evaluation taking into account only a response of irradiated film (R), red channel evaluation taking into account a response of unirradiated and irradiated film (Rcor) and multichannel evaluation in FilmQA software (RGB). Also comparison between film and MatriXX measurement was performed. Comparison showed that gamma analysis passing rates strongly depend on evaluation technique and on a model of scanner for digitizing films. The highest gamma passing rates were obtained with red channel evaluation taking into account a response of unirradiated and irradiated film using Epson V750 scanner (Rcor) and multichannel evaluation in FilmQA using Epson 11000XL scanner.

RESULTS OF CZECH NATIONAL STUDY OF RADIATION EXPOSURE FROM RADIOTHERAPY OF NON-MALIGNANT DISEASES, IN PARTICULAR OF HEEL SPURS.

About 26 000 patients are treated per year with radiotherapy for non-malignant diseases in the Czech Republic. Approximately 75% of them are treated on X-ray therapy units and most of these patients undergo radiotherapy of heel spurs. The evaluation of radiation exposure of these patients was based on measured organ doses and on data from clinical practice. Collective effective doses for particular diagnoses were calculated in order to compare doses resulting from different diagnoses treated on X-ray therapy units. The collective effective dose from radiotherapy of heel spurs in the Czech Republic in 2013 was evaluated to 77 manSv. It represents 25.6% of the total collective effective dose for all diagnoses of radiotherapy for non-malignant diseases treated on X-ray therapy units.

Measurement of stray radiation within a scanning proton therapy facility: EURADOS WG9 intercomparison exercise of active dosimetry systems.

PURPOSE: To characterize stray radiation around the target volume in scanning proton therapy and study the performance of active neutron monitors. METHODS: Working Group 9 of the European Radiation Dosimetry Group (EURADOS WG9-Radiation protection in medicine) carried out a large measurement campaign at the Trento Centro di Protonterapia (Trento, Italy) in order to determine the neutron spectra near the patient using two extended-range Bonner sphere spectrometry (BSS) systems. In addition, the work focused on acknowledging the performance of different commercial active dosimetry systems when measuring neutron ambient dose equivalents, H(∗)(10), at several positions inside (8 positions) and outside (3 positions) the treatment room. Detectors included three TEPCs--tissue equivalent proportional counters (Hawk type from Far West Technology, Inc.) and six rem-counters (WENDI-II, LB 6411, RadEye™ NL, a regular and an extended-range NM2B). Meanwhile, the photon component of stray radiation was deduced from the low-lineal energy transfer part of TEPC spectra or measured using a Thermo Scientific™ FH-40G survey meter. Experiments involved a water tank phantom (60 × 30 × 30 cm(3)) representing the patient that was uniformly irradiated using a 3 mm spot diameter proton pencil beam with 10 cm modulation width, 19.95 cm distal beam range, and 10 × 10 cm(2) field size. RESULTS: Neutron spectrometry around the target volume showed two main components at the thermal and fast energy ranges. The study also revealed the large dependence of the energy distribution of neutrons, and consequently of out-of-field doses, on the primary beam direction (directional emission of intranuclear cascade neutrons) and energy (spectral composition of secondary neutrons). In addition, neutron mapping within the facility was conducted and showed the highest H(∗)(10) value of ∼ 51 µSv Gy(-1); this was measured at 1.15 m along the beam axis. H(∗)(10) values significantly decreased with distance and angular position with respect to beam axis falling below 2 nSv Gy(-1) at the entrance of the maze, at the door outside the room and below detection limit in the gantry control room, and at an adjacent room (<0.1 nSv Gy(-1)). Finally, the agreement on H(∗)(10) values between all detectors showed a direct dependence on neutron spectra at the measurement position. While conventional rem-counters (LB 6411, RadEye™ NL, NM2-458) underestimated the H(∗)(10) by up to a factor of 4, Hawk TEPCs and the WENDI-II range-extended detector were found to have good performance (within 20%) even at the highest neutron fluence and energy range. Meanwhile, secondary photon dose equivalents were found to be up to five times lower than neutrons; remaining nonetheless of concern to the patient. CONCLUSIONS: Extended-range BSS, TEPCs, and the WENDI-II enable accurate measurements of stray neutrons while other rem-counters are not appropriate considering the high-energy range of neutrons involved in proton therapy.

Serum alkaline-stable acid thiol proteinase--a possible marker for primary liver carcinoma.

Activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (GMT), lactate dehydrogenase (LD), beta-glucuronidase (GLU) and cathepsin B-like (CB-like) were determined in blind-coded sera from 50 patients with primary liver carcinoma, liver cirrhosis and acute hepatitis, and from 40 control subjects of comparable age range. CB-like activity averaged 700% (p less than 0.01), 1590% (p less than 0.01) and 1600% (p less than 0.01) of control subjects in liver cirrhosis (n = 30), acute hepatitis (n = 5) and primary liver carcinoma (n = 15), respectively. In acute hepatitis group we have found significant correlation between CB-like and GLU activities (r greater than 0.95). This correlation, however, was not observed in primary liver carcinoma suggesting that alteration in CB-like activity is not due to generalized increases in lysosomal membrane instability. The primary liver carcinoma group exhibited also the modest increments in serum ALP, GMT and LD activities (p less than 0.01). This increment, however, was not detected in any of acute hepatitis or liver cirrhosis patients. For the first time the alkaline-stable form of CB-like in human serum is described. This form representing 40% of overall CB-like activity was present in all primary liver carcinoma patients. This form, however, was not present in sera of any of control subjects or in sera of patients with acute hepatitis and liver cirrhosis with the exception of two men, in whom we have probably dealing with an early stage of primary liver carcinoma. Although the nature of the increment in CB-like activity in cancer remains to be determined, such analyses may help to the early detection of malignant hepatoma (primary liver carcinoma).

Characterization of cathepsin B-like proteinase from ascitic fluid of patients with primary liver cancer.

Ascitic fluid of patients with primary liver cancer was shown to contain a latent thiol proteinase which can be activated by pepsin treatment or by autolysis at acidic environment. This enzyme resembles cathepsin B (EC 3.4.22.1) in many physical-chemical properties including substrate specificity, requirement for thiol activators and inhibition both by thiol blocking reagents and by peptidyl diazomethyl ketones, but has a higher molecular size even after activation. Pepsin treatment and autolysis reduce its Mr from 41 800 to 33 400 and 27 700, respectively, but all these forms are larger than human liver cathepsin B. The latent enzyme may be, therefore, an enzyme--inhibitor complex or an inactive precursor of cathepsin B due to an altered processing in Golgi endoplasmatic reticulum-lysosome compartment.

Changes in serum cathepsin B-like activity in patients with colorectal cancer.

Cathepsin B-like activity (CB-like) was estimated in sera of 30 male patients with colorectal cancer (n = 20), benign polyps of the rectum (n = 10) and in sera of control subjects (n = 50). Both total and residual activities of the enzyme in colorectal cancer patients showed a significant elevation in comparison with control subjects and patients with benign polyps. In the course of antitumor therapy a decline in catheptic activity was observed when a reduction in the volume of tumor tissue was present. On the other hand, an increment in CB-like activity was observed when antitumor therapy had no effects or tumor relapse was present.

Changes in tissue and serum activity of cathepsin B-like cysteine proteinase during colorectal carcinogenesis by 1,2-dimethylhydrazine in mice.

The activity of cathepsin B-like cysteine proteinase in the mice colon was studied during carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride (DMH). Before starting the treatment with DMH, the activity of the observed enzyme was very low in the colorectal area but the activity in the serum was rather high. In the course of carcinogenesis, the local activity markedly increased in the stroma equally as in the cells of developing tumors while the serum activity slightly decreased. Following the total ovariectomy, no significant changes in the local activity or in the serum activity were found. Possible causes of these variations are discussed.

Intraluminal brachytherapy and selfexpandable stents in nonresectable biliary malignancies--the question of long-term palliation.

BACKGROUND/AIMS: To evaluate the effect of a combination of intraluminal brachytherapy and metallic stent implantation in the treatment of patients with nonresectable biliary tumors. METHODOLOGY: Thirty-two patients aged 41-80 years with nonresectable biliary malignancies--Klatskin's tumor (n = 17), gallbladder carcinoma (n = 11) and carcinoma of papilla Vateri (n = 4)--were treated with a combination of intraluminal brachytherapy (source Ir192, high-dose radiation regimen, total dose 30 Gy) and metallic stent implantation. Intraluminal brachytherapy and stent insertion (metallic, spiral-Z stent) were performed percutaneously in all patients. RESULTS: The mean survival in patients with Klatskin's tumor was 457 days (range: 64-1186; median: 358 days), in patients with gallbladder carcinoma 237 days (range: 92-609; median: 210 days) and in patients with carcinoma of papilla Vateri 850 days (range: 48-1518; median: 1277 days). The rate of 2-year survival in these groups as 27, 0 and 50%, respectively. The survival time differed significantly at the 5% level. The mean time of stent patency was 418, 220 and 850 days, respectively. No complications related directly to intraluminal brachytherapy were observed. CONCLUSIONS: Intraluminal brachytherapy combined with stent implantation is a safe method and appears to prolong survival in inoperable patients with Klatskin's tumor and carcinoma of papilla Vateri compared with nontreated patients in previous studies. In contrast no similar effect should be expected in patients with gallbladder carcinoma.

[Regional chemotherapy in experimental cholangiocarcinoma in pigs]. / Regionální chemoterapie u experimentálního cholangiokarcinomu vepru.

BACKGROUND: Primary cholangiocarcinoma (PCC) accounts for cca 9% of all carcinomas of the liver and biliary system. Its prognosis of always unfavourable and treatment is difficult. METHODS AND RESULTS: In 25 pigs strain BU PCC was induced chemically with the aim to test the action of regional chemotherapy on the tumor tissue. For treatment 5-fluorouracil, 5-fluoro-2-deoxyuridine, mitomycin C and doxorubicin was used either as monotherapy or in combinations. During chemotherapy a significant reduction of the tumour or fibrotization occurred, as compared with animals not receiving treatment. The median of survival was prolonged from 51.3 to 210.3 days. CONCLUSIONS: Regional chemotherapy is a significant constituent of oncological treatment of PCC. Complications of treatment are negligible and the rest for further treatment are encouraging.

[Initial experience with the transjugular renal biopsy]. / První zkusenost s transjugulární renální biopsií.

Transjugular renal biopsy is a new diagnostic method used for collection of tissue specimens for morphological examination in some indicated cases where the use of the standard percutaneous technique involves risk. The method has not been used so far in Czechoslovakia.

[Regional chemotherapy in the treatment of biliary tract tumors]. / Prínos regionální chemotherapie v lécbe nádoru biliárního systému.

BACKGROUND: Subjective complaints of patients with tumours of the biliary tree are late, early diagnosis is difficult and frequently impossible, the therapeutic results are unsatisfactory and the prognosis is poor. Surgical intervention is in more than 90% palliative, the tumours are not radiosensitive and their sensitivity to systemically administered cytostatics is low. The perspective of some patients was improved by implantation of bilioduodenal endoprostheses. The objective of the submitted work was to assemble experience with this method in patients with tumours of the upper portions of the biliary tree. METHODS AND RESULTS: Between January 1991 and May 1993 75 patients (42 females and 33 males, aged 48-65 years) with malignancies of the upper and middle part of the biliary tree were treated. Bilioduodenal endoprostheses (BDE) were inserted endoscopically in 70 patients. In 21 of them stenting was combined with regional chemotherapy via an implantable portho catheter. For patients with BDE alone, the median survival time was 18 months, for those with BDE and chemotherapy the median survival was 23 months (p < 0.01). 5-fluorouracil in monocombination was as potent as in combination with carmustine and/or doxorubicin. CONCLUSIONS: Endoscopic implantation of a bilioduodenal endoprosthesis with subsequent regional administration of 5-fluorouracil is an important therapeutic procedure in the treatment of malignant tumours of the upper and middle biliary tree.

[Tumors of the biliary tract: possibilities of multimodality therapy]. / Nádory biliárního stromu: moznosti multimodální lécby.

BACKGROUND: Tumours of the biliary system (NBS) account for as many as 16% of all tumours of the GIT. Early diagnosis is difficult, contemporary treatment is not satisfactory and the prognosis is poor. It seems that one of the few therapeutic perspectives is multimodal treatment. The objective of the present work is to assemble experience with multimodal treatment of NBS. METHODS AND RESULTS: From January 1987 to December 1993 347 patients with NBS were treated, using bilioduodenal endoprostheses (BDE). In 26 patients treatment was supplemented by regional chemotherapy, in 10 by intraluminal radiotherapy, using lr 192. Average periods of survival:BDE 230 days, BDE+regional chemotherapy 662 days. Endoprostheses+intraluminal radiotherapy-survival period 96-293 days. The investigation has not yet been completed, as the majority of patients still survives. CONCLUSIONS: Implantation of BDE combined with regional chemotherapy significantly prolongs the life of patients with NBS. It seems that similar results will be obtained also by a combination of BDE and intraluminal radiotherapy. Multimodal treatment of NBS can be nowadays considered the method of choice in the treatment of tumours in this region.

[Treatment of pancreatic stones with extracorporeal lithotripsy with sonographic localization]. / Lécba pankreatikolitiázy extrakorporální litotrypsí se sonografickým zamerením.

BACKGROUND: Pancreatic stones may be treated by endoscopic extraction or by surgery. Extracorporeal shock wave lithotripsy increased possibility of noninvasive steps to their elimination. The aim of this study was to describe our first experience with this method. METHOD AND RESULTS: 10 patients (6 men and 4 women) in average age 47 years (between 19 to 72 years) were treated. The lithotriptor MEDILIT with sonographic targeting was used for fragmentation of pancreatic stones. Fragmentation was achieved in 8 patients, in 4 cases we observed spontaneous disappearnace, in 3 cases an endoscopic extraction of fragments was necessary. In one case good fragmentation was observed at control ECRP, but the repeated Wirsungography showed a big pseudocyst which had not been diagnosed at the first examination and surgery was necessary. In 2 cases no fragmentation was achieved and in these cases surgery was also indicated. No serious side effects were observed, nor elevation of amylase values compared with the situation before the shock wave treatment. CONCLUSIONS: Extracorporeal shock wave lithotripsy of pancreatic stones revealed good fragmentation and disappearance stone from ductus Wirsungi without serious side effects on clinical course and surrounding soft tissues.

[Shock-wave lithotripsy in the treatment of 12 patients with choledocholithiasis using an apparatus manufactured in Czechoslovakia]. / Litotrypse rázovou vlnou pri lécbe 12 nemocných s choledocholitiázou na Ceskoslovenském zarízení.

Lithotripsy by shock wave was performed in 12 patients with choledocholithiasis using the authors' own apparatus. The shock wave is created by an electric spark and the concentration is made by a rotational semi-elipsoid. The pressures attained in the second focus are 150 MPa. The focusing of the stones and the setting to the site of maximal pressures is made by means of two X-ray projections. Patients were indicated for the procedure when the method of endoscopic extraction had failed. Before the procedure a nasobiliary drain was inserted and after administration of analgesia on average 520 shocks were applicated. During the procedure no complications were observed. Fragmentation was achieved in 11 patients. Spontaneous release of fragments was recorded in five of the patients and in 6 during the check-up ERCP endoscopic extraction was made.

[Treatment of duodenal ulcer with pantoprazole. A multicenter study]. / Lécení dvanáctníkového vredu pantoprazolem. Multicentrická studie.

BACKGROUND: The inhibition of H+/K(+)-ATPase (proton pump) of gastric parietal cells by substituted benzimidazoles represents a new therapeutic approach in conditions connected with hypersecretion of hydrochloric acid. Pantoprazol is the newest member of this group of drugs. Monotherapy of duodenal ulcer with pantoprazole or ranitidine was evaluated in terms of healing rate, tolerance and compliance. METHODS AND RESULTS: A double-blind, parallel-group comparing study (double dummy technique) of treatment florid duodenal ulcer (diameter 5-20 mm) was performed in 95 subjects (age 18-74 years). The active substances were either pantoprazole (40 mg before breakfast-47 subjects) or ranitidine (300 mg before bedtime-48 subjects). The average diameter of the ulcer and subjective complaints before treatment were comparable in both groups. After 2 weeks of pantoprazole therapy 88.5% of ulcers (a) and 87.2% patients (b) were cured, whereas the corresponding values in the ranitidine series amounted to 66% (a) and 62.5% (b) only (p = 0.006 for both (a) and (b)). The rate of healing in relative values of reducing the ulcer size was significantly higher after 2 weeks of pantoprazole therapy (p = 0.026 (a) and 0.0027 (b)). All ulcers healed after 4 weeks of this regimen. The difference between the pantoprazole and ranitidine series after 4 weeks was closely above the 5% level of significance (p = 0.589 for (a) and 0.0588 for (b) respectively). This was due to the low number of patients in both groups at this time interval, particularly in the pantoprazole group. Pain during day-time and regurgitation were observed significantly more frequently after ranitidine therapy. The compliance was very good and practically no adverse effects of pantoprazole therapy were observed. CONCLUSIONS: The healing rate of duodenal ulcer with pantoprazole monotherapy (40 mg before breakfast) was significantly higher than with ranitidine (300 mg before bedtime). The compliance of patients and the tolerance of pantoprazole were very good and its administration was not associated with any side-effects.

[Detection of point mutations on the Ki-ras gene using the PCR technique]. / Detekce bodové mutace na Ki-ras genu PCR technikou.

Present study was undertaken to detect Ki-ras point mutation at codon 12 in pancreatic adenocarcinomas (CaP) using the polymerase chain reaction-restriction fragment lengths polymorphism (PCR-RFLP). Three modifications of PCR-RFLP were performed with a mismatched primers creating a recognition site with only one allelic from (wild or mutated). Using two-step PCR-RFLP and two modifications of one-step PCR-RFLP we examined 5 resected adenocarcinomas of pancreas, 6 pancreatic juices and one DNA sample from peripheral blood of patient with generalized stadium of CaP. We compare all techniques and conclude, that the very sensitive two step PCR-RFLP is a suitable method for detection point mutations and eliminates the need for either oligonucleotide hybridization or DNA sequencing.

[Stenosis of the papilla of Vater--clinical picture and possibilities of therapy]. / Stenóza papily vaterské--klincký obraz a moznosti lécby.

Stenosis of the ampulla of Vater is encountered in as many as 10% of patients with biliary diseases. In general it is classified as tumourous, inflammatory of functional stenosis. In the clinical picture biliary dyspepsia associated with cholestasis predominates. The cause of functional stenosis of the ampulla of Vater is not known. In the development of inflammatory stenosis most frequently iatrogenic damage of the ampulla during revision of the biliary pathways participates or repeated passage of concrements in cholecystolithiasis. Treatment of tumours of the ampulla of Vater is surgical, treatment of inflammatory stenosis is endoscopic by endoscopic papillotomy. In the treatment of functional stenosis a useful drug is hymecromon, as a rule combined with metoclopramide.

[Cathepsin B-like substance in the monitoring of chemically induced primary cholangiocarcinoma in swine]. / Prínos katepsinu B-like v monitorování chemicky indukovaného primárního cholangiokarcinomu vepru.

Activity of beta-glucuronidase (GL), placentar izoenzyme of alkaline phosphatase (PLAP), cathepsin B (CB) and concentrations of carcinoembryonic antigen (CEA) were determined in serums and bile of pigs with experimental cholangiocarcinoma and in control animals. No differences in serum GL, PLAP, CB activities or CEA were observed. The same was found in bile for GL, PLAP and CEA. However, in bile the situation was different for CB. In all the tumour bearing animals we were able to demonstrate in the course of tumour development a stricking progression in CB activity. Very impressive was namely an elevation of CB alkaline-stable form, generated (according also to the chromatographic studies of the bile) from primary cholangiocarcinoma tissue.

[Tumor markers in the diagnosis of tumors in the subhepatic area]. / Nádorové markery v diagnostice nádoru podjaterní krajiny.

Concentrations of CA 19-9, CA 50, CA 195 and DUPAN-2 were followed in serum, bile and pancreatic juice of 65 patients with malignant or benign lesions of CBD and/or pancrease. In sera, significant differences between neoplasias and benign lesions were seen only in patients with tumors in stages III. and IV. In the bile, however, the significant increase of DUPAN-2 and CA 195 were present in all stages of cholangiocarcinoma when compared with benign CBD lesions. In the pancreatic juice, the significant increase on of CA 19-9, CA 50 and DUPAN-2 in patients with pancreatic cancer (stages I-IV) could also be evidenced.

[Detection of the Ki-ras mutation as a specific and sensitive marker of pancreatic carcinoma]. / Prukaz Ki-ras mutace jako specifického a senzitivního markeru karcinomu pankreatu.

The authors describe the procedure used for assessment of a Ki-ras mutation as a specific and sensitive marker of carcinoma of the pancreas. The reliability of the method was tested in five patients with carcinoma of the pancreas.