Konstantinas Povilas Valuckas

The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone

BackgroundThe aim of our study was to investigate and evaluate the prognostic value of and correlations between preclinical and clinical factors such as the stage of the disease, blood Hb level before treatment, size of cervix and lymph nodes evaluated by CT, age, dose of irradiation and duration of radiotherapy related to overall survival, disease-free survival, local control and metastases-free survival in cervical cancer patients receiving radiotherapy alone.Methods162 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIA-IIIB cervical carcinoma treated with irradiation were analysed. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors.ResultsThe Hb level before treatment showed significant influence on overall survival (p = 0.001), desease free survival (p = 0.040) and local control (p = 0.038). The lymph node status (>10 mm) assessed on CT had impact on overall survival (p = 0,030) and local control (p = 0,036). The dose at point A had impact on disease free survival (p = 0,028) and local control (p = 0,021) and the radiotherapy duration had showed significant influence on overall survival (p = 0,045), disease free survival (p = 0,006) and local control (p = 0,033).ConclusionAnemia is a significant and independent prognostic factor of overall survival, disease-free survival and local control in cervical cancer patients treated with irradiation. The size of lymph nodes in CT is an independent prognostic factor for overall survival and local control in cervical cancer patients. The size of cervix uteri evaluated by CT has no prognostic significance in cervical cancer patients treated with radiotherapy. The prognostic value of FIGO stage of cervical cancer is influenced by other factors, analyzed in this study and is not an independent prognostic factor.

Human papillomavirus infection in pregnant women.

IntroductionHuman papillomavirus (HPV) is the most common sexually transmitted infection in the world. It has been established that about 70% of the sexually active population are exposed to this infection. The HPV prevalence rate among pregnant women ranges from 5.5 to 65.0%. Studies on HPV infection in pregnant women have yielded inconsistent results, including HPV prevalence, and HPV clearance.AimOur aim is to determine the prevalence of HPV infection in pregnant women, to identify the types of the virus, and to evaluate the changes of prevalence of HPV infection depending on the trimester of pregnancy in Lithuania.MethodsTwo hundred and thirteen pregnant women who were attending centres of the central outpatient clinic of Vilnius city (Lithuania) in 2008–2010 were studied. These women were examined for HPV infection and its type by polymerase chain reaction. Tests were performed on the first and third trimesters. The statistical analysis was done using SPSS17 and Excel software.ResultsAt the beginning of the pregnancy (first trimester of pregnancy), HPV infection was detected in 17.8% of the pregnant women (38 from 213); high oncogenic risk HPV types were identified for 52.6% of the HPV-positive pregnant women. At the end of the pregnancy (third trimester of pregnancy), HPV was identified in 10.3% of the pregnant women (15 out of 146); high-risk HPV types were identified for 66.7%.ConclusionOur study shows the high prevalence of HPV infection in pregnant women in Lithuania. The majority of pregnant women’s HPV infection was cleared during the pregnancy. Only in a few cases a new HPV infection was detected.

Occupational exposure of medical radiation workers in Lithuania, 1950-2003.

This study presents the summary of historical exposures, measurement practice and evolution of the recording of the individual doses of medical radiation workers during 1950-2003 in Lithuania. The aim of this study is to present occupational exposure of medical radiation workers in Lithuania since the earliest appearance period. Data from publications have been used for the earliest two periods prior to 1969; data from the archives of the largest hospitals, for the period 1970-1990 and data from Lithuanian Subdivision of Individual Dosimetry of Radiation Protection Center, for the period 1991-2003. The analysis of the data obtained from personal records allows to conclude that the average annual effective dose of Lithuanian medical radiation workers was greatly reduced in radiology, radiotherapy and nuclear medicine in all occupational categories from 1950 to 2003. During the last period 1991-2003 extremity doses clearly decreased and after 1994 were no longer present in Lithuania.

Second primary malignancies after radiotherapy including HDR 252Cf brachytherapy for cervical cancer

PURPOSE Second primary malignancies (SPMs) are among the most serious late adverse effects after radiotherapy experienced over time by the increasing population of cancer survivors worldwide. The study aim was to determine the rate and distribution of SPMs for neutron- and photon-emitting brachytherapy (BT) sources for patients treated for cervical cancer. METHODS AND MATERIALS The cohort comprised 662 patients with invasive cervical cancer (Stages IIB and IIIB) and contributed 5,224 patient-years (PY) of observation. These patients were treated by radiotherapy during the 1989-1999 year period with cobalt-60 source ((60)Co) teletherapy. The first group of patients (N = 375; 3,154 PY) received high-dose-rate (HDR) californium-252 source ((252)Cf) BT, whereas the second group (N = 287; 2,070 PY) received HDR (60)Co BT. RESULTS Over a 25-year period, 35 SPMs were observed, amounting to 5.3% of all observed patients: in 16 (2.4%) heavily, 2 (0.3%) moderately, 14 (2.1%) lightly irradiated body sites, and 3 (0.5%) other sites. Of these, 21 cases (5.6%) were observed in the HDR (252)Cf BT group, whereas 14 cases (4.9%) were observed in the HDR (60)Co BT group. Exposures received during (60)Co teletherapy and HDR BT with either (252)Cf or (60)Co had statistically equivalent (p = 0.68) effects on SPM development. CONCLUSIONS Cure rates are improving, and therefore, there are more long-term survivors from cervical cancer. This study shows no significant difference in rates or distribution of SPMs in women treated with neutron BT compared with photon BT (p = 0.68). After reviewing related literature and our research results, it is evident that a detailed investigation of SPM frequency, localization, and dose to adjacent organs is a suitable topic for further research.

The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer

BACKGROUND AND OBJECTIVE To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB-IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment. MATERIALS AND METHODS According to the prospective phase II study protocol, 36 patients with stage IIB-IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation. RESULTS A statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST concentrations in terms of the progression of the disease and disease without progression. CONCLUSIONS The results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed.

Treatment of hemorrhagic radiation-induced proctopathy with a 4% formalin application under perianal anesthetic infiltration.

AIM To evaluate the results of hemorrhagic radiation proctopathy treatment with a 4% formalin application. METHODS A prospective study was performed. Over a three-year period, 38 patients underwent 4% formalin application under perianal anesthetic infiltration for hemorrhagic radiation proctopathy. All patients included in the study were irradiated for prostate cancer. The patients ranged in age from 56-77 years (average 70 ± 5 years). All of the patients were referred for formalin therapy after noninvasive management had failed. Twenty-four (63.2%) patients underwent a single application, 10 (26.3%) patients underwent 2 applications, and 4 (10.5%) patients underwent 3 applications. RESULTS Two to 36 mo (average 12 ± 3 mo) following treatment, 34 patients were interviewed (four were lost to follow-up). Twenty (58.8%) subjects reported complete cure, 8 (23.5%) subjects reported significant improvement, and 6 (17.7%) subjects reported no change. One patient (who underwent a colostomy at a regional hospital with no specialized services available for previous bleeding episodes from radiation proctopathy) was cured, and the colostomy was closed. One patient (2.6%) developed rectal mucosal damage after the second application. CONCLUSION A 4-min application of 4% formalin for hemorrhagic radiation-induced proctopathy under perianal anesthetic infiltration in patients who have received external radial radiation therapy for prostate cancer is simple, reasonably safe, inexpensive, generally well tolerated, and effective.

Californium versus cobalt brachytherapy combined with external-beam radiotherapy for IIB stage cervical cancer: long-term experience of a single institute.

Purpose The purpose of this paper was to observe and compare long-term curative effects and complications of FIGO stage IIB cervical cancer patients (n = 232) treated with high-dose-rate (HDR) californium (252Cf) neutron or cobalt (60Co) photon intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT). Material and methods The EBRT dose to the small pelvis was 50 Gy in both groups. The brachytherapy component of 252Cf or 60Co was added in the 3rd week of EBRT, 5 fractions were performed once per week resulting in a total ICBT dose of 40 Gy/Gyeq (point A). Results Overall survival (OS) at 5, 10 and 15 years was 63.6%, 50.4% and 38.8% in the 252Cf group and 62.2%, 50.5%, 39.9%, in the 60Co group, respectively (p = 0.74). The percentage of tumour recurrence was statistically significantly lower in the 252Cf group with 7.4% versus 17.1% in the 60Co group (p = 0.02). Second primary cancers have developed similarly 9.1% and 8.1% cases for 252Cf and 60Co groups, respectively. Conclusions Our long-term retrospective study comparing 252Cf and 60Co isotopes with brachytherapy in combined treatment of FIGO IIB stage cervix carcinoma patients shows, that overall survival in the both groups are similar. However, the recurrence of tumour was significantly lower in the 252Cf group. The incidence of second primary cancers was similar in both groups.

Endometrial cancer and microsatellite instability status

Abstract Microsatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods: MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions: One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

Laser, gamma irradiation, and chemotherapy in treatment of experimental tumors sensitized by porphyrins

The new hematoporphyrin derivatives--HpD-1 and dimethoxyhematoporphyrin--DMHp were studied. Their physico-chemical properties, activity in tumor PDT and influence on therapeutic effect of tumor radiation therapy and on toxicity of chemotherapeutic agents were investigated. Hematoporphyrin--Hp was used as control. Data, obtained by absorption spectroscopy, indicated that HpD-1 and DMHp strongly aggregates in aqueous solution and HpD-1 has many covalently bound structures. HpD-1 and DMHp effects in tumor PDT and radiation therapy were studied using 8 species of transplantable tumors. The sensitizers were injected to the animals intraperitoneally in a dosage of 5 - 20 mg/kg. In 48-76 hours after sensitizers were injected, the tumors were irradiated by the pulsed Raman laser pumped by the SHG of YAG:Nd3+ laser. The parameters of this laser system are as follows: the wavelength 630 nm, the pulse duration (tau) equals 1 ns, energy E equals 10 mJ, the repetition rate f equals 10 Hz, average power P equals 100 mW. The goal of our investigation was to attempt to optimize tumor radiation therapy and chemotherapy.

Chemoradiotherapy in the treatment of locally advanced cervical cancer

The purpose of this article is overview of currently available knowledge found in literature about the chemoradiation for locally advanced cervical cancer. Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide. Despite the available prevention and early detection strategies, carcinoma of the uterine cervix is still diagnosed as locally advanced disease in a considerable proportion of patients. Standart treatment of locally advanced cervical cancer is cisplatin-based chemoradiation. Unfortunately, results of the treatment are not sufficient and cancer relapses are frequent. New cytostatics regimens either alone or in combination with cisplatin are searching as radiosensitizers with concurrent radiotherapy. Neoadjuvant/induction chemotherapy, adjuvant/consolidation chemotherapy strategies, molecular agents targeting critical pathways are under investigation in clinical trials to improve results of the treatment. The purpose of this article is overview of currently available knowledge found in literature about the chemoradiation for locally advanced cervical cancer. Key words: locally advanced cervical cancer, chemoradiation, adjuvant/consolidation chemotherapy, neoadjuvant/induction chemotherapy. Chemospindulinis vietiskai isplitusio gimdos kaklelio vėžio gydymas Straipsnio tikslas – apžvelgti ir pateikti siuo metu prieinamoje literatūroje sukauptas žinias apie konservatyvų chemospindulinį vietiskai isplitusio gimdos kaklelio vėžio gydymą. Gimdos kaklelio vėžys yra trecia dažniausiai pasaulyje nustatoma moterų vėžio forma ir ketvirta pagal dažnį moterų mirties nuo vėžio priežastis. Nepaisant profilaktikos priemonių bei patikros programos, nemaža dalis gimdos kaklelio vėžio atvejų nustatoma jau vietiskai isplitusios IIB–IVA stadijos. Siuo metu vietiskai isplitusio gimdos kaklelio vėžio gydymo standartas – suderintas chemospindulinis gydymas cisplatinos pagrindu. Deja, gydymo rezultatai nėra patenkinami, atkrycio dažnis islieka didelis. Siekiant geresnių gydymo rezultatų atlikta ir atliekama daug klinikinių tyrimų, spindulinio gydymo metu taikant naujus citostatikus ar jų derinius su cisplatina, tiriama neoadjuvantinės/indukcinės bei adjuvantinės/konsoliduojancios chemoterapijos reiksmė, „taikinių“ terapijos panaudojimo galimybė. Reiksminiai žodžiai: vietiskai isplites gimdos kaklelio vėžys, chemospindulinis gydymas, adjuvantinė/konsoliduojanti chemoterapija, neoadjuvantinė/indukcinė chemoterapija.