Management of patient with breast carcinoma diagnosed during pregnancy.

OBJECTIVE: To present actual complex review of diagnosis and treatment of breast cancer during pregnancy, demonstrated on particular case report. DESIGN: Case report and review article. SETTING: University Hospital Královské Vinohrady, Prague Department of Obstetrics and Gynaecology, Department of Radiotherapy and Oncology. CASE REPORT: Patient with breast cancer diagnosed in early pregnancy, her oncological treatment. Circumstantial finding was endometriosis of rectovaginal septum and dehiscence of uterotomy after C-section. DISCUSSION: On this case we demonstrate importance of all early diagnosis, prompt examination management and early therapy onset already during the pregnancy. CONCLUSION: Breast cancer therapy results are equal in pregnant and non-pregnant women, when we compare patients of same age, with same stage and same biological characteristics of tumor. The obstacle during pregnancy is often late diagnosis, which causes bigger size of tumor and more extensive affection of lymphatics in time of therapy onset.

Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors.

PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

NF-κB/p65 expression before and after treatment in rectal cancer patients undergoing neoadjuvant (chemo)radiotherapy and surgery: prognostic marker for disease progression and survival.

Nuclear factor-kappaB (NF-κB), especially p65 subunit, has been associated with origin and progression of cancer as well as with the resistance to radiotherapy and chemotherapy in experimental models. The aim of the present study was to determine expression of NF-κB/p65 in tumor specimens before and after treatment of rectal cancer patients and to evaluate possible relationship between expression of NF-κB/p65 before and after (chemo)radiotherapy, other tumor characteristics and the clinical outcome. Furthermore, NF-κB/p65 was studied in relationship to pathologic response to preoperative (chemo)radiotherapy. Fifty patients with rectal cancer undergoing neoadjuvant (chemo)radiotherapy and surgery were included in the study. Pre-treatment rectal cancer specimens were obtained from diagnostic colonoscopy. Post-treatment rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-κB/p65 expression was determined by immunohistochemistry and analysis was performed both in biopsies and in post-treatment tumor samples. Cytoplasmic positivity in tumor cells and nuclear positivity in lymphocytes were detected. High NF-κB/p65 positivity in pre-treatment tumor samples was significantly associated with shortened overall survival (OS). Disease-free survival (DFS) tends to be shortened as well. In post-treatment tumor samples, high NF-κB/p65 positivity was neither associated with shortened OS nor with shortened DFS. In post-treatment samples residual tumor cells deeply infiltrating the wall of the rectum with high NF-κB/p65 expression were found. The cells were linked to significantly worse clinical outcome in terms of shortened OS and DFS. NF-κB/p65 positivity did not correlate with pathologic response to preoperative (chemo)radiotherapy. In conclusion, our data suggest that high level of NF-κB/p65 subunit may be associated with more aggressive features of the tumor, higher metastatic potential, and shortened overall survival, but it does not correlate with resistance to (chemo)radiotherapy. Consequently, the level of NF-κB/p65 may help to select those patients who have poor prognosis and are candidates for more intensive anticancer therapy. For these purposes both pre-treatment and post-treatment tumor samples may be used.

[Position of targeted therapy in ovarian cancer management]. / Postavení cílené lécby v managementu ovariálního karcinomu.

Ovarian cancer in Czech Republic takes first place in mortality among gynecological malignant tumours. In most cases it is diagnosed in advanced stages. Initial treatment is based on combination of radical surgery and adjuvant chemotherapy. In more than two thirds of cases ovarian cancer relapses sooner or later, very often without a chance to cure the patient. Unsatisfying result of standard treatment is reason of looking for more effective procedures. Targeted therapy is subject of research in last years. Positive effect of bevacizumab has been proved. Through inhibition of angiogenesis it leads to prolonging of interval to cancer progression.

[Risk factors for recurrent disease in borderline ovarian tumors]. / Rizikové faktory pro vznik recidivy u borderline nádoru ovaria.

OBJECTIVE: To evaluate risk factors for development of recurrent disease in borderline ovarian tumors. DESIGN: Retrospective study of 10-years single institution population. SETTING: Dept. of Gynecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague. METHOD: 59 consecutive cases of borderline ovarian tumors (BOT) were analyzed for age, histopathological type, DNA ploidy, stage, presence of invasive and non-invasive peritoneal implants, type of surgical procedure, residual disease, adjuvant therapy, recurrence and long-time prognosis of the patients. RESULTS: Median follow-up was 47 months (range 1-144). There were 5 (8.5%) patients with DNA aneuploid tumors in the study group; 4 of them were younger than 50 years, 4 of them were early stage serous BOT; no one recur so far. No death of disease was described in the whole study group; only 2 patients (3.4%) developed recurrent disease - both were young patients after conservative surgery for serous diploid stage I/II BOT. Conservative surgery was the only significant factor for recurrence in univariate analysis (p = 0.0159) in our setting. CONCLUSION: DNA ploidy was not proved to be prognostic factor in borderline ovarian tumors in our study group. The only significant risk factor for development of recurrent disease was conservative surgery, with no influence on overall survival.

[Guideline for treatment of gynaecological malignant tumours 2010---endometrial carcinoma]. / Guideline gynekologických zhoubných nádoru 2010. Primární chirurgická lécba zhoubných nádoru endometria.

OBJECTIVE: To develop guideline for primary surgical treatment of endometrial carcinoma. DESIGN: Review, consensus of expert group. SETTING: Dept. of Gynaecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague. METHOD: A retrospective review of published data, analysis of statistic data from Czech Republic, consensus among proposers and opponents. RESULTS: The guideline recognizes endometrial carcinoma patients based on their risk and recommends type of surgical treatment for certain group. It emphasizes the importance of centralized oncogynaecological treatment. Surgical staging remains the basic principle for treatment of endometrial carcinoma patients. The aim of pre-operative diagnostics is to estimate the extent of the disease--"interim staging", that can be different from definitive histopathological staging. Based on risk factors patients are divided into low or high risk group. Standard procedure for low risk patients is hysterectomy and bilateral salpingoophorectomy. It is advisable to use peroperative biopsy in these patients that can shift the patient to high risk group. High risk patients are recommended for hysterectomy, bilateral salpingoophorectomy, and systematic aortopelvic lymphadenectomy. The guideline contains recommendation for young patients wishing to preserve their fertility, for cases of inadequate surgery and for follow-up. CONCLUSION: Guideline for treatment of endometrial carcinoma is recommendation for clinicians and other subjects who participate on the process of the diagnostics/treatment of endometrial carcinoma patients. All points of the guideline were discussed and voted about by all participants of expert group.

Preoperative radiotherapy of rectal cancer--influence of fractionation and dose.

BACKGROUNDS/AIMS: We have been focused on patients with preoperative irradiation and compared two modes of radiotherapy, short-term (15 days) and long-term (45 days). METHODOLOGY: Monitored group of 183 patients who had undergone a preoperative irradiation between 01/01/1998 and 12/31/2002 were irradiated in two modes: with a dose of 45Gy applied in 25 fractions/1.8Gy per fraction (CFD45) and a dose of 34.5Gy in 15 fractions/2.3Gy per fraction (CFD34.5). RESULTS: No statistically significant difference in the occurrence of acute and postoperative complications, of locoregional recurrences and secondary dissemination, was mentioned in either group. In patients irradiated with CFD34.5 amputation of the rectum followed in 55%, and unlike the group irradiated with CFD45 the percentage of amputations was significantly lower (42%). We have recorded the average 5-year overall survival (OS) in those irradiated with CFD4.5 in 54% versus 61% in those irradiated with CFD45. More considerable conclusion was made comparing a 5-year disease-specific survival (DSS) versus the mode of irradiation, CFD34.5 57%, versus CFD45 71%. The significance level reached 10% (p = 0.057). CONCLUSIONS: Pre-operative irradiation of the rectal cancer with the dose of 45Gy in 25 fractions/dose of 1.8Gy per fraction is a standard recommended procedure.

[IKARUS Project--incidence of bone events in breast cancer: retrospective analysis of patients in oncological centres in the Czech Republic and Slovakia]. / Projekt IKARUS--zjistení incidence kostních príhod u karcinomu prsu: retrospektivní analýza nemocných dispenzarizovaných v onkologických centrech Ceské a Slovenské republiky.

BACKGROUND: Bone incidents today represent, in terms of frequency and the overall effect on the quality of life of patients with breast cancer, a serious health problem. In a number of clinical studies bisphosphonates have been shown to have a positive impact on reducing the risk of bone events and therefore to be effective in the prevention of bone events. The primary objective of this project was to identify the incidence of bone events in patients with metastatic breast cancer treated in the Czech and Slovak Republics. SUBJECTS: Retrospective, multi-centre, non-interventional, epidemiological and explorative studies to identify the incidence of bone events in the defined group of patients and a description of the practice of prevention and treatment of skeletal events in the years 2000-2005. Enrolled were patients with advanced metastatic breast cancer diagnosed in 2000. METHODS AND RESULTS: Analysis of overall survival and survival to disease progression, analysis of patterns of treatment of bone events and the practice of the use of bisphosphonates in the prevention of bone events in metastatic skeleton affection in the normal conditions of clinical practice, analysis of patient compliance in the treatment with bisphosphonates, analysis of the time interval between the occurrence of bone metastases and the occurrence of bone events and, last but not least, survival analysis of patients in relation to bone events. CONCLUSION: This work has shown that the practice of treatment with bisphosphonates since 2000 and assessed the survival of patients with metastatic breast cancer.

Expression of class III beta-tubulin in colorectal carcinomas: an immunohistochemical study using TU-20 & TuJ-1 antibody.

BACKGROUND & OBJECTIVE: Expression of class III beta-tubulin represents newly discovered marker of resistance to taxol-based chemotherapy in a wide spectra of carcinomas. However, very little is known about its expression in colorectal carcinomas. This study was done to determine class III beta-tubulin expression in a large series of colonic carcinomas, covering tumours with different degree of differentiation in order to evaluate its prospective significance in resistance to taxol-based chemotherapeutics and to compare the immunostaining profile of two widely used monoclonal antibodies, TU-20 and TuJ-1 METHODS: Sixty patients with colorectal carcinoma were enrolled; all of them were treated surgically by the resection. Twenty tumours were histologically assessed as G1, 20 as G2 and 20 as G3. Routine immunohistochemical procedure using TU-20 and TuJ-1 mouse monoclonal antibodies was applied to all 60 specimen and slides were evaluated using an optical microscope. RESULTS: Expression of class III beta-tubulin was detected in 14 tumours (23.3%), while remaining tumours were negative. Relatively higher frequency of class III beta-tubulin expression was observed in G3 tumours (10 cases) in comparison with G1 (3 cases) and G2 (1 case), respectively. Seven tumours displayed positive immunostaining with both tested antibodies TU-20 and TuJ-1. Six tumours showed expression of class III beta- tubulin in more than 1 per cent of neoplastic cell population. In remaining 8 tumours only individual scattered neoplastic cells exhibited class III beta-tubulin expression either with TU-20, or with TuJ-1 antibody. INTERPRETATION & CONCLUSION: Higher frequency of immunoreactivity was observed in poorly differentiated tumours. However, more than 90 per cent of neoplastic cell population did not express class III beta-tubulin in almost all tumours. These negative cells of colonic cancer could represent the potential target for taxane-based chemotherapy in the future. Our results indicate that TU-20 and TuJ-1 antibodies exhibit very similar immunoreactivity in neoplastic tissue.

Transrectal stent in endoscopic palliative therapy of malignant stenosis of the rectum.

BACKGROUND/AIMS: To check the feasibility and safety of endoscopic stent introduction in colorectal cancer therapy. METHODOLOGY: A total of 62 patients with inoperable tumors of the rectum and rectosigmoid were treated by introducing stents. Stents were also introduced in 3 patients with advanced prostate tumors obturating (narrowing) the rectum. In 3 cases, the stents were introduced under X-ray control. In all other cases, an endoscopic approach to the stent introduction was employed. RESULTS: Stents could not be introduced in 4 patients. In 1 case, the bowel was perforated above the malignant (tumorous) stenosis. In 4 patients, it was necessary to remove the stents because of dislocation. Growth of the tumor into the stent was not experienced. Experience with acute obstruction treatment was minimal as only two patients were treated for this indication. CONCLUSIONS: Endoscopic stent introduction is a safe palliative procedure making it possible to improve the quality of life of patients with inoperable tumors of the rectum and rectosigmoid.

Changes in small intestine permeability after radiotherapy of malignant tumor.

BACKGROUND/AIMS: Radiotherapy of the malignancy in the small pelvis causes different adverse events in normal tissues. The small intestine is the most sensitive organ in this region. Its wall performs the barrier function between internal and external environments. The damage to the intestinal barrier brings increase in the intestinal permeability. The aim of this study was to find out dependency of intestinal permeability disorder on certain factors such as age, radiation dose, target volume, dose per fraction, added chemotherapy etc. METHODOLOGY: We evaluated the intestinal permeability by the LAMA (lactulose-mannitol) test in a group of 31 patients with a diagnosis of malignant gynecological tumor (24), rectal cancer (6) and prostate cancer (1) who underwent radiotherapy of the small pelvis with doses of at lest 45.0Gy. Fourteen patients underwent adjuvant radiotherapy, and 17 patients underwent a primary radical radiotherapy. In the latter group there was a tumor at the time of radiotherapy. The measurement was performed 3x (before starting radiotherapy, after its completion, and 6 months after completion). Complications after radiotherapy were assessed according to RTOG classification. LAMA test resultswere statistically worked out. RESULTS: Early complications G1, G2 were observed in 22 patients, late complications G1 in 3 patients. No dependency has been proved between grade of complications and intestine permeability changes. No evidence has been found in dependency on the patients' age, target volume, added chemotherapy, size of fraction, energy of radiation or other factors either. Connection of intestine permeability changes and total dose was on the margin of statistical significance; the only statistically significant relation was between intestinal permeability change and presence of tumor in the organism which was very surprising and cannot yet be explained. CONCLUSIONS: More patients should be involved in the study and late postirradiation changes should be assessed at a longer time interval.

Human papillomavirus infection and tumours of the anal canal: correlation of histology, PCR detection in paraffin sections and serology.

Human papillomavirus infection is an important etiological factor in squamous cell carcinoma of the anus (SCCA). Different histological variants of anal carcinomas displaying squamous differentiation, previously classified as separate tumours, were recently reclassified as SCCA by the WHO. In our recent study the presence of HPV was detected by PCR in biopsy specimens of 42 different anal tumours, including SCCA and its histological variants (n=22), adenocarcinomas (n=5), tubulovillous adenomas (n=5) and anal condylomas (n=10). HR HPV16 (high risk - HR) was detected in 18 of SCCA specimens (81.8%). All histological variants, i.e. tumours with basaloid, squamous and mixed histological patterns, were represented among the HPV-positive cancers. Four tumours (18.2%) were HPV negative. Low-risk (LR) HPV types were not detected within the SCCA group. HPV16 was identified in one adenocarcinoma, while four cases were HPV negative. Two adenomas showed presence of HPV16; one showed simultaneous positivity for HPV33. The remaining three tumours were HPV negative. Seven anal condylomas (70%) were LR HPV 6 and/or 11 positive, while three were HPV negative. The presence of HR HPV types was not observed in anal condylomas. Our results provide further evidence in support of the etiological role of HR HPV infection in the development of SCCA regardless of its histological appearance.

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.

[The quality of documentation in patients after conservative surgical procedures in breast carcinoma and its effect on subsequent therapy]. / Kvalita dokumentace u pacientek po konzervativních chirurgických výkonech pro karcinom mlécné zlázy a její vliv na následnou lécbu.

The quality of data was evaluated in 50 patients referred for adjuvant treatment to the Department of Radiotherapy and Oncology, University Hospital "Královské Vinohrady" after conservative surgery for breast cancer. The authors suggest improving the cooperation between surgeon and radiation oncologist. The purpose of this study is to establish the criteria for conservative surgery of breast carcinoma and to evaluate, if the data provided by surgery and pathology departments are sufficient for radiation oncologist to complete high quality postoperative radiotherapy.