Chemoradiotherapy in the treatment of cervical cancer - a single institution retrospective review.

BACKGROUND: The aim of this study is a retrospective analysis of treatment outcomes and toxicity in a group of patients with cervical cancer who underwent (chemo) radiotherapy at the Institute of Radiation Oncology in Bulovka University Hospital in Prague in the period 2014-2017. PATIENTS AND METHODS: During this period, 141 patients were treated, 105 (74.5%) of them underwent combined (chemo) radiotherapy with radical intent and palliative radiotherapy was performed in 36 (25.5%) cases. According to the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification, the most numerous stages were IIB in 39 (27.7%) and IIIB in 64 (45.4%) cases; according to FIGO 2018, a significant number of newly established stages is evident: IIIC1 in 55 (39.0%) patients and IIIC2 in 22 (15.6%) cases. RESULTS: The median progression-free survival (PFS) and overall survival (OS) reached 31.3, resp. 40.1 months in the whole group. In the subgroup of patients treated with radical intent, the median PFS was 44.0 months and OS 48.8 months; in the palliative subgroup, the median PFS was 9.4 months and OS 14.8 months. In a radically treated subgroup, 7 (6.7%) patients had gastrointestinal or genitourinary manifestations of G3-4 toxicity, and overall acute toxicity (including skin and haematological reactions) of G3-4 occurred in 18 (17.1%) patients. Late toxicity of G3-4 was reported in 13 (12.4%) cases. Patients who underwent complete brachytherapy (BRT) showed significantly better survival compared to patients with a lower number of BRT fractions. The prognostic potential of PS (performance status) and anemia was confirmed; significantly longer overall survival was observed in patients in good general condition or in those without anemia. CONCLUSION: Our results confirmed the key role of BRT for the delivery of the curative dose to the target volume. The prognostic role of PS and anemia is evident. The side effects were in acceptable limits but we expect improvements because of the use of modern radiotherapy technologies.

A Large Adnexal Tumor Caused by Enterobius Vermicularis Mimicking Malignancy.

Enterobius vermicularis usually causes trivial infections in the juvenile population. However, its extragenital presentation in adults is relatively rare. We present the case of a 64-year-old female suffering from poorly controlled diabetes and lower abdominal pain. CT scan showed a large tumorous expansion of the lower abdomen, mimicking malignancy. Perioperative findings revealed a large adnexal tumor adhering to the rectum. In addition, the histological examination uncovered a mixed inflammatory infiltrate with multiple surrounding eggs of the parasite and granulomatous reaction in the left fallopian tube and left ovarian cortex. As reported in our article, the rare ectopic sites of Enterobius vermicularis in postmenopause may become a diagnostic challenge.

Preoperative staging of ovarian cancer: comparison between ultrasound, CT and whole-body diffusion-weighted MRI (ISAAC study).

OBJECTIVES: To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer. METHODS: Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation). RESULTS: Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease > 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively). CONCLUSIONS: This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The changes in FIGO staging for carcinoma of the cervix uteri.

INTRODUCTION: The carcinoma of the cervix uteri is the fourth most common cancer in women worldwide and more than 85% of these cases occur in developing countries. Altogether 822 new cases were found in the Czech Republic during 2016 which means the incidence 15,3 new diseases/100,000 women. OBJECTIVE: To provide an overview of changes in FIGO (International Federation of Gynecology and Obstetrics) staging for carcinoma of the cervix uteri with an incorporation of possible imaging methods and/or pathological findings, and clinical assessment of tumor size and extent. SETTINGS: Gynecologic Oncology Center, Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague; Institute of Radiation Oncology, Hospital Na Bulovce, Prague. METHODS: For this review, we have used the results of studies, review articles, and guidelines of oncogynecologic organisations on the cervical cancer published in English. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords. We summarize the new classification, main changes compared to the former one and their clinical impact. CONCLUSION: Lateral extension measurement is removed in the stage IA, the only criterion is the measured deepest invasion.

Current FIGO Staging for Carcinoma of the Cervix Uteri and Treatment of Particular Stages.

BACKGROUND: Here, we present a review of the revised FIGO (International Federation of Gynecology and Obstetrics) staging system for carcinoma of the cervix uteri, explaining the reasons for the changes and summarizing suitable diagnostic methods and treatment options for particular stages of disease according to current guidelines. AIM: The FIGO staging system has been revised as follows. Measurement of lateral extension has been removed from stage IA; the only criterion is a measurement for the deepest invasion of < 5.0 mm. Stage IB has been divided into three subgroups: IB1, tumors with a largest diameter measuring 5 mm and < 2 cm; IB2, tumors measuring 2-4 cm; IB3, tumors measuring 4 cm. Stage IIIC includes an assessment of retroperitoneal lymph nodes: IIIC1 if only pelvic lymph nodes are involved, and IIIC2 if para-aortic nodes are infiltrated. The revised staging system does not mandate the use of a specific imaging method or surgical assessment of the extent of the tumor. The method used to assign a stage should be recorded and reported. The European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology, and the European Society of Pathology have developed clinically relevant and evidence-based guidelines to improve the quality of care for women with cervical cancer. These guidelines cover comprehensive staging, management, and follow-up for patients with cervical cancer. The guidelines are intended for use by gynaecologic oncologists, general gynaecologists, surgeons, radiation oncologists, pathologists, clinical oncologists, radiologists, general practitioners, palliative care experts, and other health professionals. CONCLUSION: We summarize the new FIGO classification system, including diagnostic methods and treatments for particular stages. We also discuss the main changes and their clinical impact. This work was supported by the Charles University project UNCE 204065. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

[The relationship between cervicovaginal and oral HPV infection]. / Vztah mezi cervikovaginální a orální HPV infekcí.

OBJECTIVE: To summarize current knowledge of the relationship of genital and oral HPV infection in women. DESIGN: Review article. SETTING: Gynecologic Oncology Center, Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague; ENT Department, Hospital Na Bulovce, Prague. METHODS AND RESULTS: The infection of human papillomavirus (HPV) is strongly associated with the development of anogenital cancers and of a subset of head and neck squamous cell cancers, yet a quite little is known about the interrelationship between oral and cervicovaginal HPV infections. A key issue in oral HPV infection is whether it can be brought about a genital HPV infection, through sexual or other contact and by autoinoculation, or whether it can be considered a fully independent event. Pertinent to this issue is the frequency of oral HPV infection in women with a cervical HPV infection. Some studies show that females with genital HPV infection are at higher risk for oral infection and HPV genotype-concordance with genital infection are more prevalent than could be expected by chance. However, more data are needed to better understand the natural history of HPV infection at each anatomic site. CONCLUSION: The relationship of oral to cervicovaginal HPV infection remains unclear. Nevertheless, published data suggest that HPV infections at these two sites are not entirely independent, although genotype-specific concordance is low.

SLN biopsy in cervical cancer patients with tumors larger than 2cm and 4cm.

OBJECTIVES: The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients. METHODS: Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma. RESULTS: The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors<2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510). CONCLUSIONS: If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors<2cm, 2-3.9cm, and ≥4cm.

Pelvic actinomycosis and IUD.

OBJECTIVE: To summarize knowledge about the mana-gement in women with proven actinomyces in uterine cervix and inserted intrauterine device (IUD). DESIGN: An overall review. RESULTS: Actinomycosis is an uncommon but important subacute or chronic infection caused by anaerobic or microaerophilic bacteria, mainly within the Actinomyces genus. Actinomycosis can affect various organs and tissues in the human body, often manifesting draining sinuses, abscess formation and fibrosis. The pelvic form in women is the most common in the developed countries. Long-duration treatment with antibiotics can be completely effective even in cases of heavy disease. Although pelvic actinomycosis is predominantly associated with the longstanding use of intrauterine device, the risk of future symptomatic infection is extremly low even in women with a cervical Pap smear positive for actinomyces-like organisms (ALO). Therefore the identification of actinomycetes by cytology after cervical Pap smears is not diagnostic nor predictive of any disease because the actinomycetes normally reside in the female genital tract. In the absence of symptoms, patients with ALO on a Pap test do not need antimicrobial treatment or IUD removal. Nevertheless, women choosing an IUD for contraception should know that there is very low risk of developing the infection in later years after insertion. CONCLUSION: The sources of literature conclude that removal of the intrauterine device in a patients with a positive ALO in the uterine cervix is not necessary and antibiotics treatment is not required. However, IUD must be changed at least every five years in order to limit the risk of the development of pelvic actinomycosis.

Pelvic floor reconstruction by modified rectus abdominis myoperitoneal (MRAM) flap after pelvic exenterations.

OBJECTIVE: To describe the technique and report experiences with pelvic floor reconstruction by modified rectus abdominis myoperitoneal (MRAM) flap after extensive pelvic procedures. METHODS: Surgical technique of MRAM harvest and transposition is carefully described. The patients in whom pelvic floor reconstruction with MRAM after either infralevator pelvic exenteration and/or extended lateral pelvic sidewall excision was carried out were enrolled into the study (MRAM group, n=16). Surgical data, post-operative morbidity, and disease status were retrospectively assessed. The results were compared with a historical cohort of patients, in whom an exenterative procedure without pelvic floor reconstruction was performed at the same institution (control group, n=24). RESULTS: Both groups were balanced in age, BMI, tumor types, and previous treatment. Substantially less patients from the MRAM group required reoperation within 60days of the surgery (25% vs. 50%) which was due to much lower rate of complications potentially related to empty pelvis syndrome (1 vs. 7 reoperations) (p=0.114). Late post-operative complication rate was substantially lower in the MRAM group (any grade: 79% vs. 44%; grade≥3: 37% vs. 6%) (p=0.041). The performance status 6months after the surgery was ≤1 in the majority of patients in MRAM (81%) while in only 38% of patients from the control group (p=0.027). There was one incisional hernia in MRAM group while three cases were reported in the controls. CONCLUSIONS: Pelvic floor reconstruction by MRAM in patients after pelvic exenterative procedures is associated with a substantial decrease in postoperative complications that are potentially related to empty pelvis syndrome.

Ultrasound in preoperative assessment of pelvic and abdominal spread in patients with ovarian cancer: a prospective study.

OBJECTIVE: To analyze the accuracy of ultrasound in assessing pelvic and intra-abdominal spread in patients with ovarian cancer. METHODS: This prospective study enrolled all consecutive patients referred to a single gynecological oncology center for suspected ovarian cancer. We analyzed only data from patients with histologically confirmed primary ovarian cancer who were evaluated following predefined preoperative ultrasound, intraoperative and pathology protocols. We evaluated the agreement of depth of infiltration of the rectosigmoid wall, tumor spread in different peritoneal compartments and presence of metastatic retroperitoneal and inguinal lymph nodes, as determined at ultrasound, with intraoperative and histopathological findings. RESULTS: In total, 578 patients were enrolled between March 2008 and January 2013, of whom 394 met the study inclusion criteria and were analyzed; 74% of these suffered from advanced-stage cancer. Our results showed excellent agreement between ultrasound and histology in assessment of rectosigmoid wall infiltration (kappa value, 0.812; area under the receiver-operating characteristics curve, 0.898). The overall accuracy in evaluating different peritoneal compartments, retroperitoneal and inguinal lymph nodes and depth of rectosigmoid wall infiltration was 85.3%, 84.8%, 99.7% and 91.1%, respectively. Ultrasound showed high sensitivity only in the assessment of rectosigmoid wall infiltration (83.1%), peritoneal spread into the pelvis (81.4%) and omentum (67.3%), and inguinal metastatic lymph nodes (100%). The specificity of ultrasound in detection of all evaluated parameters was > 90%. CONCLUSION: This is the largest imaging study to date on ovarian cancer staging. Ultrasound can be used as the method of choice to plan rectosigmoid wall resection and dissection of infiltrated inguinal lymph nodes. In assessing different peritoneal and retroperitoneal compartments, ultrasound was accurate and highly specific. However, similar to other modern imaging techniques, it had relatively low sensitivity, further supporting the role of comprehensive surgical staging. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of ultrasound in prediction of rectosigmoid infiltration in epithelial ovarian cancer.

OBJECTIVE: To examine prospectively the accuracy of ultrasound in predicting rectosigmoid tumor infiltration in patients with epithelial ovarian cancer. METHODS: Patients referred for a suspicious pelvic mass between 2012 and 2014 were examined by ultrasound following the standard protocol for assessment of tumor infiltration. Of the 245 patients examined, 191 had proven ovarian cancer and underwent primary surgery and were included in the analysis. Patients with apparently benign or inoperable disease were excluded. Rectosigmoid infiltration was evaluated by histopathology or according to perioperative findings. Clinical, pathological and laboratory parameters were analyzed as factors potentially affecting the sensitivity and specificity of sonography. RESULTS: The sensitivity of ultrasound in detecting rectosigmoid infiltration in patients with ovarian cancer was 86.3%, with specificity of 95.8%, positive predictive value of 92.6%, negative predictive value of 91.9% and overall accuracy of 92.1%. CONCLUSION: Ultrasound is a highly accurate method for detecting rectosigmoid tumor infiltration in ovarian cancer patients, and thus, can be used for planning adequate management, including patient consultation, surgical team planning, suitable operating time and postoperative care. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Contribution of sentinel lymph-node biopsy to treatment of locally advanced stages of cervical cancers]. / Prínos biopsie sentinelových uzlin pro lécbu lokálne pokrocilých stadií karcinomu delozního hrdla.

OBJECTIVE: Usage of sentinel lymph-node (SLN) concept in locally advanced cervical cancers might help to individualise management. According to SLN status could be patients refered to neoadjuvant chemotherapy (NAC) with subsequent surgery or to primary chemoradiation. The aim of our study was to evaluate sensitivity of SLN detection in locally advanced cervical cancers and to assess the impact of NAC on frequency of their metastatic involvement. DESIGN: Retrospective clinical study. SETTING: Department of Obstetrics and Gynecology, General Faculty Hospital and 1st Medical Faculty, Charles University, Prague. MATERIALS AND METHODS: Included were patients with cervical cancer stages FIGO IB1 (> 3 cm), IB2, IIA2 and selected cases of stages IIB with incipient parametrial involvement. Patients were distributed into two different protocols - patients in group NAC-SLN were refered to radical hysterectomy with SLN biopsy after 3 cycles of NAC, other patients (group SLN) underwent SLN biopsy and NAC was administered only in SLN-negative cases. RESULTS: Altogether 101 patients were included (group SLN = 62, group NAC-SLN = 39). Detection of SLN in whole cohort reached 90.1% per patient and 68.3% bilaterally. No differences were found between SLN group and NAC-SLN group in frequency of per patient SLN detection (90.3% vs 89.7%) and bilateral detection (69.4% vs 66.7%). Prevalence of macrometastases, micrometastases and ITC in the SLN group was 37.1% (23/62), 11.3% (7/62) and 8.1% (5/62), respectively. In the NAC-SLN group macrometastases in SLN were detected in 17.9% (7/39) patients, in 1 patient was detected micrometastis in SLN and no patient had ITC. Difference in frequency of metastases in SLN was significant (p = 0,013). No patient had progressed during NAC, complete response was seen in 15.1% (11/73) patients and reduction of tumour volume > 30% in 84.9% (62/73) patients. CONCLUSIONS: Detection of SLN in locally advanced cervical cancers reached comparable results to early stages. NAC did not influence frequency of SLN detection, but it significantly decreased prevalence of metastatic SLN involvement.

Risk of micrometastases in non-sentinel pelvic lymph nodes in cervical cancer.

OBJECTIVE: A high sensitivity of sentinel lymph nodes (SLN) for pelvic lymph node (LN) staging has been repeatedly shown in patients with cervical cancer. However, since only SLN are evaluated by pathologic ultrastaging, the risk of small metastases, including small macrometastases (MAC) and micrometastases (MIC), in non-SLN is unknown. This can be a critical limitation for the oncological safety of abandoning a pelvic lymphadenectomy. METHODS: The patients selected for the study had cervical cancer and were at high risk for LN positivity (stage IB-IIA, biggest diameter≥3cm). The patients had no enlarged or suspicious LN on pre-operative imaging; SLNs were detected bilaterally and were negative on intra-operative pathologic evaluation. All SLNs and all other pelvic LNs were examined using an ultrastaging protocol and processed completely in intervals of 150µm. RESULTS: In all, 17 patients were enrolled into the study. The mean number of removed pelvic LNs was 30. A total of 573 pelvic LNs were examined through ultrastaging protocol (5762 slides). Metastatic involvement was detected in SLNs of 8 patients (1× MAC; 4× MIC; 3× ITC) and in non-SLNs in 2 patients (2× MIC). In both cases with positive pelvic non-SLNs, there were found MIC in ipsilateral SLNs. No metastasis in pelvic non-SLNs was found by pathologic ultrastaging in any of the patients with negative SLN Side-specific sensitivity was 100% for MAC and MIC. There was one case of ITC detected in non-SLN, negative ipsilateral SLN, but MIC in SLN on the other pelvic side. CONCLUSIONS: After processing all pelvic LNs by pathologic ultrastaging, there were found no false-negative cases of positive non-SLN (MAC or MIC) and negative SLN. SLN ultrastaging reached 100% sensitivity for the presence of both MAC and MIC in pelvic LNs.

[Gynecological Care and Prevention of Gynecological Malignancies in BRCA1 and BRCA2 Mutation Carriers]. / Gynekologická prevence a gynekologické aspekty péce u nosicek mutací genu BRCA1 a BRCA2.

This paper summarizes the current knowledge of gynecological care aspects in women with inherited predisposition to breast and ovarian cancer, i.e. BRCA1 and BRCA2 mutation carriers, and proposes guidelines for furher management of these women, addressing follow-up recommendations, prophylactic surgery indications and preimplantation genetic conseling. It evaluates cancer risk and severity of ovarian cancer in particular with regards to its high mortality resulting from aggressive biological behavior of the tumor and late detection rates. BRCA-positive women should be enrolled in prevention programs including carefull surveillance, prophylactic surgery or pre-implantation genetic counseling. Follow-up care consists of gynecological examination, expert oncogynecological ultrasound and tumor marker CA125 examination every six months. However, the most effective strategy for mortality reduction in ovarian cancer is prophylactic surgery--salpingo-oophorectomy (and hysterectomy). The optimal age for surgery is between 35 to 40 years. Prophylactic salpingo-oophorectomy performed in premenopausal women was proved to reduce the risk of ovarian as well as breast cancer. Symptoms of estrogen deficiency after prophylactic surgery can be suppressed by administration of hormone replacement therapy without increasing the risk of breast cancer. Preimplantation genetic diagnosis is an effective way to prevent the trans--mission of hereditary predisposition to the next generation. The management of patients with hereditary suspceptibility to ovarian cancer should be confined to specialized centres.

[Breast Cancer - Specifics of Gynecological Care and Counseling]. / Karcinom prsu - specifika gynekologické péce a poradenství.

BACKGROUND: This paper summarizes current knowledge about clinically important aspects of gynecological care in female breast cancer patients. Despite the overall positive acceptance of oral contraceptives and hormone replacement drugs, hormone therapy may raise fears of developing breast cancer. Specifics of gynecological care of fertile patients are discussed as these patients face ovarian failure when undergoing oncological treatment of breast cancer. Tamoxifen is used in adjuvant therapy of breast cancer, in metastatic breast cancer or as prophylaxis of breast cancer in high-risk patients. AIM: We aim to study the influence of hormonal treatment on breast cancer development in women with and without congenital predisposition. The main risk factors for developing breast cancer are family history, increased density of breast tissue, atypical hyperplasia of the breast and previous radiotherapy to the chest area. All these factors increase the relative risk of cancer more than four times. Contraceptives and hormone replacement therapy show generally less than two-fold or no increase at all (RR 0.96-1.6). We concentrate with safety of hormonal therapy in breast cancer patients after they finish breast cancer treatment in pre- and postmenopausal period. We discuss fertility-sparing methods for preservation of ovarian function due to oncological treatment. Those methods are cryopreservation of embryos, oocytes in metaphase II and ovarian tissue. Simultaneous administration of GnRH agonists may protect ovarian function before gonadotoxic chemotherapy. We describe in detail the effects of tamoxifen on gynecological organs in both pre- and postmenopausal women in relation to the potential risk of developing secondary malignancy. In premenopausal women, tamoxifen has no increased risk of cancer of the uterine body. In postmenopausal patients, the risk after five years of tamoxifen is increased 2-3 times. Transvaginal sonography is not the screening tool for detection of the pathology in the uterine cavity during tamoxifen therapy, and so we only recommend looking for symptoms. Hysteroscopy is the golden standard for the examination of the uterine cavity in symptomatic postmenopausal patients using tamoxifen. CONCLUSION: This paper summarizes the current knowledge in areas where oncological and gynecological cares for breast cancer patients mingle. It should lead to greater understanding and deepening cooperation between clinical oncologists and oncogynecologists for the benefit of our patients.Key words: adjuvant hormonal therapy - fertility preservation - GnRH analogs - contraceptives - endometrial hyperplasia - hormone replacement therapy - breast neoplasm - tamoxifenThis work was supported by the Czech Ministry of Health - RVO (FNBr, 65269705).The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 6. 6. 2016Accepted: 22. 7. 2016.

Mutation profile and clinical outcome of mixed endometrioid-serous endometrial carcinomas are different from that of pure endometrioid or serous carcinomas.

Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.

Ductal carcinoma in situ: analysis of 250 cases.

BACKGROUND: In the mammography screening era, we experience increasing incidence of non-invasive lesions of the breast, particularly the ductal carcinoma in situ (DCIS). It is the authors' goal to better understand this disorder in order to be able to tailor therapy individually for each patient and, most of all, to avoid overtreatment. MATERIALS AND METHODS: The authors analyzed all cases of DCIS diagnosed within one mammography screening unit between 2007 and 2013. Medical reports as well as a detailed case conference protocol were used to gain all required data. RESULTS: In a seven-year period, DCIS situ has been diagnosed 250 times in 249 women. Mostly the authors were able to obtain relevant information regarding tumor size, grade, biological characteristics, as well as surgery. This data was compared with current literature. DISCUSSION: Participating women who screen positive constitute a large patient sample. Thus, we have a large amount of clinical and histological information available for planning and conducting studies regarding DCIS as well as invasive breast cancer.

Factors affecting sonographic preoperative local staging of endometrial cancer.

OBJECTIVES: To identify major factors in the under- and overestimation of cervical and myometrial invasion by endometrial cancer at preoperative staging by ultrasound. METHODS: This prospective study involved all patients with histologically confirmed endometrial cancer referred consecutively for surgical staging between January 2009 and December 2011. All patients underwent transvaginal ultrasound examination, obtaining metric and perfusion data, and the results were compared with final histology: myometrial invasion was defined at histology in the final pathology report as being either < or ≥ 50%, while cervical stromal invasion was reported as being either present or absent, and sonographic over-/underestimation was determined relative to these. RESULTS: Enrolled prospectively into the study were 210 patients. The proportion of cases with sonographic underestimation, relative to final histology, of myometrial invasion (i.e. false-negative estimation of no or superficial invasion < 50%) and of cervical invasion (i.e. false-negative finding of absence of stromal invasion) was comparable: 8.6% (n = 18) and 10.5% (n = 22), respectively. Myometrial invasion was overestimated by ultrasound (i.e. false-positive estimation of deep invasion ≥ 50%) in 15.7% (n = 33) of cases, and cervical invasion was overestimated (i.e. false-positive finding of presence of stromal invasion) in 4.8% (n = 10) of cases. These outcomes correspond to positive and negative predictive values of 67.6% (95% CI, 57.7-76.6) and 83.3% (95% CI, 74.9-89.8), respectively, for the subjective assessment of myometrial invasion, and 60.0% (95% CI, 38.2-79.2) and 88.1% (95% CI, 82.5-92.4), respectively, for that of cervical stromal invasion. The staging error in subjective assessment was not related to body mass index (BMI), to the position of the uterus in the pelvis or to image quality. Cervical and myometrial invasion were more often underestimated in well-differentiated endometrial cancers that were smaller in size, with thick minimum tumor-free myometrium and lower perfusion, and more often overestimated in moderately and poorly differentiated cancers that were larger in size, with thin minimum tumor-free myometrium and richer perfusion. CONCLUSION: The accuracy of subjective assessment of myometrial and cervical invasion by ultrasound was significantly influenced by tumor size, density of tumor vascularization, tumor vessel architecture and histological grading, while it was not significantly affected by BMI, uterine position and image quality.

[Ultrasonic staging cervical cancer -a proposal for the standard procedure]. / Ultrazvukový staging karcinomu delozního hrdla - návrh standardního postupu.

OBJECTIVE: To develop guidelines for the ultrasound examination of cervical cancer, including a unified ultrasound terminology. SUBJECT: Original paper. SETTING: Gynecological Oncology Center, Department of Obstetrics and Gynecology, Masaryk University and General Faculty Hospital Brno, and Gynecological Oncology Center, Department of Obstetrics and Gynecology, Charles University in Prague - First Faculty of Medicine and General Faculty Hospital Prague. SUBJECT AND METHOD: The standard diagnostic algo-rithm for examination of cervical cancer in oncogynecology centers in the Czech Republic is based on published studies, own experience (Oncogynecological Center, Department of Gynecology and Obstetrics,1st Medical Faculty, Charles University) and the experiences of a group of ultrasonographers involved in the grant project IGA MZ CR NT13070 focused on the implementation of an oncogynecological ultrasound into clinical practice. Standard ultrasound examination includes two-dimensional real-time ultrasound examination (sagittal and transverse views). Transrectal or transvaginal ultrasound examination is combined with transabdominal ultrasound. Prerequisites are quality ultrasound equipment, a high frequency microconvex linear probe and abdominal convex and linear probe. The examination is performed by an experienced sonographer (level 2 or 3 according to the recommendations of the Ultrasound division of the Czech Society of Obstetrics and Gynecology and the Czech Society of Ultrasound in Obstetrics and Gynecology). Intravenous administration of contrast material or three-dimensional ultrasound examination do not influence accuracy of the examination and is not a prerequisite. CONCLUSION: Based on the consensus of experienced sonographers and a review of the literature, guidelines were created for ultrasound staging of cervical cancer.

[Ultrasound staging of endometrial cancer - recommended methodology of examination]. / Ultrazvukový staging karcinomu endometria - doporucená metodika vysetrení

The extent of the staging surgery in cases of histologically proven endometrial cancer depends on whether the tumor is of high risk or low risk for extrauterine spread and recurrence. There are several significant prognostic factors - histological subtype and grade of dediferentiation from preoperative biopsy and local stage of uterine involvement based on imaging methods. The depth of myometrial invasion and presence of cervical stromal infiltration (local staging) can be assessed by ultrasound with the overall accuracy comparable to that of magnetic resonance. Transvaginal ultrasound enables to vizualize detailed pelvic anatomy and that is why it is considered to be a suitable tool for assessment of local stage of endometrial cancer. It is advisable to use the standardized terminology defined by International Endometrial Tumor Analysis group (IETA) to describe ultrasound findings. The standardized methodology of ultrasound preoperative staging examination based on prearranged protocols is recommended.