Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Th e role of CDK12 in tumor bio logy.

BACKGROUND: Physiological function of cyclin-dependent kinase 12 (CDK12) is crucial for several cellular processes, including regulation of transcription, RNA splicing, transcription termination and polyadenylation. It is well documented by now that CDK12 controls transcription of the unique set of genes involved in DNA-damage response, replication of DNA and response to cellular stress. Just recently, a key function of CDK12 in the induction of tandem duplication of specific DNA sequences within the metastatic castrate resistant prostate tumors has been documented. Therefore, it is possible to recognize CDK12 as a tumor suppressor; nevertheless, there is a growing body of evidence that CDK12 can support tumor growth under specific circumstances and thus act as a tumor oncogene. CDK12 therefore represents an alternative dia-gnostic approach for breast, ovarian and prostate tumors, especially when conventional treatment is not active and there is a need for more effective approaches, such as concept of synthetic lethality. METHODS: The discussed scientific papers can be reached at the PubMed and Scopus databases before 1th of April 2020. PURPOSE: The aim of the review is to summarize current knowledge relevant to the function of CDK12 as a tumor suppressor or oncogene in various tumors and to discuss the use of specific CDK12 inhibitors for patient treatment. At the end of the article, we discuss the potential use of CDK12 in the treatment of specific tumors by its targeted inhibition in monotherapy or in combination with poly (ADP ribose) polymerase 1 (PARP1) and checkpoint kinase 1 (CHK1) inhibitors. 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.

Bilateral simultaneous tubal pregnancy.

OBJECTIVE: We present a rare case of peroperatively diagnosed bilateral tubular pregnancy. DESIGN: Case report. SETTING: Department of Obstetrics and Gynekology, Novy Jicin Hospital. CONCLUSION: In the case of ectopic pregnancy always think about the possibility of contralateral pathology and during the surgical revision remember a thorough inspection of both fallopian tubes.

ERAS protocol in gynecologic oncology.

OBJECTIVE: To summarize current knowledge of the ERAS protocol in gynecologic oncology surgery. DESIGN: Review article. SETTINGS: Department of Obstetrics and Gynecology, University Hospital Ostrava, Ostrava, Department of Obstetrics and Gynecology, University of Ostrava, Ostrava. METHODS: Literature review, PubMed and Medline databases were used to search relevant literature from 1995 to 2019. CONCLUSION: ERAS (Enhanced Recovery after Surgery) is a perioperative treatment program based on evidence-based medicine. Guidelines consist of pre-operative, perioperative and post-operative care items. Implementation of the ERAS protocol leads to a decrease in complications up to 40% and a reduction in hospitalization by up to 30%, thereby reducing overall costs without increasing the number of rehospitalizations. Multidisciplinary cooperation not only with anesthesiologists and consultant surgeons, but also with nutritional specialists and nurses is crucial.

Gynecological tumor triplicity.

OBJECTIVE: Information about an interesting real clinical case. DESIGN: Case repor. SETTING: Clinic of Gynecology and Obstetrics, University hospital in Ostrava. METHODS AND RESULTS: A 64-year-old female patient with no family history of gynecologic tumors was indicated to total laparoscopic radical hysterectomy due to confirmed squamous cervical carcinoma stage IB1. The operation was converted to laparotomy due to unexpected peroperative finding of ovarian malignancy. Peroperatively, left ovary borderline tumor and tiny implants on the surface of uterus and small pelvis walls were confirmed. Radical abdominal hysterectomy, bilateral salpingo-oophrectomy, omentectomy, appendectomy, pelvic lymphadenectomy and peritonectomy were performed. CONCLUSION: Definitive postoperative histology further revealed an endometroid adenocarcinoma of the uterus, serous left ovary borderline tumor with non-invasive implants and no residual tumor of cervical carcinoma. In our clinic, several tumor duplicities were reported, but this is the first case of a gynecological tumor triplicity. As far we know, this is the first case report refering to a gynecological tumor triplicity in one time. Keywords gynecologic, multiple, malignancy, radical surgery.

[The possibility of using progesterone receptor modulators in the treatment of myomas]. / Moznosti uzití selektivních modulátoru progesteronových receptoru v lécbe delozních myomu.

OBJECTIVE: To summarize the knowledge about the effect of selective progesterone receptor modulators and their use in the treatment of myomas in women of childbearing age and in perimenopause. DESIGN: Review article. RESULTS: Long-term treatment with ulipristal acetate maximizes its effectiveness, it helps to achieve faster bleeding control and increases the number of pa-tients with fibroid volume reduction of more than 50%. Ulipristal acetate is the most effective drug in the medical treatment of myomas and its use will change the approach to surgical treatment.

[The use of selective progesterone receptor modulators in the treatment of myomas]. / Moznosti uzití selektivních modulátoru progesteronových receptoru v lécbe delozních myomu.

OBJECTIVE: To summarize the knowledge of the effect of selective progesterone receptor modulators and their use in the treatment of myomas in women of childbearing age and in perimenopause. DESIGN: Review articleResults: Long-term treatment with ulipristal acetate maximizes its effectiveness, it helps to achieve faster bleeding control and increases the number of patients with fibroid volume reduction of more than 50%. Ulipristal acetate is the most effective drug in the medical treatment of myomas and its use will change the approach to surgical treatment.

[Basal cell carcinoma in a young patient]. / Bazaliom vulvy u 37leté pacientky.

OBJECTIVE: The aim of this article is to highlight a possible occurrence of basal cell carcinoma in young patient. DESIGN: Case report. SETTING: Porodnicko-gynekologická klinika FN Ostrava. METHODS: We report case of a 37-year-old patient with a lesion of a vulva, which persisted for 3 years. The patient was during these free years repeatedly examined by a gynecologist and a dermatologist. She was treated by antibiotics and corticosteroids without any effect. After 3 years she was sent to an expert examination, during which was removed a biopsy. From the biopsy specimen was diagnosed basal cell carcinoma. Radical excision was indicated due tu the finding. RESULTS: Patient is now 29 months disease-free. CONCLUSION: Any persistent lesion in the vulvar region should be subjected to histological examination, even in young patients where the diagnosis of basal cell vulvar carcinoma is very unlikely.

Early identification of women with HELLP syndrome who need plasma exchange after delivery.

OBJECTIVES: To compare the laboratory course of HELLP syndrome between patients who recover and those who progress to postpartum thrombotic microangiopathic syndrome (PTMS) and require postpartum plasma exchange (PPEX) and to describe maternal characteristics and morbidity in women with PTMS. METHODS: In this retrospective analysis, 81 patients recovered and 5 progressed. Values for aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, platelets (Plt), urea, and creatinine at 0, 8, 16, 24, 48, and 72 hours postpartum in both groups were analyzed and compared. We also described maternal characteristics and morbidity of patients who progressed to PTMS. RESULTS: Patient groups differed significantly at 72 hours postpartum for Plt and LDH values and at 24 and 48 hours for bilirubin. Trends for AST and Plt differed significantly between the recovery and progression groups in the first 48 hours. Patients who progressed had acute kidney injury and other severe maternal morbidity, including one case of maternal death. CONCLUSIONS: Women with HELLP syndrome without clear Plt and AST improvement in the first 48 hours and with acute kidney injury, neurological impairment, or respiratory distress syndrome are at risk of progressing to PTMS. They should be administered PPEX between 24 and 72 hours postpartum.

Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer.

OBJECTIVE: Evaluate prognostic significance of low volume disease detected in sentinel nodes (SN) of patients with early stages cervical cancer. Although pathologic ultrastaging of SN allows for identification of low volume disease, including micro-metastasis and isolated tumor cells (ITC), in up to 15% of cases, prognostic significance of these findings is unknown. METHODS: A total of 645 records from 8 centers were retrospectively reviewed. Enrolled in our study were patients with early-stage cervical cancer who had undergone surgical treatment including SN biopsy followed by pelvic lymphadenectomy and pathologic ultrastaging of SN. RESULTS: Macrometastasis, micrometastasis, and ITC were detected by SN ultrastaging in 14.7%, 10.1%, and 4.5% patients respectively. False negativity of SN ultrastaging reached 2.8%. The presence of ITC was not associated with significant risk, both for recurrence free survival and overall survival. Overall survival was significantly reduced in patients with macrometastasis and micrometastasis; hazard ratio for overall survival reached 6.85 (95% CI, 2.59-18.05) and 6.86 (95% CI, 2.09-22.61) respectively. Presence of micrometastasis was an independent prognostic factor for overall survival in a multivariable model. CONCLUSION: Presence of micrometastasis in SN in patients with early stage cervical cancer was associated with significant reduction of overall survival, which was equivalent to patients with macrometastasis. No prognostic significance was found for ITC. These data highlight the importance of SN biopsy and pathologic ultrastaging for the management of cervical cancer.

[Parametrial involvement in early stage cervical cancer patients with tumor less 2 cm: The myth or reality?]. / Postizení parametrií u pacientek s Casným stadiem cervikáIního karcinomu s velikostí nádoru do 2 cm: mýtus, nebo realita?

OBJECTIVE: The aim is review of studies exploring the relationship of parametrial involvement with other tumor-related factors (lymphovascular space invasion, depth of stromal invasion, status of sentinel lymph node) in early stage cervical cancer patients with tumor less than 2 cm. DESIGN: Review. SETTINGS: Department of Obstetrics and Gynaecology, University Hospital Ostrava. METHODS: Searching of the literature in database PubMed by combination of the key words: early stage, cervical cancer, parametrial involvement, parametrectomy. CONCLUSION: Based on literature review, the metastatic parametrial involvement in early-stage cervical cancer patients with tumor less than 2 cm and with other tumor-related factors is very rare. Before omitting of parametrectomy in these low-risk patients, these encouraging data must be confirmed in the prospective multicentric trials.

[Lymphatic mapping in cervical cancer]. / Lymfatické mapování u karcinomu cípku delozního.

BACKGROUND AND AIMS: The aim of the study is to analyze the feasibility of intraoperative sentinel lymph nodes (SLN) detection using gamma detection probe and blue dye in patients with cervical cancer. DESIGN AND SUBJECTS: Prospective clinical study. 106 patients with cervical cancer were included into the study in the period from May 2004 to November 2006. METHODS AND RESULTS: Patients were divided into three groups according to the tumor volume. Lymphoscintigraphy was performed following an injection of 99m Tc-labeled nanocolloid and intraoperatively the SLN were identified visually after marking of lymphatic vessels with blue dye and further detected using a handheld gamma detection probe. The SLN were histologically and immunohistochemically analyzed. Total number of 309 SLN with an average of 2.9 per patient were identified. The SLN detection rate was 94.3% per patient, 84.4 % per side, and depended on the tumor volume. Metastatic disease was detected in 39 patients (36.8%) and micrometastatic disease in 15 patients (14.2%). Sensitivity and negative predictive value calculated were 93.9% and 98.0%, false negative rate reached 5.1. CONCLUSIONS: Intraoperative detection of SLN using combination of technecium-99-labeled nanocolloid and blue dye represents a feasible, safe and accurate technique to identify lymphatic spreading in stages IA2-IB1 of cervical cancer.

[Sentinel node detection in early stage of cervical carcinoma using 99mTc-nanocolloid and blue dye]. / Detekce sentinelové uzliny u casných stadií cervikálního karcinomu kombinovanou metodou s uzitím nanokoloidu technecia Tc99 a patentní modri.

OBJECTIVE: The aim of the study was to analyse the feasibility of intraoperative sentinel lymph nodes (SLN) detection using gamma detection probe and blue dye in patients undergoing radical hysterectomy for treatment of early stage of cervical cancer. DESIGN: Prospective case observational study. METHODS: In the period from May 2004 to February 2006 77 patients with early stage of cervical cancer who underwent a radical surgery were included into the study. Patients were divided into three groups according to the tumour volume. First group consists of patients FIGO IA2 and FIGO IB1 with tumour diameter less than 2 cm, second group tumours FIGO IB1 with tumour diameter more than 2 cm and third group stadium IB2. SLN was detected by blue dye and Tc99. Preoperative lymphoscintigraphy was done after Tc99 colloid injection, intraoperative detection was performed by visual observation and by hand-held gamma-detection probe. SLN were histologically and immunohistochemically analysed. RESULTS: A total number of 2764 lymph nodes with an average 36 and 202 SLN with an average 2.6 were identified. The SLN detection rate was 94.8% per patient and 85.1% for the side of dissection and depends on the tumor volume. SLN were identified in obturator area in 48%, in external iliac area in 15%, in common iliac and internal iliac both in 9%, in interiliac region in 8%, in praesacral region in 6% and in parametrial area in 5%. Metastatic disease was detected in 31 patients (40.2%), metastatic involvement of SLN only in 12 patients (15.6%). False negative rate was 2.6%, sensitivity and negative predictive value calculated by patient were 923% and 95.7%. CONCLUSIONS: Intraoperative lymphatic mapping using combination of technecium-99-labeled nanocolloid and blue dye are feasible, safe and accurate techniques to identified SLN in early stage of cervical cancer.

[Lymphatic mapping and detection of sentinel node in early stages of cervical carcinoma]. / Lymfatické mapováni a detekce sentinelové uzliny u casných stadií cervikálního karcinomu.

OBJECTIVE: The aim of the study was to analyse two methods of intraoperative sentinel node detection using blue dye and blue dye with Tc99 labeled tracer in early stage of the cervical cancer. DESIGN: Prospective case observational study. SETTING: Department of Obstetrics and Gynecology, University Hospital Ostrava. METHODS: From May 2004 to September 2005, 49 patients with cervical cancer who underwent a radical surgery were included into the study. Sentinel lymph node was detected using blue dye in the first group of 23 patients and by blue dye with Tc99 in the second group of 26 patients. Intraoperative sentinel node detection was performed by visual aspection in the first group, and by visual aspection and by hand-held gamma-probe in the second group. RESULTS: Patients were divided according to stage of the disease into three subgroups FIGO IA2, FIGO IB1 and FIGO IB2. A total number of 1561 lymph node with an average 32 and 94 SLN with an average 1.9 were identified. The specific detection rate per site was 63% in the first group and 80.8% in the second group respectively. Metastatic disease was detected in 26 patients (41%) and metastatic involvement of SLN only in 11 patients (17.4%). Sensitivity and negative predictive value were 100% in both groups, false negativity was 0%. CONCLUSION: Detection of SLN by combination of blue dye and Tc99 labeled tracer has a higher detection rate of SLN than detection by blue dye alone.

[Radical surgical therapy and role of adjuvant chemotherapy in ovarian tumors of borderline malignancy]. / Radikalita chirurgické lécby a postavení adjuvantní chemoterapie u nádoru ovaria hranicní malignity.

OBJECTIVE: Evaluation of the benefit of the radical surgical therapy in the assessment of prognostic factors and indication of adjuvant therapy in patients with borderline tumors of ovary. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynecology, University Hospital, Ostrava. METHODS: The group consists of 26 patients operated on our department, 12 of which underwent restaging operation after insufficient primary surgery in different hospital and 14 underwent primary surgery in our department. The average age was 42.9 years. RESULTS: Radical surgery with regional lymphadenectomy was performed in 18 cases (69%) and non-radical in 8 cases (31%). In 7 patients (27%) fertility preservation operation was done. According to histological results 19 tumors (73%) were of serous type, 7 being of mucinous type (27%). There were no other histological types in our group. The lymphnodes were positive in 4 cases (22%) out of 18. Eight patients were indicated for adjuvant chemotherapy (31%), 4 of them for regional lymphnodes positivity, 2 for peritoneal implants, 1 patient for tumor residuum. The last case was a patient with tumor duplicity of a borderline tumor of ovary stage FIGO IIC and corporal carcinoma stage FIGO IB. We had one case of recurrence after fertility preservation surgery. There was no case of pregnancy yet. CONCLUSIONS: Borderline tumors of ovary have good prognosis and low recurrence rate. In spite of that, there exists a group of women with higher risk of recurrence and disease progression which can be fatal. These patients may benefit from adjuvant therapy, which is indicated after evaluation of risk factors ideally acquired from the radical surgery.

[Hormone replacement therapy and ovarian tumors]. / Hormonální substitucní terapie a nádory ovaria.

OBJECTIVE: Analysis of risk and protective factors and hormone replacement therapy in the aethiology and pathogenesis of ovarian cancer. The role of hormone replacement therapy in the complex treatment in women with ovarian cancer is discussed. DESIGN: Reviewed article. SETTING: Department of Obstetrics and Gynaecology, University Hospital Ostrava. METHODS: Analysis of epidemiological studies. CONCLUSION: The role of hormone replacement therapy as a risk factor of ovarian cancer has not been confirmed. Hormone replacement therapy as a part of supportive and symptomatic therapy has been acceptable in a great deal of patients with ovarian cancer.