David Kuzel

Effect of a Selective Progesterone Receptor Modulator on Induction of Apoptosis in Uterine Fibroids In Vivo

Aim. To determine if hormonal treatment induces apoptosis in uterine fibroids. Methods. Immunohistochemical examination of fibroid tissue, using avidin-biotin complex and cleaved caspase-3 antibody for detecting apoptosis, was performed in premenopausal women who underwent 12-week treatment with oral SPRM (6 patients with 5 mg and 5 patients with 10 mg of ulipristal acetate per day) or gonadoliberin agonist (GnRHa, 17 patients) and subsequent myomectomy or hysterectomy for symptomatic uterine fibroids. Ten patients with no presurgical hormonal treatment were used as controls. Results. Apoptosis was present in a significantly higher proportion of patients treated with ulipristal acetate compared to GnRHa (P = 0.01) and to patients with no hormonal treatment (P = 0.01). In contrast to an AI of 158.9 in SPRM patients, the mean AI was 27.5 and 2.0 in GnRHa and control groups, respectively. No statistical difference in the AI was observed between the two groups of patients treated with ulipristal acetate (5 mg or 10 mg). Conclusion. Treatment with ulipristal acetate induces apoptosis in uterine fibroid cells. This effect of SPRM may contribute to their positive clinical effect on uterine fibroids.

Hysteroscopy after uterine fibroid embolization in women of fertile age

Aim:  Uterine artery embolization for fibroids is a controversial issue for women with incomplete reproductive plans. Ovarian failure and uterine infection are the most dreaded complications of this procedure. The purpose of the present study was to assess the types and the frequency of intrauterine abnormalities and the histological features of the endometrium after embolization.

Hysteroscopy after uterine fibroid embolization: Evaluation of intrauterine findings in 127 patients

Aim:  Several atypical hysteroscopy findings have been described in association with uterine artery embolization (UAE). The purpose of this study was to evaluate the types and frequency of these findings in the largest published series of patients.

Sentinel node (SLN) biopsy in the management of locally advanced cervical cancer

OBJECTIVES Sentinel lymph node (SLN) biopsy can significantly contribute to the management of locally advanced cervical cancers with high risk of lymph node (LN) positivity. However, low detection rate and sensitivity were reported in larger tumors, albeit on a small number of cases. It was the aim of our study to verify the SLN reliability in large tumors, with modified dye application technique and a careful identification of side-specific lymphatic drainage. METHODS The study involved 44 patients with tumors 3 cm in diameter or larger, stages IB1 to IIA, or selected IIB. In cases where SLN could not be detected, systematic pelvic lymphadenectomy was performed on the respective side. Systematic pelvic lymphadenectomy was performed during the second step radical procedure if not already done. RESULTS Detection rate in the whole cohort reached 77% per patient and 59% bilaterally. No significant difference was found whether a blue dye or a combined method was used (75% vs 80%, and 55% vs 67%). Systematic pelvic lymphadenectomy was performed in cases with undetected SLN unilaterally in 8 and bilaterally in 10 women. A systematic pelvic lymphadenectomy was included in the second step radical procedure in 19 cases and no positive LN were found. There was no case of false-negative SLN result in patients who underwent surgical treatment. CONCLUSION Detection rate in locally advanced cervical cancer could be improved by a careful dye application technique. Low false-negative SLN rate could be achieved if pelvic lymphatic drainage is evaluated on a side-specific principle by performing systematic lymphadenectomy if SLN is not detected.

Peritoneal Washing Cytology on Fluid Hysteroscopy and After Curettage in Women with Endometrial Carcinoma

OBJECTIVE To assess the influence of fluid hysteroscopy with target biopsy of the endometrium and the influence of added curettage on the results of peritoneal washing cytology (PWC) in endometrial carcinoma. STUDY DESIGN In 42 women at risk of endometrial carcinoma, we performed fluid hysteroscopy with target biopsy of the endometrium and curettage. Evaluation of PWC of the pouch of Douglas was performed three times during the procedure: prior to hysteroscopy, after fluid hysteroscopy with target biopsy and after curettage. RESULTS On cytologic slides from peritoneal washings in 11 patients with carcinoma of the endometrium, malignant endometrial cells were found after curettage in 72.7%. There was no statistically significant difference in PWC prior to hysteroscopy (two women, 20%) or after hysteroscopy with target biopsy (three women, 30%). There was a statistically significant difference (.05 level) in positive PWC after hysteroscopy with target biopsy (three women, 33.3%) and after curettage (eight women, 88.9%). CONCLUSION Slides from carcinoma of the endometrium in PWC do not deteriorate after hysteroscopy with target biopsy of the endometrium, but tumor cells will appear in the pouch of Douglas after curettage.

High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma

BACKGROUND Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. OBJECTIVE The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2-IIIB tumours and correlate findings with histopathology. STUDY DESIGN The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group. RESULTS The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. CONCLUSIONS Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort.

Aspiration cytology from the pouch of Douglas at hysteroscopy

Aspiration cytology from the pouch of Douglas at hysteroscopy

Fumarate hydratase gene mutation in two young patients with sporadic uterine fibroids

Fumarate hydratase (FH) is a key enzyme of the Krebs cycle. Germline mutations in the FH gene encoding fumarate hydratase cause autosomal dominant syndromes multiple cutaneous and uterine leiomyomata and hereditary leiomyomatosis and renal cell cancer (HLRCC). Few data have been published on the role of FH gene mutation in development of uterine fibroids outside the context of multiple cutaneous and uterine leiomyomata /HLRCC. We report two FH gene mutations, one novel and one previously described, in two young patients with sporadic uterine fibroids and decreased fumarate hydratase activity in lymphocytes. In patient 1, a novel heterozygous mutation c.892G>C was found. In patient 2 we detected heterozygous mutation c.584T>C. Both the patients had a negative family history for renal cancer and cutaneous leiomyomatosis. None of the relatives, however, underwent renal imaging at the time of writing. FH mutation carriers may be easily identified by analysis of fumarate hydratase activity in blood lymphocytes. We suggest performing fumarate hydratase activity or FH mutation screening in women with onset of uterine fibroids in their 20s and family history of uterine fibroids or other HLRCC‐associated malignancies.

Minimally invasive and hysteroscopic diagnosis and treatment of patients after organ transplantation.

Aim:  To assess the safety of minimally invasive and hysteroscopic diagnosis and treatment of abnormal uterine bleeding and intrauterine abnormalities in patients after organ transplantation.

Acute Exacerbation of Recurrent Pelvic Inflammatory Disease: Laparoscopic Findings in 141 Women With a Clinical Diagnosis

OBJECTIVE To evaluate the accuracy of the clinical diagnosis of recurrent pelvic inflammatory disease (PID) and to determine the positive and negative predictive value of laboratory tests for the diagnosis of PID. STUDY DESIGN According to a prospective study design, 141 consecutively hospitalized patients with the clinical diagnosis of PID were evaluated. The basic inclusion criterion was a history of at least one episode of PID. Standard laboratory tests were performed, specimens for aerobic and anaerobic culture and for Chlamydia trachomatis isolation were obtained, and temperature was regularly monitored. All patients underwent laparoscopy under general anesthesia within 24 hours of admission. RESULTS The clinical diagnosis of PID was confirmed by laparoscopy in 30% of patients. In almost one-third of patients, at laparoscopy the pelvic organs were within normal limits. Adhesions without signs of PID were found in 16%. The third-most-frequent finding was endometriosis (14%). Neither the individual monitored parameters nor their combination reached satisfactory positive and negative predictive values for diagnosing PID. CONCLUSION Recurrent clinical symptoms and laboratory signs of PID should be an indication for confirming or excluding the clinical diagnosis by laparoscopy.