David Pavlista

Abdominal radical trachelectomy in fertility-sparing treatment of early-stage cervical cancer.

Background: Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. In comparison with vaginal radical trachelectomy, the published results of ART are so far limited. Methods: Enrolled were women referred for ART either by laparoscopy or laparotomy. The main inclusion criterion was stage IA2 or IB1 with a cranial extent that allows for preservation of at least 1 cm of the endocervical canal. Results: A total of 24 women were referred for the procedure, but fertility could not be preserved in 7 (29%) of them. Four women underwent immediate completion of radical hysterectomy because of a positive cranial surgical margin (n = 2) or sentinel node macrometastasis (n = 2) on frozen section. We found no correlation between tumor volume and inability to preserve fertility. A positive sentinel node was identified in 4 patients (17%); there were no false-negative results. Of the 9 women (53%) who have tried to conceive so far, 6 (67%) have conceived and 5 given birth, 2 of which were premature deliveries. Conclusions: Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy. The main criterion for the selection of suitable patients should be the cranial extent of the tumor. Abdominal radical trachelectomy allows for achievement of satisfactory obstetrical outcomes.

Late morbidity following nerve-sparing radical hysterectomy☆

OBJECTIVES Nerve-sparing (NS) modification of radical hysterectomy (RH) has been developed with the main purpose of improving the quality of life after radical surgical treatment of early-stage cervical cancer. Although the procedure has been discussed for almost 30 years, there are only limited data available on late morbidity. The aim of the study was to prospectively evaluate the morbidity of patients before and 6 months after NS RH and compare that with the morbidity in patients following different types of parametrectomy without nerve sparing. METHODS Multiple parameters were assessed prospectively using 20-item self-reported questionnaire, focusing on three main areas of morbidity: bladder, sexual, and anorectal functions. Excluded were patients treated with adjuvant radiotherapy. RESULTS Enrolled were women following NS RH (N=32), type C RH (N=19), and type D RH (N=21). Nine parameters significantly deteriorate in the whole group after the treatment: defecation straining (p=0.03), defecation regularity (p=0.0006), defecation frequency (p=0.02), need to use laxatives (p<0.001), flatulence incontinence (p<0.001), urinary incontinence (p<0.001), nocturia (p=0.002), loss of bladder sensation (p=0.04), and straining to void (p<0.001). There were significant differences (p<0.05) between groups following NS and type C or D RH in changes of following parameters: defecation regularity, receptivity to sexual activity, urinary incontinence, nocturia, and straining to void, while no differences were found between type C and D RH. Minimal changes were observed in any of 10 parameters of sexual functions. CONCLUSIONS Our results confirmed a significant negative impact of RH on bladder and anorectal functions. Autonomic nerve preservation significantly improved morbidity 6 months after treatment.

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.

Ultrasound guided cryoablation of fibroadenomas.

PURPOSE Fibroadenoma (FA) of the breast is the most common disorders in young women. The aim of the study was to evaluate cryoablation (CA) under ultrasound guidance in the office setting for patients with FA. MATERIALS AND METHODS For this prospective multicenter trial an office-based cryosurgical system was used to treat histological confirmed benign FA with a maximum dimension of 3 cm. 23 CA procedures were performed under ultrasound guidance. The cryoprobe was inserted into the center of the FA guided by real-time ultrasound. A freeze-thaw-freeze treatment cycle was performed according to the size of the FA. During the CA procedure continuous ultrasound monitoring of the ice ball was performed, verifying engulfment of the FA. Patients attended 4 follow-up visits at 1 week, 3 months, 6 months and 1 year and underwent ultrasound and physical examinations. RESULTS Data was collected from 23 procedures. The ice ball engulfed the treated FA in 91.3 %. A sharp reduction in volume was observed at 6-month follow-up and continued more moderately up to 1 year. No serious but four minor adverse events occurred. At 1 year follow-up, lumps that were assessed pre-treatment as hard were assessed as soft or not palpable. 7 patients complained of pain caused by the lump prior to cryotherapy, while 5 of these patients felt transient pain during the follow up period. It is reasonable to assume that the pain was not related to the CA procedure as it was not consistent. In 96 % of the cases patients and physicians rated the cosmetic results of the procedure as excellent or good. CONCLUSION The cryodestruction proved functional and safe, while showing reduction in palpability and pain caused by the FA in the treated patients.

High-risk human papillomavirus DNA in the primary tumor, sentinel, and nonsentinel pelvic lymph nodes in patients with early-stage cervical cancer: a correlation with histopathology.

Introduction: Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early-stage cervical cancer. Still, approximately 15% of patients with negative pelvic nodes experience recurrence, most of them in the pelvis. The presence of human papillomavirus (HPV) DNA in histologically negative pelvic nodes is considered a subclinical metastatic spread. Methods: Patients with early-stage cervical cancer referred for surgical treatment were enrolled in the study. Cytobrush technique was used for sample collection from the fresh tissue to avoid any loss of material for histology. Results: Altogether, 49 patients were enrolled in the study. High-risk (HR) HPV DNA was identified in the tumor in 91.8% patients and in the sentinel node or other pelvic nodes in 49.9% patients. Among the 10 HR HPV genotypes detected, HPV 16 was the most frequently represented in both the tumor and the lymph nodes (66.7% and 71.4%, respectively). All metastatic lymph nodes were HR HPV positive. Conclusions: The presence of HR HPV DNA in a sentinel node had a 100% positive predictive value for metastatic involvement of pelvic lymph nodes in our study. This could be considered a sign of an early subclinical metastatic spread; however, the prognostic value has to be evaluated through a longer follow-up.

Localization of the Sentinel Node of the Upper Outer Breast Quadrant in the Axillary Quadrants

BackgroundSentinel node (SN) biopsy is associated with much less morbidity than axillary dissection. In patients with early breast cancer, lymphatic mapping and SN biopsy accurately stage the axillary nodes. Both currently available lymphatic mapping agents, radiocolloid and blue dye, have some limitations that may make perioperative or preoperative SN identification difficult. In such cases, exact knowledge of the topography of the axilla and the most probable location of the SN may be crucial.MethodsIn 12 fresh female cadavers with no history of breast carcinoma, injections of patent blue dye were used to visualize the SNs in the axillary quadrants and their lymphatic collectors from the upper outer quadrant of the breast, which is the most common location of breast cancer. The axilla was divided into quadrants with regard to the intersection of the thoracoepigastric vein and the third intercostobrachial nerve.ResultsAll SNs were located within a circle of 2-cm radius of this intersection in the fatty tissue at the clavipectoral fascia. In most cases, the SN was located in the fatty tissue near the clavipectoral fascia in the lower ventral quadrant of the axilla (n = 14, 58%). In seven cases (29%), the SN was located in the upper ventral quadrant, in two cases (8%) in the upper dorsal quadrant, and in one case in the lower dorsal quadrant.ConclusionsThe results of this anatomical study may facilitate SN biopsy in patients with breast cancer.

High frequency of BRCA1/2 and p53 somatic inactivation in sporadic ovarian cancer

Faculty of Medicine, Charles University, Prague, and theGeneral Teaching Hospital in Prague. All analysed tumourswere sporadic i.e. no other tumours were referred to in thefamily history and all the patients were more than 40 yearsold at the time of diagnosis. All participants gave their writ-ten informed consent.All freshly frozen samples were examined by a pathol-ogist to evaluate the proportion of tumourous and nontu-mourous tissue. Only samples with over 50% tumouroustissue were used for our study. The histopathological char-acteristics of analysed tumours are given in table 1. Majorityof patients (21/30 : 70%) were diagnosed in stage III Inter-national Federation of Gynocology and Obstetrics (FIGO).Stages I and IV were similarly represented (4/30 and 5/30:13.3% and 16.7%, respectively), and none of the analysedtumours belong to stage II patient.

Comparative analysis of loss of heterozygosity and expression profi le in normal tissue, DCIS and invasive breast cancer

IntroductionDuctal carcinoma in situ (DCIS) is considered to be related to the development of invasive breast cancer. The aim of molecular biological research of preinvasive breast lesion characteristics and comparison with normal tissues and tissue of invasive tumours is to identify patients at high risk of developing invasive tumour on the basis of already established preinvasive lesions, and thus influence clinical decision-making. The aim of our study was to analyse several key molecules involved in different cellular pathways important for cancer development and progression in different types of breast tissue and to describe similarities and differences between premalignant and malignant lesions.Material and methodsGenetic material isolated from both the tumour and healthy tissue was examined by loss of heterozygosity (LOH) analysis and real-time PCR using collagen 2A as a house-keeping gene.ResultsWe analysed 65 samples of healthy mammary gland, 25 DCIS and 42 invasive ductal breast cancer samples. We analysed the LOH in three genes: BRCA1, BRCA2 and p53; and the gene expression of the VEGF gene and Bcl-2 gene. LOH in the BRCA1 gene was present in 44.74% of invasive samples and in 8.69% of DCIS (p=0.026); LOH in the BRCA2 gene in 45.0% of invasive samples and in 9.52% of DCIS (p=0.036); LOH in the p53 gene in 32.5% of invasive samples and in 31.82% of DCIS (p=0.97). No LOH was observed in normal tissue samples. VEGF was overexpressed in 14.3% of invasive cancers and in 12.0% of DCIS. Overexpression of Bcl-2 was observed in 11.9% of invasive cancers and in 8.0% of DCIS.ConclusionWe have confirmed that some of the molecular characteristics of DCIS are identical to those of invasive carcinoma. This approach could lead to the identification of molecular markers as indicators for the potential development of DCIS into invasive carcinoma or identification of DCIS subgroups with latent invasion.

OC167: Ultrasound-guided tru-cut biopsy in the diagnosis and management of inoperable pelvic tumors

(p < 0.05). Post-operative survival was better in the prenatal group (p < 0.05). At long-term follow up re-intervention-free survival was longer in the prenatal group (p < 0.04). Overall survival at maximum follow up was 92% in the prenatal compared to 84% in the postnatal group (p < 0.18). Conclusions: Prenatal detection of isolated congenital heart defects improves the short and longterm prognosis of the affected children.