Petr Skapa

Fertility-sparing surgery in patients with cervical cancer

There are several types of fertility saving procedures that can be done in patients with cervical cancer, which differ in terms of surgical approach and extent of paracervical resection. This review assesses oncological and pregnancy results after different procedures. The oncological results of vaginal radical trachelectomies (VRT) and abdominal radical trachelectomies (ART) are similar for tumours less than 2 cm in size, and are now considered safe surgical procedures. Oncological outcomes of VRT and ART in tumours larger than 2 cm are also identical, but the results cannot be considered satisfactory. Preliminary findings of less radical procedures (ie, deep cone and simple trachelectomy) in patients with tumours less than 2 cm, and negative sentinel and other pelvic lymph nodes, are comparable with the results of VRT and ART. Downstaging tumours larger than 2 cm by neoadjuvant chemotherapy is still an experimental procedure and will need multicentre cooperation to verify its oncological safety. Pregnancy results vary statistically with the different methods.

A less radical treatment option to the fertility-sparing radical trachelectomy in patients with stage I cervical cancer ☆

The purpose of the two pilot studies was to determine the feasibility and safety of using less-radical fertility-preserving surgery: laparoscopic lymphadenectomy with sentinel lymph node identification (SLNI) followed by a large cone or simple trachelectomy (LAP-I protocol) and the LAP-III protocol, which includes neoadjuvant chemotherapy (NAC). LAP-I: Forty women underwent laparoscopic SLNI, frozen-section analysis, and a complete pelvic lymphadenectomy as the first step of treatment. Seven days after final histopathological processing of dissected nodes, a large cone or simple vaginal trachelectomy was performed in patients with negative nodes. Nine women had a tumor larger than 20 mm, prompting the administration of three cycles of NAC before surgery. LAP-I: Six frozen sections were positive (15%). In these cases, a type III Wertheim was immediately performed. There were no false-negative SLNs. There was one central recurrence, but after chemoradiation therapy, there was no evidence of the disease 62 months post-treatment. Twenty-four of 32 women whose reproductive ability had been maintained tried to conceive. Of these 24 women, 17 became pregnant (71% pregnancy rate). Eleven mothers gave birth to 12 children (1 at 24 weeks, 1 at 34 weeks, 1 at 36 weeks, and 9 between 37 and 39 weeks). LAP-III: Nine patients were included. In 7 of these 9 women, reproductive ability was maintained, with 3 women becoming pregnant (1 full term and 2 ongoing). SLNI improves safety in fertility-sparing surgery. Large cone or simple trachelectomy combined with laparoscopic pelvic lymphadenectomy can be a feasible method that yields a high, successful pregnancy rate. NAC followed by fertility-sparing surgery is an experimental alternative treatment for larger tumors.

Less radical fertility-sparing surgery than radical trachelectomy in early cervical cancer.

The purpose of this pilot study was to determine feasibility and safety of a novel and less radical fertility-preserving surgery; laparoscopic lymphadenectomy with sentinel lymph node identification (SLNI) followed by large cone or simple trachelectomy. Obstetrical and oncologic outcomes were evaluated. Twenty-six patients (6-IA2, 20-IB1) selected on basis of favorable cervical tumor characteristics and the desire to maintain fertility underwent laparoscopic SLNI, frozen section (FS), and a complete pelvic lymphadenectomy as first step of treatment. All of nodes were submitted for microscopic evaluation (sentinel nodes for ultramicrostaging). After a 7-day interval, large cone or simple vaginal trachelectomy was performed in patients with negative nodes. The average of sentinel nodes per side was 1.50 and the average of total nodes was 28.0. Four FS were positive (15.4%). In these cases, Wertheim radical hysterectomy type III was immediately performed. We had no false-negative SLN neither on FS nor on final pathology assessment. Median follow-up was 49 months (18–84). One central recurrence (isthmic part of uterus) was observed 14 months after surgery. This patient was treated with radical chemoradiotherapy, and there was no evidence of the disease 36 months after treatment. Fifteen women planned pregnancy, 11 women became pregnant (15 pregnancies), and 7 women delivered eight children (one in 24 weeks, one in 34 weeks, one in 36 weeks, and five between 37 and 39 weeks). We conclude that lymphatic mapping and SLNI improves safety in this fertility sparing surgery. Large cone or simple trachelectomy combined with laparoscopic pelvic lymphadenectomy can be a feasible method with a high successful pregnancy rate

Less radical surgery than radical hysterectomy in early stage cervical cancer: a pilot study.

OBJECTIVE The purpose of this pilot study was to evaluate the feasibility and safety of a less radical surgery; laparoscopic lymphadenectomy followed by a simple vaginal hysterectomy in sentinel lymph node (SLN) negative early cervical cancer patients. Treatment-associated morbidity and oncological outcome were evaluated. PATIENTS AND METHODS From December 2000 to September 2007, 60 patients (50 squamous and 10 adenocarcinoma patients) in stages 3-IA1, 11-IA2 and 46-IB1 with median age of 44.6 years (range 33-64 years) were enrolled. Patients were selected based on favorable cervical tumors (IA1 with lymph-vascular space invasion [LVSI], IA2 and IB1 with tumor size less than 20 mm and less than half of stromal invasion). All patients underwent laparoscopic SLN identification using frozen section (FS). Negative SLN patients underwent complete pelvic laparoscopic lymphadenectomy and vaginal hysterectomy. FS positive patients underwent radical hysterectomy with low paraaortic lymphadenectomy. RESULTS The average number of sentinel nodes per side was 1.4 with detection rate per side of 95%. The average number of removed nodes was 23.2. Five patients (8.3%) were SLN positive. There were two false negative FS results (both were micrometastases in SLN). Median follow-up was 47 months (range 12-92). There were no recurrences in 55 SLN negative patients and in 5 SLN positive patients. CONCLUSION Lymphatic mapping and SLN identification improved safety in less radical surgery in early stage cervical cancer. This preliminary study showed that it is both feasible and safe to reduce the radicality of parametrial resection for small tumor volume in SLN negative patients. Results also indicated that treatment-associated morbidity is low.

A prospective study of sentinel lymph node status and parametrial involvement in patients with small tumour volume cervical cancer

OBJECTIVE The purpose of prospective study is to determine incidence and distribution of pelvic lymph node (LN) involvement, sentinel lymph node (SLN) involvement and pathologic parametrial involvement (PI) in stage Ia2 and small Ib1 cervical cancer. PI is defined as positive parametrial LN or discontinuous malignant cells in parametrium. METHODS After radical abdominal hysterectomy, 158 women patients were stratified into two groups based on tumour size: In Group 1 (91 women) tumours were less than 20 mm and less than half of stromal invasion. In Group 2 (67 women) tumours were between 20 and 30 mm and infiltration was not more than 2/3 of cervical stroma. RESULTS In Group 1 positive SLN was detected in 11(12.1%) patients; of these, 3 (27.3%) had positive PI. In 80 women with negative SLN PI was not detected. In Group 2 positive SLN was detected in 14 (20.9%) patients: PI was found in four (28.6%) of these 14 patients. No PI was detected in 53 women with negative SLN. CONCLUSION No PI was observed in early cervical cancer if SLNs were negative. However, we found PI in 28.0% of women with positive SLN. Statistical analysis revealed that the results were highly significant. Based on our results, radical removal of parametrium in SLN negative patients is questionable.

Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for the classification of vulvar squamous cell carcinoma precursors and for the efficacy of prophylactic HPV vaccination.

The term vulvar intraepithelial neoplasia (VIN) introduced in 1986 incorporates 3 grades of usual VIN (u-VIN I-III) and the differentiated VIN (d-VIN). Although u-VIN is etiologically associated with the human papillomavirus (HPV) infection, d-VIN represents an alternative HPV negative pathway of vulvar carcinogenesis. In 2004, the u-VIN I category was abandoned and u-VIN II and III were merged. Further, an alternative Bethesda-like terminology scheme presenting the term vulvar intraepithelial lesion was proposed recently. To analyze the impact of HPV profiles of vulvar precancerous lesions for their classification and to assess the presumable efficacy of the prophylactic HPV vaccination, 269 vulvar excisions representing lichen sclerosus, lichen simplex chronicus, condylomata acuminata, d-VIN, all grades of u-VIN and squamous cell carcinomas were subjected to the HPV typing by use of GP5+/6+ polymerase chain reaction and reverse line blot hybridization. The results showed different HPV profiles, and also differing frequency of multiple-type HPV infection and the age structure in patients with u-VIN II and III. The biologic heterogeneity within the u-VIN II category was also demonstrated. u-VIN I was distinguished as a rare disorder associated with high-risk HPV infection. We conclude that the original VIN terminology proposed in 1986 seems to be appropriate for the classification of vulvar squamous dysplastic lesions. The spectrum of HPV types found in vulvar squamous cell carcinomas indicates that the efficacy of HPV vaccination in preventing vulvar cancer might be diminished in the studied population, because the recently developed prophylactic vaccines are targeted against a limited number of HPV types.

Further data on sentinel lymph node mapping in vulvar cancer by blue dye and radiocolloid Tc99.

We studied the distribution of sentinel lymph nodes (SLNs) in vulvar cancer using blue dye and 99mTc radiocolloid and evaluated the techniques used, including the optimum timing of preoperative scintigraphy scans and its contribution to 99mTc SLN detection over that of the intraoperative handheld gamma probe. Fifty-nine women with squamous cell cancers <4 cm treated at our institution between December 2001 and December 2005 were included in this study. Blue dye alone was used in the first 16 women (group A) and the combination of 99mTc and blue dye was used on 43 women (group B). Of the 118 SLN detected in 82 groins, 83.9% (99) were sited in the superficial medial and intermediate inguinal chain, none were in superficial lateral groin, 16.1% (19) were deep femoral. The patient-specific SLN detection and false-negative rate in group B was 100% and 0%, compared to 68.8% (11/16 cases) and 6.3% (1/16) in group A. The optimum timing for preoperative lymphoscintigraphy scans was 45 min postinjection, but intraoperative use of the handheld gamma probe yielded 15% more “hot” nodes and allowed tailored placement of the lymphadenectomy incision. Eighty-four percent of SLNs were in the medial and intermediate region of the superficial inguinal chain, 16.1% were deep femoral. The combined use of 99mTc radiocolloid and blue dye was significantly superior at SLN detection than blue dye alone. 99mTc SLN detection using the intraoperative handheld probes was not enhanced by preoperative scintigraphy scans.

Oncological and pregnancy outcomes after high-dose density neoadjuvant chemotherapy and fertility-sparing surgery in cervical cancer

OBJECTIVE 28 women under 35years with early-stage cervical cancer and strong desire for fertility preservation that do not fulfil standard criteria for fertility-sparing surgery (tumour larger than 2cm or with deep of infiltration more than half of stroma) were included in prospective study. METHODS Dose-dense neoadjuvant chemotherapy (NAC) was performed on all 28 patients in 10-day intervals: cisplatin plus ifosfamide in squamous cell cancer (15 women-53.6%) or cisplatin plus doxorubicin in adenocarcinoma (13 women-46.3%). Patients underwent laparoscopic lymphadenectomy and vaginal simple trachelectomy after NAC. Patients with positive lymph nodes or inadequate free surgical margins underwent radical hysterectomy. RESULTS No residual disease was found in 6 women (21.4%), microscopic disease was observed in 11 women (39.3%) and macroscopic tumour in was observed in 11 women (39.3%). Ten women (35.7%) lost fertility. Four women (20%) after fertility-sparing surgery recurred, two died of the disease (10%). Fertility was spared in 20 (71.4%) women and 10 of them became pregnant (50%). Eight women delivered ten babies (6 term and four preterm deliveries). There were two miscarriages in second trimester (in one woman) and one in first trimester. One woman underwent four unsuccessful cycles of IVF, one failed to become pregnant and one recurred too early. Two women underwent chemoradiotherapy for recurrence and lost chance for pregnancy. CONCLUSIONS Downstaging by NAC in IB1 and IB2 cervical cancer before fertility-sparing surgery is still an experimental procedure, but shows some promise. Long-term results in relation to oncological outcome for this concept are still needed.

Current status of sentinel lymph node mapping in the management of endometrial cancer.

The prognosis of endometrial cancer (EC) is generally favorable, while lymph node status remains the most important prognostic factor. Sentinel lymph node mapping (SLNM) could help to find women in whom adjuvant therapy could be omitted. This review analyzes different techniques of injection and histopathologic elaboration of SLNM in EC. Results of studies on SLNM in ECs seem to be promising, but only a small series have been published so far. The studies are subdivided into three groups by the technique of injection (hysteroscopic, subserosal and cervical). Range of detection rate for SLNM varies from 45 to 100%. Hysteroscopic injection is not easy to learn; moreover, exact peritumoral injection in large tumors is often impossible. Subserosal administration of tracer is difficult during laparoscopic or robotic surgery. Cervical injection is quite a controversial technique because distribution of SLNs in ECs is different from cervical cancer; moreover, there is no large study using cervical injection with systematic pelvic and para-aortic lymphadenectomy.

High–dose density chemotherapy followed by simple trachelectomy: full‐term pregnancy

We report five patients with early-stage cervical cancer who do not fulfill criteria of fertility-sparing surgery (tumor more than 2 cm in the biggest diameter or infiltrating more than half of stroma). Five patients received three cycles of dose density neoadjuvant chemotherapy (NAC) at a 10-day interval: cisplatin plus ifosfamide in squamous cell cancer or plus doxorubicin in adenocarcinoma with good tolerance. After NAC, they underwent laparoscopic pelvic lymphadenectomy and vaginal simple trachelectomy. Two patients had no residual tumor, two had only microscopic residual disease, and one had macroscopic residual disease. Two women became pregnant 5 and 8 months after surgery, one delivered in term healthy baby and one is now in the second trimester of pregnancy without any complications. NAC followed by fertility-sparing surgery seems to be feasible treatment for women with tumor bigger than 2 cm or infiltrated more than half of the stroma.