Marek Pluta

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.

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.

A prospective study in detection of lower-limb lymphedema and evaluation of quality of life after vulvar cancer surgery.

Background Lower-limb lymphedema is one of the most disabling adverse effects of vulvar cancer surgery. Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a modern noninvasive method to detect lymphedema. The first aim of this study was to prospectively determine the prevalence of secondary lower-limb lymphedema after surgical treatment for vulvar cancer using objective methods, circumference measurements and MFBIA technique. The second aim was to compare quality of life (QoL) before and 6 months after vulvar surgery. Methods Twenty-nine patients underwent vulvar cancer surgery in our study: 17 underwent inguinofemoral lymphadenectomy (RAD), and 12 underwent sentinel lymph node biopsy (CONS). Patients were examined before and 6 months after vulvar surgery by measuring the circumference of the lower limbs and with MFBIA. A control group of 27 healthy women was also measured. To evaluate QoL, the European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 months after surgery. Results Using circumference measurement, 9 lymphedemas (31%) were diagnosed: 3 (25%) in the CONS and 6 (37.5%) in the RAD group (P = 0.69). After vulvar surgery, patients in the RAD group reported more fatigue and worsening of physical and role functioning. When comparing both groups, the RAD group had significantly worse parameters in social functioning, fatigue, and dyspnea. Conclusions Lower radicality in inguinofemoral lymphadenectomy shows a trend toward lower morbidity and significantly improves QoL. Multifrequency Bioelectrical Impedance Analysis was tested in these patients as a noninvasive, objective method for lymphedema detection. Detection of lymphedema based on subjective evaluations proved to have an unsatisfactory sensitivity. Less radical surgery showed objectively better results in QoL.

High-dose density neoadjuvant chemotherapy in bulky IB cervical cancer.

OBJECTIVE The endpoint of this prospective study is to evaluate response rate, survival and toxicity of high-dose density neoadjuvant chemotherapy (NAC) in bulky IB cervical cancer. MATERIAL AND METHODS Between January 1998 and December 2009, 154 women were enrolled into study. Three patients were withdrawn. Of the 151 women, 119 had stage IB2 cervical cancer (78.8%) and 32 had stage IB1 cancer (21.2%) infiltrating the whole cervical stroma. Women received 3-4cycle cisplatin-75mg/m(2) and ifosfamide-2g/m(2) in cases of squamous-cell cancer or cisplatin-75mg/m(2) and doxorubicin-35mg/m(2) in adenocarcinoma every 10days and then underwent radical hysterectomy type III. Patients who had non-resectable disease underwent chemoradiotherapy. RESULTS The overall response rate (reduction of tumor volume more than 50%) was 78.8%. Reduction of tumor volume less than 50% was seen in 15.2%. Tumor progression during chemotherapy occurred in nine patients (6.0%). There were positive lymph-nodes in 26 patients (18.3%) of the 142 that underwent surgery. 38 women underwent adjuvant radiotherapy (26.7%). There were 26 recurrences (17.2%). After surgery 20 women recurred from 142 (14.1%) and after primary radiotherapy 6 from 9 women recurred (66.7%). 25 of 151 women died from disease (16.5%). At the time of the study, surgery was performed in 118 women 5 or more years ago, 19 of them died of disease. Five-year specific survival is 83.6%. Grade 3-4 neutropenia was found in only 7.3% of the women, and grade 3-4 thrombocytopenia were found in 1.3%. CONCLUSION High-dose density NAC appears to be feasible in the treatment IB bulky cervical cancer and toxicity is acceptable. Adjuvant radiotherapy was used only in 26.7%.