Comparative study using indocyanine green and patent blue dye for sentinel lymph node biopsy in patients with early-stage cervical cancer.

BACKGROUND: Lymphatic involvement is the most important prognostic factor in early-stage cervical cancer. Sentinel lymph node biopsy is a viable alternative to systematic lymphadenectomy and may identify metastases more precisely. OBJECTIVE: To compare two tracers (indocyanine green and patent blue) to detect sentinel nodes. METHODS: A single-center, retrospective study of women treated due to early-stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 IA1 with lymphovascular invasion, IA2, and IB1). Location and tracer of all detected sentinel nodes had been documented for a prospective, multicenter trial (SENTIX trial). All sentinel nodes were sent to frozen section and final analysis through ultrastaging using a standard protocol. RESULTS: Overall, 103 patients were included. Bilateral detection rate for indocyanine green (93.2%) was significantly higher than for blue dye (77.7%; p=0.004). Their combined use significantly increased the bilateral detection to 99.0% (p=0.031). While 97.4% of all sentinel nodes were located below the common iliac vessels, no para-aortic nodes were labeled. Simultaneous bilateral detection with both tracers was found in 71.8% of the cases, of which the sentinel nodes were identical in 91.9%. Nine positive nodes were detected among seven patients (6.8%), all marked with indocyanine green while patent blue labeled six. Frozen section failed to detect one of three macrometastases and three of four micrometastases (sensitivity 43%; negative prediction value 96%). CONCLUSION: Anatomical distribution and topographic localization of the sentinel nodes obtained with these tracers were not different. Indocyanine green provided a significantly higher bilateral detection rate and had superior sensitivity to detect positive nodes compared with patent blue. Combining indocyanine green and blue dye increased the bilateral detection rate significantly.

Radical vaginal trachelectomy: long-term oncologic and fertility outcomes in patients with early cervical cancer.

OBJECTIVE: Radical vaginal trachelectomy is a fertility-preserving treatment for patients with early cervical cancer. Despite encouraging oncologic and fertility outcomes, large studies on radical vaginal trachelectomy are lacking. METHOD: Demographic, histological, fertility, and follow-up data of consecutive patients who underwent radical vaginal trachelectomy between March 1995 and August 2021 were prospectively recorded and retrospectively analyzed. RESULTS: A total of 471 patients of median age 33 years (range 21-44) were included. 83% (n=390) were nulliparous women. Indications were International Federation of Gynecology and Oncology (FIGO, 2009) stages IA1 with lymphvascular space involvement (LVSI) in 43 (9%) patients, IA1 multifocal in 8 (2%), IA2 in 92 (20%), IB1 in 321 (68%), and IB2/IIA in 7 (1%) patients, respectively. LVSI was detected in 31% (n=146). Lymph node staging was performed in 151 patients (32%) by the sentinel node technique with a median of 7 (range 2-14) lymph nodes and in 320 (68%) by systematic lymphadenectomy with a median of 19 (range 10-59) lymph nodes harvested. Residual tumor was histologically confirmed in 29% (n=136). In total, 270 patients (62%) were seeking pregnancy of which 196 (73%) succeeded. There were 205 live births with a median fetal weight of 2345 g (range 680-4010 g). Pre-term delivery occurred in 94 pregnancies (46%). After a median follow-up of 159 months (range 2-312), recurrences were detected in 16 patients (3.4%) of which 43% occurred later than 5 years after radical vaginal trachelectomy. Ten patients (2.1%) died of disease (five more than 5 years after radical vaginal trachelectomy). Overall survival, disease-free survival, and cancer-specific survival were 97.5%, 96.2%, and 97.9%, respectively. CONCLUSION: Our study confirms oncologic safety of radical vaginal trachelectomy associated with a high chance for childbearing. High rate of pre-term delivery may be due to cervical volume loss. Our long-term oncologic data can serve as a benchmark for future modifications of fertility-sparing surgery.

Oncologic and Fertility Outcomes After Simple Trachelectomy in Women With Early Cervical Cancer.

STUDY OBJECTIVE: This study aimed to present our case series of patients with early-stage cervical cancer undergoing simple trachelectomy (ST). Currently, radical trachelectomy is considered the most appropriate fertility-preserving procedure for the treatment of early-stage cervical cancer. However, there is increasing debate on the appropriate radicality of the surgery to preserve oncologic safety. DESIGN: Descriptive retrospective analysis of patient records and evaluation of questionnaires. SETTING: 2 gynecologic oncologic centers, surgeries performed by one surgical team. PATIENTS: 36 women with early-stage cervical cancer undergoing ST. INTERVENTIONS: Laparoscopic assisted simple vaginal trachelectomy. MEASUREMENTS: Demographic, histologic, fertility, and follow-up data of all patients who underwent ST between April 2007 and July 2021 were prospectively recorded and retrospectively analyzed. MAIN RESULTS: A total of 36 women (mean age: 28 years) underwent ST of whom 81% were nulliparous. Indications for ST were multifocal International Federation of Gynecology and Obstetrics stage IA1 (n = 30), stage IA1 L1 (n = 1), stage IA2 (n = 2), and stage IB1 (n = 3). Mandatory staging procedure was laparoscopic pelvic lymphadenectomy, including bilateral sentinel biopsy in 92% of the cases and systematic in 8%. Residual tumor was histologically confirmed in 8 specimens (22%); 18 women (50%) were seeking parenthood, and 13 succeeded (72%). There were 16 live births, all on term, with a median fetal weight of 3110 grams (2330-4420). One patient had a medical abortion owing to fetal congenital malformation. One pregnancy is ongoing. After a median follow-up of 91.5 months (9-174), all women are alive with no evidence of disease. CONCLUSION: ST represents a de-escalation compared with radical trachelectomy and provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. However, clear indications for this tailored fertility-preserving surgery have to be defined in well-designed trials.

Fertility sparing therapy in women with lymph node negative cervical cancer >2cm - oncologic and fertility outcomes of neoadjuvant chemotherapy followed by radical vaginal trachelectomy.

OBJECTIVE: Simple or radical trachelectomy are accepted fertility sparing therapies for patients diagnosed with cervical cancer ≤2 cm. In patients with larger tumors a fertility sparing concept is considered experimental. The aim of our study is to present oncological and fertility outcomes of laparoscopic pelvic lymphadenectomy followed by neoadjuvant chemotherapy and subsequent radical vaginal trachelectomy. These procedures were performed in two centers in patients diagnosed with cervical cancer of diameter >2 cm. METHOD: We retrospectively analyzed the demographic, histological, fertility and follow-up data of all patients with cervical cancer assessed as stage IB2, IB3 or IIA1 under the International Federation of Gynecology and Obstetrics (FIGO) 2018 system. These patients had undergone pelvic lymphadenectomy, followed by neoadjuvant chemotherapy and radical vaginal trachelectomy between February 2006 and June 2020 at Charité University Berlin and Asklepios Hospital, Hamburg. RESULTS: A total of 31 patients (mean age 29.5 years, range; 26-40) underwent neoadjuvant chemotherapy followed by radical vaginal trachelectomy in case of proven tumor-free lymph nodes. Twenty-six (84%) of these patients were nulliparous. Across all 31 patients, the initial tumor stages were FIGO 2018 stage IB2 (n=27), IB3 (n=3) and IIA1 (n=1).Lymphadenectomy was completed in all but one patient (sentinel) with a median of 33 (range; 11-47) pelvic lymph nodes. The neoadjuvant chemotherapy regimen was two cycles of paclitaxel, ifosfamide and cisplatin in 17 patients; three cycles of paclitaxel, ifosfamide and cisplatin in eight patients; two cycles of paclitaxel and cisplatin in four patients; two cylces cisplatin monoagent in one patient; and two cycles of paclitaxel and cisplatin followed by two cycles of paclitaxel, ifosfamide and cisplatin in one patient. Residual tumor was histologically confirmed in 17 specimens (55%). The median residual tumor size following neoadjuvant chemotherapy was 12 mm (range; 1-60). Fertility could be preserved in 27 patients (87%); two patients underwent adjuvant chemoradiation after radical vaginal trachelectomy due to high-risk histological features; two other patients underwent radical hysterectomy with adjuvant chemoradiation therapy following neoadjuvant chemotherapy. Of 18 (67%) patients seeking motherhood, 13 became pregnant (72%). There were 12 live births in 10 women, with a median fetal weight of 2490 grams (range; 1640-3560) and five miscarriages. After a median follow-up of 94.5 months (range; 6-183) three recurrences (11.1%) were detected, one patient (3.7%) died of the disease. CONCLUSION: Neoadjuvant chemotherapy followed by radical vaginal trachelectomy may be offered to patients seeking motherhood with cervical cancer >2 cm and histopathologically tumor-free lymph nodes, the rate of healthy baby pregnancy on discharge was 10/18 women (55%). This fertility-preserving strategy is associated with higher recurrence and death compared with what was published in the literature for women undergoing radical vaginal trachelectomy for tumors up to 2 cm.

Prospective assessment of urinary and bowel symptoms, and sexual function between laparoscopic assisted vaginal radical trachelectomy and radical hysterectomy.

OBJECTIVE: Radical trachelectomy is a valid alternative to radical hysterectomy in women with a desire to retain their fertility. Data regarding the oncological outcomes of radical trachelectomy are comparable with those of radical hysterectomy but information regarding urinary and sexual function is limited. The aim of this study was to prospectively evaluate and compare quality of life, urinary and bowel symptoms, and sexual dysfunction between patients who underwent laparoscopic assisted vaginal radical trachelectomy versus radical hysterectomy for early-stage cervical cancer. METHODS: Patients who underwent laparoscopic assisted vaginal radical trachelectomy or radical hysterectomy along with sentinel or systemic pelvic lymphadenectomy were included between May 2015 and January 2017. Patients were asked to complete a validated questionnaire (German pelvic symptom questionnaire) on bladder, bowel, prolapse, and sexual function, and total pelvic score, at least 48 hours before surgery and 6 months after surgery. RESULTS: A total of 51 patients were included. Of these, 26 patients (50.9%) underwent laparoscopic assisted vaginal radical trachelectomy and 25 (49.1%) underwent radical hysterectomy. No patient was converted to laparotomy. The majority of patients (76%) were diagnosed with International Federation of Gynecology and Obstetrics (FIGO 2018) stage 1B1 disease, with squamous cell carcinoma (54%) and grade II tumors (52%). Four patients (7.8 %) experienced perioperative complications (two grade II and two grade III complications according to the Clavien-Dindo classification). In the preoperative evaluation, the median scores for the four items of the questionnaire (bladder, bowel, prolapse, and sexual items) and total pelvic score were comparable between the two groups. The mean scores for radical hysterectomy and radical trachelectomy at the beginning of the study for bladder, bowel, prolapse, and sexual function were 0.93 versus 0.71, 0.71 versus 1.01, 0.12 versus 0.1, and 1.06 versus 1.0, respectively. On preoperative testing, the median scores for all four items of the questionnaire (pbladder=0.821, pbowel=0.126, pprolapse=0.449, psexual=0.965) and the total pelvic score (p=0.756) were comparable between the two groups. The radical hysterectomy group had worse total pelvic scores at the 6 month postoperative survey compared with baseline (p=0.03). There was no difference in bladder (p=0.07) or bowel symptoms (p=0.07) in the radical hysterectomy group comparing baseline with the 6 month assessment. Women undergoing radical hysterectomy experienced more urinary morbidity than women undergoing vaginal trachelectomy at 6 weeks (p=0.025). However, the mean bladder and pelvic scores in the 6 month control were comparable between patients who had and those who had not experienced urinary morbidity (pbladder=0.127, ptotal pelvic score=0.480). CONCLUSION: Patients undergoing laparoscopic assisted vaginal radical trachelectomy had similar pelvic scores in both the preoperative and postoperative periods. However, patients undergoing radical hysterectomy showed worse total pelvic scores on the postoperative assessment compared with the baseline evaluation. Urinary dysfunction in the early postoperative phase was more common in the radical hysterectomy group than in trachelectomy group.

Comparison of surgical and pathological parameters after laparoscopic transperitoneal pelvic/para-aortic lymphadenectomies.

OBJECTIVE: Lymphadenectomy is an integral part of surgical staging and treatment for patients with gynecologic malignancies. Since its introduction, laparoscopic lymphadenectomy has proved feasible, safe, and oncologically adequate compared with open surgery while morbidity is lower and hospital stay considerably shorter. The aim of this study was to examine if surgical outcomes may be improved after the initial learning curve is complete. METHODS: An analysis of 2535 laparoscopic pelvic and/or para-aortic lymphadenectomies was performed between July 1994 and March 2018 by one team of gynecologic oncology surgeons but with the consistent supervision of a consultant surgeon. Data were collected prospectively evaluating operative time, intra-operative and post-operative complications, number of lymph nodes, and body mass index (BMI). Previously published data of 650 patients treated after introduction of the method (period 1, 1994-2003) were compared with the latter 524 patients (period 2, 2014-2018). RESULTS: The median age of the 2535 patients was 43 years (IQR 34-57). The most common indication for pelvic and/or para-aortic lymphadenectomy was cervical cancer (n=1893). Operative time for para-aortic lymph node dissection was shorter in period 2 (68 vs 100 min, p<0.001). The number of harvested lymph nodes was increased for pelvic (19.2 (range 2-52) vs 21.9 (range 4-87)) and para-aortic lymphadenectomy (10.8 (range 1-52) vs 14.4 (range 4-64)), p<0.001. BMI did not have a significant influence on node count or operative time, with BMI ranging from 14.6 to 54.1 kg/m2. In contrast to period 1 (n=18, 2.9%), there were no intra-operative complications in period 2 (n=0, 0.0%, p<0.001) whereas post-operative complications were similar (n=35 (5.8%) in period 1; n=38 (7.6%) in period 2; p=0.32). CONCLUSION: In this large cohort of patients who underwent laparoscopic transperitoneal lymphadenectomy, lymph node count and peri-operative complications improved after the initial learning curve.

Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff - a multicenter analysis.

OBJECTIVE: Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. METHODS: Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. RESULTS: A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2-86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1-288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. CONCLUSION: The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.

Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial.

BACKGROUND: Surgical staging is associated with a significant rate of upstaging compared to clinical/radiological staging in patients with locally advanced cervical cancer. OBJECTIVE: To analyze the stage-specific percentage of pelvic and para-aortic lymph node metastases and the upstaging ratio in a prospective randomized trial (Uterus-11). METHODS: FIGO stage IIB-IVA cervical cancer patients were randomized to surgical staging (arm A) or to clinical staging and primary chemoradiation (arm B). Arm B patients underwent CT-guided biopsy of suspicious para-aortic lymph nodes. Confirmed para-aortic metastasis patients received extended-field radiation therapy. RESULTS: A total of 234 patients were enrolled, including 120 (arm A) and 114 (arm B) treated per protocol. The groups were well balanced. Pelvic and para-aortic lymph node metastases were identified after surgical staging in 51 and 24% of patients, respectively (p < 0.001). Pelvic and para-aortic lymph node metastases were confirmed in 45 and 20% of IIB patients and in 71 and 37% of IIIB patients, respectively. Upstaging occurred in 39/120 (33%) in arm A and in 9/114 (8%) in arm B (p < 0.001). CONCLUSION: The histological results in both groups led to a considerable rate of upstaging. Oncological data from the Uterus-11 study may reveal whether modified therapy translates into a survival benefit.

Oncologic Safety of Laparoscopy in the Surgical Treatment of Type II Endometrial Cancer.

BACKGROUND: Laparoscopy is considered the method of choice in the operative treatment of type I endometrial carcinoma (EC). However, there is a paucity of data regarding the safety of endoscopy for type II EC because these malignancies have several biological similarities with ovarian cancer. OBJECTIVES: This study aimed to evaluate the feasibility, operative outcomes, and oncologic safety of laparoscopic surgery in patients with type II EC. METHODS: A retrospective study with histologically confirmed serous or clear-cell EC without peritoneal carcinomatosis treated by laparoscopy (G1) or laparotomy (G2) was conducted. Procedures included hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. RESULTS: From 2009 to 2015, 89 patients were included; 53 women underwent laparoscopy and 36 underwent laparotomy. No relevant epidemiological or oncologic difference between groups was observed. The mean number of removed pelvic nodes was 16 [±10] and 12 [±13] in group 1 (G1) and group 2 (G2), respectively (P = 0.127). The mean number of dissected para-aortic nodes was significantly greater in the laparoscopic group (11 [±9] vs 6 [±9], P = 0.006). Para-aortic metastasis was significantly more often observed in the endoscopy group (26% vs 13%, P = 0.04). Adjuvant therapies were given to 86% of the patients in the study and 75% in the control group (P = 0.157). No excessive blood loss, casualty related to surgery, intraoperative complication, or conversion to laparotomy occurred in G1. Ten (18%) women from G1 and 36% (13/36) in G2 developed relevant postoperative complications (P = 0.03). The median duration of follow-up was 38 months for the laparoscopy and 47 months for the open surgery (P = 0.12). The 5-year overall and disease-free survival were similar, 86% versus 78% and 58% versus 51% for G1 and G2, respectively (P = 0.312). CONCLUSIONS: Laparoscopy is oncologically at least not inferior to laparotomy for the surgical treatment of type II EC. Endoscopic techniques are feasible, effective, result in significantly less morbidity, and improved quality staging. Although statistical significance was not reached, laparoscopy was associated with superior oncologic results.

Symptomatic Lymphocele Formation After Sentinel Lymph Node Biopsy for Early Stage Cervical Cancer.

In early stage cervical cancer, nodal status is the most important prognostic factor, and execution of retroperitoneal lymphadenectomy is currently an integral part of surgical therapy. Sentinel lymph node biopsy has been progressively incorporated with surgical therapy and could reduce morbidity. However, the current incidence of complications exclusively related to the procedure is unknown. We report on a 29-year-old woman affected by cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique Stage 1b1), who underwent sentinel lymph node biopsy in combination with radical vaginal trachelectomy, and who later developed a symptomatic pelvic lymphocele that required surgical therapy. Conservative procedures in the pelvic lymph nodes are not free of complications, especially with regard to the formation of symptomatic lymphoceles. This report brings to light an important discussion about the exact magnitude of the complications associated with the procedure.

Molecular Diagnosis for Nodal Metastasis in Endoscopically Managed Cervical Cancer: The Accuracy of the APTIMA Test to Detect High-risk Human Papillomavirus Messenger RNA in Sentinel Lymph Nodes.

STUDY OBJECTIVE: To evaluate the feasibility and accuracy of a commercially available test to detect E6/E7 mRNA of 14 subtypes of high-risk HPVs (APTIMA; Hologic, Bedford, MA) in the sentinel lymph nodes of CC patients laparoscopically operated. DESIGN: Prospective pilot study. SETTING: The study was conducted in the Department of Advanced Operative and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. PATIENTS: 54 women with HPV-positive CC submitted to laparoscopic sentinel node biopsy alone or sentinel node biopsy followed by systematic pelvic and/or para-aortic endoscopic lymphadenectomy. INTERVENTIONS: All removed sentinel lymph nodes (SLNs) underwent sample collection by cytobrush for the APTIMA assay before frozen section. MEASUREMENTS: Results obtained with the HPV mRNA test were compared with the definitive histopathological analysis of the SLNs and additional lymph nodes removed. RESULTS: A total of 125 SLNs (119 pelvic and 6 paraaortic) were excised with a mean number of 2.3 SLNs per patient. Final histopathologic analysis confirmed nodal metastases in 10 SLNs from 10 different patients (18%). All the histologically confirmed metastatic lymph nodes were also HPV E6/E7 mRNA positive, resulting in a sensitivity of 100%. Four histologically free sentinel nodes were positive for HPV E6/E7 mRNA, resulting in a specificity of 96.4%. CONCLUSION: The HPV E6/E7 mRNA assay in the SLNs of patients with CC is feasible and highly accurate. The detection of HPV mRNA in 4 women with negative SLNs might denote a shift from microscopic identification of metastasis to the molecular level. The prognostic value of this findings awaits further verification.

Potential Surgical and Oncologic Consequences Related to Skin Tattoos in the Treatment of Cervical Cancer.

STUDY OBJECTIVE: Skin tattoos on the feet, legs, and lower abdominal wall are progressively gaining popularity. Consequently, the number of tattooed women with cervical cancer has significantly increased in the last decade. However, pigments of tattoo ink can be transported to regional lymph nodes and potentially clog lymphatic pathways that might also be used by sentinel labeling substances. Therefore, here we report whether the presence of tattoo ink affected pelvic lymph nodes in women with early cervical cancer and discuss its potential oncologic and surgical consequences. DESIGN: Prospective observational study. SETTING: University Hospital in Hamburg, Germany (Canadian Task Force classification II2). PATIENTS: Women affected by cervical cancer. INTERVENTIONS: Between January 2014 and May 2016, 267 laparoscopic oncologic operations, including at least a pelvic sentinel or complete lymphadenectomy, were performed in the Department of Advanced Surgical and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. Among these, 191 patients were affected by cervical cancer. MEASUREMENTS AND MAIN RESULTS: Data of patients in whom dyed lymph nodes without the use of patent blue as a sentinel marker or different from blue-colored pelvic lymph nodes in the case of sentinel procedure were identified and prospectively collected. RESULTS: In 9 patients, skin tattoos localized in the lower extremities caused discoloration of at least 1 pelvic lymph node. This effect was observed in 40% of women (9/23) with tattoos in this area of the body. Mean patient age was 34 years (range, 27-56). All women had cutaneous tattoos on their feet or legs, and in 1 woman an additional tattoo situated on the inferior abdominal wall was observed. The stage of cervical cancer was FIGO IB1 in all cases. One woman was at the 16th week of gestation at the time of cancer diagnosis. On average, 26 pelvic lymph nodes (range, 11-51) were harvested from both pelvic basin sides. None of the removed lymph nodes was tumor involved. Three patients (33%) developed postoperatively infected lymphoceles on the side of the tattooed lymph nodes, and 1 woman had multiple episodes of fever without a clear origin. CONCLUSION: In women affected by cervical cancer with skin tattoos located in the lower limbs, the pelvic lymph nodes can be partially or totally occupied by the ink. This must be taken into consideration, especially for women scheduled exclusively for sentinel node biopsy. Infectious complications related to nodal dissection, in particular infected lymphoceles, may be more frequent in this population.

Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy.

BACKGROUND: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. OBJECTIVES: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. METHODS: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. RESULTS: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). CONCLUSION: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.

How much platinum passes the placental barrier? Analysis of platinum applications in 21 patients with cervical cancer during pregnancy.

OBJECTIVE: Cervical cancer is the most common solid cancer diagnosed in pregnancy. Platinum is an active drug in the treatment of patients with cervical cancer. In the second and third trimesters, platinum is used to prevent cancer progression until fetal maturity is reached. However, knowledge about the transplacental passage of platinum is very limited. STUDY DESIGN: Between May 2008 and June 2014, platinum-based neoadjuvant chemotherapy was applied to 21 consecutive patients with cervical cancer diagnosed in their second trimester. At the time of delivery by cesarean delivery, synchronous samples from maternal blood, umbilical cord blood, and amniotic fluid were taken and analyzed for platinum concentrations. RESULTS: The mean week of gestation at cancer diagnosis was 17 (13-23). On average 3 (range, 2-4) cycles of chemotherapy were applied. Cesarean deliveries were carried out between 30.4 and 36.5 weeks of gestation. Twenty-two healthy babies without renal, hepatic, auditory, or hematopoietic impairment were delivered. Platinum concentrations in umbilical cord blood and amniotic fluid were 23-65% and 11-42% of the maternal blood, respectively. CONCLUSION: This series on in vivo measurement of platinum concentrations in the fetomaternal compartment observed that because of consistently lower platinum values in the fetoplacental unit, a placental filtration mechanism of platinum may be assumed.

Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.

BACKGROUND AND OBJECTIVES: Endometrial cancer (EC) has an increasing incidence worldwide. Despite the unequivocal prognostic importance of nodal status, systematic lymphadenectomy is associated to elevated morbidity. Sentinel lymph node (SLN) biopsy is designed to avoid extensive nodal dissection and provide crucial oncologic information. The goal of this prospective study was to determine the feasibility, safety, and accuracy of laparoscopic SLN biopsy in EC obtained through hysteroscopic injection of technetium-99 (Tc-99). METHODS: From January 2008 to December 2012, a total of 42 women with EC were included in the study. We injected 20 mBq of Tc-99 hysteroscopically underneath the tumor minutes before definitive surgery. Thereafter, laparoscopic SLN identification /biopsy followed by pelvic and para-aortic lymphadenectomy, hysterectomy, and bilateral salpingo-oophorectomy were executed. RESULTS: The total number of removed nodes was 970. The detection rate of the method was 73% (31/42). Among the 70 isolated SLNs, 35% (24) were exclusively identified in the para-aortic area. Fourteen patients (45%) had SLN only in the pelvic region, whereas 11 (35%) had SLN in both pelvic and para-aortic areas and 6 women (20%) had isolated para-aortic SNL. Nodal metastases were histologically confirmed in 9 patients (22%), and SLN was identified in 7 of 9 patients (78%). Although the obtained specificity was 100% and the negative predictive value was 89%, the sensitivity was only 58% (false-negative rate of 42%). CONCLUSIONS: We could demonstrate that endoscopic SLN biopsy obtained through hysteroscopic injection of Tc-99 is a feasible and safe method. Despite the restricted number of included patients in this series, the obtained sensitivity and false-negative rates raise some questions about the real accuracy of the procedure in EC. Larger validation trials requiring quality pelvic and para-aortic lymphadenectomy are essential to correctly evaluate the method.

Hard and soft tissue changes around implants installed in regular-sized and reduced alveolar bony ridges. An experimental study in dogs.

OBJECTIVE: To study bony and soft tissue changes at implants installed in alveolar bony ridges of different widths. MATERIAL AND METHODS: In 6 Labrador dogs, the mandibular premolars and first molars were extracted, and a buccal defect was created in the left side at the third and fourth premolars by removing the buccal bone and the inter-radicular and interdental septa. Three months after tooth extraction, full-thickness mucoperiosteal flaps were elevated, and implants were installed, two at the reduced (test) and two at the regular-sized ridges (control). Narrow or wide abutments were affixed to the implants. After 3 months, biopsies were harvested, and ground sections prepared for histological evaluation. RESULTS: A higher vertical buccal bony crest resorption was found at the test (1.5 ± 0.7 mm and 1.0 ± 0.7 mm) compared to the control implants (1.0 ± 0.5 mm and 0.7 ± 0.4 mm), for both wide and narrow abutment sites. A higher horizontal alveolar resorption was identified at the control compared to the test implants. The difference was significant for narrow abutment sites. The peri-implant mucosa was more coronally positioned at the narrow abutment, in the test sites, while for the control sites, the mucosal adaptation was more coronal at the wide abutment sites. These differences, however, did not reach statistical significance. CONCLUSIONS: Implants installed in regular-sized alveolar ridges had a higher horizontal, but a lower vertical buccal bony crest resorption compared to implants installed in reduced alveolar ridges. Narrow abutments in reduced ridges as well as wide abutments in regular-sized ridges yielded less soft tissue recession compared to their counterparts.

Healing at mandibular block-grafted sites. An experimental study in dogs.

AIM: The aim of this study was to evaluate the healing of autologous bone block grafts or deproteinized bovine bone mineral (DBBM) block grafts applied concomitantly with collagen membranes for horizontal alveolar ridge augmentation. MATERIAL AND METHODS: In six Labrador dogs, molars were extracted bilaterally, the buccal bony wall was removed, and a buccal box-shaped defect created. After 3 months, a bony block graft was harvested from the right ascending ramus of the mandible and reduced to a standardized size. A DBBM block was tailored to similar dimensions. The two blocks were secured with screws onto the buccal wall of the defects in the right and left sides of the mandible, respectively. Resorbable membranes were applied at both sides, and the flaps sutured. After 3 months, one implant was installed in each side of the mandible, in the interface between grafts and parent bone. After 3 months, biopsies were harvested and ground sections prepared to reveal a 6-month healing period of the grafts. RESULTS: 77 ± 6.2% and 5.9 ± 7.5% of vital mineralized bone were found at the autologous bone and DBBM block graft sites, respectively. Moreover, at the DBBM site, 63 ± 11.7% of connective tissue and 31 ± 15.5% of DBBM occupied the area analyzed. Only 0.2 ± 0.4% of DBBM was found in contact with newly formed bone. The horizontal loss was in a mean range of 0.9-1.8 mm, and 0.3-0.8 mm, at the autologous bone and DBBM block graft sites, respectively. CONCLUSIONS: Autologous bone grafts were vital and integrated to the parent bone after 6 months of healing. In contrast, DBBM grafts were embedded into connective tissue, and only a limited amount of bone was found inside the scaffold of the biomaterial.

Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature.

This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO.

Prevention of lymphoceles using FloSeal and CoSeal after laparoscopic lymphadenectomy in patients with gynecologic malignancies.

INTRODUCTION: Pelvic ± para-aortic lymphadenectomy (LAE) is an essential element of staging and treatment of different gynecologic malignancies. However, LAE can induce asymptomatic and symptomatic pelvic lymphoceles (LCs) in a considerable percentage of patients. Therapy of symptomatic LCs may cause additional morbidity. The best strategy to reduce the rate of LCs has not established yet. MATERIALS AND METHODS: Between January 2011 and May 2012, transperitoneal laparoscopic pelvic ± para-aortic LAE was performed at the Department of Gynecology at Charité University Hospital Berlin in 238 patients with cervical, endometrial, ovarian, or groin-positive vulvar cancer. The application of FloSeal (Baxter, Deerfield, IL) and CoSeal (Baxter) was used in 25 patients (group A) as an alternative to routine pelvic drainage after LAE. A case-control comparison was performed on 25 patients (group B) with bilateral drainage after complete LAE. The primary objective of this pilot study was to evaluate the feasibility and safety of the method. As a secondary objective, we evaluated the incidence of LCs and symptomatic LCs in both groups. The detection of LCs was performed during oncologic follow-up by sonography, computed tomographic imaging, or magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: Pelvic (n = 50) or pelvic + para-aortic (n = 42) LAE was performed in 44 patients with cervical, 2 with endometrial, 1 with ovarian, and 2 with groin-positive vulvar cancer, respectively. In group B (n = 25), systematic bilateral pelvic drainage was placed after finishing LAE, whereas in group A (n = 25) LAE areas were sealed with 5 mL FloSeal on each side and sprayed with CoSeal afterward without placing drains. In 14 of 50 patients (28%), LCs were detected. In a subgroup of patients with cervical cancer (88% of the cohort), symptomatic LCs occurred in 11% in group A and 18% in group B. Operative revision of symptomatic LCs was necessary in 5% and 18% in groups A and B, respectively (p = .66). Mean Hospital stay was significant shorter in group A (6 days) versus B (8 days) (p = .027). CONCLUSION: The results of this case-controlled pilot study indicate that the application of FloSeal and CoSeal after transperitoneal LAE is feasible and safe, may reduce hospital stay, and may potentially decrease the rate of symptomatic LCs in patients with gynecologic malignancies.

Vaginal Morcellation Inside Protective Pouch: A Safe Strategy for Uterine Extration in Cases of Bulky Endometrial Cancers: Operative and Oncological Safety of the Method.

OBJECTIVE: To evaluate the operative and oncologic outcomes of an innovative technique for organ morcellation in patients scheduled for laparoscopic treatment of uterine malignancies. BACKGROUND: Endoscopy is currently considered the standard of care for the operative treatment of endometrial cancer; however, the use of minimal invasive surgery (MIS) is restricted in patients with a bulky uterus or narrow vagina. Conventional unprotected intraperitoneal uterine fragmentation is indeed contraindicated in these cases. Consequently, oncologically safe methods to render these patients eligible for MIS are urgently needed. INTERVENTION: Prospective study of women with histologically proven endometrial cancer in which uterus removal was a realistic concern owing to both organ size and proportionality. The patients underwent laparoscopic staging, including retroperitoneal lymphadenectomy, total hysterectomy, and bilateral salpingo-oophorectomy, followed by vaginal morcellation of the uterus inside a protective pouch (LapSac). RESULTS: In our series of 30 cases, we achieved successful completion in all patients, without conversion to laparotomy. No surgery-related casualty or intraoperative morbidity was observed. The mean organ size was 246 g (range, 148-420 g), and the average additional operative time related to vaginal morcellation was 16 minutes (range, 9-28 minutes). Proper histopathological staging according to 2009 FIGO staging guidelines could be performed in all specimens. Two patients (6%) presented with significant postoperative complications, 1 each with vesicovaginal fistula and vaginal vault dehiscence. Fourteen patients (46%) needed adjuvant therapy. After a median follow-up of 20 months (range, 6-38 months), the 12-month and 24-month overall survival was 100% and 73.4% (95% confidence interval, 51%-96%), respectively. Four patients with positive lymph nodes died of distant metastasis. No case of pelvic or local relapse was observed. CONCLUSION: Vaginal morcellation following oncologic principles is a feasible method that permits rapid uterine extraction and potentially avoids unnecessary laparotomies. This series suggests that the technique may be oncologically safe and also can be used in cases of uterine pathology of uncertain malignancy.