Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Oncological and obstetrical outcomes after neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer ≥2 cm.

OBJECTIVE: There is significant debate between up-front radical trachelectomy versus neo-adjuvant chemotherapy before fertility-sparing surgery in patients with tumors ≥2 cm. The aim of this study was to report on the oncological and obstetrical outcome of neo-adjuvant chemotherapy followed by fertility-sparing surgery, in patients diagnosed with cervical cancer ≥2 cm. METHODS: This was a retrospective review of patients diagnosed with cervical cancer measuring ≥2 cm to ≤6 cm, who were scheduled to undergo neo-adjuvant chemotherapy before fertility-sparing surgery, at six institutions from four Latin American countries between February 2009 and February 2019. Data collected included: age, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage, histology, tumor size, pre-treatment imaging work-up, chemotherapy agents and number of cycles, toxicity, clinical and imaging response rate, type of fertility-sparing surgery, pathology results, timing of lymphadenectomy, follow-up time, and obstetrical and oncological outcomes. RESULTS: A total of 25 patients were included, with a median age of 27 years (range 20-37): 17 patients had stage IB1, 7 had stage IB2 cervical cancer, and 1 patient had stage IIA1 (FIGO 2009); 23 patients had squamous cell carcinoma and 2 patients had adenocarcinoma. The median number of chemotherapy cycles was 3 (range 3-6) and no toxicity grade 3-4 was reported. Lymphadenectomy was performed before chemotherapy in 6 (24%) patients. After neo-adjuvant chemotherapy 20 patients were scheduled for radical trachelectomy (11 abdominal and 9 laparoscopic) and 5 patients for conization. After surgery, no residual disease was found in 11 patients (44%). Fertility was preserved in 23 patients (92%) and 10 patients became pregnant (43.5%). After a median follow-up time of 47 months (13-133), 3 patients had recurrent disease (3/23=13%), 2 were alive without disease, and 1 patient had disease at last contact. CONCLUSION: Neo-adjuvant chemotherapy followed by fertility-sparing surgery is feasible in well selected patients with cervical tumors ≥2 cm. Future studies should focus on the timing of lymphadenectomy and type of cervical surgery.

Neoadjuvant chemotherapy in pregnant patients with cervical cancer: a Latin-American multicenter study.

OBJECTIVE: To describe oncologic and obstetric outcomes in patients diagnosed with cervical cancer during pregnancy who had a successful delivery after neoadjuvant chemotherapy. METHODS: A multicenter retrospective review was conducted in 12 institutions from six Latin American countries, between January 2007 and December 2018. Data collected included clinical characteristics, neoadjuvant chemotherapy agents, treatment, obstetric and oncologic outcomes. RESULTS: Thirty-three patients were included. Median age was 34 years (range 31-36). Twenty (60.6%) women were diagnosed at early stage (IB), and 13 (39.4%) with locally advanced stage (IIA-IIIB) according to FIGO 2009 classification. Carboplatin and paclitaxel was the most frequent combination used (60.6%). Partial and complete response rates were 27.3% and 9.1%, respectively. Median gestational age at delivery was 35 weeks (range 34-36). All patients had live births delivered by cesarean section. Obstetric pathology: pre-term labor, placenta percreta or intra-uterine growth restriction, was documented in seven patients (21.2%). Two (6.1%) neonates had low birth weight. Definitive treatment was primary chemo-radiation in 19 (57.6%) patients, radical hysterectomy in 11 (33.3%), abandoned radical hysterectomy with para-aortic lymphadenectomy and ovarian transposition in 1 patient (3.0%), and no further treatment in 2 (6.1%) patients. After a median follow-up of 16.3 months (range 2.0-36.9), 8 (26.7%) patients had recurrent disease. Of these, four (13.3%) died due to disease. CONCLUSION: Neoadjuvant chemotherapy may be offered to patients wishing to preserve an ongoing pregnancy in order to achieve fetal maturity. Long-term consequences of chemotherapy in the child are yet to be determined.

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

OBJECTIVE: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. METHODS: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only. RESULTS: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). DISCUSSION: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (LACC): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: In the phase 3 LACC trial and a subsequent population-level review, minimally invasive radical hysterectomy was shown to be associated with worse disease-free survival and higher recurrence rates than was open radical hysterectomy in patients with early stage cervical cancer. Here, we report the results of a secondary endpoint, quality of life, of the LACC trial. METHODS: The LACC trial was a randomised, open-label, phase 3, non-inferiority trial done in 33 centres worldwide. Eligible participants were women aged 18 years or older with International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with lymphovascular space invasion, IA2, or IB1 adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who were scheduled to have a type 2 or 3 radical hysterectomy. Participants were randomly assigned (1:1) to receive open or minimally invasive radical hysterectomy. Randomisation was done centrally using a computerised minimisation program, stratified by centre, disease stage according to FIGO guidelines, and age. Neither participants nor investigators were masked to treatment allocation. The primary endpoint of the LACC trial was disease-free survival at 4·5 years, and quality of life was a secondary endpoint. Eligible patients completed validated quality-of-life and symptom assessments (12-item Short Form Health Survey [SF-12], Functional Assessment of Cancer Therapy-Cervical [FACT-Cx], EuroQoL-5D [EQ-5D], and MD Anderson Symptom Inventory [MDASI]) before surgery and at 1 and 6 weeks and 3 and 6 months after surgery (FACT-Cx was also completed at additional timepoints up to 54 months after surgery). Differences in quality of life over time between treatment groups were assessed in the modified intention-to-treat population, which included all patients who had surgery and completed at least one baseline (pretreatment) and one follow-up (at any timepoint after surgery) questionnaire, using generalised estimating equations. The LACC trial is registered with ClinicalTrials.gov, NCT00614211. FINDINGS: Between Jan 31, 2008, and June 22, 2017, 631 patients were enrolled; 312 assigned to the open surgery group and 319 assigned to the minimally invasive surgery group. 496 (79%) of 631 patients had surgery completed at least one baseline and one follow-up quality-of-life survey and were included in the modified intention-to-treat analysis (244 [78%] of 312 patients in the open surgery group and 252 [79%] of 319 participants in the minimally invasive surgery group). Median follow-up was 3·0 years (IQR 1·7-4·5). At baseline, no differences in the mean FACT-Cx total score were identified between the open surgery (129·3 [SD 18·8]) and minimally invasive surgery groups (129·8 [19·8]). No differences in mean FACT-Cx total scores were identified between the groups 6 weeks after surgery (128·7 [SD 19·9] in the open surgery group vs 130·0 [19·8] in the minimally invasive surgery group) or 3 months after surgery (132·0 [21·7] vs 133·0 [22·1]). INTERPRETATION: Since recurrence rates are higher and disease-free survival is lower for minimally invasive radical hysterectomy than for open surgery, and postoperative quality of life is similar between the treatment groups, gynaecological oncologists should recommend open radical hysterectomy for patients with early stage cervical cancer. FUNDING: MD Anderson Cancer Center and Medtronic.

Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial.

BACKGROUND: Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. OBJECTIVE: The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. STUDY DESIGN: The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. RESULTS: Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). CONCLUSION: For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

International radical trachelectomy assessment: IRTA study.

BACKGROUND: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. PRIMARY OBJECTIVE: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. STUDY HYPOTHESIS: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. STUDY DESIGN: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. INCLUSION CRITERIA: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). EXCLUSION CRITERIA: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. PRIMARY ENDPOINT: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. SAMPLE SIZE: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete.

OBJECTIVE: The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. METHODS: A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. RESULTS: A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. CONCLUSION: Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.

Outpatient laparoscopic nerve-sparing radical hysterectomy: A feasibility study and analysis of perioperative outcomes.

OBJECTIVE: The goal of our study was to report on the feasibility of outpatient laparoscopic radical hysterectomy in patients with early-stage cervical cancer. METHODS: We included all patients who underwent a laparoscopic radical hysterectomy at the Instituto de Cancerología - Las Americas in Medellin, Colombia, between January 2013 and July 2015. The control group was a similar cohort of patients who were admitted after their surgery. RESULTS: Seventy-six patients were included [outpatient (31) and admitted (45)]. There were no statistically significant differences between groups regarding age, clinical stage, histology, nodal count, need of adjuvant treatment, visual pain scores at discharge or follow up time. All patients underwent a transversus abdominis plane block. The median operative time was 150min (range, 105-240) in the outpatient group vs. 170min (range, 97-300) in the admitted group (p=0.023). The median estimated blood loss was 50ml (range, 20-150) in the outpatient group vs. 120ml (range, 20-1000) in the admitted group (p=0.001). All patients were able to void spontaneously and tolerate a diet before discharge. In patients who were admitted, the median hospital stay was 1day, (range; 1-6), and 39 (87%) were discharged at postoperative day 1. There were 6 postoperative complications, 3 in each group. There were no recurrences in the follow-up period in the outpatient group, and there were 3 (6.6%) recurrences in the admitted group. CONCLUSION: Outpatient laparoscopic radical hysterectomy is feasible and can be performed safely in a developing country in well-selected patients.

Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm.

Radical trachelectomy in early-stage cervical cancer: A comparison of laparotomy and minimally invasive surgery.

OBJECTIVES: Radical trachelectomy is considered standard of care in patients with early-stage cervical cancer interested in future fertility. The goal of this study was to compare operative, oncologic, and fertility outcomes in patients with early-stage cervical cancer undergoing open vs. minimally invasive radical trachelectomy. METHODS: A retrospective review was performed of patients from four institutions who underwent radical trachelectomy for early-stage cervical cancer from June 2002 to July 2013. Perioperative, oncologic, and fertility outcomes were compared between patients undergoing open vs. minimally invasive surgery. RESULTS: A total of 100 patients were included in the analysis. Fifty-eight patients underwent open radical trachelectomy and 42 patients underwent minimally invasive surgery (MIS=laparoscopic or robotic). There were no differences in patient age, body mass index, race, histology, lymph vascular space invasion, or stage between the two groups. The median surgical time for MIS was 272min [range, 130-441min] compared with 270min [range, 150-373min] for open surgery (p=0.78). Blood loss was significantly lower for MIS vs. laparotomy (50mL [range, 10-225mL] vs. 300mL [50-1100mL]) (p<0.0001). Nine patients required blood transfusion, all in the open surgery group (p=0.010). Length of hospitalization was shorter for MIS than for laparotomy (1day [1-3 days] vs. 4days [1-9 days]) (p<0.0001). Three intraoperative complications occurred (3%): 1 bladder injury, and 1 fallopian tube injury requiring unilateral salpingectomy in the MIS group and 1 vascular injury in the open surgery group. The median lymph node count was 17 (range, 5-47) for MIS vs. 22 (range, 7-48) for open surgery (p=0.03). There were no differences in the rate of postoperative complications (30% MIS vs. 31% open surgery). Among 83 patients who preserved their fertility (33 MIS vs. 50 open surgery), 34 (41%) patients attempted to get pregnant. Sixteen (47%) patients were able to do so (MIS: 2 vs. laparotomy: 14, p=0.01). The pregnancy rate was higher in the open surgery group when compared to the MIS group (51% vs. 28%, p=0.018). However, median follow-up was shorter is the MIS group compared with the open surgery group (25months [range, 10-69] vs. 66months [range, 11-147]). To date, there has been one recurrence in the laparotomy group and none in the MIS group. CONCLUSIONS: Our results suggest that radical trachelectomy via MIS results in less blood loss and a shorter hospital stay. Fertility rates appear higher in patients undergoing open radical trachelectomy.

The optimal number of biopsy fragments to establish a morphologic diagnosis of eosinophilic esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF. METHODS: From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original H&E-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm(2)), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment. RESULTS: The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99, respectively. CONCLUSIONS: From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher).

Management of low-risk early-stage cervical cancer: should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?

The standard treatment for women with early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer. Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm, stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical cancer.

Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

OBJECTIVE: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. METHODS: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. RESULTS: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. CONCLUSION: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy - a systematic literature review.

OBJECTIVE: Radical trachelectomy is a standard treatment for selected patients with early-stage cervical cancer. Outcomes are well established for vaginal radical trachelectomy (VRT), but not for abdominal radical trachelectomy (ART). METHODS: We searched MEDLINE, EMBASE, and CINAHL (October 1997 through October 2012) using the terms: uterine cervix neoplasms, cervical cancer, abdominal radical trachelectomy, vaginal radical trachelectomy, fertility sparing, and fertility preservation. We included original articles, case series, and case reports. Excluded were review articles, articles with duplicate patient information, and articles not in English. RESULTS: We identified 485 patients. Ages ranged from 6 to 44 years. The most common stage was IB1 (331/464; 71%), and the most common histologic subtype was squamous cell carcinoma (330/470; 70%). Operative times ranged from 110 to 586 min. Blood loss ranged from 50 to 5568 mL. Three intraoperative complications were reported. Forty-seven patients (10%) had conversion to radical hysterectomy. One hundred fifty-five patients (35%) had a postoperative complication. The most frequent postoperative complication was cervical stenosis (n=42; 9.5%). The median follow-up time was 31.6 months (range, 1-124). Sixteen patients (3.8%) had disease recurrence. Two patients (0.4%) died of disease. A total of 413 patients (85%) were able to maintain their fertility. A total of 113 patients (38%) attempted to get pregnant, and 67 of them (59.3%) were able to conceive. CONCLUSION: ART is a safe treatment option in patients with early-stage cervical cancer interested in preserving fertility.

Laparoscopic radical trachelectomy.

INTRODUCTION: The standard treatment for patients with early-stage cervical cancer has been radical hysterectomy. However, for women interested in future fertility, radical trachelectomy is now considered a safe and feasible option. The use of minimally invasive surgical techniques to perform this procedure has recently been reported. CASE DESCRIPTION: We report the first case of a laparoscopic radical trachelectomy performed in a developing country. The patient is a nulligravid, 30-y-old female with stage IB1 adenocarcinoma of the cervix who desired future fertility. She underwent a laparoscopic radical trachelectomy and bilateral pelvic lymph node dissection. The operative time was 340 min, and the estimated blood loss was 100mL. There were no intraoperative or postoperative complications. The final pathology showed no evidence of residual disease, and all pelvic lymph nodes were negative. At 20 mo of follow-up, the patient is having regular menses but has not yet attempted to become pregnant. There is no evidence of recurrence. CONCLUSION: Laparoscopic radical trachelectomy with pelvic lymphadenectomy in a young woman who desires future fertility may also be an alternative technique in the treatment of early cervical cancer in developing countries.

Alternative management for gynecological cancer care during the COVID-2019 pandemic: A Latin American survey.

OBJECTIVE: To determine the acceptance rate of treatment alternatives for women with either preinvasive conditions or gynecologic cancers during the COVID-19 pandemic among Latin American gynecological cancer specialists. METHODS: Twelve experts in gynecological cancer designed an electronic survey, according to recommendations from international societies, using an online platform. The survey included 22 questions on five topics: consultation care, preinvasive cervical pathology, and cervical, ovarian, and endometrial cancer. The questionnaire was distributed to 1052 specialists in 14 Latin American countries. A descriptive analysis was carried out using statistical software. RESULTS: A total of 610 responses were received, for an overall response rate of 58.0%. Respondents favored offering teleconsultation as triage for post-cancer treatment follow-up (94.6%), neoadjuvant chemotherapy in advanced stage epithelial ovarian cancer (95.6%), and total hysterectomy with bilateral salpingo-oophorectomy and defining adjuvant treatment with histopathological features in early stage endometrial cancer (85.4%). Other questions showed agreement rates of over 64%, except for review of pathology results in person and use of upfront concurrent chemoradiation for early stage cervical cancer (disagreement 56.4% and 58.9%, respectively). CONCLUSION: Latin American specialists accepted some alternative management strategies for gynecological cancer care during the COVID-19 pandemic, which may reflect the region's particularities. The COVID-19 pandemic led Latin American specialists to accept alternative management strategies for gynecological cancer care, especially regarding surgical decisions.

Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. METHODS: We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery. RESULTS: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001). CONCLUSIONS: Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.

Cutaneous lymphangitic carcinomatosis: A rare metastasis from cervical cancer.

Skin metastases are a rare event in patients with cervical cancer. One form of such metastasis is carcinomatous lymphangitis, which is a rare presentation of skin metastases. Here we report a woman with cervical cancer diagnosed cutaneous lymphangitic carcinomatosis.

Traquelectomía radical laparoscópica en pacientes con cáncer de cuello uterino en estado IB1 en el Instituto de Cancerología - Las Américas, Medellín, Colombia

Objetivo: Revisar nuestra experiencia en traquelectomía radical laparoscópica en cáncer de cérvix en estado temprano. Métodos: Estudio observacional descriptivo retrospectivo de las pacientes que se sometieron a traquelectomía radical laparoscópica en el Instituto de Cancerología - Las Américas, Medellín, Colombia, entre Mayo de 2009 y Enero 2015. Resultados: Se completó satisfactoriamente el procedimiento en 13 pacientes en estadío IB1, 12 (92%) tuvieron tumores menores a 2 cm y una recibió quimioterapia neoadyuvante por un tumor de 3 cm. El tipo histológico más frecuente fue el escamoso en 7 pacientes (54%). En 5 pacientes (38%) no se evidenció enfermedad residual luego del procedimiento. El tiempo quirúrgico promedio fue de 240 min (130-340 min); la mediana de pérdida sanguínea fueron 100 ml (50-200 ml). Dos pacientes tuvieron cistotomía incidental durante la cirugía, reparadas por vía laparoscópica, una de ellas desarrollo una fístula vésico-vaginal que cerró espontáneamente. Ninguna paciente requirió transfusión sanguínea ni conversión a laparotomía. La estancia hospitalaria promedio fue de 1 día (1-3). Dos pacientes requirieron histerectomía laparoscópica. No se han reportado recurrencias ni embarazos con un seguimiento promedio 27,9 meses (8,3-64,4). Conclusión: La traquelectomía radical laparoscópica es factible y se puede realizar de manera segura en un país en desarrollo, en pacientes bien seleccionados, con cáncer de cérvix temprano que desean preservar su fertilidad. Los tiempos de seguimiento aún son cortos para conclusiones definitivas sobre el resultado obstétrico. La seguridad oncológica parece similar a la de la traquelectomía abdominal y/o vaginal.

Objective: To review our experience with laparoscopic radical trachelectomy in patients with early-stage cervical cancer. Methods: We performed a observational descriptive retrospective review of all patients who underwent a laparoscopic radical trachelectomy at the Instituto de Cancerología - Las Americas, Medellin, Colombia, between May 2009 and January 2015. Results: 13 patients completed surgery, 12 patients (92%) were diagnosed as IB1 with tumor size less than 2 cm, and one patient received neoadjuvant chemotherapy due to a 3 cm cervical tumor; histology was squamous cell carcinoma in 7 patients (54%). Five patients (38%) showed no residual disease. The mean surgical time was 240 min (130-340 min); the estimated blood loss was 100 ml (50-200 ml). Two patients had a cystotomy during surgery; one of them developed a vesicovaginal fistula that healed spontaneously. No transfusions were given. No conversions were made. Mean hospital stay 1 day (1-3 day). 2 patients required laparoscopic hysterectomy. To date, no recurrence or pregnancies has been recorded with the median follow up 27.9 months (8.3-64.4 month). Conclusion: Laparoscopic radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility. Follow up times are still too short to drive definitive conclusions on obstetric results. The oncological safety appears similar to that of the abdominal trachelectomy and/or vaginal.