Ricardo dos Reis

Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer.

OBJECTIVE: To compare intraoperative, pathologic, and postoperative outcomes of total laparoscopic radical hysterectomy with abdominal radical hysterectomy and pelvic lymphadenectomy for women with early-stage cervical cancer. METHODS: We reviewed all patients who underwent total laparoscopic radical hysterectomy or abdominal radical hysterectomy and pelvic lymphadenectomy between 2004 and 2006. RESULTS: Fifty-four patients underwent abdominal radical hysterectomy, and 35 underwent total laparoscopic radical hysterectomy. Mean age was 41.8 years, and mean body mass index 28.1. There was no difference in demographic or tumor factors between the two groups. Mean estimated blood loss was 548 mL with abdominal radical hysterectomy compared with 319 mL with total laparoscopic radical hysterectomy (P=.009), and 15% of patients who underwent abdominal radical hysterectomy required a blood transfusion compared with 11% who underwent total laparoscopic radical hysterectomy (P=.62). Mean operative time was 307 minutes for abdominal radical hysterectomy compared with 344 minutes for total laparoscopic radical hysterectomy (P=.03). On pathologic examination, there was no significant difference in the amount of parametrial tissue, vaginal cuff, or negative margins obtained. A mean 19 pelvic nodes were obtained during abdominal radical hysterectomy compared with 14 during total laparoscopic radical hysterectomy (P=.001). The median duration of hospital stay was significantly shorter for total laparoscopic radical hysterectomy (2.0 compared with 5.0 days, P<.001). For abdominal radical hysterectomy, 53% of patients experienced postoperative infectious morbidity compared with 18% for total laparoscopic radical hysterectomy (P=.001). There was no difference in postoperative noninfectious morbidity. There was no difference in return of urinary function. CONCLUSION: Total laparoscopic radical hysterectomy reduces operative blood loss, postoperative infectious morbidity, and postoperative length of stay without sacrificing the size of radical hysterectomy specimen margins; however, total laparoscopic radical hysterectomy is associated with increased operative time. LEVEL OF EVIDENCE: II

Parametrial involvement in radical hysterectomy specimens for women with early-stage cervical cancer

OBJECTIVE: To estimate the incidence of parametrial involvement and to evaluate factors associated with parametrial spread in women with early-stage cervical cancer and to identify a cohort of patients at low risk for parametrial spread who may benefit from less radical surgery. METHODS: We reviewed all patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006. All women with squamous, adenocarcinoma, or adenosquamous disease, stage IA2–IB1, who underwent completed radical hysterectomy were included in the analysis. Normally distributed continuous variables were compared using Student’s t-test for independent samples to analyze the outcome of positive or negative parametrial involvement. RESULTS: Three hundred fifty patients met the inclusion criteria. Overall, 27 women (7.7%) had parametrial involvement. The majority of specimens with parametrial involvement (52%) had tumor spread through direct microscopic extension. Patients with parametrial involvement were more likely to have a primary tumor size larger than 2 cm (larger than 2 cm: 14%, smaller than 2 cm: 4%, P=.001), higher histologic grade (grade 3: 12%, grades 1 and 2: 3%, P=.01), lymphovascular space invasion (positive: 12%, negative: 3%, P=.002), and metastasis to the pelvic lymph nodes (positive: 31%, negative: 4%, P<.001). One hundred twenty-five women (36%) had squamous, adenocarcinoma, or adenosquamous lesions, all grades, with primary tumor size 2 cm or smaller and no lymphovascular space invasion. In this group of patients, there was no pathologic evidence of parametrial involvement. CONCLUSION: We were able to retrospectively identify a cohort of women with early-stage cervical cancer who were at very low risk for parametrial involvement. If prospective application of these findings confirms our results, less radical surgery—such as simple hysterectomy, simple trachelectomy, or conization—with pelvic lymphadenectomy may be a reasonable therapeutic option for women with primary tumors 2 cm or smaller and no lymphovascular space invasion. LEVEL OF EVIDENCE: III

Risk of Thromboembolic Disease in Patients Undergoing Laparoscopic Gynecologic Surgery

OBJECTIVE: To estimate the incidence of venous thromboembolism among patients undergoing gynecologic laparoscopy and characterize the risk of venous thromboembolism among patients with gynecologic malignancy. METHODS: Data were collected for patients who underwent laparoscopic gynecologic surgery from January 2000 to January 2009. Incidence of deep vein thrombosis (DVT) or pulmonary embolism diagnosed within 6 weeks of surgery was estimated. Fishers exact test was used to estimate the association between the presence of perioperative venous thromboembolism and categorical variables. RESULTS: Six (of 849) patients developed symptomatic venous thromboembolism (0.7%, 95% confidence interval: 0.024–1.44%). The median time to diagnosis of venous thromboembolism was postoperative day 15.5 (range, 1–41 days), median body mass index was 25.4 kg/m2 (range, 18.4–50 kg/m2), median operative time was 176 minutes (range, 53–358 minutes), and median estimated blood loss was 125 mL (range, 10–250 mL). Five of 430 (1.2%) patients with a history of gynecologic malignancy developed postoperative thromboembolic events. Venous thromboembolism was diagnosed in three of 662 (0.5%) patients undergoing intermediate complexity procedures and three of 106 (2.8%) patients undergoing high-complexity procedures. Three patients with venous thromboembolism (50%) had a history of at least one previous modality of cancer treatment before laparoscopy. One patient (17%) had DVT only, four (67%) had pulmonary emboli without an identified DVT, and one (17%) had both. There were no associated mortalities. CONCLUSION: The incidence of thromboembolism in patients undergoing low- and intermediate-complexity, minimally invasive surgery was low, even among patients with a gynecologic malignancy. Patients undergoing high-complexity, minimally invasive procedures may benefit from postoperative anticoagulation. LEVEL OF EVIDENCE: II

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.

Radical hysterectomy in obese and morbidly obese women with cervical cancer.

OBJECTIVE: To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer. METHODS: A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)]2), women were categorized as normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese (BMI 30.0–34.9), or morbidly obese (BMI at least 35.0). RESULTS: Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease. CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer. LEVEL OF EVIDENCE: II

Lymphovascular space invasion portends poor prognosis in low-risk endometrial cancer

Objective The prognostic significance of lymphovascular space invasion (LVSI) in patients with early-stage endometrial cancer is not established. We sought to determine if LVSI status in patients with early-stage low-risk endometrial cancer correlates with recurrence and survival. Methods The records of all women who underwent hysterectomy for primary treatment of endometrial cancer from January 2006 through January 2011 at 1 academic institution were reviewed. Patients with grade 1 or 2 endometrioid histology, myometrial invasion less than 50%, and disease confined to the uterus (clinical International Federation of Obstetrics and Gynecology stage IA) were analyzed. Fisher exact test and the Wilcoxon rank-sum test were applied to compare patients with and without LVSI. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Two hundred forty patients met the inclusion criteria. Forty (16.7%) had LVSI. Ninety-one patients (37.9%) underwent lymphadenectomy. Median tumor size was 30 mm in patients with and 26 mm in patients without LVSI (P = 0.150). Thirty patients (12.5%) received adjuvant therapy. Site of recurrence did not differ between patients with and without LVSI. Patients with LVSI were more likely to have myometrial invasion (P < 0.001), postoperative pathologic grade 2 disease (P < 0.001), to undergo lymphadenectomy (P = 0.049) and receive adjuvant therapy (P < 0.001). The 5-year cumulative incidence of recurrence was 3.8% in the no-LVSI group and 14.2% in the LVSI group (P = 0.053). The presence of LVSI was significantly associated with worse RFS (P = 0.002) and OS (P = 0.013). Conclusions Patients with low-risk endometrial cancer and LVSI have worse RFS and OS despite being more likely to undergo lymphadenectomy and adjuvant therapy.

Significance of lymph node ratio in defining risk category in node-positive early stage cervical cancer

OBJECTIVE The ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is an important prognostic factor in several solid tumors. The objective of this study was to determine if LNR can be used to define a high-risk category of patients with node-positive early stage cervical cancer. METHODS We performed a retrospective review of patients diagnosed with node-positive stage I or II cervical cancer who underwent radical hysterectomy and pelvic +/- para-aortic lymphadenectomy at MD Anderson from January 1990 to December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free (PFS) and overall survival (OS). RESULTS Ninety-five patients met the inclusion criteria and were included in the analysis. Median total nodes removed were 19 (range 1-58), and median number of positive nodes was 1 (range 1-12). Fifty-eight patients (61%) received radiation with concurrent cisplatin and 27 patients (28%) received radiotherapy alone. Twenty-one (22%) patients recurred. On multivariate analysis, a LNR > 6.6% was associated with a worse PFS (HR = 2.97, 95% CI 1.26-7.02, p = 0.01), and a LNR > 7.6% with a worse OS (HR = 3.96, 95% CI 1.31-11.98, p = 0.01). On multivariate analysis, positive margins were associated with worse PFS (p = 0.001) and OS (p = 0.002), and adjuvant radiotherapy (p = 0.01) with improved OS. CONCLUSIONS LNR appears to be a useful tool to identify patients with worse prognosis in node-positive early stage cervical cancer. LNR may be used in addition to pathologic risk factors to tailor adjuvant treatment in this population.

Neoadjuvant chemotherapy is associated with prolonged primary treatment intervals in patients with advanced epithelial ovarian cancer

Background: We evaluated the impact of neoadjuvant chemotherapy (NC) relative to primary surgery (PS) to determine if there was a difference in the total time and number of chemotherapy cycles given in patients with advanced epithelial ovarian cancer. Methods: We identified 263 consecutive women meeting eligibility from 1993 to 2005 for this institutional review board-approved study. Eligible patients in this analysis were those women with advanced disease (stage IIIC-IV) in whom a maximal cytoreductive effort was planned either at PS or after NC. Time to start chemotherapy was defined as follows: (1) NC group: confirmation of diagnosis through biopsy, cytological diagnosis from ascites, and pleural effusion; (2) PS group: confirmation of diagnosis from the date of surgery that confirmed the diagnosis of epithelial ovarian cancer. Total chemotherapy cycles: (1) NC group: NC chemotherapy cycles plus postoperative cycles; (2) PS group: chemotherapy after primary tumor debulking surgery. Clinical information evaluated included chemotherapy type, chemotherapy cycle number, total time to administer frontline chemotherapy, and survival. Results: Median chemotherapy cycles were greater in the NC group compared with the PS group (9 [range, 4-30] vs 6 [range, 3-19]; P < 0.01). The PS group was also more likely to undergo chemotherapy regimens involving platinum and taxane treatment compared with the NC group (79% vs 65%; P = 0.017). Total time undergoing primary chemotherapy from initial diagnosis was greater in the NC group compared with PS (223 vs 151 days; P < 0.01). No significant difference was observed in overall survival and progression-free survival in the 2 groups. Conclusions: In patients with advanced ovarian cancer, NC followed by abdominal hysterectomy is associated with improved perioperative outcomes including optimal cytoreduction, decreased blood loss, and decreased inpatient hospitalization. In this cohort, NC was also associated with prolonged chemotherapy treatment intervals and increased chemotherapy cycles without improvement in survival.

Limited utility of magnetic resonance imaging in determining the primary site of disease in patients with inconclusive endometrial biopsy

Objective: To evaluate the utility of preoperative magnetic resonance imaging (MRI) in determining whether primary disease site is cervical or endometrial in patients with inconclusive preoperative endometrial biopsy. Methods: We retrospectively identified all patients who underwent pelvic MRI and who had a preoperative diagnosis of cervical or endometrial cancer at MD Anderson Cancer Center between 1990 and 2006. The subset in which endometrial biopsy did not clarify the primary disease site was analyzed. Magnetic resonance imaging results were compared with postoperative histopathologic findings. Results: A total of 168 patients who underwent MRI who had a preoperative diagnosis of cervical or endometrial cancer were identified. Of these patients, 51 had an inconclusive endometrial biopsy. Magnetic resonance imaging suggested an endometrial primary tumor without cervical invasion in 28 patients, of whom 21 (75%) actually had such a tumor and 7 had an endometrial primary tumor with cervical invasion. Magnetic resonance imaging suggested an endometrial primary tumor with cervical invasion in 3 patients, all of whom had such a tumor. Magnetic resonance imaging suggested a cervical primary tumor in 6 patients, of whom 5 had such a tumor and 1 had an endometrial primary tumor without cervical invasion. Magnetic resonance imaging was inconclusive (did not clarify primary disease site or no lesion visualized) in 14 (27%) of 51 patients, 6 of whom had an endocervical primary tumor or an endometrial tumor with cervical involvement. Overall, preoperative MRI was either inaccurate or unhelpful in 22 (43%) of 51 patients. Conclusion: Preoperative MRI in patients with inconclusive endometrial biopsy is inaccurate or unhelpful in nearly half of patients.

Carcinoma of the bartholin gland: A review of 33 cases

Objective Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland–related vulvar carcinoma. Materials and Methods A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland–related vulvar carcinoma. Results Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland–related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. Conclusions Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland–related vulvar carcinoma.