Michael R. Milam

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

Nodal metastasis risk in endometrioid endometrial cancer

OBJECTIVE: To estimate the risk for nodal metastasis in women with endometrial cancer based on uterine characteristics on pathology. METHODS: From a study of staging for uterine cancer, women were identified as being at low risk for nodal metastasis based on three specific criteria on final pathology reports: 1) less than 50% invasion, 2) tumor size less than 2 cm, and 3) well or moderately differentiated endometrioid histology. If the uterine specimen did not meet all three criteria, it was viewed as high risk for nodal metastasis. RESULTS: Nine hundred seventy-one women were included in this analysis. Approximately 40% (or 389 of 971) of patients in this study were found to be at low risk, with a rate of nodal metastasis of only 0.8% (3 of 389; exact 95% confidence interval [CI] 0.16–2.2). No statistical differences in median age, body mass index, race, performance status, missing clinical data, or open or minimally invasive techniques were found among the patients with and without nodal metastases. Patients with high-risk characteristics of their uterine specimens compared with those with low-risk characteristics have 6.3 times the risk of nodal metastasis (95% CI 1.67–23.8, P=.007). CONCLUSION: Low-risk endometrioid uterine cancer criteria may be used to help guide treatment planning for reoperation in patients with incomplete surgical staging information. LEVEL OF EVIDENCE: II

Uterine smooth muscle tumor of uncertain malignant potential: A retrospective analysis

OBJECTIVE This retrospective study was designed to evaluate the clinicopathologic features and outcomes of a cohort of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP) seen at a single institution. METHODS All patients diagnosed with uterine STUMP and seen between 1990 and 2005 at The University of Texas M. D. Anderson Cancer Center were identified using the institutions databases. Variables of interest included age at diagnosis, recurrence rate, and disease-free and overall survival. RESULTS Forty-one patients with uterine STUMP were identified and included in the study. The mean age at diagnosis was 43 years (range 25-75 years). The mean follow-up time was 45 months (range 1-171 months). Three patients (7.3%) had a recurrence during the follow-up period. One of the three patients who had recurrent disease was found to have a leiomyosarcoma at the time of recurrence. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. All three patients with recurrence were alive and disease-free at a mean follow-up time of 121 months. CONCLUSION Our results suggest that in this cohort of patients with uterine STUMP the recurrence rate was 7%. Recurrences can be in the form of STUMP or leiomyosarcoma.

Enhanced estrogen-induced proliferation in obese rat endometrium

OBJECTIVE We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals. STUDY DESIGN Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol. RESULTS No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed by estrogen treatment in both obese and lean rats; however, the decrease was more pronounced in obese rats. Estrogen more strongly induced the antiproliferative genes retinaldehyde dehydrogenases 2 and secreted frizzled-related protein 4 in lean rats but had little or no effect in obese rats. CONCLUSION Enhancement of estrogen-induced endometrial proproliferative gene expression and suppression of antiproliferative gene expression was seen in the endometrium of obese vs lean animals.

Limited public knowledge of obesity and endometrial cancer risk: what women know.

OBJECTIVE: To estimate if women in the general population are aware of the relationship between obesity and cancer risk, and to identify groups who may benefit from educational programs. METHODS: A self-administered survey was distributed to women in the Houston community. The questions were taken from a bank of validated questions published by the Center for Disease Control, Behavioral Risk Factor Surveillance System, and the Harvard Forums on Health Survey. Demographic information and participant knowledge of obesity-related cancer risk was collected. Logistic regression and Cochran-Armitage tests for trend were use to assess the association between predictor variables and knowledge. RESULTS: One thousand five hundred forty-five women completed the survey; 28% were normal weight (body mass index [BMI] less than 25 kg/m2), 24% were overweight (BMI 25–30 kg/m2), and 45% were obese (BMI at least 30 kg/m2). Fifty-eight percent (95% confidence interval 56–61%) were not aware that obesity increased risk for endometrial cancer. There was no difference in knowledge of endometrial cancer risk associated with any of the demographic characteristics studied. Black women were the most likely to respond that they did not know about the relationship between obesity and cancer. There was no association between personal weight and knowledge of obesity-associated risk. CONCLUSION: There is limited knowledge of the relationship between obesity and cancer risk, particularly among black women. Patient education regarding these risks may increase awareness of the relationship between obesity and endometrial cancer among women. LEVEL OF EVIDENCE: III

Postoperative Small Bowel Obstruction Associated with Use of Hemostatic Agents

A case of early postoperative small bowel obstruction (SBO) after intraoperative use of hemostatic agents during laparoscopic staging for endometrial cancer is reported. A 46-year-old woman underwent a laparoscopic staging procedure for endometrial cancer during which hemostatic agents were used in the management of an iatrogenic injury to the inferior vena cava. The patient returned on postoperative day 6 with SBO and was taken to the operating department. She required a small bowel resection in the specific area where the hemostatic agents were used. Pathology showed extensive fibrotic changes caused by a foreign material that was suggestive of a thrombin-related product. Use of hemostatic agents should be considered as a cause in the differential diagnosis of patients with early postoperative SBO.

Molecular clustering of endometrial carcinoma based on estrogen-induced gene expression

Identification of biomarkers potentially provides prognostic information that can help guide clinical decision-making. Given the relationship between estrogen exposure and endometrial cancer, especially low grade endometrioid carcinoma, we hypothesized that high expression of genes induced by estrogen would identify low risk endometrioid endometrial cancers. cDNA microarray and qRT- PCR verification were used to identify six genes that are highly induced by estrogen in the endometrium. These estrogen-induced biomarkers were quantified in 72 endometrial carcinomas by qRT-PCR. Unsupervised cluster analysis was performed, with expression data correlated to tumor characteristics. Time to recurrence by cluster was analyzed using the Kaplan-Meier method. A receiver operating characteristic (ROC) curve was generated to determine the potential clinical utility of the biomarker panel to predict prognosis. Expression of all genes was higher in endometrioid carcinomas compared to non-endometrioid carcinomas. Unsupervised cluster analysis revealed two distinct groups based on gene expression. The high expression cluster was characterized by lower age, higher BMI, and low grade endometrioid histology. The low expression cluster had a recurrence rate 4.35 times higher than the high expression cluster. ROC analysis allowed for the prediction of stage and grade with a false negative rate of 4.8% based on level of gene expression in endometrioid tumors. We have therefore identified a panel of estrogen-induced genes that have potential utility in predicting endometrial cancer stage and recurrence risk. This proof-of- concept study demonstrates that biomarker analysis may play a role in clinical decision making for the therapy of women with endometrial cancer.

Genetic polymorphisms and endometrial cancer risk

For most sporadic cancers, genetic susceptibility results from the additive effect of multiple genetic variants, each of which contributes a modest risk individually. The study of genetic single nucleotide polymorphisms (SNPs) may help explain the differences in individual cancer susceptibility and may assist in identifying novel markers of risk that can be utilized to create more effective and tailored cancer prevention strategies. Genetic polymorphisms in functionally critical genes have been suggested as risk factors for the development of a variety of cancers, including endometrial cancer. Candidate SNPs may be involved in DNA damage repair, steroid metabolism, carcinogen metabolism, cell-cycle control, apoptosis and steroid receptor activation pathways. In this review, recent findings of genetic association studies exploring genetic polymorphisms and their association with endometrial cancer are reported. In addition, the challenges of genetic association studies, such as power and bias, and the need for validation of promising findings are explored.

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

Preoperative factors predicting survival after secondary cytoreduction for recurrent ovarian cancer

Objective: We evaluated preoperative data that may predict benefit from secondary cytoreductive surgery (CRS) to assist in selecting therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer. Materials and Methods: Inclusion criteria included recurrent epithelial or primary peritoneal carcinoma with an initial disease-free interval more than 6 months after chemotherapy, evidence of disease on imaging studies and indication for surgery being to debulk residual disease. Preoperative CA125 values, computed tomographic findings, and time to progression were evaluated as predictors of survival in addition to postoperative information and perioperative morbidity. Results: Sixty-two patients met the inclusion criteria. In the 35.5% of patients debulked to no visible disease, median survival was significantly longer than in those with less than 1 cm of visible residual disease (5.95 vs 2.73 years, P = 0.004), but debulking to less than 1 cm visible disease was not better than those with less than 1 cm residual disease (2.02 years). Mean preoperative CA125 levels were significantly lower in the patients who could be debulked to no visible residual disease compared to less than 1 cm or more than 1 cm residual disease (69.1 vs 290.7 vs 1978.4, P = 0.001). Generation of a receiver operating characteristic curve determined that a CA125 cutoff of 250 U/mL best predicted successful cytoreduction to no visible disease. Conclusions: Only patients cytoreduced to no visible disease achieved a survival advantage, and the only preoperative factor that could predict surgical success regarding prolonging survival was a CA125 less than 250 U/mL. These data can guide physicians and patients in deciding whether or not to undergo secondary cytoreduction for first recurrence of ovarian cancer.