Jay W. Carlson

Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

PURPOSE Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC. PATIENTS AND METHODS A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P < .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively). CONCLUSION Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.

A randomized phase III trial of VH fibrin sealant to reduce lymphedema after inguinal lymph node dissection: a Gynecologic Oncology Group study.

OBJECTIVES To evaluate VH fibrin sealants influence on lower extremity lymphedema after inguinal lymphadenectomy in vulvar cancer patients. METHODS Patients undergoing an inguinal lymphadenectomy during the management of vulvar malignancy were randomized to receive sutured closure (SC) vs VH fibrin sealant sprayed into the groin followed by sutured closure (FS). Leg measurements were taken preoperatively and during postoperative encounters when surgical outcomes were assessed. Grade 2 or 3 lymphedema was defined as circumferential measurement increases of 3-5 cm and >5 cm, respectively. RESULTS 150 patients were enrolled. 137 patients were evaluable for lymphedema analysis with 67 and 70 patients in the SC arm and FS arm, respectively. The incidence of grade 2 and 3 lymphedema was 67%(45/67) in the SC arm, and 60% (42/70) FS arm (p=0.4779). The incidence of lymphedema was strongly associated with inguinal infection (p=0.0165). Lymphedema was not statistically increased in those who received adjuvant radiation. 139 patients remained evaluable for a descriptive analysis of their surgical complications. The overall incidence of complications was 61%(43/70) and 59% (41/69) for SC and FS arms, respectively. There was no statistically significant difference in duration of drains, drain output or incidence of inguinal infections, wound breakdowns or seromas. There was an increased incidence of vulvar infections in the FS arm (23/69) vs (10/70) (p=0.0098). The utilization of a Blake drain was associated with an increase in vulvar (p=0.0157) and inguinal wound breakdown (p=0.0456). CONCLUSION VH fibrin sealant in inguinal lymphadenectomies does not reduce leg lymphedema and may increase the risk for complications in the vulvar wound.

Blood flow characteristics of ovarian tumors: Implications for ovarian cancer screening

OBJECTIVES Our purpose was to investigate the blood flow characteristics of benign and malignant ovarian tumors. Questions posed by our research were as follows: (1) Can malignant ovarian tumors be predicted by color flow Doppler imaging? (2) What are the sensitivity, specificity, and positive and negative predictive values of such prediction? (3) Which color flow Doppler parameter is superior in its accuracy of prediction? STUDY DESIGN One hundred twenty-three consecutive patients seen for suspected pelvic masses were evaluated by transvaginal ultrasonography and color flow Doppler imaging. A morphologic assessment was initially performed, followed by color flow Doppler analysis. A comparison of findings between the benign and malignant tumors was made by analyzing different thresholds of the intratumoral pulsatility and resistance index values by means of receiver-operator characteristic curves. By calculation of the area index under each receiver-operator characteristic curve the efficiency of the pulsatility and resistance index values in predicting malignancy was determined. RESULTS Fifty-six benign and 23 malignant tumors were pathologically confirmed. Patients with malignant tumors were more likely to be postmenopausal and were older than patients with benign tumors. Malignant tumors were more likely to be larger and to have either a complex or solid pattern. Absent color flow was more common in benign tumors, and increased color flow was found equally among benign and malignant tumors. There was no difference in systolic, diastolic, or mean velocities between benign and malignant tumors. The calculated pulsatility and resistance index values were lower in patients with malignant tumors compared with those with benign tumors. No significant difference exists in performance of either the pulsatility or resistance index in predicting malignancy. The best thresholds for predicting malignancy were obtained with a pulsatility index of 1.0 and resistance index of 0.6. CONCLUSIONS Transvaginal ultrasonography is accurate in distinguishing benign from malignant ovarian tumors. Color flow Doppler findings are not specific enough to be used independent of gray-scale ultrasonography.

Advanced cytoreductive surgery: American perspective

Over the past 3 to 4 decades a special knowledge and understanding of the pathophysiology and behavior of gynecologic peritoneal surface malignancies has led to a significant improvement of the relevant treatment modalities, mirroring advances in chemotherapy approaches and improved knowledge of tumor biology. The surgical management of advanced ovarian, primary peritoneal, and fallopian tube cancers has evolved from the performance of basic gynecologic procedures to the incorporation of more comprehensive surgical procedures. This extensive surgical approach is of great importance for estimating the prognosis and guiding further treatment of affected patients. These complex procedures involving multi-organ resections are generally long and require excellent knowledge of upper abdominal anatomy. This article will focus on the role and program development of advanced cytoreductive surgery in patients with gynecologic peritoneal malignancies. This review is an attempt to provide guidance for the rationale and strategic approach to develop the surgical skill set, meet institutional requirements, and implement the concept of a comprehensive cytoreductive surgical team.

Transvaginal color flow Doppler sonography in the assessment of gestational trophoblastic disease.

The aim of this study was to evaluate the blood flow characteristics of the uterine artery and intratumoral vessels in patients with GTD. Twelve patients with GTD were evaluated with TVS, and 11 also had CFD sonography performed. Spectral analysis of both uterine artery and samples intratumoral and intramyometrial vessels revealed systolic frequencies and PI that were significantly higher in the uterine artery than in sampled intratumoral vessels (P < 0.05). Uterine artery PI correlated significantly with age (P = 0.043), uterine size (P = 0.003), and beta‐HCG titer (P = 0.03). Intratumoral PI correlated significantly with uterine size (P = 0.05). Intratumoral PI did not correlate with patient age, the shape or orientation of the uterus, presence or absence of subendometrial halo, endometrial thickness or echogenicity, or impression of myometrial invasion. Regression analysis of beta‐HCG titers on uterine artery and intratumoral PI revealed a linear association. TVS and color flow Doppler sonography are useful in the assessment of patients with GTD. The PI is strongly associated with prognosis and correlates with beta‐HCG titers.

Laparoscopic exposure in obese high-risk patients with mechanical displacement of the abdominal wall.

BACKGROUND: Patients with morbid obesity or pulmonary disease are at a higher risk for complications during advanced laparoscopic procedures. Higher intraperitoneal carbon dioxide pressures required to elevate the pannus can negatively impact hemodynamic and respiratory parameters. CASES: We describe a technique that uses a combination of a mechanical retractor and a Foley catheter inserted midway between the umbilicus and the pubic symphysis that assists in elevating the anterior abdominal wall. In 3 cases this technique allowed for a low-pressure pneumoperitoneum during advanced laparoscopic pelvic surgery, which resulted in improved hemodynamic parameters and pulmonary function in these high-risk patients. CONCLUSION: The Foley Lap-Lift facilitated laparoscopy through mechanical abdominal wall elevation and allowed for a lower-pressure pneumoperitoneum. This technique is an addition to traditional operative laparoscopy in select high-risk patients.

Gray scale and color flow Doppler characterization of uterine tumors.

The aim of this study was to investigate gray scale and color flow characteristics of a group of patients with a suspected uterine pathologic condition. One hundred and twenty‐two consecutive patients at the Womens Cancer Center, University of Minnesota, undergoing transvaginal sonography and color flow Doppler imaging for suspected uterine corpus abnormality made up the study group. After gray scale morphologic assessment, color flow Doppler imaging of the tumor and uterus was performed, including the ipsilateral uterine artery. Malignant tumors were confirmed pathologically in all 35 patients who had them. In comparing patients with benign versus malignant tumors, gray scale morphologic assessment confirmed that malignant uterine tumors (31 endometrial cancers and four sarcomas) were more likely to have a thickened echoic endometrium (P = < 0.0001), be enlarged (P = 0.004), to be retroverted (P = 0.02), and to lack a subendometrial halo (P < 0.0001). Patients with four benign and 13 malignant tumors demonstrated increased flow when assessed by CFD. The calculated sensitivity of increased color flow in predicting malignancy was 39%, with a specificity of 92%, a positive predictive value of 77%, and a negative predictive value of 71%. No difference existed between the benign and malignant groups for the systolic, diastolic, and mean velocities and for the calculated pulsatility index and resistive index in both sampled uterine and intramyometrial or tumor vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

A quality process study of lymph node evaluation in endometrial cancer.

Our objective was to analyze the reported lymph node counts between surgeons, histology prosectors, and pathologists using a cohort of patients enrolled on a national protocol that standardized surgical intent.This is a retrospective review of patients with uterine cancer who underwent a standardized formal staging procedure as dictated by a National Cancer Institute sponsored protocol. Patients were staged using the International Federation of Gynecology and Obstetrics 1988 guidelines. All patients required a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Lymphadenectomy specimens were separated by the following regions: external iliac, obturator, common iliac, and periaortic. Lymph node counts were analyzed by region, surgeon, histology prosector, and pathologist.There were 78 patients enrolled in the protocol during the study period. Of them, 72 (92%) patients met the inclusion criteria. A total of 2397 lymph nodes were counted, with an average total number of 33 (SD=9) lymph nodes dissected per patient. Surgeons A, B, and C had an average lymph node count of 32, 33, and 35, respectively, with no significant difference in mean node count (P=0.66). Prosectors 1 to 4 dissected an average of 34, 33, 28, and 35 lymph nodes, respectively (P=0.091). There were 2 pathologists with ≥ 10 cases. Their mean lymph node counts were 35 and 30, respectively, with no significant difference in mean node count (P=0.079).This systematic review did not identify a discrepancy in nodal count among surgeons, prosectors, or pathologists at our institution. The methods used may be helpful in structuring interdepartmental reviews for completeness of nodal dissections in cases where surgical intent has been standardized.

Prediction of malignancy using transvaginal color flow Doppler in patients with gynecologic tumors

Eighty-five patients referred to the Womens Cancer Center, University of Minnesota had transvaginal color flow Doppler performed to determine if pelvic malignancy could be predicted by blood flow assessment. Their mean age was 49 years (range 21–86 years). Thirty-five patients were subsequently found to have malignant tumors of the cervix, uterus or ovary. The presence of increased intratumoral blood flow as depicted by color flow Doppler had a sensitivity of 83%, specificity of 100%, positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89% for malignancy. The mean intratumoral Pulsatility Index (PI) of the patients with malignant tumors was 0.81 (SD 0.24; range 0.3–1.2), which was significantly lower than for the benign group (P = 0.001). A PI of ≤ 1.0 had a sensitivity of 96.3%, specificity of 94.3%, PPV of 89.7% and NPV of 98% for predicting malignancy. Transvaginal color flow Doppler shows promise as a method of predicting malignancy in patients with gynecologic pathology.

Repair of transversely incised abdominal wall fascia in a rabbit model.

Objective To compare several commonly used methods of closing transversely incised anterior abdominal wall in order to detemine which technique results in the strongest incisional tensile strength. Methods Thirty-six rabbits were randomized to receive either interrupted or continuous closure with 0-Vicryl. Within these groups, each animal was randomized to one of three different bite and interval techniques: 1-cm bites/0.5-cm intervals, 1-cm bites/1-cm intervals, and 2-cm bites/ 1-cm intervals. Each rabbit received three to four transverse abdominal wall incisions of approximately 3–8 cm in length. The incisions were excised en bloc and stored at −70C at postoperative week 1,2, or 4 in a random fashion. Representative 1-cm strips were harvested from each incision after thawing. The Instron tensiometer was used to determine the maximum intrinsic tensile strength required to disrupt each tissue strip at the incision. Statistical analysis was performed using analysis of variance, two-sample t test, Scheffé multiple comparison, and Kruskal-Wallis test. Results Two hundred thirty-seven strips were analyzed. The mean maximum tensile strength of all of the interrupted and continuous suture repairs was 48 and 38 lb, respectively (P < .001). The maximum tensile strength for interrupted closures was achieved at week 1 and was similar at week 4. The continuous closure was weakest at week 1 and increased to a maximum value during week 4. There was no difference in maximum tensile strength between the interrupted and continuous closure groups at week 4. There was no significant difference in the maximum tensile strength of the three repair techniques. The mean maximum tensile strength of all specimens was significantly less among those harvested during weeks 1 and 2 compared with week 4 (P = .001). Conclusion In this randomized study, the interrupted closure had a greater maximum tensile strength than the continuous closure in repair of transverse incisions during the first 2 postoperative weeks. Both repair methods were associated with a similar maximum tensile strength at 4 postoperative weeks. Repair techniques using different bite sizes and intervals resulted in similar maximum tensile strengths.