Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer.

BACKGROUND: Allelic imbalance (AI), the loss or gain of chromosomal regions, is found in many cancers. AI can be detected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentration, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers. METHODS: Plasma samples were obtained from 330 women (44 normal healthy control individuals, 122 patients with various cancers, and 164 control patients with non-neoplastic diseases). Plasma DNA concentration was determined in all samples. Allelic status was determined by digital single nucleotide polymorphism (SNP) analysis with eight SNP markers in plasma DNA from 54 patients with ovarian cancer and 31 control patients. CA 125 was determined in 63 samples. Receiver-operating characteristic (ROC) curves were plotted, and the areas under the ROC curves--a measure of the overall ability of a diagnostic test with multiple cutoffs to distinguish between diseased and nondiseased individuals--were determined. RESULTS: The area under the ROC curve for plasma DNA concentration was 0.90 for patients with neoplastic disease versus healthy control individuals and 0.74 for patients with neoplastic diseases versus control patients with non-neoplastic diseases. For control subjects given a specificity of 100% (95% confidence interval [CI] = 92% to 100%), the highest sensitivity achieved was 57% (95% CI = 49% to 67%). AI in at least one SNP was found in 87% (95% CI = 60% to 98%) of patients with stage I/II ovarian cancer and 95% (95% CI = 83% to 99%) of patients with stage III/IV ovarian cancer, but AI was not found in 31 patients with non-neoplastic diseases (specificity = 100%, 95% CI = 89% to 100%). The area under the ROC curve assessing AI was 0.95. Combining the serum CA 125 level with the plasma DNA concentration increased the area under the ROC curve from 0.78 (CA 125 alone) to 0.84. CONCLUSION: Plasma DNA concentration may not be sensitive or specific enough for cancer screening or diagnosis, even when combined with CA 125. AI was detected with high specificity in plasma DNA from patients with ovarian cancer and should be studied further as a screening tool.

Decreased incidence of cervical cancer in medicare-eligible California women.

OBJECTIVE: To determine if the incidence of invasive cervical cancer relative to carcinoma in situ decreased in Medicare-eligible women. METHODS: A retrospective cohort was amassed from the California Cancer Registry database. The hypothesis was prospectively specified. Mean ratio of invasive (International Federation of Gynecology and Obstetrics Stages I-IV) to in situ cervical carcinoma in 1988-1990 versus 1991-1995 was stratified by age (24 or younger, 25-44, 45-64, 65 or older) and race (all races, whites, blacks, Hispanics, Asian/Pacific Islanders). RESULTS: The mean ratio of invasive to in situ cervical cancer incidence for women at least 65 years old was lower in 1991-1995 compared with 1988-1990 (P <.001, 95% confidence interval 0.893, 0.954); and had decreased more than observed for women aged 45-64 and 25-44, for all races combined, and for white women. The decreased ratio of invasive to in situ cancer for blacks, Hispanics, and Asian/Pacific Islanders at least 65 years old was no different than the decreased ratio in younger women. CONCLUSION: In California, in the 5 years after the 1990 change in Medicare funding statutes for cervical cytology screening, the ratio of invasive cervical cancer to in situ disease decreased more in Medicare-eligible patients than in younger women.

Gynecologic abnormalities in surgically treated women with stage II or III rectal cancer.

BACKGROUND: The objective of this article is to review the incidence and management of gynecologic abnormalities in women undergoing surgery for rectal cancer. STUDY DESIGN: We performed a retrospective chart review utilizing the Johns Hopkins Tumor Registry and Pathology database. Eighty-six female patients who underwent abdominal surgery between 1985 and 1996 for Stage II or Stage III rectal cancer were identified. Data gathered included: patient demographics, history, intraoperative findings and complications, cancer stage and histology, adjuvant treatments, and followup. Specific attention was focused on the diagnosis, management, and followup of concurrent gynecologic problems. RESULTS: At the time of surgery, nineteen women (22%) had previously undergone hysterectomy and bilateral salpingo-oophorectomy. Of the remaining 67 patients, 25 (37%) were found to have gynecologic abnormalities at the time of surgery, 15 (22%) underwent adnexectomy or hysterectomy or both. Forty-two women (63%) had normal internal genitalia. Of the 61 peri- and postmenopausal women, nine underwent bilateral oophorectomy for therapeutic reasons. No prophylactic oophorectomies were performed in any of the patients. CONCLUSION: Incidental pathologic findings necessitating gynecological procedures are common in patients undergoing surgery for rectal cancer. These findings are frequently suboptimally assessed and managed in the pre-, intra-, and postoperative periods. Colorectal surgeons operating on women with Stage II and III rectal cancer should be cognizant of the high likelihood of identifying incidental gynecologic pathology and be prepared for definitive management of the pathology. The utilization of prophylactic oophorectomy in postmenopausal women undergoing surgery for rectal cancer is currently not optimal; preoperative discussion should address this option.

Radical oophorectomy with primary stapled colorectal anastomosis for resection of locally advanced epithelial ovarian cancer.

BACKGROUND: The aim of this study was to describe the feasibility, associated morbidity, and efficacy of radical oophorectomy with primary stapled colorectal anastomosis among patients with locally advanced ovarian cancer with contiguous extension to or encasement of the reproductive organs, pelvic peritoneum, cul-de-sac, and sigmoid colon. STUDY DESIGN: Thirty-one consecutive patients undergoing radical oophorectomy as part of an initial maximal surgical effort for International Federation of Obstetrics and Gynecology (FIGO) stage IIIB-IV ovarian cancer were prospectively collected from October 1, 1997 through November 30, 2001. The surgical technique, associated morbidity, and clinical outcomes are described. RESULTS: The median age was 63 years. All patients had advanced-stage epithelial ovarian cancer: FIGO stage IIIB (6.5%), stage IIIC (64.5%), stage IV (29.0%). Median operating time was 240 minutes (range 165 to 330 minutes), and the median estimated blood loss was 700 mL (range 300 to 2,900 mL). All patients underwent en bloc rectosigmoid colectomy with primary stapled anastomosis without protective intestinal diversion. There was one (3.2%) anastomotic breakdown requiring reoperation and colostomy. Complete clearance of macroscopic pelvic disease was achieved in all cases. Overall, 87.1% of patients were left with optimal (

Role of obesity in the surgical management of advanced-stage ovarian cancer.

OBJECTIVE: To assess whether obese women with advanced-stage ovarian cancer undergoing primary cytoreduction surgery were at increased risk of suboptimal cytoreduction and complications during the operative and postoperative period as compared to nonobese women. STUDY DESIGN: A retrospective, case-control study of all cases of advanced-stage epithelial ovarian cancer managed surgically at Johns Hopkins Hospital between January 1, 1990, and December 31, 1999. RESULTS: Obese patients were as likely as nonobese patients to undergo optimal cytoreduction at surgery. Obese patients were more likely than nonobese patients to be high-risk anesthesia candidates and more likely than nonobese patients to have tumors >20 cm at surgery. Obese patients were not at greater risk of surgical or postoperative complications than were nonobese patients. CONCLUSION: Obesity is not a risk factor for suboptimal surgical management of advanced-stage ovarian cancer.

Intrauterine progesterone treatment of early endometrial cancer.

OBJECTIVE: Our purpose was to assess the feasibility of using a progesterone-containing intrauterine device (IUD) to treat presumed Federation Internationale Gynecologie et d'Obstetrique (FIGO) stage IA, grade 1 endometrioid cancer in women at high risk for perioperative complications. STUDY DESIGN: Candidates were women with American Society of Anesthesiologists class III or IV grade 1 endometrioid cancer and no imaging evidence of myometrial invasion. Subjects underwent hysteroscopy, curettage, and IUD placement, followed by endometrial biopsy every 3 months for 1 year. The records of similar patients treated surgically during the 3 years before protocol initiation were reviewed for comparison. RESULTS: Sixteen patients fulfilled study criteria. Fourteen consented to participation; one was excluded at the time of IUD placement (grade 2 disease identified) and one was lost to follow-up. Twelve subjects have been followed up to 36 months; results of biopsies were negative in 7 of 11 at 6 months and 6 of 8 at 12 months. No IUD-related complications, except for expulsion, occurred. Sixteen complications (one fatal) occurred in 9 of the 15 control patients. CONCLUSION: Intrauterine progesterone appears to eradicate some cases of presumed stage IA, grade 1 endometrioid cancer in women at high risk for perioperative morbidity.

Continuous abdominal fascial closure: a randomized controlled trial of poly(L-lactide/glycolide).

OBJECTIVE: The objective was to compare the handling characteristics and

Recurrent micropapillary serous ovarian carcinoma.

BACKGROUND: The objectives of the current study were to: 1) characterize the clinical outcome of patients with recurrent micropapillary serous ovarian carcinoma (MPSC) and 2) evaluate the survival impact of secondary cytoreductive surgery and other prognostic variables. METHODS: Twenty-six patients with recurrent MPSC were identified retrospectively from hospital and tumor registry databases. Survival curves were generated from the time of tumor recurrence using the Kaplan-Meier method and statistical comparisons were performed using the log-rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS: The median age of the patients at the time of recurrence was 46 years. The mean progression-free interval was 31.6 months, and 92% of patients had advanced stage disease at the time of the initial diagnosis. Twenty-one patients underwent secondary cytoreductive surgery; tumor debulking was performed in 90.5% of cases and 52.4% of patients required an intestinal resection. Optimal resection (residual disease < or = 1 cm) was achieved in 15 patients (71.4%). Patients undergoing optimal secondary cytoreduction had a median survival time of 61.2 months from the date of disease recurrence, compared with 25.5 months for those patients in whom suboptimal residual disease remained (P < 0.02) and 29.9 months for nonsurgical patients (P < 0.01). On multivariate analysis, optimal secondary cytoreduction was found to be the only independent predictor of survival. Salvage chemotherapy produced an objective response in 25% of patients with measurable disease. The administration of chemotherapy prior to surgical intervention was associated with a trend toward worse survival and a lower likelihood of optimal secondary cytoreduction. CONCLUSIONS: Optimal secondary cytoreductive surgery is feasible in the majority of patients with recurrent MPSC and is an independent predictor of subsequent survival. Surgical intervention should be considered for those patients with recurrent MPSC. [See editorials on pages 675-6 and 677-80, this issue.]

Innovations in the treatment of invasive cervical cancer.

Invasive cervical cancer is characterized by basement membrane-invading lesions capable of metastasizing through the lymphatic and vascular systems. Treatment methods were reviewed by panelists at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), and new opportunities for translational research were discussed. Reviews encompassed hysterectomy with or without lymph node dissection or cervical conization in cases with microinvasion and radical trachelectomy with or without lymph node dissection as fertility-sparing surgery. Chemoradiation is used to treat advanced cervical malignancies, and the risks and benefits of radiotherapy are significant. Pelvic exenteration is used to treat certain types of recurrences. Use of the Miami pouch for continent urinary diversion was highlighted. Gynecologic oncologists expect novel in vivo imaging techniques currently being developed to help guide therapy choices within the next decade. The most significant research priorities are large group-randomized trials involving fertility-sparing procedures and the management of microinvasive carcinoma (MICA); better identification of candidates for chemoradiation; and the development of innovative approaches to exenteration. Improving diagnostic technologies, refining the criteria by which therapies are chosen, and preserving fertility remain challenges in selecting the most appropriate treatment for invasive cervical cancer. Research advances in both diagnosis and treatment are expected to improve therapy and outcomes.