Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

OBJECTIVE: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing. METHODS: In this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens. RESULTS: Our model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential. CONCLUSIONS: Short duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

The Use of Endometrial Cancer Patient-Derived Organoid Culture for Drug Sensitivity Testing Is Feasible.

OBJECTIVE: Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer. METHODS: Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium. An organoid growth assay was developed to assess the inhibitory effects of a variety of drugs including endocrine treatments. Organoid cultures were also prepared for histological and immunohistochemical comparison to the tumors of origin. RESULTS: Fifteen endometrial cancer specimens were successfully cultured as PDOs. Small spherical structures formed within 24 hours, and many continued to grow to larger, denser organoids, providing the basis for an organoid growth assay. The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth. Inhibition by different growth factor receptor tyrosine kinase inhibitors was observed in several PDO specimens. Four cultures were inhibited by fulvestrant, implying the importance of estrogen-receptor signaling in some PDO cultures. Organoids closely resembled their tumors of origin in both histomorphology and immunohistochemical expression. CONCLUSIONS: The use of endometrial cancer PDO cultures for development of drug sensitivity testing for individual patient tumors is feasible. The potential value of the PDO model for clinical decision making will require clinical trial evaluation.

Homage to Atlantic City.

In this article, I reflect on the unique value for the societies of academic internal medicine of their annual spring meetings that were held in Atlantic City for two generations prior to 1977 and consider whether lessons remain from those past experiences.

Ovarian cancer: predictors of early-stage diagnosis.

OBJECTIVES: Despite the lack of effective screening, almost 20% of women with ovarian cancer are diagnosed at an early stage of disease, when the prognosis is favorable. This study sought to elucidate tumor-related, census-based socioeconomic indicators, and demographic characteristics associated with early diagnosis of epithelial ovarian cancer (EOC). METHODS: The study population included 16,228 women diagnosed with epithelial ovarian cancer from 1996 through 2006 and reported to the California Cancer Registry. Women diagnosed with stage I tumors were compared to those diagnosed with stage III or IV disease with respect to several demographic and tumor-related characteristics. Logistic regression was used to estimate adjusted odds ratios (OR) and associated 95% confidence intervals. RESULTS: Age at diagnosis, tumor histology, tumor size, laterality, and grade were all strongly associated with EOC early stage at diagnosis. However, after adjusting for all relevant factors in this study, other disparities were detected. Compared with white women, the likelihood of being diagnosed with early-stage disease was significantly lower among African Americans (OR = 0.78, 95% CI = 0.55-0.92), and significantly higher among women with private insurance compared to those either uninsured or covered by Medicaid (OR = 1.6, 95% CI = 1.18-2.05). CONCLUSION: These findings suggest that, in addition to tumor biology, disparities in access to care may have a significant effect on the timely diagnosis of epithelial ovarian cancer.

Adverse obstetric events are associated with significant risk of cerebral palsy.

OBJECTIVE: To examine adverse birth events on the development of cerebral palsy in California. STUDY DESIGN: A retrospective population-based study of children with cerebral palsy (as of Nov. 30, 2006), matched to their maternal/infant delivery records (Jan. 1, 1991 to Dec. 31, 2001) was performed. Demographic data and intrapartum events were examined. Six adverse birth-related events were chosen. Children without cerebral palsy were controls. RESULTS: There were 7242 children who had cerebral palsy (59% term) and 31.3% had 1 or more of the 6 adverse intrapartum events (12.9% in controls P < .0001). This held for both term (28.3% vs 12.7% controls) and preterm (36.8% vs 15.9%, controls) neonates (both P < .0001). Maternal (15.1% vs 6.6%) and neonatal (0.9% vs 0.1%) infection were increased in cerebral palsy cases (P < .0001). CONCLUSION: Almost one-third of children with cerebral palsy had at least 1 adverse birth-related event. Higher rates in the preterm group may partially explain the higher rates of cerebral palsy in this group.

Trends in the safety of inpatient hysterectomy for benign conditions in California, 1991-2004.

OBJECTIVE: To assess the utilization rates of and complications associated with inpatient hysterectomy in California between 1991 and 2004. METHODS: We used the California Patient Discharge Database to analyze International Classification of Diseases, 9th Revision, Clinical Modification diagnostic and procedure codes for 649,758 women undergoing inpatient hysterectomy in California between 1991 and 2004 using multiple logistic regression models. RESULTS: Between 1991 and 2004, the incidence of any type of inpatient hysterectomy for benign gynecologic conditions declined 17.6%. The rates of laparoscopically assisted vaginal hysterectomy and subtotal hysterectomy increased substantially. The year of hysterectomy was a factor associated with both medical and surgical complications; the odds of inpatient complications between 1991 and 2004 steadily declined. CONCLUSION: In California between 1991 and 2004, the incidence of inpatient hysterectomy for benign gynecological conditions and the adjusted odds of complications declined substantially. Changes in practice and shorter hospital stays may have affected the changes in inpatient hysterectomy rates and associated inpatient complications.

Maternal and neonatal outcomes after attempted suicide.

OBJECTIVE: The purpose of this study was to describe identifiers and estimate maternal and neonatal outcomes in women who attempt suicide during pregnancy. METHODS: A linked Vital Statistics-Patient Discharge database of the State of California was used to identify cases of intentional injury during pregnancy. A retrospective analysis of maternal and neonatal outcomes in pregnant women who were admitted for attempted suicide is presented. RESULTS: There were 4,833,286 deliveries in California from 1991 to 1999. Of those deliveries, 2,132 were complicated by attempted suicide during pregnancy (0.4 per 1,000 pregnancies). The control population was composed of patients who did not attempt suicide. The group of women that attempted suicide during pregnancy had increases in premature labor, cesarean delivery, and need for blood transfusion. Analysis of neonatal outcomes revealed increases in respiratory distress syndrome and low birth weight infants. A subanalysis, including women who delivered at the hospitalization for attempted suicide, demonstrated increased premature delivery, respiratory distress syndrome, and neonatal and infant death. CONCLUSION: Attempted suicide is associated with significantly higher rates of maternal and perinatal morbidity, and in some cases, perinatal mortality. The best identifier for women at risk for attempting suicide is substance abuse. Care provider identification and prevention are of key importance in preventing these outcomes.

Association of maternal fractures with adverse perinatal outcomes.

OBJECTIVE: We sought to assess the effects of fracture injuries on maternal and fetal/neonatal outcomes in a large obstetric population. STUDY DESIGN: We performed a retrospective cohort study using a database in which maternal and neonatal hospital discharge summaries were linked with birth and death certificates to identify any relation between maternal fractures and maternal and perinatal morbidity. Fracture injuries and perinatal outcomes were identified with the use of the International Classification of Diseases, 9th revision, Clinical Modification codes. Outcomes were further subdivided on the basis of anatomic site of fracture. RESULTS: A total of 3292 women with > or = 1 fractures were identified. Maternal mortality (odds ratio, 169 [95% CI, 83.2,346.4]) and morbidity (abruption and blood transfusion) rates were increased significantly in women who were delivered during hospitalization for their injury. Women who were discharged undelivered continued to have delayed morbidity, which included a 46% increased risk of low birth weight infants (odds ratio, 1.5 [95% CI, 1.3,1.7]) and a 9-fold increased risk of thrombotic events (odds ratio, 9.2 [95% CI, 1.3,65.7]) Pelvic fractures had the worst outcomes. CONCLUSION: Fractures during pregnancy are an important marker for poor perinatal outcomes.

Maternal and neonatal outcomes of assaults during pregnancy.

OBJECTIVE: To assess perinatal outcomes of women hospitalized for assault during pregnancy as a function of timing of delivery. METHODS: A retrospective population-based study analyzing maternal discharge records linked to birth/death certificates in California from 1991 to 1999 was performed. International Classifications of Disease, Ninth Clinical Modification (ICD-9-CM) codes were used to identify injury types and outcomes. External causation codes identified assaults as the mechanism of the injuries. Injury Severity Scores were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and multivariate logistic regression was used for analysis of outcomes. RESULTS: A total of 2,070 women were hospitalized during pregnancy after sustaining an assault. Assaulted women were younger, multiparous, and with delayed prenatal care compared with unassaulted controls. Women delivering at the assault hospitalization had high rates of prematurity: 24%, OR 2.4 (95% CI 1.8-3.3), maternal death: 0.71%, OR 19 (95% CI 2.7-144.7), fetal death: 9.3%, OR 8 (95% CI 4.6-14.3), uterine rupture: 0.71%, OR 46 (95% CI 6.5-337.8), and other adverse outcomes compared with unassaulted women. Women discharged after an assault, delivering at a subsequent hospitalization, had increased risks of abruption: 2%, OR 1.8 (95% CI 1.3-2.5), hemorrhage: 3.2%, OR 1.8 (95% CI 1.4-2.5), prematurity: 15%, OR 1.3 (95% CI 1.2-1.5), and low birth weight: 13.4%, OR 1.7 (95% CI 1.5-1.9) at delivery. CONCLUSION: Women sustaining an assault during pregnancy experience both immediate (uterine rupture, increased fetal and maternal mortality) and long-term sequelae (prematurity and low birth weight infants), which have significant negative effects on pregnancy outcome. LEVEL OF EVIDENCE: III.

Pregnancy-associated cervical cancer: obstetric outcomes.

OBJECTIVE: Describe the obstetric outcomes among women in California with pregnancy associated cervical cancer. METHODS: Cases were identified utilizing computer-linked infant birth/death certificates, discharge records, and cancer registry files, and then assigned to a prenatal or post-partum cancer diagnosis group. Outcomes included cesarean delivery, hospitalizations, birth weight, prematurity, and infant mortality. RESULTS: Among 434 cases identified, those diagnosed prenatally (136 cases) had higher rates of cesarean section (odds ratio 3.7; 95% CI 2.6, 5.2), hospitalization >5 days (maternal: odds ratio 14.1; 95% CI 9.2, 21.5 neonatal: odds ratio 5.2; 95% CI 3.6, 7.5), low birth weight (LBW) (odds ratio 5.5; 95% CI 3.7, 8.1), very LBW (odds ratio 6.9; 95% CI 3.7, 12.8), prematurity (odds ratio 4.7; 95% CI 3.2, 6.7), and fetal deaths (odds ratio 5.5; 95% CI 2.0, 14.8) compared to non-cancer pregnant controls. Very LBW (odds ratio 2.6; 95% CI 1.4, 4.8), prematurity (odds ratio 1.5; 95% CI 1.1, 2.1), and fetal death rates (odds ratio 3.0; 95% CI 1.2, 7.4) remained elevated among those diagnosed post-partum. No neonatal deaths were attributable to elective premature delivery. CONCLUSIONS: We observed higher rates of fetal death and spontaneous prematurity among women with pregnancy-associated cervical cancer.

Risk factors associated with cerebral palsy in preterm infants.

OBJECTIVE: To examine pregnancy outcomes in preterm delivered children with cerebral palsy (CP). METHODS: A retrospective population-based cohort study of children born in California (January 1, 1991 and December 31, 2001) with CP were identified (State databases) and compared to children without CP. We examined demographic data and pregnancy outcomes by gestational age groups controlling for multiple co-founders. RESULTS: Of 2733 preterm infants (total of 8397, 33% <37 weeks of gestation) with CP, delivery <28 weeks had the largest impact upon the development of CP (Odds ratio (OR) 18.2 95%CI (16.7, 19.9)) with delivery 28-31 6/7 weeks having less impact (OR 8.8 (8.0, 9.7) when compared to term deliveries. Birth asphyxia (OR 5.9 (5.3, 6.6) was associated with the future development of CP as were birth defects (OR 4.3 (4.1. 4.5), cord prolapse (OR 2.0 (1.6, 2.4)) and fetal distress (OR 2.1 (1.9, 2.2)) the latter 2 being less so. CONCLUSION: Prematurity had the greatest impact upon the future development of CP; however, birth asphyxia, birth defects and adverse labor events contributed significantly to the future development of CP as well, suggesting that the cause of CP in the preterm infant is most likely multifactorial.

Racial, ethnic, and socioeconomic disparities in the prevalence of cerebral palsy.

OBJECTIVE: Racial and ethnic disparities in cerebral palsy have been documented, but the underlying mechanism is poorly understood. We determined whether low birth weight accounts for ethnic disparities in the prevalence of cerebral palsy and whether socioeconomic factors impact cerebral palsy within racial and ethnic groups. METHODS: In a retrospective cohort of 6.2 million births in California between 1991 and 2001, we compared maternal and infant characteristics among 8397 infants with cerebral palsy who qualified for services from the California Department of Health Services and unaffected infants. RESULTS: Overall, black infants were 29% more likely to have cerebral palsy than white infants (relative risk: 1.29 [95% confidence interval: 1.19-1.39]). However, black infants who were very low or moderately low birth weight were 21% to 29% less likely to have cerebral palsy than white infants of comparable birth weight. After we adjusted for birth weight, there was no difference in the risk of cerebral palsy between black and white infants. In multivariate analyses, women of all ethnicities who did not receive any prenatal care were twice as likely to have infants with cerebral palsy relative to women with an early onset of prenatal care. Maternal education was associated with cerebral palsy in a dose-response fashion among white and Hispanic women. Hispanic adolescent mothers (aged <18 years) had increased risk of having a child with cerebral palsy. CONCLUSIONS: The increased risk of cerebral palsy among black infants is primarily related to their higher risk of low birth weight. Understanding how educational attainment and use of prenatal care impact the risk of cerebral palsy may inform new prevention strategies.

Pregnancy-associated colon and rectal cancer: perinatal and cancer outcomes.

OBJECTIVE: Assess the impact of colorectal cancer on maternal and neonatal outcomes. METHODS: Cases were identified using several computer-generated linkage analyses. Maternal and newborn hospital discharges in California were linked to birth and if applicable infant death certificate records. This database was then linked to the California Cancer Registry, to create a cohort of women with pregnancy-associated colon and rectal cancer. This cohort was compared to pregnant women in California without colorectal cancer. Our secondary comparison was to non-pregnant, Californian women with colorectal cancer who could be aged-matched. RESULTS: Women with pregnancy-associated colorectal cancer were more likely to undergo cesarean section (OR: 1.9) and to develop puerperal infections (OR: 2.8). In addition, higher rates of preterm delivery were found both secondary to scheduled deliveries and preterm labor (OR for preterm labor, 2.8). Neonatal outcomes were fairly similar between the two groups. Pregnancy was not found to have a significant effect on survival (HR: 0.73). CONCLUSIONS: We found that women with pregnancy-associated colorectal cancer had excellent maternal and neonatal outcomes. This is likely secondary to the fact that most women are diagnosed after delivery. In addition, survival is similar between pregnancy-associated and non-pregnancy associated cases.

Early clinical detection of ovarian cancer: a review of the evidence.

Subjective and objective evidence suggest that a third to half of patients developing ovarian cancer report symptoms at 3 or more months prior to diagnosis. Early ovarian cancer-associated symptoms constitute a constellation of mostly nongynecological complaints, suggesting a visceral disturbance, which do not point immediately to a pelvic origin. Abdominal bloating and pain predominate with recent onset and multiple symptomatic episodes. Gastrointestinal and urinary symptoms and fatigue/malaise may be part of the symptom complex. Women aged 50 years and older with this constellation of symptoms should have medical evaluation and, if symptoms are unexplained or persist, should undergo pelvic imaging (e.g., transvaginal ultrasound) and serum CA125.

Adnexal masses in pregnancy: how often are they malignant?

OBJECTIVE: The primary objective was to investigate the occurrence rates of benign and malignant ovarian tumors associated with pregnancy among women identified in three large California databases between 1991 and 1999. The secondary objective was to determine maternal and perinatal outcomes among these pregnancies. METHODS: This is a population-based study of 4,846,505 obstetrical patients using California hospital discharge records from 1991-1999. The California vital statistics birth/patient discharge database was linked to the California Cancer Registry (CCR). Cases of maternal ovarian cancers and low malignant potential (LMP) tumors were separated into three periods based on the timing of diagnosis and pregnancy: prenatal, at delivery, and postpartum. International Classification of Diseases, Revision 9 (ICD-9) codes were used to identify both diagnostic and procedural factors occurring during hospitalizations. The CCR database was used to identify cancer outcomes such as stage, histology, treatments, and vital status. RESULTS: 9375 women had a hospital diagnosis of an ovarian mass associated with pregnancy. CCR database identified 87 ovarian cancers and 115 LMP tumors in the same cohort. The occurrence rates were 0.93% (87/9375) ovarian cancers per total number of ovarian masses diagnosed during pregnancy, and 0.0179 ovarian cancers per 1000 deliveries. The summary stages of the ovarian cancers and LMP tumors were (respectively): localized 65.5% and 81.7%, regional 6.9% and 7.8%, remote 23.0% and 4.4%, and unknown 4.6% and 6.1%. 34 of the 87 ovarian cancers were germ cell tumors (GCT). Malignant ovarian tumors increased the likelihood of maternal outcomes such as cesarean delivery, hysterectomy, blood transfusions, and prolonged hospitalization compared to noncancer pregnant controls, but did not adversely affect neonatal outcomes. Cause-specific maternal mortality of patients with follow-up was 4.7% (9/191) at a mean of 2.43 years after diagnosis. CONCLUSIONS: Ovarian malignancies are rare during pregnancy. Most maternal malignant ovarian neoplasms are early stage and associated with favorable maternal and neonatal outcomes. The low maternal mortality rate is likely due to the predominance of GCTs among the ovarian cancers.

Malignant melanoma in pregnancy. A population-based evaluation.

BACKGROUND: For many years, there has been controversy in the medical community regarding the correlation of female hormonal factors with the outcome of women with malignant melanoma. There have been multiple reports that women with high hormone states, such as pregnancy, had thicker tumors and/or a worse prognosis compared with a group of control women. METHODS: The authors used a database that contained maternal and neonatal discharge records from the entire state of California from 1991 to 1999 and linked those records to the California Cancer Registry, which maintains legally mandated records of all cancers reported in California during the same time period. Four hundred twelve women with malignant melanoma diagnosed during or within 1 year after pregnancy were identified (145 antepartum, 4 at delivery, and 263 postpartum) and were compared with a group of age-matched, nonpregnant women with melanoma (controls). The database captured only pregnancies at > or = 20 weeks of gestation. RESULTS: When comparing women who had pregnancy-associated melanoma with the control group, the authors found no difference in the distribution of disease stage (82.0% of pregnant and postpartum women had localized melanoma vs. 81.9% of control women) or the tumor thickness (mean: 0.77 mm for pregnant women, 0.90 mm for postpartum women, and 0.81 mm for the control group). In a multiple regression model that controlled for age, race, stage, and tumor thickness, pregnancy had no impact on survival in women with melanoma. Lymph node assessment and positivity of lymph nodes also were equivalent between the two groups. Maternal and neonatal outcomes did not differ between pregnant women with melanoma and control women who were pregnant and had no history of malignancy. Small numbers of women with advanced melanoma and the inability to capture melanoma that occurred in pregnancies that were lost or were terminated prior to 20 weeks limited the conclusions primarily to women with localized melanoma. CONCLUSIONS: In this large, population-based study of pregnant women in California from 1991 to 1999 with malignant melanoma, there were no data found to support a more advanced stage, thicker tumors, increased metastases to lymph nodes, or a worsened survival. The outcome for women with localized melanoma associated with pregnancy was excellent. Maternal and neonatal outcomes also were equivalent to those of pregnant women without melanoma.

An enhanced obstetrics track for a family practice residency program: results from the first 6 years.

BACKGROUND: Advanced training in obstetrics for family physicians occurs through a variety of methods. The program described has developed an obstetrics track for family practice residents. METHODS: Five residents have completed the 4-year residency program with enhanced obstetric training developed, and the results, in terms of procedural experience and examination scores, have been reviewed. RESULTS: These 5 family physicians performed a similar number of obstetric procedures compared with their Obstetrics and Gynecology resident counterparts, and they performed as well as their family medicine resident counterparts on national in-service examinations. CONCLUSIONS: A 4-year enhanced obstetrics track is an effective means of improving the training of family medicine residents in obstetric procedures while maintaining the other fundamental training and residency review committee requirements for family medicine residents.

Early symptoms of ovarian cancer: a case-control study without recall bias.

BACKGROUND: Ovarian cancer is usually diagnosed after it has spread and is difficult to cure. Previous attempts to identify early symptoms have either lacked a control group or have been based on interviews of cases, with possible recall bias. OBJECTIVE: The purpose of this study was to identify early symptoms of ovarian cancer by reviewing prediagnostic medical records, free of recall bias, and comparing women with and without ovarian cancer. METHODS: In an integrated health care delivery system, symptoms recorded in medical records of 102 women with ovarian cancer during the two years before diagnosis were compared with those of 102 matched control women. RESULTS: More cases than controls complained of several symptoms up to one year before diagnosis. Most of these symptoms were abdominal or gastrointestinal in nature and were more prevalent in the advanced stage cases. Other symptom sites included pelvic, urinary, back, and systemic. Because case-control differences were not large and prevalence is low, positive predictive values were generally quite low. CONCLUSION: Previous reports of early symptoms of ovarian cancer were confirmed in a study with a control group and free of recall bias. It is not clear that these symptoms occurred while the disease was still localized. Because hundreds of women would have to be investigated to detect one case of ovarian cancer, the clinical utility of these symptoms is uncertain. Nevertheless, health care providers should keep ovarian cancer in mind, when women present with symptoms such as abdominal pain and bloating.

Ovarian cancer: can we make the clinical diagnosis earlier?

BACKGROUND: Patients with ovarian cancer often report having symptoms for months before diagnosis, but such findings are subject to recall bias. The aim of this study was to provide an objective evaluation of symptoms that precede a diagnosis of ovarian cancer. METHODS: Medicare provider claims linked to records in the California Surveillance, Epidemiology, and End Results data base were utilized to extract diagnosis and procedure codes for 1985 women age 68 years or older who resided in California with ovarian cancer, 6024 elderly women with localized breast cancer, and 10,941 age-matched, Medicare-enrolled women without cancer. Prevalence of rates of symptom-related diagnoses and procedure codes in Medicare claims records were obtained during 3-month periods up to 36 months before diagnosis of ovarian cancer. RESULTS: From 1 month to 3 months before patients were diagnosed with ovarian cancer, the frequency and adjusted odds ratios (ORs) with 95% confidence intervals (95%CIs) for 4 "target symptom" code groups were: abdominal pain (frequency, 30.6%; OR, 6.0; 95%CI, 5.1-6.9), abdominal swelling (frequency, 16.5%; OR, 30.9; 95%CI, 21.4-44.8), gastrointestinal symptoms (frequency, 8.4%; OR, 2.3; 95%CI, 1.8-3.0), and pelvic pain (frequency, 5.4%; OR, 4.3; 95%CI, 2.8-6.7). The adjusted odds for abdominal swelling codes was elevated 10-12 months before diagnosis (OR, 2.4; 95%CI, 1.2-4.6) for abdominal pain codes 7-9 months before diagnosis (OR, 1.3; 95%CI, 1.1-1.7). Abdominal imaging (frequency, 7.0%; OR, 1.3; 95%CI, 1.0-1.7) and pelvic imaging/CA125 (frequency, 3.7%; OR, 2.4; 95%CI, 1.7-3.4) showed an elevated frequency and adjusted odds 4-6 months before diagnosis. Patients with claims codes for "target symptoms" 4-36 months before diagnosis were more likely to have abdominal imaging (61.1%) or gastrointestinal procedures (30.8%) than pelvic imaging/CA125 (25.3%). CONCLUSIONS: Patients with ovarian cancer were more likely than patients with breast cancer and women in a cancer-free control group to have target symptom codes (particularly abdominal swelling and pain) > 6 months before diagnosis. The evaluation of women with unexplained "target symptoms" should include pelvic imaging and/or CA125.

Cancer associated with obstetric delivery: results of linkage with the California cancer registry.

OBJECTIVE: This study provides revised population-based measurements for the occurrence rates of cancer associated with obstetric delivery and examines perinatal and cancer-related outcomes within the group of women with 4,846,505 obstetric deliveries in California, inclusive of the years 1991 through 1999. STUDY DESIGN: This observational study used a population-based retrospective review of cases identified as a result of computer linkage of maternal/neonatal hospital discharge and birth/death records with case files in the California Cancer Registry (CCR). The effect of timing of cancer diagnosis on clinical outcomes was studied by dividing the cases into three groups as follows: "prenatal" for cancer diagnosis within 9 months before delivery, "at delivery" for cancer diagnosis during delivery hospitalization, and "post partum" for cancer diagnosis within 12 months after delivery. Computerized records for 4,846,505 obstetric patients and 4,906,920 newborn infants comprising the linked vital statistics birth/patient discharge database (VS/PDD) were used to identity-match cases within the CCR case files. Cases of malignant disease were categorized into 22 anatomic or histologic subgroups. Perinatal clinical outcomes including preterm delivery, prolonged neonatal hospital stay, stillbirth, neonatal death, frequency of first trimester prenatal care, and cesarean delivery were analyzed by use of International Classification of Diseases, 9th Revision, Clinical Modification codes from the VS/PDD. Clinical cancer outcomes including cancer stage and vital status on follow-up were drawn from CCR records. Statistical comparisons for trends were performed with the Cochran-Armitage test, outcomes comparisons with the Fisher exact test, and survival comparisons were performed with the Cox proportional hazard model. RESULTS: Among 4,846,505 obstetric deliveries, 4,539 cases of invasive malignancy were identified for an observed occurrence rate of 0.94 per 1000 births. Sixty-four percent of the cases occurred post partum; cancers of the breast, thyroid, cervix, along with malignant melanoma, and Hodgkin's disease accounted for 64% of the cases. The timing of cancer diagnosis affected clinical outcomes: for all cancer cases as a group, the most favorable perinatal and cancer outcomes occurred in women whose cancer diagnosis was made 6 to 9 months before delivery (6% of cases). The most unfavorable perinatal and cancer outcomes were associated with cancer diagnosis made 0 to 3 months before delivery (14% of cases). For women whose cancer was diagnosed post partum, perinatal outcomes were minimally affected by the presumed existence of occult cancer at the time of obstetric delivery. CONCLUSION: The use of computer-linkage to the CCR files enhanced identification of cases of maternal malignancy associated with obstetric delivery. Cancer diagnosis was associated with approximately 1 in 1000 deliveries. Most cases were diagnosed after delivery and were comprised predominantly of cancers of the breast, thyroid, cervix, malignant melanoma, and Hodgkin's disease. A small group of women (approximately 1 per 5000 deliveries) are seen within a few months before delivery or at delivery with malignant disease, many of whom have rapidly progressing disease and may require high-risk perinatal and oncology services.