Biocultural perspectives on maternal mortality and obstetrical death from the past to the present.

Global efforts to improve maternal health are the fifth focus goal of the Millennium Development Goals adopted by the international community in 2000. While maternal mortality is an epidemic, and the death of a woman in childbirth is tragic, certain assumptions that frame the risk of death for reproductive aged women continue to hinge on the anthropological theory of the "obstetric dilemma." According to this theory, a cost of hominin selection to bipedalism is the reduction of the pelvic girdle; in tension with increasing encephalization, this reduction results in cephalopelvic disproportion, creating an assumed fragile relationship between a woman, her reproductive body, and the neonates she gives birth to. This theory, conceived in the 19th century, gained traction in the paleoanthropological literature in the mid-20th century. Supported by biomedical discourses, it was cited as the definitive reason for difficulties in human birth. Bioarchaeological research supported this narrative by utilizing demographic parameters that depict the death of young women from reproductive complications. But the roles of biomedical and cultural practices that place women at higher risk for morbidity and early mortality are often not considered. This review argues that reinforcing the obstetrical dilemma by framing reproductive complications as the direct result of evolutionary forces conceals the larger health disparities and risks that women face globally. The obstetrical dilemma theory shifts the focus away from other physiological and cultural components that have evolved in concert with bipedalism to ensure the safe delivery of mother and child. It also sets the stage for a framework of biological determinism and structural violence in which the reproductive aged female is a product of her pathologized reproductive body. But what puts reproductive aged women at risk for higher rates of morbidity and mortality goes far beyond the reproductive body. Moving beyond reproduction as the root causes of health inequalities reveals gendered-based oppression and inequality in health analyses. In this new model, maternal mortality can be seen as a sensitive indicator of inequality and social development, and can be explored for what it is telling us about women's health and lives. This article reviews the research in pelvic architecture and cephalopelvic relationships from the subfields of evolutionary biology, paleoanthropology, bioarchaeology, medical anthropology, and medicine, juxtaposing it with historical, ethnographic, and global maternal health analyses to offer a biocultural examination of maternal mortality and reproductive risk management. It reveals the structural violence against reproductive aged women inherent in the biomedical management of birth. By reframing birth as normal, not pathological, global health initiatives can consider new policies that focus on larger issues of disparity (e.g., poverty, lack of education, and poor nutrition) and support better health outcomes across the spectrum of life for women globally.

Lymph Node Micrometastases in Early-Stage Cervical Cancer are Not Predictive of Survival.

Although patients with early-stage cervical cancer have in general a favorable prognosis, 10% to 40% patients still recur depending on pathologic risk factors. The objective of this study was to evaluate if the presence of lymph node micrometastasis (LNmM) had an impact on patient's survival. We performed a multi-institutional retrospective review on patients with early-stage cervical cancer, with histologically negative lymph nodes, treated with radical hysterectomy and pelvic lymphadenectomy for the study period 1994 to 2004. Tissue blocks of lymph nodes from the patient's original surgery were recut and then evaluated for the presence of micrometastases. One hundred twenty-nine patients were identified who met inclusion criteria. LNmM were found in 26 patients (20%). In an average follow-up time of 70 mo, there were 11 recurrences (8.5%). Of the 11 recurrences, 2 (18%) patients had LNmM. Patients with LNmM were more likely to have received adjuvant radiation and chemotherapy. In stratified log-rank analysis, LNmM were not associated with any other high-risk clinical or pathologic variables. Survival data analysis did not demonstrate an association between the presence of LNmM and recurrence or overall survival. The presence of LNmM was not associated with an unfavorable prognosis nor was it associated with other high-risk clinical or pathologic variables predicting recurrence. Further study is warranted to understand the role of micrometastases in cervical cancer.

Ovarian tumor ascites CD14+ cells suppress dendritic cell-activated CD4+ T-cell responses through IL-10 secretion and indoleamine 2,3-dioxygenase.

The observation that Th17 infiltration in ovarian cancer correlates with markedly improved survival has prompted the question of whether ovarian tumor antigen-specific Th17 responses could be stimulated by tumor vaccination. Dendritic cells (DCs) treated with IL-15 and an inhibitor of p38 MAPK signaling (DC(IL-15/p38inhib)) bias T-cell responses toward a Th1/Th17 phenotype, raising the prospect of therapeutic vaccination; however, significant barriers remain. Tumor vaccines, including DC vaccination, usually stimulate immune responses, but the lack of clinical responses in cancer patients has been disappointing. Possible reasons may include an inability of antitumor T cells to migrate into the tumor microenvironment, and an inability of T cells to retain effector function in the face of tumor-associated immune suppression. We found that ovarian tumor antigen-specific CD4(+) T cells induced by DC(IL-15/p38inhib) migrated in response to CXCL12 and CCL22 (both highly expressed in ovarian cancer) and to ascites CD14(+) myeloid cells. Cocultures showed that ascites CD14(+) cells markedly suppressed antigen-specific CD4(+) T responses, but suppression could be alleviated by treatment with anti-IL-10 or inhibition of indoleamine 2,3-dioxygenase. These results suggest that the efficacy of DC vaccination against ovarian cancer may be boosted by agents that inhibit tumor-associated CD14(+) myeloid cell suppression or indoleamine 2,3-dioxygenase activity.

Architectural versus nuclear atypia-defined FIGO grade 2 endometrial endometrioid adenocarcinoma (EEC): a clinicopathologic comparison of 154 cases with clinical follow-up.

International Federation of Gynecology and Obstetrics (FIGO) Grade 2 endometrial endometrioid adenocarcinoma carries a 88% 5-yr survival rate. They are defined by >5% but <50% solid epithelial component. A small subset may display <5% solid growth, but marked nuclear atypia and are designated Grade 2. We compared tumor characteristics, staging, and clinical outcome of patients with architectural versus atypia-defined Grade 2 endometrial endometrioid adenocarcinoma. A total of 154 Grade 2 endometrial endometrioid adenocarcinoma cases were reviewed to confirm grade; percent solid growth, and presence of atypia. Only marked atypia (significant nuclear pleomorphism identifiable at 10× or enlarged nuclei, 1.5 to 2× normal, with irregular nuclear contours, dispersed chromatin, and prominent nucleoli) increased the FIGO Grade 1 level. Depth of invasion, tumor stage, lymph node status, and clinical outcomes were then compared. A total of 154 cases were evaluated. Twenty-three were eliminated (6 Grade 3, 17 Grade 1). Of the 131 FIGO II cases, 19 (15%) were based on the presence of severe atypia and 112 (85%) met the architecturally defined criteria. Atypia-defined versus architecturally defined Grade 2 endometrial endometrioid adenocarcinoma's show no significant difference in stage and prognosis. An increase in grade based on presence of nuclear atypia stratifies patients at increased risk as 89% of these patients have myoinvasion at the time of hysterectomy which is in distinct contrast to our previous study (International Journal of Gynecologic Pathology. 2012 July; 31(4): 337-43), where 70% of Grade I cases were noninvasive. No significant correlation between percentage of solid component and risk of recurrence was identified in this study.

Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen.

The recent finding that Th17 infiltration of ovarian tumors positively predicts patient outcomes suggests that Th17 responses play a protective role in ovarian tumor immunity. This observation has led to the question of whether Th17 cells could be induced or expanded to therapeutic advantage by tumor vaccination. In this study, we show that treatment of ovarian tumor antigen-loaded, cytokine-matured human dendritic cells (DC) with a combination of IL-15 and a p38 MAP kinase inhibitor offers potent synergy in antagonism of CD4(+) Treg induction and redirection toward CD4(+) Th17 responses that correlate with strong CD8(+) cytotoxic T lymphocyte (CTL) activation. Ovarian tumor antigen-specific CD4(+) T cells secrete high levels of IL-17 and show reduced expression of CTLA-4, PD-1, and Foxp3 following activation with IL-15/p38 inhibitor-treated DC. We further show that modulation of p38 MAPK signaling in DC is associated with reduced expression of B7-H1 (PD-L1), loss of indoleamine 2,3-dioxygenase activity, and increased phosphorylation of ERK 1/2 MAPK. These observations may allow the development of innovative DC vaccination strategies to boost Th17 immunity in ovarian cancer patients.

Binding women: Ethnology, skeletal deformations, and violence against women.

Control over women in different cultures has taken its form in many ways. Examination of direct forms of control in the bioarchaeological record have been limited to physical violence identified as traumatic bodily injury, and seen on the skeleton as healed defensive fracturing, cut marks, blunt force trauma, and in some cases burial position. But there are other forms of direct violence that reflect indirect modes of control and present as skeletal deformation yet they occur over long periods of time, and are not often included in the suite of bioarchaeological indicators of violence, or discussed as a transcription of the legacy of subornation of women in communities across time. This paper explores the "chronic" violence that is perpetrated against women and is revealed in skeletal deformation. To do this the "binding of women" in the forms of foot-binding, neck rings, and tight-lacing will be used to explore how ethnology and skeletal markers may reveal something about how the complexity of indirect cultural violence can be seen directly on the bodies of women.

Delayed treatment of papillary thyroid carcinoma arising from struma ovarii in a patient with history of bilateral salpingo-oophorectomy: a case report.

OBJECTIVE: We present a case of papillary thyroid carcinoma arising from struma ovarii treated erroneously as ovarian adenocarcinoma for more than 3 years. METHODS: We report clinical, surgical, laboratory, and imaging findings of the study patient and review the relevant literature. RESULTS: A 64-year-old woman was treated for ovarian adenocarcinoma for more than 3 years before it was determined that she likely had papillary thyroid carcinoma arising from struma ovarii. This is the first reported case of thyroid carcinoma arising from struma ovarii in a patient with a history of bilateral salpingo-oophorectomy. Possible etiologies include residual ovarian tissue after oophorectomy, ectopic thyroid, or metastatic thyroid cancer. CONCLUSIONS: It is important to include struma ovarii and thyroid carcinoma arising from struma ovarii in the differential diagnosis, even with a history of bilateral salpingo-oophorectomy. This case emphasizes the importance of effective communication among the pathologist, oncologist, and surgeon to ensure timely initiation of appropriate therapy and reduced patient morbidity.

Psychosocial adjustment among low-income Latina cervical cancer patients.

Cancer-related coping strategies and social support, life stress, and optimism were tested in regression analyses as predictors of depression, affect, and quality of life among 54 low-income, immigrant Latina cervical cancer patients. Sixty-seven percent of the patients endorsed symptoms similar to diagnosable depression. Predictors significantly accounted for 35% to 54% of the variance in outcomes. Cancer-related coping strategies were found to mediate several of the relations between life stress, social support, and optimism and outcomes. Findings emphasize the need to consider the context within which patients live when assessing adjustment to cancer and developing culturally-sensitive interventions.

Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.

BACKGROUND: Lower extremity edema remains a major postoperative complication after inguinal lymphadenectomy for vulvar cancer. This study documents the lymphatic drainage of the vulva versus the lymphatic drainage of the lower extremity coming through the femoral triangle. METHODS: Seven patients underwent either unilateral or bilateral inguinal lymphadenectomy in conjunction with a radical vulvar resection. Preoperatively, patients had technetium-99 injected into the vulvar cancer. Isosulfan blue was injected into the medioanterior thigh 10 cm below the inguinal ligament. The femoral triangle was opened, and a neoprobe was used to locate the "hot" node bearing the technetium-99. Gentle dissection located the blue lymphatic channel and any blue lymph nodes. The blue and hot nodes were resected and submitted separately. The patients then underwent a complete inguinal lymphadenectomy. RESULTS: A total of 11 groin dissections were performed. In 9 of the 11 groins, the hot node was identified, and in 8 of the 11 groins, blue node or lymphatic channel was identified. The hot nodes were uniformly located on the superior medial aspect of the femoral triangle. The blue nodes were uniformly located on the lateral aspect of the femoral triangle just anterior to the femoral artery or vein. Three patients had hot lymph nodes containing cancer. Of those 3 patients, one had an additional node positive. None of the blue lymph nodes contained cancer. CONCLUSIONS: This procedure demonstrates the alternative lymphatic drainage of the leg versus the vulva. Larger studies are necessary to document the exclusivity of these 2 drainage systems. Preservation of the lymphatic drainage of the leg may result in decreased lymphedema.

Intra-examiner and inter-examiner reproducibility of paraspinal thermography.

OBJECTIVE: The objective of this study was to evaluate the intra-examiner and inter-examiner reproducibility of paraspinal thermography using an infrared scanner. MATERIALS AND METHODS: The thermal functions of a commercially available infrared scanner (Insight Subluxation Station®) were evaluated for clinical reliability. Two practicing clinicians conducted the measures on 100 subjects. Intra class correlation coefficients (ICCs) and concordance correlation coefficients (CCCs) were calculated from the collected data. RESULTS: Mean bilateral paraspinal skin temperature was 89.78° F and ranged from 88.77° F to 91.43° F. Intra class correlation coefficients (ICCs) for agreement and consistency ranged from 0.959 to 0.976. Concordance correlation coefficients (CCCs) ranged from 0.783 to 0.859 with tight confidence intervals indicating robust estimates of these quantities. CONCLUSION: This study revealed excellent intra-examiner and inter-examiner reproducibility of paraspinal thermography using a commercially available unit.

Dendritic cell vaccination against ovarian cancer--tipping the Treg/TH17 balance to therapeutic advantage?

The pathology of ovarian cancer is characterized by profound immunosuppression in the tumor microenvironment. Mechanisms that contribute to the immunosuppressed state include tumor infiltration by regulatory T cells (Treg), expression of B7-H1 (PDL-1), which can promote T cell anergy and apoptosis through engagement of PD-1 expressed by effector T cells, and expression of indoleamine 2,3-dioxygenase (IDO), which can also contribute to effector T cell anergy. Expression of both B7-H1 and IDO has been associated with differentiation and recruitment of Treg, and clinical studies have shown that each of these mechanisms correlates independently with increased morbidity and mortality in patients with ovarian cancer. In a remarkable counterpoint to these observations, ovarian tumor infiltration with T(H)17 cells correlates with markedly improved clinical outcomes. In this Future Perspectives review, we argue that dendritic cell (DC) vaccination designed to drive tumor-antigen-specific T(H)17 T cell responses, combined with adjuvant treatments that abrogate immunosuppressive mechanisms operative in the tumor microenvironment, offers the potential for clinical benefit in the treatment of ovarian cancer. We also discuss pharmacological approaches to modulation of MAP kinase signaling for manipulation of the functional plasticity of DC, such that they may be directed to promote T(H)17 responses following DC vaccination.

Overcoming extreme obesity with robotic surgery.

BACKGROUND: Obesity is often associated with endometrial cancer and has posed a challenge in surgical management. Complications such as wound breakdown, respiratory challenges, cardiac complications and difficult intubations are associated with obesity. For the patient with uterine cancer, surgery is necessary for staging, control of symptoms and cure. With the advent of the da Vinci(™) intuitive robot, alternative surgical options can now be offered to these patients. While surgery is the principal modality for the treatment and management of uterine cancer, the morbidly obese patient faces increased complications and longer postoperative recovery. As studied in the LAP2, comparable outcomes have been noted in laparotomy vs laparoscopic surgery. Recently, minimally invasive surgery has been refined with the advent of the da Vinci robotic system. Applying a minimally invasive technique further enhanced with the da Vinci robotic system, a total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed on a patient with a BMI of 98. METHODS: A 35 year-old G0 woman with a BMI of 98 presented with heavy vaginal bleeding and anaemia. She was diagnosed with endometrioid adenocarcinoma of the uterus, FIGO grade 1. She was treated with a robotically assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. RESULTS: Her postoperative course was uncomplicated and she was discharged home on post-operative day 1. CONCLUSIONS: Since obesity is a significant risk factor for endometrial cancer and the prevalence of obesity is increasing, developing surgical techniques to appropriately manage these patients is important. Minimally invasive surgery, specifically with robotic assistance, has increased the possibilities of performing minimally invasive surgery in morbidly obese women. It allows navigation around anatomical barriers and decreases the fatigue experienced by the surgeons. With the increasing obesity of our population and the high prevalence of uterine cancer, further advancement of equipment, anaesthesia and surgical techniques to accommodate the larger patient while decreasing complications have yet to be standardized.

Recurrent endometrial carcinoma regression with the use of the aromatase inhibitor anastrozole.

Recurrent/metastatic endometrial adenocarcinoma that is not amenable to cure with local or regional therapy and/or chemotherapy represents a discouraging clinical entity for the clinician. We report the case of 58-year-old woman with recurrent endometrial carcinoma that was resistant to chemotherapy that was treated successfully with the aromatase inhibitor anastrozole.

Therapeutic vaccination for HPV induced cervical cancers.

Cervical Cancer is the second leading cause of cancer-related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

The influence of microvessel density on ovarian carcinogenesis.

OBJECTIVE: Tumor microvessel density, measured by CD31 immunohistochemistry, correlates with survival in patients with ovarian cancer. CA 125 is secreted by most ovarian cancers, and we have previously shown that the rate of decline of CA 125 is also predictive of ovarian cancer survival. Because increased tumor vascularity may allow metastases on one hand, while facilitating the delivery of chemotherapy on the other, we investigated the relationship of tumor microvessel density to preoperative CA 125, residual disease, and the initial response to treatment. METHODS: FIGO stage, grade, age, residual disease, and CD31 microvessel density count were correlated with consecutive patients (n = 202) diagnosed with epithelial ovarian cancer who met entry criteria. The relationship of CD31 staining to preoperative CA 125, and the rate of decline in CA 125 (slope) as a measure of initial response to therapy, was also evaluated based on complete CA 125 data. Spearman correlation and the Wilcoxon rank sum test were used for bivariate analyses. Linear and logistic regression was used for multivariate analysis. RESULTS: There were 21 stage I, 14 stage II, 125 stage III, and 42 stage IV patients diagnosed with epithelial ovarian cancer included in the study. More than half (N = 126) of the patients were optimally cytoreduced. Elevated microvessel density was associated with advanced stage of disease (P = 0.0453), grade (P = 0.0002), and an increased amount of residual disease (P = 0.0144). CA 125 values were higher in patients with residual disease versus patients without residual disease (P = 0.0357), and the decline in the CA 125 (slope) was less steep in patients without residual disease versus patients with residual disease (P = 0.0003). However, the initial response to chemotherapy was unrelated to the microvessel density count as measured by CD31 antibody staining (P = 0.7911). In multivariate analyses, CD31 counts remained significant in relationship to grade. Nonideal slopes, indicating decreased response, were associated with increasing age (P = 0.0008) and residual disease (P = 0.0035). CONCLUSION: Elevated ovarian cancer microvessel density count is related to advanced stage and grade of disease, and compromised potential for cytoreduction. Residual disease is associated with higher CA 125 levels and faster CA 125 decline rates. The rate of decline of CA 125 during the initial response to treatment cannot be predicted based on CD31 counts, confirming a complex relationship between tumor vascularity, metastasis, and response to treatment.