Retroperitoneal Ectopic Pregnancy.

BACKGROUND: Retroperitoneal ectopic pregnancies are rare and have a tendency to implant along major vessels of the abdomen and pelvis. Clinical manifestations can vary from no symptoms to hypovolemic shock and death. CASE: A 30-year-old woman presented in hypovolemic shock with left flank and abdominal pain after attempting to medically terminate her first-trimester pregnancy. Intraoperative findings revealed normal pelvic organs with a massive retroperitoneal hematoma containing chorionic villi confirmed on histopathology. CONCLUSIONS: In a woman with a pregnancy of unknown location presenting with worsening flank pain, a retroperitoneal ectopic pregnancy must be considered. Prompt diagnosis and management in a low-resource setting presents additional challenges.

Meigs to modern times: The evolution of debulking surgery in advanced ovarian cancer.

Joe V. Meigs was a visionary clinician and an early adopter of radical techniques in the surgical treatment of ovarian cancer. His 1934 textbook "Tumors of the Female Pelvic Organs", consolidated his approach to this "hopeless" disease, with pearls on diagnosis, outcomes, and even speculations about the benefits of minimally invasive surgery. Decades before adjuvant chemotherapy would prove of value, and in an era when sophisticated statistics were unheard of, he nonetheless tried to eke out what benefits he could using the methods available in his time. We transition his original findings and observations through the advent of platinum-based chemotherapy, retrospective cohort studies supporting the benefits of primary debulking, and finally the long-awaited randomized controlled trial. We aim to provide historical context for the underpinnings of how cytoreductive surgery has evolved into its current role in the treatment of advanced ovarian cancer.

Cancer and the world's poor: What's a gynecologic cancer specialist to do?

Women in low- and middle-income countries (LMICs) face a drastically increased burden of cervical cancer and the same burden of other gynecologic cancers as do women in high-income countries, yet there are few resources or specialists to meet their needs. 85% of deaths from cervical cancer occur in LMICs. As the population of these regions age, and as death from infectious diseases decrease, this burden will increase further without strong intervention. There are few cancer specialists in LMICs and training in gynecologic cancer care is rare. Gynecologic cancer specialists are uniquely positioned to meet this challenge as advocates, educators and experts. On behalf of the SGO International Committee, we call on our colleagues to meet this historic challenge.

Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells.

The majority of patients with stage III/IV ovarian carcinoma that respond initially to standard therapies ultimately undergo relapse due to the survival of small populations of cells with tumor-initiating potential. These ovarian cancer (OVCA)-initiating cells (OCIC) are sometimes called cancer stem cells (CSC) because they express stem cell markers, and can survive conventional therapies such as chemotherapy, which usually target rapidly replicating tumor cells, and give rise to recurrent tumors that are more chemo-resistant and more aggressive. Thus, it would be desirable to develop a therapy that could selectively target OCIC and be used to complement the conventional therapies. In this study, we isolated a subset of OVCA cells with a CD44(+) phenotype in samples from patients with OVCA that possess CSC properties including the formation of spheroids in culture, self-renewal and the ability to be engrafted in immune-compromised mice. We next explored the use of immunotherapy using fusions of dendritic cells and OCIC to specifically target the OCIC subpopulations. Fusion cells (FCs) prepared in this way activated T cells to express elevated levels of IFN-γ with enhanced killing of CD44(+) OVCA cells. We envision a combined approach where conventional therapies such as chemotherapy kill the bulk of tumor cells, whereas OCIC-reactive cytotoxic T lymphocytes target the resistant OCIC fraction. A combined therapy such as this may represent a promising approach for the treatment of OVCA.

A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use.

In previous studies, we have shown that heat shock protein 70-peptide complexes (HSP70.PCs) derived from the fusion of dendritic cells (DCs) to tumor cells (HSP70.PC-F) possess superior properties compared with HSP70.PCs from tumor cells. HSP70.PC-F are more effective in stimulation of DC maturation and induction of CTL that are able to provide protection of mice against challenge with tumor cells. To develop an improved formulation of HSP70.PC-based tumor vaccine for patient use, we extracted HSP70.PC-F from DCs fused to patient-derived ovarian cancer cells or established human breast cancer cells and examined their properties as tumor vaccines. HSP70.PC-F induced T cells that expressed higher levels of IFN-gamma and exhibited increased levels of killing of tumor cells, compared with those induced by HSP70.PC derived from tumor cells. Enhanced immunogenicity of HSP70.PC-F was associated with improved composition of the vaccine, including increased content of tumor Ags and their processed intermediates, and the detection of other heat shock proteins (HSPs) such as HSP90 and HSP110. The present study has therefore provided an alternative approach to preparation of HSP-based vaccines using DC/tumor fusion technology and gentle and rapid isolation of HSP peptide complexes.

A case of bowel perforation after neoadjuvant chemotherapy for advanced epithelial ovarian cancer.

BACKGROUND: Bowel perforation is a rare complication of chemotherapeutic treatment of cancer, and may result from tumor necrosis within involved bowel or as a function of the mechanism of the chemotherapeutic agent itself. CASE: We present a case of a 71-year-old woman who experienced a spontaneous bowel perforation after a single cycle of carboplatin and paclitaxel during neoadjuvant treatment of advanced epithelial ovarian cancer. This is, to our knowledge, the first reported case of a gastrointestinal perforation with neoadjuvant chemotherapy for ovarian cancer. The clinical circumstances were highly suggestive of a tumor lysis mechanism for the perforation. CONCLUSION: Bowel perforation can occur as a direct consequence of cytotoxic neoadjuvant chemotherapy for advanced ovarian cancer. This potential serious complication may be worthy of consideration when deciding between neoadjuvant chemotherapy and primary surgical management.

Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use.

PURPOSE: To evaluate a protocol that allowed the successful generation of DC and OVCA cells, fusion of these two cell types and assessment of stimulatory ability of the fusion cells for clinical use. PATIENTS AND METHODS: Ovarian cancer (OVCA) cells and dendritic cells (DC) were isolated or generated from 22 patients with OVCA and subsequently fused with PEG. The stimulatory ability of fusion cells including T cell proliferation and induction of cytotocic T lymphocytes (CTL) was assessed. In addition, the impact of radiation, freezing and thawing of the fusion cells was evaluated. RESULTS: OVCA cells derived from 22 patients were successfully fused with autologous DC. The created heterokaryons expressed tumor-associated antigens, such as MUC1 and CA-125, and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, CD4 and CD8 T cells derived from patients with ovarian cancer were stimulated by fusion cells and produced IFN-gamma as demonstrated with intracellular staining. Significantly, T cells primed by fusion cells produced MHC class I-dependent lysis of autologous ovarian tumor cells. One cycle of fusion-cell stimulation can maintain the CTL activity up to 25 days. CONCLUSIONS: The fusion of human OVCA cells and DC created immunogenic cells capable of stimulating CD4 and CD8 T cells. The effects of the processes required for preparing a vaccine for clinical use, including freezing and thawing and irradiation, do not interfere with the immunogenic properties of the fusion cells.

Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation.

Fusion of human dendritic cells (DC) with tumor cells is an effective approach for delivering tumor antigens to DC, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/tumor fusion cells has not been examined. In the present study, we fused patient-derived DC to autologous breast or ovarian carcinoma cells. The fusion cells possessed the properties of both parent cells. After fusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. Colocalization of MUC1 peptide and HLA-DR molecules was observed on fusion cells under the immunoelectron microscope. Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of CD4 and CD8 T cells as assessed by IFN-gamma secretion, HLA-A*0201-MUC1 tetramer, and standard cytotoxic T lymphocyte (CTL) assays. The present study provides first evidence of integration of human DC and tumor cells and links their properties to T cell activation.