Andrei Taran

Human Chorionic Gonadotropin Attracts Regulatory T Cells into the Fetal-Maternal Interface during Early Human Pregnancy

Regulatory T cells (Treg) expand during pregnancy and are present at the fetal-maternal interface at very early stages in pregnancy. The migration mechanisms of Treg to the pregnant uterus are still unclear. Human chorionic gonadotropin (hCG) is secreted by the blastocyst immediately after fertilization and has chemoattractant properties. Therefore, we sought to analyze whether hCG secreted by early trophoblasts attracts Treg to the uterus and hence contributes to maternal tolerance toward the fetus. Decidua and placenta tissue samples from patients having spontaneous abortions or ectopic pregnancies were employed to evaluate Treg and hCG levels. Age-matched samples from normal pregnant women served as controls. We further performed in vitro studies with primary first trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to evaluate the ability of secreted hCG to attract Treg. Patients having miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-β mRNA levels as compared with normal pregnant women. Using migration assays we demonstrated that Treg were attracted by hCG-producing trophoblasts or choriocarcinoma cells. Treg migration toward cells transfected with hCG expression vectors confirmed the chemoattractant ability of hCG. Our data clearly show that hCG produced by trophoblasts attracts Treg to the fetal-maternal interface. High hCG levels at very early pregnancy stages ensure Treg to migrate to the site of contact between paternal Ags and maternal immune cells and to orchestrate immune tolerance toward the fetus.

Interval between Port Catheter Flushing Can Be Extended to Four Months

Background: Little is known about proper interval periods between the flushings of totally implantable access ports after completion of chemotherapy. Manufacturer guidelines recommend flushing catheters every 4 weeks. Methods: This retrospective study examined whether flushing less than every 4 weeks conferred any benefit. Results: 349 totally implanted access ports were divided into four groups based on the different durations of the intervals between flushings. Sixteen (4.6%) complications were observed in the study population. Conclusion: Our results demonstrate that extending the flushing interval to up to 4 months remains medically safe and drastically reduces the costs.

Acute hepatic failure following monotherapy with sunitinib for ovarian cancer.

To the editor Sunitinib (Sutent; PWzer Pharmaceuticals Group, New York, NY, USA) is an orally administered vascular endothelial growth factor (VEGF) receptor tyrosine-kinase inhibitor (RTK) with demonstrated cytotoxic activity against various malignant diseases [1, 2]. We present the case of a 49-year-old patient who died of fulminant hepatic failure following third-line monotherapy with sunitinib for ovarian cancer. The patient was diagnosed with stage IIb ovarian cancer in 2002 and after R0 surgery; she received Wrst-line chemotherapy. In 2006, second-line chemotherapy was started for disease recurrence, leading to a complete remission after six cycles. Nine months later, a tumor measuring 37 £ 42 £ 50 mm in the area of the left iliac vein was diagnosed again by CT scan. An explorative laparotomy was performed revealing an entirely inconspicuous abdominal cavity except for a tumorous lesion on the left pelvic wall, about 50 mm cranial of the inguinal ligament. The tumor was removed and histology revealed a lymph node metastasis of the ovarian cancer. Additional lymph nodes, multiple biopsies of the abdominal cavity and diaphragm, as well as peritoneal Xuid cytology showed no evidence of metastatic disease. Since recurrence occurred nine months after second-line therapy, necessity of third-line chemotherapy was discussed with the patient, but she refused due to toxicities experienced with the previous treatments. At this point, the possibility of oral therapy with sunitinib was discussed. Sunitinib inhibits, amongst others, the RTKs: platelet derived growth factor (PDGF), VEGF c-KIT (produced by the KIT gene) and colony stimulating factor (CSF)-1 whose expression has been reported in ovarian cancer [1, 3]. The risks and possible complications due to side eVects of sunitinib were explained to the patient and she was thoroughly informed about prohibited co-medication during the treatment. Sunitinib therapy was started, at a dose of 50 mg given orally once daily for 4 weeks every 6 weeks. Vital signs and laboratory analysis at the start of therapy were within normal limits. No toxicities except common terminology criteria for adverse events (CTCAE) grade 2 fatigue occurred during the Wrst 4 weeks of therapy. On day 26 of the treatment, the patient presented with CTCAE grade 4 fatigue and an Eastern Cooperative Oncology Group (ECOG) performance status of 3 and was hospitalized. Abnormal laboratory reports included bilirubin 1.1 mg/dl; alanine aminotransferase (ALT) 52.5 U/l; aspartate aminotransferase (AST) 49.2 U/l; gamma glutamyl transpeptidase ( GT) 83.4 U/l; and thyroidea stimulating hormone (TSH) 27.22 mIU/l. She received 75 g Levothyroxin daily for hypothyroidism as concomitant medication. A cranial CT scan did not reveal any abnormality. Therapy with sunitinib was stopped. Twelve hours after admission, the physical condition of the patient and laboratory results had dramatically worsened. Her conscious state deteriorated, she became hypoxic and was transferred to the Intensive Care Unit for intubation and supportive measures. Liver function deteriorated rapidly (Fig. 1), hepatitis serology was negative for HBsAg, and AntiHCV, AntiHBs was 281.2 IU/l. The patient died of liver failure 29 h after hospitalization, despite maximum supportive therapy measures. Immediate family members did not agree with an autopsy. Nevertheless, we believe that the liver failure was associated A. Taran · A. Ignatov · B. Smith · S. D. Costa · J. BischoV Women’s Clinic, Otto-von-Guericke University, Magdeburg, Germany

Methotrexate monotherapy for high-risk gestational trophoblastic neoplasia after therapy with etoposide, methotrexate, and dactinomycin: a case report.

We present a case of high-risk metastatic gestational trophoblastic neoplasia treated successfully with methotrexate monotherapy after severe toxicity from the combination chemotherapy: etoposide, dactinomycin, methotrexate, vincristine, and cyclophosphamide.

Mammareduktionsplastik als Bestandteil der operativen Therapie des Mammakarzinoms – Welche Techniken sollten beherrscht werden?

Die brusterhaltende Therapie (BET) hat sich als Standardverfahren des Mammakarzinoms etabliert. Im Rahmen der BET stellt die tumoradaptierte Mammareduktionsplastik eine Moglichkeit dar, grosere Tumoren mit ausreichendem Sicherheitssaum und gutem kosmetischen Ergebnis zu resezieren. In der Literatur werden zahlreiche Techniken und Methoden der Reduktionsplastik beschrieben. Sie beinhaltet eine Kranialverlagerung des Mamillen-Areola-Komplexes, Reduktion von Drusen-, Fettgewebe und Haut sowie Brustformung. Der Einsatz dieser Operationsmethoden beim Mammakarzinom ist bislang nur selten beschrieben worden. Die Wahl der Operationsmethode richtet sich im Wesentlichen nach der Tumorlokalisation und Grose der Brust. Die wichtigsten Techniken, die man beherrschen sollte, sind die Reduktion mit zentroinferiorem Stiel bei Tumoren in den oberen Quadranten, mit kranialer Mamillenstielung bei einem Tumorsitz in den unteren Quadraten, ebenso die Reduktionsplastik mit periareolarer Narbe bei periareolaren Tumorsitz und die Mammareduktionsplastik mit freier Mamillentransplantation bei einer Gigantomastie. Entscheidende Voraussetzungen fur eine niedrige Komplikationsrate, Vermeidung von Nachresektionen und ein gutes asthetisches Resultat sind die individuelle praoperative Planung und die personliche Erfahrung des Operateurs. Dabei sollte der Operateur sowohl uber onkochirurgische als auch plastisch-rekonstruktive Kenntnisse verfugen, wenn er tumoradaptierte Reduktionsplastikoperationen beim Mammakarzinom einsetzt. Breast conserving surgery (BCS) has been established as the standard therapy for breast cancer. Tumor-adapted reduction mammoplasty as a part of BCS allows relatively large tumors to be removed with tumor-free margins and excellent cosmetic results. There are numerous reports in the literature describing different techniques and methods of reduction breast surgery. All these techniques consist of the reduction of breast skin, glandular and adipose tissue and the cranial transposition of the nipple-areola complex with excellent cosmetic results with regard to both form and symmetry. However, there are only a few reports on the use of mammoplasty techniques in breast cancer surgery. The choice of operative technique depends on tumor localization and breast size. Breast surgeons should be familiar with at least four mammoplasty techniques to allow them to remove the tumor with clear margins and achieve a good cosmesis. If the tumor is in the upper quadrants of the breast, a mammoplasty with an inferior pedicle is suitable. A superior pedicle procedure can be used for tumors in the lower quadrants, a periareolar reduction technique in cases of periareolar tumors and free nipple graft techniques in case of macromastia and ptosis. The most important prerequisites to avoid complications, lower the re-excision rate, and achieve good breast cosmesis are individual preoperative planning and the surgeon’s personal experience.

European and North American scientific meetings under review: presentation and subsequent publication of breast cancer related abstracts in peer-reviewed journals.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3115 Introduction: The number of scientific meetings with breast cancer-related topics increases constantly and therefore so does the number of presented abstracts. Many of these abstracts are not reported in peer-reviewed journals post-conference. This lack of final publication constitutes a loophole in scientific reporting. Furthermore, it retrospectively assesses the quality of the review process the abstracts undergo prior to the meetings. We critically reviewed the publication rates of breast cancer-related abstracts submitted to the four major oncology meetings for breast cancer in Europe and North America in 2002. Material and methods: The authors identified all breast cancer-related abstracts presented or published at the annual meetings of the ASCO, SABCS, EBCC and ESMO in 2002. First, a MEDLINE search identified the abstracts written by the first, second and last authors that matched a journal article by these authors. Second, the match between the study described in the abstract and full publication was determined. Results: A total number of 1620 abstracts were analyzed. Mean rate of full publication: 44,5%; publication rate of EUR meetings: 33,3%; publication rate of NA meetings: 52,7% (p<0,001). Median time to full publication: 11,55 months (CI 95%;7,58 to 15,66 months; full publication for the EUR meetings: 8,59 months; full publication for the NA meetings: 13,44 months (p<0,001). Median impact factor publishing journals: 1,95 IP (CI 95% 0,9 to 2,77 IP), published abstracts of the EUR meetings: 1,09; published abstracts of the NA meetings: 2,5(p<0,001). Estimated probability for an abstract not to be published after 60 months: 55,5%; abstract of the EUR meetings: 67,5%; abstract of the NA meetings: 47,8%(p<0,001) (Figure). Discussion: We found that only about half of all studies first presented as abstracts at major meetings were published as full papers later. Thus, those who rely on scientific evidence to make health care decisions are faced with a biased subset of scientific evidence. It is clear that full-paper reviewing in peer-reviewed journals is more complex and increases the scientific value of a paper in comparison to a meeting abstract. In the past few years the number of scientific meetings on breast cancer and the number of participants attending those has increased dramatically. Our study demonstrated that this does not imply for the quality of the presented data. We propose that scientists who publish their work in peer-reviewed journals should avoid citation of abstracts and/or talks presented even at major international meetings because they risk to rely on data that has not between reviewed thoroughly enough. ![][1] Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3115. [1]: /embed/graphic-1.gif