Andreas Kavallaris

Monitoring the Response of Circulating Epithelial Tumor Cells to Adjuvant Chemotherapy in Breast Cancer Allows Detection of Patients at Risk of Early Relapse

PURPOSE To demonstrate that it is possible to monitor the response to adjuvant therapy by repeated analysis of circulating epithelial tumor cells (CETCs) and to detect patients early who are at risk of relapse. PATIENTS AND METHODS In 91 nonmetastatic primary breast cancer patients, CETCs were quantified using laser scanning cytometry of anti-epithelial cell adhesion molecule-stained epithelial cells from whole unseparated blood before and during adjuvant chemotherapy. RESULTS Numbers of CETCs were analyzed before therapy, before each new cycle, and at the end of chemotherapy. The following three typical patterns of response were observed: (1) decrease in cell numbers (> 10-fold); (2) marginal changes in cell numbers (< 10-fold); and (3) an (sometimes saw-toothed) increase or an initial decrease with subsequent reincrease (> 10-fold) in numbers of CETCs. Twenty relapses (22%) were observed within the accrual time of 40 months, including one of 28 patients from response group 1, five of 30 patients from response group 2, and 14 of 33 patients from response group 3. The difference in relapse-free survival was highly significant for CETC (hazard ratio = 4.407; 95% CI, 1.739 to 9.418; P < .001) between patients with decreasing cell numbers and those with marginal changes and between patients with marginal changes and those with an increase of more than 10-fold (linear Cox regression model). CONCLUSION These results show that peripherally circulating tumor cells are influenced by systemic chemotherapy and that an increase (even after initial response to therapy) of 10-fold or more at the end of therapy is a strong predictor of relapse and a surrogate marker for the aggressiveness of the tumor cells.

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

IntroductionIn adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting.MethodWe used MAINTRAC® analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients.ResultsMAINTRAC® analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy.ConclusionThe response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.

94 months follow-up after laparoscopic assisted vaginal resection of septum rectovaginale and rectosigmoid in women with deep infiltrating endometriosis

BackgroundEndometriosis with bowel involvement is the most invasive form and can cause infertility, chronic pelvic pain and bowel symptoms. Effective surgical treatment of endometriosis requires complete excision of endometriosis and in same case may require segmental rectosigmoid resection.MethodsBetween December 1997 and October 2003, 55 patients with rectovaginal endometriosis underwent a combined laparoscopic vaginal technique. 30 patients were found at a follow-up and underwent a telephone interview. The questionnaire covered questions about symptoms related to recurrences of intestinal endometriosis, dyspareunia, dysmenorrhea and pregnancy.ResultsTwenty-seven of 30 (90%) women have no clinical symptoms of reported recurrence of endometriosis. Two patients (6.6%) had evidence of recurrence of bowel endometriosis. Dysmenorrhoea disappeared in 28 (93.3%), dyspareunia in 26 (86.7%) and pelvic pain in 27 (90%) patients. 17 patients (31%) tried to become pregnant and 11 of these patients (65%) became pregnant: 9 patients delivered healthy newborns, 18 pregnancies occurred and 19 healthy children were born.ConclusionsDespite the small number of follow-up patients, our 94-month follow-up data demonstrated that endometriosis with bowel involvement and radical resection was associated with significant reductions in painful and dysfunctional symptoms, a low recurrence rate (6.6%) and high pregnancy rate (36.6%).

Spontaneous uterine rupture at the 21st week of gestation caused by placenta percreta.

AbstractPurposeTo describe the management of a ruptured uterus caused by placenta percreta in the 21st week of gestation.Methods We present a case report of a 33-year-old patient with a ruptured uterus in the 21st week of gestation who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck. Therapeutic management was performed by laparoscopy, and consecutive laparotomy and hysterectomy.Results A 33-year-old patient presented with severe abdominal pain in the 21st week of gestation at the department of abdominal surgery. A laparoscopy was performed to exclude appendicitis. There was about one liter of blood in the peritoneal cavity and a small, bleeding lesion in the fundus uteri was found which was coagulated. The blood was evacuated and the patient returned to department of gynecology. One hour after the first operation, the patient developed signs of hypovolemic shock and ultrasound showed absent fetal heart beat. An immediate laparotomy was performed and a ruptured uterus was detected. The fetus was removed and a hysterectomy performed. Pathology results showed a placenta percreta. After a few days in hospital and transfusion of 4 liters of blood the patient was discharged in a healthy condition.Conclusions In a pregnant woman with severe abdominal pain even in the 21st week of gestation a placenta percreta has to be considered as a differential diagnosis. If there is no evidence of other causes, laparoscopy may help to confirm the diagnosis and hysterectomy is a life saving intervention.

Laparoendoscopic single-site surgery (LESS) - is it feasible in gynecological surgery?

Increases in technical expertise in gynecological surgery and advances in surgical instrumentation have led to the development of laparoendoscopic single‐site surgery (LESS). Between March and September 2009, 24 patients underwent adnexal surgery at our institution with laparoendoscopic single‐site surgery. The LESS technique was performed using the TriPort™ through an umbilical incision of 10 mm and bent laparoscopic instruments. We furthermore compared the LESS technique with a control group of 24 patients operated consecutively in the same period and for the same procedures with conventional multiport laparoscopy. Comparing the two techniques we found differences between the operation time and mean hospital stay. The surgeon must master the use of novel bent instruments in close proximity to each another. The LESS technique for benign adnexal surgery is technically feasible and safe, representing a reproducible alternative to conventional multiport laparoscopy.

Excessive production of ascitic fluid after laparoscopic operation for early-stage ovarian cancer

Peritoneal implants and/or venous or lymphatic obstruction, presenting in advanced stages of ovarian cancer, stimulate production of ascitic fluid [1]. Also, postoperative production of ascitic fluid after operations for advanced ovarian cancer is not rare. Especially in end-stage ovarian cancer, symptomatic and rapidly reaccumulating ascitic fluid usually needs repeated paracenteses or drainage though peritoneal catheter. In addition, thoracentesis, pleurodesis, or catheter has already been used to drain pleural fluid [2]. On the other hand, in early-stage (Ia) ovarian cancer, considering the absence of implants, postoperative ascites usually cannot be cancer-related. In this paper, a rare complication of excessive production of ascitic fluid after laparoscopic operation for early-stage clear cell ovarian carcinoma and the used of treatment method are presented. Methods