Mustafa Zelal Muallem

Abnormally invasive placenta (AIP): pre-cesarean amnion drainage to facilitate exteriorization of the gravid uterus through a transverse skin incision

Abstract The number of pregnant women with abnormally invasive placenta (AIP) including clinical relevant placenta increta and percreta has markedly increased with a reported incidence of as high as one in 731, By 2020 in the United States, there will be an estimated 4504 new cases of AIP and 130 AIP-associated maternal deaths annually. The preoperative diagnosis and operative management of AIP is challenging. In a planned cesarean delivery, a vertical lower abdominal skin incision is widely used in order to have enough space to perform a hysterotomy above the cranial edge of the placenta to avoid significant fetal and/or maternal hemorrhage. We have used preoperative drainage of the amniotic fluid after epidural anesthesia and immediately before a planned cesarean delivery through a transverse skin incision in five patients with AIP of the anterior uterine wall. With less uterine volume, exteriorization of the gravid uterus is easily performed through a transverse laparotomy. The combination of amnion drainage, transverse laparotomy and exteriorization of the gravid uterus facilitates identification of the exact site of placental implantation, provides adequate space for performing fundal or high anterior or even posterior uterine wall incisions and to deliver the fetus safely while minimizing the risk of placental separation and subsequent uncontrolled blood loss. Furthermore, this technique provides the chance to leave the untouched placenta in situ or to remove the placenta in toto with a uterine wall segment.

Checkpoint-inhibition in ovarian cancer: rising star or just a dream?

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

Preoperative Evaluation of Myometrial Invasion in Endometrial Carcinoma: Prospective Intra-individual Comparison of Magnetic Resonance Volumetry, Diffusion-weighted and Dynamic Contrast-enhanced Magnetic Resonance Imaging

Aim: The purpose of this prospective study was to compare the diagnostic performance of diffusion-weighted (DWI) and dynamic contrast-enhanced imaging (DCE) and volumetric analyses in the preoperative assessment of myometrial invasion in patients with endometrial carcinoma. Materials and Methods: Thirty-five patients with endometrial cancer underwent preoperative magnetic resonance imaging including DWI and DCE for evaluation of the depth of myometrial invasion and volumetric analyses [tumor volume (TV), uterine volume (UV), tumor to volume ratio (TVR=(TV/TU)×100)]. The results of the evaluations were compared to the histopathological examinations. Results: DWI and DCE showed a sensitivity and specificity in evaluating the depth of myometrial invasion of 92% and 96% and 92% and 86%, respectively, while volumetric analyses showed a sensitivity and specificity of 85% and 86% (TVR cut-off=10%) and 69% and 100% (TVR cut-off=25%), respectively. Conclusion: DWI and DCE are both good diagnostic tools for the preoperative assessment of myometrial invasion. From our results and literature research, there is potential for omitting gadolinium-based contrast agents given the high diagnostic value of DWI. In our patient collective, the predictive power of volumetric analyses was lower than that of DWI.

Preoperative CA-125 Value as a Predictive Factor for Postoperative Outcome in First Relapse of Platinum-sensitive Serous Ovarian Cancer

Aim: The purpose of the study was to evaluate whether preoperative cancer antigen 125 (CA-125) levels predict outcome of secondary cytoreductive surgery (SCS) in patients with serous recurrent ovarian cancer and whether this could be used as a prognostic factor for progression-free (PFS) and overall (OS) survival. Patients and Methods: A cohort of 111 patients with first recurrence of platinum-sensitive serous ovarian cancer, who had undergone SCS at the Department of Gynecology and Oncological Surgery, Charité, Campus Virchow Clinic was analyzed in correlation with the preoperative CA-125 value. Results: The median preoperative CA-125 level was 164 U/ml. Complete tumor resection was achieved in 58.6% of the patients. PFS and OS for patients with preoperative CA-125 of less than 164.5 U/ml was significantly better than those with preoperative CA-125 ≥164.5 U/ml (p=0.025 and p<0.001, respectively). Conclusion: Preoperative CA-125 is not a statistically significant predictive factor for complete tumor resection after SCS. Preoperative CA-125 <164.5 U/ml can predict significantly better PFS and OS for patients with first recurrence of platinum-sensitive ovarian cancer.

Sentinel lymph node detection in gynecologic malignancies by a handheld fluorescence camera

Near-infrared fluorescence imaging using indocyanine green (ICG) as a tracer is a promising technique for mapping the lymphatic system and for detecting sentinel lymph nodes (SLN) during cancer surgery. In our feasibility study we have investigated the application of a custom-made handheld fluorescence camera system for the detection of lymph nodes in gynecological malignancies. It comprises a low cost CCD camera with enhanced NIR sensitivity and two groups of LEDs emitting at wavelengths of 735 nm and 830 nm for interlaced recording of fluorescence and reflectance images of the tissue, respectively. With the help of our system, surgeons can observe fluorescent tissue structures overlaid onto the anatomical image on a monitor in real-time. We applied the camera system for intraoperative lymphatic mapping in 5 patients with vulvar cancer, 5 patients with ovarian cancer, 3 patients with cervical cancer, and 3 patients with endometrial cancer. ICG was injected at four loci around the primary malignant tumor during surgery. After a residence time of typically 15 min fluorescence images were taken in order to visualize the lymph nodes closest to the carcinomas. In cases with vulvar cancer about half of the lymph nodes detected by routinely performed radioactive SLN mapping have shown fluorescence in vivo as well. In the other types of carcinomas several lymph nodes could be detected by fluorescence during laparotomy. We conclude that our low cost camera system has sufficient sensitivity for lymphatic mapping during surgery.

Fluorescence-guided mapping of sentinel lymph nodes in gynecological malignancies

We have successfully applied a custom-made handheld fluorescence camera for intraoperative fluorescence detection of indocyanine green in a feasibility study on sentinel lymph node mapping in patients with vulvar, cervical, endometrial and ovarian cancer.