Alon Ben-Arie

L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas

BACKGROUND Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas. METHODS We investigated L1 expression by immunohistochemistry, RT-PCR, and Western blot analysis of tumour samples. Soluble L1 in the serum was detected by ELISA and immunoprecipitation. FINDINGS We detected the L1 adhesion molecule in ovarian and uterine tumours in a stage-dependent manner. In a retrospective study L1 was found in 46 of 58 ovarian carcinomas and 20 of 72 uterine adenocarcinomas. L1 expression was an excellent predictor of poor outlook (p<0.00001). Patients with L1 positive uterine tumours were at high risk for progression even in the endometrioid-type tumours, which usually have a favourable prognosis. In uterine tumours, expression of L1 in curettage samples enabled us to identify aggressive tumours before the operation. Soluble L1 was specifically detected in serum samples from patients with ovarian and uterine tumours. ADAM10, which was implicated in previous studies as L1 sheddase, was expressed in tumours in which soluble L1 was present in the serum. INTERPRETATION L1 is overexpressed in ovarian and uterine carcinomas and is associated with short survival. L1 can serve as a new marker for prediction of clinical outcome and could be helpful to identify patients with uterine tumours who are at high risk for recurrent disease. L1 expression and cleavage could promote dissemination of tumours by facilitating cell migration.

Up‐regulation of L1CAM is linked to loss of hormone receptors and E‐cadherin in aggressive subtypes of endometrial carcinomas

Endometrial carcinomas (ECs) are classified into type 1 (less aggressive) and type 2 (aggressive) tumours that differ in genetic alterations. So far, reliable immunohistochemical markers that can identify patients with high risk for recurrence are rare. We have defined the expression of L1 cell adhesion molecule (L1CAM), a biomarker previously identified for EC, and compared its expression to oestrogen receptor (ER)/progesterone receptor (PR) and E‐cadherin. We found that L1CAM was absent in normal endometrium and the vast majority of endometrioid ECs (type 1) but was strongly expressed in serous and clear‐cell ECs, considered as type 2. 78/272 cases were identified as L1CAM‐positive endometrioid ECs that were correlated with a poor prognosis. Strikingly, we observed an inverse relationship between L1CAM and ER/PR/E‐cadherin expression in all ECs. In mixed ECs, composed of endometrioid (L1CAM− ER/PR+ E‐cadherin+) and clear‐cell/serous (L1CAM+ ER/PR− E‐cadherin−), both phenotypes were co‐expressed. In some of these cases L1CAM was up‐regulated at the leading edge of the tumour, where ER/PR and E‐cadherin expression were selectively lost. In EC cell lines treated with the epithelial–mesenchymal transition (EMT) inducer TGFβ1, L1CAM and vimentin were strongly up‐regulated, while E‐cadherin expression was reduced. The treatment also resulted in an increased expression of the EMT transcription factor Slug and an enhanced cell invasion. Depletion of Slug by siRNA knockdown prevented both L1CAM up‐regulation and enhanced cell invasion. According to our analysis, we suggest that L1CAM is a novel marker for EMT in ECs and that L1CAM‐typing could identify endometrioid ECs that have type 2‐like features and are at high risk for recurrence. Copyright

Elevated serum alkaline phosphatase may enable early diagnosis of ovarian cancer

A case of endometrioid ovarian carcinoma associated with elevated levels of serum placental-like alkaline phosphatase (PLAP) is presented. Two and a half years before a final diagnosis was made following explorative laparotomy, an incidental blood test revealed elevated alkaline phosphatase in the patients serum. A thorough investigation for the source of this elevation was negative. Postoperative immunohistochemical staining of the tumor, showed diffuse stain with PLAP, along with gradual decline to normal values of serum total alkaline phosphatase. It is suggested, that whenever serum alkaline phosphatase is elevated due to unknown reason, an investigation including alkaline phosphatase isoenzymes, serum Ca-125, trans-vaginal pelvic sonogram and even diagnostic laparoscopy, should be considered in a search for early preclinical ovarian cancer.

Conservative treatment of stage IA2 squamous cell carcinoma of the cervix during pregnancy

BACKGROUND: The standard management of early-stage invasive cervical cancer in early pregnancy is radical hysterectomy with the fetus in situ. We describe a case of early invasive cervical cancer in pregnancy that was treated with a conservative surgical approach. CASE: A nulliparous pregnant women at 15 weeks of gestation was diagnosed with stage IA2 invasive cervical cancer. She declined a radical hysterectomy, desiring to continue the pregnancy. A repeat cervical conization with retroperitoneal lymph node dissection was followed by radical trachelectomy 6 weeks after delivery. Currently she has 2 children, and there is no evidence of recurrence. CONCLUSION: Conservative stepwise surgical management of early invasive cervical cancer in the first half of pregnancy was a feasible approach in this woman who wished to continue the pregnancy.

The role of laparoscopy in ovarian tumors of low malignant potential and early-stage ovarian cancer.

Although it is feasible today to perform laparoscopic surgical staging and treatment of ovarian low malignant potential tumors and early-stage ovarian cancer safely, it is still generally agreed that a patient with ovarian cancer should have a laparotomy. Concerns related to laparoscopy in managing gynecologic malignancy include the accuracy of intraoperative diagnosis, inadequate resection, significance of tumor spillage, improper or delay in surgical staging, delay in therapy, and the possibility of port-site metastasis. On the other hand, laparoscopy has the advantages of being a minimally invasive surgery, with shorter hospitalization, decreased postoperative pain, and quicker return to normal daily activities. We review the current literature discussing the consequences of laparoscopic surgery in ovarian tumors of low malignant potential and early-stage ovarian cancer. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to list the concerns related to laparoscopic management of ovarian malignancies, to outline the accuracy of the diagnosis of low malignant potential (LMP) ovarian tumors on frozen section, and to summarize the data on the effect of capsule rupture on overall prognosis for patients with ovarian cancer.

Can angle of progression in pregnant women before onset of labor predict mode of delivery

The angle of progression (AOP), measured by transperineal ultrasound, has been used to assess fetal head descent during labor. Our aim was to assess whether, before onset of labor, parous women have a narrower AOP than do nulliparous women and if a narrow AOP is associated with a higher rate of Cesarean delivery.

L1 (CD171) as a novel biomarker for ovarian and endometrial carcinomas

The L1 molecule has emerged as a promising new biomarker for the diagnosis and prognosis of human ovarian and endometrial tumors. It was initially described as an adhesion molecule for neural cells but its function on tumor cells is less well known. In this article, the role of L1 in promoting tumor cell adhesion and migration is discussed. The question of how L1 determination in tumor tissue samples, serum and ascites could potentially improve the diagnosis and monitoring of gynecologic tumor patients is also addressed. The presence of L1 in tissue and serum was found to be associated with recurrent disease and short survival, independently of the tumor’s histological type. This provides an alternative classification of gynecologic tumors according to their aggressiveness rather than their histology. L1 expression was correlated with disease progression even in patients with Stage I endometrioid-type endometrial tumors, identifing them as high-risk patients on preoperative curettage specimens. Monitoring of soluble L1 during the follow-up period was found to signal disease progression and recurrence before clinical symptoms occur. L1-based diagnosis and prognosis has the potential to contribute to an improved disease management and could represent the basic rationale for novel tailored therapy.

Case Series of Labor Induction inTwin Gestations with an IntrauterineBalloon Catheter

The efficacy and safety of labor induction using an intrauterine balloon catheter in twin pregnancies has been evaluated. During the study period (1992–1997), labor was induced at 36–42 weeks in 17 twin gestations. Labor induction was indicated for preeclampsia (n = 10), birth weight discordance (n = 3), suspected fetal distress (n = 2) and postdates (n = 2). Twin A was in vertex presentation in all cases. An intrauterine balloon catheter was inserted transcervically followed by augmentation whenever required. Vaginal delivery was achieved in 15 (88.2%) patients. The mean interval from balloon insertion to delivery was 17.05 h, with 80% deliveries occurring within 24 h of catheter insertion and 80% occurring within 12 h of catheter expulsion. Birth weight was 2,514 ± 244 and 2,421 ± 367 g for twin A and B, respectively. Oxytocin was required in 4 patients. Postpartum hemorrhage was noted in 1 patient. One patient with no progress of labor and 1 with suspected intrapartum fetal distress required cesarean section. All neonates had a 5-min Apgar score of 10. The data suggest that an intrauterine balloon catheter appears to be safe and effective to induce labor in twin gestations.

Trophoblastic peritoneal implants after laparoscopic treatment of ectopic pregnancy

Persistent trophoblastic activity after salpingostomy for ectopic pregnancy implies the presence of intra-abdominal trophoblastic tissue, usually within the fallopian tube. We report a case of disseminated trophoblastic peritoneal implants, presenting as hemoperitoneum three weeks after laparoscopic salpingectomy. Only 23 such cases have been reported. Surgical treatment of ectopic pregnancy, especially by the laparoscopic technique, may cause intraperitoneal spread and reimplantation of trophoblastic tissue. Precautions for minimizing this complication are discussed.

Adnexal torsion in adolescents: prompt diagnosis and treatment may save the adnexa.

Adnexal torsion, although infrequent, may have a devastating effect on the future reproductive performance of adolescents and young women. However, clear variables predicting a favorable operative outcome have not yet been identified. In this retrospective study the authors analyzed the charts of 72 adolescent girls hospitalized for acute lower abdominal pain. In 13 cases (18%) torsion of the adnexa was found and six of them ended with reproductive compromise expressed by either adnexectomy or salpingectomy. We have found that in the cases of adnexal torsion, the time factor, from admission until final diagnosis and treatment, was the only significant variable affecting the operative results. A shorter time until the operation, resulted in less harm to the reproductive organs involved. Therefore, we conclude that whenever an adnexal torsion is suspected, a quick diagnostic laparoscopy followed by an operative procedure when needed, may contribute to better reproductive performance in the future.