Ofer Lavie

Robotic-assisted laparoscopic myomectomy compared with standard laparoscopic myomectomy—a retrospective matched control study

OBJECTIVE Compare robotic-assisted laparoscopic myomectomy (RALM) to a matched control standard laparoscopic myomectomy (LM). DESIGN A retrospective matched control study. SETTING Private practice setting. PATIENT(S) Premenopausal and postmenopausal women who underwent either robotic-assisted or standard laparoscopic myomectomy. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Retrospective chart review was performed. Cases of laparoscopic robotic-assisted myomectomies were compared with a matched control group of standard LM. Comparisons were based on Fishers exact, Mann-Whitney, and exact chi-square tests. RESULT(S) Between January 2006 and August 2007, 15 consecutive RALMs were performed at our institution, compared with 35 matched control standard LMs. The two groups were matched by age, body mass index, parity, previous abdominopelvic surgery, size, number, and location of myomas. Mean surgical time for the RALM was 234 minutes (range 140-445) compared with 203 minutes (range 95-330) for standard LMs. Blood loss, hospitalization time, and postoperative complications were not significantly different. CONCLUSION(S) The RALM required a significant prolonged surgical time over LM. It appears that in the hands of a skilled laparoscopic surgeon, the RALM does not offer any major advantage. This technology, however, offers exciting potential applications while learning endoscopic surgery. Further studies are warranted to asses the utility of RALM for general gynecologic surgeons.

Intratumoral CD8+ T Lymphocytes as a Prognostic Factor of Survival in Endometrial Carcinoma

Purpose: CTLs are a prominent immune component infiltrating many solid tumors. These cells are considered to be a manifestation of host-immune response to the tumor; however, their prognostic significance remains a subject of considerable debate. The objective of this study was to evaluate the distribution pattern and prognostic value of CD8+ T cells in endometrial carcinoma. Experimental Design: We studied 90 cases of endometrial carcinoma, including 75 endometrioid and 15 papillary serous carcinomas. Immunohistochemical staining for CD8 and granzyme B was performed on paraffin-embedded sections. The number of immunohistochemically staining CD8+ T cells was enumerated in the following four regions: lymphocytes infiltrating the tumor epithelium at the invasive border, within the underlying tumor stroma, within the superficial tumor epithelium, and in the perivascular areas of the myometrium. Results: Patients with >10 CD8+ T lymphocytes/high-power field within the tumor epithelium at the invasive border displayed improved overall survival compared with patients with fewer intraepithelial CD8+ T lymphocytes (87 and 50%, respectively; P = 0.027). Multivariate analysis revealed that stage, vascular invasion, grade, and the number of intraepithelial CD8+ T lymphocytes at the invasive border were the only independent predictors of survival (P < 0.0001, P = 0.001, P = 0.011, and P = 0.025, respectively). Granzyme B+ cytoplasmatic granules were detected in a high proportion of CTLs, confirming their activated cytotoxic phenotype. Conclusions: Our study demonstrates for the first time that increased numbers of CTLs at the invasive border may be a reliable independent prognostic factor of survival in patients with endometrial carcinoma.

Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer

PURPOSE Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency-related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. PATIENTS AND METHODS The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. RESULTS Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. CONCLUSION The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.

Bell palsy complicating pregnancy: a review.

UNLABELLED The aim of the present work was to review the published evidence on the association of Bell palsy (BP), an acute idiopathic peripheral facial paralysis of unknown etiology, with pregnancy. Reports have shown that women of reproductive age are affected two to four times more often than men of the same age, and pregnant women 3.3 times more often than nonpregnant women. The apparent predisposition of pregnant women to Bell palsy has been attributed to the high extracellular fluid content, viral inflammation, and immunosuppression characteristic of pregnancy, but findings are controversial. Most cases of Bell palsy occur in the third trimester or the puerperium. Onset is acute and painful. Some authors suggest that Bell palsy increases the risk of hypertension and toxemia of pregnancy, whereas the pregnant state, in turn, may affect the course and severity of disease. Recovery is usually good; poor prognostic markers are recurrence in subsequent pregnancy and bilateral disease, both of which are rare. Neonatal outcome is apparently unaffected, although this has been studied rarely. The preferred mode of management remains undecided; it is usually confined to supportive care. Corticosteroids in pregnancy are controversial. We think clinicians should be aware of these findings to avoid unnecessary testing and treatment and to help the patient cope with this acute, painful disease. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES After completion of this article, the reader will be able to identify the potential etiologies of Bell palsy associated with pregnancy and to describe the clinical presentation of this condition in pregnancy and its likelihood for recovery.

Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath

Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases.

Maternal serum creatine kinase: a possible predictor of tubal pregnancy.

Tubal pregnancy remains a clinical challenge in spite of improvements in diagnostic tests and procedures. In a prospective study we evaluated the role of the serum creatine kinase as a possible marker for tubal pregnancy. Three groups of 17 patients each were included in the study: group A, documented tubal pregnancy; group B, spontaneous abortion; and group C, normal pregnancy. Serum was tested for creatine kinase in all of the patients. Creatine kinase level was > 45 IU/L in all patients with tubal pregnancy, significantly higher than the level in patients in either of the two other groups (p < 0.0001). We conclude that a high serum creatine kinase level can be an important diagnostic test in the evaluation of a suspected tubal pregnancy.

BRCA1 germline mutations in women with uterine serous papillary carcinoma

Objective To determine the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma. Methods We screened DNA from 12 women with uterine serous papillary carcinoma for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1–185delAG and 5382insC, BRCA2–6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity at the appropriate loci. Results Nine women were of Jewish Ashkenazi origin and three were non-Ashkenazi. Two of nine Ashkenazi women were carriers of germline mutations: one 185delAG mutation and one 5382insC mutation. Five women had histories of breast carcinoma before diagnosis of uterine serous papillary carcinoma. Family histories of seven women had at least one first-degree relative with malignant disease. Of those, four had at least one first-degree relative with breast, ovarian, or colon carcinoma. Both carriers had strong family histories of breast-ovarian carcinoma. Loss of heterozygosity analysis found loss of the wild-type BRCA1 allele in the primary uterine tumors. Conclusion BRCA1 germline mutations were observed in two of nine of the women in this series. The loss of heterozygosity in the tumor tissue of the carriers, coupled with the high frequency of family and patient histories of breast or ovarian malignancies, suggest that uterine serous papillary carcinoma might be a manifestation of familial breast-ovarian cancer.

The effect of statins on risk and survival of gynecological malignancies

PURPOSE The use of statins has been associated with reduced risk of malignancies in a variety of organ sites. This study was aimed at studying the effects of statins on gynecological cancers. METHODS The Cancer in The Ovary and Uterus Study (CITOUS) is a case-control study of newly diagnosed cases of gynecological malignancies and age/sex/clinic/ethnic-group matched population controls. Use of statins prior to and following diagnosis was assessed in a subset of 424 cases of ovarian and endometrial cancers and 341 controls, enrolled in Clalit Health Services (CHS), using pharmacy records. RESULTS The use of statins for more than one year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR=0.56, 95% CI: 0.33-0.94) and of endometrial cancer (OR=0.59, 95% CI: 0.40-0.87). The association with endometrial cancer, but not with ovarian cancer (OR=0.54, 0.26-1.13), remained statistically significant after adjustment for fruit and vegetable consumption, sports activity, family history of endometrial and colorectal cancer, ethnicity, BMI, duration of breast feeding, age at 1st pregnancy and use of menopausal hormones (RR=0.48, 0.26-0.89). Women who used statins only after diagnosis of cancer had a significantly better survival of both ovarian cancer (Log rank test, p=0.021, age adjusted HR=0.47, 0.26-0.85) and endometrial cancer (p=0.06, age adjusted HR=0.45, 0.23-0.87). CONCLUSION The use of statins for more than one year before diagnosis was associated with a reduction in the risk of endometrial cancer and possibly ovarian cancer. A significantly improved survival of cases of both malignancies was noticed when statins were taken only after diagnosis.

Robot-assisted laparoscopic surgery in gynecology: scientific dream or reality?

OBJECTIVE To analyze the feasibility, safety, advantages, and disadvantages of using robotic technology for gynecologic surgeries in a large group of patients. DESIGN Retrospective study (Canadian Task Force classification II-3). SETTING Tertiary endoscopic referral centers. PATIENT(S) Eighty-seven patients requiring laparoscopic treatments for benign gynecologic conditions. INTERVENTION(S) Charts reviewed from robotic-assisted gynecologic operative laparoscopies. MAIN OUTCOME MEASURE(S) Length of surgery, time for robot assembly and disassembly, rate of conversion to laparotomies, and complications. RESULT(S) Between January 2006 and August 2007, 137 robotically assisted gynecologic procedures were performed in 87 patients. The da Vinci Surgical System was used. The average length of the surgeries was 205 minutes (60-420 minutes). Assembly of the robot lasted 16 minutes (10-27 minutes) when disassembly took 2.5 minutes (2-6 minutes). There were no conversions to laparotomy. There were three complications. CONCLUSION(S) Robotic-assisted technology, in its present state, is enabling more surgeons to perform endoscopic surgery. Its advantages are 3D Vision and a faster learning curve for suturing and operating while sitting. Its an exciting enabling technology with a great future.

BRCA germline mutations in women with uterine serous carcinoma--still a debate.

Objective: To determine the incidence of BRCA1 and BRCA2 mutations in an enlarged series of uterine serous carcinoma (USC) patients and to determine whether patients with USC are associated with a personal or familial history of breast or ovarian carcinoma. Methods: A cohort of all consecutive patients with diagnosed USC was identified for 9 years. Family pedigrees were drawn as far back and laterally as possible. In all patients, genomic DNA was extracted from peripheral blood samples and analyzed for the 3 mutations common in Ashkenazi Jewish patients. All patients went through total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Tubal, ovarian, and peritoneal carcinoma were ruled out clinically and pathologically in all patients. Results: Of 51 consecutive patients with USC in Ashkenazi Jews studied, we identified 13 patients (25.5%) who were previously found to have breast carcinoma, 17 patients (33.3%) who had a first-degree relative with breast or ovarian carcinoma, and 8 patients (15.7%) who were found to be carriers of 1 of the 3 BRCA germline mutations. Conclusions: This series of USC patients, the largest consecutive series to date, suggests a higher incidence of BRCA carriers among Ashkenazi Jews as compared with the general population. This high rate of BRCA germline mutations in USC patients coupled with a high rate of personal and familial cancer histories may suggest that USC is associated with the hereditary breast-ovarian syndrome. This potential association of USC to the BRCA-associated cancer spectrum may have implications for the clinical management and intervention of unaffected BRCA1-2 germline mutation carriers. However, at the current time, there are insufficient data to provide evidence-based guidelines regarding the optimal timing or specific intervention to prevent cancers in these high-risk women.