Endocrine Mucin-Producing Sweat Gland Carcinoma and Primary Cutaneous Mucinous Carcinoma: A Case Series.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.

Photodynamic ablation of a selected rat embryo: a model for the treatment of extrauterine pregnancy.

BACKGROUND: To test the feasibility of photodynamic therapy (PDT)-based ablation of rat embryos as a model for PDT of extrauterine pregnancy (EUP) in humans. METHODS: A controlled pre-clinical study. Selected rat embryos [one per litter, n = 30, embryonic day 14 (E14)] were subjected to placental injection of a Palladium-bacteriochlorophyll derivative and illuminated to achieve selective photo-ablation. Histopathology studies were performed 48 h after treatment (E16). Parturition (E21) and breeding (approximately 12 weeks) after treatment were also evaluated. RESULTS: Using direct placental injection, nearly 80% of the treated rat embryos were selectively photo-ablated, leaving the remaining litter unharmed to achieve normal parturition. Treated animals retained fertility and normally implanted in both treated and untreated uterine horns attesting to the confined toxicity inherent to this approach. CONCLUSIONS: Although requiring respective adaptation to clinical application in terms of treatment protocols and designated hardware, photodynamic interventions using novel bacteriochlorophyll-based photosensitizers may prove applicable to treatment of EUP, as well as other gynecological pathologies and malignancies in a safe, minimally invasive manner.

Evaluation of patient comfort with outpatient orbital surgery.

PURPOSE: To evaluate patient comfort with outpatient orbital surgery. DESIGN: Prospective, non-randomized study. METHODS: The experience of 34 consecutive outpatient orbital procedures in 30 patients was evaluated. The data obtained included subjective postoperative pain and discomfort at 3 time intervals (immediate, postoperative day 1 and 1 week) using a 100 mm visual analogue scale (VAS). Patients were also asked to rate the overall experience after one week of follow-up. RESULTS: The average pain and discomfort scores in the immediate postoperative period measured 13.95 and 12.61, respectively. Overnight scores of 5.91 and 7.25 were determined for pain and discomfort, and at the one-week follow-up these were 0.91 and 3.42, respectively. All 30 patients reported that they were "satisfied with their overall experience." The highest VAS score for pain at any time was 50. The highest VAS score for discomfort at any time was also 50. All 30 patients had recovered or improved their visual acuity at week one. There was no incidence of retrobulbar hemorrhage, significant loss of vision (greater than two lines), increased intraocular pressure or pupillary defects in any of the patients. None of the study patients required re-hospitalization. CONCLUSIONS: This study suggests that outpatient orbital surgery, in the hands of an experienced orbital surgeon, is safe and well tolerated by the patients regardless of the type of anesthesia or type of procedure.

In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype: a murine model for studying placental angiogenesis.

Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a complex regulator of blood vessel plasticity that plays a pivotal role in both vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A] and vessel regression (in the absence of VEGF-A). Based on the spatial and temporal expression of Ang2 throughout human gestation, we recently suggested that the Ang2 may play a pivotal role in placental angiogenesis. Further, to examine this tenet we have developed a novel murine model system in which in utero Ang2 gene delivery via a non-replicating adenoviral expression vector has the potential to manipulate the blood vessel phenotype in vivo during pregnancy. Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular extracellular matrix, subsequently promoting plasticity of the maternal and fetal vessels, which appear honeycombed due to a 2-fold increase in blood vessel luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading to vascular leakiness with perivascular oedema, which increases placental weight. These observations suggest that the Ang2 overexpression may play a key role in placental vascular remodelling. Furthermore, we suggest a novel new model to study the pathobiology of placental vascularization and the effect of placental blood vessels on fetal phenotype.

The possible association between in vitro fertilization treatments and cancer development.

The objective of this paper is to assess whether ovarian hyperstimulation and in vitro fertilization (IVF) are associated with increased risk of cancer development, using an historical cohort analysis of infertile women who attended the IVF unit, Lis Maternity Hospital Tel Aviv Medical Center, Tel Aviv, Israel. One thousand and 82 women participated in the IVF treatment program between 1984 and 1992. Cancer incidence rates were determined through the National Cancer Registry and were compared to the expected rates with respect to appropriate age and continent of birth. Twenty-one cases of cancer were observed as compared to 11 that were expected (SIR 1.91; 95% CI 1.18-2.91). When cancer cases that were diagnosed within one year of the IVF treatment were excluded from the analysis (SIR = 1.46; 95% CI 0.83-2.36), no significant excess risk of cancer was noted. We conclude that in this cohort of infertile women, the higher than expected cancer rate could not be attributed to IVF treatments. Special attention should be made to women who may be diagnosed with cancer during or shortly after IVF treatment.

Accuracy of teacher assessments of second-language students at risk for reading disability.

This study examined the accuracy of teacher assessments in screening for reading disabilities among students of English as a second language (ESL) and as a first language (L1). Academic and oral language tests were administered to 369 children (249 ESL, 120 L1) at the beginning of Grade 1 and at the end of Grade 2. Concurrently, 51 teachers nominated children at risk for reading failure and completed rating scales assessing academic and oral language skills. Scholastic records were reviewed for notation of concern or referral. The criterion measure was a standardized reading score based on phonological awareness, rapid naming, and word recognition. Results indicated that teacher rating scales and nominations had low sensitivity in identifying ESL and L1 students at risk for reading disability at the 1-year mark. Relative to other forms of screening, teacher-expressed concern had lower sensitivity. Finally, oral language proficiency contributed to misclassifications in the ESL group.

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral.

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.

Role of vascular endothelial growth factor in ovarian physiology and pathology.

OBJECTIVE: To review the current literature on the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in ovarian physiology and pathology. DESIGN: A computerized search was conducted to identify relevant in vitro and in vivo studies published in English. MEDLINE, Current Contents, and the Index Medicus were searched for studies published before January 2000. RESULT(S): VEGF/VPF is an angiogenic factor and a potent mitogen for vascular endothelium. During reproductive life, VEGF/VPF plays a role in the cyclic growth of ovarian follicles and corpus luteum development and maintenance, mediating ovarian angiogenesis. VEGF/VPF expression and secretion are induced by both FSH and LH/hCG receptor-activated pathways. CONCLUSION(S): VEGF/VPF expression and production within the ovary are critical for normal reproductive function. Defects in angiogenesis may contribute to a variety of disorders including anovulation and infertility, pregnancy loss, ovarian hyperstimulation syndrome, and ovarian neoplasms.

Role of angiopoietins in reproductive tract angiogenesis.

UNLABELLED: Components of the female reproductive system undergo a number of programmed angiogenic processes coupled with cyclic evolution and decline of ovarian, endometrial, and placental structures. The development of a new vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes. This implies that the expression of the inciting angiogenic factors are hormone dependent. Recently, a second family of vascular endothelial growth factors was identified, the angiopoietins. Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. In this review, we discuss the molecular characterization and mechanism of action of angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the angiogenic process and specifically explain the role of angiopoietics in reproductive tract angiogenesis and compare the differences between the various proteins that are involved in angiogenesis.

Rectal carcinoma during pregnancy: a reminder and updated treatment protocols.

Rectal carcinoma is rare during pregnancy. Prognosis is usually unfavorable due to late diagnosis, and management, especially regarding the mode of delivery, is controversial. Current treatment of rectal carcinoma includes neoadjuvant chemoradiotherapy, which may influence obstetrical management. We present a case report and discuss obstetrical management in view of updated knowledge and therapeutic approaches.

Vascular cell adhesion molecule-1 in normal, failed, and ectopic pregnancy.

PROBLEM: Vascular cell adhesion molecule-1 (VCAM-1) is involved in early pregnancy establishment. This study sought to determine whether soluble VCAM-1 (sVCAM-1) serum levels differ among normal, failed, and ectopic pregnancy, its capacity to serve as a marker for pregnancy viability or ectopic pregnancy, and its correlation with serum progesterone and beta human chorionic gonadotrophin (PHCG) levels. METHOD OF STUDY: Maternal serum samples were obtained from 20 women with ectopic, 10 with normal, and 10 with failed intra-uterine pregnancy, all of comparable gestational age. Samples were assayed for sVCAM-1, progesterone, and betaHCG by specific assays. RESULTS: The median serum level of sVCAM-1 was comparable between the three pregnancy types (normal: 578.3 ng/mL, range 434.4-699.5 ng/mL; failed: 567.8 ng/mL, range 401.9 669.5 ng/mL; and ectopic: 470.7ng/mL range, 328.2-1151.1 ng/mL). Serum levels sVCAM-1 were not significantly correlated with betaHCG or progesterone levels. CONCLUSION: sVCAM-1 is not appropriate to serve as a marker for pregnancy viability or ectopic pregnancy.

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

OBJECTIVE: To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP). DESIGN: Prospective, case-controlled study. SETTING: A tertiary care center. PATIENT(S): Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation. INTERVENTION(S): Serum samples were obtained from all women. MAIN OUTCOME MEASURE(S): All samples were analyzed for VEGF, progesterone, and beta-hCG by specific methods. RESULT(S): Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%. CONCLUSION(S): The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.

Evaluation of fetal echogenic bowel in the second trimester.

Previous studies cite different possible etiologies for fetal echogenic bowel (FEB). The purpose of this study was to evaluate the possible etiologies for second-trimester FEB, and to provide clinical guidelines for evaluation of this finding. The study included 79 patients diagnosed with FEB in the second trimester. Fifteen cases (19%) were associated with maternal vaginal bleeding. Of these, 12 patients underwent amniocentesis, 9 of which had visible blood products in the amniotic fluid. Seven cases (8.9%) had associated severe malformation. Seven other cases (8.9%) were noted in multifetal pregnancies. Five fetuses (6.3%) had evidence of bowel obstruction or perforation not associated with cystic fibrosis (CF). Chromosomal aberrations were found in 5 fetuses (6.3%). Intrauterine infection with cytomegalovirus, herpes simplex virus, varicella-zoster virus, or parvovirus B-19 was documented in 5 patients (6.3%). Three cases (3.8%) were associated with subsequent unexplained stillbirth. Two fetuses (2.5%) were found to be affected by CF. Finally, in 30 cases (38%), no obvious reason for FEB was found. We conclude that the evaluation of second-trimester FEB should include targeted ultrasound for associated malformations, infectious studies, DNA analysis for CF mutations, amniocentesis for chromosomal analysis and evaluation of the amniotic fluid for degraded blood products, and an autopsy in cases of stillbirth. Even when no apparent reason is found, pregnancies should be considered at high risk for poor outcome.

Follicular fluid levels of vascular endothelial growth factor. Are they predictive markers for ovarian hyperstimulation syndrome?

OBJECTIVE: To determine the possible predictive role of vascular endothelial growth factor (VEGF) levels in the follicular fluid (FF) at the time of oocyte retrieval in the development of ovarian hyperstimulation syndrome (OHSS) and its possible origin. STUDY DESIGN: FF was obtained from 174 high-responder patients at the time of oocyte retrieval. The study group comprised 16 high-responder patients who developed early, severe OHSS and from whom serum and peritoneal fluid (PF) were obtained during the active phase of the syndrome. These women were compared to 16 high-responder patients who did not develop OHSS. An additional control group comprised 16 low-responder patients who also did not develop OHSS. The FF, serum and PF samples were tested for VEGF by enzymelined immunosorbent assay. RESULTS: No differences in the FF VEGF levels were found among the OHSS group (1,742.3 +/- 522.4 pg/mL), the high-responder group that did not develop OHSS (1,802.0 +/- 584.3 pg/mL) and the low-responder group (1,686.7 +/- 374.2 pg/mL). In the OHSS group, no differences were found between the serum and PF VEGF levels (247.3 +/- 31.4 and 642.9 +/- 328.3 pg/mL, respectively). No correlation was found between the FF concentrations of VEGF and the mean serum 17-beta estradiol levels or number of oocytes retrieved. CONCLUSION: We conclude that preovulatory FF levels should not serve as a possible predictive factor for development of OHSS. The increased capillary permeability found in OHSS may be due to its systemic effect.

Multifetal pregnancy reduction: a possible risk factor for periventricular leukomalacia in premature newborns.

OBJECTIVE: To investigate the possible role of multifetal pregnancy reduction as a risk factor for the development of periventricular leukomalacia, which has been associated with prematurity and twin pregnancies. DESIGN: A case-control study. SETTING: In Vitro Fertilization Unit and Intensive Care Nursery of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): A total of 1,401 consecutive preterm infants who were born between January 1, 1994, and December 31, 1995. INTERVENTION(S): Cranial ultrasonographic evaluation of each infant within 3 days of birth. MAIN OUTCOME MEASURE(S): Premature infants who developed periventricular leukomalacia (cases) were compared with premature infants who did not develop this disorder (controls) when multifetal pregnancy reduction was considered. RESULT(S): Fourteen premature infants developed periventricular leukomalacia. Of these, 28.6% (4 infants) were exposed to multifetal pregnancy reduction, compared with 1.9% of the controls, giving an odds ratio (OR) of 20.9 (95% confidence interval [CI] 5.5-79.4). Adjustment of this OR for IVF treatment (OR, 18.6; 95% CI, 1.8-140.3), twinning (OR, 6.3; 95% CI, 1.3-30.3), and for both IVF treatment and twinning simultaneously (OR, 8.5; 95% CI, 1.7-42.2) did not explain all the observed associations between periventricular leukomalacia and multifetal pregnancy reduction. CONCLUSION(S): Our data suggest that multifetal pregnancy reduction may be an additional risk factor for periventricular leukomalacia among premature infants, regardless of twinning.