Correlation of cancer risk evaluation and early detection (CADET) scores with abnormal ultrasonographic ovarian findings.

OBJECTIVE: To determine the utility of a modified version of ovarian cancer-focused cancer risk evaluation and early detection (CADET) scores as a screening tool for ultrasonographic ovarian findings. STUDY DESIGN: Prospective pilot study. MAIN OUTCOME MEASURES: CADET scores were compared with abnormal ultrasonographic ovarian findings of peri- and postmenopausal women who attended their gynecologist for a routine check-up. The women filled in the CADET questionnaire before seeing their gynecologists who were blinded to the CADET results. The women whom they referred for pelvic transvaginal ultrasonographic examination comprised the study group. The results of their scans were compared with their CADET scores. RESULTS: Of the 181 peri- and postmenopausal women who were candidates for this study, 154 were referred for ultrasonography, of whom 38 (24%, Group A) had abnormal ovarian scans (30 simple cysts and 8 complex findings). The other 116 (76%) women had normal sonograms (Group B). Demographic characteristics were similar for both groups. Thirteen Group A women (34%) and 52 Group B women (45%) had positive CADET scores (p = NS). The average group CADET scores were also not significantly different (0.8 +/- 1.7 for Group A and 1.7 +/- 2.5 for Group B). CONCLUSION: CADET scores did not correlate with abnormal ultrasonographic ovarian findings.

Early adenocarcinoma of the cervix: is radical vaginal trachelectomy safe?

OBJECTIVE: Radical vaginal trachelectomy (RVT) is a revolutionary option for fertility preservation in young women with early cervical tumors. Several series have demonstrated outcomes comparable to radical hysterectomy (RH), but none has addressed the influence of histology. We evaluated the safety of RVT in adenocarcinomas. METHODS: Data on surgically treated adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases was taken from a centralized Toronto Cervical Cancer Database. Prognostically important tumor features, lymph node status, and the use of adjuvant therapies were compared. Adenocarcinoma cases treated with RVT were compared to AC cases treated with RH, and to SCC cases that had RVT. Recurrence-free survival was calculated from the date of surgery. Medians, proportions, and survival curves were compared with the Mann Whitney test, the Chi-square test, and the Log Rank test, respectively. RESULTS: 74 patients with AC and 66 patients with SCC undergoing RVT, and 187 cases of AC undergoing RH were analyzed. Patients undergoing RVT were younger than patients having RH (31 vs. 40, p<0.001). Tumor characteristics were similar, but depth of invasion and the frequency of high grade lesions were higher in the RH group (5 mm vs. 3 mm, p<0.001; and 36% vs. 22%, p=0.04). Adjuvant treatment was given more frequently after RH (12% vs. 3%, p<0.05). There was no significant difference in recurrence-free survival between RH and RVT for AC, or between AC and SCC patients treated by RVT. CONCLUSIONS: RVT is a safe alternative for early stage cervical adenocarcinoma in appropriately selected patients wishing to preserve fertility.

A feasibility study of weekly docetaxel with capecitabine in ovarian cancer: a promising combination of two active drugs with a potential for synergism.

OBJECTIVES: To evaluate the safety and efficacy of weekly docetaxel with capecitabine in patients with recurrent/persistent epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Women treated for recurrent/persistent EOC in our department (January 2004 through December 2005) were recruited into this feasibility study. They received 35 mg/m(2) docetaxel on days 1 and 8 and 1,000 mg/m(2) capecitabine twice daily on days 1-14 in a 21-day cycle. RESULTS: Nine patients were enrolled. The median age was 64 years (37-80). Time to progression ranged from 1.67 to 11.27 months: 1 had complete response, 3 had partial responses, 4 had stable disease and 1 had disease progression. There was no grade 3 or 4 bone marrow toxicity. Nonhematological toxicity included partial hair loss (n = 4), fatigue (n = 7), hand and foot syndrome (n = 2), diarrhea (n = 5) and fluid retention syndrome (n = 1). CONCLUSION: There was good antitumor activity but frequent moderate-to-severe nonhematological toxicities when weekly docetaxel and capecitabine were used as second-line therapy for recurrent EOC. Further investigation of this combination is warranted.

Improved quality of life with hyperbaric oxygen therapy in patients with persistent pelvic radiation-induced toxicity.

AIMS: We report the results of hyperbaric oxygen therapy (HBOT) used in the treatment of radiation-induced persistent side-effects after the irradiation of pelvic tumours. MATERIALS AND METHODS: Between January 2001 and December 2005, 13 women (median age 60.3 years) with radiation combined proctitis/cystitis (n=6), longstanding vaginal ulcers and fistulas (n=5) and longstanding skin injuries (n=2) underwent HBOT in a multiplace chamber for a median of 27 sessions (range 16-40). The treatment schedule was HBOT 100% oxygen, at 2 absolute atmospheres, for 90 min, once a day. For radiation-induced toxicity grading we used the National Cancer Institute Common Toxicity Criteria (CTC) grading system, before and after HBOT. RESULTS: Thirteen patients underwent an adequate number of HBOT sessions. The mean CTC grading score before HBOT was 3.3+/-0.75, whereas the mean CTC grading score after HBOT was 0.3+/-0.63. The scores showed a significant improvement after HBOT (P=0.001; exact Wilcoxon signed-rank test). Rectal bleeding ceased in five of six patients with proctitis and dysuria resolved in six of seven cystitis patients. Macroscopic haematuria stopped in seven of seven patients. Scar complications resolved in two of two patients. None reported HBOT-associated side-effects. CONCLUSION: HBOT is apparently safe and effective in managing radiation-induced late side-effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas.

Human osteogenesis involves differentiation-dependent increases in the morphogenically active 3' alternative splicing variant of acetylcholinesterase.

The extended human acetylcholinesterase (AChE) promoter contains many binding sites for osteogenic factors, including 1,25-(OH)2 vitamin D3 and 17beta-estradiol. In differentiating osteosarcoma Saos-2 cells, both of these factors enhanced transcription of the AChE mRNA variant 3' terminated with exon 6 (E6-AChE mRNA), which encodes the catalytically and morphogenically active E6-AChE isoform. In contrast, antisense oligodeoxynucleotide suppression of E6-AChE mRNA expression increased Saos-2 proliferation in a dose- and sequence-dependent manner. The antisense mechanism of action was most likely mediated by mRNA destruction or translational arrest, as cytochemical staining revealed reduction in AChE gene expression. In vivo, we found that E6-AChE mRNA levels rose following midgestation in normally differentiating, postproliferative fetal chondrocytes but not in the osteogenically impaired chondrocytes of dwarf fetuses with thanatophoric dysplasia. Taken together, these findings suggest morphogenic involvement of E6-AChE in the proliferation-differentiation balance characteristic of human osteogenesis.

Post-hysterectomy pelvic fluid collection: is it associated with febrile morbidity?

We evaluated the clinical significance and possible association of febrile morbidity with sonographically detected post-hysterectomy fluid collections. Transvaginal ultrasound examinations were performed to assess the presence of fluid collections and correlated to clinical data. Fluid collection was detected in 27 (64%) women at postoperative day 2, in 15 (35%) at postoperative day 7 and in 5 (12%) at the fourth to fifth postoperative week. Febrile morbidity was not related to the presence, location or size of fluid collection. Postoperative pelvic fluid collections are common sonographic findings after hysterectomy and are not associated with postoperative febrile morbidity.

Deferoxamine improves left ventricular function in beta-thalassemia.

Serial echocardiographic examinations were made to study the changes in left ventricular (LV) function and wall mass in 35 patients with thalassemia followed up for 5.5 +/- 2 years (mean +/- SD). Twenty patients received deferoxamine sulfate for 2.0 +/- 0.6 years (drug group) and 15 patients did not (nondrug group). Repeated blood transfusions were used to maintain the pretransfusion hemoglobin levels at 9 g/dL (90 g/L). Deferoxamine therapy improved LV function and decreased LV wall mass. Percentage shortening of LV diameter improved in the drug group (5.0% +/- 3.9%) and deteriorated in the nondrug group (-6.8% +/- 5.6%). Similarly, the maximum velocity of LV posterior wall motion improved in the drug group (16.1 +/- 20.1 mm/s) and deteriorated in the nondrug group (-18.3 +/- 19.0 mm/s). Left ventricular wall mass decreased in the drug group when compared with the nondrug group. In a subset of the drug group, pathologic natural deterioration in LV systolic function was reversed by treatment. Correlation studies indicated that frequent blood transfusions together with chelation therapy reduced LV dilatation and wall thickness, but blood transfusions alone did not have the same effect. Thus, treatment of patients with thalassemia with modest blood transfusions and deferoxamine can prevent deterioration and may even improve their LV systolic function, associated probably with arrest and reversal of the pathologic process that increases LV wall mass.

What is the right timing for ultrasound evaluation after pregnancy termination with mifepristone?

OBJECTIVE: To determine the timing for ultrasound evaluation after medical termination of pregnancy (MTOP). STUDY DESIGN: The records of 301 consecutive women who underwent MTOP between July 2010 and July 2011 were studied retrospectively. The follow-up protocol included ultrasound evaluation 2 weeks after MTOP. Surgical termination was offered when pregnancy was found to be ongoing, and either hysteroscopy/curettage or a repeat ultrasound 2 weeks later was offered when the ultrasound findings were suspicious for retained products of conception. Pathology reports were used to confirm the presence of retained products of conception. RESULTS: Women with ultrasound findings suspicious for retained products of conception were significantly older than women with negative ultrasound findings (30.9±7.7 years vs 24.8±6 years, p<0.0001). Two weeks after MTOP, ultrasound findings were negative in 236 women and suspicious in 66 women. This rate declined as the interval between ultrasound evaluation and MTOP increased (up to 10 weeks). Of the 18 women (5.98%) who underwent hysteroscopy/curettage, pathology reports indicated that 15 (83.3%) had true residua. CONCLUSIONS: At 2 weeks after MTOP, ultrasound findings suspicious for retained products of conception do not conclusively indicate failure of the procedure. Ultrasound evaluation should be repeated 4-6 weeks later (6-8 weeks after MTOP) in women with suspected residua before diagnosing failure of the procedure.

Noonan syndrome: a cryptic condition in early gestation.

Noonan syndrome is one of the most common of genetic syndromes and manifests at birth, yet it is usually diagnosed during childhood. Although prenatal diagnosis of Noonan syndrome is usually not possible, in a few cases the ultrasonographic findings suggested the diagnosis in utero. Reported sonographic clues include septated cystic hygroma, hydrothorax, polyhydramnios, and cardiac defects, such as pulmonic stenosis and hypertrophic cardiomyopathy. During a 6-year period, 46,224 live-born infants were delivered at the Chaim Sheba Medical Center. Seven newborn infants and four fetuses were found to have Noonan syndrome. One fetus showed transient nuchal translucency of 4 mm and bilateral neck cysts at the 13th gestational week. Both findings resolved spontaneously by the 18th gestational week, but during the third trimester this fetus developed hydrothorax, skin edema, and polyhydramnios. In the three other fetuses, first- and second-trimester ultrasonographic findings were normal, and the diagnosis of Noonan syndrome was suggested only during the third trimester. All three fetuses had polyhydramnios and skin edema. A cardiac malformation, hydrothorax, and a large head were present in one fetus. Sonographic facial findings were investigated. In all four fetuses posteriorly angulated, apparently low-set ears and depressed nasal bridge were identified. Wide nasal base was seen in two fetuses. In two fetuses, persistent opening of the fetal mouth was interpreted as fetal hypotonia. One fetus developed progressive postnatal hypertrophic cardiomyopathy and in one case, pulmonic stenosis became apparent at age 6 months. This small series suggests that Noonan syndrome has an evolving phenotype during in utero and postnatal life. Amelioration of early nuchal region findings and late onset of the more "typical" ultrasonographic changes may limit early prenatal detectability.

Manipulations of ACHE gene expression suggest non-catalytic involvement of acetylcholinesterase in the functioning of mammalian photoreceptors but not in retinal degeneration.

To explore role(s) of acetylcholinesterase (AChE) in functioning and diseased photoreceptors, we studied normal (rd/+) and degenerating (rd/rd) murine retinas. All retinal neurons, expressed AChEmRNA throughout fetal development. AChE and c-Fos mRNAs peaked at post-natal days 10-12, when apoptosis of rd/rd photoreceptors begins. Moreover, c-Fos and AChEmRNA were co-overexpressed in rd/rd mice producing transgenic human (h), and host (m) AChE, but not in rd/+ mice. However, mAChE overexpression also occurred in transgenics expressing human serum albumin. Drastic variations in AChE catalytic activity were ineffective during development. Neither transgenic excess nor diisopropylfluorophosphonate (DFP) inhibition (80%) affected the rd phenotype; nor did DFP exposure induce photoreceptor degeneration or affect other key cholinergic proteins in rd/+ mice, unlike reports of adult mice and despite massive induction under DFP of c-Fos70 years). Therefore, the extreme retinal sensitivity to AChE modulation may reflect non-catalytic function(s) of AChE in adult photoreceptors. These findings exclude AChE as causing the rd phenotype, suggest that its primary function(s) in mammalian retinal development are non-catalytic ones and indicate special role(s) for the AChE protein in adult photoreceptors.

Cardiopulmonary assessment in beta-thalassemia major.

Thalassemia patients succumb at a young age to congestive heart failure. Hitherto, attention has been focused on left ventricular function. This report emphasizes right ventricular dysfunction and abnormal pulmonary function. We performed cardiopulmonary evaluation, including echo-Doppler, spirometry, CO diffusion (DCO), and blood gas analyses in 35 patients with homozygous beta-thalassemia maintained by multiple blood transfusions. Six autopsy lung specimens were studied. Thalassemia patients exhibited pulmonary dysfunction, characterized by hypoxemia (85 percent of the patients were outside the 95 percent confidence limits), reduced lung volumes (51 percent), flow rates (63 percent) and DCO (50 percent). Right ventricular dysfunction was more prevalent than left ventricular dysfunction. Furthermore, 75 percent of the patients had evidence of pulmonary hypertension consistent with more frequent right ventricular rather than left ventricular dysfunction. Our findings suggest that in thalassemia patients, complex cardiopulmonary abnormalities precede the final outcome of congestive heart failure.

Pregnancy outcome after early amniotic fluid leakage after transabdominal multifetal reduction.

OBJECTIVE: To assess the importance of amniotic fluid leakage in the early period ( < 14 days) after the fetal reduction procedure. DESIGN: Prospective clinical study. SETTING: Pregnant women who underwent fetal reduction to twins in an academic, tertiary perinatal department. PATIENTS: Sixty triplet and 31 quadruplet pregnancies were identified before the ninth postmenstrual week of gestation. All patients underwent transabdominal multifetal pregnancy reduction was performed within 14 days of the procedure. INTERVENTIONS: Transabdominal multifetal pregnancy reduction from triplets and quadruplets to twins. MAIN OUTCOME MEASURE: Amniotic fluid leakage in the early period after fetal reduction. RESULTS: Early PROM occurred in eight (13.3%) patients from the triplets group and in six (19.3%) patients in the quadruplet group. Three of 60 (5.0%) patients from the triplet group and 1 of 31 (3.2%) patients from the quadruplet group miscarried before 24 weeks gestation. However, none of these patients had had PROM during the early period after the procedure. Early PROM did not influence the incidence of premature contractions of delivery and the reduction procedure, and 59% (99/169) of those who completed 24 gestational weeks delivered between 25 and 37 weeks. CONCLUSION: The presence of amniotic fluid leakage in the period close to the multifetal reduction procedure, although alarming, is not ominous for the remaining fetuses. We see no reason for any intervention in these patients.

Pheochromocytoma in pregnancy: case report and review of the literature.

Pheochromocytoma is a rare disease that may occur during pregnancy. Only a few hundred cases have been published in the literature. Manifestations include hypertension with various clinical presentations, possibly resembling those of pregnancy-induced hypertension, or pre-eclamptic toxemia. Differentiation of these conditions is not always feasible, thus creating a serious risk, because fetal and maternal morbidity and mortality are far higher with pheochromocytoma. Biochemical measurements of catecholamines and their metabolites are apparently a convenient way to establish diagnosis during pregnancy, inasmuch as interpretation of radiological evaluation is complicated by the gravid uterus, and might even be potentially dangerous due to the use of ionizing radiation. More sophisticated methods for evaluation are not always practical during pregnancy. Medical treatment aims at controlling symptoms, mandating the use of alpha- and beta-receptors blockade medication. Surgical intervention is the only possible curative method available, but the critical issue is probably to identify the exact timing during the course of pregnancy for such intervention, or the ability to control symptoms until delivery. Although malignant transformation of pheochromocytoma have been reported, it is extremely uncommon. The overall prognosis is mainly affected by early diagnosis, and multidisciplinarian management.

Malignant fibrous histiocytoma with myofibroblastic differentiation of the vulva in an adolescent female.

Malignant fibrous histiocytoma is a rare sarcoma. Only seven cases in the vulva have been reported. We present a case of malignant fibrous histiocytoma of the vulva in an adolescent female. The elected treatment was local wide resection.

An atypical case of hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome.

An atypical case of HELLP syndrome is reported. The case is unique in that the patient lacked the usual symptoms and signs of hypertension, abdominal right upper quadrant pain, and tenderness. Early detection and immediate delivery resulted in a successful outcome.

Intraamniotic prostaglandin F2 alpha for pregnancy termination in the second and early third trimesters of pregnancy.

OBJECTIVE: To examine the effectiveness and safety of intraamniotic prostaglandin F2 alpha (PGF2 alpha) instillation during second- and early third-trimester termination of pregnancy. STUDY DESIGN: The study group consisted of 173 women between 18 and 32 weeks of gestation admitted for termination of pregnancy with a live, singleton fetus. The procedure included intraamniotic instillation of 40 mg PGF2 alpha. In cases of failed induction; after 24 hours an additional procedure (repeated PGF2 alpha injection, oxytocin augmentation or extraovular balloon installation) was performed. RESULTS: The mean induction-to-abortion interval was 27 +/- 17 hours, 26 minutes. The induction-to-abortion interval was not significantly influenced by parity, maternal age, indication for pregnancy termination or gestational age at the time of the procedure. Complications were related to a longer induction-to-abortion interval (35 hours, 41 minutes +/- 26 hours, 15 minutes in complicated cases as compared to 25 hours, 43 minutes +/- 15 hours, 28 minutes, P = .012). However, complications were uncommon. CONCLUSION: Intraamniotic PGF2 alpha instillation was safely used for termination of pregnancy, even at advanced gestational ages. The induction-to-abortion interval is the main factor influencing complications and is important as a catalyst for cases that fail to abort within 24 hours.