Collaborations in gynecologic oncology education and research in low- and middle- income countries: Current status, barriers and opportunities.

Eighty-five percent of the incidents and deaths from cervical cancer occur in low and middle income countries. In many of these countries, this is the most common cancer in women. The survivals of the women with gynecologic cancers are hampered by the paucity of prevention, screening, treatment facilities and gynecologic oncology providers. Increasing efforts dedicated to improving education and research in these countries have been provided by international organizations. We describe here the existing educational and research programs that are offered by major international organizations, the barriers and opportunities provided by these collaborations and hope to improve the outcomes of cervical cancer through these efforts.

Comparison of robotic-assisted and conventional laparoscopy in the management of adnexal masses.

STUDY OBJECTIVE: To compare the outcome of robotic-assisted laparoscopy vs conventional laparoscopy in the management of ovarian masses. DESIGN: Retrospective cohort (Canadian Task Force classification II-3). SETTING: Academic medical centre in the northeast United States. PATIENTS: Retrospective medical record review of 71 consecutive patients with presumed benign ovarian masses. INTERVENTION: Robotic-assisted laparoscopy in 30 patients with presumed benign ovarian masses was compared with conventional laparoscopy in 41 patients. MEASUREMENTS AND MAIN RESULTS: Operative outcomes including operative time, estimated blood loss, length of hospital stay, and complications were recorded. Standard statistical analysis was used to compare the outcomes in the 2 groups. Mean (SD) operative time in the robotic group was 1.95 (0.63) hours, which was significantly longer than in the conventional laparoscopic group, 1.28 (0.83) hours (p = .04). Estimated blood loss in the robotic group was 74.52 (56.23) mL, which was not significantly different from that in the conventional laparoscopic group, 55.97 (49.18) mL. There were no significant differences in length of hospital stay between the robotic and conventional laparoscopic groups: 1.20 (0.78) days and 1.48 (0.63). Conversion to laparotomy was not necessary in either group of patients. Intraoperative and postoperative complications were similar between the 2 groups. CONCLUSION: Robotic-assisted laparoscopy is a safe and efficient technique for management of various types of ovarian masses. However, conventional laparoscopy is preferred for management of ovarian masses because of shorter operative time. Prospective studies are needed to evaluate the outcomes of robotic-assisted laparoscopic management of benign and malignant ovarian neoplasms.

Recurrent retroperitoneal myxoid liposarcoma during pregnancy: a case report and literature review.

Retroperitoneal liposarcoma in pregnancy is rare, and only a few cases of primary liposarcoma during pregnancy have been reported. To the best of our knowledge, there is no published report of retroperitoneal liposarcoma that was previously treated and recurred during pregnancy. Our patient was diagnosed with a pelvic mass on ultrasound at 12-weeks' gestation. The mass was found to be a retroperitonal, well-differentiated myxoid liposarcoma and was radically excised at the time of cesarean delivery at 36-weeks' gestation. However, the tumor recurred soon and progressed rapidly, and the patient eventually died of the disease. A thorough sonographic investigation and timing of surgery may be critical in terms of finding a surgically resectable lesion and leading to a more favorable prognosis.

Cytologic and histologic review of atypical glandular cells (AGC) detected during cervical cytology screening.

This article is to determine the clinical significance and underlying pathology among patients with atypical glandular cells (AGC) identified during cervical Papanicolau (Pap) smear screening. AGC slides were searched from 51,412 computerized files of the cytology laboratory of Mackay Memorial Hospital during a 29-month period. The results of clinical evaluations were reviewed and an experienced gynecologic cytopathologist who was not involved in the original cytologic diagnosis and was not aware of the clinical results of the follow-up examinations rechecked all AGC slides. We used the z score to determine whether different results were achieved after the gynecologic cytopathologist rechecked the slides. We further analyzed all slides with different cytologic diagnoses and compared results with the histologic diagnoses. Forty-nine cases were initially identified as AGC. Among these, 29 were reviewed and identified as AGC again, and the result of biopsies revealed that they were all chronic cervicitis, ie, negative for malignancy or premalignancy. The other 20 cases were reviewed and diagnosed as non-AGC. Among the results of cytologic examinations, seven had inflammation, two had atypical squamous cells of undetermined significance (ASC-US), ten had high-grade cervical intraepithelial neoplasia (CIN), and one had adenocarcinoma. The results of histologic diagnosis included eight cases with normal tissue, two with CIN grade 1, eight with high-grade CIN, one with microinvasive squamous cell carcinoma, and one with adenocarcinoma. Histologic results revealed 20.4%1 (10/49) and 50% 1(10/20) at initial cytologic diagnosis of AGC and expert-reviewed non-AGC, respectively, which were finally at least high-grade CIN. According to the gynecologic cytopathologist's diagnosis, 59.2%1 (29/49) of cases would have eliminated unnecessary histologically diagnostic procedures. In conclusion, clinicians should be careful about the significance of the cytologic diagnosis of AGC, because there may actually be an underlying pathology, which can be identified by a pathologist who is an expert in gynecologic cytopathology. The interobserver variation in diagnosing AGC favors specialized training in gynecologic cytopathology. In addition, prompt diagnostic interventions, including colposcopy, endocervical curettage, and/or endometrial biopsy, should be performed after confirmation of the diagnosis of non-AGC by an experienced gynecologic cytopathologist.

Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin.

Densin-180 is a transmembrane protein that is tightly associated with the postsynaptic density in CNS neurons and is postulated to function as a synaptic adhesion molecule. Here we report the identification of the alpha-subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and alpha-actinin-4 as potential binding partners for the densin-180 intracellular segment. We demonstrate by yeast two-hybrid and biochemical assays that the intracellular portion of densin-180, the alpha-subunit of CaMKII (CaMKIIalpha), and alpha-actinin interact with each other at distinct binding sites and can form a ternary complex stabilized by multiple interactions. Densin-180 binds specifically to the association domain of CaMKIIalpha and does not bind with high affinity to holoenzymes of CaMKII that contain beta-subunit. The PDZ (PSD-95, DIg, Z0-1) domain of densin contributes to its binding to alpha-actinin. A distinct domain of alpha-actinin interacts with the kinase domains of both alpha- and beta-subunits of CaMKII. Autophosphorylation of CaMKII increases its affinity for densin-180 from an EC(50) of >1 micrometer to an EC(50) of <75-150 nM. In contrast, phosphorylation of densin-180 by CaMKII at serine-1397 only slightly decreases its affinity for CaMKII. The specific interaction of densin-180 with holoenzymes of CaMKII containing only alpha-subunit and the increased affinity of CaMKII for densin-180 after autophosphorylation suggest that densin-180 may be involved in localization of activated CaMKII synthesized in dendrites.

Androgen receptor gene mutations in 46,XY females with germ cell tumours.

We present clinical findings and molecular characterization in two patients previously diagnosed as 46,XY female gonadal dysgenesis with germ cell tumour. Both patients showed a female general phenotype with unambiguously female external genitalia and primary amenorrhoea compatible with complete androgen insensitivity syndrome. The first patient, at the age of 31 years, developed a dysgerminoma measuring 8 x 13 x 10 cm in one abdominal testis. Genetic analysis revealed a single nucleotide substitution on exon 4 in the hormone-binding domain of the androgen receptor (AR) gene, resulting in a change of codon 681 GAG (glutamic acid) to AAG (lysine). The second patient, at the age of 17 years, developed a dysgerminoma measuring 12 x 10 x 7 cm in one abdominal testis and gonadoblastoma in the other testis. Genetic analysis showed a point mutation on exon 3 in the DNA-binding domain of the AR gene resulting in a change of codon 607 CGA (arginine) to CAA (glutamine). Arg607-Gln and Arg608-Lys point mutations in the DNA-binding domain of the AR gene have been associated with male breast cancer in partial androgen insensitivity syndrome. A codon 607 mutation in the DNA-binding domain of the AR gene in our patient 2 is associated with early development of germ cell tumour. We suggest regular molecular genetic analysis of the AR gene in 46,XY females with germ cell tumour and androgen insensitivity syndrome to detect differences in the specific regions of AR gene involved in early progression toward oncogenesis of the dysgenetic gonads.

Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers.

Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent studies have localized the TSG101 gene in this region, and also demonstrated a high frequency of abnormalities of this gene in human breast cancer. To determine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endometrial carcinoma, as well as nearby non-cancerous tissue from the same patients, and 16 blood samples from healthy persons as normal control were analysed by Southern blot analysis of genomic DNA, reverse transcription of the TSG101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in cancerous or non-cancerous tissues of the uterus and cervix and in normal peripheral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and no definite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-cancerous tissue, normal peripheral mononuclear cells also had abnormal transcripts. Given these findings, the role of the TSG101 gene as a tumour-suppressor gene should be re-evaluated. Because some aberrant transcripts could be found at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products.

Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review.

To determine the risks when the primary methotrexate (MTX) treatment of cervical pregnancy has an unsatisfactory outcome, we conducted a Medline search on relevant literature published from January 1983 to June 1997. The search yielded 28 publications of 48 cases of cervical pregnancy. These and four new cases from our institutions were used in our study. A cervical pregnancy that presented with a serum beta-human chorionic gonadotrophin concentration of > or = 10,000 mIU/ml [odds ratio (OR) 10.82, 95% confidence interval (CI) 2.59, 45.14], gestational age at > or = 9 weeks (OR 6.44, 95% CI 1.46, 28.52), embryonic cardiac activity (OR 14.29, 95% CI 2.95, 76.92), and crown-rump length of >10 mm (OR 13.33, 95% CI 1.46, 120.48) was considered to be associated with a higher unsatisfactory rate of primary MTX treatment. A concomitant feticide was found to enhance the therapeutic effect of MTX treatment if embryonic cardiac activity was evident (OR 0.13, 95% CI 0.02, 0.68). Administration of a high dose of MTX did not seem to be more effective than a lower one. Our findings supported some previous observations and, more importantly, provided useful clinical information in selecting appropriate candidates for MTX treatment in cases of cervical pregnancy.

Enlarged cisterna magna in the third trimester as a clue to fetal trisomy 18.

Six of 19 fetuses with trisomy 18 confirmed by late karyotyping in the third trimester were found to have an enlarged cisterna magna (10 mm or more). For trisomy 18 conceptuses, there is a significant excess of females in both fetuses and livebirths; however, we found this ratio to be reversed in the third-trimester trisomy 18 fetuses with an enlarged cisterna magna (5 males vs. 1 female), indicating males are more likely to have this associated defect. Each of the 6 cases was associated with other trisomy markers including intrauterine growth retardation and polyhydramnios. Since a significant proportion of pregnancies may escape early prenatal care and some potentially detectable fetal abnormalities may be missed on early ultrasound and/or by maternal serum screenings, prenatal detection of an enlarged cisterna magna associated with intrauterine growth retardation and/or polyhydramnios in late gestation should prompt complete genetic counseling, rapid karyotyping and a careful search for other congenital anomalies.

Thy-1 is a component common to multiple populations of synaptic vesicles.

Thy-1, a glycosylphosphatidylinositol-linked integral membrane protein of the immunoglobulin superfamily, is a component of both large dense-core and small clear vesicles in PC12 cells. A majority of this protein, formerly recognized only on the plasma membrane of neurons, is localized to regulated secretory vesicles. Thy-1 is also present in synaptic vesicles in rat central nervous system. Experiments on permeabilized PC12 cells demonstrate that antibodies against Thy-1 inhibit the regulated release of neurotransmitter; this inhibition appears to be independent of any effect on the Ca2+ channel. These findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.

Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex) associated with large meningomyeloceles and severe limb defects.

Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a combination of omphalocele, exstrophy of the bladder, an imperforate anus and spinal defects, arises from a single localized defect in the early development of the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal septum, and caudal vertebrae. In this report, we document the perinatal features of two cases of OEIS complex associated with meningomyeloceles and severe lower limb defects, and discuss the prenatal diagnosis, inheritance, and differential diagnosis of this association of malformations. Although long-term survival can be achieved by successful corrective surgery, the associated structural defects such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in our patient, can influence the patient's quality of life. We would like to emphasize that an accurate prenatal diagnosis of OEIS complex and associated malformations is important for the detailed counseling of the family as well as appropriate perinatal management by the obstetricians, pediatric surgeons, urologists, neurosurgeons, and neonatologists.

Cervical cancer in young women in Taiwan: prognosis is independent of papillomavirus or tumor cell type.

The objective of this study was to address the hypotheses that younger patients with cervical cancer have a uniquely worse clinical outcome and/or are more likely to have adverse tumor cell types or specific human papillomaviruses (HPV). Cases of stage Ib-IIa cervical cancer among women 35 years of age or younger (82) and over 35 (54) were analyzed and compared with respect to the following: (1) histologic type (squamous vs nonsquamous), (2) human papillomavirus (HPV) type via polymerase chain reaction, and (3) clinical parameters, including tumor size, nodal metastases, and recurrence/persistence. Patients 35 years of age or younger had a survival similar (71.2% vs 72.4%) to that of older women from the same institution. In the younger group, outcome was not correlated with the presence or absence of HPV or HPV type. Nonsquamous carcinomas, including adenocarcinoma and small cell carcinoma, were strongly associated with HPV18, were more prevalent in the younger group, and had a slightly higher risk of recurrence/persistence; however, these differences were not significant and 71% of the recurrences were squamous cell carcinomas. Thus, in young Taiwanese women with stage Ib-IIa cervical cancer, the majority of deaths cannot be attributed to a specific HPV type or unique tumor morphology.

Selective localization and regulated release of calcitonin gene-related peptide from dense-core vesicles in engineered PC12 cells.

Introduction of the gene for calcitonin into the neuroendocrine PC12 cell line resulted in the expression of the neuronal-specific splice product, calcitonin gene-related peptide (CGRP). Expression of this neuropeptide did not require treatment of the PC12 cells with NGF. By all available criteria, including biochemical, immunological, and morphological analysis, we have determined that the CGRP in stably transfected PC12 cells is sorted selectively into the large, dense-core catecholamine-containing secretory vesicles. Conversely, the CGRP is excluded from the small, synaptophysin-rich vesicles present in the same cells. Stimulation conditions that trigger the release of catecholamines cause a parallel burst in the release of CGRP. In all these respects, the engineered PC12 cells process the foreign CGRP in a manner similar to that seen in spinal motor neurons in vivo. These results indicate that this small (37 amino acids) peptide contains sorting information sufficient for targeting to large, dense-core vesicles in heterologous cells, placing very narrow constraints on the possible location of sorting signals. In addition, this CGRP-expressing cell line opens the possibility of studying the physiological role of CGRP in the establishment and maintenance of neuromuscular contacts.

Pelvic abscess caused by Salmonella: a case report.

We report a case of a 28-year-old woman, with no history of sexual activity, who developed a cul-de-sac abscess and bilateral salpingitis caused by Salmonella group C1. This paper documents our limited experience with such an unusual event and suggests that gastrointestinal pathogens should be considered as potential etiologic organisms in patients presenting with pelvic infection and gastroenteritis.

Treatment of cervical pregnancy with methotrexate.

OBJECTIVES: To review our experience with early ultrasonographic diagnosis and fertility-preserving complete medical treatment of cervical pregnancy. METHODS: From January 1989 to December 1994, 11 cases of cervical pregnancy diagnosed by ultrasonography and treated with methotrexate were evaluated. Patients were treated as follows: systemic administration of methotrexate with leucovorin rescue, a single dose of 50 mg of methotrexate intramuscular injection, or transvaginal ultrasonographically-guided intra-amniotic instillation of 50 mg of methotrexate. RESULTS: The mean age of these patients was 33.3 +/- 6.2 years and gestational age at diagnosis ranged from 32 to 73 days. The maximal serum beta-hCG measured was 135,000 mIU/ml, and the time required for return to normal levels ranged from 20 to 157 days. The ectopic gestation was successfully ablated in all cases, and none required hysterectomy. CONCLUSION: If a cervical pregnancy is present and diagnosed early, methotrexate treatment, administered either systemically or locally, is effective as the definitive therapy.

Sonographic and clinical findings of granulosa cell tumor.

BACKGROUND: Granulosa cell tumor (GCT) accounts for roughly 1.5% of all ovarian neoplasms and 5-10% of ovarian cancers. GCT, which may have profound end-organ effects, has attracted a significant amount of attention despite its rarity. This tumor is rare, and difficult to diagnose before operation. Until now, no specific sonographic findings have been reported. METHODS: Twelve cases of pathologically proven GCTs were diagnosed from June 1985 to March 1993. Nine of those cases had preoperative sonographic pictures taken. RESULTS: Eight out of the nine cases tested exhibited a complex multicystic sonographic pattern. For a case evaluated by a transvaginal color and pulsed Doppler assessment, the blood vessels located in the central part with diffuse dispersed vascular arrangement were found to have a resistance index of 0.38 and a pulsatility index of 0.50. The most common complaints of our patients were postmenopausal bleeding and lower abdominal pain. CONCLUSIONS: We conclude that complex multicystic sonographic features observed by high-resolution ultrasonography, in conjuction with a high preoperative estradiol level and clinical symptoms, may help to establish a preoperative diagnosis of GCT.

Spontaneous rupture of the liver associated with pregnancy: a report of two cases.

Spontaneous rupture of the liver associated with pregnancy is a rare and grave complication, usually occurring in preeclampsia or eclampsia. Two cases of ruptured subcapsular hematoma of the right liver during pregnancy are reported. The first case was a 19-year-old woman who had suffered from epigastralgia and absent fetal heart beat in the 32nd week of gestation. The second case was a 31-year-old female who complained of nausea and right upper quadrant pain in the 35th week of pregnancy. Both had preeclampsia, and developed shock with disseminated intravascular coagulation soon after admission. Both received surgery and were found to have ruptured hematoma over the right liver. Finally, the first patient died of renal failure, but the second survived because preoperative diagnosis had been exact. Greater suspicion, then awareness of diagnosis can lead to better timing of surgery and an improved prognosis for mother and child.

Doppler velocimetry study of maternal hemodynamics and fetal vascular pattern in a case of chronic hypertension with superimposed severe preeclampsia and impending fetal death.

A case is presented of chronic hypertension with superimposed severe preeclampsia; absence of end-diastolic velocity in the umbilical artery had been noted at gestational age of 20 weeks. Because the fetus was previable, the mother was treated with pharmacotherapy according to the maternal hemodynamics; uteroplacental circulation and fetal vascular blood flow were monitored by Doppler velocimetry. Deterioration of the fetal condition occurred during crossover of maternal hemodynamics from a low-resistance to a high-resistance state. Serial Doppler velocimetry studies done within 40 minutes of fetal death are described. There were two types of absent end-diastolic velocity in the umbilical artery, and the pathophysiology and clinical management may be quite a different in these two situations.

Pregnancy associated with primary hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is a rare complication of pregnancy. CASES: Three cases of pregnancy complicated by primary hepatocellular carcinoma were seen at our hospital in 3 years. Two were diagnosed antepartum and one postpartum. In one instance, the diagnosis came from finding elevated maternal serum alpha-fetoprotein (MSAFP) with normal amniotic fluid (AF) AFP. Positive hepatitis B surface antigen and liver cirrhosis were found in all three cases, but liver enzymes were only slightly elevated. All three women died, as did one of the fetuses. CONCLUSION: Careful MSAFP screening and interpretation, followed by AFAFP and abdominal sonography, seem to be the best tools for early diagnosis of primary hepatocellular carcinoma in pregnant women.

Decreased amniotic fluid index in term pregnancy. Clinical significance.

In a study of 331 term pregnancies a four-quadrant technique was used to obtain amniotic fluid index measurements, and the results were compared with the current widely used single-pocket measurement. In contrast to the "2-cm rule," the amniotic fluid index measurements consistently demonstrated higher sensitivity in predicting poor fetal outcome with no decrease in specificity. It was noted that pregnancies with an index of < or = 8 cm showed higher incidences of meconium staining, cesarean delivery for fetal distress, abnormal fetal heart rate monitoring and Apgar scores of < or = 7 or less at one minute.