DNA nanotherapy for pre-neoplastic cervical lesions.

OBJECTIVE: This study aims to test the hypothesis that targeted nanoparticle delivery of DNA encoding HPV16-regulated diphtheria toxin (DT-A) will result in the death of HPV16-infected cells. MATERIALS AND METHODS: Plasmid constructs containing a HPV16 Long Control Region (LCR) DNA sequence upstream of DT-A or luciferase reporter (Luc) DNA sequences were used to formulate poly(ß-amino ester) nanoparticles. The effect on tumor growth of HPV/DT-A-nanoparticle injection directly into HPV16(+) CaSki human cervical cancer cell-derived xenografts in mice was determined. To evaluate the ability of the HPV16 LCR regulatory sequence to activate gene expression specifically in HPV16-infected cells, mice underwent bioluminescent optical imaging following intraperitoneal injection of HPV/Luc-nanoparticles. The use of Lutrol F127, a thermal-sensitive gel, to target delivery of nanoparticles and subsequent gene expression to cervical epithelial cells was evaluated in ex vivo cultures of mouse cervix and following intravaginal delivery of nanoparticle/gel in mice, as well as in ex vivo cultures of surgical LEEP samples. RESULTS: The selected HPV16 LCR regulatory sequence activates gene expression in both HPV16-infected cells and non-infected cells. However, in the cervix, it is specifically active in epithelial cells. Following exposure of cervical cells to HPV/DT-A-nanoparticles mixed with Lutrol F127 gel, DT-A is expressed and cells die. CONCLUSIONS: An HPV16 DNA sequence that targets gene expression specifically to HPV16-infected cells remains to be discovered. Topical application of a Lutrol F127 thermal gel/nanoparticle mix is illustrative of how to restrict exposure of cells to therapeutic nanoparticles, thereby allowing for targeted DNA delivery to cervical pre-cancerous lesions.

Posthysterectomy cytology screening: indications and clinical implications.

OBJECTIVE: To review the results of patients who were referred for posthysterectomy of abnormal cytology based on screening indications. MATERIALS AND METHODS: We performed a retrospective review of 64 patients who have been referred for posthysterectomy vaginal colposcopy to the gynecologic oncology service. Patients' demographics, clinical features, reason for screening, and final diagnosis were recorded. Patients were divided into 2 groups based on posthysterectomy screening guidelines. Group A was considered to have undergone unnecessary screening based on national guidelines, and group B had risk factors that appropriately called for continued surveillance. The number of colposcopic examinations and the incidence of neoplasia were recorded for each group. RESULTS: The mean age of the patients was 65 years (range = 35-95 y). Group A included 22 patients with history of abnormal cytology posthysterectomy for benign disease. Of the 22 abnormal cytology results, 21 were low-grade squamous intraepithelial lesion (n = 14) or atypical squamous cells of undetermined significance (n = 7) with 1 high-grade squamous intraepithelial lesion. After referral and colposcopy of this group, no neoplasia was found. Group B included 42 total patients. Of these 42 patients, 20 (48%) had a history of cervical intraepithelial neoplasia, 12 (28%) had a history of vaginal intraepithelial neoplasia, 6 (14%) had history of cervical cancer, 2 (5%) had history of diethylstilbestrol exposure, and 2 (5%) had a history of radiation therapy. In group B, 8 (9%) and 1 (2%) of the patients had vaginal intraepithelial neoplasia 2/3 and squamous cell carcinoma, respectively. CONCLUSIONS: Current national guidelines are appropriate. Adherence to these guidelines will decrease intervention and not affect the detection of vaginal neoplasia. Patients with risk factors for lower genital tract neoplasia warrant continued screening after hysterectomy.

Full-term pregnancy and vaginal delivery after treatment for non-Hodgkin's lymphoma of the cervix and lower uterine segment: a case report.

BACKGROUND: Primary gynaecologic non-Hodgkin's lymphomas are rare. We present a case of primary large B-cell lymphoma localized to the lower uterine segment and endocervical stroma that was successfully treated with chemotherapy and immunotherapy. Treatment was followed by a disease-free interval and successful term vaginal delivery. CASE: A 21-year-old nulliparous woman presented with dysfunctional uterine bleeding. Radiologic assessment of a posterior lower uterine segment mass and pathologic evaluation of cervical biopsies demonstrated diffuse large B-cell lymphoma involving the endocervical stroma. The patient was treated with chemotherapy and immunotherapy. She had a normal, uncomplicated full-term pregnancy and spontaneous vaginal delivery six years after treatment. CONCLUSION: Aggressive diagnosis and treatment of primary non-Hodgkin's lymphomas of the cervix do not preclude the possibility of a successful pregnancy and term vaginal delivery.

Addiction in pregnancy.

Substance abuse in pregnancy has increased over the past three decades in the United States, resulting in approximately 225,000 infants yearly with prenatal exposure to illicit substances. Routine screening and the education of women of child bearing age remain the most important ways to reduce addiction in pregnancy. Legal and illegal substances and their effect on pregnancy discussed in this review include opiates, cocaine, alcohol, tobacco, marijuana, and amphetamines. Most literature regarding opiate abuse is derived from clinical experience with heroin and methadone. Poor obstetric outcomes can be up to six times higher in patients abusing opiates. Neonatal care must be specialized to treat symptoms of withdrawal. Cocaine use in pregnancy can lead to spontaneous abortion, preterm births, placental abruption, and congenital anomalies. Neonatal issues include poor feeding, lethargy, and seizures. Mothers using cocaine require specialized prenatal care and the neonate may require extra supportive care. More than 50% of women in their reproductive years use alcohol. Alcohol is a teratogen and its effects can include spontaneous abortion, growth restriction, birth defects, and mental retardation. Fetal alcohol spectrum disorder can have long-term sequelae for the infant. Tobacco use is high among pregnant women, but this can be a time of great motivation to begin cessation efforts. Long-term effects of prenatal tobacco exposure include spontaneous abortion, ectopic pregnancy, placental insufficiency, low birth weight, fetal growth restriction, preterm delivery, childhood respiratory disease, and behavioral issues. Marijuana use can lead to fetal growth restriction, as well as withdrawal symptoms in the neonate. Lastly, amphetamines can lead to congenital anomalies and other poor obstetric outcomes. Once recognized, a multidisciplinary approach can lead to improved maternal and neonatal outcomes.

Placenta percreta with invasion of the bladder wall: management with a multi-disciplinary approach.

Placenta percreta with pelvic organ invasion carries a high mortality for mother and fetus. Appropriate multidisciplinary consultation, strategy, and preoperative planning for Cesarean hysterectomy permitted caregivers to provide a maternal-infant bonding experience, surgical hemostasis, preservation of bladder function, and a healthy, vigorous neonate.

Mallory-Weiss tear diagnosed in the immediate postpartum period: a case report.

BACKGROUND: Mallory-Weiss tears occur rarely during pregnancy, labour and delivery, and the puerperium, despite the increased frequency of retching and vomiting. CASE: We describe a Mallory-Weiss syndrome diagnosed during the immediate postpartum period in a 34-year-old primigravida. The syndrome initially manifested as lower gastrointestinal bleeding and melena. CONCLUSION: If unrecognized, this complication may lead to life-threatening internal bleeding. It is important to look for an occult bleeding source with such a presentation, and prompt intervention is essential.

Interpretability of excisional biopsies of the cervix: cone biopsy and loop excision.

OBJECTIVE: To compare the results of cold knife conization (CKC) and loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia to determine if excisional method has effects on pathologic interpretation. METHODS: Retrospective review of the perioperative medical records of patients who had a CKC and electrosurgical loop excision of cervix. Patients selected had either primary treatment for cervical intraepithelial neoplasia, suspected invasion, glandular abnormalities or discordant cytology. RESULTS: Among the eligible patients, 61 had CKC and 96 had LEEP. Overall, CKC specimens had interpretable surgical margins more frequently than LEEP (95% vs 85%); however, it was not statistically significant (p=.1). Margins were less likely to be involved with neoplasia in CKC specimens (16% vs 38%; p=.005). Loop electrosurgical excision procedure specimens were less likely to yield a single intact specimen (1.1 vs 1.9; p=.000). Logistic regression showed a significant effect of specimen number (p=.04) on interpretability. CONCLUSION: Current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for diagnostic excisional procedure used for glandular lesions suggest that the procedure provides "an intact specimen with interpretable margins." Loop electrosurgical excision procedure in the current study was associated with an increased number of specimens that limited interpretability and an increased number of positive margins. Cold knife conization is preferred in cases where margin status is critical, such as glandular lesions and suspected microinvasion. If LEEP is performed, clinicians should attempt to obtain a single surgical specimen maximizing the pathologic interpretation and disease-free margins.