Head and Neck Cancer in Haiti: A Case Series from Hopital de L'Universite d'Etat d'Haiti.

This manuscript characterizes the demographics, presenting symptoms and risk factors of patients diagnosed with head and neck cancer at Hopital de L'Universite d'Etat d'Haiti (HUEH), Haiti's single largest healthcare facility. We conducted a prospective study of patients who presented to HUEH between January and March of 2016 with a lesion of the head or neck suspicious for cancer. All patients who met eligibility criteria received a biopsy, which was interpreted by a Haitian pathologist and when the specimen was available was confirmed by a team of pathologists from Stanford University. A total of 34 participants were identified. The biopsy-confirmed diagnoses were squamous cell carcinoma (n=7), benign (n=7), large cell lymphoma (n=2), ameloblastoma (n=2), pleomorphic adenoma (n=1), and adenocarcinoma (n=1). Fourteen patients were unavailable for biopsy. Patients with head and neck cancer had a mean age of 63.4 years, were majority male (62.5%), waited on average 10.9 months to seek medical attention, and most commonly presented with T-stage 3 or higher disease (87.5%). By characterizing patterns of head and neck cancer at HUEH we hope to facilitate efforts to improve early detection, diagnosis, and management of this important public health condition.

The Life Cycle of the Uterine Fibroid Myocyte.

PURPOSE OF REVIEW: Uterine fibroids are common benign tumors of women in the USA and worldwide, yet the biological nature and pathogenesis of these tumors remain largely unknown. This review presents our view of the stages in the life cycle of a subset of uterine fibroid myocytes, introduces hypothetical concepts and morphological data to explain these changes, and relates these changes in individual myocytes to the phases of fibroid tumor development. RECENT FINDINGS: The observations gained from light and electron microscopic, immunohistochemical, and morphometric studies in our laboratory have led to the hypothesis that fibroid changes over time may relate to the excessive production of collagen by phenotypically transformed myocytes. This accumulation of collagen results in decreased microvessel density, followed by myocyte injury and atrophy, with eventual senescence and involution through ischemic cellular degeneration and inanition. SUMMARY: Uterine leiomyomas, or fibroids, are characterized by two histologic features-proliferation of myocytes and production of an extracellular collagenous matrix. In the larger tumors, the collagenous matrix is often abundant. Within those regions in which the accumulating collagen is excessive, the myocytes are progressively separated from their blood supply, resulting in myocyte atrophy and eventually cell death. It is within these hypocellular, hyalinized areas that the complete lifecycle of the fibroid myocyte is realized. It begins with the phenotypic transformation of a contractile cell to one characterized by proliferation and collagen synthesis, progresses through an intermediate stage of atrophy related to interstitial ischemia, and eventuates in cell death due to inanition. Lastly, resorption of inanotic cells appears to occur by a non-phagocytic, presumably enzymatic process of degradation and recycling that we refer to as reclamation.

Otorhinolaryngology/Head and Neck Surgery in a low income country: The Haitian experience.

OBJECTIVE: Little is known regarding the diagnosis and management of pediatric surgical conditions of the head and neck in low-income countries. Haiti, the western hemisphere's poorest country, recently developed its first Otorhinolaryngology (ORL) department at the Hopital de L'Universite d'Etat d'Haiti (HUEH). This manuscript assesses the caseload at HUEH with a special emphasis on pediatric cases, with the aim of characterizing ORL related conditions and their treatments in low-income countries. METHODS: We conducted a retrospective chart review of surgical case logs at HUEH for the calendar year of 2014 and recorded patient age, diagnosis, and surgical intervention for all ORL surgeries. RESULTS: A total of 229 ORL surgeries were performed at HUEH during this time. The average age of the patient was 21.8 years and 54.2% of patients were 18 years or younger. The five most common diagnoses were tonsillar hypertrophy (23.6%), ingested foreign body (18%), mandibular fracture (9.2%), unspecified head or neck mass (6%), and thyroid goiter (4.8%). The five most common surgeries performed were tonsillectomy (23.6%), foreign body retrieval (17.9%), open reduction of mandibular fracture with direct skeletal fixation (6.9%), thyroidectomy (7.9%), and excision of unspecified mass. Trauma accounted for 33.6% of all ORL surgeries. CONCLUSIONS: Diseases related to the head and neck constitute a common yet underserved surgical problem. Strengthening ORL surgical capacity in Haiti should focus on improving capacity for the most common conditions including tonsillar disease, ingested foreign bodies, and facial trauma, as well as improving capacity for rarely performed surgeries, such as ear surgery, nose and sinus surgery, and cancer resections.

Vaginal Self-Sampling for Human Papillomavirus Infection as a Primary Cervical Cancer Screening Tool in a Haitian Population.

BACKGROUND: Human papillomavirus (HPV) testing as primary cervical cancer screening has not been studied in Caribbean women. We tested vaginal self-collection versus physician cervical sampling in a population of Haitian women. METHODS: Participants were screened for high-risk HPV with self-performed vaginal and clinician-collected cervical samples using Hybrid Capture 2 assays (Qiagen, Gaithersburg, MD). Women positive by either method then underwent colposcopy with biopsy of all visible lesions. Sensitivity and positive predictive value were calculated for each sample method compared with biopsy results, with κ statistics performed for agreement. McNemar tests were performed for differences in sensitivity at ≥cervical intraepithelial neoplasia (CIN)-I and ≥CIN-II. RESULTS: Of 1845 women screened, 446 (24.3%) were HPV positive by either method, including 105 (5.7%) only by vaginal swab and 53 (2.9%) only by cervical swab. Vaginal and cervical samples were 91.4% concordant (κ = 0.73 [95% confidence interval, 0.69-0.77], P < 0.001). Overall, 133 HPV-positive women (29.9%) had CIN-I, whereas 32 (7.2%) had ≥CIN-II. The sensitivity of vaginal swabs was similar to cervical swabs for detecting ≥CIN-I (89.1% vs. 87.9%, respectively; P = 0.75) lesions and ≥CIN-II disease (87.5% vs. 96.9%, P = 0.18). Eighteen of 19 cases of CIN-III and invasive cancer were found by both methods. CONCLUSIONS: Human papillomavirus screening via self-collected vaginal swabs or physician-collected cervical swabs are feasible options in this Haitian population. The agreement between cervical and vaginal samples was high, suggesting that vaginal sample-only algorithms for screening could be effective for improving screening rates in this underscreened population.

The natural history of uterine leiomyomas: light and electron microscopic studies of fibroid phases, interstitial ischemia, inanosis, and reclamation.

We propose, and offer evidence to support, the concept that many uterine leiomyomas pursue a self-limited life cycle. This cycle can be arbitrarily divided on the basis of morphologic assessment of the collagen content into 4 phases: (1) proliferation, (2) proliferation and synthesis of collagen, (3) proliferation, synthesis of collagen, and early senescence, and (4) involution. Involution occurs as a result of both vascular and interstitial ischemia. Interstitial ischemia is the consequence of the excessive elaboration of collagen, resulting in reduced microvascular density, increased distance between myocytes and capillaries, nutritional deprivation, and myocyte atrophy. The end stage of this process is an involuted tumor with a predominance of collagen, little to no proliferative activity, myocyte atrophy, and myocyte cell death. Since many of the dying cells exhibit light microscopic and ultrastructural features that appear distinct from either necrosis or apoptosis, we refer to this process as inanosis, because it appears that nutritional deprivation, or inanition, is the underlying cause of cell death. The disposal of myocytes dying by inanosis also differs in that there is no phagocytic reaction, but rather an apparent dissolution of the cell, which might be viewed as a process of reclamation as the molecular contents are reclaimed and recycled.

Human papillomavirus prevalence in a population of women living in Port-au-Prince and Leogane, Haiti.

BACKGROUND: There have been no published studies of carcinogenic human papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation that has one of the greatest burdens of cervical cancer globally. OBJECTIVE: Characterize prevalence of carcinogenic HPV and the prevalence of individual carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+). METHODS: Women (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV positives was tested for individual HPV genotypes using a GP5+/6+ assay. RESULTS: The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%-19.9%) and decreased with increasing age (ptrend < 0.001). Women with 3 or more sexual partners and who started sex before the age of 18 years had twice the age-adjusted prevalence of carcinogenic HPV of women with one partner and who started sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the most common HPV genotypes detected in CIN2+ and more common in women with CIN2+ than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n = 42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5). CONCLUSIONS: The prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in other Latin American countries. High carcinogenic HPV prevalence and a lack of cervical cancer screening may explain the high burden of cervical cancer in Haiti.

Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and their associations with human semen quality measurements.

A total of 256 men were studied to evaluate whether serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) impacted semen quality or reproductive hormones. Blood and semen were collected and analyzed for perfluorochemicals and reproductive and thyroid hormones. Semen quality was assessed using standard clinical methods. Linear and logistic modeling was performed with semen profile measurements as outcomes and PFOS and PFOA in semen and plasma as explanatory variables. Adjusting for age, abstinence, and tobacco use, there was no indication that PFOA or PFOS was significantly associated with volume, sperm concentration, percent motility, swim-up motility and concentration, and directional motility (a function of motility and modal progression). Follicle-stimulating hormone was not associated with either PFOA or PFOS. Luteinizing hormone was positively correlated with plasma PFOA and PFOS, but not semen PFOS. Important methodological concerns included the lack of multiple hormonal measurements necessary to address circadian rhythms.

Towards a field-compatible optical spectroscopic device for cervical cancer screening in resource-limited settings: effects of calibration and pressure.

Quantitative optical spectroscopy has the potential to provide an effective low cost, and portable solution for cervical pre-cancer screening in resource-limited communities. However, clinical studies to validate the use of this technology in resource-limited settings require low power consumption and good quality control that is minimally influenced by the operator or variable environmental conditions in the field. The goal of this study was to evaluate the effects of two sources of potential error: calibration and pressure on the extraction of absorption and scattering properties of normal cervical tissues in a resource-limited setting in Leogane, Haiti. Our results show that self-calibrated measurements improved scattering measurements through real-time correction of system drift, in addition to minimizing the time required for post-calibration. Variations in pressure (tested without the potential confounding effects of calibration error) caused local changes in vasculature and scatterer density that significantly impacted the tissue absorption and scattering properties Future spectroscopic systems intended for clinical use, particularly where operator training is not viable and environmental conditions unpredictable, should incorporate a real-time self-calibration channel and collect diffuse reflectance spectra at a consistent pressure to maximize data integrity.

A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test.

The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings ("triage test"). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5000 viral copies, the clinically relevant threshold.

A feasibility study to evaluate pelvic peritoneal anatomy with a saline intraperitoneal sonogram (SIPS).

OBJECTIVE: To prove the safety and feasibility of evaluating pelvic anatomy with a new imaging technique called saline intraperitoneal sonogram (SIPS). DESIGN: Prospective clinical case series. SETTING: Outpatient fertility clinic. PATIENT(S): Ten women with unexplained infertility and normal hysterosalpingograms (HSG). Five women with no known risk factors and five women with known risk factors for adhesive disease were enrolled. INTERVENTION(S): Step 1 required performing a sonohysterogram. Step 2 involved directing a 17-g oocyte retrieval needle into a pocket of peritoneal fluid under ultrasound guidance and infusing normal saline. The pelvic anatomy was evaluated with the three-dimensional and four-dimensional mode on pelvic ultrasound. MAIN OUTCOME MEASURE(S): Technical feasibility, safety, time, fluid infusion, and deficit volumes. RESULT(S): All 10 patients successfully completed the protocol. One of the five women with no risk factors for adhesive disease and a normal HSG was discovered to have a unilateral hydrosalpinx and filmy adhesive disease on SIPS. Both findings were confirmed on laparoscopy. Three out of the five women with known risk factors had abnormal SIPS imaging and were confirmed on laparoscopy to have significant adhesive disease. The average procedure time was 45 minutes (±15 minutes). CONCLUSION(S): This study demonstrates that SIPS is a safe, quick, and potentially cost-effective method for evaluating pelvic adhesive disease in an outpatient facility in women with unexplained infertility and a normal HSG.

Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture.

BACKGROUND: Uterine leiomyomas (fibroids) are benign smooth muscle tumors that often contain an excessive extracellular matrix (ECM). In the present study, we investigated the interactions between human uterine leiomyoma (UtLM) cells and uterine leiomyoma-derived fibroblasts (FB), and their importance in cell growth and ECM protein production using a coculture system. RESULTS: We found enhanced cell proliferation, and elevated levels of ECM collagen type I and insulin-like growth factor-binding protein-3 after coculturing. There was also increased secretion of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor-2, and platelet derived growth factor A and B in the media of UtLM cells cocultured with FB. Protein arrays revealed increased phosphorylated receptor tyrosine kinases (RTKs) of the above growth factor ligands, and immunoblots showed elevated levels of the RTK downstream effector, phospho-mitogen activated protein kinase 44/42 in cocultured UtLM cells. There was also increased secretion of transforming growth factor-beta 1 and 3, and immunoprecipitated transforming growth factor-beta receptor I from cocultured UtLM cells showed elevated phosphoserine expression. The downstream effectors phospho-small mothers against decapentaplegic -2 and -3 protein (SMAD) levels were also increased in cocultured UtLM cells. However, none of the above effects were seen in normal myometrial cells cocultured with FB. The soluble factors released by tumor-derived fibroblasts and/or UtLM cells, and activation of the growth factor receptors and their pathways stimulated the proliferation of UtLM cells and enhanced the production of ECM proteins. CONCLUSIONS: These data support the importance of interactions between fibroid tumor cells and ECM fibroblasts in vivo, and the role of growth factors, and ECM proteins in the pathogenesis of uterine fibroids.

Estrogenic ovulatory dysfunction or functional female hyperandrogenism: an argument to discard the term polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders seen among reproductive-age women, with a prevalence of 4%-9% depending on the criteria used to define the syndrome. The diagnostic criteria for PCOS have been surprisingly controversial and confusing for patients, clinicians, and researchers. We believe that the confusion surrounding PCOS arises almost entirely because its name refers to a trait that is inconsistently present and irrelevant to both the etiology and the treatment of the disorder. We suggest that merely abandoning the term PCOS will cure much of what has ailed us for decades and allow us to focus on the etiology and treatment of the causes of what the experts in this field have come to recognize as functional female hyperandrogenism.

Ectopic pregnancy in a preexisting hydrosalpinx during a spontaneous pregnancy.

OBJECTIVE: To discuss the possible role of abnormal embryo migration as a cause of ectopic pregnancy during IVF with hydrosalpinges. DESIGN: Case report. SETTING: University-based reproductive endocrinology and fertility clinic. PATIENT(S): A patient presenting with a tubal ectopic pregnancy after spontaneous conception in a preexisting hydrosalpinx. INTERVENTION(S): Laparoscopic salpingectomy. MAIN OUTCOME MEASURE(S): Ultrasound and operative findings. RESULT(S): Case demonstration of abnormal embryo migration into a surgically documented preexisting hydrosalpinx during a spontaneous conception. CONCLUSION(S): The mechanism of increased tubal ectopic pregnancy rates during IVF with hydrosalpinges remains unexplained. This case supports abnormal embryo migration due to the hydrosalpinx as a contributing factor.

Mullerian agenesis and thrombocytopenia absent radius syndrome: a case report and review of syndromes associated with Mullerian agenesis.

UNLABELLED: Mullerian agenesis, commonly referred to as Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS), is a congenital defect that is most commonly associated with renal and spinal malformations. It is very rare for Mullerian agenesis to be accompanied by malformations of the extremities. In this report, we describe a 22-year-old woman with Mullerian agenesis and thrombocytopenia absent radius syndrome (TARS). We also review rare syndromes associated with Mullerian anomalies, including Mullerian hypoplasia/aplasia-renal agenesis-cervicothoracic somite dysplasia (MURCS), Roberts syndrome, Bardet-Biedl syndrome (BBS), McKusick-Kaufman syndrome (MKS), Wolf-Hirschhorn syndrome, and others. The pathogenesis of these complex malformation syndromes is not well understood as a result of their sporadic occurrence. However, some of these syndromes do follow a pattern of inheritance, suggesting that they could provide insights into our understanding of their origins. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to review the rare congenital defects associated with Mullerian agenesis, to determine the genetic etiologies of the associated syndromes with Mullerian agenesis, and to discuss information for parental counseling related to inheritance patterns and growth and development of the affected child.

Successful pregnancies in patients with estrogenic anovulation after low-dose human chorionic gonadotropin therapy alone following hMG for controlled ovarian hyperstimulation.

OBJECTIVE: To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS). CASE REPORT: Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy. INTERVENTIONS: After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2-3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer. MAIN OUTCOME MEASURES: Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound. RESULTS: After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles >14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation. CONCLUSION: The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.

Portable colposcopy in low-resource settings.

Screening for cervical dysplasia is an important public health effort worldwide. In unscreened populations, the incidence of cervical cancer ranges between 2 and 4% of the adult female population, whereas less than 0.1% of the screened population of Caucasian women has cervical cancer in the United States. In developing countries, cervical cytology is difficult to implement successfully because of the cost, cultural constraints, limited access to pathology services, etc. Bypassing cytology and going directly to colposcopy has been successfully implemented as a screening strategy for dysplasia in low resource settings. In this article we describe the development and utilization of a portable binocular colposcope that does not require electricity.

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.

Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P