Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Periurethral adenocarcinoma of mesonephric origin: A case report and review of the literature.

Periurethral mesonephric adenocarcinoma is a rare tumor. To the best of our knowledge, only 13 cases have been reported in the literature to date. We report the case of a 36-year-old lady who presented with periurethral mesonephric adenocarcinoma, treated by surgery followed by adjuvant chemotherapy and pelvic radiotherapy. We demonstrate the unusual histology of mesonephric adenocarcinoma and the necessity to consider this tumor in the differential diagnosis of all unusual genito-urologic tumours. In the present literature, combination of surgery followed by chemotherapy and radiotherapy is the most suitable treatment for locally advanced periurethral mesonephric adenocarcinoma.

Undifferentiated Endometrial Carcinoma, an Immunohistochemical Study Including PD-L1 Testing of a Series of Cases From a Single Cancer Center.

Undifferentiated endometrial carcinoma (UEC) is a rare and poorly recognized entity, associated with a poor outcome. The clinical, pathologic, and immunohistochemical features of 17 cases diagnosed at our center are described. The median age was 60 yr. Postmenopausal bleeding was the most common presenting symptom (76.9%). Most patients presented with advanced stage (64.7%). Total hysterectomy with bilateral salpingo-oophorectomy was the commonly offered surgical treatment (80.0%). Nine (52.9%) patients received adjuvant treatment. The median overall survival was 11 mo. Pure UEC was seen in 8 cases (47.0%), while dedifferentiated carcinoma in 5 cases (29.4%). The epithelial component was part of carcinosarcoma or was mixed with serous carcinoma in 2 cases (11.8%) each. Positivity for one or more of the cytokeratin cocktails, mostly as strong focal staining, was evident in 16 cases (94.1%). PAX-8 was negative in 13 cases (86.7%). BRG-1/SMARCA4 was lost in 3 cases (20.0%). Eleven cases (64.7%) were MLH1/PMS2 deficient. Ten cases (66.7%) were positive for programmed death ligand 1, with positivity in 10%, 20%, and 100% of tumor cells detected in a single case each. Only 2 of 11 (18.2%) referral cases were correctly diagnosed as UEC. UEC is a rare tumor that is frequently misdiagnosed. A panel of immunostains is necessary to make the correct diagnosis. The range of positivity for programmed death ligand 1 testing suggests that immunotherapy might be considered in the adjuvant setting, especially with the poor response of this tumor to traditional therapies.

Prevalence of Abnormal Pap Smears: A Descriptive Study from a Cancer Center in a Low-Prevalence Community

Background and aims: Cervical cancer is the fourth most common cancer in women worldwide and the 13th in Jordan. The cervical smear (Pap smear) is a simple approach to detect pre-cancerous cervical lesions. The aim of this study was to evaluate the prevalence of abnormal cervical smears in women seen at the Early Detection/Community Outreach clinic of King Hussein Cancer Center (KHCC). Materials and Methods: In this retrospective study, reports of routine cervical Pap smears performed in the pathology department at KHCC from January 2007 to December 2016, were reviewed. During this period, a total of 5,529 routine smears were assessed for epithelial abnormalities and histopathological grading. Results: A total of 210 (3.8%) abnormal Pap smears were found, with atypical squamous cell of undetermined significance (ASC-US) reported in 110 (52.4%) cases, atypical glandular cells of undermined significance (AGUS) in 58 (27.6%), low grade squamous intra-epithelial lesion (LSIL) in 27 (12.9%) and high grade intra-epithelial lesion (HSIL) in 13 (6.2%). Only single cases of ASC-H and squamous cell carcinoma were reported. The available biopsies showed benign findings in 70.1% of cases, low grade squamous intraepithelial lesions in 11.5% and high grade squamous intraepithelial lesions in 18.4%. Conclusions: The low epithelial cell abnormality (EPCA) prevalence illustrated in this study argues against introduction of population-based HPV testing and vaccination. It calls for a more cost-effective measures in a country with limited resources, where a more widely available Pap-smear testing might suffice.

The relationship of Candida colonization of the oral and vaginal mucosae of mothers and oral mucosae of their newborns at birth.

OBJECTIVE: Vaginal Candida colonization is common during pregnancy. Vaginal Candida may transmit vertically to the mouth of newborns during labor. The aim of this study was to assess and compare oral Candida colonization between vaginally born newborns and cesarean-born newborns and to investigate the association of the mother's vaginal and oral Candida colonization and the newborn's oral colonization at the time of delivery. STUDY DESIGN: Culture swabs were collected from the oral and vaginal mucosae of 100 pregnant women and from the oral mucosa of their 100 full-term newborns. Fifty (50%) of the mothers gave birth vaginally and the other 50 (50%) by cesarean section. RESULTS: The prevalence of oral and vaginal Candida in pregnant mothers was 49% and 40%, respectively. Oral Candida colonization in newborns was 7%. Oral Candida was isolated from 5 of 50 (10%) in the vaginally born group and from 2 of 50 (4%) in the cesarean-born group (P = .44). In vaginally born group, oral Candida was isolated from 5 of 20 (25%) in those born to mothers with vaginal colonization of Candida, and 0 of 30 (0.0%) in mothers without vaginal colonization of Candida (P = .007). CONCLUSIONS: The mother's vaginal Candida may constitute an important source of oral Candida in the newborns, particularly in those delivered vaginally.

Survival outcome after radiation therapy for patients with early cervical carcinoma undergoing inadequate primary surgery.

OBJECTIVE: The aim of this study was to investigate the survival outcome after radiation therapy for patients with early cervical carcinoma undergoing inadequate primary surgery. METHODS: A retrospective analysis of medical charts of all patients with stage IA2 to IIA carcinoma who were referred with inappropriate primary surgery and treated with radiation therapy was reviewed. The collected data include age, presenting symptoms, retrospective stage, lymph node status, histology type, type of surgery, baseline radiologic status before radiotherapy, details of radiation therapy, follow-up, and details of disease recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier survival curves were used to show the OS and recurrence-free survival. RESULTS: A total of 32 patients were treated. The median age of the patients was 48.2 years, with a range of 27.6 to 79.2 years. Twenty-three patients had retrospective stage IB1, and 9 had stage IIA disease. The most common type of surgery (62.5%) was total abdominal hysterectomy with or without bilateral salpingo-oophorectomy. The pelvic lymph node dissection (PLND) status was not determined in 20 patients, 11 had PLND surgical assessment (2 were positive), and 1 had bulky PLND by computed tomographic scan.Baseline assessment showed that 14 patients had no residual disease, 11 had microscopic disease, and 7 had macroscopic disease. The follow-up ranged from 3.3 to 77.8 months, with a median of 24.3 months. Eleven patients developed disease recurrence, and all of them died of their disease. Two- and 5-year OS rates were 79% and 51.7%. Univariate analysis did not show a statistically significant effect of either the disease stage or residual disease survival. CONCLUSIONS: Survival outcome after radiation therapy for patients with early-stage cervical cancer undergoing inadequate surgery seems to be markedly worse than that for patients of comparable stage treated initially with radical radiation.

Ovarian transposition before pelvic irradiation: indications and functional outcome.

AIM: To investigate the indications and effectiveness of ovarian transposition before pelvic irradiation. METHODS: This was a retrospective analysis of patients with malignancies who underwent ovarian transposition before pelvic irradiation. The collected data included age of patient, type and stage of cancer, details of irradiation treatment, and clinical and biochemical parameters of ovarian function during the period of follow-up. RESULTS: Fourteen adult and four pediatric patients with different types of cancers underwent ovarian transposition during the study period. The common tumor types for the adult patients were cervical cancer (n = 4), rectal cancer (n = 4) and medulloblastoma (n = 3), and for pediatric patients was medulloblastoma (n = 2). The mean age for adult patients was 31 years (range, 21-40) and for pediatric patients was 7 years (range, 4-10). Of the adult patients, 10 had adjuvant chemotherapy and four had neoadjuvant chemotherapy added to their radiotherapy program. All pediatric patients received adjuvant chemotherapy. Thirteen of 14 (92.85%) adult patients had normal serum level of follicle-stimulating hormone (FSH; ≤12 IU/L) and E2 (>50 pg/mL). Only one patient had premature menopause. All pediatric patients demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6 months after completion of their treatment. The mean follow-up was 42 months (range, 34-50). CONCLUSION: Ovarian transposition is an effective procedure for the preservation of ovarian function. Young patients with non-hormone-dependent pelvic tumors should be offered a laparoscopic ovarian transposition before the start of pelvic radiotherapy.

Villoglandular papillary adenocarcinoma of the cervix: a series of 28 cases including two with lymph node metastasis.

OBJECTIVE: To investigate the clinicopathologic features, the management, and the outcome of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix. METHODS: A retrospective review of patients' clinical characteristics, pathology, and the disease management, together with outcome information. RESULTS: A total of 28 patients with VGPA were treated. The median age of the patients was 38 years with a range of 26 to 65 years. Sixteen of the 21 patients presented with abnormal bleeding, and 5 patients had an abnormal Papanicolaou (Pap) test result. Nineteen patients had International Federation of Gynecology and Obstetrics stage IB disease, and 5 patients had stage IIB disease. Two of 24 patients, where the lymph node status was known, had positive nodes. Twenty patients underwent different types of radical surgery with or without pelvic radiotherapy, and 8 patients received platinum-based chemotherapy and pelvic radiotherapy with no surgery. The follow-up ranged from 5 to 168 months with a median of 35 months. Twenty-one patients are alive with no evidence of recurrent disease, 5 patients have died because of the disease recurrence, and 2 patients were lost to follow-up. The overall and disease-free 5-year survival for these patients was 82% and 75%, respectively. CONCLUSION: This study confirms the excellent prognosis of VGPA overall compared to the common forms of cervical cancer, but the prognosis is related to stage and pathology. A large multicenter prospective study is warranted to determine the most appropriate treatment for the disease. Until then, a meta-analysis on the subject would be of benefit.

Management of cancer during pregnancy: obstetric and neonatal outcomes.

OBJECTIVE: This study aimed to assess the management and the obstetric and neonatal outcomes of pregnancies complicated by cancer. METHODS: A retrospective analysis of patients with cancer during pregnancy who were treated at King Hussein Cancer Center and King Abdullah University Hospital in Jordan between January 2002 and December 2009 was conducted. The medical records of patients with invasive cancer diagnosed during pregnancy and their newborns were reviewed to retrieve information on treatment and obstetric and neonatal outcomes. Numerical data were tested for normal distribution using Kolmogorov-Smirnov. Statistical analyses were conducted using SPSS 18.0. RESULTS: A total of 46 patients with a diagnosis of cancer in pregnancy were treated. The most common tumor types were breast cancer, hematologic malignancies, and gastrointestinal malignancies. In 17 patients, a miscarriage or a termination of pregnancy occurred in the first trimester. In 25 of 46 patients, a single or a combination of treatment modalities was commenced. The distribution of therapies was as follows: chemotherapy alone, n = 5; surgery alone, n = 7; surgery and chemotherapy, n = 6; surgery and radiation therapy, n = 1; surgery with chemotherapy and radiation therapy, n = 3; chemotherapy and radiation therapy, n = 1; interferon, n = 1; and hormonal therapy, n = 1. The mean (SD) gestational age at delivery was 35.7 (2.7) weeks. The mean birth weight was 2580 (870) g. Preterm delivery occurred in 17 patients. There were 4 neonatal deaths, 2 of them delivered at 33 weeks, 1 delivered at 34 weeks, and 1 delivered at 35 weeks gestation. There were no congenital malformations. CONCLUSIONS: The remarkable finding is a high rate of iatrogenic preterm delivery with a high rate of neonatal mortality. Delivery should be postponed preferably until after a gestational age of 35 weeks.

The association between second hand smoke and low birth weight and preterm delivery.

To determine the association between maternal exposure to SHS and low birth weight and preterm delivery. This cross-sectional study was carried out in the four main governmental hospitals dealing with deliveries in the north of Jordan. A consecutive 8,490 women who delivered in these hospitals between April 2007 and September 2007 were included in the study after excluding those who reported active smoking during the current pregnancy. Pre-structured questionnaire and review of hospital records were used to collect data about maternal background, obstetric history, medical history, and data related to second hand smoke exposure. Overall, 13.8% of women gave birth to a preterm baby and 10.0% gave birth to a low birth weight baby. About 12.6% of women who were exposed to SHS delivered low birth weight babies compared to 7.7% for non exposed women. The rate of preterm delivery among the exposed group was significantly higher than that among the non-exposed group (17.2 vs. 10.6%). In the multivariate analysis, exposure to SHS during pregnancy was significantly associated with increased odds of low birth weight (OR = 1.56 (95% CI 1.31, 1.89)) and preterm delivery (OR = 1.61 (95% CI: 1.30, 1.99)). Exposure of women to SHS during pregnancy is associated with increased odds of low birth weight and preterm delivery. Health care professionals should carry out educational programs to increase awareness and understanding of pregnant women and their husbands about the harmful effects of second hand smoke on birth outcomes.

Haploidentical stem cell transplantation as a salvage therapy for cord blood engraftment failure in a patient with Fanconi anemia.

A 7-year-old male with Fanconi Anemia who developed primary graft failure following one antigen-mismatched unrelated cord blood transplantation and a nonradiation-based conditioning, underwent a second hematopoietic stem cell transplantation (HSCT) from his 2-loci mismatched haploidentical father, using a nonradiation-based regimen, 79 days after the first HSCT. A sustained hematological engraftment was achieved at 9 days post-second HSCT. At 15 months post-second HSCT; the patient demonstrated normal blood counts, sustained donor chimerism, and no evidence of GVHD. Haploidentical HSCTs as primary or secondary sources of stem cells, with appropriate T-cell depletion, may be a readily available option in the absence of HLA-matched related or unrelated donors.

Primary repair of a large incomplete sternal cleft in an asymptomatic infant with Prolene mesh.

A cleft of the sternum is a rare congenital anomaly, often diagnosed as an asymptomatic condition at birth. We present a case of a large incomplete sternal cleft in a full-term baby boy. Surgical repair of the sternum with the use of Prolene mesh was performed during the neonatal period without cardiac compression.

Herniation of part of the breast through a congenital defect of the superficial fascia of the anterior thoracic wall.

This report describes the management of a 28-year-old female patient who had herniation of part of her left breast through a defect in the superficial fascia of the anterior thoracic wall. Closure of the defect was associated with correction of the deformity. To the best of our knowledge, this is the first report describing such a lesion.

Stage IIB carcinoma of the cervix that is associated with pelvic kidney: A therapeutic dilemma.

Locally advanced cervical cancer with congenital pelvic kidney is reported uncommonly. A 50-year-old patient with stage IIB cervical cancer and pelvic kidney was treated with irradiation and concurrent chemotherapy. Follow-up evaluation for 2 years revealed normal renal function and no evidence of recurrent disease.

Presenting symptoms of epithelial ovarian cancer.

OBJECTIVES: Epithelial ovarian cancer is a common disease with a high mortality, the latter being frequently attributed to late diagnosis due to failure to recognise symptoms of early disease. This study was designed to determine any differences in symptomatology between patients with early and advanced stage disease. DESIGN: A retrospective cohort study of 100 patients with stage 1 disease and 100 with stage 3 disease. Ten consecutive patients with stage 1 disease and 10 with stage 3 disease were identified from the database of patients treated each year from 1990 to 1999. SETTING: A tertiary referral centre for gynecological malignancy. OUTCOME MEASURES: The nature and duration of symptoms, age at presentation, and the size, histologic type and grade of tumour were determined by chart review, and the findings compared using logistic regression analysis. RESULTS: Ninety percent of women with early, and 100% with advanced disease reported at least one symptom. With early disease, abdominal pain was reported by 51% and abdominal swelling by 32%, and with advanced disease abdominal swelling by 62% and abdominal pain by 44%. Seventy percent of the early stage and 69% of the advanced stage cohorts reported symptoms of less than 3 months duration. Tumours less than 5 cm diameter were three times more likely to have advanced disease (P = 0.02). Grade 1 tumours were 40 times more likely to be early stage than grade 3 tumours. Serous tumours occurred in 25% of patients with early disease, and 45% with advanced disease (P = 0.01). CONCLUSION: Patients with early stage ovarian cancer are likely to be younger and to have larger, better differentiated tumours that are more often non-serous histologically. Advanced disease is not invariably due to delayed diagnosis.

Patterns of recurrence and disease-free survival in advanced squamous cell carcinoma of the vulva.

OBJECTIVE: To compare patterns of recurrence and disease-free survival (DFS) of node-positive and node-negative patients with advanced vulval squamous cell carcinoma (SCC). METHODS: Fifty-five patients with FIGO stage III/IVA vulval SCC who had surgery at the Queensland Centre for Gynaecological Cancer from 1989 to 1999 were included. Patients were grouped as follows: Group A, pT3 N0; Group B, pT3 N1; Group C, pT4 N2. Treatment included surgery +/- postoperative radiotherapy. Multivariate Cox models were calculated to identify independent prognostic factors. RESULTS: After a median follow-up of 96 months, 25 patients (45.5%) experienced recurrence at the vulva (n = 2), pelvis (n = 8), or distant sites (n = 15). Recurrence in the pelvis and at distant sites was more likely for patients in groups B and C (P 0.003). At 5 years the probability of DFS was 66.6%, 35.3%, and 39.8% for patients in groups A, B, and C, respectively (P 0.085). Patients with negative nodes (n = 15), one microscopic positive node (n = 11), and two or more positive nodes (n = 29) had a probability of DFS of 66.6%, 67.3%, and 26.1% at 5 years, respectively (P 0.005). CONCLUSION: Patients with > or =2 positive groin nodes are at risk for distant failure. The DFS of patients with negative groin nodes and those with only one microscopic positive node is very similar. The prognosis of patients with > or =2 positive unilateral or bilateral groin nodes is similar. The current FIGO staging system inaccurately reflects prognosis for patients with advanced vulval cancer. Clinical trials are warranted to investigate the benefit of systemic treatment.