Genetically re-engineered K562 cells significantly expand and functionally activate cord blood natural killer cells: Potential for adoptive cellular immunotherapy.

Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562). NK cell expansion; expression of lysosome-associated membrane protein-1 (LAMP-1), granzyme B, and perforin; and in vitro and in vivo cytotoxicity against B-cell non-Hodgkin lymphoma (B-NHL) were evaluated. In vivo tumor growth in B-NHL-xenografted nonobese diabetic severe combined immune deficient (NOD-scid) gamma (NSG) mice was monitored by tumor volume, cell number, and survival. CB MNCs cultured with MODK562 compared with WTK562 demonstrated significantly increased NK expansion (thirty-fivefold, p < 0.05); LAMP-1 (p < 0.05), granzyme B, and perforin expression (p < 0.001); and in vitro cytotoxicity against B-NHL (p < 0.01). Xenografted mice treated with MODK562 CB experienced significantly decreased B-NHL tumor volume (p = 0.0086) and B-NHL cell numbers (p < 0.01) at 5 weeks and significantly increased survival (p < 0.001) at 10 weeks compared with WTK562. In summary, MODK562 significantly enhanced CB NK expansion and cytotoxicity, enhanced survival in a human Burkitt's lymphoma xenograft NSG model, and could be used in the future as adoptive cellular immunotherapy after umbilical CB transplantation. Future directions include expanding anti-CD20 chimeric receptor-modified CB NK cells to enhance B-NHL targeting in vitro and in vivo.

Hyperreactio luteinalis in pregnancy and hyperandrogenism: a case report.

BACKGROUND: Hyperreactio luteinalis in pregnancy is associated with theca lutein cysts (TLCs) and androgenization. CASE: A 24-year-old, primigravid woman was referred at 35 weeks' gestation for bilateral enlarged cystic ovaries. She showed signs of androgenization. On ultrasonogram the ovaries bore a spoke-wheel appearance. A nonvirilized female infant was subsequently delivered by cesarean section because of obstruction of the birth canal by a large impacted ovarian cyst. There was an initial delay in lactogenesis; however, it was well-established after regression of the TLC, by postpartum week 6. Signs ofandrogenization resolved and testosterone levels returned to normal by 3 months postpartum. CONCLUSION: Hyperreactio luteinalis is associated with TLC and maternal androgenization in the antepartum period and persists into the postpartum period with subsequent resolution. Aromatization of testosterone in hyperreactio luteinalis prevents fetal virilization, unlike that seen with masculinizing ovarian tumors. There is some evidence of genetic predisposition and a possibility for recurrence in future pregnancies.

Complete hydatidiform mole and live fetus in a singleton pregnancy with confined placental mosaicism and fetomaternal hemorrhage: a case report.

BACKGROUND: Coexistence of complete mole and a live fetus is uncommon (1:22,000-100,000), more so with euploidy. CASE: We present a case of a molar pregnancy with a euploid fetus who had close fetal evaluation for second trimester bleeding. The patient presented at 29 weeks' pregnancy with decreased fetal movements, a result of fetomaternal hemorrhage. She underwent cesarean section and delivered a live infant. By close follow-up and a multidisciplinary approach, the appropriate diagnosis and a favorable outcome were achieved. Both mother and the child at 5 years of age are doing well. CONCLUSION: Detailed anatomic and molecular studies demonstrated a complete mole resulting from confined placental mosaicism, with molar tissue showing a single paternal allele at 8/8 informative loci, all shared with the fetus, thus this coexistent molar pregnancy was not that of a separate conceptus.

Overexpression of HOXB5, cyclin D1 and PCNA in congenital cystic adenomatoid malformation.

OBJECTIVE: We investigated the patterns of expression of HOXB5, cyclin D1 and proliferating cell nuclear antigen (PCNA) proteins in human congenital cystic adenomatoid malformation (CCAM) to establish the molecular basis of its etiology. METHODS: Immunohistochemistry was performed on frozen archival specimens of CCAM and normal lung tissue as controls using antibodies against HOXB5, cyclin D1 and PCNA proteins. RESULTS: Immunohistochemistry revealed a higher level of expression of HOXB5, cyclin D1 and PCNA predominantly in mesenchymal cells of the CCAM tissues as compared to normal adjacent control lung tissues. CONCLUSION: Elevated levels of immunohistochemical detection of HOXB5, cyclin D1 and PCNA were characteristic properties of lung tissue cells in CCAM. This elevated HOXB5 expression may correlate with the aberrant cellular differentiation observed in the CCAM disorder. Elevated expression of cyclin D1 and PCNA further suggests that increased cellular proliferation contributes to the overgrowth of lung tissue in CCAM.

Prenatal diagnosis of urinary ascites in a fetus with meningomyelocele.

Fetal or neonatal urinary ascites is a rare phenomenon, particularly when secondary to rupture of a neuropathic bladder in a fetus with meningomyelocele. To date, all similar cases have only been diagnosed in the neonatal period. We report a case of urinary ascites secondary to rupture of a neuropathic bladder, which was successfully diagnosed via fetal paracentesis at 37 weeks. The infant was delivered by elective cesarean section and managed immediately with therapeutic paracentesis and bladder catheterization. Voiding cystourethrogram on the fifth day of life showed the bladder had spontaneously healed. Early diagnosis and prompt intervention for bladder complications diagnosed in utero may prevent or minimize adverse consequences.

Monoamniotic twins in contemporary practice: a single-center study of perinatal outcomes.

OBJECTIVE: The previous studies of monochorionic monoamniotic (MCMA) twins reported perinatal mortality rates as high as 70-80%. The recent trends have been towards significantly improved outcomes, though results from all studies have not been consistent. METHOD: A retrospective cohort analysis of all MCMA pregnancies > or =20 weeks delivered in a single university institution from 2001 to 2009, using a computerised hospital database. MCMA twins are managed by a close antenatal surveillance program, preferably elective admission at 26-28 weeks, daily non-stress tests, regular assessment of fetal growth with the goal of cesarean delivery by 34 weeks. RESULTS: Of the 25 MCMA pregnancies delivered, 98% (49/50) of twins were live-born. All women were delivered by cesarean section. There was one intrauterine fetal demise, which was secondary to anencephaly. There were three neonatal deaths, two in association with complex congenital heart disease. One twin died outside the neonatal period following cardiac surgery. In total, 28% (7/25) of pregnancies were complicated by major congenital anomalies. There was one case of mild transient twin-twin transfusion syndrome (TTTS). The overall perinatal mortality rate for non-anomalous twins was 2.4% (95% CI = 0.06%-13.59%). CONCLUSIONS: Traditionally quoted as up to 80%, perinatal mortality rates <10% for MCMA twins are achievable in contemporary practice. It is vital that these high-risk pregnancies are managed in experienced centers with close surveillance and appropriate pediatric support.

Peritoneal inclusion cysts: a review.

OBJECTIVE: To provide a comprehensive review of peritoneal inclusion cysts in the female patient population. To define the optimal diagnostic modalities and review the medical and surgical options for management, enabling the gynecologist to individualize treatment for patients. DATA SOURCES: We searched the MEDLINE database for articles with keywords "peritoneal inclusion cyst" and "benign (multicystic) mesothelioma." Our search was limited to the English language. All reports included a tissue-confirmed diagnosis, except 1. Case reports and case series with adolescent and adult patients were reviewed. METHOD OF STUDY: We evaluated all studies meeting our criteria for clinical features, histologic criteria for diagnosis, imaging and laboratory studies, and treatment modalities. TABULATION, INTEGRATION, AND RESULTS: Fifty-two descriptive studies and 1 prospective cohort study meet criteria for review. Eleven articles focused on imaging modalities. Nineteen articles depicted histopathology. Eight addressed treatment modalities. CONCLUSION: This is a comprehensive review of peritoneal inclusion cysts. We specifically focus on the method of diagnosis and management. There is no standard algorithm by which the patients are evaluated, treated, or followed up. Peritoneal inclusion cysts have minimal mortality but high morbidity. Diagnosis is made by clinical history, ultrasound imaging, and CA-125 correlation. Magnetic resonance imaging is useful if ultrasound is unclear. Tissue sample is necessary for definitive diagnosis. Prior studies have suggested that cure is only accomplished with surgical resection; however, patients have a 50% risk of recurrence. We suggest that the goal for such a chronic disease should not be cure, but symptomatic relief through individualization of treatment. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize imaging characteristics of peritoneal inclusion cysts, explain the epidemiology and risk factors for the development of peritoneal inclusion cysts, and describe possible treatment options for peritoneal inclusion cysts.

Peritoneal inclusion cyst: effects on fertility and antepartum course.

BACKGROUND: Hormone changes are thought to influence the etiology and disease process of peritoneal inclusion cysts. The effects of fertility and pregnancy on preexisting cysts are unknown. CASE: A 29-year-old woman with recurrent peritoneal inclusion cyst and primary infertility conceived spontaneously after hysterosalpingogram. She presented in the first trimester with rapid, symptomatic enlargement of a 22-cm peritoneal inclusion cyst. Ultrasonogram-guided aspiration was performed. The remainder of her pregnancy and postpartum course were uncomplicated. CONCLUSION: The presence of a large peritoneal inclusion cyst does not preclude fertility. Pregnancy, a hyperestrogenic state, together with rising human chorionic gonadotropin is a risk for recurrence or enlargement of a preexisting peritoneal inclusion cyst. After conservative management with cystocentesis, there was no further enlargement as pregnancy progressed.

Rupture of the primigravid uterus: a review of the literature.

UNLABELLED: Uterine rupture is a catastrophic obstetric complication, associated with high rates of perinatal morbidity and mortality. The most common risk factor is previous uterine surgery, and most cases of uterine rupture occur in women with a previous cesarean delivery. Traditionally, the primigravid uterus has been considered almost immune to spontaneous rupture. In fact, although spontaneous rupture of the primigravid uterus is indeed a very rare event, a number of such cases have been reported recently. Prompt recognition of uterine rupture and expeditious recourse to laparotomy are critical in influencing perinatal and maternal morbidity. Not all uterine ruptures present with the typical clinical picture of abdominal pain, hypovolemia, vaginal bleeding, and fetal compromise. Therefore, it is important to maintain a high index of suspicion for uterine rupture in women presenting with some, or all, of these features, regardless of parity. Here we provide a systematic review of cases of spontaneous uterine rupture in primigravid women reported in the literature to date. Clinical presentation, differential diagnosis, common etiological factors, complication rates, and appropriate management of this rare obstetric event are discussed. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that uterine rupture in a primigravida is a rare event, without typical signs and symptoms, and explain that the morbidity and mortality of the mother and child is directly related to a high index of suspicion and prompt treatment by the clinician.