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1.
Hum Mutat ; 43(12): 1732-1744, 2022 12.
Article in English | MEDLINE | ID: mdl-35842788

ABSTRACT

Hydatidiform mole (HM) is an abnormal human pregnancy characterized by excessive growth of placental trophoblasts and abnormal early embryonic development. Following a first such abnormal pregnancy, the risk for women of successive molar pregnancies significantly increases. To date variants in seven maternal-effect genes have been shown to cause recurrent HMs (RHM). NLRP7 is the major causative gene for RHM and codes for NOD-like receptor (NLR) family pyrin domain containing 7, which belongs to a family of proteins involved in inflammatory disorders. Since its identification, all NLRP7 variants have been recorded in Infevers, an online registry dedicated to autoinflammatory diseases (https://infevers.umai-montpellier.fr/web/). Here, we reviewed published and unpublished recessive NLRP7 variants associated with RHM, scored their pathogenicity according to the American College of Medical Genetics classification, and recapitulated all functional studies at the level of both the patients and the conceptions. We also provided data on further variant analyses of 32 patients and genotypes of 36 additional molar pregnancies. This comprehensive review integrates published and unpublished data on NLRP7 and aims at guiding geneticists and clinicians in variant interpretation, genetic counseling, and management of patients with this rare condition.


Subject(s)
Hydatidiform Mole , Uterine Neoplasms , Humans , Female , Pregnancy , Adaptor Proteins, Signal Transducing/genetics , Placenta , Hydatidiform Mole/genetics , Genotype , Uterine Neoplasms/genetics
2.
BMC Pregnancy Childbirth ; 22(1): 681, 2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36057566

ABSTRACT

BACKGROUND: Coexistence of molar pregnancy with living fetus represents a challenge in diagnosis and treatment. The objective of this study to present the outcome of molar pregnancy with a coexisting living fetus who were managed in our University Hospital in the last 5 years. METHODS: We performed a retrospective analysis of patients who presented with molar pregnancy with a coexisting living fetus to our Gestational Trophoblastic Clinic, Mansoura University, Egypt from September, 2015 to August, 2020. Clinical characteristics of the patients, maternal complications as well as fetal outcome were recorded. The patients and their living babies were also followed up at least 6 months after delivery. RESULTS: Twelve pregnancies were analyzed. The mean maternal age was 26.0 (SD 4.1) years and the median parity was 1.0 (range 0-3). Duration of the pregnancies ranged from 14 to 36 weeks. The median serum hCG was 165,210.0 U/L (range 7662-1,200,000). Three fetuses survived outside the uterus (25%), one of them died after 5 months because of congenital malformations. Histologic diagnosis was available for 10 of 12 cases and revealed complete mole associated with a normal placenta in 6 cases (60%) and partial mole in 4 cases (40%). Maternal complications occurred in 6 cases (50%) with the most common was severe vaginal bleeding in 4 cases (33.3%). There was no significant association between B-hCG levels and maternal complications (P = 0.3). CONCLUSION: Maternal and fetal outcomes of molar pregnancy with a living fetus are poor. Counseling the patients for termination of pregnancy may be required. TRIAL REGISTRATION: The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492).


Subject(s)
Hydatidiform Mole , Uterine Neoplasms , Adult , Female , Fetus/pathology , Humans , Hydatidiform Mole/complications , Hydatidiform Mole/drug therapy , Hydatidiform Mole/pathology , Maternal Age , Pregnancy , Retrospective Studies , Uterine Neoplasms/drug therapy
3.
Clin Genet ; 99(6): 823-828, 2021 06.
Article in English | MEDLINE | ID: mdl-33583041

ABSTRACT

Recurrent hydatidiform moles (RHMs) are human pregnancies with abnormal embryonic development and hyperproliferating trophoblast. Biallelic mutations in NLRP7 and KHDC3L, members of the subcortical maternal complex (SCMC), explain the etiology of RHMs in only 60% of patients. Here we report the identification of seven functional variants in a recessive state in three SCMC members, five in NLRP7, one in NLRP5, and one in PADI6. In NLRP5, we report the first patient with RHMs and biallelic mutations. In PADI6, the patient had four molar pregnancies, two of which had fetuses with various abnormalities including placental mesenchymal dysplasia and intra-uterine growth restriction, which are features of Beckwith-Wiedemann syndrome and Silver Russell syndrome, respectively. Our findings corroborate recent studies and highlight the common oocyte origin of all these conditions and the continuous spectrum of abnormalities associated with deficiencies in the SCMC genes.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Autoantigens/genetics , Hydatidiform Mole/genetics , Mitochondrial Proteins/genetics , Mutation/genetics , Neoplasm Recurrence, Local/genetics , Nuclear Proteins/genetics , Protein-Arginine Deiminase Type 6/genetics , Beckwith-Wiedemann Syndrome/genetics , Beckwith-Wiedemann Syndrome/pathology , Female , Humans , Hydatidiform Mole/pathology , Neoplasm Recurrence, Local/pathology , Oocytes/pathology , Placenta/pathology , Pregnancy , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology
4.
Mod Pathol ; 31(7): 1116-1130, 2018 07.
Article in English | MEDLINE | ID: mdl-29463882

ABSTRACT

Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Hydatidiform Mole/genetics , Neoplasms, Second Primary/genetics , Proteins/genetics , Uterine Neoplasms/genetics , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Genotype , Humans , Pregnancy
5.
J Exp Ther Oncol ; 12(1): 9-15, 2017 May.
Article in English | MEDLINE | ID: mdl-28472559

ABSTRACT

BACKGROUND: Ovarian cancer has the highest mortality rate amongst all gynecologic malignancies. 90% of the cases are epithelial ovarian cancer (EOC). Ovarian cancer associated with reduction in the serum level of antioxidants super oxide dismutase (SOD) and glutathione peroxidase (GPX) and increasing in the serum level of Malondialdehyde (MDA). OBJECTIVE: To find correlation between oxidative stress and epithelial ovarian cancer. METHODS: In this cross-sectional study fifty-six female patients with EOC, twenty four female patients with benign ovarian tumors and ten healthy females were included in the current research study where serum level of SOD, GPX and MDA were measured. RESULTS: Levels of SOD and GPX were found to be significantly higher in benign group when compared with malignant group (P1<0.05). There was a significant negative association between malignancy and each of SOD and GPX (p<0.05). While there was a significant positive association between malignancy and MDA (p<0.05). There was a significant negative correlation between tumor stage and level of SOD and GPX (p<0.05). Moreover, there was a significance positive correlation between tumor stage and MDA (p< 0.05). CONCLUSION: Patients with epithelial ovarian cancer has decreased preoperative serum level of SOD and GPX antioxidants and increased level of MDA. These findings were associated with advanced tumor stage. The study confirmed the role of oxidative stress in development of epithelial ovarian cancer.


Subject(s)
Neoplasms, Glandular and Epithelial/blood , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Oxidative Stress/physiology , Adult , Aged , Aged, 80 and over , Antioxidants/metabolism , Carcinoma, Ovarian Epithelial , Case-Control Studies , Cross-Sectional Studies , Egypt , Female , Glutathione Peroxidase/blood , Humans , Male , Malondialdehyde/blood , Middle Aged , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Superoxide Dismutase/blood , Young Adult
6.
Int J Gynecol Cancer ; 26(7): 1351-3, 2016 09.
Article in English | MEDLINE | ID: mdl-27465884

ABSTRACT

Recurrent hydatidiform moles are defined by the occurrence of two or more molar pregnancies in the same patient. Familial recurrent hydatidiform moles (FRHM) is a rare autosomal recessive condition where women have an inherited predisposition to have molar pregnancies. Genotyping demonstrated that they are diploid and biparental. We report a case of FRHM from Egypt with a history of 6 recurrent complete moles. Sequencing of the NLPR7 gene revealed a deleterious homozygous base change in exon 2, c.197G>A, which would result in a truncated protein p.W66*. To the best of our knowledge, this mutation has not been described before.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Hydatidiform Mole/genetics , Adult , Female , Humans , Male , Mutation , Pregnancy , Recurrence
8.
J Exp Ther Oncol ; 10(4): 247-53, 2014.
Article in English | MEDLINE | ID: mdl-25509977

ABSTRACT

BACKGROUND: Cervical cancer remains a significant problem worldwide particularly in underdeveloped countries. It is necessary to have a persistent infection of the cervix with a high-risk or oncogenic human Papillomavirus (HPV) virus to develop cervical cancer. OBJECTIVES: To study the association between HPV and pre-invasive and invasive cancer cervix among patients referred to Early Cancer Detection Clinic of Obstetrics and Gynecology Department, Mansoura University Hospital, Delta region, Egypt. METHODS: Cervical specimens of 100 histologically confirmed premalignant and malignant cervical lesions were subjected to HPV detection and genotyping by extraction of DNA from cervical biopsy using a commercial PCR kit. RESULTS: HPV DNA testing was done, 36 cases were positive (36%). Correlations of age, duration of marriage, and parity were non significant (P = 0.56, 0.72, and 0.35 respectively) while correlations of residence, oral contraceptive use, smoking, and immunosuppresion were sig- nificant (P = 0.006, 0.001, 0.001, and 0.01 respectively). The prevalence of HPV in premalignant and malignant cervical lesions in our study was 39.5% & 33.3% respec tively. The commonest HPV genotypes associated with premalignant cervical lesions were HPV16; 11/17(64.7%) and HPV18; 11/17 (64.7%) mostly in the form of mul- tiple infections with HPV16+18; 7/17 (41.17%). The commonest HPV genotypes associated with malignant cervical lesions in our cases were HPV16; 15/19 (78.9%) and HPV18; 13/19 (68.42%) also in the form of multiple infections with HPV16+18; 10/19 (52.63%). CONCLUSION: The prevalence of HPV in premalignant and malignant cervical lesions was 39.5% & 33.3% respectively, this means that HPV is not the main cause of premalignant and malignant cervical lesions in Delta region in Egypt. HPV infection mostly in the form of multiple infections with HPV16+18 genotypes. Further studies are needed to clarify actual association of HPV and premalignant and malignant cervical lesions to determine the usefulness of HPV vaccination in our locality.


Subject(s)
Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Egypt , Female , Genotype , Human Papillomavirus DNA Tests/methods , Humans , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/pathology , Prevalence , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology
9.
J Exp Ther Oncol ; 10(3): 181-7, 2013.
Article in English | MEDLINE | ID: mdl-24416992

ABSTRACT

BACKGROUND: Ovarian tumors in the pediatric age group are not infrequent. Germ-cell tumors are the commonest ovarian neoplasm in the first two decades of life. Sex cord-stromal tumors are the most common ovarian tumors to cause precocious puberty in girls. PATIENTS AND METHODS: This retrospective study included all managed cases of malignant germ-cell and sex cord-stromal tumors in the pediatric age (less than 18 years). The medical records of the admitted cases from first of January, 2008 to 31 December, 2012 were reviewed and the following information was collected: patient age, clinical presentation, surgical stage, tumor histology, therapy, clinical course, and outcome. Serum alpha-fetoprotien on admission was studied. RESULTS: The study included 42 pediatric cases of germ-cell and granulosa cell tumors of the ovary. Mean age of the cases was 11.26 years (range: 7-15 years). Abdominal pain was the commonest presentation. Twenty-two cases (52.4%) were diagnosed as stage I disease. Twenty-eight cases (66.7%) were exposed to fertility sparing surgery. Age of the patient and site of tumor were significantly correlated to the survival (p value: 0.04 & 0.09 respectively). The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant (P value: 0.007, 0.001, and 0.001 respectively). Tumor size and histologic types were not significantly correlated to survival (P value: 0.19 & 0.67 respectively). CONCLUSION: The cumulative survival rate was 76.2%. The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant. Tumor size and histologic types were not significantly correlated to survival. Initial level of alpha-fetoprotein was not significantly correlated to survival or recurrence.


Subject(s)
Neoplasms, Germ Cell and Embryonal/mortality , Ovarian Neoplasms/mortality , Sex Cord-Gonadal Stromal Tumors/mortality , Adolescent , Child , Female , Humans , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Prognosis , Retrospective Studies , Sex Cord-Gonadal Stromal Tumors/pathology , Sex Cord-Gonadal Stromal Tumors/therapy
10.
J Exp Ther Oncol ; 10(3): 165-8, 2013.
Article in English | MEDLINE | ID: mdl-24416990

ABSTRACT

OBJECTIVES: To study the agreement of preoperative curettage and definitive histology after hysterectomy as well as the correlation of time factor and hormonal therapy to this agreement. METHODS: This retrospective study was done in the Departments of Obstetrics and Gynecology and Pathology, Faculty of Medicine, Mansoura University, Egypt. Pathology reports of patients exposed to dilatation and curettage followed by hysterectomy during the period from May, 2004 to April, 2011 were reviewed. RESULTS: We reviewed 83 cases who fulfilled the inclusion criteria. There were non-significant differences between findings of D&C and hysterectomy specimens (P = 0.42). The concordance rate between D&C and hysterectomy was 79.5%. One case of endometrial carcinoma (1.2%), one case of simple endometrial hyperplasia, one case of atrophic endometrium, and two cases of endometrial polyp were diagnosed only after hysterectomy (4.8%). Furthermore, histologic examination of hysterectomy specimens confirmed only 8 of 13 cases (61.5%) of endometrial hyperplasia with atypia. No significant correlation of time factor and hormonal therapy to the agreement between findings of D&C and hysterectomy specimens (P = 0.58 & 0.19 respectively). CONCLUSION: There was no significant difference between preoperative endometrial histology and hysterectomy specimens (P = 0.41).This agreement had not been significantly affected by time interval and hormonal therapy. Future researches with larger number of cases are needed to confirm or disagree with our findings.


Subject(s)
Dilatation and Curettage , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/pathology , Hysterectomy , Uterus/pathology , Adolescent , Adult , Aged , Endometrial Hyperplasia/surgery , Endometrial Neoplasms/surgery , Female , Humans , Middle Aged , Retrospective Studies , Time Factors
11.
J Exp Ther Oncol ; 10(2): 135-7, 2012.
Article in English | MEDLINE | ID: mdl-23350353

ABSTRACT

OBJECTIVES: To present our single institution experience with 10 cases of embryonal rhabdomyosarcoma diagnosed over 5 years. METHODS: Retrospective analysis of the medical records of 10 patients. The initial presenting data as age, complains and staging were analyzed. Surgical interference of all cases was studied. The follow up data regarding survival and recurrences were analyzed. RESULTS: The mean age at diagnosis was 4.3 years (range: 2-12). Six cases (60%) were subjected to "True Cut" biopsy and 4 cases (40%) were subjected to complete surgical excision of the tumor. All cases received chemotherapy. "Vincristine, Actinomycin D, Cyclophosphamide" combination was the most commonly used. Radiation therapy was used in 3 patients (30%) in the form of external beam radiation. The 5-year overall survival of our studied cases were 80%. CONCLUSION: The recurrence rate of our retrospectively studied 10 cases of embryonal rhabdomyosarcoma of vagina and cervix was high (70%). However, five-year survival was 80%. Combined modality treatment is essential to improve prognosis.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rhabdomyosarcoma, Embryonal/mortality , Uterine Cervical Neoplasms/mortality , Child , Child, Preschool , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dactinomycin/administration & dosage , Female , Follow-Up Studies , Humans , Medical Records , Prognosis , Radiotherapy Dosage , Retrospective Studies , Rhabdomyosarcoma, Embryonal/therapy , Survival Rate , Time Factors , Uterine Cervical Neoplasms/therapy , Vincristine/administration & dosage
12.
Arch Gynecol Obstet ; 285(2): 469-71, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21701836

ABSTRACT

OBJECTIVES: To study the outcome of fertility conserving surgery for ovarian tumors in children and young adults (≤ 20 years) over 6 years (2003-2009). METHODS: This prospective study included 183 patients diagnosed with ovarian cysts or tumors requiring surgical excision. Ovarian cystectomy/ovariectomy was carried out followed by frozen section histopathology. Malignant cases were subjected to staging laparotomy and fertility sparing surgery. RESULTS: The median age at diagnosis was 17 years (range 7-20 years). 160/183 (87.4%) were non-neoplastic ovarian cysts or benign tumors. In 131/160 (81.8%) of non-neoplastic and benign tumors, it was possible to preserve the affected ovary. Twenty cases (11%) were diagnosed as primary malignant ovarian tumors, 2/183 (1.1%) were borderline tumors and 1 case (0.55%) was metastatic colonic carcinoma. The median follow up of cases with primary malignant ovarian tumors was 36 months. During this period, two recurrences (9.1%) were detected, both of the germ cell type (immature teratoma and yolk sac tumor). Recurrent cases were managed by local excision and lymph node sampling followed by chemotherapy. CONCLUSION: Fertility sparing surgery for malignant ovarian tumors in children and young adults has excellent prognosis and should be attempted whenever possible.


Subject(s)
Fertility Preservation , Neoplasm Recurrence, Local/therapy , Organ Sparing Treatments , Ovarian Cysts/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Carboplatin/administration & dosage , Chemotherapy, Adjuvant , Child , Cisplatin/therapeutic use , Etoposide/therapeutic use , Female , Humans , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovariectomy , Paclitaxel/administration & dosage , Prospective Studies , Young Adult
13.
Arch Gynecol Obstet ; 286(2): 283-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22410958

ABSTRACT

OBJECTIVES: To study the outcome of pregnancies complicated by malignant disease, in particular neonatal morbidity and mortality after in utero exposure to chemotherapy. METHODS: This prospective study included 118 patients diagnosed with malignant disease for the first time during pregnancy over an 8-year period (March 2003-March 2011). Outcome of neonates born to mothers who received chemotherapy during pregnancy was studied and compared with a control group. RESULTS: The commonest cancer type diagnosed during pregnancy (56/118 = 47.45 %) was breast carcinoma followed by lymphoma/leukemia (32 = 27.12 %). Gynecological tumors (all ovarian) represented 10.16 %, soft tissue tumors 5.08 %, colorectal 4.23 %, thyroid 2.54 % and others 3.38 %. Sixty-one (51.64 %) women received chemotherapy (average 3 ± 2 cycles) during the second and third trimesters. The incidence of neonatal survival, preterm birth, small for gestational age and congenital malformations was not significantly different between women who received chemotherapy during pregnancy and the control group. Five (4.23 %) women with advanced disease died during or shortly after termination of pregnancy. CONCLUSION: In utero exposure to chemotherapy during the second and third trimesters of pregnancy carries minimal morbidity to the unborn fetus.


Subject(s)
Antineoplastic Agents/adverse effects , Pregnancy Complications, Neoplastic/drug therapy , Pregnancy Outcome/epidemiology , Adolescent , Adult , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Carcinoma/drug therapy , Carcinoma/mortality , Congenital Abnormalities/epidemiology , Female , Humans , Incidence , Infant, Newborn , Infant, Small for Gestational Age , Leukemia/drug therapy , Leukemia/mortality , Lymphoma/drug therapy , Lymphoma/mortality , Pregnancy , Pregnancy Complications, Neoplastic/mortality , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Premature Birth/epidemiology , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Young Adult
14.
J Exp Ther Oncol ; 9(3): 217-20, 2011.
Article in English | MEDLINE | ID: mdl-22070053

ABSTRACT

BACKGROUND: Post molar GTN was reported to occur in 7.5-20% of patients following evacuation of complete hydatidiform moles and in 2.5-7.5% following evacuation of partial moles. The role of uterine re-curettage in post molar GTN is not clear. OBJECTIVES: Study of the correlation of pre-evacuation and week- one level of hCG, and uterine re-curettage to the number of chemotherapy courses in treatment of post molar GTN. PATIENTS AND METHODS: This retrospective study included 29 cases of post molar GTN through reviewing their medical records. RESULTS: There were 25 cases (86.21) of low risk, and 4 cases of high risk score (13.79%). The 3 year survival was 96.6%. There were non-significant correlation of age, parity, pre-evacuation level and hCG in week-1 to number of chemotherapy courses, while uterine re-curettage was significantly correlated to number of chemotherapy courses (p = 0.04). CONCLUSION: Uterine re-curettage was significantly correlated to less number of chemotherapy courses in patients with post molar GTN (p = 0.04). Pre-evacuation and week-1 hCG were not correlated to number of chemotherapy cycles. A large prospective randomized trial to clarify the beneficial effect of uterine re-curettage is recommended.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/blood , Chorionic Gonadotropin/blood , Dilatation and Curettage , Hydatidiform Mole/drug therapy , Uterine Neoplasms/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Hydatidiform Mole/blood , Hydatidiform Mole/surgery , Leucovorin/administration & dosage , Methotrexate/administration & dosage , Pregnancy , Retrospective Studies , Uterine Neoplasms/blood , Uterine Neoplasms/surgery , Young Adult
15.
Arch Gynecol Obstet ; 283(3): 617-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20422422

ABSTRACT

PURPOSE: To study the value of pretreatment testing of P53 overexpression in selection of candidates for pelvic lymphadenectomy in clinical stage I endometrial carcinoma. PATIENTS AND METHODS: This prospective randomized clinical study included 38 patients with histologically confirmed endometrial carcinoma and staged clinically as stage I. Immunohistochemical staining of the tumor specimens obtained by dilatation and curettage with P53 monoclonal antibodies was done. The patients were randomized into two groups according to the planned surgical treatment: hysterectomy group and hysterectomy plus pelvic lymphadenectomy group. RESULTS: There was no significant difference in mean age, parity, medical status, surgical stage, histologic types, grade of differentiation, and myometrial invasion between the two groups. The survival rate in the hysterectomy group in our study was 82.4% and the recurrence rate was 17.6%, while in hysterectomy and lymphadenectomy group the survival rate was 81.0% and the recurrence rate was 19%. Adding pelvic lymphadenectomy was found to be associated with prolonged recurrence time in the P53-positive patients (24.07 vs. 17.8 months for group A). CONCLUSION: Pretreatment testing of P53 expression is recommended to help with other prognostic factors in the selection of candidates for pelvic lymphadenectomy in clinical stage I endometrial carcinoma.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/surgery , Endometrial Neoplasms/surgery , Hysterectomy , Lymph Node Excision , Tumor Suppressor Protein p53/metabolism , Biomarkers, Tumor/analysis , Carcinoma/mortality , Endometrial Neoplasms/mortality , Female , Humans , Immunohistochemistry , Neoplasm Staging , Survival Rate , Treatment Outcome , Tumor Suppressor Protein p53/analysis
16.
Afr Health Sci ; 20(1): 73-82, 2020 Mar.
Article in English | MEDLINE | ID: mdl-33402895

ABSTRACT

BACKGROUND: Gestational trophoblastic disease (GTD) defines a spectrum of proliferative disorders of trophoblastic epithelium of the placenta. Incidence, risk factors, and outcome may differ from one country to another. OBJECTIVE: To describe incidence, patient characteristics, treatment modalities, and outcome of GTD at Mansoura University which is a referral center of Lower Egypt. METHODS: An observational prospective study was conducted at the GTD Clinic of Mansoura University. The patients were recruited for 12 months from September 2015 to August 2016. The patients' characteristics, management, and outcome were reported. RESULTS: We reported 71 clinically diagnosed GTD cases, 62 of them were histologically confirmed, 58 molar (33 CM and 25 PM) in addition to 4 initially presented GTN cases. Mean age of the studied cases was 26.22 years ± 9.30SD. Mean pre-evacuation hCG was 136170 m.i.u/ml ±175880 SD. Most of the cases diagnosed accidentally after abnormal sonographic findings (53.2%). Rate of progression of CM and PM to GTN was 24.2% and 8%, respectively. CONCLUSION: The incidence of molar pregnancy and GTN in our locality was estimated to be 13.1 and 3.2 per 1000 live births respectively. We found no significance between CM and PM regarding hCG level, time to hCG normalization, and progression rate to GTN.


Subject(s)
Chorionic Gonadotropin/blood , Gestational Trophoblastic Disease/epidemiology , Hydatidiform Mole/blood , Placenta/pathology , Adolescent , Adult , Egypt/epidemiology , Female , Gestational Trophoblastic Disease/blood , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/surgery , Humans , Hydatidiform Mole/epidemiology , Hydatidiform Mole/pathology , Hydatidiform Mole/surgery , Incidence , Pregnancy , Prospective Studies , Treatment Outcome , Uterine Neoplasms/pathology , Vacuum Curettage , Young Adult
17.
Obstet Gynecol ; 133(5): 1024-1031, 2019 05.
Article in English | MEDLINE | ID: mdl-30969220

ABSTRACT

OBJECTIVE: To investigate the effect of second uterine curettage on the number of chemotherapy courses and relapse rate in low-risk postmolar gestational trophoblastic neoplasia. METHODS: In a phase III trial, patients with low risk gestational trophoblastic neoplasia were randomised (1:1) to a second curettage or no curettage group before methotrexate treatment. Eligibility criteria were serum human chorionic gonadotropin (hCG) level 5,000 international units/L or less and fit for treatment with methotrexate. Exclusion criteria were previous uterine perforation and life-threatening bleeding. With a two-sided 5% significance level and a power of 99%, a sample size of 44 patients per group was necessary to detect a mean reduction in 2.3 chemotherapy courses. The primary outcome was the number of chemotherapy courses required for hCG normalization. Secondary outcomes were needed for second-line treatment, toxicity, relapse rates, and variables associated with number of chemotherapy courses. RESULTS: From October 2011 through February 2016, 89 patients entered the study at the Mansoura Trophoblastic Clinic; in each group, 43 patients were included in the intention-to-treat analyses. Surgical complications did not occur. The mean number of chemotherapy courses required to reach hCG normalization was 4.4±2.2 SD in the control group vs 3.8±2.3 SD in the intervention group (P=.14). Groups were comparable in terms of second-line treatment needed to reach hCG normalization, and relapse within the first year. Only hCG levels related to the number of chemotherapy cycles required for hCG normalization. CONCLUSION: Second uterine curettage did not reduce the number of chemotherapy courses required or affect relapse rate in patients with low-risk postmolar gestational trophoblastic neoplasia. CLINICAL TRIALS REGISTRATION: Dutch Trial Registry, NTR3390.


Subject(s)
Curettage , Gestational Trophoblastic Disease/surgery , Uterine Neoplasms/surgery , Adult , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Combined Modality Therapy , Female , Gestational Trophoblastic Disease/drug therapy , Humans , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Pregnancy , Treatment Outcome , Uterine Neoplasms/drug therapy
18.
J Pathol Transl Med ; 53(3): 164-172, 2019 May.
Article in English | MEDLINE | ID: mdl-30813708

ABSTRACT

BACKGROUND: In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. METHODS: We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. RESULTS: The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). CONCLUSIONS: The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

19.
J Pathol Transl Med ; 51(4): 381-387, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28607326

ABSTRACT

BACKGROUND: Although the morphological features characteristic of products of conception specimens including molar pregnancies are well described, substantial histopathological similarities are observed between the different entities, especially in cases of early pregnancies. Furthermore, there are no current solid criteria that could predict cases with progression to persistent gestational trophoblastic disease. In this study, we aimed to determine the most specific histopathological and immunohistochemical features required for accurate diagnosis that can reliably predict the clinical behavior. METHODS: Sixty-five cases of products of conception were reviewed clinically and pathologically, and any progression to persistent gestational trophoblastic disease (GTD), if present, was noted. Pathological assessment of the archival material included re-cut sections of 5 µm in thickness, routine staining with hematoxylin and eosin and immunohistochemical staining of p57Kip2. RESULTS: Certain histopathological criteria were found to be significant in differentiation between complete hydatidiform mole (CHM) and partial hydatidiform mole including villous shape and outline, villous trophoblast hyperplasia, and atypia in extravillous trophoblasts. There were no significant differences in any morphological or immunohistochemical features between cases with or without subsequent development of GTD. CONCLUSIONS: Histopathological diagnosis of molar pregnancy remains problematic especially in early gestation. Their diagnosis should be stated after a constellation of specific histopathological criteria in order not to miss CHM. p57Kip2 immunohistochemistry is of great value in diagnosis of cases that had equivocal morphology by histopathological examination. However, there were no significant features to predict cases that subsequently developed persistent GTD.

20.
J Obstet Gynaecol India ; 66(5): 316-20, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27486275

ABSTRACT

BACKGROUND: Congenital anomalies of the kidney and urinary tract in the developing countries have a poor prognosis due to limited experience in antenatal and postnatal management. PATIENTS AND METHODS: A 3-year retrospective study was carried out from January 2011 to December 2013. The following data were collected and analyzed: maternal age, gravidity, parity, gestational age at diagnosis, and ultrasonography findings. Final diagnosis after birth, the performed surgeries, follow-up data, as well as survival at one year were also analyzed. RESULTS: The mean age of the included patients was 28 years (range 20-35 years). The mean parity was 1.7 (range 0-4). The mean gestational age at diagnosis was 26 weeks (range 15-36 weeks). Consanguinity was reported in 10 cases (24.4 %). There were 25 males and 16 females. Bilateral renal agenesis was the commonest type (19.5 %). The anomalies of kidneys and urinary tract in our cases were associated with other anomalies in 8 cases (19.5 %). Oligohydramnios was detected in bilateral renal agenesis and posterior urethral valve. Surgical interference during the first 6 months was performed in 6 cases; pyeloplasty for unilateral or bilateral hydronephrosis was performed in 5 cases; and excision of solitary renal cyst performed in one case. By the end of the first year, two of the three cases with chronic renal disease, who were under peritoneal dialysis, died, and three cases who had undergone pyeloplasty were lost to follow-up. CONCLUSION: Among the 41 cases with antenatally diagnosed renal and urinary malformations; bilateral renal agenesis was the commonest anomaly (19.5 %). There were high rates of induction of abortion, IUFD, and neonatal deaths. The poor outcome may be due to lack of experience in performing invasive therapeutic fetal procedures.

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