Sentinel Node Mapping in Ovarian Tumors: A Study Using Lymphoscintigraphy and SPECT/CT.

Purpose: Ovarian cancer in the early stage requires a complete surgical staging, including radical lymphadenectomy, implying subsequent risk of morbidity and complications. Sentinel lymph node (SLN) mapping is a procedure that attempts to reduce radical lymphadenectomy-related complications and morbidities. Our study evaluates the feasibility of SLN mapping in patients with ovarian tumors by the use of intraoperative Technetium-99m-Phytate (Tc-99m-Phytate) and postoperative lymphoscintigraphy using tomographic (single-photon emission computed tomography/computed tomography (SPECT/CT)) acquisition. Materials and Methods: Thirty-two patients with ovarian mass participated in this study. Intraoperative injection of the radiopharmaceutical was performed just after laparotomy and before the removal of tumor in utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum. Subsequently, pelvic and para-aortic lymphadenectomy was performed for malignant masses, and the presence of tumor in the lymph nodes was assessed through histopathological examination. Conversely, lymphadenectomy was not performed in patients with benign lesions or borderline ovarian tumors. Lymphoscintigraphy was performed within 24 hr using tomographic acquisition (SPECT/CT) of the abdomen and pelvis. Results: Final pathological examination showed 19 patients with benign pathology, 5 with borderline tumors, and 6 with malignant ovarian tumors. SPECT/CT identified SLNs in para-aortic-only areas in 6 (20%), pelvic/para-aortic areas in 14 (47%), and pelvic-only areas in 7 (23%) cases. Notably, additional unusual SLN locations were revealed in perirenal, intergluteal, and posterior to psoas muscle regions in three patients. We were not able to calculate the false negative rate due to the absence of patients with involved lymph nodes. Conclusion: SLN mapping using intraoperative injection of radiotracers is safe and feasible. Larger studies with more malignant cases are needed to better evaluate the sensitivity of this method for lymphatic staging of ovarian malignancies.

Single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Background: Low-risk gestational trophoblastic neoplasia could be cured in the case of appropriate management with single-agent chemotherapy. This study was carried out to compare the efficacy of single-dose methotrexate versus Actinomycin-D in low-risk gestational trophoblastic neoplasia to analyze the most effective agent. Methods: This retrospective cohort study was conducted on the medical record of 170 cases with the diagnosis of low-risk gestational trophoblastic neoplasia from 2012 to 2019 to evaluate the response rate of single-dose weekly-methotrexate versus biweekly-Actinomycin-D. Results: Single agent chemotherapy was required in 170 patients with final risk score of less than 7. Among the 100 cases under weekly-methotrexate therapy, 29 patients were required second-line chemotherapy with Actinomycin-D and combination therapy which means complete remission of 71% with methotrexate, in comparison with 78.5% in the other group. Resistance was mostly seen in patients with documented choriocarcinoma in histology who had not received timely diagnosis and treatment. Conclusion: Individualized decision in the management of low-risk gestational trophoblastic neoplasia cases, based on histology, HCG, and history is the corn stone in successful treatment.

Feasibility of sentinel lymph node mapping in ovarian tumors: A systematic review and meta-analysis of the literature.

Purpose of the report: Since the presence of lymph node metastases upstages the disease and to reduce the morbidity of total lymphadenectomy, sentinel lymph node (SLN) mapping in ovarian mass has been the focus of extensive research. This study aims to review all the literature associated with ovarian SLN mapping and assess the feasibility of ovarian SLN mapping. Materials and methods: PubMed and Scopus were searched using the following keywords: (Sentinel lymph node) AND (Ovary OR Ovarian) AND (Tumor OR Neoplasm OR Cancer). All studies with information regarding sentinel node biopsy in ovaries were included. Different information including mapping material, injection sites, etc., was extracted from each study. In total, two indices were calculated for included studies: detection rate and false-negative rate. Meta-analysis was conducted using Meta-MUMS software. Pooled detection rate, sensitivity, heterogeneity, and publication bias were evaluated. Quality of the studies was evaluated using the Oxford center for evidence-based medicine checklist. Results: Overall, the systematic review included 14 studies. Ovarian SLN detection rate can vary depending on the type of tracer, site of injection, etc., which signifies an overall pooled detection rate of 86% [95% CI: 75-93]. The forest plot of detection rate pooling is provided (Cochrane Q-value = 31.57, p = 0.003; I2 = 58.8%). Trim and fill method resulted in trimming of 7 studies, which decreased the pooled detection rate to 79.1% [95% CI: 67.1-87.5]. Overall, pooled sensitivity was 91% [59-100] (Cochrane Q-value = 3.93; p = 0.41; I2 = 0%). The proportion of lymph node positive patients was 0-25% in these studies with overall 14.28%. Conclusion: Sentinel lymph node mapping in ovarian tumors is feasible and seems to have high sensitivity for detection of lymph node involvement in ovarian malignant tumors. Mapping material, injection site, and previous ovarian surgery were associated with successful mapping. Larger studies are needed to better evaluate the sensitivity of this procedure in ovarian malignancies.

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.

Covid-19: What is the best approach in gynecological oncology patient management during the coronavirus pandemic?

Coronavirus (COVID-19) infection is a new major concern and a global emergency in almost all countries worldwide; due to the higher sensibility of cancer patients, they are more susceptible to severe and fatal infections, being nearly 10 times more likely than in healthy individuals infected with this virus. Although the aggressive nature of a cancer is a matter of concern, our exact role as oncologists in this time of restricted resources is not fully clarified. Regarding some consensus recommendation for postponing surgery, there is still an essential need for a single approved protocol regarding each type of malignancy. Iran, as one of the first involved countries in this crisis in Asia, which also has a high prevalence of gynecological malignancies, will certainly require an individualized decision-making schedule based on the most accepted global consensus opinion. Considering our restricted health system resources, herein we tried to introduce a logical gynecologic cancer management protocol based on the stage and survival expectancy of each tumor, along with reviewing all recent recommendations. The limited statistics published in this short period of time have obliged us to mainly focus on expert opinions, and the individualized clinical judgments should be agreed upon by multidisciplinary tumor board consensus. In conclusion, the COVID-19 pandemic overshadows all aspects of medicine, and decision making in gynecological oncology patients requires precise and appropriate judgment based on the available local resources.

Small Cell Neuroendocrine Cervical Carcinoma: A Case Report.

Objective: Small cell neuroendocrine cervical carcinoma is a neuroendocrine tumor with the great aggravation that comprises 0.5 to 3 percent of cervical tumors and progresses rapidly with early lymphogenous and hematogenous metastases. Case report: We reported a 40 years old woman with cervical cancer in stage IB2 that had radical hysterectomy with mistaken diagnosis of squamous cervical cancer. The disease has progressed after 50 days of surgery with a 6 cm tumor in vaginal cuff; review of pathology demonstrated small cell neuroendocrine cervical carcinoma. Conclusion: Recognition of this separate histopathological entity with IHC analysis is important. Chemoradiotherapy and multimodality therapeutic approaches could improve the survival rates.

Molar Changes With a Normal Viable Fetus: A Case Report.

Objective: The presence of a normal fetus with normal karyotype accompanied by molar changes in the placenta is a rare condition, which carries a significant risk to the mother and fetus. There is a controversy regarding the proper management of this condition. Here, we present the case of a singleton pregnancy that showed molar changes in the pathological study of the placenta, but ended up with a normal viable neonate. Case Report: A 23-year-old primigravida woman, with a 3-year history of infertility, presented with vaginal bleeding and spotting. Her ß-human chorionic gonadotropin (HCG) at 13th week was 36500 mIU/ml. Serial sonography assessments were suggestive for molar changes and a normal fetus with growth retardation but normal Doppler assessment. The patient underwent elective Cesarean section at 37 weeks gestation and a healthy female neonate with an Apgar score of 9-10, weighing 2270 g was born. Pathological assessment of the placenta confirmed the diagnosis of incomplete hydatidiform mole. After two months, the mother had no complications, her ß-HCG level was untraceable, and the infant was in good condition. Conclusion: Despite being a rare condition, partial moles can be accompanied by delivery of a normal fetus. The management of this condition still remains challenging and should be done under close monitoring with extreme caution.

Concordance Between Intracervical and Fundal Injections for Sentinel Node Mapping in Patients With Endometrial Cancer?: A Study Using Intracervical Radiotracer and Fundal Blue Dye Injections.

OBJECTIVE: A major controversy in sentinel node (SN) biopsy of endometrial cancer is the injection site of mapping material. We compared lymphatic drainage pathways of the uterine cervix and uterine body in the same patients by head-to-head comparison of intracervical radiotracer and fundal blue dye injections. METHODS: All patients with pathologically proven endometrial cancer were included. Each patient received 2 intracervical injections of Tc-phytate. At the time of laparotomy, the uterus was exposed, and each patient was injected with 2 aliquots of patent blue V (2 mL each) in the subserosal fundal midline locations. The anatomical locations of all hot, blue, or hot/blue SNs were recorded. RESULTS: Overall, 45 patients entered the study. At least 1 SN could be identified in 75 of 90 hemipelves (83.3% overall detection rate, 82.2% for radiotracer [intracervical] alone, and 81.1% for blue dye [fundal] alone). In 71 hemipelves, SNs were identified with both blue dye (fundal) and radiotracer (intracervical) injections. In 69 of these 71 hemipelves, at least 1 blue/hot SN could be identified (97.18% concordance rate). In 10 patients, para-aortic SNs were identified. All of these nodes were identified by fundal blue dye injection, and only 2 were hot. CONCLUSIONS: Our study shows that lymphatic drainage to the pelvic area from the uterine corpus matches the lymphatic pathways from the cervix, and both intracervical and fundal injections of SN mapping materials go to the same pelvic SNs.

Effect of Combination Therapy of Methotrexate with Vitamin A in Patients with Low Risk GTN (Gestational Trophoblastic Neoplasia).

Methotrexate as a single agent chemotherapy in most women with low risk gestational trophoblastic neoplasia (GTN) has been associated with high treatment rate. Combination of methotrexate with Vitamin A due to reduced number of chemotherapy regime courses is one of the treatment options for patients with low-risk GTN. Therefore, this study was performed with aim to determine the efficacy of combination therapy of Methotrexate with Vitamin A in low risk GTN treatment. This randomized clinical trial was performed on 49 patients with low risk gestational trophoblastic neoplasia. The treatment group (Group A = 19 cases) weekly received Methotrexate 50 mg/m2, and Vitamin A 200000 IU, intra-muscular, and the control group (Group B = 30 cases) only received Methotrexate 50 mg/m2 weekly. All patients were followed up for 8 weeks. Then, treatment outcomes were compared between two groups, and response to therapy was assessed in two groups by evaluation of HCG serum level. P < 0.05 was considered significant.Mean of B-HCG serum level after 4 weeks in Group A and Group B was 68.5 mIu/mL and 360 mIu/mL, respectively (P = 0.018), and after 8 weeks was 1 mIu/mL and 12 mIu/mL, respectively (P = 0.074). Combination therapy of Methotrexate and Vitamin A in low risk GTN is associated with shorter duration of chemotherapy.

Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer.

Genetic susceptibility in cervical cancer: From bench to bedside.

Cervical cancer (CC) is the third most common malignancy in women globally, and persistent infection with the oncogenic human papillomaviruses (HPV) is recognized as the major risk factor. The pathogenesis of CC relies on the interplay between the tumorigenic properties of the HPV and host factors. Host-related genetic factors, including the presence of susceptibility loci for cervix tumor is substantial importance. Preclinical and genome-wide association studies (GWAS) have reported the associations of genetic variations in several susceptibility loci for the development of cervical cancer. However, many of these reports are inconsistent. In this review, we discuss the findings to date of candidate gene association studies, and GWAS in cervical cancer. The associations between these genetic variations with response to chemotherapy are also discussed.

Therapeutic Potential of Targeting PI3K/AKT Pathway in Treatment of Colorectal Cancer: Rational and Progress.

PI3K/AKT/mTOR signaling pathway is one of the key dysregulated pathways in different tumor types, including colorectal cancer (CRC). Activation of this pathway is shown to be related with cellular transformation, tumor progression, cell survival, and drug resistance. There is growing body of data evaluating the value of PI3K/AKT/mTOR inhibitors in CRC (e.g., BEZ235, NVP-BEZ235, OSI-027, everolimus, MK-2206, KRX-0401, BYL719, and BKM120). This report summarizes the current knowledge about PI3K/AKT pathway and its cross talk with ERK/MAPK and mTOR pathways with particular emphasis on the value of targeting this pathway as a potential therapeutic target in treatment of colorectal cancer. J. Cell. Biochem. 119: 2460-2469, 2018. © 2017 Wiley Periodicals, Inc.

Clinical Significance and Prognosis Value of Wnt Signaling Pathway in Cervical Cancer.

Cervical cancer is among the most commonly diagnosed cancer in women, supporting the need for identification of novel prognostic and predictive biomarkers to predict the risk of developing of this malignancy or predict the prognosis of patients. Against this background, the activation of the Wingless-type (Wnt)/ß-catenin pathway has been suggested as the main dysregulated pathways, which is involved in the multistep process of cervical carcinogenesis, suggesting its value as a potential biomarker or therapeutic target. The aim of current review is to give an overview about the potential application of WNT pathway and its value which is differentially expressed in cervical cancer versus non-tumorigenic tissue as biomarker for risk stratification and predict the prognosis of patients with cervical cancer. J. Cell. Biochem. 118: 3028-3033, 2017. © 2017 Wiley Periodicals, Inc.

Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar Pregnancy.

BACKGROUND: Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies. OBJECTIVES: In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy. PATIENTS AND METHODS: In a prospective cross sectional study by using a high accuracy technique EnVision Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls. RESULTS: We studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%. CONCLUSIONS: Our data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages.