Clear-cell carcinoma originating from cesarean section scar: two case reports

Background: Clear-cell carcinoma arising from the surgical cesarean section scar is very infrequent. The present study reports two patients with clear-cell carcinoma arising from an abdominal wall scar 20 and 23 years after their last cesarean section. Case presentation: Both Iranian patients had prior cesarean sections nearly 20 years earlier. Patients 1 and 2 had transverse and vertical abdominal incisions, respectively. The initial clinical presentation was a huge lower abdominal mass at the site of the previous cesarean section scar. Both patients underwent abdominal wall mass biopsy. The histological analysis revealed the presence of malignancy. Both patients underwent full-thickness resection of the abdominal wall mass. All surgical margins were tumor-free; however, patient 1 had a very narrow tumor-free margin near the pubic symphysis. As the imaging report of patient 2 revealed the presence of a pelvic mass, the exploration of the intraperitoneal space, simple total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and the excision of enlarged pelvic lymph nodes were performed during the surgery. Six cycles of paclitaxel and carboplatin every 3 weeks as adjuvant chemotherapy was administered for both patients after the surgery. One of the patients had disease recurrence 5 months after the termination of chemotherapy, and the other is still disease-free. These two patients had similar pathology and received a similar initial adjuvant treatment; however, they were different in terms of the direction of tumor spread, tumor distance from the pubic symphysis, status of tumor margins, and surgical procedures. Conclusions: We encountered distinct prognoses in the clear-cell carcinoma of cesarean section scars presented herein. The researchers can recommend complete surgical excision of the abdominal wall mass with wide tumor-free margins, exploration of the abdominopelvic space, TAH, and BSO during the first surgery. © 2021, The Author(s)

Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial

Background: Human papillomavirus (HPV) is one of the most significant risk factors for cervical cancer. The HPV vaccine has a very significant impact on the incidence of cervical cancer. The present study aimed to investigate the impact of prophylactic quadrivalent HPV vaccine in the treatment of women with cervical intraepithelial neoplasia (CIN 1-3). Methods: This randomized controlled trial was conducted in the Shahid Sadoughi University of Medical Sciences (SSUMS), Yazd, Iran, from October 2011 to November 2015 in women with histologically confirmed residual/recurrent CIN 1 or high-grade CIN (CIN 2-3). Eligible women were assigned randomly to an intervention and a control group. Women in the intervention group were given HPV vaccinations while those in the control group were not. Participants were followed up for 24 months. Primary and secondary outcomes, and adverse effects of the treatment in the two groups were compared using Student's t test, the chi-square test, or Fisher's exact test. P values < 0.05 or less were considered statistically significant. Results: Three-hundred and twelve women were randomized to the two groups; the data of 138 in the intervention group and 104 in the control group were analyzed. The mean age of the women was 32.59 ± 4.85 years. Differences in age, marital status, and grades of CIN weren't significant between the two groups. At the end of the two-year follow-up period, the number of women with CIN 2-3 in the intervention and control groups was reduced by 75 (from 93 to 23) versus 40 (from 69 to 41). The efficacy of the HPV vaccine in women with CIN 1-3 was 58.7 (p = 0.018). No serious adverse effects related to the vaccines were reported. Conclusions: The prophylactic quadrivalent HPV vaccine after treatment may have a therapeutic effect in women with residual/recurrent CIN 1 or high-grade CIN (CIN 2-3). Trial registration: Iranian Registry of Clinical Trials, IRCT20190603043801N1. Registered 24 July 2019 - Retrospectively registered, http://www.irct.ir/user/trial/40017/view © 2020 The Author(s)

Hemoperitoneum due to bleeding from a vein overlying a subserous uterine myoma: A case report

Background: Fibroids are the most common pelvic tumors in women; serious complications are rare but can be life-threatening. Case presentation: We present a case report of a 38-year-old Persian woman with acute abdominal pain and a history of uterine fibroids. The patient refused to undergo a laparoscopic myomectomy. Her ultrasound examination revealed free fluid in the abdominal cavity, and her vital signs were indicative of vasogenic shock. A diagnostic laparoscopy was performed to identify and control the source of bleeding: 400 ml of blood and blood clots were removed. Active bleeding was seen from a vein overlying a subserosal myoma. A laparotomic myomectomy was performed, and the patient was discharged 3 days after surgery with no complications. Conclusion: Surgeons should consider the possibility of this complication in women with acute abdominal pain and a history of uterine leiomyoma. © 2020 The Author(s)

Accuracy of the Triple Test Versus Colposcopy for the Diagnosis of Premalignant and Malignant Cervical Lesions

Background: Despite the World Health Organization (WHO) recommendations concerning the use of alternative tests for the detection of cervical cancer precursor lesions in low-income countries, the accuracy of these tests is a debated issue. In the present study we compare the diagnostic accuracy of the triple test with that of colposcopy for the diagnosis of premalignant and malignant cervical lesions. Methods: A cross-sectional study was performed in 328 women referred to the gynecology clinic at Shahid Sadoughi Hospital, affiliated to Yazd University of Medical Sciences (SSUMS), Yazd, Iran, from March 2016 to June 2018. As the first step, a Pap smear was obtained from all participants. Visual inspection with acetic acid (VIA) and Lugol�s iodine (VILI) was performed in accordance with the known protocol. A colposcopy was then conducted in all participants, biopsy samples were obtained, and histological features studied. Finally, the results were compared by statistical analysis. Results: The age range of the participants was 30 - 50 years. Of 328 women, 60 (18.3 ) were postmenopausal. Two-hundred and five patients (62.5 ) had an abnormal Pap smear, 165 (50.3 ) had abnormal results on colposcopy, and 141 (43 ) had abnormal histopathology reports. The VIA was positive in 129 patients (39.3 ) and the VILI in 177 (54 ). The results of the triple test were reported to be positive in 205 cases (51.52 ). The sensitivity of the triple test in the detection of premalignant and malignant cervical lesions was 78.7 and 69 , respectively. The sensitivity and specificity of colposcopy in the detection of premalignant and malignant cervical lesions was 80.1 and 72.2 , respectively. The diagnostic accuracy of the triple test and colposcopy in the detection of premalignant and malignant cervical lesions was 73 versus 75 . Conclusion: Since the results of the study showed that the diagnostic accuracy of the triple test is equivalent that of colposcopy, the former may be used in low-income countries and areas lacking access to colposcopy. © 2020. All rights reserved

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Influence of the second stage of labor on maternal and neonatal outcomes in vaginal births after caesarean section: a multicenter study in Germany

Background: The American College of Obstetricians and Gynecologists (ACOG) introduced a new standard of care in 2014, extending the duration of the second stage of labor in order to reduce caesarean delivery (CD) rates and its severe complications. The aim of the present study is to evaluate success rates of trial of labor after caesarean section (TOLAC), as well as maternal and neonatal outcomes after the establishment of the recent guidelines. Methods: A retrospective study was performed at two large departments in Germany from January 2008 to January 2018. Patients undergoing TOLAC were divided into two groups. Group I (958 patients) was constituted before the establishment of the current guidelines, and Group II (588 patients) after the establishment of the guidelines. A subgroup analysis was performed to compare neonatal outcomes after successful TOLAC and operative vaginal delivery with those after failed TOLAC and secondary CD. Results: The success rate of vaginal births after cesarean section (VBAC) fell from 66.4 in Group I to 55.8 in Group II (p < 0.001). The median duration of the second stage of labor was statistically significantly longer in Group II than in Group I (79.3 ± 61.9 vs. 69.3 ± 58.2 min) for patients without previous vaginal birth. The incidence of operative vaginal delivery decreased from Group I to Group II (9.6 vs. 6.8). The incidence of third- and fourth-degree perineal lacerations, blood loss and emergency CD were similar in the two groups. Concerning the neonatal outcome, our groups did not differ significantly in regard of rates of umbilical artery cord pH < 7.1 (p = 0.108), the 5-min Apgar scores below 7 (p = 0.224) and intubation (p = 0.547). However, the transfer rates to the neonatal care unit were significantly higher in Group II than in Group I (p < 0.001). Neonatal outcomes did not differ significantly in the subgroup analysis. Conclusion: Extending the second stage of labor does not necessarily result in more vaginal births after TOLAC. Maternal and neonatal outcomes were similar in both groups. Further studies will be needed to evaluate the role of operative vaginal delivery and the duration of the second stage of labor in TOLAC. © 2021, The Author(s)

The Spatial Distribution of LGR5+ Cells Correlates With Gastric Cancer Progression

In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5+ cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5+ cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5+ cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5+ cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5+ cells were localized at the crypt base, and in GC LGR5+ cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category) and the nodal spread (N-category). Furthermore, patients with LGR5+ GCs had a shorter median survival (28.0±8.6 months) than patients with LGR5− GCs (54.5±6.3 months). Our results show that LGR5 is differentially expressed in gastrointestinal cancers and that the spatial histoanatomical distribution of LGR5+ cells has to be considered when their tumour biological significance is sought