Fertility outcomes after treatment with intraperitoneal chemotherapy.

Intraperitoneal chemotherapy (IPC) administration has been added to the therapeutic protocols of cancers, confined to the abdominal cavity. Since, a survival benefit in patients treated with adjuvant IPC has been demonstrated, fertility questions are raised in these patients. A comprehensive search of the English literature of PubMed/MEDLINE, EmBase and Google Scholar databases was conducted, from their inception until April 2021, following the MOOSE guidelines. Twelve out of 473 studies were included in the final review and analysis. After treatment with IPC for peritoneal carcinomatosis, 19 women, who underwent fertility-sparing surgery, with 20 successful pregnancies were reported. The mean interval time between IPC and pregnancy was 38.4 months (range 9-168 months). In 16 cases, conception was spontaneous, three required in vitro fertilisation, whereas one pregnancy was achieved through intrauterine insemination. Mean disease-free survival was 76 months (range 24-177 months). Childbearing is a feasible approach in selected patients, after treatment with IPC. When future pregnancy is desirable, a multidisciplinary team of surgeons, gynaecologists, oncologists and reproductive specialists is required, to inform the patient thoroughly about the fertility preservation alternatives, without endangering patient's survival.

A comprehensive review of childbearing after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: Our aim is to present a review on childbearing following CRS and HIPEC for peritoneal malignancy. METHODS: A review of the English literature, up to December 2019, was conducted, using PubMed/MEDLINE, EmBase and Google Scholar bibliographic databases, following the MOOSE guidelines. The terms "Cytoreductive Surgery", "Hyperthermic Intraperitoneal Chemotherapy", "Peritoneal Carcinomatosis", "Pregnancy", "Fertility Preservation", "Conception" were used. All study designs were eligible for inclusion in the final analysis. RESULTS: In total, 7 studies (5 case reports and 2 case series) were included in the final analysis, reporting on 14 successful pregnancies after CRS and HIPEC. The mean age of patients at the time of CRS/HIPEC was 28.8 ± 5.9 years (range 18-36), while the mean interval between CRS/HIPEC and pregnancy was 29.6 ± 20.3 months (range 9-80 months). Nine patients were treated for pseudomyxoma peritonei, four for primary peritoneal mesothelioma and one for endocrine carcinoma. Mean Peritoneal Carcinomatosis Index was 9.8 ± 7.8 (range 1-26). All patients underwent fertility-sparing CRS (preservation of at least one ovary and the uterus). In 12 cases, conception was spontaneous, whereas two pregnancies were achieved through in-vitro fertilization. One patient developed gestational hypertension, while two labors were preterm. Mean disease-free survival was 64.1 months (range 24-106 months). CONCLUSION: A successful pregnancy is feasible in selected patients, after CRS and HIPEC. Assisted reproduction techniques (IVF using frozen oocytes or frozen embryos, ovarian tissue cryopreservation, preoperative treatment with GnRH analogs) should be discussed pre-operatively with the patient, without, however, compromising overall survival or risking locoregional recurrence.

Budesonide use and misuse in sports: Elimination profiles of budesonide and metabolites after intranasal, high-dose inhaled and oral administrations.

Budesonide (BUD) is a glucocorticoid (GC) widely used in therapeutics. In sports, the World Anti-doping Agency (WADA) controls the use of GCs, and WADA-accredited laboratories use a reporting level of 30 ng/mL for 6ß-hydroxy-budesonide (6ßOHBUD) to detect the systemic administration of BUD. In the present work, we examined the urinary excretion profile of 6ßOHBUD, BUD, and 16α-hydroxy-prednisolone (16αOHPRED) after intranasal (INT), inhaled (INH) (at high doses) and oral administrations in male and female volunteers. BUD was administered to healthy volunteers using INT route (256 µg/day for three days, n = 4 males and 4 females), INH route (800 µg/day for three days, n = 4 males and 4 females, and 1600 µg/day for three days, n = 4 males) or oral route (3 mg, n = 8 females). Urine samples were collected before and after administration at different time periods, and were analyzed by liquid chromatography-tandem mass spectrometry. 6ßOHBUD and BUD concentrations were very low after INT treatment (0.0-7.1 and 0.0-8.1 ng/mL, respectively), and higher after INH treatments (0.0-35.4 and 0.0-48.3 ng/mL, respectively). For 16αOHPRED, elevated concentrations were detected after INT and INH treatments (2.6-66.4 and 3.4-426.5 ng/mL, respectively). Concentrations obtained following oral administration were higher than after therapeutic administrations (2.8-80.6, 1.5-36.1, and 10.4-532.2 ng/mL for 6ßOHBUD, BUD, and 16αOHPRED, respectively). After all administrations, concentrations were higher in males than in females. Results demonstrated that 6ßOHBUD is the best discriminatory marker and a reporting level of 40 ng/mL was found to be the best criterion to distinguish allowed from forbidden administrations of BUD.

Management of stage Ia1 squamous cervical cancer and the importance of excision margins: a retrospective study of long-term outcome after 25 years of follow-up.

OBJECTIVE: The aim of this study was to assess the effect of the excision margin after cone for stage Ia1 cervical cancer on long-term outcomes. STUDY DESIGN: Retrospective observational study. Patients were divided into 3 groups. Group A underwent immediate reflex hysterectomy; group B had cervical intraepithelial neoplasia (CIN) at the margins but were followed up; group C had clear margins. RESULTS: We identified 111 women: 19 (17.1%) in group A; 29 (26.1%) in group B; and 63 (56.8%) in group C. Women in group A were older (median, 40 years vs 35 years; P = .0001) with higher rate of endocervical margin involvement (89.5 vs 48.1%, P = .007) than in group B. The women had been followed for a total of 960 woman-years with median follow-up of 398 weeks (quartiles: 258,612). Women with clear margins in the initial excision were more likely to remain free of disease than those with involved (P < .0001). Further surgery was required due to abnormal cytology in 9 (31.0%) women from group B and 7 (11.1%) from group C (P = .04). The cumulative rate of recurrent CIN2+ was 6.4% in group B and 2.7% in group C (P = .17). In group B, recurrences were more common in positive endocervical rather than ectocervical margins (66.6% vs 33.4%, P < .05); all had high-grade CIN at the margins. CONCLUSION: The risk of posttreatment CIN2+ is substantially reduced when complete excision is achieved at first treatment. Conservative management is contraindicated in women with microinvasion at the margin. When CIN involves the margin, there is a greater risk of residual disease and of further treatment.

Long-term compliance with follow-up after treatment for cervical intra-epithelial neoplasia.

OBJECTIVE: To assess the level of compliance with follow-up over time after treatment for preinvasive and Stage Ia1 lesions of the cervix. To compare the average interval between visits with the interval prescribed by protocol and to evaluate the use of this difference as a measure of compliance. DESIGN: Retrospective observational study. Setting. London university hospital. POPULATION: Women who received treatment for preinvasive (CINI-III, AIS) or Stage Ia1 cervical lesions. METHODS: Attendance data were obtained from hospital-based colposcopy and community-based databases. MAIN OUTCOME MEASURES: The average interval between the appointments attended by each woman was compared with the planned interval between visits. The time that elapsed since the previous appointment attended was calculated for each visit and correlated with the time since treatment. RESULTS: 1013 women attended 4128 follow-up visits in the colposcopy clinic and in the community. Twenty-two (2.2%) women never attended any post-treatment appointment and 209 (21.0%) of the 991 women who attended at least once, did so on average more than 12 months later than specified by the follow-up protocol. There was a highly significant correlation between the interval since the previous appointment and the time since treatment (Kendall's tau b = 0.529614, two-sided p < 0.0001), showing that compliance deteriorates with increasing time since treatment. CONCLUSIONS: Comparing the average interval between attendances with the planned interval prescribed by protocol is a sensitive measure of compliance. Compliance with follow-up deteriorates significantly with time since treatment. This decline in compliance may contribute to the increased risk of invasive disease after treatment.

Antepartum and postpartum serum heme oxygenase-1 levels in preeclamptic and normotensive pregnant women.

AIM: To determine antepartum and postpartum serum heme oxygenase-1 (HO-1) levels in pre-eclamptic (PE) and normotensive pregnant women and to investigate the relationship between HO-1 levels and severity of PE. PATIENTS AND METHODS: Ten normotensive women were compared to 9 women with mild PE and 12 women with severe PE. Serum HO-1 levels were measured at 30-34 gestational weeks and 12-14 weeks postpartum. RESULTS: The severe PE group had significantly higher serum HO-1 levels antepartum compared to the mild PE and normotensive groups (5.50 ± 1.54 vs. 3.04 ± 0.72 ng/ml, p=0.0003, and 5.50 ± 1.54 vs. 3.12 ± 1.57 ng/ml, p=0.002, respectively). Serum HO-1 levels decreased significantly postpartum in the normotensive group only (3.12 ± 1.57 vs. 2.00 ± 0.97 ng/ml, p=0.0005). In the severe PE group, HO-1 levels antepartum were positively correlated to mean blood pressure (r=+0.79, p=0.004). CONCLUSION: Severe PE is associated with elevated serum HO-1 levels both antepartum and postpartum, suggesting a key role of chronic oxidative stress in the pathogenesis of PE and the endothelial dysfunction of these patients later in their life.

Antepartum and postpartum maternal plasma levels of E-selectin and VE-cadherin in preeclampsia, gestational proteinuria and gestational hypertension.

OBJECTIVE: To investigate the alterations of maternal antepartum and postpartum plasma levels of sE-selectin and VE-cadherin in normotensive pregnant women, women with preeclampsia (PE), gestational hypertension (GH), and gestational proteinuria (GP). METHODS: A total of 37 pregnant women were included in the present study; 12 with PE, 10 with GH, 5 with GP, and 10 controls. sE-selectin and VE-cadherin levels were assessed in maternal plasma at three periods; before delivery, 3-6 days after delivery, and 12-14 weeks postpartum. RESULTS: Women with severe preeclampsia (SPE) and GP had significantly higher plasma sE-selectin levels as compared to controls in all three periods of sampling. In the GH group, sE-selectin levels did not differ from controls. During the study, even after 12 weeks postpartum, the plasma sE-selectin levels remained unchanged in all preeclamptic groups (PE, GH, and GP). There was no difference in VE-cadherin levels between women with preeclampsia (PE, GH, and GP) and normal pregnancies. CONCLUSIONS: We found no changes in VE-cadherin levels in preeclamptic groups. Increased antepartum and postpartum levels of sE-selectin in women with SPE and GP suggest that endothelial dysfunction may be one of the key processes in the pathogenesis of PE and the underlying mechanism, as well, that links PE with cardiovascular disease in later life. GP, also, appears to be a mild variant of PE.

Complete pelvic lymphadenectomy in patients with clinical early, grade I and II endometrioid corpus cancer.

AIM: To investigate the risk of pelvic lymph node metastasis in patients with a preoperative diagnosis of early endometrial cancer with favorable histological characteristics, assessed by complete pelvic lymphadenectomy. PATIENTS AND METHODS: A total of 108 patients with clinical early endometrioid grade I or II endometrial carcinoma underwent complete pelvic lymphadenectomy between 2001-2007. Only cases with at least 15 nodes histologically examined were included. All operations were performed by the same team. The preoperative tumor histology was compared with the final pathological findings. The incidence of pelvic nodal involvement was estimated in relation to the final grade and depth of myometrial invasion in halves. RESULTS: The median age of patients was 63 years. In the final histology, 10 tumors (9.3%) of non-endometrioid histology were found. The discordance between pre- and postoperative tumor grade was 32.4%, with 24.1% being upgraded. Nine patients (8.3%) had poorly differentiated tumors and 23 (21.3%) deep (>50%) myometrial invasion in the final pathology. A total of 11 patients (10.2%) had pelvic nodal metastasis. The rate of lymph node metastasis in relation to final grade I and II and myometrial invasion was as follows: grade I, 1.8% (inner half 0%, outer half 14.3%); grade II, 15.9% (inner half 12.1% outer half 27.3%). Overall 19.4% of patients were upstaged at surgery. CONCLUSION: A significant proportion of patients presenting with early endometrial cancer of optimal characteristics will have a more advanced disease at surgical staging. Complete pelvic lymphadenectomy may increase the possibility of detecting metastatic disease in the lymph nodes.

Full-term pregnancies after multiple hepatobiliary operations for choledochal cyst: a case report.

Choledochal cysts are rare congenital cystic dilatations of the biliary tree. Choledochal cysts in pregnancy are a rare entity and represent a diagnostic and therapeutic challenge. The authors present a case of two full-term pregnancies in a woman who underwent multiple hepatobiliary operations for a choledochal cyst. The patient had two major problems: a type IV(a) choledochal cyst with atrophy of the left side of the liver and a congenitally dilated pancreatic duct in the head of the gland. She underwent a drainage surgical procedure using a Roux loop of jejunum and a revision surgery in which complete excision of the cyst and hepaticojejunostomy was performed. The surgical management was completed by a left lateral hepatic segmentectomy. During her first pregnancy, she experienced an episode of cholangitis, most probably due to the remaining congenitally dilated pancreatic duct. In succeeding years, the patient presented with recurrent pancreatitis and finally she underwent a Whipple operation. After that, the patient had a second pregnancy without any complications from the biliary tract system. Although choledochal cysts rarely occur in pregnancy, clinicians should be aware of this condition, as delayed or inappropriate therapy may be catastrophic for both the mother and the fetus.

Intraoperative gross assessment of myometrial invasion and cervical involvement in endometrial cancer: Role of tumor grade and size.

OBJECTIVES: To evaluate the accuracy of visual examination of myometrial invasion and the involvement of the cervix in the hysterectomy specimen and to explore the role of tumor grade and size in the accuracy of gross estimation of myometrial invasion. METHODS: In 142 patients with apparent early endometrial cancer the uterus was opened after its removal and inspected. The size of the tumor (2 cm), the depth of myometrial invasion (less or greater than 50%) and the involvement of the cervix (as positive or negative) were visually estimated and recorded. All patients underwent surgical staging. The gross findings were compared with the final histological results. Estimations of myometrial invasiveness were analyzed according to the tumor grade and size. Accuracy, specificity, sensitivity, positive and negative predictive values were calculated. RESULTS: The overall accuracy rate for myometrial invasion was 81.7% (116/142). False positive and false negative results noted in 17/101 (17%) and 9/41 (21.9%) of patients. Sensitivity, specificity, positive and negative predictive values were 78%, 83.2%, 65.3% and 90.3% respectively. Gross estimation of invasion was more often successful in patients with smaller (

Abnormal uterine bleeding as a presentation of metastatic breast disease in a patient with advanced breast cancer.

BACKGROUND: Extragenital carcinomas secondarily involving the uterus are very rare and they usually occur as a manifestation of widespread disease. When the metastases involve the endometrium in a diffuse, permeative pattern, sparing the glands, they may cause problems in the diagnosis. CASE: A case of metastatic carcinoma to the endometrium with a decidua-like pattern is reported. The patient had a history of breast carcinoma and presented with vaginal bleeding. The pathologic findings in the uterine curettings raised the differential diagnosis between metastatic breast carcinoma and non-neoplastic stromal lesions. The presence of nuclear atypia and mitotic activity along with the appropriate immunohistochemical findings revealed the neoplastic nature of the endometrial lesion and confirmed its origin from the breast. CONCLUSION: Unusual uterine bleeding in a patient with breast cancer should alert the gynecologist to the possibility of metastatic breast disease. Furthermore, the metastasis to the uterus and to other organs of the genital tract can be considered as a preterminal event.

Adnexal torsion during pregnancy: report of four cases and review of the literature.

Adnexal torsion is a rare cause of acute abdominal pain during pregnancy. It is frequently associated with ovarian stimulation for in vitro fertilization (IVF) or with ovarian masses, mainly of functional origin. The clinical, laboratory and imaging findings are non-specific. The authors present four cases with adnexal torsion diagnosed during the first trimester of pregnancy. The clinical picture, the mode of diagnosis, and the therapeutic approach are discussed. In two cases, the adnexa was removed, because there was extensive hemorrhage and ischemia. In the other two cases, unwinding of the adnexa was carried out and the ovary was preserved. The diagnosis of adnexal torsion is difficult, especially during pregnancy, and occasionally remains a diagnostic dilemma. It necessitates a prompt surgical intervention, because any delay leads to irreversible ovarian necrosis, so that adnexectomy is ultimately required.

Clinical experience of five fetal ovarian cysts: diagnosis and follow-up.

BACKGROUND: Ovarian cysts are the most frequent type of abdominal tumor, in female newborns. The most of the cases resolve spontaneously with no clinical significance. However, ovarian cysts often present complications such as torsion. CASE: The authors reviewed the pre- and postnatal records and ultrasonograms of five fetuses, who were diagnosed with ovarian cysts. No complication was observed prenatally. However, one infant 2 months after birth required surgical intervention because of cyst torsion. The cysts of the other four infants showed complete resolution in a time interval of 3-9 months. CONCLUSION: An ovarian cyst is not a life-threatening condition, so they should be just closely monitored pre- and postnatally until spontaneous resolution. When torsion of the cyst is suspected, surgical intervention is necessary.

Juvenile granulosa cell tumor associated with pregnancy: Report of a case and review of the literature.

BACKGROUND: Juvenile granulosa cell tumors account for about 5% of all granulosa cell tumors and are diagnosed in nearly 80% of cases during the first two decades of life. Only 10% of granulosa cell tumors present during pregnancy. The incidence of ovarian malignancies during pregnancy varies from 0.05 to 0.07 per 1000 pregnancies. CASE: A 31-year-old pregnant woman was admitted to our university hospital due to an adnexal mass, 9.5 cm in diameter, which was detected at 34 weeks of gestation. At 37 + 5 weeks of gestation, a cesarean section with right salpingo-oophorectomy and removal of the tumor was performed. Histopathological findings, including immunohistochemical study, led to the diagnosis of juvenile granulosa cell tumor (JGCT). CONCLUSION: The histological features and the differential diagnosis of the JGCT are discussed. The optimal management of such adnexal masses during pregnancy is also discussed. A JGCT that is confined to the ovary appears to have an excellent prognosis and can be treated by unilateral salpingo-oophorectomy.