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While cancer during pregnancy and its treatment has grown to be a popular topic in recent years, little is known on how to advise patients looking to conceive or conceiving after cancer treatment. The aim of this paper is to review the available literature on the impact of pregnancy on survivors of the most common childhood cancers, brain cancer, haematological malignancies, thyroid cancer, melanomas and sarcomas. Its main objective is to be a source of information for clinicians looking to counsel patients in these delicate moments exploiting all the available literature, albeit scarce. Given the available literature, we conclude that the presence of a multidisciplinary team is of great importance in supporting the patient and her loved ones when facing pregnancy with a previous cancer diagnosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Adenocarcinoma accounts for 10-25% of all cervical cancers, and its relative and absolute rate has raised over the past decades. Most, but not all the authors, reported that adenocarcinoma has a greater propensity to lymph node, ovarian and distant metastases and a worse prognosis compared with squamous cell carcinoma. However, whether histologic type is an independent prognostic factor is still a debated issue. Moreover, adenocarcinoma is a very heterogenous disease, including different histological subtypes. Whereas radical hysterectomy and definitive radiotherapy achieve the same clinical outcome in early stage squamous cell carcinoma, surgery seems to obtain better survival compared with definitive radiotherapy in early stage adenocarcinoma. Chemoradiation is the standard treatment for locally advanced cervical cancer regardless of histologic type, although several retrospective studies showed that patients with adenocarcinoma were more likely to die than those with squamous cell carcinoma both before and after concurrent chemoradiation era. The prognostic relevance of biological variables, such as cyclin-dependent kinase inhibitors, p53, cyclooxygenase-2 [COX-2], cell surface tyrosine-kinases and programmed death-ligand [PD-L1], is still under investigation. Palliative chemotherapy is the only treatment option for persistent or recurrent cervical adenocarcinoma not amenable with surgery and radiotherapy. The use of immune checkpoint inhibitors as well as a therapeutic strategy targeting cell surface tyrosine kinases should be adequately explored in this clinical setting., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mature cystic teratomas of the ovary have an incidence of 1.2-14.2 cases per 100.000 people per year. Malignant transformation occurs in approximately 2% of the cases, and usually consists of squamous cell carcinoma. The preoperative detection is difficult and the diagnostic accuracy of ultrasound, magnetic resonance imaging, and computed tomography is debated. The diagnosis is frequently made in the operating room or on final histological examination. Standard treatment consists of bilateral salpingo-oophorectomy, total hysterectomy and comprehensive surgical staging in early disease and optimal cytoreductive surgery in advanced disease. Paclitaxel/carboplatin- based chemotherapy is the most used adjuvant treatment, whereas more aggressive regimens can be adopted in patients with high tumor burden or recurrent disease. The efficacy of radiotherapy is still unproven. The prognosis is poor when the tumor has spread beyond the ovary. There are few information to provide commonly accepted guidelines for this malignancy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition. This drug leads to activation of the cellular energy-sensing liver kinase B1 [LKB1]/AMPK pathway. LKB1 is implicated as a tumor suppressor gene in molecular pathogenesis of different malignancies. AMPK is a serine/threonine protein kinase that acts as an ultra-sensitive cellular energy sensor maintaining the energy balance within the cell. AMPK activation inhibits mRNA translation and proliferation in cancer cells via down-regulation of PI3K/Akt/mTOR pathway. Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti-angiogenetic effects. Recent in vitro and experimental data suggest that metformin electively targets cancer stem cells, and acts together with chemotherapy to block tumor growth in different cancers. Several epidemiological studies and meta-analysis have shown that metformin use is associated with decreased cancer risk and/or reduced cancer mortality for different malignancies. The present review analyzes the recent biological and clinical data suggesting a possible growth-static effect of metformin also in gynecological cancers. The large majority of available clinical data on the anti-cancer potential of metformin are based on observational studies. Therefore long-term phase II-III clinical trials are strongly warranted to further investigate metformin activity in gynecological cancers., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

FIGO stage, tumor grade, depth of myometrial invasion, lymph-vascular space status and lymph node status are the most important clinical-pathological prognostic variables for endometrioid-type endometrial carcinoma. In the last years, several investigations have assessed different biological variables in tissue and serum samples from patients with this malignancy in order to detect biomarkers able to predict the clinical outcome. The present paper reviewed the literature data about the prognostic relevance of mutational status and/or immunohistochemical expression of p53, PTEN, PIK3, mTOR, β-catenin, k-ras and RASSF1A, microsatellite instability, vascular endothelial growth factor expression, DNA aneuploidy, and serum assay of CA125 and other tumor associated antigens. Tissue and serum biomarkers could be used, in addition to the conventional clinical-pathological variables, for the stratification of patients into categories with different risk of recurrence to better tailor adjuvant treatment., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Major extensive surgery still represents a cornstone of therapy of gynaecological cancer, and the adoption of implemented clinical guidelines for perioperative management can significantly decrease patient morbidity and mortality and reduce hospital stay. The overall risk of deep venous thrombosis in patients undergoing gynaecological surgery ranges from 7% to 45%, and fatal pulmonary embolism occurs in approximately 1% of these women. A meta-analyses of randomised trials showed a significant decrease in deep venous thrombosis in women receiving unfractioned heparin [UFH] compared with controls, and revealed no significant difference in deep venous thrombosis and pulmonary embolism between patients who received UFH and those who received low-molecular weight heparin [LMWH]. Potential advantages favouring LMWH over UFH include once-daily versus repeated daily injections and a lower risk of heparin-induced thrombocytopenia. All patients undergoing major surgical operations should receive LMWH that should be started preoperatively and then given for 7-10 days at least and prolonged for up to 4 weeks in high-risk cases. Antithrombotic mechanical methods can be added to pharmacological agents, but should not been used alone. Cephalosporins and amoxicillin-clavulanic acid have been widely used in gynaecological surgery prophylaxis. Both amoxicillin-clavulanic acid and cefazolin have good in vitro activity against the microbes more frequently involved in postoperative infections, such as Gram-negative bacilli, but amoxicillin-clavulanic acid is more effective against anaerobes. A single dose of antibiotics has been shown to be as effective as multiple doses in many trials that have compared a single-dose regimen with a multiple-dose regimen. Amoxicillin-clavulanic acid prophylaxis at the induction of anaesthesia can be suggested for gynaecological cancer patients undergoing major gynaecological surgery with or without colorectal resection. An additional antibiotic dose is recommended for prolonged operations or when intraoperative blood loss is important. Cephalosporins can be administered to women with a history of penicillin allergy not manifested by an immediate hypersensitivity reaction, whereas tigecyclin should be reserved to patients with a prior anaphylactic reaction to beta-lactams. Recent meta-analyses of randomised trials on patients undergoing elective colorectal surgery found more anastomotic leakages in patients who had preoperative mechanical bowel preparation with oral administration of different solutions than in those who had not, whereas there were no significant differences between the two arms as for wound infections, other septic complications, and non-septic complications. Therefore, preoperative mechanical bowel cleansing is not warranted for gynaecological cancer patients scheduled for surgery that may involve colon-rectum. After major abdominal gynaecological surgery, early oral feeding (within the first 24h regardless of the resolution of postoperative ileus) appears to be associated with increased nausea, shorter time to the presence of bowel sound, shorter time to first solid diet, and a trend toward shorter hospital stay when compared with delayed feeding. Since early oral feeding is safe but associated with increased nausea, the decision whether to adopt this postoperative regimen should be individualised. Decision making processes about thromboprophylaxis, antibiotic prophylaxis, bowel preparation for surgery that may involve colon-rectum, and timing of postoperative oral feeding will become more and more relevant for improved safety and quality of life of women with gynaecological cancer., (2009 Elsevier Ireland Ltd. All rights reserved.)

The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice. Serum CA 125 assay, physical examination, and imaging examinations have been employed with different time schedules for the follow-up of asymptomatic patients. Rising serum CA 125 levels may precede the clinical detection of relapse in 56-94% of cases with a median lead time of 3-5 months. An ongoing randomised phase III European trial is comparing the benefits of early administration of chemotherapy based on serum CA 125 assay alone versus delaying treatment until clinical or radiological detection of recurrent disease. Physical examination, with or without ultrasound, is very useful for the surveillance of these patients, since approximately 25-50% of relapses involve the pelvis. Additional radiological imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), are usually performed in asymptomatic patients with rising CA 125 levels as well as in patients with suspicious symptoms or signs. Integrated positron emission tomography (PET) and CT scanners (PET/CT) can identify recurrent disease in tissues that appear normal at CT imaging as well as metastatic lesions intimately associated with the bowel wall that are difficult to detect with CT or MRI, so that in most series PET/CT has a higher diagnostic reliability than that of conventional imaging techniques. Moreover, PET/CT can disclose unusual supra-diaphragmatic spreading of the disease and may be very helpful for treatment planning, especially for the selection of patients suitable for secondary surgical cytoreduction. A prospective, randomised trial of therapeutic interventions based on stratification by PET/CT disease status could elucidate the real impact of this diagnostic procedure in the management of patients with recurrent ovarian cancer.

Tumour stage, residual disease after initial surgery, histological type and tumour grade are the most important clinical-pathological factors related to the clinical outcome of patients with epithelial ovarian cancer. In the last years, several investigations have assessed different biological variables in sera and in tissue samples from patients with this malignancy in order to detect biomarkers able to reflect either the response to chemotherapy or survival. The present paper reviewed the literature data about the predictive or prognostic relevance of serum CA 125, soluble cytokeratin fragments, serum human kallikreins, serum cytokines, serum vascular endothelial growth factor and plasma d-dimer as well as of tissue expression of cell cycle- and apoptosis-regulatory proteins, human telomerase reverse transcriptase, membrane tyrosine kinase receptors and matrix metalloproteinases. A next future microarray technology will hopefully offer interesting perspectives of translational research for the identification of novel predictive and prognostic biomarkers for epithelial ovarian cancer.

Pre-treatment serum squamous cell carcinoma antigen [SCC] levels are elevated in 28-88% of patients with squamous cell cervical cancer, and are related to tumour stage, tumour size, depth of stromal invasion, lymph-vascular space status, parametrial involvement and lymph node status. The clinical relevance of pre-treatment serum SCC assay is still debated. Some authors reported that it has no prognostic value, some others found that it is related to survival at univariate analysis, and some others detected that is an independent prognostic variable for survival. Serial SCC measurements reflect both the tumour response to treatment and the clinical outcome of patients. Increasing SCC levels can precede the clinical diagnosis of recurrent disease in 46-92% of the cases, with a mean lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a positron emission tomography [PET] in patients with asymptomatic SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. SCC is a more sensitive serum tumour marker than CYFRA 21-1 for squamous cell cervical cancer in most series. Pre-treatment CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumour stage, tumour size, histological grade, cervical stromal invasion, lymph-vascular space status and lymph node status. Elevated serum CA 125 has been also detected in patients with squamous cell cervical cancer, but with a positivity rate lower than that found in patients with cervical adenocarcinoma. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 during follow-up may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. Serum levels of vascular endothelial growth factor [VEGF] are often elevated in patients with cervical cancer, and decrease significantly after successful treatment. However, the clinical relevance of serum VEGF assay is still investigational.

Uterine sarcomas include a heterogeneous group of rare tumours that usually have an aggressive clinical behaviour and a poor prognosis. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard surgical treatment. Pelvic and/or para-aortic lymphadenectomy is indicated for carcinosarcoma, but not for leiomyosarcoma and undifferentiated endometrial sarcoma. Some recent data on low numbers of patients with low-grade endometrial stromal sarcoma appear to show an incidence of nodal involvement higher than previously expected, thus suggesting a role for lymphadenectomy in this malignancy. Carcinosarcoma also requires a comprehensive surgical peritoneal staging. Postoperative treatment of uterine sarcomas has been long debated. Adjuvant pelvic radiotherapy appears to improve local control without any significant impact on overall survival. There is little evidence in the literature supporting the use of adjuvant chemotherapy in any gynaecological sarcomas except for carcinosarcomas. However, uterine sarcomas have a high tendency to develop distant recurrences, and recent data on adjuvant chemotherapy in soft tissue sarcomas are promising. As for the drugs to be used, it is worth noting that in a Swiss study, the combination of ifosfamide (IFO) and doxorubicin (DOX) obtained similar response rates in advanced gynaecological sarcomas and in advanced soft tissue sarcomas of other sites. In our decision-making scheme for early-stage disease, patients with leiomyosarcoma or undifferentiated endometrial sarcoma should receive adjuvant doxorubicin/epidoxorubicin (EPIDX)+ifosfamide, and those with carcinosarcoma should be treated with adjuvant cisplatin (CDDP)-based chemotherapy. The same drug regimens are used for the treatment of advanced disease. Sequential pelvic radiotherapy following chemotherapy could be delivered to selected cases. Recurrent disease often requires the integration of different therapeutic modalities, but no curative option is currently available with the possible exception of surgery for lung metastases and hormone therapy with or without debulking surgery for recurrent low-grade endometrial stromal sarcoma. Patients should be encouraged to enter clinical trials designed to identify new active drugs for these malignancies.

Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Progesterone therapy obtains overall response rates ranging from 11% to 25% in patients with endometrioid-type tumours, and oral medroxyprogesterone acetate 200mg daily appears to be a reasonable therapeutic option for those lesions that are well differentiated and/or have a high progesterone receptor (PgR) content. However, the activity of progestins is often compromised by the down-regulation of PgR within the target tissues, and therefore therapeutic strategies designed to enhance PgR expression are warranted. Little data are currently available about the new aromatase inhibitors and selective estrogen receptor modulators. As for chemotherapy, the combination of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less toxic combination of TAX+carboplatin. Chemotherapy is active against both endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this latter endometrial malignancy is less chemosensitive than the histologically similar high-grade serous ovarian carcinoma. Interesting fields of research are represented by investigational agents directed against specific intracellular signal transduction pathways involved in the proliferation, invasiveness and metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody trastuzumab, and the Clostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer. Further investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.

Most patients with advanced epithelial ovarian cancer experience objective responses to paclitaxel/platinum-based chemotherapy, but responses are generally short-lived and the clinical outcome is still unsatisfactory. Therefore, the strategy to consolidate and to prolong the duration of response is very attractive. Different consolidation or maintenance treatments have been attempted, such as whole abdomen radiotherapy, intraperitoneal chromic phosphate, radioimmunotherapy, intraperitoneal chemotherapy, high-dose chemotherapy with haematopoietic support, prolonged administration of the first-line regimen, second-line single-agent chemotherapy, and biological agents. Clinical studies have given conflicting, inconclusive, and generally disappointing results. A recent US randomised trial appeared to show that the prolonged administration of single-agent paclitaxel (175 mg/m2 every 3 weeks) significantly improved the progression-free survival of complete responders to paclitaxel/platinum-based chemotherapy. Alternative less toxic, and probably more effective schedules of administration of chemotherapy (i.e. weekly paclitaxel) might assure a better balance between quality of life and anti-tumor activity in patients previously exposed to chemotherapy.

Objective: To investigate the prevalence of renal impairment in patients with ovarian cancer at the time of the diagnosis., Study Design: Creatinine clearance was estimated according to Cockcroft and Gault (C&G Ccr), glomerular filtration rate (GFR) was determined as renal clearance of 99mTc-DTPA, and renal ultrasound was performed in 60 consecutive patients with newly diagnosed ovarian cancer., Results: A 28% of the total population studied had a GFR <60 ml/min/1.73 m(2). A moderate/severe dilation of the upper urinary tract was found in 12% of patients. The length of kidneys ranged between 9.0 and 13.5 cm, and a statistically significant correlation was found between kidney length and values of GFR., Conclusion: A reduction in renal function and a moderate to severe dilation of upper urinary tract frequently occur in patients with ovarian cancer at the time of the diagnosis.