Post-traumatic Stress and Depressive Symptoms in Women With Ovarian Cancer 3-6 Months After Diagnosis.

BACKGROUND/AIM: The potentially traumatic role of severe life-threatening medical conditions is still debated in psychiatry and not yet recognized, particularly among post-traumatic stress disorders. However, increasing evidence suggests the psychopathological impact of severe medical conditions related to their poor prognosis, high lethality, treatments heaviness and invasiveness. Ovarian cancer (OC) is one of the malignancies with the highest mortality and the aim of this study was to investigate post-traumatic stress and depressive symptoms in women 3 to 6 months after diagnosis. PATIENTS AND METHODS: A sample of 83 women diagnosed with OC at different stages (from AI to IV) was recruited and assessed by means of the: Structural Clinical Interview for Mental Disorders according to DSM-5 (SCID-5), Trauma and Loss Spectrum Self-Report (TALS-SR), Impact Event Scale-Revised (IES-R), Hamilton Rating Scale for Depression (HAM-D), Mood Spectrum-Self Report (MOOD-SR), Work and Social Adjustment Scale (WSAS). RESULTS: Full data on the psychiatric assessments were available for 45 patients: 13 (28.9%) patients reported a diagnosis of PTSD. Patients with PTSD reported statistically significant higher depressive symptoms and more severe impact on work and social functioning compared to those without PTSD. CONCLUSION: Our results highlight the need to carefully assess the potentially traumatic burden of a diagnosis of OC and its association with depressive symptoms for their impact on patients' global functioning, in order to provide appropriate preventive and therapeutic interventions.

Positive p16 Immunostaining Is an Independent Prognostic Variable for Disease-free Survival and Overall Survival in Patients With Squamous Cell Carcinoma of the Vulva Treated With Radical Surgery and Inguinofemoral Lymphadenectomy: An Italian Single Center Retrospective Study.

BACKGROUND/AIM: The expression of the cyclin-dependent kinase inhibitor p16 correlates with the presence of human papillomavirus. The purpose of this investigation was to assess the prognostic relevance of p16 expression in patients with vulvar squamous cell carcinoma (VSCC) treated with radical surgery followed by adjuvant (chemo) radiation in selected cases. PATIENTS AND METHODS: Seventy-eight patients were analyzed retrospectively. RESULTS: Positive p16 immunostaining was detected in 19 (24.4%) patients. Five-year disease-free survival (DFS) and 5-year overall survival (OS) were better in p16-positive compared to p16-negative patients (83.9% versus 37.3% p=0.002 and 91.7% versus 57.6%, p=0.003, respectively). p16 expression retained prognostic relevance at multivariate analysis for both DFS and OS. CONCLUSION: p16 expression was detected in 24.4% of patients with VSCC and was found to be an independent prognostic variable for both DFS and OS.

Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes.

Endometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100'000 women, mainly affecting peri- or postmenopausal women. The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17)(q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors. Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy ± radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy ± radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation. LG-ESSs are indolent tumor with a 5-year overall survival (OS) of 80-100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with a median OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV. The aim of this review is to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs.

Cervical Adenocarcinoma: A Still Under-investigated Malignancy.

BACKGROUND/AIM: The aim of the study was to correlate the expression of mismatch repairs proteins (MMR), programmed-death-ligand1 (PDL-1), and estro-progestinic receptors (ER/PgR) in tissue samples from a series of cervical adenocarcinoma (ADC) patients with their clinicopathological features. MATERIALS AND METHODS: Thirty-nine ADC specimens were retrospectively retrieved from the Division of Pathology of the University Hospital of Pisa from 2015 to 2021. Histological subtype, grade (G), Silva pattern, presence of lymph vascular space invasion (LVI), and perineural invasion (PNI) were annotated. On representative samples, immunostaining for ER/PgR, MLH1, PMS2, MSH2, MSH6, and PDL-1(sp142) was performed. RESULTS: Thirty-five ADCs were HPV-associated usual type (24 invasive and 11 in situ), 2 were clear cell type, one was a minimal deviation adenocarcinoma (MDA), and one was an invasive stratified mucin-producing carcinoma (iSMC). ADC associated with LVI were mostly G2-3, whereas those associated also with PNI were G3 with Silva pattern C. No difference in the expression of ER/PgR was observed with a dichotomic age stratification (51 years) of patients. Only 6 ADCs were MMR-deficient, all of them were of the usual type (4 invasive and 2 in situ). The heterodimer MLH-1/PMS2 was the one most frequently altered (5/6), whereas only one case had MSH6 loss. None of ADCs express PDL-1, except iSMC which showed PDL-1 expression >1% in neoplastic cells. CONCLUSION: Both invasive and in situ usual type ADCs indicate MMR deficiency, highlighting how this could be an early event in tumorigenesis. None of the cases, except for iSMC, express PDL-1.

Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma.

The ecteinascidins trabectedin and lurbinectedin are very interesting antineoplastic agents, with a favorable toxicity profile and peculiar mechanisms of action. These drugs form adducts in the minor groove of DNA, which produce single-strand breaks (SSBs) and double-strand breaks (DSBs) and trigger a series of events resulting in cell cycle arrest and apoptosis. Moreover, the ecteinascidins interact with the tumor microenvironment, reduce the number of tumor-associated macrophages, and inhibit the secretion of cytokines and chemokines. Trabectedin has been approved by the Federal Drug Administration (FDA) for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-based regimen. Moreover, trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been approved in the European Union for the treatment of platinum-sensitive recurrent ovarian cancer. Lurbinectedin has been approved by the FDA for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The review assesses in vitro and in vivo experimental studies on the antineoplastic effects of both ecteinascidins as well as the clinical trials on the activity of trabectedin in uterine sarcoma and ovarian carcinoma and of lurbinectedin in ovarian carcinoma and endometrial carcinoma.

Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Epithelial Ovarian Cancer: A Debated Issue for Gynecologic Oncologists.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status.

Screening for Ovarian Cancer in the General Population: State of Art and Perspectives of Clinical Research.

BACKGROUND/AIM: Screening for ovarian cancer in the general population is a challenging issue. The aim of this review was to analyze both the studies based on serum CA125 assay and ultrasound (US) and the novel perspectives of clinical and biological research on this issue. MATERIALS AND METHODS: The trials on the combination of serum CA125 and vaginal/pelvic US as well as the investigations on microRNA (miRNA)s, circulating tumor DNA and tumor protein 53 (TP53) variants in DNA purified from Pap smears have been critically analyzed. RESULTS: Two large randomized trials failed to detect a reduction in ovarian cancer-related deaths in women who underwent serum CA125- and US-based screening compared to those who had no screening. The United Kingdom Collaborative Trial of Ovarian Cancer Screening reported a 39.2% higher incidence of stage I-II and 10.2% lower incidence of stage III-IV disease in women who underwent annual multimodal screening with serum CA125 and vaginal US compared to women who had no screening, but this stage shifting did not translate into a survival benefit. A longitudinal, multiple biomarker algorithm-based strategy might improve ovarian cancer detection compared with serial CA125 alone. The use of serum tumor-associated autoantibodies, circulating tumor DNA and microRNA is still investigational. The identification of TP53 clonal variants in DNA purified from Pap smears can detect early steps of serous ovarian carcinogenesis. CONCLUSION: The availability of sensitive next-generation sequencing-based approaches for TP53 assessment in PAP smears may allow the reliability of this genetic marker for early detection of ovarian cancer to be verified.

Response to Chemotherapy and Clinical Outcome of Patients With Recurrent Epithelial Ovarian Cancer After PARP Inhibitor Maintenance Treatment: A Multicenter Retrospective Italian Study.

BACKGROUND/AIM: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. PATIENTS AND METHODS: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI). RESULTS: Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. CONCLUSION: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Computed Tomography-assessed Skeletal Muscle Index and Skeletal Muscle Radiation Attenuation in Patients With Ovarian Cancer Treated With Primary Surgery Followed by Platinum-based Chemotherapy: A Single-center Italian Study.

AIM: To assess the prognostic relevance of baseline and post-treatment skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) at the level of third lumbar vertebra in patients with ovarian cancer who underwent primary surgery and platinum-based chemotherapy. PATIENTS AND METHODS: This retrospective investigation analyzed 134 patients who underwent staging computed tomography, surgery, chemotherapy and post-treatment computed tomography. RESULTS: At univariate analysis, stage (p<0.0001), histotype (p=0.01), residual disease (p<0.0001) and treatment response (p<0.0001) correlated with progression-free survival (PFS), whereas age (p=0.004), stage (p=0.006), residual disease (p<0.0001) and treatment response (p<0.0001) were associated with overall survival (OS). Neither baseline nor post-treatment SMI and SMRA had prognostic relevance. At multivariate analysis, residual disease and treatment response correlated with PFS (p<0.0001 and p<0.0001) and OS (p=0.007 and p<0.0001), whilst age was an independent prognostic variable for OS (p=0.02). CONCLUSION: Baseline and post-treatment SMI and SMRA did not correlate with patient outcome in this clinical setting.

Molecular Characterization of Peritoneal Involvement in Primary Colon and Ovary Neoplasm: The Possible Clinical Meaning of the P2X7 Receptor-Inflammasome Complex.

INTRODUCTION: Colon cancer (CC) and epithelial ovarian cancer (EOC) are common and severe neoplasms frequently sharing a massive inflammatory involvement of peritoneum. A detailed molecular characterization of such carcinomatosis has not been performed, so far. METHODS: Omental adipocytes were isolated from thirty-three adult women who underwent primary surgery for CC or EOC. Expression of several pro-inflammatory genes was determined by real-time PCR and immunofluorescence. Data were related to the clinical phenotype of the patients. RESULTS: CD68, FGFR1, and IL-6 were significantly more expressed in adipocytes from CC patients and VEGF in adipocytes from EOC. TNFα, TGFß, or MCP-1, as well as the pro-inflammatory platform P2X7R-NLRP3, did not differ between the 2 cancers. White blood cell count, mirroring systemic inflammation, was related to adipocyte P2X7R (R = 0.508, p = 0.003), NLRP3 (R = 0.405; p = 0.02), and MCP-1 (R = 0.448; p = 0.009). P2X7R and NLRP3 were the only inflammatory factors significantly more expressed in patients carrying both omental and peritoneal carcinosis, who were also characterized by a higher leukocytosis. None of the tested inflammatory markers was associated with tumor grading for both neoplasms; however, the presence of metastases was associated with a higher adipocyte expression of FGFR1 and TGFß. CONCLUSION: We show here that rarely measured molecules seem to specifically characterize omental carcinomatosis of CC or EOC, while more common inflammatory agents like TNFα, TGFß, or MCP-1 do not; the P2X7R-NLRP3 complex marks omental and peritoneal carcinosis and is related to circulating white blood cells and MCP-1, involved in monocyte-macrophage tissue infiltration; increased TGFß and FGFR1 characterize the tumoral dissemination.

Pharmacological Treatment of Advanced, Persistent or Metastatic Endometrial Cancer: State of the Art and Perspectives of Clinical Research for the Special Issue "Diagnosis and Management of Endometrial Cancer".

Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43-62%, a median progression-free survival (PFS) of 5.3-15 months and a median overall survival (OS) of 13.2-37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27-47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.

The Role of Skin Tests in the Prevention and Diagnosis of Hypersensitivity Reactions to Platinum Agents in Gynecological Cancer: A Single-Center Italian Retrospective Study.

BACKGROUND: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs. METHODS: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure. RESULTS: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients. CONCLUSIONS: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents.

Randomized Clinical Trials and Real World Prospective Observational Studies on Bevacizumab, PARP Inhibitors, and Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Ovarian Carcinoma: A Critical Review.

Platinum/paclitaxel-based chemotherapy is able to obtain a clinical response in up to 80% of patients with advanced ovarian carcinoma, but most of them will subsequently develop recurrent disease. Several therapeutic approaches, including prolonged administration of the first-line regimen and the concomitant or sequential addition of a third cytotoxic agent to standard chemotherapy, failed to improve the clinical outcome of patients. In the last years, the implementation of the biological knowledge on ovarian carcinoma and the introduction of bevacizumab (BEV) and poly(ADP-ribose) polymerase inhibitors (PARPi) in first-line treatment have improved patient prognosis. In this review, we have analyzed the randomized clinical trials and real world observational studies on these issues, with the aim to suggest an algorithm for a rational use of BEV and PARPi in patients with newly diagnosed advanced ovarian carcinoma.

Primary Perivascular Epithelioid Cell Tumor (PEComa) of the Ovary: A Case Report and Review of the Literature.

BACKGROUND: Perivascular epithelioid cell tumors (PEComa)s are mesenchymal neoplasms located at various anatomic sites, which usually express both melanocytic and myogenic markers. CASE REPORT: A 60-year-old woman underwent laparotomy for a huge, heterogeneous, right ovarian mass. The histological examination of the surgical specimen revealed a neoplasm consisting of both cells with clear or eosinophilic cytoplasm and spindle cells in a myxoid stroma. Immunostaining was positive for human melanoma black-45, h-caldesmon, desmin, actin, and transcription factor 3. Cell atypias were moderate, mitoses were 4/10 high power fields (HPF) and margins were focally infiltrative. These findings pointed to a diagnosis of ovarian PEComa. Twenty-five months later, two subcutaneous lesions were surgically removed on the left trapezius muscle and the median subumbilical area, respectively. The former was a desmoid fibromatosis, whereas the latter was a recurrence of PEComa with greater nuclear pleomorphism and higher number of mitoses (26/50 HPF) compared to the primary tumor. The patient was free of disease 11 months later. CONCLUSION: A long-term follow-up of gynecological PEComas is strongly recommended.

Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes.

Clear cell carcinoma of the ovary is a rare and distinct histotype of epithelial ovarian carcinomas. Women diagnosed with clear cell carcinomas are usually younger and diagnosed at earlier stages than those with the most common high-grade serous histology. Endometriosis is considered a main risk factor for the development of clear cell carcinoma of the ovary, and it can be considered a precursor of of this tumor, as it is identified in more than 50% of patients with clear cell carcinoma. Different molecular pathways and alterations heve been identified in ovarian clear cell carcinoma, including the most common mutations of AT-rich interaction domain 1A [ARID1A] and phosphatidylinositol-4,5-bisphosphate 3-kinase [PIK3] catalytic subunit alpha [PIK3CA]. The prognosis of patients at early stage is favorable, while patients with advanced or recurrent disease experience a poor oncologic outcomes. Despite a lower rate of responses due to an intrinsic chemoresistance, the treatment strategy for advanced disease resembles the treatment of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and platinum-based chemotherapy. For this reason, the role of adjuvant chemotherapy in patients with stage I disease undergoing complete surgical staging is still under debate. Alternative treatments, including biological agents that target different pathways constitute the most promising treatment strategies, and well-designed, collaborative international trials should be designed in order to improve the oncologic outcomes and the quality of life of patients with this aggressive disease.

Have Volume-based Parameters of Positron Emission Tomography/Computed Tomography Prognostic Relevance for Patients With Potentially Platinum-responsive Recurrent Ovarian Cancer? A Single Center Italian Study.

BACKGROUND/AIM: To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. PATIENTS AND METHODS: This retrospective investigation analyzed 67 patients at first relapse. RESULTS: At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. CONCLUSION: Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy.

BACKGROUND/AIM: The aims of the study were: i) to assess the incidence of perineural invasion (PNI) in squamous cell carcinoma of the vulva and ii) to correlate PNI with common pathological prognostic variables and clinical outcome of patients. PATIENTS AND METHODS: The hospital records of 64 patients with vulvar squamous cell carcinoma who underwent primary radical surgery were reviewed. RESULTS: PNI was significantly related to stage (p=0.038), size (p=0.038), lymph-vascular space involvement (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion. Five-year disease-free survival was 30.0% in patients with PNI and 53.1% in those without PNI (p=0.018), and the corresponding 5-year overall survival was 50.0% and 77.1% (p=0.031), respectively. CONCLUSION: PNI was associated with common pathological prognostic variables and with a poorer clinical outcome in patients with vulvar squamous cell carcinoma.

The Prognostic Relevance of Computed Tomography-assessed Skeletal Muscle Index and Skeletal Muscle Radiation Attenuation in Patients With Gynecological Cancer.

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer.

Dose-dense Neoadjuvant Chemotherapy With Paclitaxel and Carboplatin in Cervical Cancer: Efficacy on Pathological Response.

BACKGROUND/AIM: The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). PATIENTS AND METHODS: A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. RESULTS: A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. CONCLUSION: Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

A narrative review of pregnancy after malignancies in young women that don't originate in the female genital organs or in the breast.

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.