CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line.

BACKGROUND: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. METHODS: The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). RESULTS: In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. CONCLUSION: High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.

The impact of COVID-19 on menstrual cycle's alterations, in relation to depression and sleep disturbances: a prospective observational study in a population of medical students.

BACKGROUND: The sars-Cov-2 pandemic has determined psychological stress, particularly in the young population of medical students. We studied the impact of the pandemic on menstrual cycle alteration in relation to psychological stress, presence of depression, sleep disturbances and post-traumatic stress, on a population of medical students. METHODS: 293 female students at the Faculty of Medicine and Psychology of the Sapienza University of Rome (23.08 years old ± 3.8) were enrolled. In March 2021, one year after quarantine, a personal data sheet on menstrual cycle, examining the quality of the menstrual cycle during the pandemic, compared to the previous period. Concomitantly, the Beck Depression Inventory and the Impact of Event Scale have been administered. A Pearson chi-square test was assessed to evaluate the difference between the characteristics of the menstrual cycle and the scores obtained with the questionnaires. RESULTS: A statistically significant association between menstrual alterations and stress during pandemic had been found. The onset of depressive symptoms and sleep disturbances was observed in 57.1% and in 58.1% of young women with cycle's alterations, respectively. Amenorrhea was three times more common in female students with depressive symptoms, premenstrual syndrome had a significant correlation with both depression and sleep disturbances. The pandemic has been related to menstrual alterations, with depressive symptoms and sleep disorders. Amenorrhea is connected to depression, as observed on the functional hypothalamic amenorrhea. CONCLUSIONS: The pandemic affected the menstrual cycle as well as the depressive symptoms and sleep. Practical implications of the study lead to the development of strategies for psychological intervention during the pandemic experience, in order to help medical trainees, with specific attention to women's needs. Future studies should analyze the impact of other types of social stress events, on sleep, depression and the menstrual cycle beside the pandemic.

Low endometrial beta-catenin and cadherins expression patterns are predictive for primary infertility and recurrent pregnancy loss.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (ß-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of ß-catenin (p = .001), E-cadherin (p = .001) and K-cadherin (p = .002), compared to the fertile ones. Furthermore, ß-catenin and E-cadherin intensity gradients of expression at glandular level were found totally reversed in infertile patients. Significant lower expression levels of K-catenin (p = .016) and E-cadherin (p < .0001) at glandular level were found in RPL patients. Results showed that the low endometrial expression of ß-catenin, E-cadherin and K-cadherin were associated to fertility-related problems, such as primary intertility and RPL.

The prognostic impact of cancer stem-like cell biomarker aldehyde dehydrogenase-1 (ALDH1) in ovarian cancer: A meta-analysis.

OBJECTIVE: To investigate the association of cancer stem cell biomarker aldehyde dehydrogenase-1 (ALDH1) with ovarian cancer patients' prognosis and clinico-pathological characteristics. METHODS: The electronic searches were performed in January 2018 through the databases PubMed, MEDLINE and Scopus by searching the terms: "ovarian cancer" AND "immunohistochemistry" AND ["aldehyde dehydrogenase-1" OR "ALDH1" OR "cancer stem cell"]. Studies evaluating the impact of ALDH1 expression on ovarian cancer survival and clinico-pathological variables were selected. RESULTS: 233 studies were retrieved. Thirteen studies including 1885 patients met all selection criteria. ALDH1-high expression was found to be significantly associated with poor 5-year OS (OR = 3.46; 95% CI: 1.61-7.42; P = 0.001, random effects model) and 5-year PFS (OR = 2.14; 95% CI: 1.11-4.13; P = 0.02, random effects model) in ovarian cancer patients. No correlation between ALDH1 expression and tumor histology (OR = 0.60; 95% CI: 0.36-1.02; P = 0.06, random effects model), FIGO Stage (OR = 0.65; 95% CI: 0.33-1.30; P = 0.22, random effects model), tumor grading (OR = 0.76; 95% CI: 0.40-1.45; P = 0.41, random effects model) lymph nodal status (OR = 2.05; 95% CI: 0.81-5.18; P = 0.13, random effects model) or patients' age at diagnosis (OR = 0.83; 95% CI: 0.54-1.29; P = 0.41, fixed effects model) was identified. CONCLUSIONS: Basing on the available evidence, this meta-analysis showed that high levels of ALDH1 expression correlate with worse OS and PFS in ovarian cancer patients.

Hyperandrogenism in a postmenopausal woman: a rare case of ectopic adrenal cortical gland.

Most frequent causes of androgenic manifestation are Cushing's syndrome, PCO, benign and malignant androgen-secreting non adrenal tumors and iatrogenic hirsutism. Hyperplasia or neoplasms of ectopic adrenocortical gland are rare. We report a case of a 63-year old female with hirsutism and alopecia. Laboratory data highlighted increased levels of androgens. Diagnostic imaging revealed normal morphology of adrenocortical gland and ovaries. In view of the clinical picture and suspected diagnosis of extra-adrenal cause, she underwent bilateral salpingo-oophorectomy. Histologic examination showed an ectopic adrenal gland with adenoma in the ovarian and peri-ovarian tissue. At six months of follow up, the patients has no sign of hyperandrogenism. In case of hyperandrogenism in postmenopausal women and in the absence of the adrenocortical gland abnormality, ovarian origin should be considered in the differential diagnosis.

Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-A Meta-Analysis.

BACKGROUND: Historically, blue dyes, (99)Tc or a combination of the two tracers have been used for sentinel lymph node (SLN) mapping in cervical and endometrial cancer patients. Indocyanine green (ICG), as a tracer, has been recently introduced in this setting. Our goal was to assess the differences in overall and bilateral detection rates as well as in false-negative rates among the different tracers. METHODS: The electronic databases PubMed, MEDLINE, and Scopus were searched in January 2016 by searching the terms "sentinel lymph node" and "dye" and "indocyanine green," and "cervical cancer" or "endometrial cancer." Series comparing different tracers injected intracervically and reporting the detection rate and/or SLN false-negative rate were selected. RESULTS: Forty-five studies were retrieved. Six studies including 538 patients met selection criteria. Compared with blue dyes, ICG SLN mapping had higher overall (odds ratio [OR] 0.27; 95 % confidence interval [CI] 0.15-0.50; p < 0.0001) and bilateral detection rates (OR 0.27; 95 % CI 0.19-0.40; p < 0.00001). No differences were found between ICG and (99)TC, although these results are based on data of a single series. No differences in overall and bilateral detection rates were found between ICG and the combination of blue dyes and (99)TC. The pooled analysis of false-negative rates data showed no difference in false-negative rates between tracers. CONCLUSIONS: In cervical and endometrial cancer, ICG SLN mapping seems to be equivalent to the combination of blue dyes and (99)TC in terms of overall and bilateral detection rates. Its safety profile and ease of use may favor its employment respect to conventional tracers.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

BACKGROUND: The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. METHODS: A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. RESULTS: Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. CONCLUSIONS: FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

BACKGROUND: Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. METHODS: Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. RESULTS: Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. CONCLUSIONS: Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other "imitators of preeclampsia." Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life. CASE REPORT: We describe a rare case of successful pregnancy after TTP manifestations occurring in the first trimester; most importantly, our experience represents the first case of atypical manifestation due to neurologic and kidney manifestations preceding laboratory assay alterations. RESULTS: We treated a patient with plasma replacement of 30 mL/kg/day and daily plasmapheresis in combination with continuous infusion of fresh-frozen plasma 10 mL/kg/day. The response of clinical manifestation immediately improved. At 30 weeks, the patient had multiple episodes of high blood pressure and concomitant decrease of hemoglobin and platelet count, so a cesarean section was immediately performed. She delivered a healthy female baby. CONCLUSION: Early diagnosis by ADAMTS13 activity, occasionally occurring before clinical manifestations, aided us in promptly administering commended and life-saving treatments.

Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells.

According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN-γ or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines.

Effects of unilateral ovariectomy on female fertility outcome.

PURPOSE: To compare the fertility outcome among women subjected to unilateral ovariectomy and other abdominal or non-gynaecologic pelvic surgery. METHODS: In this retrospective cohort study, 113 fertile women, surgically treated between 1990 and 2001 at Sapienza University of Rome with unilateral ovariectomy (UO), appendectomy (AP) or cholecystectomy (CO) for benign disease, were analysed for fertility outcome. Patients with assessed pre-surgical fertility defects, previous abdominal or pelvic surgeries and post-surgical contraception were not included. RESULTS: Thirty-five women underwent UO, 39 were subjected to AP and 39 were treated with CO. After a minimum 10-year post-surgical interval, the overall number of successful pregnancies was 75. The rate of women who experienced at least one post-operative successful pregnancy was: 48.5 % in UO, 41 % in AP and 53.8 % in CO (UO vs. AP, P = 0.55; UO vs. CO, P = 0.99; AP vs. CO, P = 0.53). One patient (2.8 %) in UO, one patient (2.6 %) in AP and two patients (5.1 %) in CO underwent Assisted Reproductive Technology to become pregnant. The rate of women who reported at least one miscarriage was: 10/35 (28.5 %) in UO, 11/39 (28.2 %) in AP, 12/39 (30.8 %) in CO (UO vs. AP, P = 0.93; UO vs. CO, P = 0.89; AP vs. CO, P = 0.81). One ectopic pregnancy was reported in CO group and one stillbirth occurred in one AP patient. CONCLUSIONS: No statistical difference in terms of post-operative fertility outcome between patients subjected to UO, AP or CO was found, thus allowing to suppose that the removal of one ovary does not significantly worsen the female fertility outcome respect to other abdominal or pelvic procedures.

Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation.

Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C-lectin receptor (MGL), expressed by immature DCs (iDCs), as a molecular target for α-N-acetylgalactosamine (GalNAc or Tn)-carrying tumor-associated antigens to improve DC performance. MGL expressed by ex vivo-generated iDCs from healthy donors was engaged by a 60-mer MUC1(9Tn) -glycopeptide as a Tn-carrying tumor-associated antigen, and an anti-MGL antibody, as a specific MGL binder. We demonstrated that MGL engagement induced homotrimers and homodimers, triggering the phosphorylation of extracellular signal-regulated kinase 1,2 (ERK1,2) and nuclear factor-κB activation. Analysis of DC phenotype and function demonstrated that MGL engagement improved DC performance as antigen-presenting cells, promoting the upregulation of maturation markers, a decrease in phagocytosis, an enhancement of motility, and most importantly an increase in antigen-specific CD8(+) T-cell activation. These results demonstrate that the targeting of MGL receptor on human DCs has an adjuvant effect and that this strategy can be used to design novel anticancer vaccines.

Chemotherapy in elderly patients with gynecological cancer.

OBJECTIVE: The aim of this study was to determine the tolerability, safety and feasibility of chemotherapy in very elderly patients with gynecological cancers. METHODS: We included all patients ≥ 75 years of age affected by endometrial, ovarian or cervical cancer treated with neoadjuvant, adjuvant or palliative chemotherapy. Data regarding age, stage of the disease, comorbidities, performance status (PS), chemotherapy regimen and dosing, toxicity, treatment delay and dose adjustments were recorded. RESULTS: Forty-nine patients were included in the study. Their median age was 77.5 years. The vast majority of patients (89.8%) presented with advanced neoplastic disease. Twenty-nine of the 49 patients were treated with full-dose chemotherapy; 41% were subjected to the weekly dose. One toxic death was recorded; grade 2 anemia was reported in 8 patients, and grade 2 and 3 neutropenia was recorded in 2 and 3 patients, respectively. Sixty-one percent of the patients completed the planned treatment. CONCLUSION: Chemotherapy in very elderly patients is feasible with an acceptable toxicity profile. Careful evaluation of PS and assessment of physical and psychological health are necessary to predict tolerability of chemotherapy. A weekly schedule is better tolerated in this setting.

CO2 laser treatment for Bartholin gland abscess: ultrasound evaluation of risk recurrence.

STUDY OBJECTIVE: To evaluate the efficacy of CO2 laser treatment and parameters correlated with recurrence in patients with Bartholin gland abscesses treated using this approach. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One hundred forty-seven patients who met eligibility criteria. INTERVENTION: Preoperative ultrasound evaluation of Bartholin gland lesions and CO2 laser treatment. MEASUREMENTS AND MAIN RESULTS: All patients received CO2 laser therapy, with median operative time 15 minutes (range, 12-35 minutes). Median postoperative stay was 1 hours (range, 1-4 hours). Estimated 3-year relapse-free rate was 88.56%. Lesion wall thickness 0.5-1.5 mm, multilocular lesion, and hyperechogenic lesion were correlated with recurrence. CONCLUSION: CO2 laser of Bartholin gland abscesses could be a valid option. Ultrasound characteristics of Bartholin gland lesions could predict lesion recurrence rate.

First case of isolated vaginal metastasis from breast cancer treated by surgery.

BACKGROUND: Breast cancer is a leading cause of death in developed countries. This neoplasm frequently relapses at distant sites such as bone, lung, pleura, brain and liver but rarely in the lower female genital tract. CASE PRESENTATION: We present the first case of isolated vaginal breast cancer metastasis and its surgical treatment. CONCLUSION: This case report focuses on the importance of an accurate genital tract examination as part of regular follow up in breast cancer survivors. Indeed, after this experience we feel that surgery could be considered a valid option for the treatment of an isolated vaginal metastasis.

Simple extrafascial trachelectomy and pelvic bilateral lymphadenectomy in early stage cervical cancer.

OBJECTIVE: To determine the feasibility and safety of simple extra-fascial trachelectomy plus pelvic lymphadenectomy in young patients affected by early stage cervical cancer. METHODS: We have prospectively identified all patients with early-stage cervical cancer (stages IA2-IB1) referred to our department. Inclusion criteria were: age ≤ 38 years, strong desire to maintain fertility, FIGO stage ≤ IB1, tumor size<2 cm, no LVSI, no evidence of nodal metastasis. Surgical technique included two steps: laparoscopic pelvic lymphadenectomy and vaginal simple extrafascial trachelectomy. Patients were followed up for oncological and obstetrical outcomes. RESULTS: Fourteen patients were enrolled in the study. Median age was 32 years (range 28-37); histotype was squamous in 11/14 (79%) cases and adenocarcinoma in 3/14 cases (21%); FIGO stage was IA2 in 5/14 (36%) patients, IB1 in 9/14 (64%) patients; median tumor size was 17 mm (range 14-19); median operative time was 120 min (range 95-210). No severe intraoperative complications were recorded. Postoperative complications were observed in two patients. No recurrences were detected. One patient died for other disease. Eight patients became pregnant and 3 of them had a term delivery. CONCLUSION: Low risk early-cervical cancer patients could be safely treated by simple extrafascial trachelectomy in order to maintain fertility. More studies are needed to better define the role of conservative and ultraconservative surgical approaches (i.e. conization) in this setting, either for fertility purposes or to minimize surgical complications.

Intraperitoneal chemotherapy by ultrasound-guided direct puncture in recurrent ovarian cancer: feasibility, compliance, and complications.

OBJECTIVE: This prospective pilot study investigated the feasibility, complications, and compliance of the administration of intraperitoneal (IP) chemotherapy by direct puncture under ultrasonographic guidance performed on consecutive patients with recurrent ovarian cancer (ROC). METHODS: Patients were evaluated to undergo secondary cytoreduction and/or to receive IP chemotherapy. Patients received standard intravenous therapy for ROC plus IP administration by direct puncture needle, under ultrasonographic guidance. RESULTS: From January 2008 to January 2011, 38 patients were enrolled. A total of 402 IP procedures were performed, with a mean of 10.5 procedures per patient. The feasibility rate was 97.4%. In 237 cases (98.8%) of subgroup 1 (abdominal wall thickness ≤6 cm), the procedure was performed after 1 attempt, meanwhile in 6% of cases of subgroup 2 (abdominal wall thickness >6 cm), more than 1 attempt was necessary (P < 0.01). The mean procedure time was 10 minutes (range, 5-30 minutes). We recorded a total of 2.25% mild intraprocedure complications. No significant difference was identified for the complication rate according to the abdominal wall thickness or according to the number of previous laparotomies. A total of 5 procedures (1.2%) were not performed as a result of patients' noncompliance. The mean pain score according to the visual analog pain scale was moderate at the first evaluation (after 3 minutes) and mild at the final evaluation (after 10 minutes). CONCLUSIONS: The administration of IP chemotherapy with a direct puncture, under ultrasound guidance, for patients with ROC, is a safe and feasible method, with a high acceptance from patients.

Thinking twice before abandoning first-line chemotherapy in ovarian cancer: report of two cases and literature review. Passing from tri-weekly to weekly regimens.

We present two cases of advanced ovarian cancer treated with neoadjuvant chemotherapy with standard tri-weekly carboplatin and paclitaxel. Therapy was converted to weekly regimens because of disease progression, resulting in disease response. Weekly regimens could overcome drug resistance and this strategy should be attempted before abandoning first-line chemotherapy in favor of palliation.

Feasibility and safety of type C2 total extraperitoneal abdominal radical hysterectomy (TEARH) for locally advanced cervical cancer.

INTRODUCTION: Radical hysterectomy represents the gold standard treatment in patients with early-stage cervical cancer and a valid choice of treatment, after neoadjuvant chemotherapy (NACT), in locally advanced tumors. Laparotomy is still considered the standard approach for radical hysterectomy; however, the extraperitoneal route has been described as a valid alternative for pelvic lymphadenectomy, with shorter operative time, shorter ileus and reduced postoperative pain and hospitalization. We designed the first prospective study to evaluate the technique of total extraperitoneal radical hysterectomy for surgical treatment of locally advanced cervical cancer after platinum-based NACT, in terms of feasibility and safety. METHODS: Consecutive patients affected by locally advanced cervical carcinoma were considered for eligibility in this observational study. After a primary complete evaluation, all patients were submitted to platinum-based NACT. Inclusion criteria were: stage IB2-IIIB cervical carcinoma already submitted to neoadjuvant chemotherapy with a complete or partial response after three cycles of chemotherapy, WHO performance status≤1, adequate renal, hepatic and cardiac function, BMI<40, age≤75 years, no concurrent or previous malignant disease, no previous radiation therapy, and signed informed consent. Patients included in the study were submitted to type C2 extraperitoneal radical hysterectomy. RESULTS: From January 2006 to October 2008, 46 patients were enrolled and compared with a control group selected from the historical database. The mean operative time in the extraperitoneal radical hysterectomy group was 195 min (range: 120-240) versus 235 min (range: 215-310) in the intraperitoneal radical hysterectomy group (P<0.05). Median postoperative ileus was 32 h (range: 24-36) versus 67 h (range: 42-78) (P<0.05). VAS (Visual Analogue Scale) score at 24 and 48 h was 8 (range: 6-8) versus 8 (range: 6-9) (P=NS) and 3.5 (range: 2-7) versus six (range: 5-9) (P<0.05) respectively. No differences in terms of intraoperative and postoperative complications were recorded. CONCLUSIONS: Total extraperitoneal radical hysterectomy in locally advanced cervical cancer is feasible and safe. If compared with intraperitoneal abdominal radical hysterectomy, no significant differences in terms of surgical data or complications were found. Extraperitoneal radical hysterectomy seems to compare favorably to the intraperitoneal approach in terms of operative time, postoperative ileus, and VAS score at 48 h.