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1.
Eur J Surg Oncol ; 50(4): 108252, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38471373

ABSTRACT

BACKGROUND: This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer. METHOD: We systematically searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate [OR = 0.88; 95% CI (0.50, 1.57); P = 0.68] and Overall Survival (OS) [OR = 1.23; 95% CI (0.69, 2.19), P = 0.48]. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury [OR = 0.28; 95% CI (0.08, 0.94), P = 0.04] and bladder disfunction [OR = 0.10; 95% CI (0.02, 0.53), P = 0.007] of the RH group were higher compared to the SH group. CONCLUSION: This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Disease-Free Survival , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Neoplasm Staging , Hysterectomy/methods , Neoplasm Recurrence, Local/pathology , Retrospective Studies
2.
Eur Rev Med Pharmacol Sci ; 27(17): 8190-8197, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37750647

ABSTRACT

Mindfulness-based stress reduction, a complementary and alternative therapy, is able to decrease cancer-related fatigue, and stress and to improve the quality of life in cancer patients. Some studies evaluated if mindfulness-based stress reduction could improve some cardiometabolic and cancer risk factors, including systemic chemokines, growth factors, and pro-inflammatory biomarkers (e.g., C-reactive protein, Interleukin-1). In this narrative review, we highlight the pleiotropic beneficial effects of mindfulness-based stress reduction and its clinical impact on cardiovascular and cancer risk factors among patients with cancer in different stages. Moreover, improvements in the overall quality of life, sleep quality, and immune functions [changes in plasma levels of interleukin-4 (IL-4), interferon-γ (INF-γ), and interleukin-10 (IL-10)] will also be discussed. Albeit few clinical studies available in the literature, evidenced the beneficial effects of mindfulness-based stress reduction on the immune and cardiometabolic profile in cancer patients, providing important insights into the closest collaboration between psycho-oncologists, oncologists, and cardiologists.


Subject(s)
Cardiovascular Diseases , Mindfulness , Neoplasms , Humans , Quality of Life , Stress, Psychological/therapy , Stress, Psychological/etiology , Risk Factors , Neoplasms/therapy , Cardiovascular Diseases/prevention & control
3.
Radiol Case Rep ; 16(3): 638-641, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33437346

ABSTRACT

Rare vascular anomaly, the persistent sciatic artery (PSA) has an extremely low incidence, likely 0.04%-0.06%. This vessel is prone to thrombosis, distal thromboembolization, rupture, and aneurysmal formation, while its symptoms can vary considerably, from completely asymptomatic pictures to cases with pain, claudication or ischemia of the lower limbs. It is essential to diagnose this anomaly in time, in order to avoid dangerous complications for the patient's life. The main methods of diagnosis are given by vascular ultrasound, CT, or MRI. Here we present a case of a bilateral PSA diagnosed in a 77-year-old woman as an incidental finding in angio-CT of the lower limbs.

4.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 19-25. DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-31538446

ABSTRACT

Oral mucosa pigmentations belong to a heterogeneous variety of lesions, which are usually divided into two groups: exogenous or endogenous pigmentations. The pigmented lesions most frequently found in the oral mucosa are the amalgam tattoo, the melanotic macula and the nevus. All these lesions may affect every part of the oral mucosa, and they may represent a hard diagnostic challenge for the clinician; the clinical objective examination is not sufficient to make a correct diagnosis. Reflectance Confocal Microscopy provides a real-time microscopic evaluation of tissue layers, and is widely considered a useful auxiliary tool in monitoring skin and mucosa lesions. In this context, Reflectance Confocal Microscopy imaging is a valid aid in the management of oral mucosa pigmented lesions, to corroborate and support the diagnostic process.


Subject(s)
Lip/diagnostic imaging , Microscopy, Confocal , Nevus, Pigmented/diagnostic imaging , Pigmentation , Humans , Skin Neoplasms/diagnostic imaging
5.
Andrology ; 7(6): 804-817, 2019 11.
Article in English | MEDLINE | ID: mdl-31350821

ABSTRACT

BACKGROUND: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment. OBJECTIVES: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (Tonset ) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate. MATERIAL AND METHODS: An online PubMed literature search was conducted to identify English language publications from inception to January 2019. RESULTS: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long Tonset , further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a 'difficult' molecule, but Tonset can be improved following absorption by buccal mucosa using appropriate excipients. CONCLUSIONS: We conclude that several ODT and ODF formulations can improve the 'discretion' issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter Tonset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.


Subject(s)
Erectile Dysfunction/drug therapy , Patient Compliance/psychology , Phosphodiesterase 5 Inhibitors/pharmacokinetics , Sildenafil Citrate/pharmacokinetics , Tadalafil/pharmacokinetics , Vardenafil Dihydrochloride/pharmacokinetics , Administration, Mucosal , Adult , Aged , Aged, 80 and over , Erectile Dysfunction/epidemiology , Humans , Male , Middle Aged , Mouth Mucosa/physiology , Patient Satisfaction , Phosphodiesterase 5 Inhibitors/therapeutic use , Quality of Life , Sexual Behavior/drug effects , Sildenafil Citrate/therapeutic use , Tadalafil/therapeutic use , Vardenafil Dihydrochloride/therapeutic use
6.
Harmful Algae ; 80: 64-71, 2018 12.
Article in English | MEDLINE | ID: mdl-30502813

ABSTRACT

In the last few decades, Ostreopsis spp., toxic benthic dinolagellates of tropical origin, generated large interest in the Mediterranean Sea, where several bloom events have been observed. Ecology and proliferation dynamics of O. cf. ovata are driven by complex interactions among biotic and abiotic drivers, and understanding mechanisms triggering bloom events is still far from being complete. The aim of the present study is to highlight the role of different habitat conditions, elucidating the effects of i) exposure to hydrodynamic conditions, ii) macroalgal community and iii) urbanisation level, in driving O. cf. ovata bloom dynamics. A significant effect of hydrodynamics was observed only for cells in seawater, with higher abundances in sheltered zones, irrespective of the urbanisation level. Similarly, a significant effect of the dominant macroalgal community, with higher abundances in Corallinales and turf dominated communities, and lower ones in Cystoseira amentacea canopies, has been recorded, consistently in the differently urbanised sites. Additionally, stretches of the coast suffering from a more intense anthropic exploitation are in general more prone to the proliferation of potentially toxic benthic microalgae. All these results imply a larger risk exposure to toxic effects for humans in urban beaches and sheltered areas, usually more attended by swimmers and bathers. These findings underline the need to preserve, and eventually restore, canopy dominated assemblages, which presently are under regression because of human threats, providing a straightforward example that restoration of relevant habitats implies a cascading improvement of human welfare.


Subject(s)
Dinoflagellida/physiology , Ecosystem , Environmental Monitoring , Harmful Algal Bloom , Hydrodynamics , Marine Toxins/toxicity , Mediterranean Sea , Seawater , Temperature
7.
Int J Surg Case Rep ; 46: 50-55, 2018.
Article in English | MEDLINE | ID: mdl-29684805

ABSTRACT

INTRODUCTION: Diagnosing lymphoma continues to prove challenging in the clinical practice. Composite lymphoma (CL) is defined by the coexistence of different lymphoma subtypes in the same anatomical location. This condition has seldom been witnessed in the gastrointestinal (GI) tract. We weren't able to find previous cases in the literature about small bowel CL with follicular lymphoma (FL) and classical Hodgkin lymphoma (CHL). Surgery is the treatment of choice to obtain accurate histology, to manage and prevent acute complications. We state that this work has been reported in line with the SCARE criteria. CASE PRESENTATION: We describe an extremely rare case of small bowel CL, presenting as an intestinal bulky mass with circumferential infiltration of bowel loops. The small bowel tumor was incidentally detected by abdominal Magnetic Resonance Imaging (MRI) in a 64-year-old man who suffered from rectal discomfort and non-specific clinical symptoms. After this radiological finding, the patient underwent multiphase contrast computed tomography (MDCT) for initial staging and to study vascular involvement. Surgery was recommended to obtain an accurate diagnosis both due to initial symptoms of the intestinal obstruction and to avoid small bowel complications. The histopathological examination revealed a small bowel CL composed mainly of B cells FL with also CHL components. CONCLUSION: It is important to note that involvement of the proximal ileal loops is very rare in small bowel lymphoma. MRI represents a precious diagnostic tool to evaluate the intra and extramural extent of the tumor.

10.
Gynecol Oncol ; 143(3): 516-520, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27769526

ABSTRACT

OBJECTIVE: To further investigate the role of MIS comparing patients submitted to MI-IDS with a balanced population treated by standard laparotomy. METHODS: The investigational arm (Cases) includes 30 AEOC patients treated with MI-IDS. The Control arm included a consecutive series of 65 AEOC patients submitted to laparotomic IDS. Inclusion criteria were: age>18years, histologically proven EOC, clinical complete/partial response after NACT, and ECOG PS <2. Preoperative clinical data, perioperative and oncological outcomes were analyzed. General Well-Being Schedule (GWBS) was administered to evaluate quality of life before and after surgery. RESULTS: Both groups were well-balanced. A higher percentage of women among Cases received bevacizumab-containing NACT compared with Controls. No statistical differences were registered in terms of surgical procedures and residual tumor. A significantly longer median OT in Cases was counterbalanced by more favorable EBL and median length of stay and TTC. No statistically significant differences were registered in terms of postoperative complications. Cases showed a 6months longer PFS compared to Controls. However, in multivariate analysis only the administration of Bevacizumab and a shorter TTC were independently associated with a longer PFS. Regarding QoL, no statistically significant differences were registered in Cases between pre- and postoperative GWBS score. Differently from Controls where this difference was statistically significant and a more intense distress were recorded. CONCLUSIONS: Minimally invasive approach could represent an advantageous alternative surgical way to perform interval debulking surgery in this specific subset of patients, with no impact on PFS. Based on these findings a randomized clinical trial is now under evaluation in our Institution.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures/methods , Laparoscopy/methods , Neoplasms, Cystic, Mucinous, and Serous/surgery , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Case-Control Studies , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Laparotomy , Middle Aged , Minimally Invasive Surgical Procedures , Neoadjuvant Therapy , Neoplasm Grading , Neoplasms, Cystic, Mucinous, and Serous/pathology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Proportional Hazards Models , Retrospective Studies
11.
Gynecol Oncol ; 142(2): 231-6, 2016 08.
Article in English | MEDLINE | ID: mdl-27215633

ABSTRACT

OBJECTIVE: To evaluate the timing and pattern of relapse, and duration of response to second line chemotherapy in advanced ovarian cancer (AOC) patients treated with first line carboplatin-paclitaxel chemotherapy with or without bevacizumab. PATIENTS AND METHODS: This is a case-control study including 222 AOC patients. Seventy-four women treated with first line carboplatin-paclitaxel-bevacizumab chemotherapy (Cases) were matched based on laparoscopic predictive index value, and residual tumor at first surgery with 148 AOC patients treated with carboplatin-paclitaxel. Distribution of pattern of relapse, and response to second line chemotherapy was compared between the two groups. Time to Progression (TTP) for second line chemotherapy was also analyzed for study purpose. RESULTS: Median platinum-free interval (PFI) was 16months (range 2-65) in Cases, compared with 9months (1-83) in Controls (p-value=0.001). Twenty patients (51.3%) among Cases showed recurrence in multiple anatomic sites, compared with 31 (31.9%) in the Control group (p-value=0.035). Peritoneal recurrence occurred as diffuse in 30 Cases (96.8%), and 60 Controls (82.2%; p-value=0.046). Secondary cytoreductive surgery (SCS) was successfully completed in 53.5% of Controls compared to 10.0% of Cases (p-value=0.016). In women with fully platinum-sensitive relapse, response rate to second line chemotherapy was 85.2% in Controls, compared to 38.4% in Cases (p-value=0.002). Finally, Cases showed a shorter TTP, compared to Controls (5months vs 8months; p-value=0.041). CONCLUSIONS: Incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with wider presentation of relapse, lower rate of complete SCS, and shorter TTP to second line chemotherapy in women with platinum-sensitive disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Case-Control Studies , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage
12.
Gynecol Oncol ; 142(1): 176-183, 2016 07.
Article in English | MEDLINE | ID: mdl-27058837

ABSTRACT

OBJECTIVE: As a result of relevant achievements in the field of translational research, several active drugs and multiple biological targets are available in ovarian cancer (OC). In this complex scenario, there is an urgent need to effectively summarize the available data in order to update conclusions, and outline perspectives. METHODS: The results in terms of target identification and drug development have been summarized using the well-known hallmarks of cancer firstly described, and recently modified by Hanahan and Weinberg [1-2]. Published data from clinical trials have been retrieved from PubMed, Embase, CINAHL and Cochrane database. Ongoing clinical trials were searched using clinicaltrials.gov web platform, and identified using NCT number. RESULTS: Genomic instability and angiogenesis are the most actively investigated hallmarks in high-grade serous OC, and the inhibition of tumor immune evasion appears as the emerging strategy for molecularly-driven therapy. Targeting sustained proliferative signaling through MEK and mTOR inhibitors seems the most promising approach in clear cell, and low-grade serous OC. CONCLUSIONS: This substantial amount of data suggests that targeted therapies are already part of the clinical and therapeutic management of OC patients. The expectations of getting from translational research a better knowledge of tumor biology and therefore personalized drugs are high and worthy of maximum effort from referral centers.


Subject(s)
Ovarian Neoplasms/drug therapy , Female , Genomic Instability , Humans , Molecular Targeted Therapy , Neovascularization, Pathologic , Ovarian Neoplasms/blood supply , Ovarian Neoplasms/genetics
13.
Ann Oncol ; 27(4): 625-34, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26782955

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. PATIENTS AND METHODS: One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. RESULTS: Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression-free survival (P < 0.05); miR-199a-3p, miR-199a-5p and miR-181a-5p associated with residual tumor volume and Pt-free interval (P < 0.05). Immuno-histochemical staining confirmed an enrichment of P-Smad2, a marker of transforming growth factor-ß activation, in tumors from patients with shorter PFS and OS, and with high levels of expression of miR-181a-5p (P < 0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P < 0.001). CONCLUSIONS: This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.


Subject(s)
Cystadenocarcinoma, Serous/drug therapy , MicroRNAs/biosynthesis , Neoadjuvant Therapy , Ovarian Neoplasms/drug therapy , Smad2 Protein/biosynthesis , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Biopsy , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , MicroRNAs/genetics , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Prognosis , Smad2 Protein/genetics
14.
Ann Surg Oncol ; 23(5): 1660-5, 2016 May.
Article in English | MEDLINE | ID: mdl-26714958

ABSTRACT

BACKGROUND: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. RESULTS: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). CONCLUSIONS: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.


Subject(s)
Adenocarcinoma, Clear Cell/mortality , Cystadenocarcinoma, Serous/mortality , Cytoreduction Surgical Procedures , Endometrial Neoplasms/mortality , Hyperthermia, Induced , Neoplasm Recurrence, Local/mortality , Ovarian Neoplasms/mortality , Platinum/therapeutic use , Adenocarcinoma, Clear Cell/secondary , Adenocarcinoma, Clear Cell/therapy , Adult , Aged , Combined Modality Therapy , Cystadenocarcinoma, Serous/secondary , Cystadenocarcinoma, Serous/therapy , Endometrial Neoplasms/secondary , Endometrial Neoplasms/therapy , Female , Follow-Up Studies , Humans , Injections, Intraperitoneal , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Prognosis , Retrospective Studies , Survival Rate
15.
Gynecol Oncol ; 139(1): 5-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26196319

ABSTRACT

OBJECTIVE: To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal surgery (UAS). PATIENTS AND METHODS: The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity≥75%, PPV≥50%, and NPV≥50% received 1 point score, with an additional one point in the presence of an accuracy of ≥60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. RESULTS: No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV≥10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885). CONCLUSIONS: S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.


Subject(s)
Models, Biological , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Female , Gynecologic Surgical Procedures/methods , Gynecologic Surgical Procedures/standards , Humans , Laparoscopy/methods , Laparoscopy/standards , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Predictive Value of Tests , Retrospective Studies
16.
Gynecol Oncol ; 139(1): 47-51, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26166805

ABSTRACT

OBJECTIVE: To analyze the feasibility of total mesometrial resection by laparoscopy (L-TMMR) in a multicentric series of early stage cervical cancer. METHOD: We prospectively evaluated a consecutive series of cervical cancer patients with pre-operative FIGO stages IA2-IB1 at the Catholic University in Rome and in Campobasso and the Charitè University in Berlin. All cases were assessed at pre-operative MRI scan and clinically confirmed by investigation under anesthesia, adhering strictly to the FIGO criteria. The surgical and post-surgical data were collected. RESULTS: 104 women with cervical cancer were admitted between July 2013 and August 2014 and among them 71 patients with pre-operative FIGO stages IA2-IB1 were treated with L-TMMR. One laparotomic conversion was registered. The median operative time was 260min (120-670min), estimated blood loss was 100cm(3) (25-900cm(3)), and the median length of hospital stay was 6days (2-26days). We observed 8 intra-operative complications including a vascular injury of the left internal iliac vein that caused conversion, 6 vesical injuries and 1 ureteral injury managed laparoscopically. Two vescico-vaginal fistula and one hemoperitoneum were observed as major post-operative complications (4.2%). CONCLUSION: L-TMMR can be safely performed in selected cervical cancer patients. Further larger prospective trials are needed to evaluate the oncological outcome of patients undergoing this surgical procedure.


Subject(s)
Hysterectomy/methods , Uterine Cervical Neoplasms/surgery , Adult , Aged , Female , Humans , Hysterectomy/adverse effects , Laparoscopy/adverse effects , Laparoscopy/methods , Lymph Node Excision/methods , Middle Aged , Neoplasm Staging , Prospective Studies , Uterine Cervical Neoplasms/pathology
17.
Ann Oncol ; 26(7): 1363-71, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25846551

ABSTRACT

BACKGROUND: The majority of patients with stage III-IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in drug resistance are unknown. To unravel some of these features, we investigated the mutational profile of genes involved in pathways related to drug sensitivity in a cohort of matched tumors obtained at first surgery (Ft-S) and second surgery (Sd-S). PATIENTS AND METHODS: Matched biopsies (33) taken at Ft-S and Sd-S were selected from the 'Pandora' tumor tissue collection. DNA libraries for 65 genes were generated using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were analyzed using a high-performance cluster computing platform (Cloud4CARE project) and independently validated. RESULTS: A total of 2270 somatic mutations were identified (89.85% base substitutions 8.19% indels, and 1.92% unknown). Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft-S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of mutations were conserved between matched Ft-S and Sd-S. Mutations detected at second surgery clustered patients in two groups characterized by different mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and signal transduction. CONCLUSIONS: There was a low level of concordance between Ft-S and Sd-S in terms of mutations in genes involved in key processes of tumor growth and drug resistance. This result suggests the importance of future longitudinal analyses to improve the clinical management of relapsed EOC.


Subject(s)
Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Mucinous/genetics , Cystadenocarcinoma, Serous/genetics , Endometrial Neoplasms/genetics , Genes, Neoplasm/genetics , High-Throughput Nucleotide Sequencing/methods , Mutation/genetics , Ovarian Neoplasms/genetics , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/secondary , Adenocarcinoma, Clear Cell/therapy , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/secondary , Adenocarcinoma, Mucinous/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Combined Modality Therapy , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/secondary , Cystadenocarcinoma, Serous/therapy , Drug Resistance, Neoplasm/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/secondary , Endometrial Neoplasms/therapy , Female , Follow-Up Studies , Homologous Recombination , Humans , Longitudinal Studies , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Prognosis , Retrospective Studies , Survival Rate
18.
Cell Death Differ ; 22(1): 118-30, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25168242

ABSTRACT

The transcription factor p53 regulates the expression of genes crucial for biological processes such as cell proliferation, metabolism, cell repair, senescence and apoptosis. Activation of p53 also suppresses neoplastic transformations, thereby inhibiting the growth of mutated and/or damaged cells. p53-binding proteins, such as mouse double minute 2 homolog (MDM2), inhibit p53 activation and thus regulate p53-mediated stress responses. Here, we found that long glucocorticoid-induced leucine zipper (L-GILZ), a recently identified isoform of GILZ, activates p53 and that the overexpression of L-GILZ in p53(+/+) HCT116 human colorectal carcinoma cells suppresses the growth of xenografts in mice. In the presence of both p53 and MDM2, L-GILZ binds preferentially to MDM2 and interferes with p53/MDM2 complex formation, making p53 available for downstream gene activation. Consistent with this finding, L-GILZ induced p21 and p53 upregulated modulator of apoptosis (PUMA) expression only in p53(+/+) cells, while L-GILZ silencing reversed the anti-proliferative activity of dexamethasone as well as expression of p53, p21 and PUMA. Furthermore, L-GILZ stabilizes p53 proteins by decreasing p53 ubiquitination and increasing MDM2 ubiquitination. These findings reveal L-GILZ as a regulator of p53 and a candidate for new therapeutic anti-cancer strategies for tumors associated with p53 deregulation.


Subject(s)
Proto-Oncogene Proteins c-mdm2/metabolism , Transcription Factors/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cell Line, Tumor , HEK293 Cells , Humans , Male , Mice , Mice, Knockout , Protein Stability , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Transcription Factors/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Ubiquitination/genetics
19.
Hum Reprod ; 29(9): 1918-24, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25006204

ABSTRACT

STUDY QUESTION: What is the risk of complications after uterine leiomyoma embolization and what are the factors associated with complications? SUMMARY ANSWER: The cumulative risk of complications after embolization is relatively low even in the long term, but submucosal leiomyoma location may increase the risk. WHAT IS KNOWN ALREADY: A broad spectrum of complications after leiomyoma embolization have been described with widely varying rates. There is uncertainty over the actual risk of complications and the factors associated with this risk. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study of 288 consecutive women undergoing leiomyoma embolization in the general gynaecology clinic of a university teaching hospital between January 2001 and December 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Complications occurring after embolization were categorized as major or minor according to the severity of their impact on health, the level of care required and the outcome. Cumulative complication rates were estimated by survival analysis and log-rank tests according to baseline variables. Multivariable Cox proportional hazards analysis was performed to adjust for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: There were 48 patients who experienced a complication at a median of 5 months (95% confidence interval, 4.1-11.4) after embolization. Complications were minor in 38 patients and major in 10 patients. The cumulative overall complication rate was 13% (95% CI, 9.0-17.0) at 6 months, 16% (95% CI, 11.0-20.0) at 1 year, 17% (95% CI, 12.0-22.0) at 3 years and 18% (95% CI, 12.9-22.8) at 5 years. The most frequent complication (19/48, 39.6%) was leiomyoma expulsion, which occurred spontaneously in 13 (68.4%) of these cases and required assistance in 6 (31.6%) cases. Eight (2.8%) patients underwent re-intervention, including six hysteroscopic myomectomies, one laparoscopic myomectomy and one hysteroscopic adhesiolysis, as a result of a complication. Submucosal leiomyoma location was the only baseline variable associated with an increased risk for complications [Hazard ratio (HR), 2.28, 95% CI, 1.24-4.18, P = 0.008]. LIMITATIONS, REASONS FOR CAUTION: Our population did not include women of African descent, who have been reported to be at higher risk of post-procedural complications compared with Causcasian women. If such women were involved in the study, higher morbidity rates might have been observed. WIDER IMPLICATIONS OF THE FINDINGS: Women with submucosal leiomyomas at the time of embolization are more likely to have post-procedural complications. This is important new information for counselling patients contemplating this therapeutic approach. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests to declare. The study was not supported by any external grant.


Subject(s)
Embolization, Therapeutic/adverse effects , Leiomyoma/surgery , Postoperative Complications/epidemiology , Uterine Neoplasms/surgery , Adult , Female , Humans , Incidence , Middle Aged , Prospective Studies , Risk Factors , Survival Analysis
20.
Gynecol Oncol ; 134(2): 257-61, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24910451

ABSTRACT

OBJECTIVE: To analyze the impact of secondary cytoreductive surgery (SCS) on survival outcome in a retrospective series of isolated platinum-resistant recurrent ovarian cancer. METHODS: We evaluate a consecutive series of 268 ovarian cancer patients with platinum-resistant relapse. Isolated recurrence was defined as the presence of a single nodule, in a single anatomic site, and was observed in 27 cases (10.1%). In all women the presence of isolated relapse was assessed at radiological evaluation, and surgically confirmed in the SCS group. RESULTS: Among the 27 patients with isolated recurrence, 16 (59.3%) received chemotherapy alone, and 11 (40.7%) complete SCS followed by non-platinum based chemotherapy. No significant differences were observed in the distribution of baseline clinico-pathological characteristics, pattern of recurrent disease, duration of PFI, and type of salvage chemotherapy between the two groups. In the SCS group, 6 patients (54.5%) showed isolated peritoneal relapse and 5 women (45.4%) showed isolated lymph nodal recurrence, and were treated with peritonectomy and lymphadenectomy, according with site of relapse. Two post-operative complications (18.2%) occurred: asymptomatic lymphocele and groin wound dehiscence. SCS significantly prolonged median time to first progression (12 months vs 3 months; p-value=0.016), median time to second progression (8 months vs 3 months; p-value=0.037), and post-relapse survival (PRS) (32 months vs 8 months; p-value=0.002). Residual tumor at 1st surgery (X(2)=5.690; p-value=0.017), duration of PFI (X(2)=5.401; p-value=0.020), and complete SCS (X(2)=4.250; p-value=0.039) retains independent prognostic role for PRS in multivariate analysis. CONCLUSIONS: SCS prolongs PRS compared to chemotherapy alone in isolated platinum-resistant recurrent ovarian cancer.


Subject(s)
Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Retrospective Studies
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