The use of sealing hemostat patch (HEMOPATCH®) in laparotomic myomectomy: a prospective case-control study.

PURPOSE: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair. METHODS: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH®) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH® is applied in group A, and spray electrocoagulation is applied in group B. RESULTS: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B. CONCLUSIONS: HEMOPATCH®, during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study.

OBJECTIVES: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. DESIGN: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T0) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T1) with the Patients' Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. PARTICIPANTS: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. SETTING: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of "Campus Bio-Medico" and visited again 3 months (T1) after the initiation of therapy. METHODS: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T0 and T1 with the paired Student's t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. RESULTS: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T1 (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. LIMITATIONS: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. CONCLUSIONS: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

Efficacy of termoablative fractional CO2 laser (Monnalisa Touch) in stress urinary incontinence.

PURPOSE: Usually, in stress urinary incontinence (SUI), nonsurgical therapy such as pelvic floor muscle training (PFMT) and lifestyle changes are proposed before surgical treatment. Laser therapy has recently been recommended for the treatment of SUI, helping to reconstruct the collagen that supports the vagina and the pelvic floor. The aim of the study was to evaluate the efficacy of SUI treatment with a CO2 intravaginal laser in patients waiting for anti-incontinence surgery (TVT-O). METHODS: This is a prospective, case-control study. Fifty-two patients have been included in our study and we divided them into two groups: atrophy and no atrophy. We also adopted a control group retrospectively identified from our database of patients undergoing PFMT. The subjective estimation of SUI symptoms before and after treatment was evaluated using the Visual Analog Scale before and after 1, 6, and 12 months of treatment. The objective evaluation with the urodynamic study with the stress test and a 3-day voiding diary to count the number of episodes of incontinence, before and after treatment. RESULTS: The intravaginal CO2 laser improved all the parameters considered for SUI in both groups. Its results were more relevant in the atrophy group, in comparison to the no atrophy group, even if they were both statistically significant. There were no statistically significant differences for all the parameters evaluated for SUI between laser treatment and PFMT in the control group. CONCLUSION: The CO2 laser is well-tolerated, minimally invasive, safe, and showing efficacy for SUI. More studies are needed to consider it as first-instance therapy, like PFMT, or at least, as a bridge therapy to surgery.

Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact.

Introduction: After the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP. Materials and Methods: We enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2. Results: We prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25-30 years 85%, aged 30-35 years 94.4%, aged 35-40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function. Conclusion: Based on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study.

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.

Tailoring parametrectomy for early cervical cancer (Stage IA-IIA FIGO): a review on surgical, oncologic outcome and sexual function.

INTRODUCTION: Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear. EVIDENCE ACQUISITION: Searching on PubMed, we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review. EVIDENCE SYNTHESIS: Modified radical hysterectomy (Piver II/Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III/Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/Querleu-Morrow Type C1) compared to CRH (Piver III/Type C2) in the ECC, with our data we can confirm a non-inferiority regarding the oncological outcome. CONCLUSIONS: Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Sentinel lymph node in cervical cancer: a literature review on the use of conservative surgery techniques.

INTRODUCTION: Sentinel lymph node detection is a surgical procedure that allow to avoid systematic lymphadenectomy in those tumors in early stage where lymph node spread is not sure. If the sentinel lymph node is not involved by tumor in 98-99% of case other lymph nodes are clean. The reason why less radical surgery is chosen is linked to the lower postoperative morbidity rate, the risk of lower limb lymphedema decreases. The aim of this review was to summarize what is the state of art of using the sentinel lymph node dissection (SLD) technique and what are the future goals to improve the safety and the reliability. EVIDENCE ACQUISITION: We have conducted a review of the literature of the past 10 years to understand the attitudes of oncologist gynecologists in the world to the conservative treatment of cervical cancer. We only selected articles from 2010 onwards, which meet the inclusion criteria. EVIDENCE SYNTHESIS: The detection rate varies from 83% to 100%. The bilateral detection rate, on the other hand, varies from 42% to 100%. The false negative rate ranges from 4% to 12%. Sensitivity varies from 20.7% (considering the frozen section) to 100%. CONCLUSIONS: Indocyanine green is the most reliable and performing tracer for the search of the sentinel lymph node; that the false intraoperative negative rate is too high to be sure not to subject the patient to an incorrect therapeutic procedure; data concerning the safety and survival of conservative lymphadenectomy (SLND) compared to systematic lymphadenectomy are still lacking in the literature and therefore we are awaiting the results of the two ongoing randomized clinical trials that will allow us to have more significant scientific data.

Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients.

OBJECTIVE: There are no current guidelines regarding evaluation of patients with normal CA125 at initial diagnosis during routine surveillance after completion of treatment. Thus, the purpose of this study was to evaluate the role of human epididymis protein 4 (HE4) in the detection of recurrence in patients with ovarian cancer and a negative CA125 at diagnosis. METHODS: All patients with ovarian cancer with a negative CA125 referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were included in the study. Inclusion criteria were: age between 18 and 70 years old, diagnosis of epithelial ovarian cancer, optimal primary surgery (residual tumor <1 cm), and normal CA125 at initial diagnosis. Patients with other malignancies or chronic diseases were excluded from the study. Statistical analysis was based on the calculation of percentages, means, medians, and ranges of the values. RESULTS: A total of eight patients were included in the study. The median age was 53 years (range 40-75). All patients had a normal CA125 at initial diagnosis while seven (87.5%) patients had abnormal HE4 levels at diagnosis. The International Federation of Gynecology and Obstetrics (FIGO) stages at enrollment varied from IC to IIIC (IB (1), IC (3), IIC (1), IIIC (3)). The most common histologic subtype was serous (62.5%). Seven patients recurred and had abnormal HE4 and normal CA125 values. The median HE4 at recurrence was 107 pmol/L. The median disease-free interval was 55 months (range 5-108) and all the patients underwent optimal cytoreductive surgery. CONCLUSIONS: HE4 levels may serve as a marker for recurrence in patients with a normal CA125 at initial diagnosis. Future studies are needed to evaluate the role of HE4 levels in earlier detection of recurrent ovarian cancer.

The role of human epididymis protein 4 as a biomarker in gynecologic malignancies.

INTRODUCTION: The serum levels of glycoprotein human epididymis protein 4 (HE4) have been widely investigated in patients with ovarian cancer as a tumor marker to differentiate benign gynecological tumors from ovarian cancers (OC). A few studies demonstrated the promising role of HE4 in endometrial cancer (EC) too. The aim of this review is to provide an outline of published studies investigating HE4 in the diagnosis of gynecologic malignancies, focusing on its role in OC and EC. EVIDENCE ACQUISITION: We conducted a systematic review of literature from January 1952 to June 2018 on the role of HE4 in OC and EC focusing on the diagnostic power in terms of sensitivity and specificity. EVIDENCE SYNTHESIS: We identified 49 articles with an overall sample size of 12,631 patients in OC group and five studies with an overall sample size of 1221 patients in EC group. We stated that HE4 had a pooled sensitivity of 78% and specificity of 86% in the detection of borderline or malignant OC and a pooled sensitivity of 78.8% and specificity of 100% in EC diagnosis. CONCLUSIONS: This systematic review confirms the importance of HE4 in the diagnosis of epithelial ovarian cancer and its promising role in endometrial cancer (endometrioid histology).

The challenge of preoperative identification of uterine myomas: Is ultrasound trustworthy? A prospective cohort study.

PURPOSE: To correlate preoperative ultrasound examination with intraoperative and anatomo-pathological findings, including estimation of number, localization and size of uterine myomas, uterine diameters and volume. METHODS: A prospective study on 126 women undergoing surgery for uterine myomatosis at Campus Bio-medico between May 2013 and April 2014. The patients were divided into two groups: one submitted to hysterectomy and the other submitted to open myomectomy. Ultrasound scans were performed 1 day before surgery by the same expert sonographer. The number of myomas at ultrasound was compared to intraoperative visualization and anatomo-pathological findings. Wilcoxon Test was applied to compare data registered with each technique. RESULTS: There was no significant difference between the number of myomas recorded at visualization and at ultrasound, while there was a significant difference between visualization and anatomo-pathology (p = 0.0006). The analysis showed a non-significant difference between myoma number at ultrasound and at anatomo-pathology in the two groups, if the number of myomas was less than or equal to six. Contrarily, we observed a significant difference if the number of myomas was more than six (p = 0.003). CONCLUSIONS: Our data show that ultrasound has limits in identifying the exact number of uterine myomas. This mapping is particularly needed in a minority of patients with usually desiring fertility who need a debulking procedure due to the large size and/or number of myomas or myoma location causing symptomatology. In patients with more than six myomas, voluminous uterus, a second-level examination such as Magnetic Resonance may be helpful.

Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study.

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.

Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer?

Actually, in literature there are not valid tools able to predict the chemotherapy response during first-line ovarian cancer treatment. CA125 and human epididymis protein 4 (HE4) levels of consecutive single-institution patients with epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and until 6 months follow-up. First, patients were divided into two groups according to a temporal criterion: patients treated during 2009 (group A: training group) and patients treated during 2010 (group B: verification group). At sixth months follow-up, patients were sub-classified, within both groups, as platinum resistant or platinum sensitive/intermediate, according to Response Evaluation Criteria in Solid Tumors criteria, and the serum marker courses were further analyzed in each subgroup. Moreover, we performed a logistic regression analysis to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A total of 76 patients were divided into two groups: group A (n = 42) and group B (n = 34). After 6 months of follow-up, 40 patients were classified as platinum sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle, in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases, although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4 reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of 83 % with a specificity of 87 % (positive predictive value = 0.86, negative predictive value = 0.85) in predicting chemoresponse. On the contrary, CA125 values during chemotherapy did not result statistically significant in predicting platinum response. Our findings suggest that HE4 values during first-line chemotherapy could predict chemotherapy response in EOC patients.

Surgical treatment of rectovaginal endometriosis with extensive vaginal infiltration: results of a systematic three-step vagino-laparoscopic approach.

OBJECTIVE: Recto-vaginal endometriosis remains a surgical challenge. We propose a systematic surgical approach combining vaginal and laparoscopic steps for patients affected by deep endometriosis infiltrating the vaginal wall. STUDY DESIGN: This is a prospective observational study, performed at Campus Bio-Medico of Rome, University Teaching Hospital. All consecutive patients, from 2008 to 2011, affected by symptomatic deep recto-vaginal endometriosis with full thickness vaginal wall involvement, underwent a systematic surgical approach, based on three consecutive surgical steps: vaginal route, laparoscopic approach and final vaginal excision. All patients included in the study were scheduled for two years' follow-up with pelvic examination, transvaginal ultrasound and visual analog scale (VAS) evaluation of symptoms (dysmenorrhea, dyspareunia and chronic pelvic pain) at 3, 6, 12 and 24 months. RESULTS: Thirty-four patients were enrolled. No major complications were registered. Complications included superficial vascular lesions in two cases (5.9%), ureteral stenosis two weeks after surgery in one patient (2.9%), and bowel obstruction for paralytic ileus in one patient (2.9%). A de novo endometrioma was found at 12 months after surgery and a recurrent endometrioma was evident at 24 months. For all symptoms evaluated, there was a significant improvement within 3 months after surgery (p<0.05) and no statistically significant difference during follow-up (at 3, 6, 12 and 24 months). CONCLUSION: The proposed systematic surgical approach consisting of three consecutive steps could simplify the approach to deep endometriosis while at the same time increasing the quality of endometriosis surgery, with important benefit for the women affected.

Feasibility and safety of carboplatin plus paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: a pilot study.

The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Between June 2007 and May 2012, all patients with a diagnosis of locally advanced cervical cancer (IB2­IIB) were eligible for this protocol. All patients have received 3 cycles of carboplatin (AUC6) and paclitaxel 175 mg/mq in neoadjuvant setting. The NACT-induced toxicity and the response to treatment were evaluated according to the World Health Organization (WHO) criteria. After NACT, all patients with complete or partial response were submitted to classical radical hysterectomy type III or C2, according to different classifications, and were submitted to four adjuvant cycles of platinum-based chemotherapy. The primary endpoints of the study were to evaluate the efficacy and feasibility of carboplatin regimen. Thirty-five patients with locally advanced cervical cancer were considered. A total of 23 patients completed 3 cycles of NACT. The overall clinical response rate after NACT was 78.3% including 43.5% (n = 10) with complete response, 34.8% (n = 8) with partial response, 17.4% (n = 4) with stable disease and 4.3% (n = 1) of those who suffered disease progression. The most common toxicity was haematologic, nausea/vomiting and neuropathy with grades 1 and 2 and occurred in 56.5, 56.5 and 17.4%, respectively. No renal toxicity was registered. Our results suggest that carboplatin is a well-tolerated drug with a response rate similar to standard cisplatin. Then, it represents, in neoadjuvant setting, a valid alternative in patients affected by locally advanced cervical cancer.

Quality of life in patients with endometrial cancer treated with or without systematic lymphadenectomy.

OBJECTIVE: To compare the quality of life (QoL) of women affected by endometrial cancer treated with surgery with or without systematic lymphadenectomy. STUDY DESIGN: Consecutive patients affected by stages I and II endometrial cancer and treated with surgery between 2008 and 2011 were selected. Eligible subjects were divided into two groups: Group A consisted of 36 patients who had hysterectomy plus bilateral salpingo-oophorectomy without lymphadenectomy; Group B consisted of 40 patients who had hysterectomy plus salpingo-oophorectomy plus pelvic and aortic lymphadenectomy. The EORTC Quality of Life Questionnaire-Cancer Module (QLQ-C30) and Quality of Life Questionnaire-Endometrial Cancer Module (QLQ-EN24) were administered to selected patients. All data were recorded and then analyzed using the scoring manual of the EORTC Quality of Life Group. RESULTS: Among symptom scales, only lymphedema gave a statistically significant difference among two groups, with a score of 10.64 ± 17.43 in Group A and 21.66 ± 24.51 in Group B (p=0.0285). The p value obtained comparing the "Global Health Status" (items 29 and 30) in Group A and in Group B was not statistically significant. CONCLUSION: Lymphadenectomy did not influence negatively global health status, but lymphadenectomy maintained its importance in determining a patient's prognosis and in tailoring adjuvant therapies. We therefore support its practice as part of the surgical procedure in patients affected by high risk endometrial cancer.

Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD-chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.

HER2/neu as a potential target for immunotherapy in gynecologic carcinosarcomas.

Carcinosarcomas of the female genital tract are rare tumors with an aggressive clinical behavior. Trastuzumab, a humanized monoclonal antibody, acts by binding to HER2/neu extracellular domain and exhibits therapeutic efficacy in HER2/neu-overexpressing cancers. Two uterine carcinosarcomas (UMMT-ARK-1, UMMT-ARK-2) and 2 ovarian carcinosarcomas (OMMT-ARK-1, OMMT-ARK-2) were established as primary tumor cell lines in vitro and evaluated for HER2/neu expression by immunohistochemistry, fluorescent in situ hybridization analysis, quantitative real-time polymerase chain reaction, and for membrane-bound complement regulatory proteins CD46, CD55, and CD59 by flow cytometry. Sensitivity to trastuzumab-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was studied in 5-hr chromium release assays. HER2/neu expression was demonstrated in OMMT-ARK-1 and OMMT-ARK-2. OMMT-ARK-2 demonstrated an amplification of the c-erbB2 gene by fluorescent in situ hybridization analysis and a high sensitivity to ADCC (mean killing, 45.6%; range, 32.3%-72.6%). A lower level of killing was detected against the fluorescent in situ hybridization analysis-negative OMMT-ARK-1 cell line (mean, 26.5%; range, 21.0%-31.8%). CD46, CD55, and CD59 membrane-bound complement regulatory proteins were expressed at high levels in all primary mixed müllerian tumor cell lines, and all these tumors were found to be highly resistant to complement-dependent cytotoxicity with or without trastuzumab. Addition of untreated and heat-inactivated plasma did not significantly decrease ADCC against OMMT-ARK-2 cell line, suggesting that while the cell line is highly resistant to complement, irrelevant IgG does not significantly alter the ability of trastuzumab to mediate ADCC. Our results suggest that HER2/neu may represent a novel target for the immunotherapy of a subset of human carcinosarcomas refractory to salvage chemotherapy.

The use of novel hemostatic sealant (Tisseel) in laparoscopic myomectomy: a case-control study.

BACKGROUND: This is the first case-control study on the use of a fibrin sealant (Tisseel) on uterine suture during laparoscopic myomectomy (LM), with the primary endpoint to evaluate the intraoperative bleeding and postoperative blood loss. In addition, we evaluated the time required to achieve hemostasis using Tisseel and how much it can influence operative time. METHODS: From December 2009 to January 2011, consecutive patients older than 18 years with symptomatic isolate intramural myoma with maximal diameter B6 cm and ≥ 4 cm and with a sonographically diagnosed free myometrium margin ≥ 0.5 cm were included in the study. We selected from our institute's database a group of consecutive patients with homogeneous features of the study group, who underwent laparoscopic myomectomy without Tisseel application. RESULTS: Fifteen women with symptomatic myoma were enrolled in the study (group A). Regarding the control group (group B), we selected a homogenous group of 15 patients with the same preoperative characteristics of the study group. Mean operative time was 47.7 min and 62.1 min, for groups A and B respectively (p < 0.05). Mean time required to achieve complete haemostasis was 195.5 s in group A and 361.8 in control group B (p < 0.0001). Mean estimated blood loss was 111.3 mL and 230 mL in groups A and B, respectively (p < 0.05). Mean hemoglobin decrease was 1.36 g/dL and 2.04 g/dL in groups A and B, respectively (p < 0.05). CONCLUSIONS: The use of Tisseel during LM may represent a valid alternative solution for obtaining hemostasis, reducing intra- and postoperative bleeding. Furthermore, it may help the surgeon to obtain a rapid healing of the injured surfaces, probably reducing the use of electrocoagulationand traumatisms.

Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcoma cell lines is linked to tubulin-beta-III expression.

OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas (CS). METHODS: Five primary carcinosarcoma cell lines, two from uterine and three of ovarian origin, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. To identify potential mechanisms underlying the differential sensitivity/resistance to patupilone, expression levels of ß-tubulin III (TUBB3) were determined with quantitative-real-time-polymerase-chain-reaction (q-RT-PCR) in primary uterine and ovarian CS cell lines and in 26 uterine and 9 ovarian CS fresh-frozen-tissues. RESULTS: No appreciable difference in sensitivity to patupilone versus paclitaxel was noted in ovarian CS cell lines, or when uterine and ovarian CS cell lines were compared in their response to paclitaxel. In contrast, uterine CS cell lines were found to be significantly more sensitive to patupilone than to paclitaxel (P<0.002) and demostrated lower IC(50s) to patupilone (range 0.76-0.93nM) when compared to ovarian CS (range 1.9-3.4 nM, p<0.05). Higher levels of TUBB3 were detected in uterine CS cell lines and fresh frozen tissues when compared to ovarian CS (P<0.05). CONCLUSIONS: Uterine CS cell lines are significantly more sensitive than ovarian CS cell lines to patupilone versus paclitaxel. High expression of TUBB3 is associated with sensitivity to patupilone in primary CS cell lines and may act as a genetic marker to predict chemotherapy efficacy. Patupilone may represent a promising drug in the treatment of this subset of rare but highly aggressive gynecological tumors.