The Role of TAP/RS Block in Minor Gynecologic Laparoscopic Surgery: A Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.

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.

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.

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.

Effectiveness of CO2 laser on urogenital syndrome in women with a previous gynecological neoplasia: a multicentric study.

BACKGROUND: Many women diagnosed with gynecological cancers undergo adjuvant therapy, which may lead to transient or permanent menopause that ultimately leads to urogenital syndrome and vulvovaginal atrophy. Studies advise against the use of estrogen in women with a history of hormone-dependent cancer. One alternative is vaginal microablative fractional CO2 laser, which promotes tissue regeneration through the production of collagen and elastic fibers. OBJECTIVE: To evaluate the effectiveness of CO2 laser in the treatment of urogenital syndrome-in particular, symptomatic vulvovaginal atrophy in women who have survived gynecological cancers. METHODS: A retrospective study was carried out, including all patients with a history of gynecological cancers and vulvovaginal atrophy who underwent CO2 laser treatment between November 2012 and February 2018 in four Italian centers. The study was approved by the local ethics committee of each participating institution. The inclusion criteria were women aged between 18 and 75; Eastern Cooperative Oncology Group performance status <2; and history of breast, ovarian, cervical, or uterus cancer. Patients had to have vulvovaginal atrophy and at least one of the following symptoms of urogenital syndrome: vaginal dryness, dyspareunia, vaginal introitus pain, burning, or itching. Three applications were administered at baseline, 30 days, and 60 days. All patients were evaluated before the first laser session, at each session, and 4 weeks after the last session. In particular, patients were asked to indicate the intensity of symptoms before the first session and 4 weeks after the last session, using Visual Analog Scale (VAS) scoring from 0 ('no discomfort') to 10 ('maximum discomfort'). RESULTS: A total of 1213 patients underwent CO2 laser treatment and of these, 1048 were excluded because they did not meet the inclusion criteria in the analysis. Finally, a total of 165 patients were included in the study. The mean age at the time of treatment was 53 years (range 31-73). Dryness improved by 66%, dyspareunia improved by 59%, burning improved by 66%, pain at introitus improved by 54%, and itching improved by 54%. The side effects were evaluated as pain greater than VAS score 6 during and after the treatment period. No side effects were seen in any sessions. CONCLUSIONS: Fractional microablative CO2 laser therapy offers an effective strategy in the management of the symptoms of genitourinary syndrome in post-menopausal women and in survivors of gynecological cancer.

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.

Anterior colporrhaphy plus inside-out tension-free vaginal tape for associated stress urinary incontinence and cystocele: 10-year follow up results.

AIMS: We report the success rate and complications rate of combined ultralateral anterior Colporrhaphy plus Tension-free Vaginal Tape (TVT-O) in a long-term (10 year) follow-up prospective survey. METHODS: Patients previously treated for associated stress urinary incontinence (SUI) and cystocele were subjected to annual follow-up for 10 year with a complete urogynecologic evaluation. Furthermore, an urodynamic assessment and a quality of life questionnaire (ICIQ-UI SF) were recorded at the 5th and 10th year of follow up. RESULTS: Fifty patients treated between June 2004 and May 2006 were included in the analysis. Five patients did not return to 5-yr follow-up: two patients developed a median tape erosion and three patients withdraw. At 10-yr follow-up two more patients withdraw for a total of seven patients lost to follow-up. After 10 years patients objectively cured from cystocele were 41 (95%) while patients objectively cured from SUI were 39 (91%). At 10th year follow-up 38 patients (89%) result cured from both SUI and cystocele, 3 (7%) patients result cured only from prolapse, 1 (2%) patient only from SUI, and 1 (2%) patient result objectively failed for both SUI and cystocele. The ICIQ-UI SF scores at 10th year follow-up was 6.2 ± 3.7. The late complication rate at 10th year follow-up was 32% (OAB symptoms 20%; Mixed incontinence 2%; Bladder outlet obstruction 0%; Dyspareunia 6%; Chronic pelvic pain 0%; Vaginal tape erosion 4%; Detrusor hyperactivity 0%). CONCLUSIONS: The combined procedures shown proved to be an effective and safe procedure to treat concomitant SUI and cystocele.

Assessment of Quality of Life and Urinary and Sexual Function After Radical Hysterectomy in Long-Term Cervical Cancer Survivors.

AIMS: The aim of this study was to evaluate long-term quality of life and urinary and sexual function in long-term cervical cancer survivors previously treated with radical hysterectomy (RH) type C2/type III. METHODS: All patients who presented at Campus Bio-Medico of Rome for RH type C2/type III for cervical cancer were considered eligible for this retrospective study protocol. We included exclusively patients with complete response to primary treatment with at least 36 months of follow up. Included subjects were interviewed with the European Organization for Research and Treatment of Cancer QLQ-CX24 Questionnaire, European Organization for Research and Treatment of Cancer QLQ-C30, and an Incontinence Impact Questionnaire 7. RESULTS: From January 2004 to June 2014, 251 patients affected by locally advanced cervical cancer were treated at Campus Bio-Medico of Rome treated with type C2/type III RH. At time point of March 2017, 90 patients were included with a mean age of 55.6 ± 8.5 years. The questionnaires were administered after a median follow-up of 49 months after the end of therapy. The symptoms of fatigue, nausea and vomiting, appetite loss, pain, insomnia, and dyspnea, as well as a negative financial impact, were reported as not frequent and rarely disabling. On the contrary, patients frequently reported gastrointestinal complaints. Diarrhea was present in 6% of patients and was referred as mild; constipation was present in 75% of women and was reported as mild in 30% of cases, moderate in 30%, and severe in 15%. Concerning sexual activity, data indicated a good level of sexual enjoyment with a slight worsening of sexual activity. Incontinence was reported in 28% of cases and appeared to be mild and rarely disabling (all mean values <2). CONCLUSIONS: Waiting for ongoing randomized controlled trials, this study confirmed that RH may be considered as a useful treatment plan, according to its negligible long-term impact on quality of life, urinary dysfunction, and sexual function.

The Role of HE4, a Novel Biomarker, in Predicting Optimal Cytoreduction After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer.

OBJECTIVES: This study aimed to evaluate serum human epididymis protein 4 (HE4) changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography (CT) taken together are better able to predict complete cytoreduction after NACT in advanced ovarian cancer patients. METHODS: From January 2006 to November 2015, patients affected by epithelial advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV), considered not optimally resectable, were included in this prospective study. After 3 cycles of NACT, all patients underwent debulking surgery and were allocated, according to residual tumor (RT), into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were recorded during NACT and compared singularly and with each other in term of accuracy, sensitivity, specificity, and positive and negative predictive value. RESULTS: A total of 94 and 20 patients were included in group A and group B, respectively. The HE4 values recorded before debulking surgery correlated with RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and a specificity of 85% (positive predictive value, 0.87; negative predictive value, 0.70). The combination of CA125, HE4, and CT imaging resulted in the best combination with a sensitivity of 96% and a specificity of 92% (positive predictive value, 0.96; negative predictive value, 0.94). CONCLUSIONS: The novel biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at debulking surgery and the prognosis of patients.

Role of paroxetine in the management of hot flashes in gynecological cancer survivors: Results of the first randomized single-center controlled trial.

OBJECTIVES: To examine the effects of paroxetine supplementation on hot flashes and sleep in gynecological cancer survivors. METHODS: In a randomized, double-blind, placebo-controlled study, postmenopausal women with a prior history of stage 0-III gynecological cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 7.5mg oral paroxetine or placebo daily for 16weeks. Sleep and hot flashes were assessed at baseline, week 4 and week 16. RESULTS: Eighty women (91%) completed the study. We found out a statistically significant difference in weekly reductions in VMS frequency and severity for paroxetine 7.5mg than for placebo on week 4 and 16. Regarding sleep characteristics, the analysis of data through week 16 reported a statistically significant reduction in the number of nighttime awakenings attributed to VMS among participants receiving paroxetine than among participants receiving placebo on baseline and weeks. The duration of sleep per night increased significantly more among participants receiving paroxetine than among those receiving placebo at all post baseline time points. No significant differences in sleep-onset latency were noted between the two treatment arms during the course of the study. Paroxetine was well-tolerated with a high level of compliance. In our cohort of patients, no serious adverse events have been reported. CONCLUSIONS: This is the first randomized placebo-controlled study in gynecological cancer survivors that demonstrates that paroxetine significantly reduces hot flashes in weekly frequency and severity and the number of nighttime awakenings attributed to vasomotor symptoms, increasing sleep duration.

Quality of Life in Platinum-Sensitive Recurrent Ovarian Cancer: Chemotherapy Versus Surgery Plus Chemotherapy.

PURPOSE: This study was designed to compare quality of life in a sample of Italian patients affected by platinum-sensitive recurrent ovarian cancer and submitted to chemotherapy alone or secondary cytoreductive surgery plus chemotherapy through validated questionnaires. METHODS: From January 2007 to December 2012, consecutive patients with suspicious recurrence of ovarian cancer, referred to the Division of Gynecologic Oncology at the University Campus Bio-Medico of Rome, were assessed for this prospective, case-control study. After a diagnostic laparoscopy, surgical resectable patients were enrolled in group A (surgery plus chemotherapy). Patients not suitable for optimal debulking surgery and all patients who refused surgery were enrolled in group B (chemotherapy alone). At beginning of treatment, after the third and sixth cycle of chemotherapy, all eligible patients were asked to fill in QLQ-C30 (version 3.0) and EORTC QLQ-OV28 questionnaires. RESULTS: Group A included 38 patients and underwent SCS followed by chemotherapy; group B included 16 patients that were submitted to chemotherapy alone. Quality-of-life scores of both questionnaires were comparable between groups, with the exception of constipation and pain, which resulted significantly worsened in Group A at 3 months. This difference was no longer present at 6 months. Median overall survival was 72 % for Group A and 56 % in Group B at median follow-up of 35 months for Group A and 32 months for Group B. CONCLUSIONS: Both surgery followed by chemotherapy and chemotherapy alone seem to have a negligible impact on QOL. SCS plus chemotherapy seems to be an effective and tolerable therapeutic option in platinum-sensitive recurrences.

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.

A randomized controlled trial comparing four versus six courses of adjuvant platinum-based chemotherapy in locally advanced cervical cancer patients previously treated with neo-adjuvant chemotherapy plus radical surgery.

OBJECTIVES. The aim of this study was to compare 4 versus 6 courses of adjuvant chemotherapy after neoadjuvant chemotherapy plus radical surgery in terms of overall survival (OS), disease-free survival (DFS), recurrence rate and toxicity profile. METHODS. We randomly assigned 200 patients with IB2-IIB cervical cancer to receive 4 (Group A) or 6 (Group B) courses of cisplatin 100 mg/mq and paclitaxel 175 mg/mq every 21 days. RESULTS. At 4-years follow-up, the comparison of recurrence rate (p = 1; RR = 1.005; 95% CI = 0.87 to 1.161), OS (p = 0.906) and DFS (p = 0.825) did not show statistically significant differences between the two groups. Data analysis showed statistically significant differences between the two groups in term of episodes of leukopenia (p = 0.0072; RR = 1.513; 95% CI = 1.127-2.03), anemia (p = 0.048; RR = 1.188; CI = 1.012-1.395) and febrile neutropenia (p = 0.042; RR = 1.119; 95% CI = 1.014-1.235), in favor of Group A. As regards non-hematological toxicities, there were no statistically significant differences in terms of gastrointestinal symptoms (p = 0.49; RR = 1.046; CI = 0.948-1.153. On the contrary, there was a statistically significant difference regarding neurological symptoms (p=0.014; RR=1.208; CI=1.046-1.395), that were less frequent in Group A (13%) than in Group B (28%). CONCLUSIONS. Adjuvant treatment with 4 or 6 courses of platinum-based chemotherapy showed similar results in terms of OS and DSF, with a favorable toxicity profile in favor of the first regimen.

Chemotherapy as Adjuvant Treatment for Intermediate-High Risk Early-Stage Endometrial Cancer: A Pilot Study.

OBJECTIVE: This study aimed to assess primarily the role of chemotherapy as adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) stage IA G3, IB G2-G3, and II endometrial cancer (EC) in terms of disease-free interval and overall survival, and secondarily, the rate of local and distant recurrence. METHODS: The present prospective pilot study includes 68 patients with surgical staged EC who referred between 2007 and 2011 to the Division of Gynecologic Oncology at the University Campus Bio-Medico of Rome. All enrolled patients received adjuvant chemotherapy every 3 weeks according to the scheme carboplatin, dosed at an area under the curve of 6, and paclitaxel 175 mg/mq given every 3 weeks for at least 3 cycles. RESULTS: The median number of chemotherapy cycles was 6 (range, 3-6 cycles). Chemotherapy was well tolerated. The 3-year overall survival was 92.8% and 91.6% for stages I and II, respectively. The 3-year disease-free interval was 91.8% and 83.3% for stages I and II, respectively. Of 68 patients, 7 (10.3%) relapsed: 5 patients with a FIGO stage I and 2 patients with FIGO stage II EC. CONCLUSIONS: Platinum-based chemotherapy is feasible and safe and it could be used in adjuvant setting for early-stage ECs. Although its effectiveness is comparable to radiotherapy, chemotherapy represents an excellent treatment option due to its systemic action. Further randomized studies will be needed to confirm our promising data.

Influence of pneumoperitoneum pressure on surgical field during robotic and laparoscopic surgery: a comparative study.

PURPOSE: Studies on the influence of CO2 pneumoperitoneum on the abdominal cavity during robotic procedures are lacking. This is the first study to evaluate surgical field modifications related to CO2 pressure, during laparoscopic and robotic surgery. METHODS: Consecutive patients scheduled for laparoscopic or robotic hysterectomy were enrolled in the study. To evaluate the level of operative field visualization, a dedicated form has been designed based on the evaluation of four different areas: Douglas space, vesico-uterine fold and, bilaterally, the broad ligament. During the initial inspection, an assistant randomly set the CO2 pressure at 15, 10 and 5 mmHg, and the surgeon, not aware of the CO2 values, was asked to give an evaluation of the four areas for each set pressure. RESULTS: In laparoscopic group, CO2 pressure significantly influenced the surgical field visualization in all four areas analyzed. The surgeon had a good visualization only at 15 mmHg CO2 pressure; visualization decreased with a statistically significant difference from 15 to 5, 15-10 and 10-5 mmHg. In robotic group, influence of CO2 pressure on surgical areas visualization was not straightforward; operative field visualization remained stable at any pressure value with no significant difference. CONCLUSIONS: Pneumoperitoneum pressure significantly affects the visualization of the abdomino-pelvic cavity in laparoscopic procedures. Otherwise, CO2 pressure does not affect the visualization of surgical field during robotic surgery. These findings are particularly significant especially at low CO2 pressure with potential implications on peritoneal environment and the subsequent post-operative patient recovery.

A critical review on HE4 performance in endometrial cancer: where are we now?

To date, no good marker for endometrial cancer (EC) that may be routinely used in clinical practice for diagnosis, prognosis and monitoring is available; besides the use of tumour markers is not recommended by international guidelines. However, during the last years, an increasing interest in literature has been growing on human epididymis protein 4 (HE4) that demonstrated to be a useful clinical marker with high sensitivity and specificity even at early stage. However, published studies differ for some variables such as HE4 cut-off and sample size. Therefore, we assess this comprehensive review to gather all the evidence reported in literature on HE4 potential value in diagnosis, prognosis, and recurrence of EC. A systematic literature search was performed using PubMed/PubMed Central/MEDLINE predefined keywords from January 1952 to June 2013. We divided all the relevant studies into three different clinical issues: "Diagnosis", "Prognosis" and "Disease monitoring". The analysis of published data suggests that HE4 is the most accurate and sensitive EC marker identified to date. In particular, this new marker seems to have a good performance in diagnosis. The best cut-off of HE4 in diagnosis ranges between 50 and 70 pmol/L, resulting at least in 78.8 % of sensitivity and 100 % of specificity in all stages. Another important aspect to consider is HE4 capacity in predicting the stage of disease and myometrial involvement, which can help scheduling the appropriate timing of imaging and surgery in a more individualised fashion and as indicator of patients prognosis.

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.

Old Issues and New Perspectives on Endometrial Cancer Therapy: How Molecular Characteristics Are Changing the Therapeutic Pathway.

The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis.

Tailored Treatment Strategies in First Line Therapy for Ovarian Cancer Patients: A Critical Review of the Literature.

BACKGROUND: Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi). MATERIALS AND METHODS: This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov. RESULTS: The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients. CONCLUSIONS: PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.