Surgical nodal assessment for endometrial hyperplasia - A meta-analysis and systematic review.

OBJECTIVE: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. METHODS: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). RESULTS: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. CONCLUSIONS: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy.

Fine-tuning the needle: analysis of acupuncturist response to alarming events during gynecological oncology surgery.

OBJECTIVE: Examining an intra-operative acupuncture/acupressure setting, with real-time "fine-tuning" in response to alarming events (AEvs) during gynecological oncology surgery. METHODS: Narratives of acupuncturists providing intraoperative acupuncture during gynecological oncology surgery were qualitatively analyzed. These described real time "fine-tuning" in response to AEvs during surgery, identified through hemodynamic changes (e.g., systolic/diastolic arterial pressure); bispectral index (BIS) elevation; and feedback from surgeons and anesthesiologists. Documentation of acupuncturist responses to AEvs was addressed as well. RESULTS: Of the 48 patients in the cohort, 33 had at least one intraoperative AEv (69%), of which 30 were undergoing laparoscopic surgery and 18 laparotomies. A total of 77 AEvs were documented throughout surgery (range 1-7; mean: 2.3 events per patient), identified through increased (63 events) or decreased (8) mean arterial pressure (MAP); increased BIS levels (2), or other hemodynamic parameters (4). Integrative oncology interventions implemented in response to AEs included acupressure alone (59); combining acupressure with acupuncture (10); or acupuncture alone (4). In 54 (70%) events, documentation was provided from beginning to conclusion of the AEv, with a mean duration of 9.7 min, with 32 events including a documented anesthesiologist intervention. CONCLUSION: The present study demonstrated the feasibility of intraoperative acupuncture with acupressure, with ongoing "fine-tuning" to AEvs identified through objective pain-related parameters (MAP, heart rate and BIS) and real-time input from surgeons and anesthesiologists. Documentation of the intraoperative IO practitioner's response to these AEvs is important, and should be addressed in future research of the innovative integrative model of care. TRIAL REGISTRATION NUMBER: CMC-18-0037 (Carmel Medical Center, June 11, 2018).

Acupuncture during gynecological oncology surgery: A randomized controlled trial assessing the impact of integrative therapies on perioperative pain and anxiety.

BACKGROUND: In this study, the impact of a multimodal integrative oncology pre- and intraoperative intervention on pain and anxiety among patients undergoing gynecological oncology surgery was explored. METHODS: Study participants were randomized to three groups: Group A received preoperative touch/relaxation techniques, followed by intraoperative acupuncture; Group B received preoperative touch/relaxation only; and a control group (Group C) received standard care. Pain and anxiety were scored before and after surgery using the Measure Yourself Concerns and Wellbeing (MYCAW) and Quality of Recovery (QOR-15) questionnaires, using Part B of the QOR to assess pain, anxiety, and other quality-of-life parameters. RESULTS: A total of 99 patients participated in the study: 45 in Group A, 25 in Group B, and 29 in Group C. The three groups had similar baseline demographic and surgery-related characteristics. Postoperative QOR-Part B scores were significantly higher in the treatment groups (A and B) when compared with controls (p = .005), including for severe pain (p = .011) and anxiety (p = .007). Between-group improvement for severe pain was observed in Group A compared with controls (p = .011). Within-group improvement for QOR depression subscales was observed in only the intervention groups (p <0.0001). Compared with Group B, Group A had better improvement of MYCAW-reported concerns (p = .025). CONCLUSIONS: A preoperative touch/relaxation intervention may significantly reduce postoperative anxiety, possibly depression, in patients undergoing gynecological oncology surgery. The addition of intraoperative acupuncture significantly reduced severe pain when compared with controls. Further research is needed to confirm these findings and better understand the impact of intraoperative acupuncture on postoperative pain. PLAIN LANGUAGE SUMMARY: Integrative oncology programs are increasingly becoming part of supportive/palliative care, with many working within the Society for Integrative Oncology. This study examined the impact of a multimodal integrative oncology program on pain and anxiety among 99 patients undergoing gynecological oncology surgery. Participants were randomized to three groups: preoperative touch/relaxation treatments, followed by intraoperative acupuncture; preoperative touch/relaxation without acupuncture; and a control group receiving standard care only. The preoperative touch/relaxation intervention significantly reduced perioperative anxiety, with the addition of intraoperative acupuncture significantly reducing severe pain as well, when compared with controls. Further research is needed to confirm these findings.

Attitude of BRCA1/2 mutation carriers towards surgical risk reduction for breast, ovarian and uterine cancer: still much to be done.

OBJECTIVE: To study and quantify the attitude of BRCA1/2 mutation carriers towards surgical risk reduction procedures. METHODS: This cross-sectional national study was conducted by distribution of an anonymous questionnaire on social media platforms and to BRCA1/2 carriers' medical clinic. RESULTS: 530 BRCA1/2 mutation carriers answered the survey. Risk reduction bilateral salpingo-oophorectomy was discussed with 447/489 (91%) of patients and performed in 260/489 (53%). Hormonal replacement therapy was discussed in 280/474 (59%) of patients. Addition of hysterectomy to risk reduction bilateral salpingo-oophorectomy was discussed in 129/481 (27%) of patients and performed in 44/443(10%). Age over 35 years at time of mutation detection was found to be significant in raising risk reduction bilateral salpingo-oophorectomy and hysterectomy performance rates. Risk reduction mastectomy was discussed in 390/471 (83%) of patients and performed in 156/471 (33%). In a multivariate analysis, BRCA1 mutation carriers (OR=1.66 (95% CI 1.07 to 2.57), p=0.024) and a personal cancer history leading to the mutation detection (OR=4.75 (95% CI 1.82 to 12.4), p=0.001) were found to be significant in increasing the likelihood of opting for risk reduction mastectomy. Additionally, highest risk reduction mastectomy performance rates were observed in the group of patients with a first-degree family history of breast cancer under the age of 50 years (OR=1.58 (95% CI 1.07 to 2.32), p=0.01). CONCLUSIONS: This study highlights the high performance rates of risk reduction bilateral salpingo-oophorectomy, while hysterectomy was added in 10%, and that despite high awareness and acceptance rates for risk reduction mastectomy, only 33% had the procedure. The data presented provides insights for the clinician counseling BRCA1/2 mutation carriers, with regards to adherence to recommendations, understanding their concerns towards treatment and management alternatives; and finally, to construct a personalized management medical plan.

Sentinel lymph node sampling versus full lymphadenectomy in endometrial cancer: a SEER database analysis.

OBJECTIVE: To assess the long term outcomes and prognosis of sentinel lymph node sampling compared with full lymph node dissection in endometrial cancer patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for information on women diagnosed with endometrial cancer from 2010 to 2019. We conducted a comparison including overall survival between patients who had undergone sentinel lymph node sampling only and patients who had undergone formal lymph node dissection. Propensity score matching was performed according to the patient's age, type of endometrial cancer, grade and stage of disease, and adjuvant therapy. Subgroup analyses were performed according to type and grade of endometrial cancer. RESULTS: 41411 endometrial cancer patients were identified through the database. After matching, 6019 patients each were included in the sentinel lymph node and lymph node dissection groups. Median (interquartile range (IQR)) follow-up time was 16 (7-31) months in both groups. One year survival rates were longer in the sentinel lymph node group compared with the lymph node dissection group (hazard ratio (HR) 1.61 (95% confidence interval (CI) 1.17 to 2.21); p=0.004). Subgroups analysis according to grade of disease showed that 1 year survival rates were longer in the sentinel lymph node group in patients with endometrioid-type grade 1-2 endometrial cancer (HR 1.70 (95% CI 1.31 to 2.56); p=0.01), while no difference in survival was found between the sentinel lymph node and lymph node dissection groups in the subgroup of patients with high grade endometrial cancer (HR 1.40 (95%CI 0.94 to 2.24); p=0.17). In patients with low grade endometrial cancer included in the sentinel lymph node group, only 7% had lymph nodes positive for malignancy compared with 17% in the high grade group. CONCLUSION: Survival rates were not compromised in endometrial cancer patients undergoing sentinel lymph node sampling versus full lymph node dissection for all grades of disease.

Endometrial carcinosarcoma.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer-Implications for counseling-A SEER analysis.

OBJECTIVE: To assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging. STUDY DESIGN: With permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years. RESULTS: A total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56-1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo-oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83-1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment. CONCLUSION: Ovarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

Clear cell carcinoma of the endometrium.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Five-year survival decreases over time in patients with BRCA-mutated ovarian cancer: a systemic review and meta-analysis.

INTRODUCTION: Short-term survival rates of patients with BRCA-mutated ovarian cancer have been previously shown to be longer than those of non-carriers. We aimed to study the long-term survival rates of these patients and investigate whether the 5-year advantage decreases over time. METHODS: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes (PRISMA) statement. The study protocol can be assessed at PROSPERO International prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42019137455). We considered for inclusion studies providing Kaplan-Meier survival curves up to and including 10 years, comparing patients with ovarian cancer with and without BRCA mutations. Our main outcome was the conditional probability of surviving an additional 5 years. RESULTS: A total of 13 references comprising 4565 patients was analyzed, of which 1131 BRCA1/2-mutated carriers and 3434 non-carriers were included. The expected higher 5-year survival rate in BRCA-mutated patients was observed (risk difference (RD)=14.9%, p=0.0002, risk ratio (RR)=1.36, p=0.001). Ten-year survival rates were comparatively less improved in BRCA-mutated patients (RD=8.6%, p=0.042, RR=1.25, p=0.12). After already surviving 5 years, no advantage in probability of further surviving 5 additional years was observed for the BRCA-mutated group (RD=2.9%, p=0.71, RR=0.97, p=0.78). CONCLUSION: Our results provide insight into long-term survival rates and prognosis in patients with BRCA-mutated ovarian cancer which suggest that, despite the improved 5-year prognosis, the conditional probability of surviving an additional 5 years does not show the same advantage. The relatively low long-term advantage highlights the significance of epithelial ovarian cancer recurrence prevention. In the era of poly adenosine ribose inhibitors, future studies should explore the adequate follow-up and the benefit of a longer maintenance treatment phase, aiming to prolong the long-term survival of BRCA-mutated patients.

Prognosis of Human Papillomavirus-Negative Compared to Human Papillomavirus-Positive Cervical Cancer.

OBJECTIVES: The aims of the study were to evaluate the prevalence and prognosis of human papillomavirus (HPV)-negative cervical cancer (CC) and to compare these to data for HPV-positive CC. MATERIALS AND METHODS: This retrospective cohort study compared between HPV-negative CC and HPV-positive CC patients. Primary end points were disease-free survival and overall survival. Secondary end points were demographic and clinical variables including histological diagnosis, stage, and treatment. RESULTS: Of 233 women with CC, 18 (8%) tested HPV-negative. During a median follow-up of 45 months, 33 (14%) recurrences and 41 (18%) deaths were observed. Eleven of the 18 women (61%) who tested HPV-negative and 41 of the 215 (19%) who tested HPV-positive had only adenocarcinoma (p < .001). In a multivariate logistic regression analysis, advanced age (p = .003) and primary treatment with chemotherapy and/or radiotherapy (p < .001) remained statistically significant for recurrence or mortality (disease-free survival). The factors associated with lower survival were advanced age (p = .008), higher stage at diagnosis (p < .001), and HPV negativity (p = .062). Median overall survival for HPV-positive CC was not reached, compared with 24 months for HPV-negative CC. Kaplan-Meier curves showed lower rates of disease-free survival (p = .008) and overall survival (p = .011), for women with HPV-negative compared with HPV-positive CC. CONCLUSIONS: The relatively poor prognosis of HPV-negative CC is important in light of its relatively high prevalence, which could increase proportionally to HPV-positive CC due to increased HPV screening and vaccination. Further studies are needed to confirm whether HPV status is truly an independent prognostic factor in CC.

[GESTATIONAL TROPHOBLASTIC DISEASE: THE NEED FOR CENTRALIZATION OF TREATMENT CENTERS IN ISRAEL].

INTRODUCTION: Gestational trophoblastic disease comprises a spectrum of pregnancy-related disorders, consists of premalignant disorders of complete and partial hydatidiform mole, and malignant disorders such as invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumor/epithelioid trophoblastic tumor. These malignant forms are termed Gestational Trophoblastic Neoplasia (GTN). Until the early 1960's, hysterectomy was the treatment of choice for women with malignant trophoblastic diseases. The five-year survival rate was 40% for local disease, and around 20% in women with metastases. Chemotherapy, treatment according to the various risk factors and the use of ß-hCG values as a marker for monitoring the disease, resulted in a cure rate exceeding 98%, while preserving patient's fertility. Due to its` extremely low incidence with relatively complex treatment protocols, in the presence of high potential for side effects, in most countries there are tertiary centers that coordinate the treatment and follow-up of these diseases. In this review, we will summarize strategies for the primary management of gestational trophoblastic disease, the evaluation and management of malignant gestational trophoblastic neoplasia (GTN) and surveillance after treatment.

Should the risk for uterine cancer influence decision making for prophylactic hysterectomy in BRCA1/2 mutated patients- a systematic review and meta-analysis.

OBJECTIVE: To study the possible association between uterine cancer and the BRCA1/2 associated cancer syndrome and discuss the implications of such an association on the clinical managment of patients with BRCA1/2 mutations. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Study protocol was prospectively registered at PROSPERO International prospective register of systematic reviews (registration number CRD42020193496). Considered for inclusion were studies providing the diagnosis rate of uterine cancer in patients with BRCA1/2 mutations by comparing observed and expected rate according to a known disease incidence. The results were measured by standardized incidence ratio (SIR). The primary outcome was defined as any uterine cancer diagnosis and subgroup analyses were conducted for uterine serous papillary cancer (USPC) specifically and for BRCA1 and BRCA2 mutations separately. RESULTS: 4591 records were identified through database search; eight studies were finally included, comprising 13,098 patients with BRCA1/2 mutations. BRCA1/2 mutated patients were found to have a significantly higher risk for uterine cancer compared to the general population (SIR = 2.22, 95% CI 1.76-2.8, p < 0.001). A higher incidence of USPC was also found in patients with BRCA1/2 mutations (SIR = 17.97, 95% CI 9.89-32.66, p < 0.001), as well as in a separate analysis for BRCA1 (SIR = 2.81, 95% CI 2.09-3.79, p < 0.001) and BRCA2 (SIR = 1.75, 95% CI 1.09-2.80, p < 0.001) mutations. CONCLUSION: Patients who carry a BRCA1/2 mutation are at a significantly higher risk of developing uterine cancer, specifically USPC, supporting that USPC may be a component of the BRCA1/2 syndrome. The decision to perform concurrent hysterectomy at the time of the risk reduction bilateral salpingo -oophorectomy surgery should be considered individually.

Uterine serous carcinoma.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

Correlation between an integrative oncology treatment program and survival in patients with advanced gynecological cancer.

OBJECTIVE: Integrative oncology (IO) is increasingly becoming part of palliative cancer care. This study examined the correlation between an IO treatment program and rates of survival among patients with advanced gynecological cancer. METHODS: Patients were referred by their oncology healthcare professionals to an integrative physician (IP) for consultation and IO treatments. Those undergoing at least 4 treatments during the 6 weeks following the consultation were considered adherence to the integrative care program (AIC), versus non-adherent (non-AIC). Survival was monitored for a period of 3 years, comparing the AIC vs. non-AIC groups, as well as controls who did not attend the IP consultation. RESULTS: A total of 189 patients were included: 71 in the AIC group, 44 non-AIC, and 74 controls. Overall 3-year survival was greater in the AIC group (vs. non-AIC, p = 0.012; vs. controls, p = 0.003), with no difference found between non-AIC and controls (p = 0.954). Multimodal IO programs (≥ 3 modalities) were correlated in the AIC group with greater overall 3-year survival (p = 0.027). Greater rates of survival were also found in the AIC group at 12 (p = 0.004) and 18 months (p = 0.001). When compared with the AIC group, a multivariate analysis found higher crude and adjusted hazard ratios for 3-year mortality in the non-AIC group (HR 95% CI 2.18 (1.2-3.9), p = 0.010) and controls (2.23 (1.35-3.7), p = 0.002). CONCLUSION: Adherence to an IO treatment program was associated with higher survival rates among patients with advanced gynecological cancer. Larger prospective trials are needed to explore whether the IO setting enhances patients' resilience, coping, and adherence to oncology treatment.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer.

OBJECTIVES: We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS: Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS: The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS: Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Enhanced Recovery after Surgery is Feasible and Beneficial and Should Be the Standard in Major Gynecological Surgeries.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs. OBJECTIVES: To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries. METHODS: We compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017 to December 2018) and after (January 2019 to March 2020) the implementation of the ERAS protocol. Eighty women were included in each group. RESULTS: The clinical and demographic characteristics were similar among the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89 ± 2.56 to 4.09 ± 1.65 days, P = 0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%), P = 0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%), P < 0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications. CONCLUSIONS: Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding, and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications or with re-admissions.

End-of-life Care Among Gynecological Oncology Patients in a Single Institute in Israel.

BACKGROUND: Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time. OBJECTIVES: To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies. METHODS: The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013-2014 to the years 2015-2019. RESULTS: We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients' relatives were satisfied with EOL care. CONCLUSIONS: Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

The added benefit of transvaginal sonography in the clinical staging of cervical carcinoma.

INTRODUCTION: Patients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high-detail TVS, and positron emission tomography with 18 F-labeled fluoro-2-deoxyglucose and computed tomography (18 F-FDG PET/CT) may contribute to triage efficiency of cervical cancer patients. MATERIAL AND METHODS: This is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010-2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities-a thorough physical examination, a high-detail TVS, and positron emission tomography (PET) with 18 F-FDG and computed tomography (18 F-FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation. RESULTS: Seventy-three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone. CONCLUSIONS: The combination of high-detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18 F-FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.

Is There a Survival Advantage in Diagnosing Endometrial Cancer in Asymptomatic Patients? A Systemic Review and Meta-analysis.

Data supporting a survival advantage of endometrial cancer diagnosed before the onset of postmenopausal bleeding are lacking. This study sought to compare overall survival and disease recurrence between women who were asymptomatic at diagnosis and women who were symptomatic at diagnosis. A systemic search was conducted in databases using the terms: "asymptomatic," "ultrasound," "screening," and "endometrial cancer." Only original research studies that compared characteristics of tumour advancement and survival measures were included. The six articles included in the meta-analysis comprised 2961 patients. Data were collected on study design and period, number and characteristics of participants, and outcomes in terms of tumour histology and survival measures. Higher rates of stage I tumours were shown among asymptomatic patients (relative risk 1.19). The proportion of high-grade histology did not differ between the two groups (relative risk 0.92). The crude pooled estimate for overall survival did not yield statistical significance, nor did recurrence-free survival (which was reported by three studies). In conclusion, endometrial cancer diagnosed in asymptomatic women is not associated with higher survival than in symptomatic women. Invasive procedures in asymptomatic women with incidental ultrasonographic findings should be carefully weighed because no survival advantage is expected.