Robotic approach for the treatment of gynecological cancers recurrences: A ten-year single-institution experience.

INTRODUCTION: Although the management of gynecological cancers recurrences may be challenging, due to the heterogeneity of recurrent disease, the aim of this work is to present a descriptive analysis of gynecological malignancies recurrences in our institution treated by robotic approach. MATERIALS AND METHODS: We performed a retrospective review and analysis of data of patients who underwent robotic surgery for recurrent gynecological malignancies at Catholic University of the Sacred Hearth, Rome, from January 2013 to January 2024. RESULTS: A total of 54 patients underwent successful robotic cytoreductive surgery. The median age was 63 years; the median BMI was 33 kg/m2 and most of the patients (59 %) were obese. In 12 cases (22 %) the relapse presented was the second or third relapse. The most frequent patterns of recurrence were represented by lymph nodes (41 %), followed by peritoneal (26 %), pelvic (22 %) and parenchymal (11 %). In all patients complete cytoreduction was achieved. In 29 patients (54 %) the surgical field was previous treated. The median operative time and estimated blood loss were, respectively, 270 min and 100 ml. There were 2 intraoperative complications, managed endoscopically; 10 early postoperative complications, and 3 late postoperative complications. The 2-year progression-free-survival and overall survival were, respectively, 39.8 % and 72.3 %. CONCLUSION: Robotic approach in the treatment of recurrent gynecological cancers should be considered in selected patients with oligometastatic disease, in high-volume centers with expert surgeons, particularly in obese patients.

Survival associated with the use of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node metastasis in cervical cancer.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is part of surgical treatment of apparent early-stage cervical cancer. SLN is routinely analyzed by ultrastaging and immunohistochemistry. The aim of this study was to assess the survival of patients undergoing SLN analyzed by one-step nucleic acid amplification (OSNA) compared with ultrastaging. METHODS: Single-center, retrospective, cohort study. Patients undergoing primary surgery and SLN mapping ( ±pelvic lymphadenectomy) for apparent early-stage cervical cancer between May 2017 and January 2021 were included. SLN was analyzed exclusively with OSNA or with ultrastaging. Patients with bilateral SLN mapping failure, with SLN analyzed alternatively/serially with OSNA and ultrastaging, and undergoing neo-adjuvant therapy were excluded. Baseline clinic-pathological differences between the two groups were balanced with propensity-match analysis. RESULTS: One-hundred and fifty-seven patients were included, 50 (31.8%) in the OSNA group and 107 (68.2%) in the ultrastaging group. Median follow up time was 41 months (95%CI:37.9-42.2). 5-year DFS in patients undergoing OSNA versus ultrastaging was 87.0% versus 91.0% (p = 0.809) and 5-year overall survival was 97.9% versus 98.6% (p = 0.631), respectively. No difference in the incidence of lymph node recurrence between the two groups was noted (OSNA 20.0% versus ultrastaging 18.2%, p = 0.931). In the group of negative SLN, no 5-year DFS difference was noted between the two groups (p = 0.692). No 5-year DFS and OS difference was noted after propensity-match analysis (87.6% versus 87.0%, p = 0.726 and 97.4% versus 97.9%, p = 0.998, respectively). CONCLUSION: The use of OSNA as method to exclusively process SLN in cervical cancer was not associated with worse DFS compared to ultrastaging. Incidence of lymph node recurrence in the two groups was not different.

The potential role of systemic inflammatory markers in predicting recurrence in early-stage cervical cancer.

INTRODUCTION: The influence of systemic inflammatory markers on early-stage cervical cancer (ECC) patients is contradictory. No previous study analyzed whether these markers may be suggestive of recurrence. The aim of this study was to assess whether the inflammatory markers level of patients with recurrence during surveillance was different from those of patients without recurrence representing a risk factor for recurrence. METHODS: Retrospective, single-center, observational study. Patients with 2009 FIGO EEC surgically treated between 2012 and 2019 were included. Baseline inflammatory markers were evaluated on the results of the complete blood count (CBC) and coagulation tests. Inflammatory markers of relapsed patients were evaluated on the last CBC performed before the relapse diagnosis. Inflammatory markers of patients with no recurrence were evaluated on the available CBC taken at the same median follow-up time as the one from relapsed patients. RESULTS: 174 patients were included. Baseline Systemic immune inflammation index (SII) > 663 and Systemic inflammation response index (SIRI) > 0.98 were associated with significant risk of recurrence. SII>663 and Neutrophil to lymphocyte ratio (NLR) > 2.41 were associated with increased risk of death. Significant changes between relapsed (n = 23) and non-relapsed (n = 151) patients in median values of SII (615 versus 490, p-value = 0.001), SIRI (0.74 versus 1.05, p-value = 0.005), NRL (2.95 versus 2.15, p-value = 0.0035), and MLR (0.26 versus 0.22 p-value = 0.020), showed that different levels of inflammatory markers could help identifying recurrent disease during surveillance. CONCLUSION: Baseline SII>663 and SIRI>0.98 were associated with increased risk of recurrence. Higher median values of SII, SIRI, NLR and MLR in relapsed patients highlight their potential association with recurrence.

Can the Modified Frailty Index (mFI) Predict Intraoperative and Postoperative Complications in Older Women with Endometrial Cancer Undergoing Laparoscopic or Robotic Surgery? A Multicenter Observational Study.

BACKGROUND: This study aims to evaluate the strength of the association between frailty and intraoperative/postoperative complications in patients undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: In this retrospective observational multicenter cohort study, frailty was defined beforehand by a modified frailty index (mFI) score of ≥3. Multiple logistic regressions were performed to investigate possible preoperative predictors-including frailty, age, and body mass index-of intraoperative and early (within 30 days from surgery) or delayed (beyond 30 days from surgery) postoperative complications. RESULTS: The study involved 577 women, of whom 6.9% (n = 40) were frail with an mFI ≥ 3, while 93.1% (n = 537) were non-frail with an mFI of 0-2. Frail women had a significantly higher rate of intraoperative complications (7.5% vs. 1.7%, p = 0.01), with odds 4.54 times greater (95% CI: 1.18-17.60, p = 0.028). There were no differences in the rate of early postoperative complications (15% vs. 6.9%, p = 0.06) and delayed postoperative complications (2.5% vs. 3.9%, p = 0.65) for frail versus non-frail patients. The odds of early postoperative complications increased by 0.7% (95% CI: 1.00-1.15) for every one-unit increase in age (p = 0.032). CONCLUSIONS: Frailty was associated with a significantly higher risk of intraoperative complications in older women undergoing MIS for endometrial cancer. Likewise, increasing age was an independent predictor of early postoperative complications. Our findings support the practice of assessing frailty before surgery to optimize perioperative management in this patient population.

Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy.

OBJECTIVE: Aim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS. MATERIAL AND METHODS: The study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018. RESULTS: The study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group. CONCLUSIONS: MIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.

Minimally-Invasive Secondary Cytoreduction in Recurrent Ovarian Cancer.

The role of secondary cytoreductive surgery (SCS) in the treatment of recurrent ovarian cancer (ROC) has been widely increased in recent years, especially in trying to improve the quality of life of these patients by utilising a minimally-invasive (MI) approach. However, surgery in previously-treated patients may be challenging, and patient selection and surgical planning are crucial. Unfortunately, at the moment, validated criteria to select patients for MI-SCS are not reported, and no predictors of its feasibility are currently available, probably due to the vast heterogeneity of recurrence patterns. The aim of this narrative review is to describe the role of secondary cytoreductive surgery and, in particular, minimally-invasive procedures, in ROC, analyzing patient selection, outcomes, criticisms, and future perspectives.

Robotic surgery in ovarian cancer.

Ovarian cancer (OC) represents one of the most lethal cancers in women. The aim of surgical treatment is complete cytoreduction in advanced stages and a surgical staging in early stages. Although the guidelines still suggest laparotomy as the standard approach, in recent years minimally invasive surgery (MIS) has become increasingly popular in the treatment of OC, especially in early stages, because the 5-year relative survival exceeds 90% and the patients' quality of life cannot be overshadowed. However, MIS has been demonstrated to have a role even in advanced stages, in the prediction of optimal cytoreduction, identification patients who may benefit from neoadjuvant chemotherapy, and, more recently, in the interval debulking surgery, as in selected cases of secondary cytoreduction for recurrent ovarian cancer. The aim of this review is to describe the MIS (especially robotic surgery), with its advantages and pitfalls, in the treatment of OC.

Special Issue: "Management of Early Stage Cervical Cancer".

Cervical carcinoma is a common gynecological malignancy that remains a challenge for oncologic gynecologists around the world [...].

Ultrastaging of the Parametrium in Cervical Cancer: A Clinicopathological Study.

Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1-IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu-Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node.

Prognostic Significance of Ultrasound Characteristics and Body Mass Index in Patients with Apparent Early-Stage Cervical Cancer: A Single-Center, Retrospective, Cohort Study.

The primary aim of the present study was to investigate the prognostic impact (defined as disease-free-DFS and overall survival-OS) of the ultrasound scan tumor parameters, patients' anthropometric parameters, and their combination in early-stage cervical cancer. The secondary aim was to assess the relation between ultrasound characteristics and pathological parametrial infiltration. This is a retrospective, single-center, observational cohort study. Consecutive patients with clinical FIGO 2018 stage IA1-IB2 and IIA1 cervical cancer who underwent preoperative ultrasound examination and radical surgery between 02/2012 and 06/2019 were included. Patients who underwent neo-adjuvant treatment, fertility sparing surgery, and pre-operative conization were excluded. Data from 164 patients were analyzed. Body mass index (BMI) ≤20 Kg/m2 (p < 0.001) and ultrasound tumor volume (p = 0.038) were related to a higher risk of recurrence. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI were significantly related to a higher risk of recurrence (p = 0.011, p = 0.031, and p = 0.017, respectively). The only anthropometric characteristic related to a higher risk of death was BMI ≤20 Kg/m2 (p = 0.021). In the multivariate analysis, the ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter (with 37 as the cut-off) was significantly associated with pathological microscopic parametrial infiltration (p = 0.018). In conclusion, a low BMI was the most significant anthropometric biomarker impairing DFS and OS in patients with apparent early-stage cervical cancer. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI significantly affected DFS but not OS. The ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter was related to parametrial infiltration. These novel prognostic parameters may be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer.

Beyond Sentinel Lymph Node: Outcomes of Indocyanine Green-Guided Pelvic Lymphadenectomy in Endometrial and Cervical Cancer.

BACKGROUND: The aim of our study was to compare the number of lymph nodes removed during indocyanine green (ICG)-guided laparoscopic/robotic pelvic lymphadenectomy with standard systematic lymphadenectomy in endometrial cancer (EC) and cervical cancer (CC). METHODS: This is a multicenter retrospective comparative study (Clinical Trial ID: NCT04246580; updated on 31 January 2023). Women affected by EC and CC who underwent laparoscopic/robotic systematic pelvic lymphadenectomy, with (cases) or without (controls) the use of ICG tracer injection within the uterine cervix, were included in the study. RESULTS: The two groups were homogeneous for age (p = 0.08), Body Mass Index, International Federation of Gynaecology and Obstetrics (FIGO) stages (p = 0.41 for EC; p = 0.17 for CC), median estimated blood loss (p = 0.76), median operative time (p = 0.59), and perioperative complications (p = 0.66). Nevertheless, the number of lymph nodes retrieved during surgery was significantly higher (p = 0.005) in the ICG group (n = 18) compared with controls (n = 16). CONCLUSIONS: The accurate and precise dissection achieved with the use of the ICG-guided procedure was associated with a higher number of lymph nodes removed in the case of systematic pelvic lymphadenectomy for EC and CC.

Locally advanced cervical carcinoma patients treated with chemoradiation followed by radical surgery: clinical response and oncological outcomes according to histotype after propensity score analysis.

INTRODUCTION: The aims of this study were to analyze the pathological response, and survival outcomes of adenocarcinoma/adenosquamous (AC/ASC) versus squamous cell carcinoma (SCC) in patients with locally advanced cervical cancer (LACC) managed by chemoradiotherapy followed by radical surgery. METHODS: Retrospective, multicenter, observational study, including patients with SCC and AC/ACS LACC patients treated with preoperative CT/RT followed by tailored radical surgery (RS) between 06/2002 and 05/2017. Clinical-pathological characteristics were compared between patients with SCC versus AC/ASC. A 1:3 ratio propensity score (PS) matching was applied to remove the variables imbalance between the two groups. RESULTS: After PS, 320 patients were included, of which 240 (75.0%) in the SCC group, and 80 (25.0%) in the AC/ASC group. Clinico-pathological and surgical baseline characteristics were balanced between the two study groups. Percentage of pathologic complete response was 47.5% in SCC patients versus 22.4% of AC/ASC ones (p < 0.001). With a median follow-up of 51 months (range:1-199), there were 54/240 (22.5%) recurrences in SCC versus 28/80 (35.0%) in AC/ASC patients (p = 0.027). AC/ASC patients experienced worse disease free (DFS), and overall survival (OS) compared to SCC patients (p = 0.019, and p = 0.048, respectively). In multivariate analysis, AC/ACS histotype, and FIGO stage were associated with worse DFS and OS. CONCLUSION: In LACC patients treated with CT/RT followed by RS, AC/ASC histology was associated with lower pathological complete response to CT/RT, and higher risk of recurrence and death compared with SCC patients. This highlights the need for specific therapeutic strategies based on molecular characterization to identify targets and develop novel treatments.

Comparison Between Laparoscopic and Robotic Surgery in Elderly Patients With Endometrial Cancer: A Retrospective Multicentric Study.

INTRODUCTION: Elderly endometrial cancer (EEC) patients represent a challenging clinical situation because of the increasing number of clinical morbidities. In this setting of patients, minimally invasive surgery (MIS) has been shown to improve surgical and clinical outcomes. The aim of this study was to evaluate the peri-operative and oncological outcomes of EEC patients who had undergone laparoscopic (LS) or robotic surgery (RS). MATERIALS AND METHODS: This is a retrospective multi-institutional study in which endometrial cancer patients of 70 years or older who had undergone MIS for EC from April 2002 to October 2018 were considered. Owing to the non-randomized nature of the study design and the possible allocation biases arising from the retrospective comparison between LS and RS groups, we also performed a propensity score-matched analysis (PSMA). RESULTS: A total of 537 patients with EC were included in the study: 346 who underwent LS and 191 who underwent RS. No significant statistical differences were found between the two groups in terms of surgical and survival outcomes. 188 were analyzed after PSMA (94 patients in the LS group were matched with 94 patients in the RS group). The median estimated blood loss was higher in the LS group (p=0.001) and the median operative time was higher in the RS group (p=0.0003). No differences emerged between LS and RS in terms of disease free survival (DFS) (p=0.890) and overall survival (OS) (p=0.683). CONCLUSIONS: Our study showed that when compared LS and RS, RS showed lower blood losses and higher operative times. However, none of the two approaches demonstrated to be superior in terms of survival outcomes. For this reason, each patient should be evaluated individually to determine the best surgical approach.

Role of minimally invasive surgery versus open approach in patients with early-stage uterine carcinosarcomas: a retrospective multicentric study.

OBJECTIVE: The aim of this retrospective study was to compare surgical and survival outcome in only patients with early-stage UCSs managed by laparotomic surgery (LPT) versus minimally invasive surgery (MIS). METHODS: Data were retrospectively collected in four Italian different institutions. Inclusion criteria were UCS diagnosis confirmed by the definitive histological examination, and stage I or II according to the FIGO staging system. RESULTS: Between August 2000 and March 2019, the data relative to 170 patients bearing UCSs were collected: of these, 95 were defined as early-stage disease (stage I-II) based on the histological report at the primary surgery, and thus were included in this study. Forty-four patients were managed by LPT, and 51 patients were managed by MIS. The operative time was lower in the MIS group versus the LPT group (p value 0.021); the median estimated blood loss was less in the MIS group compared to the median of LPT group (p value < 0.0001). The length of hospital stay days was shorter in the MIS patients (p value < 0.0001). Overall, there were eight (8.4%) post-operative complications; of these, seven were recorded in the LPT group versus one in the MIS group (p value 0.023). There was no difference in the disease-free survival (DFS) and overall survival (OS) between the two groups. CONCLUSION: There was no difference of oncologic outcome between the two approaches, in face of a more favourable peri-operative and post-operative profile in the MIS group.

Prognostic Role of the Removed Vaginal Cuff and Its Correlation with L1CAM in Low-Risk Endometrial Adenocarcinoma.

OBJECTIVE: The aim of our study was to investigate the role of the excised vaginal cuff length as a prognostic factor in terms of DFS and recurrence rate/site, in low-risk endometrial cancer (EC) patients. Moreover, we correlated the recurrence with the expression of L1CAM. MATERIAL AND METHODS: From March 2001 to November 2016, a retrospective data collection was conducted of women undergoing surgical treatment for low-risk EC according to ESMO-ESGO-ESTRO consensus guidelines. Patients were divided into three groups according to their vaginal cuff length: V0 without vaginal cuff, V1 with a vaginal cuff shorter than 1.5 cm and V2 with a vaginal cuff longer than or equal to 1.5 cm. RESULTS: 344 patients were included in the study: 100 in the V0 group, 179 in the V1 group and 65 in the V2 group. The total recurrence rate was 6.1%: the number of patients with recurrence was 8 (8%), 10 (5.6%) and 3 (4.6%), in the V0, V1 and V2 group, respectively. No statistically significant difference was found in the recurrence rate among the three groups. Although the DFS was higher in the V2 group, the result was not significant. L1CAM was positive in 71.4% of recurrences and in 82% of the distant recurrences. CONCLUSIONS: The rate of recurrence in patients with EC at low risk of recurrence does not decrease as the length of the vaginal cuff removed increases. Furthermore, the size of the removed vaginal cuff does not affect either the site of recurrence or the likelihood of survival.

Screening for cervical cancer in Africa: A proposal of a different combination of VIA test and cervical smear in Uganda.

OBJECTIVE: To evaluate the efficacy of visual inspection with acetic acid (VIA) screening combined with a cervical smear in Uganda. METHODS: Nine screening campaigns were held in Uganda between January 2011 and October 2019. In the last three campaigns, a new approach was used: the cervical smear was performed before the VIA test and, in case of a positive VIA test, the slide was sent for examination. The data collected were divided into two groups: the first six campaigns and the last three campaigns. RESULTS: During the study period, 10 520 women were screened, of whom 911 had a positive VIA test. The VIA test showed 84.2% false positives. In the first group, the VIA test was positive in 516 women, of whom 93% were referred for further examinations. In the second group, the VIA test was positive in 395 women, but the cervical smear was positive in only 65 women. Thus, only 16.5% women were referred for further examinations. CONCLUSION: Combining cervical smear, VIA test, and slide analysis in positive VIA tests may allow women who need treatment to be selected more effectively, while waiting for other more expensive solutions to become more affordable for this setting.

Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem.

Iron needs increase exponentially during pregnancy to meet the increased demands of the fetoplacental unit, to expand maternal erythrocyte mass, and to compensate for iron loss at delivery. In more than 80% of countries in the world, the prevalence of anemia in pregnancy is > 20% and could be considered a major public health problem. The global prevalence of anemia in pregnancy is estimated to be approximately 41.8%. Undiagnosed and untreated iron deficiency anemia (IDA) can have a great impact on maternal and fetal health. Indeed, chronic iron deficiency can affect the general wellbeing of the mother and leads to fatigue and reduced working capacity. Given the significant adverse impact on maternal-fetal outcomes, early recognition and treatment of this clinical condition is fundamental. Therefore, the laboratory assays are recommended from the first trimester to evaluate the iron status. Oral iron supplementation is the first line of treatment in cases of mild anemia. However, considering the numerous gastrointestinal side effects that often lead to poor compliance, other therapeutic strategies should be evaluated. This review aims to provide an overview of the current evidence about the management of IDA in pregnancy and available treatment options.