Surgical Oncology

Pathologic chemotherapy response score in epithelial ovarian cancer: Surgical, genetic, and survival considerations

A pathologic chemotherapy response score (CRS) is used to grade ovarian cancer response to neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of the CRS in a single institution cohort. A retrospective review of all consecutive epithelial ovarian cancer patients undergoing interval debulking surgery (IDS) after NACT from 2016 to 2017 were included. Clinical, pathologic, surgical, outcomes, and genetic data were abstracted from medical records. CRS was assigned by pathology based on a section of omentum as follows: 1 = minimal response, 2 = moderate response, and 3 = near complete response. Among the 50 subjects, 14 (28%) were classified as CRS1, 29 (58%) as CRS2, and 7 (14%) as CRS3. The majority of patients were diagnosed with high grade serous histology (94%). Most women in this cohort underwent either an optimal or complete cytoreduction to no gross residual disease (96%). Women in the CRS2 group were most likely to have a pathogenic variant (51.7%) while those in the CRS1 were least likely (7.1%). Most women recurred regardless of CRS. CRS was not associated with progression-free survival (log-rank p = 0.82) or overall survival (log-rank p = 0.30). Though previous data support the use of CRS as a prognostic indicator, we failed to show a correlation between CRS and survival in our continuous single institution cohort. The high rate of optimal debulking across all CRS groups in this study may mitigate the prognostic significance of the scoring system. Nevertheless, tumors that respond poorly to traditional chemotherapy should remain of avid interest for potential novel therapies.

Time interval from biopsy to surgery and risk for adjuvant therapy in patients with low-risk endometrial cancer

Among patients with endometrial cancer, longer wait times to surgery were associated with decreased survival. Although endometrial cancer survival rate is high, about 45% of patients receive adjuvant therapy. The aim of this study was to examine whether a longer interval from diagnosis to surgery is associated with increased need for adjuvant treatment among patients with low-risk endometrial cancer. A retrospective cohort study of endometrioid endometrial cancer patients treated with surgery between the years 1999 and 2013 was conducted. Patients with pre-operative histology of hyperplasia, grade 1/2 cancers were included. Patients with stage IV disease were excluded. Demographic, clinicopathologic and surgical parameters were collected and correlation with wait time was evaluated. The risk for adjuvant therapy was in two-week intervals from biopsy to hysterectomy. 468 patients were included in the final cohort. 84.3% had stage I disease and 43.8% patients received adjuvant treatment. Mean time from diagnosis to surgery was 63.88 days (SD 10.3, 31-94). The risk for adjuvant therapy was not increased at any of the time intervals that were examined. In low risk endometrial cancer, longer time interval between diagnosis and surgery did not increase the need for adjuvant therapy.

Outcomes of robotic surgery for endometrial cancer in elderly women

Few data have been reported on robot-assisted surgery in elderly. The objectives were to compare feasibility, complication data, and survival of patients under and upper the age of 70 who are managed for endometrial cancer by robot-assisted laparoscopy. This is a retrospective comparative single-center study including patients treated between January 2007 and December 2016. Patients were divided into 2 groups: less than 70 years and greater than or equal to 70 years. The primary endpoint was the rate of complications. The secondary endpoints were conversion rate and follow-up. 148 patients were included: 86 under 70 (group A) and 62 aged 70 and over (group B). More adhesiolysis was performed in group B (p < .01); the pelvic and para-aortic lymph node dissection rates were not different between both groups (p = .2 and p = .9). The operating times were significantly longer in group B (220.1 vs. 234.4 min, p = .02). The conversion rate was similar between the 2 groups (p = .7). The tumors were endometrioid adenocarcinomas for 77.9 and 66.7% respectively (p = .2), with grade 3 tumors more represented in older patients (24.4% vs. 48.4%, p < .01). There were more tumors at high risk of recurrence after 70 years (33.7 vs. 45.2%, p = .04). No significant difference was found for postoperative complications. There was no difference in overall survival (p = .7) or progression-free survival (p = .2). Undertreated women rate was similar in both groups (p = .1). Robotic surgery appears feasible and reproducible and could bring a benefit and allow optimal surgery without increasing the morbidity in the management of endometrial cancers whatever the age is.

Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier?

Endometrial cancer is the most common malignancy of the female genital tract. For cancers detected at an advanced stage or intraperitoneal relapse, the prognosis is poor. Optimal cytoreductive surgery (CRS) is the most accepted treatment; however, patients with advanced intraperitoneal disease might benefit from hyperthermic intraoperative peritoneal chemotherapy (HIPEC). The aim of this study was to analyze recurrence-free survival (RFS) after CRS and HIPEC in a large series of patients with peritoneal metastases from endometrial cancer. Patients with a diagnosis of endometrial cancer with primary or recurrent peritoneal dissemination were included. All patients underwent CRS plus HIPEC. Data were prospectively collected in the Spanish Group of Peritoneal Oncological Surgery (GECOP) database. Forty-three patients with endometrial cancer and peritoneal metastasis were included. Fifteen patients (35%) were diagnosed with G3 endometrioid carcinomas and 28 (65%) with other non-endometroid histologies. A completeness of cytoreduction score of CC-0 was achieved in 41 patients (95%). RFS at 5 years was 23%, being factors related to worse RFS: treatment with preoperative chemotherapy (p = 0.027), resection of more than three peritoneal areas (p = 0.010), cytoreduction of the upper abdominal space (p = 0.023), HIPEC treatment with paclitaxel (p = 0.013), and the presence of metastatic lymph nodes (p = 0.029). Better RFS rates after CRS and HIPEC were observed for patients with the following characteristics: cytoreductive surgery without preoperative chemotherapy, complete surgery performed with limited surgical maneuvers, treated with cisplatin, and no lymph node metastases. Endometrial cancer has a poor prognosis when diagnosed at advance stage. Patients with intraperitoneal metastases from endometrial cancer may benefit from CRS plus HIPEC with improvement in the recurrence-free survival results.

Surgical and oncologic outcomes of minimally invasive surgery for stage I high-grade endometrial cancer

To evaluate the prevalence and outcomes of minimally invasive surgery for stage I high grade endometrial cancer. We hypothesized that route of surgery is not associated with survival. Patients diagnosed between 2010 and 2014, with stage I grade 3 endometrioid, serous, clear cell and carcinosarcoma endometrial carcinoma, who underwent hysterectomy with lymphadenectomy were drawn from the National Cancer Database. Patients converted to open surgery were excluded. Overall survival was assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. A total of 12852 patients were identified. The rate of minimally invasive surgery was 62.2%. An increase in the use between 2010 and 2014 was noted (p < 0.001). Open surgery was associated with longer hospital stay (median 3 vs 1 day, p < 0.001), higher 30-day unplanned re-admission rate (4.5% vs 2.4%, p < 0.001) and 30-day mortality (0.6% vs 0.3%, p = 0.008). There was no difference in overall survival between patients who had open or minimally invasive surgery, p = 0.22; 3-yr overall survival rates were 83.7% and 84.4% respectively. After controlling for patient age, tumor histology, substage, type of insurance, type of reporting facility, receipt of radiation therapy and chemotherapy, extent of lymphadenectomy, the presence of comorbidities and personal history of another tumor, minimally invasive surgery was not associated with a worse survival (hazard ratio: 1.06, 95% confidence interval: 0.97, 1.15). Minimally invasive surgery for patients with stage I high grade endometrial cancer, was associated with superior short-term outcomes with no difference in overall survival noted.

Letter-to-the-Editor “Laparoscopic treatment of early-stage endometrial cancer with and without uterine manipulator: Our experience and review of literature” by Tinelli R et al. (Surgical Oncology 25 (2016) 98–103)

Urinary and fecal incontinence in patients with advanced ovarian cancer treated with CRS + HIPEC

The objective of this work was to analyze the long-term prevalence of urinary and fecal incontinence and their impact on quality of life in patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (CRS + HIPEC). This cross-sectional study included a series of patients with advanced and recurrent ovarian cancer treated by CRS + HIPEC, with a disease-free period of at least 12 months after the procedure. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), fecal incontinence using the Wexner test and the Fecal Incontinence Quality of Life (FIQL) questionnaire and global quality of life using the Short Form 36 (SF-36) survey. A total of 64 patients were included in the study, with a median age of 55 years (range 28-78). The urinary incontinence rate was 45% and the fecal incontinence rate was 20%. Up to 14% of the patients presented both types of incontinence. The presence of urinary or fecal incontinence generated a significant negative impact on quality of life in relation to patients without incontinence. Urinary and fecal incontinence is frequent in the follow-up of ovarian cancer patients treated with CRS + HIPEC. Reconsidering the approach to the pelvis without peritoneal metastases in the peritoneum could modify the incidence of these pelvic floor dysfunctions.

Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) for omentectomy – A case series

Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has been applied massively in the gynecological field in recent years. The aim of the current study is to present the surgical technique of vNOTES omentectomy and to evaluate the feasibility of this procedure. A case series study of the first 5 vNOTES omentectomy procedures performed for surgical staging of suspicious early stage ovarian cancer, at Rambam Health Care Campus (Israel) and Imelda Hospital (Belgium) between November 2018 and August 2019. Sociodemographic and clinical data were retrieved from patients' electronic charts. Primary points of interest included intra-operative bleeding, length of surgery, length of hospitalization, and surgical complications. The median age was 61 years (range 50-72), and the median BMI was 27 kg/m vNOTES is a feasible technique for omentectomy in early stage ovarian cancer, with low rates of complications and improved cosmetic results.

Systemic inflammatory markers for the detection of infectious complications and safe discharge after cytoreductive surgery and HIPEC

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in patients with ovarian peritoneal carcinomatosis may be associated with a high postoperative morbidity. An early discrimination of postoperative complications is crucial for both improving clinical outcomes and proposing a safe discharge. In a cohort of 122 patients with advanced ovarian cancer (FIGO III-IV), we analyzed the diagnostic performance of three systemic inflammatory markers (C-reactive protein, white blood cell count and systemic immune-inflammation index) between the 5th to 8th postoperative days to prediction postoperative infectious complications. An optimal cut-off value was established in order to discriminate between the group of patients who developed infectious complications or not during the postoperative period. The median peritoneal carcinomatosis index (PCI) was 15. The overall infectious morbidity was 25.4% (31 patients out of 122), of which, 32% (10 patients out of 31) had suffered severe postoperative complications (Dindo-Clavien III-IV). The most accurate results for detecting infectious complications were obtained by using C-reactive protein, which presented an excellent diagnostic performance, especially on the 7th and 8th postoperative days (AUC = 0,857 and 0,920; respectively). These results support that it is safe to discharge patients with C-reactive protein concentrations lower than 88 mg/L and 130 mg/L, on the 7th and 8th postoperative days, respectively.

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31). Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC. A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26-45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29-76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19-27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors. A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.

Predicting the rate of adjuvant postoperative chemo/radiation in cervical cancer with tumor size ≥2 cm and &lt;4 cm: An Israeli Gynecologic Oncology Group study

Women with cervical cancer who undergo radical hysterectomy are often treated postoperatively with chemoradiation. Patient selection that minimizes adjuvant treatment is valuable. We compared two methods for predicting postoperative adjuvant treatment of women with tumor size ≥2 cm and 70% rate of adjuvant treatment, and LVSI was associated with a >80% rate. These data should be weighed in multidisciplinary consultation with radiation oncologists when deciding treatment strategy.

A Clinician's perspective on the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer management

The prevention of intraperitoneal spread is of utmost importance in the management of advanced ovarian cancer (OC), thus demanding the exploration of innovative treatment techniques. The propensity of OC to spread to the peritoneum has highlighted the potential of local therapy as a promising approach. Among the proposed treatments thus far are several local intraperitoneal therapies, with hyperthermic intraperitoneal chemotherapy (HIPEC) being one of them. The application of HIPEC may potentially enhance the survival rates of patients with OC, as indicated by a recent publication of high-quality prospective data. The incorporation of HIPEC in conjunction with primary cytoreductive surgery (CRS) does not have a significant impact on either overall survival (OS) or disease-free survival (DFS). However, the incorporation of HIPEC alongside interval CRS, followed by systemic chemotherapy (CTH), markedly enhances both OS and DFS. The most recent data also substantiates the effectiveness of HIPEC in recurrent ovarian cancer (ROC), resulting in an improvement of survival outcomes. Additional research will contribute to the improvement of the HIPEC regimen and technique, as well as the precise identification of patients who will gain the most advantage from this treatment approach. It is recommended to discuss and update (inter)national clinical guidelines for managing patients with advanced OC and peritoneal involvement.

Risk reduction bilateral salpingo-oophorectomy with vNOTES: A new era in cancer prevention strategies

Is the extent of pelvic lymphadenectomy in the staging of endometrial cancer associated with the yield of metastatic nodes? An Israeli Gynecologic Oncology Group study

Primary, to explore correlation between the extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer and the number of nodes with metastasis. Secondary, evaluate survival measures in relation to the number of excised nodes. A retrospective multi-center study of prospectively collected information of 2014 women with endometrial cancer, 1032 of whom underwent lymph node staging. Spearman's rank correlation was used to assess the correlation between the number of pelvic nodes excised and the number of metastatic nodes. Women's data were dichotomized by the median number of excised pelvic nodes. Kaplan-Meier and log rank tests were used to examine the effect of the number of pelvic nodes excised on survival. There was no significant correlation between the number of pelvic nodes harvested and the number of metastatic lymph nodes (r = 0.301; p = 0.28). The median number of excised pelvic nodes was 9 (range 1-77). There was no difference between women with up to 9 and women with more than 9 lymph nodes excised in the 5-year recurrence-free survival (82.4% vs. 83.9%; p = 0.90), disease-specific survival (83.6% vs. 86.7%; p = 0.37), or overall survival (75.8% vs. 82.8%; p = 0.11). The extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer is not associated with a higher yield of metastatic nodes or with longer survival. Current focus should be on sentinel node procedures that offer women the benefit of accurate staging without the complications associated with extensive lymphadenectomy.

Impact of age on surgical excision margins for vulvar squamous cell carcinomas: A multicenter study by the francogyn group

Vulvar cancer is a rare cancer, it most often affects older women, with tumours of more advanced size and stage than in younger patients. The first-line treatment for vulvar cancer is surgery. Current European and American guidelines recommend negative histological margins. As tumor size is greater in older patients, the aim of this study was to assess the impact of patient age on surgical excision margins in squamous cell carcinomas of the vulva. This was a retrospective multicenter observational study. A descriptive analysis of the population was performed and a univariate analysis was performed according to patient age. Survival data were plotted using the Kaplan-Meier method and compared using a log rank test. Survival was analyzed using a Cox model to calculate the Hazard Ratio. Among the 547 patients included, there were 206 patients <65 years and 341 ≥ 65 years, including 135 ≥ 80 years. Median postoperative histological lesion size and interquartile range was greater in patients ≥65 years (30 mm [18-45] versus 26 mm [14-34], p < 0.001). Patients ≥65 years of age more often benefited from radical total vulvectomy (n = 103 (28.8 %) versus n = 44 (20.4 %), p = 0.03). However, negative surgical excision margins were identical between the 2 groups (n = 180 (87.4 %) versus n = 286 (83.9 %), p = 0.21). Revision surgery was performed more frequently in patients <65 years. Recurrence-free survival was better in patients aged <65 years (HR = 0.60; CI95 % (0.45-0.82), p = 0.001). Despite larger tumour size, age is not a factor influencing the achievement of negative excision margins in squamous cell carcinomas of the vulva, at the cost of more radical surgery.

The modified 5-factor frailty index predicts postoperative outcomes in patients with ovarian cancer undergoing hyperthermic intraperitoneal chemotherapy

The objective of this research is to compare the ability of mFI5 to the mFI11 to predict frailty, postoperative complications, discharge location for patients with ovarian cancer undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) at time of cytoreductive surgery. This is a single-institution retrospective study in patients with advanced (Stage III, IV) or recurrent ovarian cancer treated with surgical cytoreduction with HIPEC. Logistic regression was used to evaluate frailty as well as factors associated with moderate to severe Accordion postoperative complications and discharge to home. Correlation was calculated between mFI5 and mFI11. Of 141 patients who received HIPEC between 2010 and 2020, 23 patients were classified as frail (mFI5 score ≥2), while 118 were not frail. Frail patients were significantly older with mean age 65.9 compared to non-frail patients who had mean age of 59.1 (p = 0.005), as well as a higher Charlston Comorbidity Index (p < 0.001), and more renal disease (p = 0.025), hypothyroidism (p = 0.005), and hyperlipidemia (p = 0.004). mFI5 and mFI11 scores for frailty were highly correlated (spearman rho 0.98, p < 0.001). Frail patients were more likely to be discharged to a skilled nursing facility (22.7 %) vs. 6.8 % of non-frail patients, or require home services (18.2 % vs 8.5 %, p = 0.025). On multivariable logistic regression, frail patients were more likely to experience moderate or higher Accordion postoperative complications (OR 3.08, p = 0.024). The mFI5, a simpler tool than the mFI11, is also highly associated with postoperative complications and need for postoperative services in patients with ovarian cancer undergoing HIPEC at time of cytoreductive surgery.

Variability in the identification of lymphovascular space invasion for early stage cervical cancer

To evaluate the inter- and intra-rater variability of lymphovascular space invasion (LVSI) in early stage cervical cancer. We identified invasive cervical cancer tissue samples from radical hysterectomies in our institutional pathology database. The cases were stained with Hematoxylin & Eosin (H&E) and immunostains (CD-31 and D2-40). They were evaluated for the presence of LVSI by 6 pathologists on 3 separate occasions: with H&E staining only, then with H&E and immunostained specimens, and finally using a shared written criterion for diagnosis of LVSI. With 80 cases, a two-sided 95% confidence interval for the Kappa of 0.7 with a precision of 0.1 on each side was estimated. Stage distribution was: IA 10%, IB 85%, and IIA 5%. The majority of cases were squamous cell carcinoma (55%), followed by adenocarcinoma (39%) and adenosquamous or other histology (6%). The mean inter-rater Kappa was 0.41 (95% CI: 0.37-0.45) for H&E. Usage of immunohistochemistry made a statistically significant improvement in the mean Kappa, but it still remained low: 0.52 (p = 0.02). Adding evaluation criteria for LVSI did not significantly increase the mean Kappa: 0.49 (p = 0.16). The mean intra-rater variability of H&E staining alone compared with H&E staining plus immunostaining was 0.53 (range: 0.43-0.64). The mean Kappa comparing H&E staining and H&E staining with criteria was 0.50 (range: 0.40-0.59). We noted high inter- and intra-rater variability in the diagnosis of LVSI underscoring the challenges of LVSI diagnosis. Considering the significance assigned to LVSI and its implication for treatment, comprehensive guidelines with regards to determination of LVSI status are of paramount importance.

Impact of the completeness of cytoreductive surgery on the prognostic role of the KELIM score in patients treated for ovarian peritoneal metastasis

The two major treatment related prognostic factors for peritoneal metastasis of ovarian cancer (PMOC) are chemosensitivity and completeness of cytoreduction (CC). Chemosensitivity can be assessed by the CA-125 elimination rate constant K (KELIM) score, based on CA-125 kinetics. CC is evaluated by residual macroscopic disease. The aim of this study was to evaluate the prognostic impact of KELIM score versus CC, in a population who underwent complete (CC-0) and near-complete (CC-1) debulking. Monocentric retrospective study including patients with primary PMOC treated with curative intent between January 2010 and December 2021. The Biomarker Kinetics website (CA-125 KELIM Calculator) was used to calculate the KELIM score. Univariate and multivariate analysis were performed to assess the impact of CC and KELIM score on PFS and OS. A total of 111 patients were included in the study. Kaplan-Meier analysis showed that PFS and OS were significantly influenced by KELIM, CC, PCI, and BRCA mutation (p < 0.05). Multivariate Cox analysis showed that PFS was significantly influenced by CC (HR = 0.481, p = 0.0027), while OS was influenced by KELIM (HR 0.561, p = 0.0408). These results suggest that PFS is more impacted by the completeness of the surgery than the KELIM score and the KELIM score influences OS more than the completeness of surgery.

Outcomes of risk-reducing surgeries in women at high risk for gynaecological cancers: A tertiary center experience

Ovarian and endometrial carcinomas are the most common gynecologic malignancies, with general population risks of 1.4 % and 2.5 % respectively. Certain genetic factors can raise these risks to 44 % and 60 % respectively. The most effective risk-reduction (RR) method is the removal of the fallopian tubes, ovaries, and/or uterus. This study investigates surgical outcomes and occult cancer rates following RR surgery in high-risk women. This is a retrospective cohort study of all women identified as high-risk for gynaecologic cancer who were referred to a high-volume tertiary centre and underwent RR surgery. All pathology specimens were assessed by sectioning and extensively examining the fimbriated end (SEE-FIM) protocol. The analysis included patients' demographics, peri- and post-operative evaluation, and final histopathological reports. Between 2008 and 2024, 576 women completed RR surgery in our centre. The rates of intra- and post-operative complications were 3.1 % and 4.5 %, respectively. The overall occult cancer rate was 3.4 % (n = 20). Of these, 11 (55 %) patients had high-grade serous carcinoma of the ovary/fallopian tube, and seven (35 %) patients were found to have endometrial cancer. Two cases had unexpected metastasis in the ovaries (10 %). Of the whole cohort, 12 (2.1 %) patients were found to have premalignant disease; eight serous tubal intraepithelial carcinoma; two atypical endometrial hyperplasia and two dysplasia of the cervix. RR surgeries are safe with a low complication rate. The incidence of occult cancer at the time of RR surgery is low but significant. Endometrial sampling is to be considered, and all fallopian tubes should be examined with the SEE-FIM protocol.

Transvaginal natural orifice transluminal endoscopic surgery (VNOTES) retroperitoneal sentinel lymph node BIOPSY compared with conventional laparoscopy in patients with endometrial cancer

To explore the possibility of treatment with VNOTES sentinel lymph node dissection concept in patients with endometrial cancer. Patients who underwent VNOTES sentinel lymph node biopsy with the Comba modification were compared to patients who underwent conventional laparoscopic sentinel lymph node biopsy performed by the same surgical team. A total of 38 patients who underwent sentinel lymph node biopsy + total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (BSO) were compared with 19 patients who underwent VNOTES retroperitoneal sentinel lymph node biopsy + hysterectomy and BSO. Surgical steps were described. The average operation time, perioperative blood loss, the number of sentinel lymph nodes, presence of complications, and preoperative-postoperative hemoglobin-hematocrit differences, tumor stages, grades, largest tumor diameter, depths of invasion, and histological subtypes were similar in both the VNOTES and conventional laparoscopy groups. The postoperative pain scores were lower and the hospital stay was shorter in the VNOTES group than in the conventional laparoscopy group. No disease recurrence had been detected in either group at the time of writing. Compared to conventional laparoscopy, sentinel lymph node biopsy with the VNOTES technique provides similar surgical results and is more advantageous in terms of postoperative pain and hospital length of stay.

Comparison of robotic and natural orifice transluminal endoscopic surgical technique procedures in patients undergoing sentinel lymph node biopsy during endometrial cancer surgery

The role of sentinel lymph node dissection in the surgical management of endometrial cancer limited to the uterus is gaining recognition. The safety and applicability of two methods were assessed by examining the results of our patients in the identification of the sentinel lymph node during endometrial cancer surgery. The methods were robotic surgery, a critical component of minimally invasive surgery, and the vNOTES (Natural Orifice Transluminal Endoscopic Surgery Technique), which has recently been introduced for malignant indications. Patients who had endometrial cancer surgery at our center employing robotic and vNOTES technologies between January 2023 and June 2024 were included in this retrospective study. We conducted the dissection of sentinel lymph nodes utilizing a near-infrared technology camera method with indocyanine green (ICG) in both robotic and vNOTES techniques. The patients' records were retrospectively obtained from patient files and hospital records. Among the 76 patients who underwent surgery for endometrial cancer, 24 were treated with vNOTES surgery, whereas 52 received robotic surgery. No statistically significant differences were seen between the two groups for age (p = 0.447), body mass index (p = 0.506), prior abdominal operations (p = 0.209), predicted blood loss (p = 0.155), and surgical duration (p = 0.298). The detection rates of sentinel lymph nodes (SLN) were similar across the groups: 97 % (n = 50) in the robotic group and 96 % (n = 23) in the vNOTES group (p = 0.493). The only statistically significant difference was observed in postoperative pain scores at the 12th hour, which were lower in the vNOTES group (p = 0.023). The vNOTES technique demonstrates comparable sentinel lymph node detection rates to robotic surgery in the management of uterine endometrial cancer. Moreover, it has the advantage of markedly less postoperative discomfort. vNOTES is a secure and efficacious minimally invasive option, especially for patients with comorbidities or those deemed unsuitable for robotic surgery.

Surgical treatment in older patients with endometrial cancer: A retrospective study

Older patients (OP) diagnosed with endometrial cancer (EC) are less likely to receive an optimal surgical treatment compared with non-older patients (NOP). This undertreatment along with the presence of more aggressive tumours at diagnosis can explain the worse prognosis of EC in OP. There is limited evidence comparing perioperative outcomes between OP and NOP, and the benefit of applying complex procedures to OP is still controversial. The primary objective of the study was to compare intraoperative and postoperative complications between NOP and OP with EC that underwent primary surgery. Secondary objectives were to compare surgical management and survival rates. This is a retrospective single-centre observational study including women undergoing surgery for EC between 2010 and 2019. Patients were classified according to age as NOP (younger than 75 years) or OP (75 years or older). Basal characteristics and surgical outcomes of groups were compared using Chi-square, Fisher's exact tests, student T-tests or Mann Whitney tests. Kaplan Meier analysis was used to evaluate survival. In total 281 patients underwent primary surgery for EC between 2010 and 2019 in our centre. At diagnosis, 184 patients were younger than 75 years while 97 were 75 and older. No differences were found in disease characteristics. Most of our patients (83,3%) underwent laparoscopic surgery. Pelvic (58,2% vs. 37,1%, p = 0,001) and para-aortic (46,7% vs. 23,7%, p < 0,001) lymphadenectomies were performed more frequently in NOP compared with OP. Rates of intra-operative (6,5% vs. 12,4%, p = 0,116) and post-operative (13,0% vs. 20,6%, p = 0,120) complications were not statistically different between NOP and OP, and neither was the rate of severe complications according to Clavien-Dindo classification (5,4% vs. 8,2% of complications grade III-V respectively, p = 0,387). The 5-year disease-specific survival (DSS) rate tended to be lower in the OP than in the NOP (74,8% vs. 82,5%, p = 0,071). Considering only patients in whom complete surgical staging was performed, OP presented similar DSS to NOP, with comparable complication rate. OP do not present a significantly higher rate of perioperative complications compared to NOP. However, they underwent fewer lymphadenectomies and tended to present poorer DSS. Further studies are needed to standardize the surgical management of these patients.

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter

To analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers. Retrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis. A total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6-10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14-6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use. Size ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.

Learning curve of laparoscopic extraperitoneal para-aortic lymphadenectomy for endometrial carcinoma: A cumulative sum analysis

Minimally invasive surgery including lymphadenectomy for endometrial cancer is widely standardized for the management of endometrial cancer in recent decades. However, the learning curve for laparoscopic para-aortic lymphadenectomy is poorly reported, specifically that for the extraperitoneal approach. We examined the learning curve for laparoscopic extraperitoneal para-aortic lymphadenectomy by cumulative sum (CUSUM) analysis by retrospectively analyzing 134 patients with early-stage endometrial cancer who had undergone laparoscopic extraperitoneal para-aortic lymphadenectomy, including the first case. Data on the surgical factors that improved and were statistically correlated with the number of procedures experienced were extracted and used to create CUSUM curves. The average time for para-aortic lymphadenectomy was 149.4 min to harvest an average of 65.3 para-aortic lymph nodes. Intra- and postoperative complications were observed in nine cases (6.7%). A switch to the transperitoneal approach was necessary in three cases (2.2%). The number of harvested para-aortic lymph nodes and the procedure time were strongly correlated with the number of procedures the patient underwent (p < 0.01). The CUSUM curve of the number of harvested para-aortic lymph nodes indicated an inflection point at the 51st case. The procedure time for para-aortic lymphadenectomy stabilized after the 59th case. CUSUM analysis of "unexpected events," including intra- and postoperative complications and switch to the transperitoneal approach, showed an improved incidence at 60 cases and later. Gaining proficiency in laparoscopic extraperitoneal thorough para-aortic lymphadenectomy is associated with a long learning curve of over 60 procedures. Careful management is required when introducing the procedure.

Accuracy of preoperative endometrial biopsy and intraoperative frozen section in predicting the final pathological diagnosis of endometrial cancer

Histotype and grade of endometrial cancer (EC) are prognostic factors of nodal involvement and thus of survival. Preoperative biopsy (PB) and intraoperative frozen section (FS) are usually used to guide surgical staging on which the choice of adjuvant therapy will be based successively. The aim of this study was to assess the agreement rate between PB and FS with final diagnosis (FD) in a series of surgically resected EC. All patients submitted to hysterectomy for EC or atypical endometrial hyperplasia in the Reggio Emilia Province hospitals from 2007 to 2018 were included. Concordance rate differences in histotype, grading, myoinvasion, risk of recurrence between PB, FS and FD were assessed with Fisher's exact test and Mc Nemar contingency test. A total of 352 patients were identified. For 345 patients it was possible to compare PB and FD results. FS examination was performed in 201/352 (57%) cases, while for 21/352 (6%) patients only an intraoperative macroscopic evaluation was done; in the remaining women, FS-exam was omitted. In 14/201 (7%) cases the tumor wasn't grossly identifiable and the random FS-sampling wasn't able to find the tumor site. High diagnostic concordance of tumor type between PB and FD was observed: no significant differences were registered in type 1 and type 2-endometrial cancer identification (83%, 73%, p = 0.121). Significant differences (p = 0.005) were observed comparing FS and FD results: 95% of type 1-ECs were correctly diagnosed by FS, while only 76% of type 2-ECs received a correct diagnosis on FS. PB showed a concordance with FD among tumor grading close to 55% whilst concordance achieved 71% grouping low grade (G1-G2) EC. No significant differences in FS and FD concordance rate were observed between tumor grades. Concordance for low grade was significantly higher than for high grade ECs (89% vs 50%, respectively, p value = 0.014). The concordance rate in evaluating the myoinvasion status between FS and FD was 80% (n: 199 patients), reaching 99% after combining the first 2 groups (0-49% vs ≥ 50%). Twenty-two cases underwent only intraoperative macroscopic evaluation of the myoinvasion, with an accuracy of 91%: only in 1 case the invasion of the cervical stroma was not detected (Stage II), and 1 case the patient was overstaged as Ib. Discrepancies were observed in FS capacity to correctly predict the final ESMO risk group in stage I patients: FS resulted particularly reliable in predicting a low-risk (concordance with FD: 91%) while the accuracy sharply decreased for intermediate- and high-risk patients (62% and 40%, respectively). To investigate the usefulness of FS in EC management, we compared patients who underwent FS (FS-group) or not (no-FS-group). Especially for low risk patients, the FS significantly increased the adequacy of surgical treatment from 53% (no-FS-group) to 72% (FS-group) (p = 0.016). FS remains a useful tool to tailor surgery in EC-patients, avoiding secondary surgery to complete staging particularly in patients with AH + AHBA, low and intermediate risk ECs that could benefit from adjuvant therapy.

Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer

The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum. A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining. With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors. The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.

Complications of ovarian metastases from well-differentiated small bowel neuroendocrine neoplasms: a focus on bowel and ureteral obstruction

Ovarian metastasis from small bowel neuroendocrine neoplasms (SBNENs) was traditionally considered rare, but more recent series have suggested a higher prevalence. This case series seeks to examine the features and outcomes of patients with neuroendocrine ovarian metastases (NOM). Female patients with histologically confirmed well-differentiated SBNENs were identified using a prospectively maintained database (2014-2024). The electronic medical record was reviewed for details of diagnosis, histopathology, biomarkers, and outcomes among patients with and without NOM. 175 patients met inclusion criteria. 35 patients (20 %) had ovarian metastasis; for this group, 31.4 % had small bowel obstruction only, 5.7 % had ureteral obstruction only, and 14.3 % had both SBO and ureteral obstruction. 22 (62.9 %) also had peritoneal metastasis. 13 patients had ovarian metastasis but no peritoneal metastasis; within this group, 38.5 % had SBO, 15.4 % had ureteral obstruction, 76.9 % developed carcinoid syndrome, and 7.69 % died. There were no significant differences in rate of SBO (p = 0.280), ureteral obstruction (p = 0.716), or death (p = 0.091) between those with ovarian metastasis only and those with peritoneal metastasis only. Median overall survival was not reached. This case series of female patients with SBNENs represents one of the largest available in the literature and demonstrates high rates of complications for those with ovarian metastasis, even in the absence of peritoneal metastasis. Prophylactic oophorectomy may be considered for SBNEN patients given the known development of severe complications throughout the progression of this disease where expectation for survival is lengthy.

Survival outcomes of single-port access laparoscopic radical hysterectomy for early-stage cervical cancer

Emerging data from the Laparoscopic Approach to Cervical Cancer trial (NCT00614211) suggested that minimally invasive surgery (MIS) for cervical cancer is correlated with worse survival outcomes than open surgery. This finding could be attributed to the different learning curves for laparoscopic surgery among surgeons. This study aimed to assess the feasibility, safety, and survival outcomes of single-port access (SPA) laparoscopic radical hysterectomy (LRH) for treating early cervical cancer. This was a retrospective cohort study of consecutive patients with early-stage cervical cancer who underwent SPA LRH between 2009 and 2018 performed by a single surgeon with expertise in SPA laparoscopy using conventional instrumentation and a homemade glove port system. Type C (93.2%) and B (6.8%) radical hysterectomy were performed in 59 women with cervical cancer classified as IA (3.4%), IB (94.9%), and IIA (1.7%). Forty-one patients (69.5%) had squamous cell carcinoma and 32 patients (52.5%) had tumors < 2 cm. The median operative time was 235 (125-382) minutes. There were no perioperative complications or cases of conversion to open surgery. Postoperative complications, including chylous ascites, low hemoglobin, lymphedema, and vault dehiscence, were observed in 5 patients (8.5%). Median follow-up time was 3.1 (0.6-8.6) years and 3 patients experienced recurrence (1 local and 2 distant failures). Five-year disease-free survival was 94.9% (56/59) and the 5-year overall survival rate was 98.3% (58/59). SPA LRH is feasible and safe for patients with early-stage cervical cancer when performed by experienced surgeons without compromising the radicality and oncologic outcomes.

Vulvar Paget's disease and stromal invasion: Clinico-pathological features and survival outcomes

To evaluate clinico-pathological features, treatments and survival outcomes of vulvar Paget's disease (VPD). We retrospectively reviewed VPD diagnosed between 1983 and 2018 at the Department of Surgical Sciences, Sant'Anna Hospital, Turin. Clinico-pathological characteristics and surgical treatment outcomes were investigated according to the depth of invasion. A total of 122 patients were identified. Eighty-seven patients were diagnosed with intraepithelial VPD, 22 with microinvasive (<=1 mm) VPD and 16 with invasive VPD. The median follow-up was 94.6 months (interquartile range 25th-75th, 26-120). Most of patients 95/122 (77%) were treated by surgery. Local recurrence was observed in 69/95 (73%) patients without significant difference between the 3 groups (p = 0.33), however, total vulvectomy showed better local control in microinvasive and invasive VPD than in intraepithelial tumors. At 120 months the cancer-specific survival was 100% for intraepithelial and microinvasive VPD versus 31% for invasive VPD (log-rank p = <0.0001) Age ≥65 years (OR: 4.17 CI 1.12-15.5, p = 0.03) and VPD's area ≥15 cm Microinvasive VPD has an identical prognosis to intraepithelial VPD, suggesting the omission of lymphadenectomy or adjuvant treatments are safe in this subset of patients. We recommend caution to propose medical treatment in patients who are ≥65 years old and with wide tumor area, as they are at the greatest risk of invasiveness.

Reduced morbidity by using LigaSure compared to conventional inguinofemoral lymphadenectomy in vulvar cancer patients: A randomized controlled trial

Inguinofemoral lymphadenectomy (IFL) is part of the surgical treatment of different malignancies of the genital tract and/or the lower limb including vulvar carcinoma, penile carcinoma and melanoma. IFL is associated with morbidity in up to 85% of the patients. The aims of this MAMBO-IC study (Morbidity And Measurement of the Body) are to study the feasibility of using LigaSure for IFL and to assess the differences in the incidence of short-term complications using LigaSure versus conventional IFL randomized within each individual patient. In this multicenter randomized controlled trial (RCT), women diagnosed with squamous cell carcinoma of the vulva with an indication for bilateral IFL were included. It was randomly assigned for which groin the LigaSure was used; the other groin was treated with conventional IFL (sharp/diathermia). We estimated the incidence of ≥1 complication(s) per groin using logistic regression and compared this between the two surgical methods, adjusting for possible confounders. We included 40 groins of 20 patients. The estimated incidence of ≥1 complication(s) was 29% after LigaSure versus 70% after conventional IFL (risk difference 41% (95% CI 19-62), p < 0.001). Patients' reported restriction of daily living activities and maximum pain score were equal for both treatment methods. There were no differences in the surgeon reported workload scores. This RCT shows that LigaSure for IFL is feasible and associated with significantly less short-term surgical complications compared to conventional IFL. Further studies with a larger sample size are needed to validate our findings. ISRCTN15057626.