A restrictive stoma policy after colorectal anastomosis in ovarian cancer based on ghost ileostomy use.

BACKGROUND: The incidence of anastomotic leak after colorectal anastomosis in ovarian cancer has been reported to be much lower than that in colorectal cancer patients. Regarding the use of protective manoeuvres (diverting ileostomy) as suggested by clinical guidelines, the goal should be the implementation of a restrictive stoma policy for ovarian cancer patients, given the low rate of anastomotic leakage in this population. MATERIAL AND METHODS: Patients who underwent cytoreduction surgery in a single centre (University Hospital La Fe, Valencia Spain) due to ovarian cancer between January 2010 and June 2023 were classified according to two groups: a non-restrictive stoma policy group (Group A) and a restrictive stoma policy group (Group B). RESULTS: A total of 256 patients were included in the analysis (group A 52 % vs group B 48 %). The use of protective diverting ileostomy was lower in the restrictive stoma policy group (14 % vs 6.6 %), and the use of ghost ileostomy was 32 % vs 87 % in groups A and B, respectively (p < 0.00001). No differences were found in the anastomotic leak rate, which was 5.2 % in the non-restrictive group and 3.2 % in the restrictive stoma policy group (p = 0.54). CONCLUSION: The use of a restrictive stoma policy based on the use of ghost ileostomy reduces the rate of diverting ileostomy in patients with ovarian cancer after colorectal resection and anastomosis. Furthermore, this policy is not associated with an increased rate of anastomotic leakage nor with an increased rate of morbi-mortality related to the leak.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role.

INTRODUCTION: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. MATERIALS AND METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. CONCLUSION: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Accuracy of ICG compared with technetium-99 m for sentinel lymph node biopsy in vulvar cancer.

PURPOSE: Sentinel lymph node biopsy with radioactive tracer is the standard-of-care in lymph node status assessment in vulvar cancer. Indocyanine green fluorescence-ICG is a promising detection method, due to its advantages over technetium-99 m. In vulvar cancer, the procedure is controversial due to study heterogeneity and the small sample size in previous studies. This study evaluates ICG sentinel lymph node detection compared with the criterion-standard with technetium (dual modality method). METHODS: Preoperative technetium and intraoperative ICG for sentinel lymph node have been prospectively evaluated in early-stage vulvar cancer. The primary endpoint was to determine accuracy in the detection rate for ICG compared with technetium. Secondary objectives included tracer modality relationship with obesity, tumor size and location. RESULTS: In total, 75 patients participated at 8 centers; 38 had lateral and 37 had midline vulvar tumors. The overall sentinel lymph node detection rate was 85.3 % for technetium and 82.7 % for ICG. For lateral tumors, the detection rate was 84.2 % vs. 89.5 %, while it was 86.5 % vs. 75.7 % for middle tumors, using technetium and ICG, respectively. The median sentinel node harvest was 1.7 (range 1-4), with 24 % metastatic involvement. The sensitivity and positive predictive value for ICG based on the standard technique with technetium was 91.08 % (95 % CI, 83.76-95.84) and 94.8 % (95 % CI, 84.84-96.48), respectively. No significant differences were found comparing the two tracers in patients with midline lesions, obesity (body mass index ≥ 30) and tumor size ≥ 2-4 cm. CONCLUSION(S): ICG shows comparable performance parameters to the gold-standard of radioisotope localization.

Endometrial cancer: predictors and oncological safety of tumor tissue manipulation.

PURPOSE: The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results. METHODS: We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen. RESULTS: A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479). CONCLUSION: Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.

An Easy Learning Approach to a Complex Surgical Technique: A Step-by-Step Site-Relapse Lateral Extended Endopelvic Resection (LEER).

Lateral pelvic sidewall involvement by gynecological tumors has been considered traditionally an absolute contraindication to curative resection.1 Moreover, the involvement of the pelvic sidewall at the time of relapse in cervical cancer after primary or adjuvant pelvic radiation occurs in 8.3% of patients.2,3 Laterally extended endopelvic resection (LEER), based on the ontogenetic compartment theory, provides a potential surgical option for patients for whom palliative therapy is the only alternative.4 This complex and ultraradical, surgical technique allows a high rate of complete resection in more than 70% of patients with gynecological cancers and lateral pelvic sidewall involvement. An adequate selection of patients and a deep knowledge of pelvic anatomy are crucial to obtain acceptable morbimortality rates and improved overall survival in this population.5 To deconstruct this complex procedure, we show a detailed step-by-step technique to facilitate the easy learning curve of this surgical technique. We review the Höckel original technique with different site-relapse adapted steps. We provide a pedagogical high-quality video (Video 1) and anatomical outline drawings (Fig. 1) to understand lateral pelvic wall anatomy and standardize this surgical technique. Our purpose is to bring this knowledge to gynecologists and pelvic surgeons in which pelvic lateral approach may be useful beyond gynecological oncologic surgery (Table 1).

Comparation between the Bricker ileal conduit vs double-barrelled wet colostomy after pelvic exenteration for gynaecological malignancies.

BACKGROUND: After exhausting other therapeutic options, pelvic exenteration is performed in patients who suffer from relapsed gynaecologic tumours, with most of them requiring some sort of urinary diversion. MATERIAL AND METHODS: The main objective of this study was to assess the short- and medium/long-term urinary complications associated with the Bricker ileal conduit versus double-barrelled wet colostomy after performing a pelvic exenteration for gynaecologic malignancies. RESULTS: A total of 61 pelvic exenterations were identified between November 2010 and April 2022; 29 Bricker ileal conduits and 20 double-barrelled wet colostomies were included in the urinary diversion analysis. Regarding the specific short-term urinary complications, no differences were found in the rate of urinary leakage (3 vs 0 %; p = 1), urostomy complications (7 vs 0 %; p = 0.51), acute renal failure (10 vs 20 %; p = 0.24) or urinary infection (0 vs 5 %; p = 0.41). Up to 69 % of patients with Bricker ileal conduits and 65 % of double-barrelled wet colostomies (p = 0.76) presented specific medium/long-term urinary complications. No differences in the rates of pyelonephritis (59 vs 53 %; p = 0.71), urinary fistula (0 vs 12 %; p = 0.13), ureteral stricture (10 vs 6 %; p = 1), conduit failure and reconstruction (7 vs 0 %; p = 0.53), renal failure (38 vs 29 %; p = 0.56) or electrolyte disorders (24 vs 18 %; p = 0.72) were found. CONCLUSIONS: There are no significant differences in the rate of complications between double-barrelled wet colostomy and the Bricker ileal conduit. The long-term complications related to urinary diversion remained high regardless of the type of technique. In this context, the double-barrelled wet colostomy presents advantages such as the single stoma placement and the simplicity of the technique.

Low-grade endometrial stromal sarcoma with intravenous thrombus extension: a multidisciplinary surgical challenge.

Low-grade endometrial stromal sarcoma (LG-ESS) usually exhibits indolent behavior, often misdiagnosed and is associated with a favorable prognosis [1]. Despite the indolent nature of LG-ESS, recurrence is common, the risk is as high as 1 in 3 to 1 in 2 [2]. The behavior of such tumors can lead to invade blood vessels [3]. An intravascular tumor is associated with direct risk of sudden death from pulmonary embolism. There are very few reported cases with clinically obvious intravascular extension. Chemotherapy, radiotherapy and hormone therapy are adjuvant treatments that have not been able to demonstrate a definitive benefit in survival [4]. We want to take advantage of the opportunity, so far unpublished, to demonstrate with this case the surgical challenge described step by step, as well as to demonstrate the importance of surgery as the only curative treatment even in extended intravascular disease [5]. Here in, we present the surgical challenge of a LG-ESS in a 59-year old woman with iliac and cava vein tumoral thrombus extension. We performed a tumoral thrombectomy and vascular repair, with a pelvic exenteration and double barrel wet colostomy. After performing pelvic exenteration, the thrombus with intravascular involvement was addressed at 2 points: inferior cava vein and right common iliac vein with the extraction of the entire thrombus. These defects are corrected by angioplasty and venorrhaphy, respectively. The surgery got a complete cytoreduction. It lasted 290 minutes, with 430 mL blood loss. In patients with LG-ESS, cytoreduction is a reliable option even in extended metastatic disease.

Molecular Management of High-Grade Serous Ovarian Carcinoma.

High-grade serous ovarian carcinoma (HGSOC) represents the most common form of epithelial ovarian carcinoma. The absence of specific symptoms leads to late-stage diagnosis, making HGSOC one of the gynecological cancers with the worst prognosis. The cellular origin of HGSOC and the role of reproductive hormones, genetic traits (such as alterations in P53 and DNA-repair mechanisms), chromosomal instability, or dysregulation of crucial signaling pathways have been considered when evaluating prognosis and response to therapy in HGSOC patients. However, the detection of HGSOC is still based on traditional methods such as carbohydrate antigen 125 (CA125) detection and ultrasound, and the combined use of these methods has yet to support significant reductions in overall mortality rates. The current paradigm for HGSOC management has moved towards early diagnosis via the non-invasive detection of molecular markers through liquid biopsies. This review presents an integrated view of the relevant cellular and molecular aspects involved in the etiopathogenesis of HGSOC and brings together studies that consider new horizons for the possible early detection of this gynecological cancer.

OVA-LEAK: Prognostic score for colo-rectal anastomotic leakage in patients undergoing ovarian cancer surgery.

OBJECTIVE: The objective of the present study was to define and validate an anastomotic leak prognostic score based on previously described and reported anastomotic leak risk factors (OVA-LEAK: https://n9.cl/ova-leakscore) and to establish if the use of OVA-LEAK score is better than clinical criteria (surgeon's choice) selecting anastomosis to be protected with a diverting ileostomy. MATERIAL & METHODS: This is a retrospective, multicentre cohort study that included patients who underwent cytoreductive surgery for primary advanced or relapsed ovarian cancer with colorectal resection and anastomosis between January 2011 and June 2021. Data from patients already included in the previous predictive model were not considered in the present analysis. To validate the performance of our logistic regression model, we used the OVA-LEAK formula (Annex I: https://n9.cl/ova-leakscore) for estimating leakage probabilities in a new independent cohort. Then, receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC) was used to measure the performance of the model. Additionally, the Brier score was also estimated. 95% confidence intervals (CI) for each of the estimated performance measures were also calculated. RESULTS: 848 out of 1159 recruited patients were finally included in the multivariable logistic regression model validation. The AUC of the new cohort was 0.63 for predicting anastomotic leak. Considering a cut-off point of 22.1% to be 'positive' (to get a leak) this would provide a sensitivity of 0.45, specificity of 0.80, positive predictive value of 0.09 and negative predictive value of 0.97 for anastomotic leak. If we consider this cut-off point to select patients at risk of leak for bowel diversion, up to 22.5% of the sampled patients would undergo a diverting ileostomy and 47% (18/40) of the anastomotic leaks would be 'protected' with the stoma. Nevertheless, if we consider only the 'clinical criteria' for performing or not a diverting ileostomy, only 12.5% (5/40) of the leaks would be 'protected' with a stoma, with a rate of diverting ileostomy of up to 24.3%. CONCLUSIONS: Compared with subjective clinical criteria, the use of a predictive model for anastomotic leak improves the selection of patients who would benefit from a diverting ileostomy without increasing the rate of stoma use.

Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG).

OBJECTIVE: The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment. MATERIAL AND METHODS: This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study. RESULTS: The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases. CONCLUSIONS: Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques.

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk.