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.

Optimal cytoreduction: is a CT's picture worth a surgeon's word?

INTRODUCTION: The presence of residual disease after cytoreductive surgery is subjectively determined by the surgeon at the end of the operation. Nevertheless, in up to 21-49% of CT scans, residual disease can be found. The aim of this study was to establish the relationship between post-surgical CT findings after optimal cytoreduction in patients with advanced ovarian cancer and oncological outcome. MATERIAL AND METHODS: Patients with advanced ovarian cancer (FIGO II and IV), diagnosed between 2007 and 2019 in Hospital La Fe Valencia, in whom cytoreductive surgery was performed, achieving R0 or R1, were assessed for eligibility (n = 440). A total of 323 patients were excluded because a post-operative CT scan was not performed between the third and eighth post-surgery week and prior to the start of chemotherapy. RESULTS: 117 patients were finally included. The CT findings were classified into three categories: no evidence, suspicious or conclusive of residual tumour/progressive disease. 29.9% of CT scans were "conclusive of residual tumour/progressive disease". No differences were found when the DFS (p = 0.158) and OS (p = 0.215) of the three groups were compared (p = 0.158). CONCLUSION: After cytoreduction in ovarian cancer with no macroscopic disease or residual tumour < 1 cm result, up to 29.9% of post-operative CT scans before chemotherapy found measurable residual or progressive disease. Notwithstanding, a worse DFS or OS was not associated with this group of patients.

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.

Ultrastaging protocol in sentinel lymph node for apparent early stage ovarian cancer.

OBJECTIVE: The objective of the present study is to determine the role of sentinel lymph node (SLN) ultrastaging in apparent early-stage ovarian cancer. METHODS: We previously demonstrated the feasibility of SLN in early-stage ovarian cancer in a pilot study and in a clinical trial (NCT03452982). The SLN of the 30 patients involved in both were processed following an ultrastaging protocol. The cost of ultrastaging processing was also reported. RESULTS: A SLN was detected in up to 91.3% and 90% in the pelvic and para-aortic region, respectively. In all cases, a SLN was detected at least in one field, pelvic or para-aortic. The mean time from injection to SLN resection was 53.3 ± 20.3 min. Two of 30 (6.6%) patients had a contralateral SLN in the para-aortic field, but no patients had contralateral SLN within the pelvic field after injection. The mean number of harvested SLN was 2.1 ± 1.4 (range: 0-5) and 2.7 ± 1.5 (range: 0-7) in the pelvic and para-aortic region, respectively. Two patients were upgraded to stage IIIA1 because of lymph node metastasis. In the first case, based on single sections and haematoxylin and eosin (H&E) examination, a pelvic SLN micrometastasis (1 mm) was found on the first H&E section. By using the ultrastaging protocol, the size of the metastasis was increased to 2.1 mm (macrometastasis). In the same patient, the ultrastaging study of the inframesenteric para-cava SLNs found isolated tumour cells in the subcapsular and interfollicular lymph nodes sinus in one of the two SLN harvested (in one of the sections at the fourth and fifth ultrastage levels). The other upstaged case was a para-aortic macrometastasis in a patient in whom the SLN was not identified in the para-aortic field because of the absence of migration from the infundibulo-pelvic stump injection. The cost of ultrastaging in each patient depended on the total number of SLN retrieved, averaging 96.8 € (range: 0-230.5) and 124.5 € (range: 0-322.7€) for pelvic and para-aortic SLN, respectively. CONCLUSIONS: A uniform protocol for ultrastaging is essential for lower-volume metastasis detection and to provide reproducible information between upcoming studies, as evidence about SLN in ovarian cancer is growing.

Protective Maneuver to Avoid Tumor Spillage during Laparoscopic Radical Hysterectomy: Vaginal Cuff Closure.

OBJECTIVE: To demonstrate the feasibility of a protective maneuver to avoid tumor exposure during laparoscopic radical hysterectomy. DESIGN: This video illustrates the vaginal cuff closure technique in cervical cancer surgery. SETTING: The Oncologic Gynecology Department at the University Hospital La Fe. INTERVENTIONS: After the Laparoscopic Approach to Cervical Cancer trial [1], the laparoscopic approach to the surgical treatment of cervical cancer has been questioned: laparotomic surgery has been associated with a better cancer outcome. This publication has changed the current approach recommendation for performing radical hysterectomy from minimally invasive surgery to open surgery. There are some theories that might justify these findings. In minimally invasive surgery, the use of a uterine manipulator can condition the spread owing to erosion and friction caused on the tumor, even leading to the perforation of the tumor. In addition, intraperitoneal colpotomy can lead to pelvic peritoneum contamination by the tumor. To close the gap between laparoscopy and laparotomy, some protective maneuvers, such as vaginal cuff closure, have been proposed [2,3]. These strategies aim to reduce the possibility of manipulation or exposure of the tumor to the pelvis during colpotomy in laparoscopic radical hysterectomy. These protective maneuvers have been shown to decrease the relapse rate in retrospective studies [4]. However, prospective trials are needed to elucidate and confirm these findings. In this video, we explain step-by-step the technique of vaginal cuff closure before a radical hysterectomy performance for uterine cervical cancer. First, the nodal status is established by laparoscopic sentinel lymph node dissection and frozen section study. Bilateral pelvic lymphadenectomy is completed according to the size of the tumor. In the case of negative nodal status, the vaginal cuff is closed: Approximately 2 to 3 cm from the tumor (depending on its size), a circumferential incision of the vaginal mucosa is performed, followed by the dissection of the vaginal wall, which should be sufficient to allow a tension-free vaginal closure. The vaginal cuff is then closed with a running suture. A laparoscopic radical hysterectomy is then completed, and the surgical specimen is removed without any manipulation of the tumor. CONCLUSION: Avoiding manipulation of the tumor during cancer surgery is crucial. A vaginal cuff closure technique appears to be an easy protective maneuver that prevents tumor exposure and manipulation during laparoscopic radical hysterectomy.

Port site resection after laparoscopy in advance ovarian cancer surgery: Time to abandon?

INTRODUCTION: The use of laparoscopy in the treatment and management of advanced ovarian cancer is increasing among the gynaecologic oncologists. The development of port site metastases after laparoscopy is a concern and a matter of debate due to theoretical iatrogenic disease spread. Port site resection (PSR) has been proposed as an option to avoid this scenario. MATERIAL AND METHODS: One hundred and twenty-three patients with advanced ovarian cancer (FIGO III-IV) and with diagnostic laparoscopy were included and after cytoreductive surgery were classified into two groups: no port site resection (No-PSR) and port site resection (PSR). Based on the pathological results of all port site specimens, PSR was classified as positive port site metastasis (PSM+) and negative port site metastasis (PSM-). RESULTS: In 82 cases, the laparoscopic port site access was resected in the debulking surgery. At the final specimen examination, 49% presented as PSM+. No statistical differences regarding survival were found, either between the No-PSR and PSR groups (p = 0.28) or between the PSM+ and PSM - groups (p = 0.92). A higher wound complication rate was found in the PSR group (17% vs. 34%; p = 0.047). The RR (Relative Risk) of wound events for PSR was 2.42 (95% CI 1.09-5.35; p = 0.0296). CONCLUSIONS: To date, not only there is no data supporting PSR after laparoscopy in advanced ovarian cancer, but the role of PSM+ in prognosis also remains unclear. In patients in which laparoscopy is performed prior to the debulking procedure, the PSR may not be recommended in those cases of no macroscopic port site metastasis.

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications.

BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN: A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). CONCLUSION: Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages.

Dental Shade Guide Variability for Hues B, C, and D Using Cross-Polarized Photography.

This study evaluated the color variability of hues B, C, and D between the VITA Classical shade guide (Vita Zahnfabrik) and four other VITA-coded ceramic shade guides using a digital camera (Canon EOS 60D) and computer software (Adobe Photoshop CC). A cross-polarizing filter was used to standardize external light sources influencing color match. A total of 275 pictures were taken, 5 per shade tab, for 11 shades (B1, B2, B3, B4, C1, C2, C3, C4, D2, D3, and D4), from the following shade guides: VITA Classical (control); IPS e.max Ceram (Ivoclar Vivadent); IPS d.SIGN (Ivoclar Vivadent); Initial ZI (GC); and Creation CC (Creation Willi Geller). Pictures were evaluated using Adobe Photoshop CC for standardization of hue, chroma, and value between shade tabs. The VITA-coded shade guides evaluated here showed an overall unmatched shade in all their tabs when compared to the control, suggesting that shade selection should be made with the corresponding manufacturer guide of the ceramic intended for the final restoration.

Radical en bloc peritonectomy in advanced ovarian cancer.

In order to reach cytoreduction in advanced ovarian cancer, peritonectomy and diaphragmatic stripping are procedures required to remove the disease in the upper abdomen. Diaphragm involvement is estimated in up to 40% of cases. Nevertheless, in some of these patients, the tumour volume may constitute a limitation of the technique due to the association with abdominal wall involvement, bulky tumour at the Morrison's pouch or liver infiltration. Extensive upper abdominal procedures should represent a basic resource for the gynaecologic oncologist in order to reach an optimal cytoreduction. A radical peritonectomy with en bloc resection for treating advanced ovarian cancer with extensive widespread diaphragmatic peritoneal carcinomatosis is showed in this surgical film.

Evaluation of Dental Shade Guide Variability Using Cross-Polarized Photography.

This study evaluated color variability in the A hue between the VITA Classical (VITA Zahnfabrik) shade guide and four other VITA-coded ceramic shade guides using a Canon EOS 60D camera and software (Photoshop CC, Adobe). A total of 125 photographs were taken, 5 per shade tab for each of 5 shades (A1 to A4) from the following shade guides: VITA Classical (control), IPS e.max Ceram (Ivoclar Vivadent), IPS d.SIGN (Ivoclar Vivadent), Initial ZI (GC), and Creation CC (Creation Willi Geller). Photos were processed with Adobe Photoshop CC to allow standardized evaluation of hue, chroma, and value between shade tabs. None of the VITA-coded shade tabs fully matched the VITA Classical shade tab for hue, chroma, or value. The VITA-coded shade guides evaluated herein showed an overall unmatched shade in all tabs when compared with the control, suggesting that shade selection should be made using the guide produced by the manufacturer of the ceramic intended for the final restoration.

Murine model for non-invasive imaging to detect and monitor ovarian cancer recurrence.

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer.

Embryonic miRNA profiles of normal and ectopic pregnancies.

Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p) and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223) in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans.

The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy.

Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7-9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤ 6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤ 6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans.