Mesh exposure following minimally invasive sacrocolpopexy: a narrative review.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy is considered mainstay treatment for apical or vaginal vault prolapse and is currently most often performed via a minimally invasive approach. Although mesh-related complications after this procedure are uncommon, mesh exposure can have an important impact on the patient's quality of life. Our objective is to perform a literature review on this complication post laparoscopic or robotic sacrocolpopexy. METHODS: Web of Science and MEDLINE databases were searched for relevant articles published between 2005 and 2021. We retrieved 272 articles of which 83 ultimately were withheld. RESULTS: Minimally invasive sacrocolpopexy (MISC) implies a low risk of mesh exposure, which is currently estimated at 3.5%. Literature however is marked by substantial methodological heterogeneity. Controversy remains in the debate over prevention of mesh exposure after MISC. Performing a concomitant total hysterectomy is associated with an increased risk compared to subtotal hysterectomy or hysteropexy. Treatment of mesh exposure is challenging as guidelines are lacking. Although supported by few prospective data, patients with asymptomatic mesh exposure are managed conservatively. Surgical intervention, preferentially performed by an experienced pelvic surgeon, is indicated in symptomatic patients. CONCLUSIONS: Mesh exposure is often undiagnosed and remains untreated. There is a gap in evidence exploring risk factors for mesh-related complications and efficient measures for reducing them. Choosing the best treatment option is still difficult. Management should be individualized and optimized at the time of diagnosis. Lack of acknowledgement and experience can result in increased morbidity.

The use of methotrexate in conservative treatment of placenta accreta spectrum disorders.

Aim of the study: This article reports on a series of patients with placenta accreta spectrum (PAS) disorder who were treated conservatively with Methotrexate (MTX) administration with or without embolization. We investigate whether there is a place for MTX in conservative treatment of PAS.Methods: We present a single-center retrospective case series of five patients. In all patients, diagnosis was unexpected and not made prenatally.Conclusion: The benefits should be weighed against the possible drug toxicity. Today high-quality evidence is lacking. PAS covers a broad spectrum of pathology, standardization in prenatal and postnatal diagnosis can help to compare evidence on treatment.

Terminal deletion of chromosome 13 in a fetus with normal NIPT: The added value of invasive prenatal diagnosis in the NIPT era.

In the age of noninvasive prenatal testing, there is still an important role for invasive prenatal diagnosis, even for chromosomes 13, 18, and 21.

Oncological outcome, postoperative complications, and mammographic changes after intraoperative radiotherapy with electrons (IOERT) as a boost in a large single-institution cohort of breast cancer patients.

Advantages of using intraoperative radiotherapy with electrons (IOERT) as a boosting modality in breast-conserving therapy include the direct visualization of the tumor bed, a reduced skin dose, and patient convenience. We report oncological outcome, postoperative complication rate, and mammographic changes on follow-up imaging in women treated at our institution with IOERT as a boost modality in breast-conserving therapy for early-stage breast carcinoma. Between January 2007 and June 2018, 763 consecutive patients were enrolled. During breast-conserving surgery, an IOERT boost of 9 Gy was applied, followed by whole breast irradiation (WBI). At a median follow-up of 62.2 months (range: 0.5-135), 13 in-breast recurrences were observed, yielding a local tumor control rate of 98.4% at 5 years. In multivariable analysis, high tumor grading was predictive for local recurrence (HR = 5.6; 95%CI: 1.19-26.2). A total of 27 (3.5%) patients developed any kind of postoperative complication. None of the tumor characteristics nor any of the IOERT technical parameters were predictive for development of a postoperative complication. On follow-up imaging, 145 patients with mammographic changes BIRADS score ≥3 were found of which 50.3% required a biopsy. Only 17 patients had positive biopsies; none of the IOERT parameters were predictive for false-positive imaging. A 9 Gy IOERT boost combined with postoperative WBI provided outstanding local control rates, was well-tolerated, with limited postoperative complications. However, radiologists must be aware of a presumable higher prevalence of mammographic changes after IORT as a boost.

A core invasiveness gene signature reflects epithelial-to-mesenchymal transition but not metastatic potential in breast cancer cell lines and tissue samples.

INTRODUCTION: Metastases remain the primary cause of cancer-related death. The acquisition of invasive tumour cell behaviour is thought to be a cornerstone of the metastatic cascade. Therefore, gene signatures related to invasiveness could aid in stratifying patients according to their prognostic profile. In the present study we aimed at identifying an invasiveness gene signature and investigated its biological relevance in breast cancer. METHODS & RESULTS: We collected a set of published gene signatures related to cell motility and invasion. Using this collection, we identified 16 genes that were represented at a higher frequency than observed by coincidence, hereafter named the core invasiveness gene signature. Principal component analysis showed that these overrepresented genes were able to segregate invasive and non-invasive breast cancer cell lines, outperforming sets of 16 randomly selected genes (all P<0.001). When applied onto additional data sets, the expression of the core invasiveness gene signature was significantly elevated in cell lines forced to undergo epithelial-mesenchymal transition. The link between core invasiveness gene expression and epithelial-mesenchymal transition was also confirmed in a dataset consisting of 2420 human breast cancer samples. Univariate and multivariate Cox regression analysis demonstrated that CIG expression is not associated with a shorter distant metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186). DISCUSSION: These data demonstrate that we have identified a set of core invasiveness genes, the expression of which is associated with epithelial-mesenchymal transition in breast cancer cell lines and in human tissue samples. Despite the connection between epithelial-mesenchymal transition and invasive tumour cell behaviour, we were unable to demonstrate a link between the core invasiveness gene signature and enhanced metastatic potential.

A dynamic clinical pathway for the treatment of patients with early breast cancer is a tool for better cancer care: implementation and prospective analysis between 2002-2010.

BACKGROUND: Due to increasing the complexity of breast cancer treatment it is of paramount importance to develop structured care in order to avoid a chaotic and non-consistent management of patients. Clinical pathways, a result of the adaptation of the documents used in industrial quality management namely the Standard Operating Procedures, can be used to improve efficiency and quality of care. They also aim to re-centre the focus on the patient's overall journey, rather than the contribution of each specialty or caring function independently. METHODS: The effect of the implementation and prospective systematic evaluation of a clinical care pathway for the management of patients with early breast cancer in a single breast unit is evaluated over a long time interval (between 2002 and 2010). Annual analysis of predefined clinical outcome measures, service indicators, team indicators, process indicators and financial indicators was performed. Pathway quality control meetings were organized at least once a year. Systematic feedback was given to the team members, and if necessary the pathway was adapted according to evidence based literature data and in house pathway related data in order to improve quality. RESULTS: The annual number of patients included in the pathway (289 vs. 390, P <0.01), proportion of patients with Tis-T1 tumors (42% vs. 58%, P <0.01), negative lymph nodes (44% vs. 58%, P <0.01) and no metastases at diagnosis (91.5% vs. 95.9%) has risen significantly between 2002 and 2010. Evolution of mandatory quality indicators defined by EUSOMA shows a significant improvement of quality of cancer care. Particularly, the proportion of patients having anti-hormonal therapy (84.8% vs. 97.4%, P = 0.002) and adjuvant chemotherapy according to the guidelines (72% vs. 95.6%, P = 0.028) increased dramatically. Patient satisfaction improved significantly (P <0.05). Progression free 4-year survival was significantly higher for all patients, for T1 tumors only and for T2-T4 tumors only, treated between 2006 to 2008 compared to between 1999 to 2002 and 2003 to 2005 (P = 0.006, P = 0.05, P = 0.06, respectively). Overall 4-year survival of the entire population treated between 2006 and 2008 was significantly better (P = 0.05). CONCLUSIONS: Although the patient characteristics changed over the years due to better screening, this clinical pathway and regular audit of quality indicators for the treatment of patients with operable breast cancer proved to be important tools to improve the quality of care, patient satisfaction and outcome.

The interaction between ER and NFκB in resistance to endocrine therapy.

Endocrine therapy is a commonly used treatment for estrogen receptor (ER)-positive breast cancer. Although endocrine therapy has a favorable outcome in many patients, development of resistance is common. Recent studies have shown that NFκB, a transcription factor regulating a wide variety of cellular processes, might play a role in the development of endocrine resistance. The precise interaction between ER and NFκB and how this contributes to the attenuated responsiveness of ER-positive breast cancer cells to hormonal treatment remains unclear. This review provides an overview of the mechanisms of action for both transcription factors and focuses on the current knowledge explaining how ER and NFκB affect each other's activity and how this cross-talk might contribute to the development of an endocrine resistance phenotype in breast cancer cells.

Management of women with surgically staged 1 uterine papillary serous cancer.

Objective. To review the management and outcomes of women with surgically staged 1 UPSC. Methods. We report on a case series from 2008-2010 from Hamilton Canada. We summarize the data from a literature search on surgically staged 1 UPSC. Results. There is a group women with Stage 1A UPSC with no residual disease at time of surgery who do not require adjuvant therapy. Vault recurrences appear to be lower in women who received adjuvant vault radiation. Chemotherapy appears to confer longer survival for those women with Stage 1B or 1C disease compared of those observed or who had radiation alone. Conclusion. Adjuvant therapy appears to confer benefit in certain groups of women with stage 1 UPSC. A randomized controlled study would clarify the degree of benefit.

Are costs of robot-assisted surgery warranted for gynecological procedures?

The exponential use of robotic surgery is not the result of evidence-based benefits but mainly driven by the manufacturers, patients and enthusiastic surgeons. The present review of the literature shows that robot-assisted surgery is consistently more expensive than video-laparoscopy and in many cases open surgery. The average additional variable cost for gynecological procedures was about 1600 USD, rising to more than 3000 USD when the amortized cost of the robot itself was included. Generally most robotic and laparoscopic procedures have less short-term morbidity, blood loss, intensive care unit, and hospital stay than open surgery. Up to now no major consistent differences have been found between robot-assisted and classic video-assisted procedures for these factors. No comparative data are available on long-term morbidity and oncologic outcome after open, robotic, and laparoscopic gynecologic surgery. It seems that currently only for very complex surgical procedures, such as cardiac surgery, the costs of robotics can be competitive to open surgical procedures. In order to stay viable, robotic programs will need to pay for themselves on a per case basis and the costs of robotic surgery will have to be reduced.

Characterizing the learning curve for laparoscopic radical hysterectomy: buddy operating as a technique for accelerating skill acquisition.

OBJECTIVE: Total laparoscopic radical hysterectomy (TLRH) requires advanced skill in laparoscopy. We evaluated various objective measurements of surgical skill representing the learning curve throughout the first 2 years of implementation of TLRH at our institution. We also describe our technique of "buddy operating," where 2 surgeons combine referrals and operate together, thereby increasing the rate of skill acquisition. METHODS: Charts were retrospectively reviewed for 45 patients undergoing TLRH and pelvic lymphadenectomy at the Hamilton Health Sciences from August 14, 2007, to August 14, 2009. A discriminant function analysis was used to describe the learning curve. χ² and t tests were used for discrete variables. RESULTS: The most predictive learning curve model divided the sample in two, with an accurate group assignment 72.1% of the time. After the first 23 procedures, operative time was significantly shorter (201.7 vs 176.6 min, P=0.02), estimated blood loss was significantly lower (355.7 vs 196.3 mL, P=0.01), the number of lymph nodes removed was significantly higher (11.5 vs 15.3, P=0.02), and hospital length of stay was significantly shorter (1.57 vs 0.14 days, P=0.002). There were nonsignificant trends toward decreasing intraoperative complications and postoperative morbidity. CONCLUSIONS: Total laparoscopic radical hysterectomy with pelvic lymphadenectomy is an important procedure in gynecologic oncology. After a fellowship training program including laparoscopy, we demonstrate the learning curve improves after only 23 cases. This is shorter than previously reported and may be due to "buddy operating," a novel technique for reducing the learning curve in infrequently performed complex procedures.

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

PURPOSE: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. METHODS AND MATERIALS: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. RESULTS: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. CONCLUSION: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

Laparoscopic surgery for endometrial cancer: a review.

Uterine cancer is the fourth most common cancer in Canadian women, with an estimated 4200 new cases and 790 disease-related deaths in 2008. We investigated the domains that are important for further implementation of minimally invasive surgery for the management of endometrial cancer by performing a literature review to assess the available data on overall and disease-free survival in laparoscopic versus open surgery. We also investigated the influence of patient- related factors, surgical factors, quality of life, and cost implications. Among the 23 articles reviewed, five were randomized controlled trials (RCTs), four were prospective reviews, and 14 were retrospective reviews. The RCTs showed no difference in overall and disease-free survival for patients with endometrial cancer who had undergone laparoscopic hysterectomy compared with open surgery. Morbid obesity is a limiting factor for the feasibility of complete laparoscopic staging. Laparoscopy seems to decrease complications and decrease blood loss. It also shortens hospital stay, with improved short-term quality of life and cosmesis, while yielding similar lymph node counts. Overall, laparoscopy is cost-effective, because the increased operation cost of laparoscopy is offset by the shorter hospital stay and faster return to work. On the basis of currently available data, patients with endometrial cancer should be offered minimally invasive surgery as part of their treatment for endometrial cancer whenever possible.

Microarray expression identification of differentially expressed genes in serous epithelial ovarian cancer compared with bulk normal ovarian tissue and ovarian surface scrapings.

The lack of reliable early detection of ovarian cancer and the absence of specific symptoms result in diagnosis of ovarian cancer at advanced stage in the majority of the patients. Through gene expression profiling we can identify important genes that may help understand the evolution from normal ovarian tissue to ovarian cancer. The gene expression profiles of 7 normal ovaries and 26 ovaries with serous epithelial ovarian cancer (SEOC) were examined by cDNA microarrays using supervised and unsupervised analysis, with sequential significance filtering. Real-time RT-PCR was used to measure and compare the expression levels of 5 selected genes: WAP four-disulfide core domain protein HE4 (WAP, up-regulated), secreted phosphoprotein 1 (SPP1, osteopontin; up-regulated), activin A receptor, type I (ACVR1, up-regulated), tumor necrosis factor (TNF superfamily, member 2; TNF, up-regulated) and decorin (DCN, down-regulated) in 4 epithelial scrapings and in 6 bulk-extracted normal ovaries. The gene expression profile of SEOC was not dependent on the stage of the disease at diagnosis. A supervised microarray data analysis identified a subset of 329 genes showing significant differential expression between SEOC samples and bulk normal ovarian tissue and ovarian surface scrapings, including several new genes such as TNFalpha and activin A receptor type I. The real-time RT-PCR for the up-regulated genes did not differ significantly between normal ovarian epithelial scrapings and bulk-extracted ovaries. However, decorin showed a statistically significant difference (P=0.0073) in expression between epithelial scrapings and bulk-extracted ovaries. Previously uncharacterized genes are associated with the malignant phenotype of SEOC. Bulk normal ovarian tissue may serve as control for SEOC tissue in gene expression profiling. Gene expression profiling and sequential statistical analyses of gene subsets can identify new genes and molecular pathways affecting development of SEOC. The genes of interest can be potential targets for future research of SEOC.

Sentinel lymph node in vulvar cancer.

BACKGROUND: The aim of the study was to assess the feasibility, efficacy, and accuracy of the sentinel lymph node (SLN) procedure in vulvar cancer. METHODS: From April 2004 to September 2006, all patients with vulvar cancer, clinical stages I and II, underwent SLN detection, followed by a complete inguinofemoral lymphadenectomy. Demographic, surgical, and pathologic data on all patients were prospectively entered in a database. RESULTS: Forty-two patients underwent the SLN procedure. One patient was excluded from further analysis due to metastases to the vulva. The detection rate for at least 1 SLN per patient was 95%, with bilateral SLNs detected in 46% of patients. There was a trend toward improved ability to detect bilateral SLNs and proximity of the cancer to the midline (r = 0.996; P = .057). No contralateral SLNs were identified in patients with lateral vulvar lesions (>1 cm from the midline). For 'close-to-midline' (< or =1 cm from the midline) lesions, SLNs were detected in 93% of ipsilateral groins and bilateral SLNs were found in 46% of patients, whereas lesions abutting the midline had unilateral and bilateral SLN detected in 100% and 93%, respectively. Sixteen of 41 patients (39%) and 18 of 68 groins (26%) revealed metastatic disease in the lymph nodes; all were correctly identified by the SLN procedure. There were no false-negative SLN results. CONCLUSIONS: SLN dissection is feasible and safe to perform in vulvar cancer. The ability to identify bilateral sentinel inguinal lymph nodes appears to be related to the proximity of the vulvar cancer to the midline.

Cytoreductive surgery for recurrent ovarian cancer.

PURPOSE OF REVIEW: The issue facing clinicians managing ovarian cancer has evolved over the past three decades from treatment for cure and subsequently palliation, to prolongation of survival for most patients. The purpose of this paper is to review the data, rationale, and issues surrounding cytoreductive surgery in recurrent ovarian cancer and its potential role in this new paradigm shift. RECENT FINDINGS: Abundant retrospective series report prolongation of survival with secondary cytoreductive surgery in recurrent ovarian cancer. Selection bias, publication bias, and subsequent therapies, however, are confounding factors for survival. As management of ovarian cancer has recently evolved to a treatment of a 'chronic disease', surgery (which has a definite role in primary therapy) should be considered. SUMMARY: No prospective randomized studies have been performed to date, and therefore adoption of this method of management has been limited. The absence of good data leaves clinicians without clear direction on how to best manage patients. Patients with favorable characteristics such as a long disease-free interval, good performance status, a single or few small intra-abdominal recurrences may benefit from secondary cytoreduction. A prospective randomized study is needed.

Sentinel node metastasis in the groin detected by technetium-labeled nannocolloid in a patient with cervical cancer.

OBJECTIVE: The aim of this study was to describe the first sentinel groin node metastasis detected by technetium-labeled nanocolloid in a patient with cervical carcinoma. METHOD: Preoperatively, 60 mBq technetium-labeled nannocolloid was injected at 3 and 9 o'clock in the uterine cervix. Sentinel nodes were detected using a handheld and laparoscopic probe (Navigator) and removed for pathological assessment. RESULTS: A 52-year-old diagnosed with FIGO stage IIA squamous cervical carcinoma was referred to our unit. On physical examination a bulky cervical tumor and a 1.5-cm enlarged left inguinal lymph node were found. No other abnormalities were seen on pelvic MRI scan and CT scan of the abdomen and lower pelvis. Preoperative lymphoscintigraphy showed that a left groin node and three nodes located in the right obturator fossa were the sentinel nodes. They were easily detected using, respectively, a hand-held and a laparoscopic probe and removed. As both the inguinal and the obturator lymph nodes contained metastatic deposits, the patient was treated with the combination of chemotherapy and radiotherapy. CONCLUSION: Inguinal lymph nodes can rarely be the sentinel nodes in patients with cancer of the uterine cervix.