Use of electrochemotherapy in women with vulvar cancer to improve quality-of-life in the palliative setting: a meta-analysis.

INTRODUCTION: Electrochemotherapy involves the use of transient tumor permeabilization via electric pulses in combination with low-dose chemotherapeutic agents. It has recently emerged as an alternative treatment modality in vulvar cancer. The aim of this meta-analysis was to ascertain the effectiveness of electrochemotherapy in the context of palliative care. METHODS: The following databases were searched: MEDLINE, Scopus, and Cochrane Database, to identify all registered articles pertaining to palliative vulvar cancer treatment with electrochemotherapy from inception until August 2019, in line with PRISMA guidelines. A single-proportion meta-analysis was performed for the outcomes of overall response, complete response, partial response, stable disease, and progressive disease raterespectively, using the random-effect model. Sensitivity analysis was performed to address heterogeneity. RESULTS: Four studies were included totaling 104 women. The studies were of moderate quality. Pooled results from four studies rendered a summary proportion of 78.8% (95% CI 70.4% to 86.1%) for the outcome of overall response. The median age ranged between 68 and 85 years. The sample size per study ranged between eight and 61 women. The tumors' histological types included: squamous-cell carcinoma (96.2%), Paget's disease (2.9%), and malignant melanoma (0.9%). A total of 65 patients (62.5%) presented with a single nodule, whilst 39 patients (37.5%) presented with multiple nodules. Eighty-nine women (85.6%) were previously submitted to other treatment modalities. The overall response rate ranged from 73.2% to 80.9%. The pooled proportion for the outcomes of complete and partial response rate was 48.7% (95% CI 30.74% to 61.5%) and 30.2% (95% CI 21.7% to 39.4%), respectively. The follow-up ranged from 1 to 51 months. No severe adverse effects were reported. The safety profile of electrochemotherapy was favorable. CONCLUSIONS: Electrochemotherapy is an effective and minimally invasive treatment modality in the palliative care management of patients with vulvar cancer. The effective control of vulvar tumors by electrochemotherapy may contribute to improvement of quality-of-life. In light of the moderate quality of evidence, a multi-center cooperation is warranted to confirm its palliative benefit.

Prognostic implications of histological tumor regression (Böhm's score) in patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian carcinoma.

OBJECTIVE: Primary objective of this study was to determine prognostic significance of Bohm's histopathological regression score in patients who received neoadjuvant chemotherapy (NACT) for treatment of high grade serous (HGS) tubal & ovarian carcinoma. METHODS: This was a retrospective cohort study of patients who received NACT between 2010 and 2015. The 3 point histopathological regression score of Böhm was used to classify chemotherapy response. Survival outcomes between the 3 different subgroups was analysed and compared with standard clinico-pathological variables using the Cox proportional hazards model and log-rank test. RESULTS: Study cohort comprised 111 patients. Chemotherapy response score (CRS) 3 was observed in 47 (42.4%) and CRS 1and CRS 2 in 22 (19.8%) and 42 (37.8%) women respectively. Women with CRS score of 1 and 2 combined showed a three-fold increased risk of progression on both univariate and multivariate assessment (HR 3.54; C.I 2.19-5.72, p < 0.001). The median overall survival for patients with CRS 1 was 34 months, CRS 2 was 30 months and 47 months for CRS 3. CRS 1 and 2 combined was the only variable that held significance in prediction of reduced overall survival on multivariate assessment (HR 3.26, C.I 1.91-5.54, p 0.0006). CRS 1 and 2 were also associated with 5.15-fold increased risk of relapse within 6 months of completion of chemotherapy (Odds ratio OR 5.15, C.I 0.07-0.47, p - 0.002). CONCLUSION: CRS is an independent prognosticator of survival and reliable predictor of relapse within 6 months in advanced high grade serous tubal and ovarian carcinoma patients receiving NACT.

Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia after large loop excision of transformation zone: do we need a different follow-up strategy?

AIMS: The aim of this study was to determine the effect of endocervical crypt involvement in specimens with clear margins on recurrence following large loop excision of transformation zone (LLETZ). MATERIAL AND METHODS: This was an observational cohort study. In the colposcopy unit in a university teaching hospital we prospectively collected data for women who underwent LLETZ treatment for high-grade cervical intraepithelial neoplasia (CIN) between 2003 and 2004. We determined the difference in recurrence rate and need for repeat treatment between groups with and without crypt involvement in the primary histology. We prospectively collected data of follow up until 2010. The recurrence was analyzed using Cox regression. RESULTS: A total of 309 women had complete excision of the margins following LLETZ treatment for CIN 2 or 3. There was no significant difference in age between groups with (30.2) and without (29.7) crypt involvement (P<0.25). There was a significant difference in the prevalence of abnormal smear results before and after LLETZ between groups with or without crypt involvement (P=0.043). The need to perform a repeated treatment was significantly different between groups with and without crypt involvement (P<0.024). A full model significantly predicted recurrence of cervical pathology (P<0.009) that necessitated treatment when crypt involvement was present. The odds ratio for repeat treatment with crypt involvement was 2.67 (confidence interval, 1.27-5.64). CONCLUSIONS: Our study showed that positive involvement of endocervical crypt by CIN in a cervical loop excision specimen increases the frequency of subsequent episodes of treatment.

A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

OBJECTIVE: To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. MATERIALS AND METHODS: Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. RESULTS: The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). CONCLUSION: Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

Fertility-sparing surgery for early cervical cancer-approach to less radical surgery.

OBJECTIVE: To evaluate whether certain patients with early-stage cervical cancer are candidates for less radical surgery when considering fertility-sparing surgery. DESIGN: Prospective cohort study. SETTING: Two gynecologic cancer centers (St Thomas' Hospital, London; and West Kent Gynaecological Cancer Centre, Maidstone). POPULATION: Women with early-stage cervical cancer (n = 66) undergoing fertility-sparing surgery, either simple (SVT) or radical vaginal trachelectomy (RVT). METHODS: Prospective clinical data collection and review of patient notes, pathology and radiology data, and pregnancy outcomes. MAIN OUTCOME MEASURES: Postoperative complications, surgical specimen histologic analysis, follow-up data, and obstetric outcome. RESULTS: A total of 66 women underwent either SVT (n = 15) or RVT (n = 51), with pelvic lymphadenectomy, for stage IA2 or IB1 cervical cancer. There was no residual disease in the SVT specimen in 53% versus 29% after RVT. Clear surgical margins in 100% of SVT specimens with residual disease versus 94% after RVT. Two patients had positive lymph nodes after RVT; one of these declined adjuvant treatment until after egg harvesting and subsequently died of disease (1.5%). Median follow-up was 96 months (range, 12-120 months). One patient had a mid vaginal recurrence (1.5%). Twenty-four women have tried to conceive to date, with 14 women having 17 live births. Live birth pregnancy rate was 70.8%. CONCLUSIONS: It is possible to select patients for a less radical fertility-sparing procedure through identification of measurable low-risk factors and thus reduce the morbidity caused by conventional RVT. The selection criteria should be stringent and applied within the setting of a cancer center.

Gynae-Oncology Surgeons' Preparedness to Undertake Colorectal Procedures during Cytoreductive Surgery for Ovarian Cancer: A Cross Sectional Survey.

Cytoreductive surgery for advanced ovarian cancer commonly involves bowel resection. Although UK gynaecological oncologists are trained in bowel surgery, the degree to which they perform bowel surgery independently varies nationally. A recent joint policy statement from the British Gynaecological Cancer Society (BGCS) emphasises the need for formalised colorectal support. An anonymous, online survey was emailed to BGCS members to assess the status of multidisciplinary working between UK gynaecological oncology and colorectal/general surgical teams. A total of 46 members responded (8.2% response rate). There was a large variety in the involvement of colorectal/general surgical teams in preoperative planning. A total of 13% of respondents had no formalised agreement for intraoperative support, 72.1% of respondents independently performed rectal peritoneal stripping and 60.5% independently performed small bowel resection. This was reduced to 27.9% for right hemicolectomy with primary anastomosis and 16.3% for left hemicolectomy with primary anastomosis. Respondents often involved colorectal support for post-operative complications. The majority of UK gynaecological oncologists involve colorectal/general surgical teams in bowel procedures, more commonly for large bowel procedures compared to small bowel and for left colon compared to right colon procedures. A total of 16.3% of respondents independently performed all surveyed bowel procedures. Future research should examine training and experience within these groups to address this disparity.

Does hydrothermal ablation avoid hysterectomy? Long-term follow-up.

OBJECTIVE: We sought to assess the long-term success rate of the HydroThermAblator system (HTA). STUDY DESIGN: We conducted a retrospective cohort study of 376 patients who underwent HTA at our hospital during an 8-year period, following case note review and distribution of a validated menorrhagia questionnaire. RESULTS: The mean age of patients was 43 years. Operative complications included 3 women (0.8%) who experienced intraoperative burns. Of the 248 (66%) returned questionnaires, satisfaction rates were high at 77%. The amenorrhea rate was 38%, with a further 37% of women reporting a substantial decrease in their blood loss. In all, 29 (11%) women underwent subsequent hysterectomy for persistent menorrhagia or dysmenorrhea. Younger women had a significantly higher chance of proceeding to subsequent (P < .05) hysterectomy. CONCLUSION: This study confirms the long-term patient satisfaction with HTA and that the overall probability of proceeding to subsequent hysterectomy over 8 years was only 11%.

A prospective study of sentinel lymph node detection in vulval carcinoma: is it time for a change in clinical practice?

OBJECTIVES: To determine the accuracy of sentinel lymph node (SLN) detection in vulval carcinoma and to report the reliability and safety of this procedure. METHODS/MATERIALS: For a period of 6 years, we recruited women undergoing surgery for vulval carcinoma. All women had a preoperative biopsy confirming the depth of invasion greater than 1 mm. Sentinel lymph node detection was performed using the combined method (Tc-99m and methylene-blue dye). The standard management included complete inguinofemoral lymphadenectomy. When inguinofemoral lymph nodes were found grossly to be enlarged, these nodes were debulked, and the women subsequently treated with radiotherapy with or without chemotherapy. During the last 2 years of the study, a selected group of women had an SLN dissection alone. The SLNs were ultrastaged when they were negative on routine hematoxylin and eosin examination. RESULTS: Among 60 women undergoing SLN detection, SLN was detected in 59 women (98.3%) with combined method. Blue dye did not detect an SLN in 3 women resulting in a 93.3% detection rate. The median SLN count was 2 nodes (range, 1-9). Of the 60 women, 41 had inguinofemoral lymphadenectomy, 4 had only enlarged inguinofemoral nodes debulked, and 15 had the SLN only removed. The non-SLN count was 9 nodes (range, 3-17). There were no false-negative SLNs. Twenty-one women (35%) had positive nodes on final histology. Ultrastaging increased detection of metastases in 6.9% of nodes relative to routine hematoxylin and eosin examination and upstaged 12% of women. The median follow-up was 24 months (range, 2-66 months). CONCLUSIONS: Sentinel lymph node detection is safe and accurate in assessing lymph node status in women with vulval cancer undergoing staging. The combined method using Tc-99m and methylene blue dye injection for SLN detection has the best detection rate. Routine ultrastaging of negative SLN improves the detection of nodal metastases.

Closed-Incision Negative Pressure Wound management Following Midline Laparotomy in Gynecological Oncology Operations: A Feasibility Pilot Study.

Introduction Surgical site infections (SSIs) are a cause of considerable morbidity and mortality in healthcare. Increasingly, closed-incision negative pressure wound therapy (ciNPWT) is being studied as a potential method of reducing incidence of SSI with conflicting results in the literature. Few studies however have looked at its use in the field of gynecological oncology. Objectives We aimed to compare the incidence of SSI when using ciNPWT dressings versus conventional dressings in gynecological oncology patients undergoing midline laparotomies. Methods This was a pilot study involving 14 patients receiving the ciNPWT dressing and 26 control patients. All patients were followed up for a period of 30 days. We used the American College of Surgeons (ACS) risk calculator to estimate each patient's risk of SSI in order to risk stratify the groups. Results The incidence of wound infection was 21% (3/14) in the ciNPWT group and 23% (6/26) in the control group (p=0.886). The ciNPWT group was found to be at significantly higher risk for SSI as calculated by the ACS tool (8.8% ciNPWT, 6% control, p=0.004). After stratifying for this difference in risk, still no significant difference in incidence of SSI was found between the two groups (27% (3/11) ciNPWT, 29% (2/7) control p=0.929). Conclusion The incidence of SSI does not appear to decrease by the prophylactic use of the closed-incision negative pressure wound dressing.

Surgery of Benign Ovarian Masses by a Gynecological Cancer Surgeon: A Cohort Study in a Tertiary Cancer Centre.

Objectives This study aimed to evaluate diagnostic performance in characterising ovarian masses by our gynaecological oncology multidisciplinary team meeting (MDM). Surgical outcome and overall impact on patients and healthcare service were also assessed. Methods This was a prospective cohort study of all women with adnexal masses presenting to the gynaecological oncology MDM at a central London tertiary cancer centre between February 2017 and February 2018. The multidisciplinary team (MDT) outcome, imaging details, subjective opinion, tumour markers, surgical details, and final histological diagnosis were collected. Diagnostic performance was also determined. Results There were 200 eligible patients in the study period. MDM imaging review demonstrated a sensitivity of 98.4% (95% CI: 94.3% to 99.8%) and a specificity of 52% (95% CI: 40.2% to 63.7%). Thirty-five cases were false positive, either presumed invasive cancers (51%) or borderline tumours (49%). The most common histological types were serous (37%) and mucinous (31%) cystadenomas. A retrospective application of the International Ovarian Tumor Analysis (IOTA) Assessment of Different NEoplasias in the adneXa (ADNEX) model suggests a potential reduction in false-positive rates (17%). Among the false-positive cases, there was no postoperative (90 days) mortality and postoperative morbidity was 14% with only grade 2 (CD2) complications according to Clavien and Dindo's CD classification. Conclusion An MDT has high sensitivity but low specificity when characterising ovarian masses referred with possible ovarian cancer to the tertiary centre. False-positive values in ovarian cancers are an important indicator of over-treatment. More research is required to assess other methods, such as the IOTA ADNEX model, to reduce the false-positive value.

Spontaneous Heterotopic Pregnancy Associated with Massive Intraperitoneal Haemorrhage and a Normal Heart Rate, Illustrating the Concept of Relative Bradycardia.

A 28-year-old, 9 and a half weeks pregnant (spontaneous conception) multigravida presented with abdominal pain and vaginal bleeding. On examination, her abdomen was diffusely tender, particularly in the right iliac fossa, though guarding was absent. Transabdominal and transvaginal ultrasonography demonstrated a viable intrauterine pregnancy and large-volume intraperitoneal haemoperitoneum; the right ovary could not be identified. The patient became hypotensive with decreased responsiveness, yet her heart rate remained normal. She proceeded to surgery where a ruptured right tubal ectopic pregnancy was identified and right salpingectomy was performed. Estimated blood loss was 3900ml. Postoperative recovery was uneventful. Ultrasound 3 days after surgery demonstrated a viable intrauterine pregnancy of gestational age 9 weeks + 1 day. The patient remains well. Her anomaly scan at 20 weeks and 6 days showed normal growth, amniotic fluid, and Dopplers with no obvious structural defects. She is currently 27 weeks pregnant and will be rescanned at 36 weeks.

Advanced stage (IIIC/IV) endometrial cancer: Role of cytoreduction and determinants of survival.

OBJECTIVE: Primary aim of this study was to assess the impact of optimal cytoreduction in women who had surgical treatment of advanced stage (IIIC/IV) endometrial cancer. Secondary objective was to define demographic and surgico-pathologic variables that exerted a significant influence on survival outcomes. STUDY DESIGN: Records of 45 patients with stage IIIC/IV Endometrial cancer who underwent surgery with cytoreductive intent between 2010 and 2016 were analysed. Data on disease distribution, surgical procedures, adjuvant therapy and survival times was collated. Survival curves were plotted by Kaplan Meier method and median survival estimates were compared using log rank test. Cox proportional hazards model was used to identify independent variables predictive of survival. RESULTS: 28 women (62.2%) had undergone primary surgery and 17 (37.8%) received neoadjuvant chemotherapy prior to delayed primary surgery. Optimal cytoreduction to 1 cm residual disease (p = 0.02). Median overall survival was 29 months in patients who had optimal cytoreduction and 17.5 months in women who had bulky residual disease (p=0.002). Only poor performance status (p = 0.035), presence of bowel disease (p = 0.05) and suboptimal cytoreduction (p = 0.006) retained significance as predictors of poor survival on multivariate analyses. Suboptimal cytoreduction surgery, compared to optimal cytoreduction, showed a 3.55-fold increased risk of death independent of performance status and anatomic region with disease (Hazard Ratio 3.55 (95% confidence interval 1.44-8.73) p = 0.006). CONCLUSION: Survival analyses demonstrate significantly better progression free survival and overall survival when optimal cytoreduction is achieved. A prospective, multicentre study is recommended to establish conclusive evidence.

Interleukin-10 and prostaglandin E2 have complementary but distinct suppressive effects on Toll-like receptor-mediated dendritic cell activation in ovarian carcinoma.

Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists. Our results show that ascites reduces the TLR-mediated up-regulation of CD86 and partially inhibits the production of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-12 and tumour necrosis factor α (TNFα) in monocyte-derived DC from healthy controls. We further observe an impaired T cell stimulatory capacity of DC upon activation with TLR agonists in the presence of ascites, indicating that their functionality is affected by the immunosuppressive factors. We identify IL-10 and prostaglandin E2 (PGE2) as the pivotal immunosuppressive components in OC-associated ascites compromising TLR-mediated DC activation. Interestingly, IL-10 is present in both ascites from patients with malignant OC and in peritoneal fluid from patients with benign ovarian conditions and both fluids have similar ability to reduce TLR-mediated DC activation. However, depletion of IL-10 from ascites revealed that the presence of paracrine IL-10 is not crucial for ascites-mediated suppression of DC activation in response to TLR activation. Unlike IL-10, PGE2 is absent from peritoneal fluid of patients with benign conditions and selectively reduces TNFα induction in response to TLR-mediated activation in the presence of OC-associated ascites. Our study highlights PGE2 as an immunosuppressive component of the malignant OC microenvironment rendering PGE2 a potentially important target for immunotherapy in OC.

Behavioral characteristics of manual palpation to localize hard nodules in soft tissues.

Improving the effectiveness of artificial tactile sensors for soft-tissue examination and tumor localization is a pressing need in robot-assisted minimally invasive surgery. Despite the availability of tactile probes, guidelines for optimal palpation behavior that best exploit soft-tissue properties are not available as yet. Simulations on soft-tissue palpation show that particular stress-velocity patterns during tissue probing lead to constructive dynamic interactions between the probe and the tissue, enhancing the detection and localization of hard nodules. To the best of our knowledge, this is the first attempt to methodically evaluate the hypothesis that specific human palpation behaviors (defined by the fingers' velocity, trajectory, and exerted force) directly influence the diagnosis of soft-tissue organs. Here, we use simulation studies involving human participants to establish open hypotheses on the interaction and influence of relevant behavioral palpation variables, such as finger trajectory, its velocity, and force exerted by fingers on the accuracy of detecting embedded nodules. We validate this hypothesis through finite element analysis and the investigation of palpation strategies used by humans during straight unidirectional examination to detect hard nodules inside silicone phantoms and ex-vivo porcine organs. Thus, we conclude that the palpation strategy plays an important role during soft-tissue examination. Our findings allow us, for the first time, to derive palpation behavior guidelines suitable for the design of controllers of palpation robots.