Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions.

The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included.

The effect of total knee arthroplasty on patients' balance and incidence of falls: a systematic review.

PURPOSE: Despite the high incidence of falls in patients with OA, few studies have explored whether falls risk is affected after patients undergo total knee arthroplasty (TKA). Therefore, the aim of this systematic review was to identify the extent of the effects of TKA on balance and incidence of falls by critically reviewing the available literature. METHODS: A systematic review of published literature sources was conducted up to March 2014. All studies assessing balance and incidence of falls after TKA (without physiotherapeutic intervention) were included. The methodological quality of each study was reviewed using the Critical Appraisal Skill Programme tool. RESULTS: Thirteen studies were included, comprising of ten cohort studies (Level II) and three studies with Level of evidence III. CONCLUSIONS: Findings provide evidence that TKA improves significantly single-limb standing balance (~60%) and dynamic balance up to 1-year following surgery (Level of evidence II). Moreover, TKA influences positively fear of falling and incidence of falls by switching 54.2 % of pre-operative fallers to post-operative non-fallers (Level of evidence II-III). It is highlighted that knee extension strength, proprioception and symmetrization of postural strategies have not fully recovered post-TKA and influence balance performance. Clinically, these persistent deficits need to be mitigated by physiotherapy even before TKA takes place.

A review of the open laparoscopic Hasson technique and retrieval of adnexal specimen via umbilicus.

Laparoscopic entry techniques vary amongst surgeons and gynaecologists, with gynaecologists favouring Veress needle entry. Recent RCOG/BSGE recommendations have recommended retrieval of ovarian masses via the umbilical port with resultant less postoperative pain and a faster retrieval time than with retrieval through lateral ports of the same size. This is a prospective observational study reviewing the Hasson entry technique and the introduction of retrieval of specimens via the umbilicus in patients scheduled for a laparoscopy procedure at our day surgery unit. We found no immediate or major surgical complications and all specimens were successfully retrieved through the umbilicus. Pain scores were low. We recommend the technique for extirpative gynaecological surgery. Impact Statement This study confirms that conversion from the closed Veress to the open Hasson technique is achievable in a university hospital setting. Operator confidence during the learning phase is enhanced by the use of ultrasound to locate and measure the depth of the umbilical ligament. Retrieval of benign adnexal specimens through the umbilicus was very satisfactory.

Negative pressure wound treatment (NPWT) in vulva and groin wounds in gynaecologic oncology.

Secondary healing of complicated vulvar and groin wounds is a major challenge due to its moist condition and at risk of contamination by colonic flora. Vacuum assisted closure is the controlled application of sub-atmospheric pressure to the local wound environment using a sealed dressing connected to a vacuum pump. MATERIALS AND METHODS: The NPWT consists of an open-pore polyurethane ether foam sponge, an adhesive cover, fluid collection system, and suction pump that generates negative pressure. Direct application of sponge to blood vessels, bone, nerves or intact skin is avoided. The dressing and tubing are changed every 48-72 hours. RESULTS: Eight patients had NPWT following the vulva and/or groin surgery. Pain during removal of the sponge was the main adverse event requiring narcotic analgesia. All wounds healed completely. One patient is dead of disease progression. Others are alive without disease at four to 48 months. CONCLUSION: Wound breakdown in vulvar and groin surgery is an infrequent occurrence because of the rarity of full radical excision for vulva cancer and infralevator pelvic exenterative surgery. The present experience with NPWT was favourable.

Selective arterial embolisation for intractable vaginal haemorrhage in genital tract malignancies.

PURPOSE OF INVESTIGATION: Embolisation of the internal iliac artery has been described as an effective and safe method of treating massive vaginal haemorrhage in small series of advanced uterine cancer and case reports of cervical cancer. Selective embolization of the bleeding vessel is potentially less morbid. The aim of this study was to assess the efficacy of selective arterial embolisation (SAE) in controlling intractable haemorrhage due to gynaecological malignancy. MATERIALS AND METHODS: This retrospective observational study comes from in a tertiary cancer center with 300 new gynecologic cancers per annum. The authors reviewed all gynecology cancer patients who had intractable major vaginal haemorrhage in the first five years following the introduction of selective arterial embolisation at their unit. The outcomes measured were the control of acute haemorrhage and discharge to planned pathway of treatment. RESULTS: SAE was successful in all cases. Identification of the bleeding point facilitated highly selective embolisation in more than half of the patients. The uterine arteries were embolised in the remaining cases. Bleeding stopped immediately. The expedient control of haemorrhage facilitated early discharge to commencement/continuation of radiation treatment or palliative care as appropriate. CONCLUSIONS: Since the introduction of SAE the authors have avoided emergency radiotherapy, surgery, and repeat vaginal packing in patients with intractable vaginal bleeding due to gynaecological cancer. Patients were discharged to their appropriate treatment pathways in a timely manner. The authors recommend the application of SAE.

Comparison of blood transfusion and surgical complications in peripartum hysterectomy when anticipated and unanticipated.

The aim of the study was to determine the incidence and aetiology of peripartum hysterectomy (PH) for major obstetric haemorrhage (MOH) in our population and to compare estimated blood loss (EBL), blood transfusion, surgical complications and duration of hospital stay in PH that was anticipated and PH that was unanticipated. 26 cases of MOH requiring PH were identified from 50,548 women who delivered between 1 January 2006 and 31 December 2011 (0.5/1000). PH was anticipated in 17 and unanticipated in 9 cases. When compared, the anticipated group was more likely to have placenta accreta 15/17 (88%) vs 4/9 (44%): p = 0.03 and a gynaecological oncologist as the principal operator 15/17 (88%) vs 3/9 (33%): p = 0.007. The EBL 5.5 ± 3.7 SD vs 6.6 ± 3.9 SD l; p = 0.5, units of red cell concentrate or RCC transfused 7 ± 5 SD vs 9 ± 5 SD: p = 0.3, and mean operating time 134 ± 60 SD vs 190 ± 96 SD min: p = 0.07 were less in the anticipated than the unanticipated group, but not significantly so. The intraoperative complication rate 7/17 (41%) vs 3/9 (33%): p = 1.0 and the mean duration of hospital stay 7 ± 1 SD vs 8 ± 3 SD days: p = 0.27 were similar in both groups. PH is associated with a large volume of blood loss and significant surgical complications regardless of whether the procedure is anticipated or not.

Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.

UNLABELLED: There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery. MATERIALS AND METHODS: This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period. RESULTS: Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group. DISCUSSION: Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

Whole-body [18F]fluoro-2-deoxyglucose positron emission tomography scan as combined PET-CT staging prior to planned radical vulvectomy and inguinofemoral lymphadenectomy for squamous vulvar cancer: a correlation with groin node metastasis.

Surgery is the mainstay of treatment for vulvar cancer. FIGO staging requires histopathological detail of the primary tumor and inguinofemoral lymph nodes but groin node dissection carries a substantial risk of short and long-term morbidity. The trend in current practice is towards sentinel lymphadenectomy for cancers with a low risk of metastases. Full lymphadenectomy is undertaken if the sentinel lymph node contains metastasis. The predictive value of 18F-FDG-PET in preoperative assessment of the groin in vulvar squamous cancer was assessed in retrospect at a single institution. A period of three years prior to the introduction of sentinel lymph node mapping was chosen in order to have full histopathological assessment of inguinal and femoral lymph nodes available as the gold standard for correlation with positron emission tomography-computerized tomography (PET-CT) to determine the accuracy of the enhanced radiological technique. In patients with histologically proven metastases to groin nodes, comparisons between PET-CT positive (True-positive/TP) and negative (False-negative/FN) groups vis-à-vis histology showed a tendency towards higher FDG avidity in the vulvar lesions, more bilateral nodes, multiple metastases, larger metastases and more extra-capsular extension in the TP group. Calculations per patient for PET-CT yielded a sensitivity of 50% and specificity at 100%. The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 57.1%. The test accuracy was 70% per patient. The high positive predictive value of PET-CT can be used to advance treatment planning prior to surgical staging of patients identified with Stage III disease. The poor sensitivity makes it unsuitable as a substitute for staging lymphadenectomy.

A randomised prospective trial of intra-operative oesophageal Doppler-guided fluid administration in major gynaecological surgery.

Intra-operative oesophageal Doppler monitor-guided fluid management has been associated with improved postoperative length of hospital stay and morbidity in gastrointestinal and orthopaedic surgery. We designed a randomised controlled trial to test the hypothesis that this approach to intra-operative fluid management in major elective open gynaecological surgery would shorten the length of postoperative stay, defined as time to readiness for hospital discharge. Postoperative morbidity was evaluated as a secondary outcome. The oesophageal Doppler monitor group underwent intra-operative fluid management using an oesophageal Doppler-guided stroke volume optimisation algorithm. Control group (conventional fluid therapy) intra-operative fluid management was based on conventional haemodynamic indices. In a single centre, 102 patients were randomly assigned: 51 to the oesophageal Doppler monitor group (51 analysed) and 51 to the control group (50 analysed). Evaluators who were blinded to patient assignment collected postoperative outcome data. There was no difference in the length of postoperative hospital stay between the groups: median (IQR [range]) number of days until ready for discharge was 6 (5-8 [4-25]) days in the oesophageal Doppler monitor group compared with 7 (5-9 [4-42]) days in the control group, p = 0.5. There was no difference between the groups in postoperative morbidity survey scores on postoperative days 1, 3 or 5. Seven patients in the oesophageal Doppler monitor group and 11 in the control group experienced postoperative complications (p = 0.41). These findings question whether intra-operative oesophageal Doppler-guided fluid therapy is of benefit in patients undergoing open gynaecological surgery.

Myomectomy: a suturing technique for the open procedure.

Uterine fibroids are common among women of reproductive age. In women who have not completed their family, a myomectomy is often suggested to preserve and improve fertility. Here, we would like to describe our technique of myomectomy in an open laparotomy procedure.

CTC-5: A novel digital pathology approach to characterise circulating tumour cell biodiversity.

Metastatic progression and tumor evolution complicates the clinical management of cancer patients. Circulating tumor cell (CTC) characterization is a growing discipline that aims to elucidate tumor metastasis and evolution processes. CTCs offer the clinical potential to monitor cancer patients for therapy response, disease relapse, and screen 'at risk' groups for the onset of malignancy. However, such clinical utility is currently limited to breast, prostate, and colorectal cancer patients. Further understanding of the basic CTC biology of other malignancies is required to progress them towards clinical utility. Unfortunately, such basic clinical research is often limited by restrictive characterization methods and high-cost barrier to entry for CTC isolation and imaging infrastructure. As experimental clinical results on applications of CTC are accumulating, it is becoming clear that a two-tier system of CTC isolation and characterization is required. The first tier is to facilitate basic research into CTC characterization. This basic research then informs a second tier specialised in clinical prognostic and diagnostic testing. This study presented in this manuscript describes the development and application of a low-cost, CTC isolation and characterization pipeline; CTC-5. This approach uses an established 'isolation by size' approach (ScreenCell Cyto) and combines histochemical morphology stains and multiparametric immunofluorescence on the same isolated CTCs. This enables capture and characterization of CTCs independent of biomarker-based pre-selection and accommodates both single CTCs and clusters of CTCs. Additionally, the developed open-source software is provided to facilitate the synchronization of microscopy data from multiple sources (https://github.com/CTC5/). This enables high parameter histochemical and immunofluorescent analysis of CTCs with existing microscopy infrastructure without investment in CTC specific imaging hardware. Our approach confirmed by the number of successful tests represents a potential major advance towards highly accessible low-cost technology aiming at the basic research tier of CTC isolation and characterization. The biomarker independent approach facilitates closing the gap between malignancies with poorly, and well-defined CTC phenotypes. As is currently the case for some of the most commonly occurring breast, prostate and colorectal cancers, such advances will ultimately benefit the patient, as early detection of relapse or onset of malignancy strongly correlates with their prognosis.

Surgeon-administered ilio-inguinal and pudendal nerve blocks for major vulval surgery: An observational study with visual analogue pain scoring.

Surgical excision of the groin and vulva is a painful procedure. Traditionally following general or regional anaesthesia, local anaesthetic was infiltrated around the wound. Thedistribution varied and the somatic pain control was not reliable. Inspired by the success of the application of peripheral nerve blocks for postoperative pain control with open abdominal procedures, we introduced blockade of the ilioinguinal nerve (IIN) and pudendal nerve (PN) into our vulval surgery to assess the requirement for parenteral and oral analgesia in the postoperative period. This is an observational study of all patients undergoing major vulval and/or related groin surgery. Sampling biopsies were excluded. Levobipuvicaine 0.25% (2.5 mg/ml) or 0.5% (5 mg/ml) was used for and dosage was calculated based on the patient's weight with no more than 2 mg/kg. For example, using 0.25% of levobupivacaine (2.5 mg/ml) for a 70 kg patient, 56 ml is administered divided into 4, giving 14mls at each site (2 sites abdominally for IIN block and 2 sites for pudendal block). Eighteen women were included in the analysis. Median age was 67 (range 34-81) years and thirteen (72%) were >60 years. Visual analogue scores (VAS) ranged from 0 to 3 for seventeen patients from day 0 to day 1 and fifteen patients from day 2 to day 5. Two patients had pain scores >4 on one or more postoperative days: one had chronic arthralgia and one had received a lower volume of bupivacaine. This observational study demonstrates that ilioinguinal and pudendal nerve LA blocks may be a valuable addition to the multimodal postoperative analgesic pathway for women undergoing major surgical excision in the vulva and groin.

GCIG-Consensus guideline for Long-term survivorship in gynecologic Cancer: A position paper from the gynecologic cancer Intergroup (GCIG) symptom benefit committee.

INTRODUCTION: Long-term survivors of gynecological cancers may be cured but still have ongoing health concerns and long-term side effects following cancer treatment. The aim of this brainstorming meeting was to develop recommendations for long-term follow-up for survivors from gynecologic cancer. METHODS: International experts, representing each member group within the Gynecologic Cancer InterGroup (GCIG), met to define long-term survival, propose guidelines for long term follow-up and propose ways to implement long term survivorship follow-up in clinical trials involving gynecological cancers. RESULTS: Long-term survival with/from gynecological cancers was defined as survival of at least five years from diagnosis, irrespective of disease recurrences. Review of the literature showed that more than 50% of cancer survivors with gynecological cancer still experienced health concerns/long-term side effects. Main side effects included neurologic symptoms, sleep disturbance, fatigue, sexual dysfunction, bowel and urinary problems and lymphedema. In this article, long-term side effects are discussed in detail and treatment options are proposed. Screening for second primary cancers and lifestyle counselling (nutrition, physical activity, mental health) may improve quality of life and overall health status, as well as prevent cardiovascular events. Clinical trials should address cancer survivorship and report patient reported outcome measures (PROMs) for cancer survivors. CONCLUSION: Long-term survivors after gynecological cancer have unique longer term challenges that need to be addressed systematically by care givers. Follow-up after completing treatment for primary gynecological cancer should be offered lifelong. Survivorship care plans may help to summarize cancer history, long-term side effects and to give information on health promotion and prevention.

Extended thromboprophylaxis post gynaecological cancer surgery; the effect of weight adjusted and fixed dose LMWH (Tinzaparin).

OBJECTIVE: Gynaecological cancer surgery is associated with high rates of venous thromboembolism (VTE) despite recommended prophylaxis. We sought to investigate the impact of extended prophylaxis with fixed dose and weight based LMWH in patients undergoing gynaecological cancer surgery. METHODS: VTE rates were recorded in patients who received LMWH prophylaxis (4500 IU Tinzaparin once daily) for the duration of hospital stay (2006-2012) (n = 610) and were compared with VTE rates in patients who underwent surgery after the introduction of extended prophylaxis (3500/4500 IU Tinzaparin for patients with BMI < 40kg/m2 and 75 IU/kg for BMI > 40 kg/m2) (2012-2017) (n = 651). Peak (4 h) anti-Xa levels in a subset of patients were also evaluated. RESULTS: 73 (5.7%) cases of VTE were recorded during 1 year of follow-up. 20 cases occurred during hospital stay. There was no significant difference in the rate of VTE between the extended prophylaxis cohort and the standard prophylaxis cohort. 23/24 patients who developed VTE in the extended prophylaxis cohort received a fixed (4500 units) dose of Tinzaparin. 63% of patients who received a fixed LMWH dose had peak anti-Xa levels below the target range (0.2-0.4 IU/ml). Peak anti-Xa was lower in patients who subsequently developed VTE compared with those who received either fixed dose (P = 0.041) and weight adjusted Tinzaparin (P = 0.0006). CONCLUSIONS: Extended prophylaxis with Tinzaparin does not significantly reduce VTE rates in gynaecological cancer patients post surgery. Peak anti-Xa levels may be suboptimal in many patients receiving a fixed LMWH dose. Further studies are required to determine whether weight adjusted doses of Tinzaparin may provide more effective prophylaxis following gynaecological cancer surgery.

Vaginal cytology following primary hysterectomy for cervical cancer: is it useful?

BACKGROUND: Vaginal intraepithelial neoplasia (VAIN) is usually detected in patients with synchronous or antecedent cervical or vulval intraepithelial or invasive cancer. VAIN has the potential to progress to malignancy. AIMS: To determine the incidence and severity and analyse the management of vaginal dysplasia in patients undergoing primary hysterectomy for cervical cancer. METHODS: A retrospective study (1984-1998) identified 210 primary invasive cervical cancers. One-hundred and twenty-three patients had a primary hysterectomy. RESULTS: In follow-up six patients were found to have dyskaryosis in a second vaginal smear. Biopsies in the six patients with colposcopic lesions showed VAIN II (n=2), VAIN III (n=1),VAIN III / possible early invasion (n = 1) and invasive carcinoma (n=2). One patient with recurrent squamous cancer received salvage radiotherapy and one with recurrent adenocarcinoma received high dose progestogens and topical 5-fluorouracil. CONCLUSION: All patients are disease-free at follow-up.

Broken bones: common pediatric fractures--part I.

Musculoskeletal injuries are one of the most frequently encountered problems in pediatric practice, with fractures accounting for a surprisingly large percentage of these injuries. A fracture occurs when bone is subjected to more energy than it can absorb. Pediatric healthcare providers must have a good understanding of normal bone growth and development and must recognize common mechanisms of injury and fracture patterns seen in children. Nearly 20% of children who present with an injury have a fracture, and it is estimated that 42% of boys and 27% of girls will sustain a fracture during childhood (Wilkins, 1996). The immature skeleton has several unique properties that directly affect the management of fractures in children.

Developmental dysplasia of the hip: nursing implications and anticipatory guidance for parents.

Developmental dysplasia of the hip (DDH) is a comprehensive term used to describe an abnormal relationship between the femoral head and the acetabulum. Developmental dysplasia of the hip includes a very wide spectrum of abnormality from a frank dislocation (very unstable) to a stable hip with a slightly shallow acetabulum. As many of these findings may not be present at birth, the term developmental more accurately reflects the biologic features than does the term congenital. Despite the recent increased awareness of DDH and the importance of thorough screening programs, hip dysplasia continues to be a frequently missed diagnosis in pediatrics. Earlier detection and diagnosis of DDH is associated with a much more successful and less invasive outcome.