Prognostic utility of serum YKL-40 in patients with cervical cancer.

Inflammation is one of the hallmarks of cancer and plays a crucial role in the development and progression. The objective of the present study was to investigate if high serum YKL-40 is related to poor prognosis in cervical cancer (CC) patients. A prospective biomarker study of 116 patients with CC (FIGO stage Ia: n = 4; Ib: n = 55; II: n = 26; III: n = 26; IV: n = 5) and 152 patients with cervical intraepithelial neoplasia (CIN). The patients received primary surgery, radiotherapy and chemotherapy according to standard guidelines during the period 2001-2004. Seventy patients died during the follow-up period (median 117 months, range 104-131). Serum concentrations of YKL-40 were measured by ELISA. Serum concentrations of YKL-40 were increased (p < .001) in CC patients (median 76 µg/L, IQR 45-148) compared to CIN patients (44 µg/L, IQR 30-61) and healthy women (41 µg/L, IQR 29-58). YKL-40 was elevated (>age-corrected 95th percentile of YKL-40 in healthy women) in 30 (26%) of the CC patients. Univariate Cox analysis demonstrated that YKL-40 (included as a log-transformed continuous variable (base 2)) was associated with recurrence-free survival (RFS) (HR = 1.48, 95% CI: 1.11-1.98, p = .008) and overall survival (OS) (HR = 1.74, 1.44-2.10, p < .0001). Multivariate Cox analysis showed that stage (II + III vs. I: HR = 2.92, 1.37-6.20, p = .005), YKL-40 (HR = 1.35, 1.06-1.73, p = .018) and age (HR = 1.56, 1.21-1.99, p = .0005) were independent prognostic variables of OS. During treatment, a 2-fold increase in YKL-40 compared to baseline level was associated with short RFS (HR = 1.87, 1.27-2.77, p = .0016) and OS (HR = 1.78, 1.26-2.50, p = .0010). Serum YKL-40 is an independent biomarker of OS in patients with cervical cancer.

Health-related quality of life after robotic-assisted laparoscopic hysterectomy for women with endometrial cancer--A prospective cohort study.

OBJECTIVE: The aim of this prospective cohort study using patient-reported outcome measures (PROMs) was to detect short term changes in functioning, symptoms and health-related quality of life (HRQoL) after robotic-assisted laparoscopic hysterectomy (RALH) for endometrial cancer or atypical complex hyperplasia. METHODS/MATERIALS: A total of 139 women answered the EORTC C-30, EN-24 and EQ-5D-3L preoperatively (baseline) by face to face interview and again 1 week, 5 weeks and 4 months postoperatively by telephone interview. The women furthermore reported their level of activity compared to their habitual level in a diary during the first 5 weeks after surgery. RESULTS: We found a clinically relevant decrease in HRQoL after 1 week. At 5 weeks postoperatively, HRQoL was again at the preoperative level. Fatigue, pain, constipation, gastrointestinal symptoms, and appetite were all negatively affected 1 week postoperatively, but back to baseline level at 5 weeks. Ability to perform work or hobbies and change of taste were still affected at 5 weeks. CONCLUSIONS: HRQoL and postoperative symptoms were overall back to the preoperative level 5 weeks after RALH. These findings indicate fatigue, pain, constipation, gastrointestinal symptoms, appetite, ability to perform work and hobbies, change of taste and sexually related problems should be addressed in future research and in the pre- and postoperative care for women undergoing RALH.

Cost-analysis of robotic-assisted laparoscopic hysterectomy versus total abdominal hysterectomy for women with endometrial cancer and atypical complex hyperplasia.

INTRODUCTION: The aim of this study was to analyse the hospital cost of treatment with robotic-assisted laparoscopic hysterectomy and total abdominal hysterectomy for women with endometrial cancer or atypical complex hyperplasia and to identify differences in resource use and cost. MATERIAL AND METHODS: This cost analysis was based on two cohorts: women treated with robotic-assisted laparoscopic hysterectomy (n = 202) or with total abdominal hysterectomy (n = 158) at Copenhagen University Hospital, Herlev, Denmark. We conducted an activity-based cost analysis including consumables and healthcare professionals' salaries. As cost-drivers we included severe complications, duration of surgery, anesthesia and stay at the post-anesthetic care unit, as well as number of hospital bed-days. Ordinary least-squares regression was used to explore the cost variation. The primary outcome was cost difference in Danish kroner between total abdominal hysterectomy and robotic-assisted laparoscopic hysterectomy. RESULTS: The average cost of consumables was 12,642 Danish kroner more expensive per patient for robotic-assisted laparoscopic hysterectomy than for total abdominal hysterectomy (2014 price level: 1€ = 7.50 Danish kroner). When including all cost-drivers, the analysis showed that the robotic-assisted laparoscopic hysterectomy procedure was 9386 Danish kroner (17%) cheaper than the total abdominal hysterectomy (p = 0.003). When the robot investment was included, the cost difference reduced to 4053 Danish kroner (robotic-assisted laparoscopic hysterectomy was 7% cheaper than total abdominal hysterectomy) (p = 0.20). Increasing age and Type 2 diabetes appeared to influence the overall costs. CONCLUSION: For women with endometrial cancer or atypical complex hyperplasia, robotic-assisted laparoscopic hysterectomy was cheaper than total abdominal hysterectomy, mostly due to fewer complications and shorter length of hospital stay.

Common filaggrin gene mutations and risk of cervical cancer.

BACKGROUND: As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. METHODS: We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. RESULTS: The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). CONCLUSION: Carriage of FLG mutations was not associated with the risk of cervical cancer.

Positron emission tomography-computed tomography has a clinical impact for patients with cervical cancer.

INTRODUCTION: Many studies have found that positron emission tomography-computed tomography (PET-CT) has a high sensitivity and specificity in the identification of metastasis in cervical cancer. Herlev Hospital, Denmark, has been performing PET-CTs in stage I-IV cervical cancer since 1 May 2006. The present study investigates the positive (PPV) and negative predictive value (NPV) of PET-CT in stage I disease and the clinical impact of the scan results in all disease stages. MATERIAL AND METHODS: In this retrospective study, 83 consecutive patients with cervical cancer were included between 1 May 2006 and 1 November 2007. Data were collected from patient records and PET-CT reports. RESULTS: Among 47 stage I patients, four had PET-positive findings on the scan in addition to cervical cancer. Only one was a true positive finding. Pelvic lymphadenectomy was performed in 36 stage Ia2-Ib1 patients. Histology from stage I patients revealed a PPV of 25% and a NPV of 88%. Among a total of 36 stage II-IV patients, 14 had PET-positive findings. Five patients had a biopsy performed. Three of these patients were true positives and two were true negatives. Taking of biopsies in the remaining patients was clinically irrelevant. Five patients (6%), all in stage ≥ IIb, were offered an alternative treatment owing to the additional information obtained from the PET-CT. CONCLUSION: PET-CT is useful in the identification of metastatic disease in cervical cancer and it may assist optimal treatment planning; especially in International Federation of Gynecologists & Obstetricians (FIGO) stage > I cancers. Histological verification of PET-positive findings is necessary. The clinical value of PET-CT in early stage cervical cancer may be questioned.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer.

INTRODUCTION: Robotic-assisted laparoscopic hysterectomy (RALH) has become a widely used approach for women with endometrial cancer and has replaced laparotomy. It has been questioned if the increased costs are justified by superior surgical outcomes. The aim of the present study was to examine the frequency, types and severity of post-operative complications after total abdominal hysterectomy (TAH) and RALH using the Clavien-Dindo classification of surgical outcomes. METHODS: A non-randomised, controlled before and after study of 360 women was conducted; 202 underwent RALH and 158 TAH (historical controls). RESULTS: RALH had significant advantages compared with TAH: fewer and less severe post-operative complications and a shorter length of hospital stay. The absolute risk reduction for post-operative complications was 13% (95% confidence interval: 4.29-20.87%). Women treated with TAH had significantly more severe complications (grade ≥ 3) than those treated with RALH; 12% versus 3% (p = 0.001). Infections (urinary and port site) were the most frequent post-operative complications overall. The duration of RALH in the operation theatre was longer, while the duration of stay in the post-anaesthesia care unit was shorter for patients undergoing RALH. CONCLUSIONS: RALH appears advantageous for women treated for endometrial cancer in terms of post-operative complications. We recommend the use of the Clavien-Dindo classification of surgical outcomes for quality assessment. FUNDING: departmental only. TRIAL REGISTRATION: Danish Health Authority (3-2013-111/1/KAHO).

The Experience of Robotic-Assisted Laparoscopic Hysterectomy for Women Treated for Early-Stage Endometrial Cancer: A Qualitative Study.

BACKGROUND: An increasing number of women are offered robotic-assisted laparoscopic hysterectomy as treatment for early-stage endometrial cancer in the developed world. OBJECTIVE: The aim of this study was to explore how women diagnosed with early-stage endometrial cancer experienced robotic-assisted laparoscopic hysterectomy. METHODS: Semistructured interviews were carried out with 12 women, and interview data were analyzed by qualitative content analysis. RESULTS: Four overarching themes emerged: "surgery was a piece of cake," "recovering physically after surgery," "going from being off guard to being on guard," and "preparing oneself by seeking information." The women had confidence in the robotic technique and experienced fast recovery after robotic-assisted laparoscopic hysterectomy; however, they had uncertainties and unanswered questions concerning the postoperative course. Shortly after discharge, the women did not consider themselves surviving cancer patients but as cured. The women searched for information from various sources, for example, the Internet and the online patient chart, to prepare for surgery and to come to terms with the diagnosis. CONCLUSIONS: Although the women had confidence in the robotic technique and recovered quickly physically, they lacked information about what went on in the operation theatre and about their new anatomy. IMPLICATIONS FOR PRACTICE: Patient education about the normal postoperative course in regard to vaginal bleeding, bowel function, and level of physical activity is needed. Individualized information about anatomical changes after surgery is warranted, preferably using anatomical drawings. Potentially, the women could benefit from attending a nursing clinic during the first postoperative months.

Robotic-assisted laparoscopic hysterectomy seems safe in women with early-stage endometrial cancer.

INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine the incidence of complications according to the Clavien-Dindo scale after robotic-assisted laparoscopic hysterectomy (RALH) for early-stage endometrial cancer and atypical complex hyperplasia. The Clavien-Dindo scale grades the severity of complications. METHODS: This was a retrospective, descriptive cohort study of 235 women with endometrial cancer or atypical complex hyperplasia who had RALH. Surgeries were stratified into two groups: with or without pelvic lymphadenectomy. RESULTS: A total of 6% developed a grade 3 or higher complication with no significant difference (p = 0.24) between the groups. The overall incidence of complications was 15%, also with no significant difference between groups (p = 0.32). The most frequent complications were urinary tract infections (6%) and port site/wound infections (3%). A total of 21% of the women who had lymphadenectomy developed lymphoedema within 12 months. CONCLUSION: The types and frequency of complications observed in this study resemble those reported in similar studies of RALH for malignant gynaecologic conditions. Health-care professionals treating and caring for women with early-stage endometrial cancer should know of the types and frequency of post-operative complications following RALH. FUNDING: none. TRIAL REGISTRATION: not relevant.

Implementation of a multidisciplinary robotic centre in a high-volume university hospital.

INTRODUCTION: We describe the initiation of a multidisciplinary centre for robotic surgery including the implementation of robotic-assisted procedures as standard procedure for the majority of cancer operations in urology, gynaecology and gastrointestinal surgery. METHODS: All robotic procedures performed from 2008 to 2013 were included. The information gathered included body mass index, the American Society of Anesthesiologists' physical status classification value (ASA), age, sex, time and type of surgery, duration of procedure, conversion to open surgery, length and type of anaesthesia, re-operations, length of hospital stay and 30-day mortality. RESULTS: The implementation strategy was to start with one specialty at a time, passing on experience from one specialty to the next. The surgical strategy was to begin with standard procedures for which international experience was available and subsequently perform more complex procedures, ending up with robotic-assisted procedures as the standard for most cancer surgery procedures. A total of 2,473 procedures were performed. The operative time was reduced over the period for the main procedures of all three specialties. For prostatectomies, hysterectomies and colectomies, conversion to open surgery occurred in 1.2, 3.8 and 7.7%; the risk of re-operation was 0.2, 2.3 and 7.3%; and, finally, the 30-day mortality was 0.1, 0 and 1%, respectively. CONCLUSION: The implementation was possible as a stepwise introduction across three specialties with low conversion and re-operation rates and a low mortality. A high-volume centre for robotic surgery was developed and patients with malignant diagnoses were offered robotic-assisted surgery within the framework of multidisciplinary cooperation. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency R. No.: 2007-58-0015.

[Clear cell adenocarcinoma of the uterine cervix in a 17-year-old girl].

Clear cell adenocarcinoma of the uterine cervix (CCEA) is a rare disease, accounting for only 1% of all cervical cancers. The disease in young women is linked to diethylstilbestrol (DES) exposure in utero. Following the ban of DES in 1979, CCEA rarely occurs in young women, but still remains a challenge in diagnosis and fertility preservation. We report on a 17-year-old girl, unexposed to DES, diagnosed with clear cell adenocarcinoma in a cervical polyp.

[Challenging investigation of a metastatic adnexal cutaneous tumour].

Adnexal cutaneous tumours are very rare. A lack of knowledge about their clinical presentations can lead to prolonged diagnostic investigations and disease progression. This case report presents a challenging investigation of a metastatic malignant adnexal tumour due to misleading histology, immunohistochemical analysis and clinical findings.

[Epithelioid trophoblastic tumour]. / Epiteloid trofoblasttumor.

Epithelioid trophoblastic tumour is a rare gestational trophoblastic disease. The diagnosis is based on microscopic morphology and immunohistochemical staining. It is important to avoid misdiagnosis, as this tumour is primarily treated by surgery rather than chemotherapy. We report a case and describe diagnostic criteria and differential diagnoses.

Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during cancer development.

Persistent infection with high-risk human papillomavirus (HPV) and expression of the proteins E6 and E7 is a prerequisite for development of cervical cancer. The distal non-coding part of E6/E7 messengers from several HPV types is able to downregulate synthesis of a reporter gene through mechanisms with involvement of cytoplasmic polyadenylation elements (CPEs) in the messengers. We here show that the mRNA levels of one of the four known CPE-binding proteins (CPEBs), the CPEB3, were downregulated in HPV-positive cervical cancers, whereas in ovarian cancer the CPEB1 mRNA level was downregulated. In addition, we showed that the RNA levels of the widely used reference marker GAPDH were upregulated in both cancer forms, and the level of the reference marker U6snRNA was upregulated in cervical cancers. Moreover, a possible correlation between the degree of U6snRNA upregulation and cervical cancer propagation was shown. These changes observed in CPEB1 and CPEB3 might indicate regulatory functions of CPEBs in cancer development of HPV-positive and HPV-negative tumors, respectively, and the U6snRNA, GAPDH mRNA and CPEB1 mRNA levels may be useful as tumor markers for genital cancers although further investigations are needed.