Surgeons' posture and muscle strain during laparoscopic and robotic surgery.

BACKGROUND: It is assumed that conventional laparoscopy (LAP) and robotic-assisted laparoscopic surgery (RALS) differ in terms of the surgeon's comfort. This study compared muscle workload, work posture and perceived physical exertion of surgeons performing LAP or RALS. METHODS: Colorectal surgeons with experience in advanced LAP and RALS performed one of each operation. Bipolar surface electromyography (EMG) recordings were made from forearm, shoulder and neck muscles, and expressed relative to EMG maximum (%EMGmax ). The static, median and peak levels of muscle activity were calculated, and an exposure variation analysis undertaken. Postural observations were carried out every 10 min, and ratings of perceived physical exertion before and after surgery were recorded. RESULTS: The study included 13 surgeons. Surgeons performing LAP showed higher static, median, and peak forearm muscle activity than those undertaking RALS. Muscle activity at peak level was higher during RALS than LAP. Exposure variation analysis demonstrated long-lasting periods of low-level intensity muscle activity in the shoulders for LAP, in the forearms for RALS, and in the neck for both procedures. Postural observations revealed a greater need for a change in work posture when performing LAP compared with RALS. Perceived physical exertion was no different between the surgical modalities. CONCLUSION: Minimally invasive surgery requires long-term static muscle activity with a high physical workload for surgeons. RALS is less demanding on posture.

ANTECEDENTES: Se asume que la cirugía laparoscópica (laparoscopic, LAP) y la cirugía laparoscópica asistida por robot (robotic-assisted laparoscopic surgery, RALS) difieren en cuanto a la comodidad del cirujano. En este estudio se comparó la carga de trabajo muscular, la postura de trabajo y el esfuerzo físico percibido por los cirujanos al realizar LAP o RALS. MÉTODOS: Trece cirujanos colorrectales con experiencia en LAP avanzada y RALS realizaron una operación con cada uno de los abordajes. Se registró la electromiografía de superficie bipolar en los músculos del antebrazo, del hombro y del cuello, y se expresó en relación con el EMG máximo (% EMGmax). Se calculó el nivel de actividad muscular estático, mediano y pico, y se realizó un análisis de variación de la exposición. Las observaciones posturales se llevaron a cabo cada diez minutos y se registraron las valoraciones del esfuerzo físico percibido antes y después de la cirugía. RESULTADOS: La práctica de LAP mostró una mayor actividad muscular estática, mediana y pico del antebrazo en comparación con la práctica de RALS. El hombro izquierdo mostró la mayor actividad muscular en RALS a nivel máximo. El análisis de variación de exposición demostró periodos prolongados de actividad muscular de baja intensidad para LAP en los hombros, para RALS en los antebrazos y para ambos en el cuello. Las observaciones posturales mostraron una mayor necesidad de un cambio en la postura de trabajo al realizar LAP en comparación con RALS. El esfuerzo físico percibido no fue diferente entre ambas modalidades quirúrgicas. CONCLUSIÓN: La cirugía mínimamente invasiva requiere una actividad muscular estática prolongada con una alta carga de trabajo físico para los cirujanos. RALS es menos exigente en el aspecto postural.

New insights into early recovery after robotic surgery for endometrial cancer.

OBJECTIVE: To assess early recovery of physical health after robotic minimally invasive surgery (RMIS) for early-stage endometrial cancer using the European Organisation of Research and Treatment of Cancer Computer Adaptive Test Core questionnaire (EORTC CAT Core). The EORTC CAT Core provides individualised measurements while maintaining comparability. A hypothesis of individual complete recovery to baseline within three post-surgical weeks was evaluated. METHODS: Ninety-four women who underwent RMIS for early-stage endometrial cancer were included consecutively. The EORTC CAT Core was distributed before surgery and prospectively every week during the first post-operative month. Repeated measures models were fitted for each of the four domains (physical functioning, role function, fatigue, and pain) and tested for impact of age, ASA score, minor/major surgery, and the individual baseline scores (poorest, intermediate, best). RESULTS: Women with the lowest physical functioning, lowest role function, highest fatigue level, and highest pain level at baseline all recovered within three weeks. Women with the highest physical functioning, highest role function, lowest level of fatigue, and lowest level of pain at baseline did not reach their individual baselines within the first post-operative month but had the most favourable domain-scores three weeks post-operatively. CONCLUSION: The individual woman's physical health baseline score is predictive for her postoperative recovery following RMIS for early-stage endometrial cancer. Women with the best physical health had the best postoperative functions and lowest level of symptoms; however their recovery to baseline was prolonged. Computer adaptive testing may be a valuable tool for individualised pre-operative information and supportive care during surveillance.

Cost-effectiveness of incisional negative pressure wound therapy compared with standard care after caesarean section in obese women: a trial-based economic evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section. DESIGN: A cost-effectiveness analysis conducted alongside a clinical trial. SETTING: Five obstetric departments in Denmark. POPULATION: Women with a pregestational body mass index (BMI) ≥30 kg/m2 . METHOD: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth. MAIN OUTCOME MEASURES: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained. RESULTS: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m2 . CONCLUSION: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m2 . TWEETABLE ABSTRACT: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Patient-initiated follow up affects fear of recurrence and healthcare use: a randomised trial in early-stage endometrial cancer.

OBJECTIVE: To test the hypothesis that patient-initiated follow up reduces the fear of cancer recurrence (FCR) and healthcare use when compared with traditional hospital-based follow up. DESIGN: Pragmatic, multicentre randomised trial. SETTING: Four Danish departments of gynaecology between May 2013 and May 2016. POPULATION: One hundred and fifty-six women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I low-intermediate risk endometrial carcinoma. METHODS: Women allocated to the control group attended hospital-based follow up consisting of regular outpatient visits for 3 years after primary treatment. Women in the intervention group were instructed in patient-initiated follow up, which included careful instruction in alarm symptoms and options for self-referral rather than a schedule of examinations. MAIN OUTCOME MEASURES: The primary end point was FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) after 10 months of follow up. Secondary end points included cancer-related use of primary and secondary health care during the first 10 months after treatment. RESULTS: In the primary analysis, FCR decreased significantly more in the control group from baseline to 10 months of follow up (difference -5.9, 95% CI -10.9 to -0.9). The majority of this improvement happened after only 3 months of follow up. Women receiving the intervention had fewer examinations at the department compared with the control group (0 versus 2 median visits, P < 0.01) and 58% of these examinations were scheduled because of vaginal bleeding. CONCLUSIONS: Hospital-based follow up alleviates FCR significantly more than patient-initiated follow up, though the estimated difference was small. Patient-initiated follow up is a feasible, potentially cost-reducing follow-up approach in a population of endometrial cancer survivors with low risk of recurrence. The decision to use patient-initiated follow up should balance these benefits and harms. TWEETABLE ABSTRACT: Patient-initiated follow up reduces healthcare use but maintains fear of recurrence in endometrial cancer. PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? Follow up of women with endometrial cancer is resource consuming and previous research suggests that it is not effective. Even though the women benefit from reassurance at follow up, routine examinations may also remind the women of the disease and induce fear of cancer recurrence. Furthermore, routine follow up may delay recurrence diagnosis, because the women do not report their symptoms until the next scheduled visit. In the research explained in this article, patient-initiated follow up was evaluated as an alternative to traditional follow up. The women were randomly assigned to one of two follow-up programmes: regular gynaecological examinations at the department of gynaecology or self-referral with careful instruction in alarm symptoms, that is, patient-initiated follow up. The level of fear of cancer recurrence in the two groups was obtained by questionnaires. Information on healthcare use was obtained by questionnaires and a chart review. What were the main findings? Regular examinations at the department of gynaecology reduced the fear of cancer recurrence significantly more than patient-initiated follow up, though the difference was small. Women who were instructed in alarm symptoms, under self-referral, were able to monitor their symptoms, and this approach significantly reduced the number of examinations at the department of gynaecology. What are the limitations of the work? Participants in the self-referral group knew that they were examined less than other women, and this may have induced fear of cancer recurrence. Similarly, the regular completion of questionnaires regarding fear of cancer recurrence may have reminded the women of the disease and diminished the difference between the two groups. What are the implications for patients Patient-initiated follow up reduced healthcare use but maintained fear of cancer recurrence in women who had survived early-stage endometrial cancer. Future analyses on quality of life and cost-effectiveness are needed to balance the benefits and harms of patient-initiated follow up.

Fertility after uterine artery embolization of fibroids: a systematic review.

PURPOSE: The impact of uterine artery embolization (UAE) for the purpose of diminishing the effect of uterine fibroids on fertility is unclear. We have investigated the reported rates of pregnancy and miscarriage after treatment of uterine fibroids with UAE. MATERIALS AND METHODS: We searched for relevant information in PubMed and Embase for randomized controlled trials (RCT), controlled clinical trials, comparative before-after trials, cohort studies, case-control studies and case series where UAE treatment of premenopausal women was performed for uterine fibroids with and where a control intervention was included. The PRISMA guideline was used to do a systematic review using the main outcomes pregnancy rate and miscarriage rate. Risk of bias was assessed by the Cochrane risk of bias tool or by ROBINS-I. The quality of evidence was assessed by the GRADE approach. RESULTS: We included 17 studies (989 patients): 1 RCT, 2 cohort studies, and 14 case series. Pregnancy rates after UAE were 50% in the RCT and 51 and 69% in the cohort studies. Among the case series median pregnancy rate was 29%. Miscarriage rates were 64% in the RCT. Miscarriage rates at 56 and 34% were found in the cohort studies after UAE. The median miscarriage rate was 25% in the case series. CONCLUSION: Pregnancy rate was found to be lower and miscarriage rate higher after UAE than after myomectomy. However, we found very low quality of evidence regarding the assessed outcomes and the reported proportions are uncertain. There is a need for improved prospective randomized studies to improve the evidence base. Systematic review registration number: CRD42016036661.

Meta-analysis of negative-pressure wound therapy for closed surgical incisions.

BACKGROUND: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions. METHODS: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions. RESULTS: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0·54, 95 per cent c.i. 0·33 to 0·89) and seroma formation (RR 0·48, 0·27 to 0·84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence. CONCLUSION: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet.

Rehabilitation of women with gynaecological cancer: the association between adult attachment, post-traumatic stress disorder and depression.

OBJECTIVE: We hypothesised that being diagnosed with gynaecological cancer influences adult attachment and occurrence of depression and post-traumatic stress disorder (PTSD). The main aim of the study was to assess changes in the attachment dimensions, PTSD and depression from baseline to 5-month post-treatment. Further, we evaluated the association between attachment avoidance/anxiety dimensions and PTSD/depression among women newly diagnosed with ovarian, endometrial, or cervical cancer. METHODS: Consecutive Danish-speaking women aged 20 to 75 years and treated surgically for primary gynaecological cancer were eligible. All patients were offered a rehabilitation programme consisting of two face-to-face sessions and two phone calls carried out by a nurse. Patients were asked to complete the Revised Adult Attachment Scale, the Harvard Trauma Questionnaire and the Major Depression Inventory at baseline and at 5-month follow-up. In all, 151 women consent to participate in the sessions where 51 fulfilled Revised Adult Attachment Scale questionnaire and contribute with socio-demographic data. RESULTS: We found significant positive changes within the attachment anxiety dimension among women with ovarian cancer, a significant reduction of PTSD among endometrial cancer patients and insignificant changes in depression among all cancer types. The attachment anxiety dimension significantly increased the odds for PTSD and depression. CONCLUSIONS: Depression and PTSD were prevalent among ovarian and cervical cancer patients. The adjustment of rehabilitation according to patients' attachment anxiety dimension contains possibilities for indirect impact on PTSD and depression symptoms. Copyright © 2015 John Wiley & Sons, Ltd.

Surgeons' muscle load during robotic-assisted laparoscopy performed with a regular office chair and the preferred of two ergonomic chairs: A pilot study.

Surgeons work in awkward work postures and have high precision demands - well-known risk factors for musculoskeletal pain. Robotic-assisted laparoscopy is expected to be less demanding compared to conventional laparoscopy; however, studies indicate that robotic-assisted laparoscopy is also associated with poor ergonomics and musculoskeletal pain. The ergonomic condition in the robotic console is partially dependent upon the chair provided, which often is a regular office chair. Our study quantified and compared the muscular load during robotic-assisted laparoscopy using one of two custom built ergonomic chairs and a regular office chair. The results demonstrated no differences that could be considered clinically relevant. Overall, the study showed high levels of static and mean muscular activity, increased perceived physical exertion from pre-to-post surgery, and moderate to high risk for musculoskeletal injuries measured by the Rapid Upper Limb Assessment worksheet. Authors advocate for further investigation in surgeons' ergonomics and physical work demands in robotic surgery.

Stage Ib cervical cancer during pregnancy: planned delay in treatment--case report.

Approximately 0.05% of pregnancies are complicated with cervical cancer. Treatment of this malignancy during pregnancy depends on the stage of disease and gestational age at the time of diagnosis. In women with Stage IB cervical cancer immediate treatment, without regard to the pregnancy, is traditionally advocated in the first and second trimester. A planned delay of treatment, to achieve foetal maturity, may be acceptable if there are no adverse maternal and foetal consequences. We present a case of a Stage IB1 cervical cancer, diagnosed during a twin pregnancy, and treated with a planned delay of 19 weeks. We have reviewed the literature and focused on what is known about planned delay in therapy of Stage IB cervical cancer, diagnosed before 30 weeks of gestational age.

Immunogenicity and safety of the 9-valent HPV vaccine in men.

OBJECTIVES: This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16-26 years of age (the population that was used to establish 9vHPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. METHODS: This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3-dose regimen (Day 1, Month 2, Month 6) of 9vHPV vaccine. Serum samples were collected for anti-HPV assays. Safety information was collected for ∼ 12 months. RESULTS: The geometric mean titers (GMTs) for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 for HM were non-inferior to those of women at Month 7. For all vaccine HPV types, Month 7 GMTs were numerically lower in MSM than in HM. Over 99.5% of subjects were seropositive at Month 7 for each vaccine HPV type. Administration of 9vHPV vaccine to both 16-26 year old men and women was generally well tolerated. CONCLUSIONS: These results support bridging the efficacy findings with 9vHPV vaccine in young women 16-26 years of age to men 16-26 years of age.

Elevated serum insulin-like growth factor-binding protein 2 (IGFBP-2) and decreased IGFBP-3 in epithelial ovarian cancer: correlation with cancer antigen 125 and tumor-associated trypsin inhibitor.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) recently have been shown to play a physiological role in the female genital system, including the ovarian follicular system. However, little is known about the role of the IGF system in malignant ovarian disease. To assess possible mutual correlations between alterations in circulating IGFBP profiles and tumuor markers in patients with epithelial ovarian cancer, we performed an RIA for IGFBP-2 and IGFBP-3 and a Western ligand blotting (WLB) in serum samples from 20 patients with epithelial ovarian cancer, 10 patients with benign ovarian tumors, and 8 healthy age-matched controls. The epithelial ovarian cancer group had a mean IGFBP-2 level that was 253% (RIA) and 105% (WLB) above that of controls. IGFBP-2 even correlated positively with the highly sensitive serum tumor marker, cancer antigen 125 (CA 125) (r = 0.71, P < 0.001) but not with the less sensitive tumor-associated trypsin inhibitor. In contrast, serum IGFBP-3 (by RIA and WLB) was decreased in patients with ovarian cancer, and IGFBP-3 proteolytic activity was detectable in some of the patients. Neither IGFBP-3 nor IGFBP-3 proteolytic activity correlated with CA 125; but the former correlated inversely, and the latter positively, with tumor-associated trypsin inhibitor. In conclusion, IGFBP-2 levels are high in serum of epithelial ovarian cancer patients, and the increment in serum IGFBP-2 correlates positively with CA 125. Alterations in serum IGFBP-2 levels may therefore, serve as a potential additional marker for ovarian cancer.

Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia.

The present investigation evaluated the relationship between dysplasia of the uterine cervix and telomerase activity, expression of p53, MIB-1 and PCNA. Telomerase activity was measured on cervical cytobrush material from 126 women suspected of having dysplasia and 61 controls using the telomeric repeat amplification protocol. Immunohistochemistry was used to detect the tumor suppressor protein p53 and cell proliferation, the latter by MIB-1 and PCNA expression. Infection with human papillomavirus 16 was detected by PCR amplification and Southern blot hybridization of DNA extracted from the same brush material. Positive telomerase activity was found in 5 of 43 (11.6%) normal samples, 12 of 57 (21.1%) samples with inflammation or koilocytosis, 7 of 17 (41.2%) CIN 1 (cervical intraepithelial neoplasia, grade 1), 8 of 20 (40.0%) CIN 2, and 25 of 42 (59.5%) CIN 3/ CIS. Telomerase activity was significantly related to the level of dysplasia (p<0.001) and proliferation measured by MIB-1 (p=0.019), but not to the level of PCNA (p=0.445), HPV 16 status (p=0.098) or staining for p53 (p=0.271). Dysplasia was also related to PCNA, MIB1, p53, and presence of HPV 16. A sequential increase in the examined parameters, paralleling the progression of abnormality, was observed. PCNA and telomerase showed an increase in CIN 1, MIB-1 and HPV16 in CIN 2, and finally p53 in CIN 3/CIS.

Value of quantitative pathological variables as prognostic factors in advanced ovarian carcinoma.

AIMS: To evaluate correlations among clinical, pathological, morphometric, stereological, and DNA flow cytometric variables and their prognostic value in advanced ovarian cancer. METHODS: Tissue was collected from 180 patients with advanced ovarian cancer. All 180 had undergone debulking surgery and were being treated with cisplatin. Long term follow up was available for all patients. The mitotic activity index (MAI), volume % of epithelium (VPE), mean nuclear area (MNA), standard deviation of the nuclear area (SDNA), estimates of volume weighted mean nuclear volume (nu v), and variables obtained from minimum spanning tree (MST) analysis were assessed in the least differentiated tumour section in each case. DNA flow cytometry was also performed. RESULTS: Quantitative pathological features differed significantly with respect to histological grade. The MAI, MNA, SDNA, and the number of points connected to three neighbours differed significantly among the different DNA ploidy groups. The VPE and number of points connected to two or three neighbours differed significantly between FIGO stages III and IV. Fifty two (29%) patients survived. FIGO stage, residual disease and SDNA had prognostic significance on both univariate and multivariate survival analysis. In patients with FIGO III stage disease and residual tumour nodes < or = 2 cm in diameter (67 patients, 29 (43%) survivors) a prognostic index was established based on SDNA and of the line length of the MST. The median survival time was not reached in a subgroup of patients with favourable prognosis (overall survival 57%). Median survival was 32 months for patients with an unfavourable index score (overall survival 28%). CONCLUSION: Morphometric variables have important additional value in predicting prognosis in patients with advanced ovarian cancer.

CA 125 measurements in ovarian cancer patients during their first postoperative week.

Cancer antigen 125 (CA 125) was measured in 17 patients with ovarian carcinoma before their primary operation and during the first week after surgery. The purpose was to correlate the change in the antigen level with the patient's survival. Before surgery normal (16-30 U ml-1 CA 125 values were measured in four patients and 13 had increased (75-11.356 U ml-1) antigen concentrations. After surgery the marker increased to 104-931% of the preoperative level in five patients. In 12 patients the post-operative antigen level decreased to 20-96% of the preoperative level. In seven of these patients CA 125 increased without exceeding the preoperative level, after the initial postoperative fall. Thus, the CA 125 level during the first week after primary operation of ovarian cancer patients seems to be influenced by other variable factors besides a reduced amount of tumor tissue. Therefore, an investigation of the correlation between the change in the CA 125 concentration within the first week after surgery and the survival of the patient cannot be performed for the time being.

Nuclear volume and prognosis in ovarian cancer.

The prognostic value of the volume-weighted mean nuclear volume (MNV) was investigated retrospectively in 100 ovarian cancer patients with FIGO-stage IB-II (n = 51) and stage III-IV (n = 49) serous tumors. No association was demonstrated between the MNV and the survival or between the MNV and two of five additional parameters: age and amount of residual tumor. However, both in stage IB-II and stage III-IV carcinomas, the MNV increased significantly with increasing tumor grade and DNA-index. Furthermore, FIGO-stage IB-II patients had significantly smaller nuclei than patients with stage III-IV disease.

The significance of differences in prognostic value of quantitative pathologic features in FIGO stage III and IV serous adenocarcinoma of the ovary between a group of Danish patients and other groups.

Previous studies have shown DNA cytometric, morphometric and stereologic features to be strong prognosticators in advanced ovarian cancer. However, in one Danish study a new stereologic parameter, the volume-weighted mean nuclear volume ( nuv), was not of prognostic significance. In that study, sampling was performed in the whole tumor section, contrary to that in other studies where measurements were performed in the worst differentiated area (the measurement area). The aim of the present investigation was, therefore, to confirm or reject the hypothesis that random estimates of nuclear {ovbar|nu}v over the whole tumor, rather than in the measurement area, are the cause for the lack of prognostic value in the Danish patients. Additionally, the mitotic activity index (MAI), volume percentage of epithelium (VPE), mean nuclear area (MNA) and standard deviation of the nuclear area (SDNA), which have proved to be of strong prognostic significance in advanced ovarian cancer, were assessed in the measurement area. The MAI, VPE, MNA, SDNA and nuclear {ovbar|nu}v were well reproducible, but prognostically not significant. This study thus excludes differences in microscopic sampling as an explanation for the contrasting findings in the Danish study and other ones. Possible remaining explanations are: (i) differences in sampling at the macroscopic level; (ii) fixation differences; (iii) patient selection bias; and (iv) geographic differences in the degree of malignancy of advanced ovarian cancer in Denmark and the Netherlands. As to the latter, in comparison with two Dutch studies the Danish ovarian cancers in this series had residual disease <2 cm (33% vs 50%) less often, were less often well differentiated (4% vs 19%), and less often had favorable morphometric characteristics (6% vs 15%). Further studies are required to analyze whether other Danish patient groups with advanced ovarian cancers differ from the Dutch.

Mean nuclear volume: a supplementary prognostic factor in endometrial cancer.

We evaluated the following nine parameters with respect to their prognostic value in females with endometrial cancer: four stereologic parameters [mean nuclear volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the immunohistochemical expression of cancer antigen (CA125) and the postsurgical stage (P-stage), the malignancy grade, the depth of myometrial tumor invasion and the age of the female. Tissue was obtained from 68 consecutive endometrial cancer patients with clinical FIGO stage I tumors who were registered in the Danish endometrial cancer study (DEMCA). The primary operation included total abdominal hysterectomy and bilateral salpingo-oophorectomy. All patients underwent radical operations. The tumors were classified postsurgically as P-stage I-III. All patients received the same postoperative radiation therapy. The surviving patients were observed for a median of 6.4 years (range 5.0-8.4 years). Cox regression analysis (automatic forward selection) showed the MNV to be the most significant prognostic parameter followed by the P-stage. Patients who had localized tumors or tumors with small nuclei had a better probability of surviving than did women with advanced tumors or tumors with large nuclei. No significant relationship between survival and the remaining seven parameters was demonstrated. This first investigation of the prognostic value of the MNV in females with endometrial cancer demonstrates that it may assist the distinction between those patients who can be cured by hysterectomy alone and those who need adjuvant therapy.

Combined prognostic importance of CA 125, histopathologic grade and DNA-index in advanced ovarian cancer.

PURPOSE: To analyse the possible prognostic importance of a combination of serum CA 125 levels, tumor cell DNA distribution and histopathologic grade in patients with epithelial ovarian cancer. METHOD: The study included 41 patients with ovarian cancer stages II-IV. CA 125 was measured before the start of chemotherapy and after every course. The DNA distribution was analysed by flow cytometry in biopsy specimens from the primary tumour. The histopathologic grading was performed according to WHO criteria. RESULTS: The CA 125 level was of major prognostic significance. All patients with an abnormal value (> 35 U/ml) after three courses died within 16 months. The DNA distribution did not add significant prognostic information, but the histopathologic grade was of significant prognostic importance as investigated by Cox analysis. CONCLUSION: CA 125 is an important prognostic marker in epithelial ovarian cancer. The value after three courses of chemotherapy is significant. The histopathologic grade adds further prognostic information.