Spindle cell morphology is related to poor prognosis in vulvar squamous cell carcinoma.

BACKGROUND: Vulvar cancer is the fourth most common gynaecological malignancy, with an annual incidence of 2 out of 100,000 women. Although most cases of early stage vulvar cancer have a good prognosis, recurrence and rapid tumour progression can occur. We investigated the prevalence of spindle cell morphology in vulvar cancer and its association with survival. METHODS: This retrospective cohort study included 108 patients with primary vulvar squamous cell carcinoma who were treated at the Leiden University Medical Center during 2000-2009. Paraffin-embedded tissue was examined for the presence of spindle cell morphology. Survival and histology data were compared between cases with spindle and without spindle cell morphology. RESULTS: Twenty-two (20%) tumours showed spindle cells infiltrating the stromal tissue. All spindle cell tumours were human papillomavirus (HPV) negative. Spindle cell morphology was strongly associated with poor prognosis and with a high risk of lymph node involvement at the time of diagnosis (relative risk 2.26 (95% CI 1.47-3.47)). Five-year disease-specific survival was lower in patients with vs without spindle cell morphology (45.2% vs 79.7%, respectively; P=0.00057). CONCLUSION: Vulvar spindle cell morphology occurs frequently and seems to develop through the non-HPV pathway. It is associated with a worse prognosis than conventional vulvar squamous cell carcinoma.

Near-infrared fluorescence sentinel lymph node biopsy in vulvar cancer: a randomised comparison of lymphatic tracers.

This study aims to confirm the feasibility of near-infrared (NIR) fluorescence imaging for sentinel lymph node (SLN) biopsy in vulvar cancer and to compare the tracer indocyanine green (ICG) bound to human serum albumin (HSA) versus ICG alone. Women received 99mTc-nanocolloid and patent blue for SLN detection. Subsequently, women randomly received ICG:HSA or ICG alone. In 24 women, 35 SLNs were intraoperatively detected. All SLNs detected were radioactive and NIR fluorescent and 27 (77%) were blue. No significant difference was found between ICG:HSA and ICG alone. This trial confirms the feasibility of NIR fluorescence imaging for SLN mapping in vulvar cancer.

Single-visit approach of cervical cancer screening: see and treat in Indonesia.

BACKGROUND: We performed a cross-sectional study in Indonesia to evaluate the performance of a single-visit approach of cervical cancer screening, using visual inspection with acetic acid (VIA), histology and cryotherapy in low-resource settings. METHODS: Women having limited access to health-care facilities were screened by trained doctors using VIA. If the test was positive, biopsies were taken and when eligible, women were directly treated with cryotherapy. Follow-up was performed with VIA and cytology after 6 months. When cervical cancer was suspected or diagnosed, women were referred. The positivity rate, positive predictive value (PPV) and approximate specificity of the VIA test were calculated. The detection rate for cervical lesions was given. RESULTS: Screening results were completed in 22 040 women, of whom 92.7% had never been screened. Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The approximate specificity was 98.1%, and the detection rate for CIN I or greater was 2.6%. CONCLUSION: The single-visit approach cervical cancer screening performed well, showing See and Treat is a promising way to reduce cervical cancer in Indonesia.

Parental acceptance of human papillomavirus (HPV) vaccination in Indonesia: a cross-sectional study.

BACKGROUND: Cervical cancer ranks the second most frequent cancer in Indonesian women. In Indonesia, human papillomavirus (HPV) vaccine acceptance has not been studied before. OBJECTIVE: To determine parental HPV vaccine acceptance in Indonesia, and factors that influence their decision. Factors include sociodemographic factors, knowledge of HPV, HPV vaccination and cervical cancer, health beliefs about cervical cancer, and attitudes towards vaccination in general. METHODS: 746 parents, with at least 1 daughter aged 0-14, were interviewed using questionnaires based on published and adjusted interviews. Interviews were done in sub district public health centers, general governmental hospitals, and via house-visits, in 5 Indonesian provinces. RESULTS: Parental HPV vaccine acceptance was 96.1%. Logistic regression revealed that age, beliefs regarding cervical cancer, and attitudes towards vaccination in general were significantly associated with HPV vaccine acceptance. Of the participants, 66.0%, 16.6%, and 15.8% had heard about cervical cancer, HPV, and HPV vaccination respectively. The mean total knowledge score was 1.91(Standard Deviation 2.31) on a 0-8 scale. Health beliefs about cervical cancer and attitudes towards vaccination in general were positive. Participants named the high cost of the vaccine, fear for side-effects, and chosen vaccination locations as possible barriers towards HPV vaccine implementation. DISCUSSION: Parental HPV vaccine acceptance is high, but knowledge about HPV and cervical cancer is low. During HPV vaccination programs, focus should not only be on providing information, but also on existing beliefs and attitudes towards cervical cancer and vaccination in general. If HPV vaccination programs were to be implemented in Indonesia, the indicated barriers should be taken into account.

Prevalence of human papillomavirus in Indonesia: a population-based study in three regions.

Cervical cancer is the most common cancer among women in the Indonesian population, yet little is known about the prevalence of human papillomavirus (HPV). We investigated age-specific prevalence of HPV types and possible risk factors of HPV positivity in a population-based sample of 2686 women, aged 15-70 years, in Jakarta, Tasikmalaya, and Bali, Indonesia. The overall HPV prevalence was 11.4%, age-standardized to the world standard population 11.6%. The most prevalent types found were HPV 52, HPV 16, HPV 18, and HPV 39, respectively, 23.2, 18.0, 16.1, and 11.8% of the high-risk HPV types. In 20.7% of infections, multiple types were involved. Different age-specific prevalence patterns were seen: overall high in Jakarta, and in Tasikmalaya, and declining with age in Bali. The number of marriages was most associated with HPV positivity (OR 1.81 95% CI 1.31-2.51)). Remarkably, in Indonesia HPV 16 and HPV 18 are equally common in the general population, as they are in cervical cancer. HPV 52 was the most prevalent type in the general population, suggesting that this type should be included when prophylactic HPV vaccination is introduced in Indonesia.

Myomatous erythrocytosis syndrome: further proof for the pathogenic role of erythropoietin.

BACKGROUND: Myomatous erythrocytosis syndrome is defined by the combination of erythrocytosis, myomatous uterus and persistent restoration of normal haematological values after hysterectomy. A pathogenic role of erythropoietin is suggested by clinical and experimental data. CASE REPORT: A postmenopausal patient is described with the classical clinical signs of the myomatous erythrocytosis syndrome. During hysterectomy we demonstrated a large gradient between the erythropoietin levels in the uterine vein and artery, providing direct evidence for in vivo erythropoietin production by the myomatous uterus. CONCLUSION: While erythropoietin and its receptor are consecutively expressed in normal and myomatous uterine tissue, it is amazing that erythrocytosis occurs so rarely in such a frequent disorder as uterine myomatous. We strongly advocate cytogenetic examination of the myomatous tissue of subsequent patients with this entity.

The difficult patient in gastroenterology: chronic pelvic pain, adhesions, and sub occlusive episodes.

Chronic pelvic pain (CPP) with or without adhesions and symptoms of intestinal occlusion is a complex but relatively common complaint. The etiology and pathophysiology of CPP and adhesions are unclear, as is their possible relation. However, it is evident that continuous abdominal pain leads to evident suffering and disability. Unfortunately, there is little proof or evidence of success for many of the currently used diagnostic and therapeutic interventions. Laparoscopy is neither the ultimate evaluation nor the panacea for CPP or intra abdominal adhesions. An integral approach to CPP has shown beneficial results. In this multidisciplinary approach dealing with the pain is far more important than finding an organic cause and cure for the pain. Equal and simultaneous attention is paid to psychosocial, sexual and somatic aspects. The treatment of adhesions depends on the extent of symptoms and complaints. Because of the questionable relation between adhesions and pain, and the probability of reformation and de novo adhesion formation after surgery, adhesiolysis should be avoided. Even for patients with signs and symptoms of small bowel obstruction a conservative treatment is often justified. These patients require careful evaluation and management. Frequent reassessment is important to rule out impending strangulation, complete obstruction or perforation. Water soluble contrast can be useful to justify prolongation of conservative treatment and by that postpone unnecessary surgery. Most adhesive small bowel obstructions resolve following conservative treatment. The unsolved questions about etiology, diagnosis, treatment and prevention, and the great individual and community burden of CPP and adhesions clearly show that further research is needed.

Decreased prevalence of dysplasia in high-risk population immigrants in a low-risk area for cervical cancer.

Incidence rates of cervical cancer and its precursors vary considerably, with the highest rates found in developing countries. Differences are influenced by endogenous and exogenous factors. Comparing cytologic abnormality incidence rates from a high-risk population in the original high-risk area, with those of women from this high-risk population who have immigrated to a low-risk area could give insight in the significance of endogenous versus environmental factors. Smears collected from Surinamese women attending the Surinamese screening program and smears collected from immigrant Surinamese women attending the Dutch screening program were cytologically analyzed using the Dutch microscopical coding system KOPAC. Statistical analysis was performed by using logistic regression to calculate (age-adjusted) odds ratios (ORs). The age-adjusted ORs of having dysplasia were higher for Surinamese women living in Suriname versus Surinamese immigrant women and increased with increasing P-scores: 0.77 (0.31-1.91) for borderline changes, 1.62 (0.58-4.57) for mild dysplasia, and 3.20 (1.55-6.60) for moderate to severe dysplasia/neoplasia. We conclude that fewer cases with dysplasia are present in a high-risk population that has immigrated to a low-risk area for cervical cancer than in the high-risk population continuously living in a high-risk area. This finding emphasizes the importance of environmental factors.

The number of pelvic lymph nodes in the quality control and prognosis of radical hysterectomy for the treatment of cervical cancer.

AIMS: To determine if the number of removed lymph nodes in radical hysterectomy with lymphadenectomy (RHL) influences survival of patients with early stage cervical cancer and to analyze the relation of different factors like patient age, tumour size and infiltration depth with the number of nodes examined in node-negative early stage cervical cancer patients. METHODS: Of consecutive patients, who underwent RHL between January 1984 and April 2005, 331 had negative nodes (group A) without adjuvant therapy and 136 had positive nodes (group B). The Kaplan-Meier method and Cox regression model were used to detect statistical significance. Factors associated with excision of nodes were confirmed with linear regression models. RESULTS: The median number of removed nodes was 19 and 18 for group A and group B, respectively. There was no significant relationship between the number of removed nodes and the cancer specific survival (CSS) or disease free survival (DSF) for patients of group A (p=0.625 and p=0.877, respectively). The number of removed nodes in group B was not significantly associated with the CSS (p=0.084) but it was for the DSF (p=0.014). Factors like patient age, tumour size and infiltration depth were not associated with the number of nodes. CONCLUSIONS: No relation was found between the number of negative nodes examined after RHL for the treatment of early stage cervical cancer and CSS or DFS. However, a higher amount of removed lymph nodes leaded to a better DFS for patients with positive nodes. It is suggested that patients with positive nodes benefit from a complete pelvic lymphadenectomy and a sufficient yield of removed nodes.

Human papillomavirus type 18 and other risk factors for cervical cancer in Jakarta, Indonesia.

Infection with human papillomavirus (HPV) has now been established as a necessary cause of cervical cancer. Indonesia is a country with a high cervical cancer incidence and with the world's highest prevalence of HPV 18 in cervical cancer. No information exists about the prevalence of HPV 18 or other HPV types in the Indonesian population. We conducted a hospital-based case-control study in Jakarta, Indonesia. A total of 74 cervical carcinoma cases and 209 control women, recruited from the gynecological outpatient clinic of the same hospital, were included. All women were HPV typed by the line probe assay, and interviews were obtained regarding possible risk factors for cervical cancer. HPV was detected in 95.9% of the cases and in 25.4% of the controls. In the control group, 13.4% was infected with a high-risk HPV type. HPV 16 was detected in 35% of the case group and in 1.9% of the control group and HPV 18 was identified in 28% of the case group and in 2.4% of the control group, suggesting that the oncogenic potentials of HPV 16 and HPV 18 in Indonesia are similar. In addition to HPV infection, young age at first intercourse, having a history of more than one sexual partner, and high parity were significant risk factors for cervical cancer. Within the control group, we did not identify determinants of HPV infection. We hypothesize that the high prevalence of HPV 18 in cervical cancer in Indonesia is caused by the high prevalence of HPV 18 in the Indonesian population.

Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study.

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (> or =40 mm), invasion (> or =15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR- (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.

[Three patients with differing manifestations of uterine sarcoma]. / Drie patiënten met verschillende manifestaties van uterussarcoom.

A 70-year-old woman with postmenopausal blood loss proved to have a stage-IV high-grade endometrial stromal sarcoma; 9 months after resection the patient was well. In a 53-year-old woman with symptoms of neurological deficit and weight loss accompanying an increase in abdominal girth and postmenopausal vaginal blood loss a high-grade leiomyosarcoma at stage IV was diagnosed. Despite treatment the neurological symptoms worsened and the patient died within 2 months of diagnosis. Another woman, aged 53, with abdominal pain but no blood loss proved to have a high-grade leiomyosarcoma at stage 1. Nine months after resection and radiotherapy the patient was well. The incidence of carcinomas of the uterus in The Netherlands is on average 113 women per year. They manifest themselves in different ways which can sometimes be misleading. The most common symptom is vaginal bleeding, in combination with abdominal pain or a pelvic mass. The only curative therapy is surgical excision. The 5-year survival rate is 50% in tumours confined to the uterus as opposed to 20% in those that spread further.

Psychosocial factors and the course of cervical intra-epithelial neoplasia: a prospective study.

OBJECTIVE: To investigate the influence of psychosocial factors on the course of cervical intra-epithelial neoplasia (CIN). METHODS: A group of 93 patients with CIN 1 or 2 was followed for 2.25 years by half-yearly colposcopy and cytology. Negatively-rated life events, social support, and coping style were studied in relation to distress during follow-up and in relation to time till progression and regression of CIN. Human papillomavirus (HPV) infection was controlled for as well as sick role bias caused by suspicion of having cervical cancer and distress due to the abnormal cervical smear. RESULTS: During follow-up, progression was found in 20 patients (22%), stable disease in 22 patients (24%), and regression in 51 patients (55%). Negatively-rated life events and lack of social support predicted distress longitudinally. No association was found between progression or regression of CIN and negatively-rated life events, lack of social support, coping style, and distress. CONCLUSION: We found no evidence that psychosocial factors influence the course of CIN.

Prognostic difference of surgical treatment of exophytic versus barrel-shaped bulky cervical cancer.

OBJECTIVE: The aim of the study was to evaluate the prognostic significance of tumor geography, defined as exophytic or barrel-shaped growth, in bulky (>4 cm) cervical cancer. METHODS: Four hundred women with cervical cancer, treated by primary radical hysterectomy between January 1984 and November 2000, were followed in a prospective cohort study. Clinical and pathology data were stored in a databank and the clinical protocol was unchanged during the study except for the amendment of additional indications of postoperative radiation in 1997. The assessment of tumor geography was based on pelvic examination at the time of tumor staging or radical hysterectomy or from the pathology report. Survival probabilities were calculated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: The mean age of the patients was 45 years and the mean follow-up duration 48 months. Tumors were of squamous cell type in 291 patients (73%). Lymph node metastases were present in 91 patients (24%) and postoperative radiation was given in 179 patients (45%). In 291 patients, tumor diameter was <4 cm; in 58 patients, the tumor was defined as bulky exophytic and in 51 patients as bulky barrel shaped. There were no differences among these three groups in terms of operating time, blood loss during surgery or complications at 3 or 6 months postoperatively. Bulky exophytic tumors had an identical overall survival as compared to small-diameter (<4 cm) tumors. The overall survival (OS) of bulky barrel-shaped tumors was significantly worse (P < 10(-4)). The same was found for disease-free survival (DFS). CONCLUSION: Bulky exophytic cervical cancer has an identical surgical morbidity, overall and disease-free survival as compared to nonbulky (<4 cm) cervical cancer. In view of these identical characteristics, primary surgical treatment should be considered for patients with bulky exophytic cervical cancer.

Long-term outcomes and quality of life after laparoscopic adhesiolysis for chronic abdominal pain.

STUDY OBJECTIVE: To evaluate clinical outcome in terms of pain and quality of life after laparoscopic adhesiolysis. DESIGN: Prospective observational study (Canadian Task Force II-3). SETTING: University-affiliated medical center. PATIENTS: Twenty-three patients (22 women). INTERVENTION: Laparoscopic adhesiolysis for chronic abdominal pain. MEASUREMENTS AND MAIN RESULTS: Pain was assessed by validated McGill score. Patients with an intraindividual decrease in pain score of 5 points or more were considered successes. Quality of life was assessed by the SF-36 and gastrointestinal quality of life index. Patients were evaluated before and at intervals until 2 years after adhesiolysis. The mean pain score before adhesiolysis was 30.5 (range: 17-40). At 2 years of follow-up, 10 (45%) of 22 patients (95% CI 0.244-0.678) were considered successes. They reported significant improvement in quality of life on scales physical, role physical, and social function, and fewer gastrointestinal symptoms. Twelve women (55%) had a complete relapse, and most were not motivated to visit the pain clinic after 6 months. CONCLUSION: Laparoscopic adhesiolysis for chronic abdominal pain was successful in only 45% of patients.

Postoperative complications after vulvectomy and inguinofemoral lymphadenectomy using separate groin incisions.

The focus of this study was to document postoperative complications after vulvectomy and inguinofemoral lymphadenectomy using separate incisions. Data from 172 consecutive patients with newly diagnosed carcinoma of the vulva were studied. One hundred and one patients primarily treated with modified radical vulvectomy and complete inguinofemoral lymphadenectomy using separate groin incisions (n = 187) were included in this study. One or more complications were documented in 77 of the 101 (76%) patients. Complications after groin dissection were observed in 66% of the patients. The main complications were wound breakdown (17%) and/or infection (39%) of the groin, lymphocyst formation (40%), and lymphedema (28%). In 98 of 187 (52%) groin dissections, one or more complications were documented. The presence of lymph node metastases, postoperative radiation, age older than 65 years, and removal of the vena saphena magna were not significant risk factors for the occurrence of complications. The occurrence of early complications after groin dissection was significantly related to the late-complication lymphedema (P = 0.002). Our results confirm relatively high rates of wound breakdown, infection, lymphocyst formation, and lymphedema even with separate groin incisions. The occurrence of early complications was related to lymphedema. No other risk factors could be identified.

Visualising scanning patterns of pathologists in the grading of cervical intraepithelial neoplasia.

AIM: To investigate how effectively eye tracking devices can visualise the scanning patterns of pathologists, for application in studies on diagnostic decision making. METHODS: EyeCatcher, an eye tracking device, was used to visualise and compare the scanning patterns of five pathologists while they graded two projections of cervical intraepithelial neoplasia. Density cloud images were created from the scanning patterns. A questionnaire and interview provided information on the following steps in the diagnostic process. RESULTS: EyeCatcher successfully registered the scanning patterns of the pathologists. A "scanning style" and a "selective style" of visual search were distinguished. The scanning patterns, in addition to the interpretation and combination of the information ultimately leading to a diagnosis, varied between the various observers, resulting in a broad range of final diagnoses. CONCLUSIONS: Eye gaze tracking devices provide an excellent basis for further discussion on the interpretation and grading criteria of lesions. As such, they may play an important role in studies on diagnostic decision making in pathology and in the development of training and quality control programmes for pathologists.

Human papillomavirus in malignant cervical lesions in Surinam, a high-risk country, compared to the Netherlands, a low-risk country.

In various countries epidemiologic studies show an association between human papillomavirus (HPV) and cancer of the uterine cervix. We determined the presence of HPV and the distribution of the different HPV genotypes in cervical carcinomas from Surinam, a high-incidence country. The results were compared to the Netherlands where the incidence is five times lower. One hundred thirty cervical carcinomas from patients in Surinam were randomly selected and compared to an unselected group of 128 cervical carcinomas from caucasoid Dutch patients. Presence of HPV and distribution of HPV genotypes was determined in DNA extracted from paraffin-embedded specimens by polymerase chain reaction and sequence analysis. HPV DNA was detected in 82% of the Surinamese cervical cancer patients and in 87% of the Dutch patients. Thirteen different HPV genotypes were detected in the Surinamese group, and nine different HPV genotypes were detected in the Dutch group. Among the HPV-positive samples, HPV 16 was present in 68% in the Netherlands compared to only 49% in Surinam, where less common genotypes such as HPV 35, 45, and 58 were more prevalent. The results show a strong association between HPV and cervical cancer in both groups. However, the observed significant variation in distribution of the genotypes in the two populations with a large difference in cervical carcinoma incidence is important to the general understanding of the etiology of cervical cancer and to the development of HPV vaccination strategies.

Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion.

The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min (P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml (P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.