Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience.

OBJECTIVE: In centres in which intra-operative frozen section (FS) analysis is not performed, 'apparent' early-stage ovarian cancer diagnosed after surgery on paraffin section may require further restaging laparotomy or adjuvant chemotherapy. Previous studies on FS analysis have reported high sensitivity, specificity and overall accuracy. The objective of this article is to present the largest published dataset on the accuracy of FS analysis over an 11-year period from a single institution. DESIGN: Diagnostic test accuracy. SETTING: Northern Gynaecological Oncology Centre and Department of Cellular Pathology, Gateshead, UK. POPULATION: 1439 intra-operative FS analyses performed between January 2000 and December 2010 for suspected ovarian cancer. METHODS: Prospectively collected data on FS analysis were compared with gold standard paraffin section. MAIN OUTCOME MEASURES: Sensitivity, specificity, likelihood ratios and post-test probability. RESULTS: The overall sensitivity and specificity of FS analysis were 91.2% and 98.6%, respectively. Positive and negative likelihood ratios were 64.7% and 0.09%, respectively. The pre-test probability of an ovarian tumour being borderline or malignant was 45.8%. When FS analysis was reported to be positive, the post-test probability increased to 98% (confidence interval, 97-99%). Conversely, when FS analysis was reported to be negative, the post-test probability decreased to 7% (confidence interval, 6-9%). The majority of false test results were either borderline tumours or of mucinous differentiation. CONCLUSIONS: Intra-operative FS analysis has excellent diagnostic test accuracy and assists gynaecological oncologists to perform the appropriate surgery in 95% of cases, thereby preventing the morbidity of surgical staging in benign cases and the morbidity of restaging procedures or chemotherapy in early-stage malignant tumours.

Evaluation of prognostic factors and treatment outcomes in uterine carcinosarcoma.

OBJECTIVE: The aims of this study were to determine the prognostic factors, survival outcomes and response to adjuvant therapy in women with uterine carcinosarcoma treated in a single institution. STUDY DESIGN: This is a cohort study of women diagnosed with carcinosarcoma and treated at the Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, UK. The medical records of all patients diagnosed with carcinosarcoma between January 1960 and July 2002 were reviewed. RESULTS: A total of 93 women were identified during this period. The median age was 67 years. The most common presentation was abnormal vaginal bleeding, occurring in 85%, followed by pelvic mass in 45%, and abdominal pain in 38%. At surgery there was extra-uterine spread in 54% of women. The median follow-up was 33 months (range 4-146 months). Adjuvant therapy was not associated with survival advantage. Recurrence was diagnosed in 55 patients (59%) and the overall 5-year survival for all stages was 33%. On multivariate analysis depth of myometrial invasion, stage and pelvic nodes metastasis were associated with poor survival. CONCLUSION: The poor outcome for these patients may reflect the aggressive nature of carcinosarcoma and that at the time of presentation more than 50% have extra-uterine disease, which was associated with significant poorer survival. Systemic adjuvant therapy has not been associated with significant improvement in the outcome. More studies are needed to better define the appropriate treatment for this rare cancer.

Primary endometrial squamous cell carcinoma.

Primary squamous cell carcinoma of the endometrium (PESCC) is rare and its pathogenesis is unclear. Identification of PESCC and its differentiation from endometrial involvement by squamous cell carcinoma is essential for correct patient management and is based on strict pathological criteria. We present a case of a 71-year-old patient satisfying the proposed diagnostic criteria for PESCC together with a review of the literature.

Vulvar intraepithelial neoplasia--the need for auditable measures of management.

OBJECTIVES: Surgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We propose auditable indicators of performance to benchmark management and outcomes. This may also enable definition of a surgical control arm for future novel therapy studies. STUDY DESIGN: Data from the Northern Gynaecological Oncology Centre (NGOC), UK on women with proven VIN diagnosed between 1989 and 2004 who attended the vulvar review clinic are presented and analysed alongside three large retrospective series by Jones et al. [Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 2005;106(6):1319-26], Herod et al. [Herod JJ, Shafi MI, Rollason TP, Jordan JA, Luesley DM. Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women. Br J Obstet Gynaecol 1996;103(5):446-52], McNally et al. [McNally OM, Mulvany NJ, Pagano R, Quinn MA, Rome RM. VIN 3: a clinicopathologic review. Int J Gynecol Cancer 2002;12(5):490-5] against proposed performance indicators to illustrate the deficiencies in current data presentation. RESULTS: Demographics and indicators such as degree of pathological expertise, definition of early stromal invasion and use of International Society for the study of Vulvovaginal Disease (ISSVD) classification were usually well documented. The description of lesions including size and focality were not always documented, nor the proportion examined by co-specialists. Numbers of primary treatments were well described but the indications for treatment, completeness of excision and VIN subclassification were not. Subsequent surgical treatments were inconsistently reported including the pathological details and intervals between treatments. Symptomatology was not well reported. Information on follow-up intervals and duration of follow-up with an indication of patient compliance was inadequate. Outcome data on recurrence of VIN and progression to carcinoma (early stromal invasion or frankly invasive carcinoma) were included in all series. CONCLUSIONS: Consensus on the ideal management of VIN or evaluation of new strategies will prove impossible without standardised data presentation. We propose a number of performance indicators that will facilitate evaluation of future studies or series against the current benchmark of surgical treatment for VIN.

Outcome of suicidal ideation and behavior in a young, help-seeking population over a 2-year period.

Suicidal behavior is associated with negative outcomes, including completed suicide. This study examined the prevalence of suicidal behavior in a sample of referrals to a youth psychiatric service and investigated the stability of suicidality over 2 years. Of the 140 people (mean age 17.8) who were referred to a youth psychiatric service, 82 who were accepted for treatment (RA group) and 58 who were not accepted (RNA group) were assessed; 57% reported considering suicide and 39% reported attempting suicide in the 12 months prior to referral. Participants who reported suicidal ideation were significantly more likely than nonsuicidal participants to have multiple Axis I diagnoses and lower levels of functioning. At the 2-year follow-up there was a significant reduction in suicidality in the RA group, but not in the RNA group. In conclusion, suicidality is prevalent among young people referred to psychiatric services. Even brief contact with services results in a reduction in suicidality over 2 years.

Risk adjusted surgical audit in gynaecological oncology: P-POSSUM does not predict outcome.

AIMS: To assess the Physiological and Operative Severity Score for the enumeration of mortality and morbidity (POSSUM) and its validity for use in gynaecological oncology surgery. METHODS: All patients undergoing gynaecological oncology surgery at the Northern Gynaecological Oncology Centre (NGOC) Gateshead, UK over a period of 12months (2002-2003) were assessed prospectively. Mortality and morbidity predictions using the Portsmouth modification of the POSSUM algorithm (P-POSSUM) were compared to the actual outcomes. Performance of the model was also evaluated using the Hosmer and Lemeshow Chi square statistic (testing the goodness of fit). RESULTS: During this period 468 patients were assessed. The P-POSSUM appeared to over predict mortality rates for our patients. It predicted a 7% mortality rate for our patients compared to an observed rate of 2% (35 predicted deaths in comparison to 10 observed deaths), a difference that was statistically significant (H&L chi(2)=542.9, d.f. 8, p<0.05). CONCLUSION: The P-POSSUM algorithm overestimates the risk of mortality for gynaecological oncology patients undergoing surgery. The P-POSSUM algorithm will require further adjustments prior to adoption for gynaecological cancer surgery as a risk adjusted surgical audit tool.

Unilateral groin and pelvic irradiation for unilaterally node-positive women with vulval carcinoma.

It is essential that any patient with resected vulval cancer and significant nodal disease receive optimal adjuvant treatment with radiation. Adequate radiotherapy for such patients with unilateral positive groin nodes has not been defined. Whether both groins and pelvic sidewalls should be irradiated or only the affected (node positive) side remains unclear. From our registry, we identified all patients with primary, previously untreated squamous cell carcinoma of the vulva undergoing bilateral inguinofemoral lymphadenectomy (superficial and deep nodes) and having unilaterally positive groin nodes treated with unilateral groin and pelvic radiotherapy (44 Gy in 22 fractions). Clinical and pathologic records were reviewed to identify the anatomical site and timing of recurrences in these patients and determine whether unilateral groin and pelvic irradiation was sufficient for disease control on the node-negative side. From 1983 to 2002, 20 patients with unilateral positive nodes treated with unilateral groin and pelvic irradiation were identified. Nineteen patients were classed as having FIGO stage III disease and one as FIGO stage IV due to involvement of the rectal mucosa. There were nine patients with disease recurrences in this group (45%). The disease-free interval ranged from 4 to 31 months (median time to recurrence, 9 months). All nine patients had local or regional failures, the most common site being the ipsilateral groin (six of nine patients). One patient was also found to have distant metastases. There were no recurrences noted in the contralateral (nonirradiated) groin or pelvic sidewall. Recurrence was generally fatal. Eight of the nine patients subsequently died of their disease. The ninth patient died of another cause. There was a high incidence of regional failure after unilateral groin and pelvic radiotherapy, but there were no recurrences on the nonirradiated, node-negative side. Although a small series, we speculate that there is no apparent disadvantage to administering unilateral adjuvant radiotherapy for unilaterally positive groin nodes and encourage further studies in order to more confidently determine whether the tendency observed in our center holds true.

A prospective randomised controlled trial of intermittent self-catheterisation vs. supra-pubic catheterisation for post-operative bladder care following radical hysterectomy.

OBJECTIVE: To determine the potential benefits of ISC (intermittent self-catheterisation) over SPC (supra-pubic catheterisation) in the post-operative bladder care of women following radical hysterectomy. METHODS: A prospective randomised controlled trial of women treated by radical hysterectomy for early stage cervical cancer. RESULTS.: 40 women were recruited to the study, 21 to ISC and 19 to SPC. All patients randomised to ISC were able to learn the technique of ISC satisfactorily following a period of pre-operative training. The day 3 and day 5 positive CSU (catheter specimen of urine) rate was significantly higher in the ISC group (42% and 63%) compared to the SPC group (6% and 18%), P = 0.05 and P = 0.004, respectively). Eight of 17 patients randomised to SPC (47%) documented having symptoms/problems arising from the SPC site of which 4 (23%) were shown to have a positive wound swab. There was no significant difference in length of period for bladder care between the two groups, P = 0.83. However, there were significant differences in patient acceptability (P = 0.009), freedom to lead a normal life (P = 0.000), disturbance at night (P = 0.006) and patient anxiety/embarrassment (P = 0.005) between the two groups. CONCLUSIONS: Patients are able to learn the technique of ISC without difficulty. Despite a greater urinary tract infection rate, the high incidence of SPC site problems can be avoided by use of ISC. The technique of ISC was seen to be more acceptable to patients allowing fewer disturbances at night, greater freedom to lead a normal life during the day and less anxiety/embarrassment compared to SPC.

Recurrent smear abnormalities where repeat loop treatment is not possible: is hysterectomy the answer?

OBJECTIVE: The objective of this study was to determine the outcome of women who underwent hysterectomy for recurrent cytological abnormalities where repeat loop treatment was considered not to be technically possible because of insufficient remaining cervical tissue. METHODS: Women undergoing a hysterectomy for the above indication at the Northern Gynaecological Cancer Centre over a period of 10 years (1992-2001) were identified from a prospectively collected database. Case notes were then reviewed and women undergoing hysterectomy for other indications were excluded. Relevant demographic and clinical data were then extracted. RESULTS: 33 patients meeting the above criteria were identified. The overall hysterectomy rate for this indication was 0.73%. 20 out of the 33 women had significant pathology on the hysterectomy specimen. 95% of these had high-grade disease with one having a Stage 1A1 squamous carcinoma. None of the patients required more radical treatment than a simple hysterectomy. There were no major complications following the hysterectomy. Positive endocervical margins on the previous loop specimen (P = 0.05) was an important correlating factor predicting the presence of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%) performed using the vaginal route had incomplete excision compared to one of three (33%) using the abdominal route. Hysterectomy was successful in treating 85.2% of the women; only 4 women subsequently developed vaginal intraepithelial neoplasia. CONCLUSION: Simple hysterectomy appears to be a suitable diagnostic and treatment option for women with recurrent high-grade cytological abnormalities where further loop treatment is technically not possible. Incomplete excision at the endocervical margin on the previous loop specimen was the main factor associated with the presence of cervical intraepithelial neoplasia at hysterectomy.

Laparoscopically assisted radical vaginal hysterectomy vs. radical abdominal hysterectomy for cervical cancer: a match controlled study.

OBJECTIVES: The technical feasibility of laparoscopically assisted radical vaginal hysterectomy has been well described, but its advantages over the open technique remain largely unproven. We reviewed and compared our experiences with both approaches. METHODS: All patients undergoing laparoscopically assisted radical vaginal hysterectomy (LARVH) between 1996 and 2003 were identified and matched for age, FIGO stage, histological subtype and nodal metastases using a control group of women who underwent radical abdominal hysterectomy (RAH) during the same time period. RESULTS: Fifty-seven women were listed for LARVH, resulting in five conversions. Fifty cases were matched successfully using the criteria above. The majority of cases were FIGO stage 1B1. Statistically significant differences (P < 0.05) were present when the following were compared for LARVH vs. RAH: duration of surgery (median 180 vs. 120 min), blood loss (median 350 vs. 875 ml), hospital stay (median 5 days vs. 8 days) and duration of continuous bladder catheterisation (median 3 days vs. 7 days). There were no statistically significant differences with regard to nodal yield, completeness of surgical margins or perioperative complication rate. Four major complications (8%, three cystotomies and one enterotomy) occurred in the LARVH group and three in the RAH group (6%, one pulmonary embolism, one ureteric injury and one major haemorrhage). Three women in LARVH group had seen a specialist regarding postoperative bladder dysfunction, versus 12 in the RAH group (P = 0.04). No patients in the LARVH group reported constipation requiring regular laxatives, versus six in the RAH group (P = 0.03). Median follow-up was 52 months for LARVH and 49 months for RAH. There was no significant difference between recurrence rates or overall survival (94% for LARVH vs. 96% for RAH). CONCLUSIONS: Despite the inherent limitations of LARVH and its associated learning curve, the procedure conveys many advantages over the open technique in terms of blood loss, transfusion requirement and hospital stay. In addition, the incidence of postoperative bladder and bowel dysfunction appears low-suggesting improved quality of life-without compromising survival.

Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

A new pictorial instrument for child and adolescent psychiatry: a pilot study.

A pictorial instrument was developed to assess psychopathology in children aged 6 to 16 years. Symptom pictures (n = 137) representing DSM-III-R criteria were organized into seven diagnostic subscales. Clarity of the pictures was assessed in 31 normal children. Fifty-one psychiatric inpatient children completed the instrument using a 6-point visual analogue scale. Sensitivity to change was assessed in 15 children. The subscales' internal consistencies (Cronbach's alpha) ranged from 0.54 to 0.86. A canonical discriminant analysis among four diagnostic groups achieved a Wilks' lambda of 0.67 (p = 0.02). This instrument may be a valuable adjunct to psychiatric interviews in children.

Repeated episodes of neuroleptic-related dyskinesias in autistic children.

The objective of this study was to examine data from 14 autistic children who developed repeated episodes of haloperidol-related dyskinesias in an ongoing, long-term maintenance clinical trial. The sample consisted of 9 males and 5 females, whose ages ranged from 3.4 to 6.7 years. These 14 children are a subsample of 29 children who developed dyskinesias at least once. In each subsequent episode, the dyskinesias tended to occur increasingly earlier and to last longer. Most of the dyskinesias developed upon haloperidol withdrawal. The topography of dyskinesias, the relationship of behavioral symptoms to severity of dyskinesias, and an attempt to characterize subgroups with dyskinesias are also presented.

Changes in serum uric acid concentrations during normal pregnancy.

Serial changes in serum uric acid concentrations have been studied in a group of healthy women before conception, at regular intervals throughout pregnancy and finally 12 weeks after delivery. Compared with pre-pregnancy values uric acid concentrations decreased significantly by 8 weeks gestation and this reduced level was maintained until about 24 weeks. Thereafter the concentrations increased such that by term they were greater than the pre-pregnancy values in the majority of patients and remained elevated until at least 12 weeks after delivery. If clinical management during the second half of pregnancy is to be based on increases in serum uric acid concentrations then such increases will have to be carefully interpreted against the background of rising concentrations which occur as part of the physiological response to normal pregnancy.

A microcomputer measuring system applied to real-time ultrasound video imaging.

The high-resolution graphics facility of a microcomputer has been synchronized with real-time ultrasound images on a television monitor, allowing quick and accurate measurements of linear distances, are lengths, perimeter lengths, and areas, whether regular or irregular in shape. No particular knowledge of computers is required, as the program gives step-by-step directions. However, the full facilities of a 48K microcomputer using BASIC language remain accessible, which is a considerable advantage over equivalent measuring systems currently available.