Tumour-free distance from serosa is a better prognostic indicator than depth of invasion and percentage myometrial invasion in endometrioid endometrial cancer.

OBJECTIVE: To evaluate the prognostic performance of tumour-free distance (TFD) compared with depth of invasion (DOI) and percentage of myometrial invasion (MI). DESIGN: Retrospective cohort study. SETTING: Regional gynaecological oncology centre. POPULATION: All women identified with stage I-III endometrioid endometrial carcinoma from January 2000 to December 2007, who had surgery at the Northern Gynaecological Oncology Centre (NGOC). METHODS: Surgicopathological, follow-up and survival data were collected. Univariate and multivariate analyses were performed comparing TFD, DOI and MI with known prognostic factors. The prognostic accuracy of TFD was assessed by receiver operating characteristic (ROC) curve analyses, and an optimum cut-off was proposed. MAIN OUTCOME MEASURES: Death from disease, recurrence and pelvic lymph node involvement. RESULTS: A total of 288 women were identified. The median follow-up time was 67 months, with 40 recurrences and 32 disease-related deaths. When TFD, DOI and MI were separately examined in multivariate analyses with other covariates, TFD was an independent predictor of death from disease (HR 1.22; 95% CI 1.00-1.48; P = 0.05). In multivariate analyses including all three measures together (TFD, DOI and MI), TFD was an independent predictor of death from disease (HR 1.49; 95% CI 1.03-2.16; P = 0.04) and recurrence (HR 1.39; 95% CI 1.01-1.91; P = 0.05). TFD was also an independent predictor of lymph node involvement when examined separately (OR 0.74; 95% CI 0.56-0.96; P = 0.03), and together with DOI and MI (OR 0.67; 95% CI 0.49-0.92; P = 0.01), in women who had pelvic lymphadenectomy (n = 86). A TFD cut-off of 1.75 mm showed good prognostic performance. CONCLUSIONS: The TFD measure may be a more accurate method of representing myometrial invasion in the staging for endometrial cancer.

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.

Conservative surgical management of small-volume stage IB1 cervical cancer.

OBJECTIVE: To determine outcomes of women with small-volume stage IB1 disease managed by conservative surgical treatment. DESIGN: A retrospective review. SETTING: The Northern Gynaecological Oncology Center, Queen Elizabeth Hospital, Gateshead, UK. POPULATION: Women with stage IB1 cervical cancer who were managed by conservative surgery over a 6-year period between 1 January 2000 and 31 December 2005. MAIN OUTCOME MEASURES: Pelvic lymph node metastases, recurrence rates and outcome survival. RESULTS: A total of 17 women with conservatively managed stage IB1 cervical cancer were identified. Their ages were 25-67 years, median 37 years, 4 women were nulliparous. All women presented with an abnormal screening smear showing at least severe dyskaryosis. Estimated tumour volumes ranged from 16 to 640 mm3, median 72 mm3. Four women showed multifocal invasion. All four nulliparous women and one parous woman underwent fertility-sparing treatment, i.e. loop cone +/- laparoscopic pelvic node dissection. The other 12 women underwent laparoscopic assisted vaginal hysterectomy/total abdominal hysterectomy +/- pelvic lymph node dissection. There were no cases of residual disease in any of the definitive treatment specimens. There were no cases of metastatic spread to pelvic lymph nodes. To date, no women have developed recurrent disease, and all women are alive and well (median follow up, 29 months). CONCLUSIONS: The conservative surgical management of small-volume stage IB1 cases in this series showed an excellent outcome with no cases showing pelvic lymph node involvement and no cases developing recurrent disease. A more formal assessment of tumour volume with a more active approach to determining the third dimension will allow more women the option of conservative treatment, thereby minimising the adverse effects of radical surgery.

Echo contrast-enhanced diagnosis of atrial septal defect.

Pulsed wave, continuous wave, and color flow Doppler imaging as well as intravenously administered agitated saline solution can detect intracardiac shunts during transthoracic echocardiography. Ultrasonographic contrast agents have greatly improved the visualization of left heart chambers and can enhance signals from blood flow within chambers and across valves, increasing the sensitivity of Doppler techniques. We describe a patient in whom the use of echo contrast media during transthoracic echocardiography allowed the detection of a previously unseen atrial septal defect. Combining such modalities may help to increase the sensitivity of transthoracic echocardiography and may eliminate the need for transesophageal echocardiography in selected patients.

Comparison of examination of the entire uterine cervix with routine cervical sampling in hysterectomy specimens from women with endometrial cancer.

BACKGROUND: Cervical involvement by endometrial cancer alters the FIGO stage and determines clinical management, but there are no accepted guidelines for cervical sampling of these cases. AIM: To assess whether sampling more than two "routine" blocks of the cervix (anterior and posterior) alters the pathological staging of hysterectomy specimens for endometrial cancer. METHODS: Histological involvement of the cervix was prospectively compared in hysterectomies performed for proven endometrial cancer (n = 61). Specimens had two "routine" blocks taken from anterior and posterior cervix; all of the remaining cervix was also processed for histological assessment. RESULTS: 61 cases of endometrial cancer had the entire uterine cervix processed. There were 54 cases of endometrioid adenocarcinoma and 7 special types. Twelve cases had cervical involvement (stage 2A or 2B), and seven cases were stage 3A or above, of which three also had cervical involvement. In none of the 61 cases did the additional cervical blocks (n = 544) taken alter the staging made on the "routine" blocks. CONCLUSION: Sampling of two blocks from the cervix appears sufficient for histological staging of endometrial cancer in hysterectomy specimens.

Epidermoid cyst of the pineal region.

An epidermoid cyst in the pineal region is reported to underscore the feasibility of successful surgical excision of such lesions and the need to review the management of posterior third ventricular lesions. An interesting, but unexplained, feature in this patient was renal glycosuria which cleared after excision of the tumour.

Quantitative triple fluorochrome labeling study of lathyritic-rat mandible.

The present study was conducted to quantify the amount and distribution of new bone formation by triple fluorochrome labeling sequence in different areas of the mandibular bone of the control and lathyritic animals. The data was subjected to statistical analysis. Osteolathyrism significantly impaired the turnover and remodeling rates of periosteal and endosteal bone. The fluorescent bands were distinct and wider in the control than in the experimental animals. Mean ratio values for labeled bone showed considerable variations in different regions and age groups. The amount of labeled bone in the condyle and molar region of control animals was 1.49 to 1.77 and 1.41 to 1.78 times higher than in the lathyritic animals.

Very brief transient ischemic attack.

TIA is an important risk factor for ischemic stroke. Early diagnosis and management can result in a significant reduction in the risk of subsequent stroke. We report the case of a 54-year-old man who developed a 5-second episode of leg weakness and in whom a tight stenosis of the appropriate carotid artery was found. TIAs can sometimes be brief and have an atypical presentation, requiring a high level of suspicion for early diagnosis.

Evidence for the induction of casein kinase II in bovine lymphocytes transformed by the intracellular protozoan parasite Theileria parva.

Theileria parva is an obligate, intracellular, parasitic protozoan that causes East Coast fever, an acute leukemia-like disease of cattle. T. parva and the related parasite, Theileria annulata, are unique among protozoa in that their intralymphocytic stages induce transformation of bovid lymphocytes. Comparison of in vitro protein kinase activities between uninfected IL-2-dependent T lymphoblasts and T. parva-infected lymphocytes revealed a 4.7- to 12-fold increase in total phosphorylation and the induction of a group of Theileria infection-specific phosphoproteins. The enzyme that phosphorylates these substrates is a serine/threonine kinase with substrate and effector specificities of casein kinase (CK) II. Northern blot analyses revealed a 3.9- to 6.0-fold increase in CKII alpha mRNA in the infected cells relative to the controls. Furthermore, a marked increase of CKII antigen was observed on Western blots of materials prepared from the infected cell lines. The antibovine CKII antibody used in these studies immunoprecipitated a protein kinase that phosphorylated casein in a reaction that was inhibited by low (nM) quantities of heparin. Our data show marked increases of bovine CKII at the transcriptional, translational and functional levels in T. parva-infected lymphocytes, relative to quiescent cells or IL-2-dependent parental lymphoblasts. Bovine CKII thus appears to be constitutively activated in these cells and we propose that this kinase may be an important element in the signal-transducing pathways activated by Theileria in bovid lymphocytes and perhaps in some leukemic cells.

Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach.

AIMS: Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs. METHODS AND RESULTS: Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl-2 and cyclin D1. Complete follow-up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c-kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease-specific survival: size > or =50 mm; necrosis, no intratumoral lymphocytes; mitotic count > or =5/50 high power fields; Ki67 labelling index > or =5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators. CONCLUSIONS: Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl-2 and cyclin D1 immunohistochemistry provide no additional prognostication.