Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study.

Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; non-invasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone.

Recent developments in vascular ultrasound technology.

This article describes four technologies relevant to vascular ultrasound which are available commercially in 2015, and traces their origin back through the research literature. The technologies are 3D ultrasound and its use in plaque volume estimation (first described in 1994), colour vector Doppler for flow visualisation (1994), wall motion for estimation of arterial stiffness (1968), and shear wave elastography imaging of the arterial wall (2010). Overall these technologies have contributed to the understanding of vascular disease but have had little impact on clinical practice. The basic toolkit for vascular ultrasound has for the last 25 years been real-time B-mode, colour flow and spectral Doppler. What has changed over this time is improvement in image quality. Looking ahead it is noted that 2D array transducers and high frame rate imaging continue to spread through the commercial vascular ultrasound sector and both have the potential to impact on clinical practice.

A Protocol for Improved Measurement of Arterial Flow Rate in Preclinical Ultrasound.

PURPOSE: To describe a protocol for the measurement of blood flow rate in small animals and to compare flow rate measurements against measurements made using a transit time flowmeter. MATERIALS AND METHODS: Measurements were made in rat and mice using a Visualsonics Vevo 770 scanner. The flow rate in carotid and femoral arteries was calculated from the time-average maximum velocity and vessel diameter. A correction factor was applied to correct for the overestimation of velocity arising from geometric spectral broadening. Invasive flow rate measurements were made using a Transonics system. RESULTS: Measurements were achieved in rat carotid and femoral arteries and in mouse carotid arteries. Image quality in the mouse femoral artery was too poor to obtain diameter measurements. The applied correction factor in practice was 0.71-0.77. The diameter varied by 6-18% during the cardiac cycle. There was no overall difference in the flow rate measured using ultrasound and using transit-time flowmeters. The flow rates were comparable with those previously reported in the literature. There was wide variation in flow rates in the same artery in individual animals. Transit-time measurements were associated with changes of a factor of 10 during the typical 40 min measurement period, associated with probe movement, vessel spasm, vessel kinking and other effects. CONCLUSION: A protocol for the measurement of flow rate in arteries in small animals has been described and successfully used in rat carotid and femoral arteries and in mouse carotid arteries. The availability of a noninvasive procedure for flow rate measurement avoids the problems with changes in flow associated with an invasive procedure.

Phase coupling in the cardiorespiratory interaction.

Markovian analysis is applied to derive nonlinear stochastic equations for the reconstruction of heart rate and respiration rate variability data. A model of their 'phase' interactions is obtained for the first time, thereby gaining new insights into the strength and direction of the cardiorespiratory phase coupling. The reconstructed model can reproduce synchronisation phenomena between the cardiac and the respiratory systems, including switches in synchronisation ratio. The technique is equally applicable to the extraction of the multi-dimensional couplings between many interacting subsystems.

The effect of low-frequency oscillations on cardio-respiratory synchronization: Observations during rest and exercise.

We show that the transitions which occur between close orders of synchronization in the cardio-respiratory system are mainly due to modulation of the cardiac and respiratory processes by low-frequency components. The experimental evidence is derived from recordings on healthy subjects at rest and during exercise. Exercise acts as a perturbation of the system that alters the mean cardiac and respiratory frequencies and changes the amount of their modulation by low-frequency oscillations. The conclusion is supported by numerical evidence based on a model of phase-coupled oscillators, with white noise and low-frequency noise. Both the experimental and numerical approaches confirm that low-frequency oscillations play a significant role in the transitional behavior between close orders of synchronization.

Primitive neuroectodermal tumour of the tongue.

Peripheral primitive neuroectodermal tumours, which belong to the Ewing sarcoma tumour family, are extremely rare. These tumours are highly aggressive and are known to have a poor prognosis. Immunostaining with at least two neural markers and evidence of an abnormal t(11;22)(q24;q12) translocation are hallmark features in this diagnosis. We present the first reported case of peripheral primitive neuroectodermal tumour to occur in the tongue.

Chronic exposure to schistosome eggs reduces serum cholesterol but has no effect on atherosclerotic lesion development.

Previous studies have shown that people infected with schistosomiasis have lower levels of serum cholesterol than uninfected controls. To better understand the impact of this parasitic infection on serum cholesterol levels and on atherosclerotic lesion development induced by hypercholesterolemia, apolipoprotein E (ApoE)-deficient mice were chronically exposed to the eggs of Schistosoma mansoni over a period of 16 weeks. Total serum cholesterol and low-density lipoprotein (LDL) were reduced in egg-exposed ApoE-deficient mice fed a diet high in cholesterol compared to unexposed controls. However, exposure to eggs had no effect on atherosclerotic lesion size or progression in ApoE-deficient mice. Macrophages isolated from egg-exposed mice had an enhanced ability to take up LDL but not acetylated LDL (acLDL). This study suggests that schistosome eggs alone may alter serum lipid profiles through enhancing LDL uptake by macrophages, but these changes do not ultimately affect atherosclerotic lesion development.

Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy.

BACKGROUND: Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. CASE: We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. CONCLUSIONS: This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.

The presence of atypical small acinar proliferation in prostate needle biopsy is predictive of carcinoma on subsequent biopsy.

OBJECTIVE: To determine the clinical significance of nondiagnostic small acini showing cellular atypia (atypical small acinar proliferation) in prostatic biopsies of patients with clinical findings suggestive of malignancy. PATIENTS AND METHODS: Of 331 patients who underwent thin-core biopsy of the prostate over a 30-month period, 21 (6.3%) had atypical histological features, and of these 17 underwent repeat biopsy. In addition, a further 20 patients with normal histology underwent repeat biopsy for persistent abnormal clinical findings. The incidence and Gleason score of carcinomas subsequently diagnosed in the two groups were compared. The predictive significance of patient age, prostate specific antigen (PSA) level and digital rectal examination (DRE) findings were compared between both patient groups, those in each group subsequently found to have carcinoma, and between patients with malignant or normal repeat biopsies who had either atypical or normal initial biopsies. RESULTS: Nine patients with atypical histology and four with normal histology on initial biopsy were found to have carcinoma on subsequent biopsy (P = 0.036). The site of carcinoma diagnosed in the repeat biopsy frequently differed from that of the initial atypical biopsy. The Gleason primary pattern was not significantly different between the groups. Neither patient age, PSA level nor DRE findings differed between patients with initial normal or atypical biopsy, or in these groups for those in whom carcinoma was subsequently diagnosed. These clinical features did not distinguish between those with carcinoma or normal findings on repeat biopsy who had an initial atypical biopsy, while only PSA level varied significantly in patients with normal or malignant repeat biopsy in the group with an initial normal biopsy. CONCLUSION: The presence of atypia on initial biopsy is a strong predictor of malignancy in subsequent biopsy specimens.

Fine needle aspiration cytodiagnosis of leiomyosarcoma of the breast. A case report.

BACKGROUND: Leiomyosarcoma of the breast is a rare tumor. Here we present a case in an elderly female in which the diagnosis was suggested from an aspirate sample. CASE: An 80-year-old female presented with an irregular, firm mass in the left breast of a few months' duration. In view of the clinical suspicion of a tumor, fine needle aspiration was performed. It showed a large number of dissociated cells and compact sheets of spindly and round cells with pleomorphic, hyperchromatic and anaplastic nuclei; mitoses; nucleoli; and somewhat-vacuolated, eosinophilic cytoplasm. Examination of the cell block, tumor tissue and immunostaining further suggested the cytologic impression of a leiomyosarcoma. CONCLUSION: Although leiomyosarcoma of the breast is very rare, fine needle aspiration cytology may allow the diagnosis to be suggested. Correlation with cell block findings and the application of appropriate immunostains as an adjuvant to standard cytologic and histologic stains may allow a more confident diagnosis.

The usefulness of a panel of immunostains in the diagnosis and differentiation of metastatic malignancies in pericardial effusions.

Pericardial effusions are not uncommon in patients with an advanced malignancy Rarely malignancies may present initially with a pericardial effusion. Cytological examination of pericardial fluid may be valuable in differentiation of these cases. However, a metastatic tumour in serous effusion may not always show the functional differentiation of the primary tumour. In such a situation, although a wide range of special studies have been suggested for the diagnosis of malignancy we have found the use of a panel of a few common immunostains to be useful in confirming or suggesting the site of a primary tumour. The material for this study consisted of 76 pericardial fluids obtained between January 1991 and October 1998 from 46 males (mean age 59 years) and 30 females (mean age 52 years). Metastatic malignancy was diagnosed in 22 of the 76 patients and in 7/22 cases pericardial effusions were the initial presentation. The subsequent follow-up in the seven cases revealed adenocarcinoma of lung (n = 2), small cell anaplastic carcinoma of lung (n = 1), squamous cell carcinoma lung (n = 1), melanoma leg (n = 1), non-Hodgkin's lymphoma retroperitoneal lymph nodes (n = 1) and carcinoma of the breast (n = 1). Of the remaining 15 cases with a known history of malignancy, eight had cancers (three adeno; two small cell; one poorly differentiated, and two squamous cell types) of the lung; breast (n = 3); colon (n = 1); melanoma (n = 2) and non Hodgkin's lymphoma (n = 1). Immunostains which were useful in the diagnosis were EMA, CEA, cytokeratin, B72.3, HMB45, vimentin, S100, LCA, L26 and kappa and lambda light chains.

Aspiration cytodiagnosis of small cell malignancies found in fine needle aspirate (FNA) of the liver: an immunocytochemical study.

In this study the features of small cell malignancies found in the liver by fine needle aspiration cytology (FNAC) and immunostains required for a diagnosis and differential diagnosis are presented. The material consisted of 197 fine needle aspirates which were performed under image guidance between January 1982 to October 1999. Of these, 30 were diagnosed as small cell malignancies. The age of patients ranged between 46 and 68 years. The aspirated material was examined using Papanicolaou-stained filter preparations and cell blocks, the latter stained with hematoxylin and eosin and a panel of immunoperoxidase stains. The diagnoses based on a correlation of relevant clinical history, cytohistological findings and immunostaining were: metastatic small cell anaplastic carcinoma of lung (n = 6); neuroendocrine tumour (n = 9); non-Hodgkin's lymphoma (n = 4); well-differentiated cholangiocarcinoma (n = 2); metastatic carcinoma of the prostate (n = 2); metastatic adenocarcinoma (n = 4) and metastatic carcinoma breast (n = 3). This study emphasizes the wide range of neoplasms that enter into the differential diagnosis of small cell malignancies found in the liver and a correlation of clinical, cytohistological and immunostaining findings which seem to be useful in suggesting a diagnosis.

Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast.

Secretory carcinoma (SC) of the breast is a rare variant of breast malignancy and its cytological features in fine needle aspirates have only recently been described. In this communication, our experience with four cases of SC of the breast is presented in which the diagnosis was established on fine needle aspiration cytology (FNAC). In all cases, the samples were cellular and featured diffuse, prominent, intracytoplasmic vacuoles and secretion in malignant cells and occasional signet-ring like forms. The cytodiagnosis of SC in all the cases correlated with subsequent examination of cell blocks of the aspirate and tissue. Cytochemical stains showed diffuse positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red O staining was negative. Immunopositivity to carcinoembryonic antigen, cytokeratin (CAM 5.2), B72.3 and epithelial membrane antigen was found in malignant cells. The cytodiagnostic criteria for SC of the breast, characteristic cytological features which are useful in a correct FNAC diagnosis and differentiation from other pertinent breast carcinomas, are discussed.

Luminal epithelial antigen (LEA.135) expression in adenocarcinoma of the colon.

BACKGROUND: Luminal Epithelial Antigen (LEA.135) is a cell surface glycoprotein, whose expression has been shown to have prognostic significance in breast carcinoma and transitional cell carcinoma of the bladder, but has not been previously evaluated in adenocarcinoma of the colon. PATIENTS AND METHODS: This study examines LEA.135 expression in 134 archival cases of colon adenocarcinoma obtained from Wellington Hospital Pathology Department between 1985 and 1990 inclusive. The findings were compared with tumor grade, stage and survival, to determine whether LEA.135 could serve as a useful indicator of the progression of colonic adenocarcinoma. RESULTS: Analysis of results showed that LEA.135 expression was not related to depth of invasion (p = 0.097), grade (p = 0.14) or clinical outcome (p = 0.27). Both luminal and cytoplasmic labelling of LEA.135 was seen in tumor cells however there was no association between LEA.135 distribution and either tumor grade or patient survival. CONCLUSION: The results suggest that the expression of LEA.135 does not provide a useful indication of clinical progression or outcome in patients with colonic adenocarcinoma.

Vasculitis-induced colonic strictures: report of two cases.

PURPOSE: The clinical presentations of gastrointestinal involvement from systemic vasculitis are diverse. Colonic involvement from systemic vasculitis is unusual. We report the first case of a symptomatic colonic stricture associated with rheumatoid vasculitis and another associated with systemic lupus erythematosus. METHODS: The clinical, radiologic, and histologic features of two cases of symptomatic colonic strictures secondary to colonic involvement with vasculitis are described. The literature covering gastrointestinal involvement from vasculitis in these conditions is reviewed. RESULTS: Surgical resection of the colonic strictures was required in both patients and had a satisfactory outcome. CONCLUSIONS: These cases provide further evidence of the protean clinical presentations of intestinal involvement in systemic vasculitis. Although immunosuppression has been shown to be of value in the treatment of vasculitis affecting the gastrointestinal tract, surgical resection is required for established strictures.

Reproducibility of new classification schemes for the pathology of ductal carcinoma in situ of the breast.

AIM: To compare the interobserver variation in the pathological classification of ductal carcinoma in situ of the breast using two recently proposed classification schemes. METHODS: 11 pathologists classified a set of 25 cases of ductal carcinoma in situ chosen to reflect a range of lesions, using the traditional architectural classification together with the modified cytonuclear grading scheme of Holland et al and the Van Nuys classification scheme. Participating pathologists received a standard tutorial, written information, and illustrative photomicrographs before their assessment of the cases. RESULTS: Interobserver agreement was poorest when using the architectural scheme (kappa = 0.44), largely owing to variations in classifying lesions with a mixed component of patterns (kappa = 0.13). Agreement was better using the modified cytonuclear grading scheme (kappa = 0.57), with most consistency achieved using the Van Nuys scheme (kappa = 0.66). Most discordant results using the later scheme were due to inconsistency in assessing the presence or absence of luminal necrosis. CONCLUSIONS: Both the new classification schemes assessed in this study were an improvement over the traditional architectural classification system for ductal carcinoma in situ, and resulted in more reproducible pathological assignment of cases. The Van Nuys classification scheme is easy to apply, even to small areas of carcinoma, resulting in acceptable interobserver agreement between reporting pathologists. Additional work will be required to arrive at a consensus definition of necrosis for cases in the non-high-grade group.

Fine-needle aspiration cytology of a minimal carcinoma of the breast with neuroendocrine features.

A case of breast carcinoma with neuroendocrine features is described in a 62-year-old nulliparous female, in which the fine-needle aspiration cytodiagnosis was of a breast carcinoma. Carcinoma of the breast with neuroendocrine features is an unusual variant which may be observed in several histologic types of mammary carcinoma. An awareness of this tumor is essential in view of the increasing use of fine-needle aspiration cytology as a minimally invasive, first line of investigation of a breast abnormality. The case presented here is also of interest since the tumor was only 5 mm in diameter (a minimal carcinoma).